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This scientometric analysis explores the evolution and dynamics of Early Childhood STEAM education. Web of Science database is employed as a primary data source and visualization tools like CiteSpace and HistCite are used to systematically investigate 179 publications published between 2008 and 2023. It looks at research patterns to unearth notable shifts in focus and intensity influenced by the COVID-19 pandemic. Keyword analysis reveals the field's evolution, from foundational elements to broader dimensions encompassing technology, pedagogy, and gender disparities. A transition towards experiential learning, emotional identity, and professional development is evident, which reflects a pedagogical shift towards comprehensive and inclusive education. Temporal analysis using Citation Burst Analysis delineates phases of research, emphasizing shifts from fundamental exploration to pedagogical methods and experiences. Acknowledgement of influential scholars, collaborations, and global trends underscores events of interdisciplinary partnerships and international collaborations. The study's implications highlight pedagogical transformations, gender disparity, and the potential for technology in early childhood education. This could inform policy directions and foster collaborations for innovative education.

Abstract “The narrative” is a complex cognitive process that has sparked a debate on whether its features age through maintenance or decline. To address this question, we attempted to uncover the narrative aging and its underlying neural characteristics with a cross-validation based cognitive neuro-decoding statistical framework. This framework used a total of 740 healthy older participants with completed narrative and extensive neuropsychological tests and MRI scans. The results indicated that narrative comprises macro and micro structures, with the macrostructure involving complex cognitive processes more relevant to aging. For the brain functional basis, brain hub nodes contributing to macrostructure were predominantly found in the angular gyrus and medial frontal lobe, while microstructure hub nodes were located in the supramarginal gyrus and middle cingulate cortex. Moreover, networks enriched by macrostructure included the default mode network and fronto-parietal network, indicating a higher functional gradient compared to the microstructure-enriched dorsal attention network. Additionally, an interesting finding showed that macrostructure increases in spatial contribution with age, suggesting a compensatory interaction where brain regions related to spatial-constructional ability have a greater impact on macrostructure. These results, supported by neural-level validation and multimodal structural MRI, provide detailed insights into the compensatory effect in the narrative aging process.

Abstract Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder characterized by physical, cognitive, and behavioral impairments. The PSP Rating Scale (PSPRS) is a widely used and validated, clinical scale to monitor disease progression. Here we show the modification of PSPRS to improve clinical meaningfulness and sensitivity. A conceptual framework was used to select meaningful items. Datasets were analyzed to improve the psychometric properties, understand factor structure, and develop a scoring algorithm. Fifteen items of the PSPRS were selected based on whether the items reflect concepts specific to the disease and those responsive to change over 12 months. Some items were rescored to reflect meaningful changes and to improve discrimination and reliability. The rescored 15-item PSPRS was more interpretable and sensitive to disease progression over 12 months. The approach to develop the 15-item PSPRS provides an example of how to modify an existing clinical outcome assessment for use as a primary endpoint in a clinical trial of a progressive neurological disorder.

Trans fatty acids (TFAs) have attracted considerable attention from all sectors of the community. As vegetable oils are the major source of TFAs in the daily diet, it is essential to understand the formation of TFAs in vegetable oils for accurate regulation. In recent years, a number of studies have explored the amount of TFAs generated in different vegetable oils and breakthroughs have been made in understanding the formation pathways and regulatory mechanisms of different TFAs isomers, but a systematic and comprehensive review has not yet been conducted. In this review, a systematic summary of the types and contents of TFAs in different vegetable oils, their formation mechanisms, regulatory measures and mechanisms is presented, with a view to providing references for people’s daily intake of TFAs through vegetable oils as well as subsequent research on TFAs in vegetable oils.

After tooth extraction, alveolar bone absorbs unevenly, leading to soft tissue collapse, which hinders full regeneration. Bone loss makes it harder to do dental implants and repairs. Inspired by the biological architecture of bone, a deformable SIS/HA (Small intestinal submucosa/Hydroxyapatite) composite hydrogel coaxial scaffold was designed to maintain bone volume in the socket. The SIS/HA scaffold containing GL13K as the outer layer, mimicking compact bone, while SIS hydrogel loaded with bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos) was utilized as the inner core of the scaffolds, which are like soft tissue in the skeleton. This coaxial scaffold exhibited a modulus of elasticity of 0.82 MPa, enabling it to adaptively fill extraction sockets and maintain an osteogenic space. Concurrently, the inner layer of this composite scaffold, enriched with BMSCs-Exos, promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and BMSCs into the scaffold interior (≈3-fold to the control), up-regulated the expression of genes related to osteogenesis (BMP2, ALP, RUNX2, and OPN) and angiogenesis (HIF-1α and VEGF). This induced new blood vessels and bone growth within the scaffold, addressing the issue of low bone formation rates at the center of defects. GL13K was released by approximately 40.87 ± 4.37 % within the first three days, exerting a localized antibacterial effect and further promoting vascularization and new bone formation in peripheral regions. This design aims to achieve an all-around and efficient bone restoration effect in the extraction socket using coaxial scaffolds through a dual internal and external mechanism.

