Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation.

Objective: This study investigated the significance of HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) in esophageal cancer (ESCA) and its underlying mechanism in ESCA regulation through the induction of RAC1 ubiquitination and degradation. Methods: Characterization studies of HACE1 in ESCA clinical tissues and cell lines were performed. Next, the effects of HACE1 on the biological behavior of ESCA cells were examined by silencing and overexpressing HACE1. Protein-protein interactions (PPIs) involving HACE1 were analyzed using data from the String website. The function of HACE1 in RAC1 protein ubiquitination was validated using the proteasome inhibitor MG132. The effects of HACE1 on ESCA cells through RAC1 were elucidated by applying the RAC1 inhibitor EHop-016 in a tumor-bearing nude mouse model. To establish the relationship between HACE1 and TRIP12, rescue experiments were conducted, mainly to evaluate the effect of TRIP12 silencing on HACE1-mediated RAC1 regulation in vitro and in vivo. The PPI between HACE1 and TRIP12 and their subcellular localization were further characterized through co-immunoprecipitation and immunofluorescence staining assays, respectively. Results: HACE1 protein expression was notably diminished in ESCA cells but upregulated in normal tissues. HACE1 overexpression inhibited the malignant biological behavior of ESCA cells, leading to restrained tumor growth in mice. This effect was coupled with the promotion of RAC1 protein ubiquitination and subsequent degradation. Conversely, silencing HACE1 exhibited contrasting results. PPI existed between HACE1 and TRIP12, compounded by their similar subcellular localization. Intriguingly, TRIP12 inhibition blocked HACE1-driven RAC1 ubiquitination and mitigated the inhibitory effects of HACE1 on ESCA cells, alleviating tumor growth in the tumor-bearing nude mouse model. Conclusion: HACE1 expression was downregulated in ESCA cells, suggesting that it curbs ESCA progression by inducing RAC1 protein degradation through TRIP12-mediated ubiquitination.

Identification of bioactive ingredients and potential mechanisms of flowers of Hosta Plantaginea in treating pneumonia based on network pharmacology and experimental validation.

Flowers of Hosta plantaginea (H. plantaginea), a widely utilized medicinal herb in Mongolian medicine, holds a significant historical background in terms of its medicinal applications. This herb is renowned for its ability to clear heat and detoxify the body, alleviate cough, and provide relief to the throat. However, the active ingredients and the potential mechanism of action remain ambiguity. The objective of this study was to conduct a comprehensive analysis of the efficacy of H. plantaginea in treating pneumonia, identify its active ingredients and unveil the pharmacological mechanism in the treatment of pneumonia. In vivo experiments demonstrate the plant's anti-pneumonia properties, while mass spectrometry analysis identifies 62 chemicals, with 14 absorbed into the bloodstream. Network pharmacology and Venn analysis reveal 195 targets of 52 active ingredients, with 49 gene targets common to H. plantaginea and pneumonia. Protein-protein interaction (PPI) network construction and enrichment analysis highlight the key targets and pathways such as AKT, EGFR, IL-17. Western blotting confirms downregulation of these pathways, indicating the anti-inflammatory effects of H. plantaginea in treating acute lung injury. Our findings showed that the treatment of ALI with the H. plantaginea exerts its anti-inflammatory effects through multiple components, targets, and pathways. This study established a solid experimental foundation for investigating the various components, targets, and pathways involved in the treatment of pneumonia using H. plantaginea. It offers valuable insights from multiple perspectives and can serve as a reference for the clinical application of this plant in pneumonia treatment.

Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11.

BACKGROUND: Luteolin (3,4,5,7-tetrahydroxy flavone) is reported to strongly protect from acute carbon tetrachloride (CCl4) -induced liver injury or fibrosis. Ferroptosis can be induced by hepatic injury, and contributes to liver fibrosis development. The exact functional mechanism underlying luteolin inhibition of hepatic injury and whether ferroptosis is involved are unclear. METHODS: Mice model and cell model of liver injury were constructed or induced to explore the effect and molecular mechanisms of Luteolin in the treatment of hepatic injury using CCl4. Cell Counting Kit-8 (CCK-8) and flow cytometry were used to evaluate HepG2 cell viability and apoptosis. The differential expressed genes involved in liver injury were scanned using RNA-seq and confirmed using functional study. Western blot was used to detect the indicators related to ferroptosis. RESULTS: Luteolin attenuated hepatic injury by alleviating cell morphology and decreasing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in vivo mice models, and increasing cell viability, downregulating arachidonate 12-lipoxygenase (ALOX12), cyclooxygenase-2 (COX-2) and P21 protein expression, suppressing apoptosis in vitro cell models. Luteolin also inhibited ferroptosis by stimulating glutathione peroxidase 4 (GPX4) and mitochondrial ferritin (FTMT) protein expression, increasing glutathione (GSH) content, and minimizing Fe2+ and malondialdehyde (MDA) levels. Solute carrier family 7a member 11 (SLC7A11) was identified to be a key regulatory gene that participated in luteolin attenuation of CCl4-induced hepatic injuries in HepG2 cells using Microarray assay. Functional study showed that SLC7A11 can alleviate hepatic injury and ferroptosis. CONCLUSION: Luteolin attenuated CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. SLC7A11 may serve as a novel alternative therapeutic target for hepatic injury.

FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage.

Nasal septal cartilages (NSCs) and mandibular condyle cartilages (MCCs) are two important cartilages for craniomaxillofacial development. However, the role of FLRT2 in the formation of NSCs and MCCs remains undiscovered. NSCs and MCCs were used for immunocytochemistry staining of collagen II, toluidine blue staining, and alcian blue staining. Quantitative reverse transcription­PCR and western blot were used to detect mRNA and protein expressions of FLRT2, N-cadherin, collagen II, aggrecan, and SOX9. Cell proliferation of MCCs and NSCs was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell counting kit­8 assay. Cell migration of MCCs and NSCs was examined by wound healing assay and Transwell. Chondrogenesis of MCCs and NSCs were similar in morphological characteristics, while different in cell proliferation, migration, and extracellular matrix. FLRT2 promotes the proliferation and migration of NSCs. There were up-regulation of N-cadherin and down-regulation of collagen II, aggrecan, and SOX9 in NSC with knock down FLRT2. The current study, as demonstrated by Xie et al., reveals that FLRT2 overexpression in Sprague-Dawley neonatal rats promotes the proliferation and migration of NSCs and MCCs, decreases N-cadherin while increases collagen II, aggrecan, and SOX9 in NSC and MCCs. Altogether, FLRT2 mediates chondrogenesis of NSCs and MCCs.

Emerging advances in delivery systems for mRNA cancer vaccines.

The success of lipid nanoparticles (LNPs) in treating COVID-19 promotes further research of mRNA vaccines for cancer vaccination. Aiming at overcoming the constraints of currently available mRNA carriers, various alternative nano-vectors have been developed for delivering tumor antigen encoding mRNA and showed versatility to induce potent anti-tumor immunity. The rationally designed nano-vaccines increase the immune activation capacity of the mRNA vaccines by promoting crucial aspects including mRNA stability, cellular uptake, endosomal escape and targeting of immune cells or organs. Herein, we summarized the research progress of various mRNA based nano-vaccines that have been reported for cancer vaccination, including LNPs, lipid enveloped hybrid nanoparticles, polymeric nanoparticles etc. Several strategies that have been reported for further enhancing the immune stimulation efficacy of mRNA nano-vaccines, including developing nano-vaccines for co-delivering adjuvants, combination of immune checkpoint inhibitors, and optimizing the injection routes for boosting immune responses, have been reviewed. The progress of mRNA nano-vaccines in clinical trials and the prospect of the mRNA vaccines for cancer vaccination are also discussed.

A study on the subchronic toxicity of triclocarban to the early-life development of oryzias melastigma and focused on the analysis of osmoregulatory regulation mechanisms.

Triclocarban (TCC), a novel antimicrobial agent found in personal care products, has been extensively detected in marine environments. However, research on the toxic effects of TCC on marine organisms remains inadequate. This study delved into the subchronic toxic effects of TCC on the early life stages of marine medaka (Oryzias melastigma, O. melastigma), revealing that TCC could reduce embryo heart rate and hatching rate while diminishing the survival rate of larvae. Biomarker assays indicated that TCC could inflict damage on the embryos' antioxidant and nervous systems. Transcriptomic analysis suggested that TCC could impact cell growth, reproduction, and various life processes, activating cancer signaling pathways, increasing the likelihood of cancer, and exerting toxic effects on the immune and osmoregulatory systems. To validate and enhance our understanding of TCC's unique toxic impact on the osmoregulatory system of O. melastigma, we conducted homology modeling and molecular docking analyses on the protein involved in osmoregulation. The study intuitively revealed the potential binding affinity of TCC to sodium/potassium-transporting ATPase subunit alph (ATP1A1), indicating its ability to disrupt osmotic balance in marine fish by affecting this target protein. In summary, the results of this study will further enhance our comprehension of the potential toxic effects and mechanisms of TCC on the early stages of marine fish, with a specific focus on its unique toxic effects