Background: Breast cancer had been the most frequently diagnosed cancer among women, making up nearly one-third of all female cancers. Hormone receptor-positive breast cancer (HR+BC) was the most prevalent subtype of breast cancer and exhibited significant heterogeneity. Despite advancements in endocrine therapies, patients with advanced HR+BC often faced poor outcomes due to the development of resistance to treatment. Understanding the molecular mechanisms behind this resistance, including tumor heterogeneity and changes in the tumor microenvironment, was crucial for overcoming resistance, identifying new therapeutic targets, and developing more effective personalized treatments. Methods: The study utilized single-cell RNA sequencing (scRNA-seq) data sourced from the Gene Expression Omnibus database and The Cancer Genome Atlas to analyze HR+BC and identify key cellular characteristics. Cell type identification was achieved through Seurat's analytical tools, and subtype differentiation trajectories were inferred using Slingshot. Cellular communication dynamics between tumor cell subtypes and other cells were analyzed with the CellChat. The pySCENIC package was utilized to analyze transcription factors regulatory networks in the identified tumor cell subtypes. The results were verified by in vitro experiments. A risk scoring model was developed to assess patient outcomes. Results: This study employed scRNA-seq to conduct a comprehensive analysis of HR+BC tumor subtypes, identifying the C3 PCLAF+ tumor cells subtype, which demonstrated high proliferation and differentiation potential. C3 PCLAF+ tumor cells subtype was found to be closely associated with cancer-associated fibroblasts through the MK signaling pathway, facilitating tumor progression. Additionally, we discovered that MAZ was significantly expressed in C3 PCLAF+ tumor cells subtype, and in vitro experiments confirmed that MAZ knockdown inhibited tumor growth, accentuating its underlying ability as a therapeutic target. Furthermore, we developed a novel prognostic model based on the expression profile of key prognostic genes within the PCLAF+/MAZ regulatory network. This model linked high PCLAF+ tumor risk scores with poor survival outcomes and specific immune microenvironment characteristics. Conclusion: This study utilized scRNA-seq to reveal the role of the C3 PCLAF+ tumor cells subtype in HR+BC, emphasizing its association with poor prognosis and resistance to endocrine therapies. MAZ, identified as a key regulator, contributed to tumor progression, while the tumor microenvironment had a pivotal identity in immune evasion. The findings underscored the importance of overcoming drug resistance, recognizing novel treatment targets, and crafting tailored diagnosis regimens.

Objectives Acute type A aortic dissection is a life-threatening cardiovascular disease commonly seen in emergency department, resulting in substantial mortality and morbidity. We aimed to investigate the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) among this critically ill population.Design The design of this study was a retrospective cohort study.Setting The study population was recruited in the Emergency Department of Fuwai hospital in China from 2018 to 2020.Participants We consecutively enrolled 829 patients with acute type A aortic dissection and measurable baseline NT-proBNP.Primary outcome The primary endpoint was 1-year all-cause death.Results Based on tertiles of NT-proBNP (pg/mL), patients were stratified into low (≤150.3, n=276), intermediate (150.3–667.6, n=277) and high (>667.6, n=276) NT-proBNP groups. Compared with patients with low NT-proBNP, the Kaplan-Meier estimates for primary 1-year mortality were higher in intermediate (32.5% vs 18.1%; HR 1.91, 95% CI 1.35 to 2.69) and high (42.0% vs 18.1%; HR 2.56, 95% CI 1.84 to 3.57) NT-proBNP groups, respectively. After multivariable regression adjusted for confounders, NT-proBNP tertiles were independent predictors for 1-year mortality (adjusted HR for intermediate group 1.52, 95% CI 1.02 to 2.27; adjusted HR for high group 2.17, 95% CI 1.41 to 3.32). Notably, the predictive performance of NT-proBNP for 1-year mortality was greater in patients receiving surgery than conservative treatment (between-cohorts difference in area under the curve 0.13, Delong’s test p=0.04).Conclusion NT-proBNP provides incremental prognostic information for mortality in patients with acute type A aortic dissection who underwent surgical repairment, which could aid in risk stratification as a pragmatic and versatile biomarker in this critically ill population while having limited prognostic value for those receiving conservative treatment.

BackgroundHigh-grade serous ovarian cancer (HGSOC), the predominant subtype of epithelial ovarian cancer, is frequently diagnosed at an advanced stage due to its nonspecific early symptoms. Despite standard treatments, including cytoreductive surgery and platinum-based chemotherapy, significant improvements in survival have been limited. Understanding the molecular mechanisms, immune landscape, and drug sensitivity of HGSOC is crucial for developing more effective and personalized therapies. This study integrates insights from cancer immunology, molecular profiling, and drug sensitivity analysis to identify novel therapeutic targets and improve treatment outcomes. Utilizing single-cell RNA sequencing (scRNA-seq), the study systematically examines tumor heterogeneity and immune microenvironment, focusing on biomarkers influencing drug response and immune activity, aiming to enhance patient outcomes and quality of life.MethodsscRNA-seq data was obtained from the GEO database in this study. Differential gene expression was analyzed using gene ontology and gene set enrichment methods. InferCNV identified malignant epithelial cells, while Monocle, Cytotrace, and Slingshot software inferred subtype differentiation trajectories. The CellChat software package predicted cellular communication between malignant cell subtypes and other cells, while pySCENIC analysis was utilized to identify transcription factor regulatory networks within malignant cell subtypes. Finally, the analysis results were validated through functional experiments, and a prognostic model was developed to assess prognosis, immune infiltration, and drug sensitivity across various risk groups.ResultsThis study investigated the cellular heterogeneity of HGSOC using scRNA-seq, focusing on tumor cell subtypes and their interactions within the tumor microenvironment. We confirmed the key role of the C2 IGF2+ tumor cell subtype in HGSOC, which was significantly associated with poor prognosis and high levels of chromosomal copy number variations. This subtype was located at the terminal differentiation of the tumor, displaying a higher degree of malignancy and close association with stage IIIC tissue types. The C2 subtype was also associated with various metabolic pathways, such as glycolysis and riboflavin metabolism, as well as programmed cell death processes. The study highlighted the complex interactions between the C2 subtype and fibroblasts through the MK signaling pathway, which may be closely related to tumor-associated fibroblasts and tumor progression. Elevated expression of PRRX1 was significantly connected to the C2 subtype and may impact disease progression by modulating gene transcription. A prognostic model based on the C2 subtype demonstrated its association with adverse prognosis outcomes, emphasizing the importance of immune infiltration and drug sensitivity analysis in clinical intervention strategies.ConclusionThis study integrates molecular oncology, immunotherapy, and drug sensitivity analysis to reveal the mechanisms driving HGSOC progression and treatment resistance. The C2 IGF2+ tumor subtype, linked to poor prognosis, offers a promising target for future therapies. Emphasizing immune infiltration and drug sensitivity, the research highlights personalized strategies to improve survival and quality of life for HGSOC patients.

IntroductionBladder cancer was recognized as one of the most common malignant tumors in the urinary system, and treatment options remained largely limited to conventional surgery, radiotherapy, and chemotherapy, which limited patient benefits.MethodsResearchers constructed an RNA transcriptome map of bladder cancer by integrating single-cell RNA sequencing and clinical data, identifying potential molecular targets for diagnosis and treatment. We also verified the antitumor activity of the target through in vitro experiment.ResultsA distinct tumor cell subpopulation characterized by elevated S100A8 expression exhibited high copy number variation, high stemness, and low differentiation. It interacted with myeloid cells via the MIF-(CD74+CD44) and MIF-(CD74+CXCR4) signaling pathways. This study underscored KDELR2’s role in promoting cell proliferation, invasion, and migration, providing new therapeutic insights. Prognostic analysis revealed that KDELR2 correlated with poor survival, higher immune scores, and increased macrophage infiltration.DiscussionThe findings suggested that patients with high KDELR2 expression might benefit from immune checkpoint therapy. KDELR2 was also shown to enhance bladder cancer cell proliferation, invasion, and migration, highlighting it as a promising target for macrophage-focused drug development.

Background: Ischemic stroke (IS), generally referred to as cerebral infarction (CI), is a high-risk stroke. After CI, blood vessels need to be reopened, and cerebral ischemia–reperfusion injury (CIRI) is prone to occur during this period. Taohong Siwu Decoction (THSWD) is a traditional Chinese herbal formula that has been used to activate blood circulation and remove blood stasis. It has been confirmed that THSWD can improve CIRI caused by ischemic stroke, but its specific mechanism is not clear. Methods: We observed the protective effect of THSWD on rats that had undergone middle cerebral artery occlusion and reperfusin (MCAO/R) and PC12 cells after oxygen glucose deprivation/re-oxygenation (OGD/R) injury based on the silent information regulator 1/forkhead box protein O1 (SIRT1/FOXO1) signaling pathway. We explored the role of the SIRT1/FOXO1 signaling pathway on the use of THSWD for ischemic stroke (IS) and its mechanism from the perspectives of oxidative stress, autophagy and apoptosis. Experimental tools included neurological deficit assessment, staining, Tunel assay, transmission electron microscopy, flow cytometry, immunofluorescence, immunohistochemistry, and Western blot. Results: We detected activation of the SIRT1/FOXO1 signaling pathway after THSWD administration on MCAO/R rats and PC12 cells after OGD/R. THSWD attenuated oxidative stress, enhanced autophagy, and inhibited apoptosis. Conclusion: THSWD can improve CIRI by modulating the SIRT1/FOXO1 signaling pathway.

Type I interferons (IFN-Is) have key roles in immune defense and treatments for various diseases, including chronic hepatitis B virus (HBV) infection. All IFN-Is signal through a shared IFN-I heterodimeric receptor complex comprising IFN-α receptor 1 (IFNAR1) and IFNAR2 subunits, but differences in antiviral and immunomodulatory responses among IFN-I subtypes remain largely unknown. Because the IFN-IFNAR interactions are species-specific, mice exhibit weak responses to human IFN-I. To more fully characterize the actions of human IFN-α and its subtypes in vivo, a gene targeting strategy was employed to generate gene knock-in mice with extracellular-humanized IFNAR1/2 (IFNAR-hEC) in the C57BL/6N strain. IFNAR-hEC mice actively responded to human IFN-I, and endogenous mouse IFN-I signalling remained active in heterozygous mice (IfnarhEC/+). Analyses of IFNAR-hEC mice and isolated cells showed that human IFN-α2 and α14 subtypes exerted differential effect on the activation of JAK-STAT signalling and immune responses. Compared with IFN-α2, IFN-α14 induced greater activation of STAT1/2 and IFN-stimulated genes, synergistically elicited IFN-α and -γ signalling, and induced higher numbers of antigen-specific CD8+ T cells. Moreover, IFNAR-hEC mice with HBV replication displayed long-term viral suppression upon treatment with the clinically-used PEGylated hIFN-α2. These results indicate that IFNAR-hEC mice may be useful for elucidating antiviral and immunomodulatory functions of human IFN-Is and for conducting preclinical studies. A better understanding of the distinct activities of IFN-α subtypes can provide insights concerning the development of improved IFN-based therapy.

Abstract Background The global prevalence of obesity has escalated into a formidable health challenge intricately linked with the risk of developing cardiac diastolic disfunction and heart failure with preserved ejection fraction (HFpEF). Abnormal fat distribution is potentially strongly associated with an increased risk of cardiac diastolic dysfunction, and we aimed to scrutinize and elucidate the correlation between them. Methods Following the Cochrane Handbook and PRISMA 2020 guidelines, we systematically reviewed the literature from PubMed, Embase, and Web of Science. We focused on studies reporting the mean and standard deviation (SD) of abnormal fat in HFpEF or cardiac diastolic dysfunction patients and the Pearson/Spearman correlation coefficients for the relationship between abnormal fat distribution and the risk of developing cardiac diastolic dysfunction. Data were standardized to the standard mean difference (SMD) and Fisher’s z value for meta-analysis. Results After progressive filtering and selection, 63 studies (43,113 participants) were included in the quantitative analyses. Abnormal fat distribution was significantly greater in participants with cardiac diastolic dysfunction than in controls [SMD 0.88 (0.69, 1.08)], especially in epicardial adipose tissue [SMD 0.99 (0.73, 1.25)]. Abnormal fat distribution was significantly correlated with the risk of developing cardiac diastolic dysfunction [E/E’: 0.23 (0.18, 0.27), global longitudinal strain: r=-0.11 (-0.24, 0.02)]. Meta-regression revealed sample size as a potential heterogeneous source, and subgroup analyses revealed a stronger association between abnormal fat distribution and the risk of developing cardiac diastolic dysfunction in the overweight and obese population. Conclusion Abnormal fat distribution was significantly associated with the risk of developing cardiac diastolic dysfunction. Trial registration CRD42024543774.

BackgroundThe widespread adoption of information and communication technologies (ICTs) further deepens disparities in resource access, particularly among the aging population. However, the relationship between these factors and their resulting impact on cognitive abilities remains uncertain. ObjectiveThis study aims to investigate the potential impact of the digital divide on individuals’ cognitive function and its association with the development and reversion of mild cognitive impairment (MCI). MethodsThis cohort study used data from Beijing Aging Brain Rejuvenation (BABRI) study applying a multistage cluster sampling design between 2008 and 2020. The digital divide was quantified by the frequency of using ICTs. Analysis of covariance (ANCOVA), mixed linear models, and Cox proportional hazards models were used to model the association of digital divide and multidomain cognition. ResultsAmong the 10098 participants, nearly half (n=4941, 48.9%) faced the digital divide, which was associated with a worse performance in processing speed (F10096=10.67; P

Lactate has been traditionally regarded as a mere byproduct of glycolysis or metabolic waste. However, an increasing body of literature suggests its critical role in regulating various physiological and pathological processes. Lactate is generally associated with hypoxia, inflammation, viral infections, and tumors. It performs complex physiological roles by activating monocarboxylate transporter (MCT) or the G protein-coupled receptor GPR81 across the cell membrane. Lactate exerts immunosuppressive effects by regulating the functions of various immune cells (such as natural killer cells, T cells, dendritic cells, and monocytes) and its role in macrophage polarization and myeloid-derived suppressor cell (MDSC) differentiation in the tumor microenvironment. Lactic acid has also recently been found to increase the density of CD8+ T cells, thereby enhancing the antitumor immune response. Acute or chronic inflammatory diseases have opposite immune states in the inflammatory disease microenvironment. Factors such as cell types, transcriptional regulators, ionic mediators, and the microenvironment all contribute to the diverse functions lactate exhibits. Herein, we reviewed the pleiotropic effects of lactate on the regulation of various functions of immune cells in the tumor microenvironment and under inflammatory conditions, which may help to provide new insights and potential targets for the diagnosis and treatment of inflammatory diseases and malignancies.

ObjectiveTo evaluate the association between systemic inflammatory markers and clinical outcomes (all-cause mortality, cardiovascular mortality, and rehospitalization) in patients with heart failure with preserved ejection fraction (HFpEF).MethodsWe conducted a comprehensive literature search in PubMed, Embase, and Ovid Medline databases from inception to June 27, 2024. Studies were included if they were observational clinical studies involving HFpEF patients over 18 years old, with exposure to systemic inflammatory markers and reporting on adverse prognosis outcomes. The Newcastle-Ottawa Scale (NOS) was used to assess study quality.ResultsEight studies ultimately included in the meta-analysis which involved 9,744 participants from six countries. The meta-analysis showed that systemic inflammatory markers were significantly associated with all-cause mortality (HR 1.43, 95% CI 1.19–1.72, p

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins——nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim.

Abstract Aging is a complex and multifaceted process involving a variety of interrelated molecular mechanisms and cellular systems. Phenotypically, the biological aging process is accompanied by a gradual loss of cellular function and the systemic deterioration of multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that aging is closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis. These age-related changes may be alleviated by intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, and targeted longevity genes. In this review, we summarise the key historical progress in the exploration of important causes of aging and anti-aging strategies in recent decades, which provides a basis for further understanding of the reversibility of aging phenotypes, the application prospect of synthetic biotechnology in anti-aging therapy is also prospected.

Scaffold materials, seed cells and growth factors are referred to as the three elements of bone tissue engineering (BTE). However, the physical properties and biocompatibility of these scaffolds and the safety and cost of their growth factors limit their clinical application. Therefore, it is critical to develop a novel scaffold modified with efficient growth factors that meets the requirements of BTE. Herein, 3D-printed poly (lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) composite scaffolds modified with new fusion peptides, which can effectively promote the regeneration and repair of bone defects, were developed. 3D-printed PLGA/HA composite scaffolds with appropriate HA contents were prepared and had appropriate mechanical properties. In addition, the surface of the 3D-printed PLGA/HA composite scaffold was modified with new fusion peptides to provide osteogenic, antimicrobial, and angiogenesis-promoting effects. In vitro experiments showed that the fusion peptide-modified scaffolds had good biocompatibility and a certain degree of antibacterial activity. Moreover, the fusion peptide-modified scaffolds significantly improved the migration ability of BMSCs and Ea.hy926 cells, promoted the expression of osteogenesis-related factors (BMP2, RUNX2, ALP, OPN) in BMSCs, and promoted the expression of angiogenesis-related factors (VEGF and HIF-1α) in Ea.hy926 cells. In vivo experiments showed that the fusion peptide-modified scaffolds had good osteogenic ability. This study reveals considerable application potential for bone defect repair and provides a new option of scaffold material for BTE.

Abstract Poa pratensis L. (Poaceae) is a valuable grass across the north hemisphere, inhabiting diverse environments with wide altitudinal span, where ubiquitous various kinds of stresses. Phytohormones would be helpful to improve tolerance to abiotic and biotic stresses, but the responses of transcriptome regulation of P. pratensis to exogenous phytohormones application remain unclear. In this study, we explored the alteration of plant physiological responses by the application of phytohormones. Aiming to achieve this knowledge, we got full-length transcriptome data 42.76 Gb, of which 74.9% of transcripts were completed. Then used 27 samples representing four treatments conducted at two time points (1 h and 6 h after application) to generate RNA-seq data. 371 and 907 common DEGs were identified in response to four phytohormones application, respectively, these DEGs were involved in “plant hormone signal transduction”, “carbon metabolism” and “plant-pathogen interaction”. Finally, P. pratensis basic research can gain valuable information regarding the responses to exogenous application of phytohormones in physiological indicators and transcriptional regulations in order to facilitate the development of new cultivars.

Abstract Background and aims Recent studies have shown that intestinal flora are involved in the pathological process of ischemic stroke (IS). The potential protective effect of the traditional Chinese prescription, Tao Hong Si Wu Decoction (THSWD), against inflammatory injury after IS and its underlying mechanisms of action were investigated in the current study. Methods Fifty SPF(Specefic pathogen Free) male C57 mice were randomly assigned to sham operation, model, THSWD low-dose (6.5 g/kg), medium-dose (13 g/kg) and high-dose (26 g/kg) groups (10 mice per group). Mouse models of transient middle cerebral artery occlusion were prepared via thread embolism. Neurological function score, hematoxylin-eosin (HE) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), 16S ribosomal DNA (rDNA) sequencing, quantitative reverse transcription PCR (qRT-PCR) and other methods were employed to elucidate the underlying molecular mechanisms. Results Notably, THSWD induced a reduction in the neurological function score (P

Abstract Background Previously, we have demonstrated that the batch variations of human platelet lysate (conventional MSC expansion medium) induce MSC heterogeneity and therapeutic inconsistency. On the other hand, the MSCs expanded with chemical defined medium have improved therapeutic consistency. Methods In the current study, we studied the MSC subpopulation composition and variation in different types and batches of MSC expansion medium with scRNA-seq analysis. Results MSCs expanded with different batches of media have higher levels of heterogeneity from the perspective of cell subpopulation composition at transcriptome levels and therapeutic inconsistency. The CD317+ subpopulation has enhanced immune suppression activities. And the percentage of CD317+ MSCs within MSCs is tightly correlated with its immune suppression activities, and also contributes to the heterogeneity and therapeutic inconsistency of MSCs. the CD317+ MSCs have increased expression levels of PTX3, which might stabilize the TSG6 protein and improve the therapeutic effects Conclusions Thus, purifying CD317+ MSCs is one efficient strategy to reduce MSC heterogeneity and increase the therapeutic consistency of MSCs.

Glycophagy has evolved from an alternative glycogen degradation pathway into a multifaceted pivot to regulate cellular metabolic hemostasis in peripheral tissues. However, the pattern of glycophagy in the brain and its potential therapeutic impact on ischemic stroke remain unknown. Here, we observed that the dysfunction of astrocytic glycophagy was caused by the downregulation of the GABA type A receptor-associated protein like 1 (GABARAPL1) during reperfusion in ischemic stroke patients and mice. PI3K-Akt pathway activation is involved in driving GABARAPL1 downregulation during cerebral reperfusion. Moreover, glycophagy dysfunction-induced glucosamine deficiency suppresses the nuclear translocation of specificity protein 1 and TATA binding protein, the transcription factors for GABARAPL1, by decreasing their O-GlcNAcylation levels, and accordingly feedback inhibits GABARAPL1 in astrocytes during reperfusion. Restoring astrocytic glycophagy by overexpressing GABARAPL1 decreases DNA damage and oxidative injury in astrocytes and improves the survival of surrounding neurons during reperfusion. In addition, a hypocaloric diet in the acute phase after cerebral reperfusion can enhance astrocytic glycophagic flux and accelerate neurological recovery. In summary, glycophagy in the brain links autophagy, metabolism, and epigenetics together, and glycophagy dysfunction exacerbates reperfusion injury after ischemic stroke.

Research purpose: This study aims to outline the fundamental status of the German academic community's research in the field of renewable energy and to foster collaboration between China and Germany in this area. Research methods: This study examines documents published by German scholars from 2008 to 2023, which are part of the “Web of Science (WOS) Core Collection” database and related to renewable energy issues, using the bibliometric visualization tool CiteSpace 6.2.R6. Research conclusions: The study examines the co-occurrence and burst of keywords, changes in publication volume, international collaboration networks, research institution collaboration networks, and researcher collaboration networks. It concluded that: (1) German academic research in the field of renewable energy can be divided into three phases: nascent (2008–2014), surge (2015–2021), and decline (2022–2023). (2) The Helmholtz Association and Reinhard Madlener, among other prominent institutions and academicians, are responsible for the close cooperation among personnel and institutions, the significant leading effect, and the emphasis on cutting-edge topics. Research in this field notably focuses on cutting-edge issues like life cycle assessment and developing countries. The study observes a transition in research concentration from macro to micro perspectives. In the context of a global collective response to climate change, the analysis of the German academic community’s overall situation will enhance the collaboration between the two countries in the field of renewable energy research.

Background and aimsTaohong Siwu Decoction (THSWD) is a traditional Chinese herbal prescription that is effective for ischemic stroke, Whether THSWD regulates the CCL2/CCR2 axis and thus reduces the inflammatory response induced by ischemic stroke is not known. The aim of this study was to elucidate the mechanism of action of THSWD in the treatment of ischemic stroke using bioinformatics combined with in vitro and in vivo experiments.MethodsR language was used to analyze middle cerebral artery occlusion/reperfusion (MCAO/R) rat transcriptome data and to identify differential gene expression following THSWD treatment. Gene set enrichment analysis (GSEA) was used to analyze the gene set enrichment pathway of MCAO/R rats treated with THSWD. PPI networks screened key targets. The Human Brain Microvascular Endothelial Cells (HBMEC) Oxygen Glucose Deprivation/Reoxygenation (OGD/R) model and SD rat models of MCAO/R were established. FITC-dextran, immunofluorescence, flow cytometry, ELISA, immunohistochemistry, Western blotting, and RT-qPCR were performed to identify potential treatment targets.ResultsA total of 515 differentially expressed genes of THSWD in MCAO/R rats were screened and 92 differentially expressed genes of THSWD potentially involved in stroke intervention were identified, including Cd68, Ccl2, and other key genes. In vitro, THSWD reversed the increase in permeability of HBMEC cells and M1/M2 polarization of macrophages induced by CCL2/CCR2 axis agonists. In vivo, THSWD improved nerve function injury and blood-brain barrier injury in MCAO/R rats. Further, THSWD inhibited the infiltration and polarization of macrophages, reduced the expression of IL-6, TNF-α, and MMP-9, and increased the expression of IL-4, while reducing the gene and protein expression of CCL2 and CCR2.ConclusionTHSWD may play a protective role in ischemic stroke by inhibiting the CCL2/CCR2 axis, reducing the infiltration of macrophages, and promoting the polarization of M2 macrophages, thereby reducing inflammatory damage, and protecting injury to the blood-brain barrier.

BackgroundMyelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis associated with substantial morbidity and mortality. The therapeutic landscape for MF has advanced with the development of Janus kinase inhibitors (JAKis) like ruxolitinib (RUX), fedratinib (FED), pacritinib (PAC), and momelotinib (MMB), aiming to alleviate symptoms and enhance patient comfort.MethodsA network meta-analysis was conducted to assess the efficacy and safety of eleven JAKi treatment regimens across nine randomized controlled trials (RCTs) with a total of 2340 participants. Outcomes were evaluated in terms of spleen volume reduction (SVR), total symptom score reduction (TSSR), hematological safety profiles, and overall survival (OS).ResultsRUX and MMB were superior in achieving SVR and TSSR, with significant dose-response relationships observed. PAC and MMB were associated with a decreased risk of grade 3/4 anemia and thrombocytopenia compared to other JAKis. However, no substantial benefits in OS were observed with newer JAKis compared to RUX. The poorer OS outcomes with certain PAC dosages were likely influenced by baseline patient characteristics, particularly severe cytopenias.ConclusionThe introduction of JAKis significantly changed the treatment of MF. This meta-analysis reaffirms the core role of RUX and positions MMB as a potentially powerful alternative for treating symptoms and reducing spleen size. Meanwhile, MMB and PAC have a positive effect on anemia in MF while FED is more tolerable for patients with thrombocytopenia. However, it should be noted that these results are influenced by baseline patient characteristics, particularly cytopenias, which affects both management and overall survival. Therefore, there is an urgent need for personalized dosing strategies to optimize the balance between efficacy and safety, with careful consideration of patient-specific factors.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023424179.

Bone defect disease seriously endangers human health and affects beauty and function. In the past five years, the three dimension (3D) printed radially graded triply periodic minimal surface (TPMS) porous scaffold has become a new solution for repairing bone defects. This review discusses 3D printing technologies and applications for TPMS scaffolds. To this end, the microstructural effects of 3D printed TPMS scaffolds on bone regeneration were reviewed and the structural characteristics of TPMS, which can promote bone regeneration, were introduced. Finally, the challenges and prospects of using TPMS scaffolds to treat bone defects were presented. This review is expected to stimulate the interest of bone tissue engineers in radially graded TPMS scaffolds and provide a reliable solution for the clinical treatment of personalised bone defects.

This study aimed to determine the toxic effects of vascular CCM3 gene deficiency and lead (Pb) exposure on the nervous system. Lentiviral transfection was performed to generate a stable strain of brain microvascular endothelial cells with low CCM3 expression. MTT assay assessed the survival rate of cells exposed to Pb, determining the dose and duration of Pb exposure in vitro. Proteomic analysis was performed on the differentially expressed proteins in bEnd3 and HT22 cells and flow cytometry was used to detect cell apoptosis. Finally, urine samples from pregnant and postpartum women were subjected to ICP-MS to detect Pb levels and HPLC to detect neurotransmitter metabolites. Based on the proteomic analysis of bEnd3 (CCM3-/-) cells co-cultured with HT22 cells, it was determined that HT22 cells and CCM3 genes interfered with bEnd3 cell differential proteins,22 Abbreviations: SNP, FGF2, EGF, AD including apoptosis and ferroptosis pathways. Electron microscopy observation, ICP-MS iron ion loading detection, and WB determination of protein GPX4 expression confirmed that HT22 cells undergo apoptosis, while bEnd3 cells undergo multiple pathways of iron death and apoptosis regulation. Furthermore, a linear regression model showed the interaction between maternal urine Pb levels, the rs9818496 site of the CCM3 SNP in peripheral blood DNA, and the concentration of the neurotransmitter metabolite 5-HIAA in maternal urine (F=4.198, P < 0.05). bEnd3 cells with CCM3 gene deficiency can induce HT22 cell apoptosis through iron death and apoptosis pathways under Pb exposure in a combined cell culture Pb exposure model, and CCM3 gene deficiency in endothelial cells and Pb exposure interacts with neural cell HT22. Epidemiological studies on maternal and newborn infants further confirmed the interaction between urine Pb levels in mothers and the SNP rs9818496 site of the CCM3 gene in peripheral blood DNA.

Abstract Background Although both preclinical and clinical studies have shown the great application potential of MSCs (mesenchymal stem/stromal cells) in treating many kinds of diseases, therapeutic inconsistency resulting from cell heterogeneity is the major stumbling block to their clinical applications. Cell population diversity and batch variation in the cell expansion medium are two major inducers of MSC heterogeneity. Methods Cell population diversity was investigated through single-cell RNA sequencing analysis of human MSCs derived from the umbilical cord and expanded with fully chemically defined medium in the current study. Then, the MSC subpopulation with enhanced anti-inflammatory effects was studied in vitro and in vivo. Results Our data showed that MSCs contain different populations with different functions, including subpopulations with enhanced functions of exosome secretion, extracellular matrix modification and responses to stimuli (regeneration and immune response). Among them, CD317+ MSCs have improved differentiation capabilities and enhanced immune suppression activities. Underlying mechanism studies showed that higher levels of TSG6 confer enhanced anti-inflammatory functions of CD317+ MSCs. Conclusions Thus, CD317+ MSCs might be a promising candidate for treating immunological disorder-related diseases.

Abstract Objectives To explore the correlation between Blood urea nitrogen to creatinine ratio (BUN/Scr ratio) and prognosis of patients with chronic heart failure complicated with renal injury. Methods A retrospective analysis of 504 patients hospitalized in Guang 'anmen Hospital, Chinese Academy of Traditional Chinese Medicine from March 2006 to June 2014 was conducted. The baseline data were analyzed, and the cutoff value was obtained by receiver operator characteristic curve (ROC) analysis, according to the cutoff value, all the participants were divided into two groups, BUN/Scr

Summary: Facioscapulohumeral dystrophy (FSHD) is linked to contraction of D4Z4 repeats on chromosome 4q with SMCHD1 mutations acting as a disease modifier. D4Z4 heterochromatin disruption and abnormal upregulation of the transcription factor DUX4, encoded in the D4Z4 repeat, are the hallmarks of FSHD. However, defining the precise effect of D4Z4 contraction has been difficult because D4Z4 repeats are primate-specific and DUX4 expression is very rare in highly heterogeneous patient myocytes. We generated isogenic mutant cell lines harboring D4Z4 and/or SMCHD1 mutations in a healthy human skeletal myoblast line. We found that the mutations affect D4Z4 heterochromatin differently, and that SMCHD1 mutation or disruption of DNA methylation stabilizes otherwise variegated DUX4 target activation in D4Z4 contraction mutant cells, demonstrating the critical role of modifiers. Our study revealed amplification of the DUX4 signal through downstream targets, H3.X/Y and LEUTX. Our results provide important insights into how rare DUX4 expression leads to FSHD pathogenesis.

Abstract We aimed to develop a prognostic model for primary pontine hemorrhage (PPH) patients and validate the predictive value of the model for a good prognosis at 90 days. A total of 254 PPH patients were included for screening of the independent predictors of prognosis, and data were analyzed by univariate and multivariable logistic regression tests. The cases were then divided into training cohort (n=219) and validation cohort (n=35) based on the two centers. A nomogram was developed using independent predictors from the training cohort to predict the 90-day good outcome and was validated from the validation cohort. Glasgow Coma Scale score, normalized pixels (used to describe bleeding volume), and mechanical ventilation were significant predictors of a good outcome of PPH at 90 days in the training cohort (all P

Summary: Despite adjuvant chemotherapy and endocrine therapy in luminal breast cancer (LBC), relapses are common. Addressing this, we aim to develop a prognostic model to refine adjuvant therapy strategies, particularly for patients at high recurrence risk. Notably, obesity profoundly affects the tumor microenvironment (TME) of LBC. However, it is unclear whether obesity-related biological features can effectively screen high-risk patients. Utilizing weighted gene coexpression network analysis (WGCNA) on RNA sequencing (RNAseq) data, we identified seven obese LBC genes (OLGs) closely associated with patient prognosis. Subsequently, we developed a luminal obesity-gene clinical prognostic index (LOG-CPI), combining a 7-gene signature, TNM staging, and age. Its predictive efficacy was confirmed across validation datasets and a clinical cohort (5-year accuracy = 0.828, 0.760, 0.751, and 0.792, respectively). LOG-CPI emerges as a promising predictor for clinical prognosis and treatment response, helping distinguish molecular and immunological features in LBC patients and guiding clinical practice by identifying varying prognoses.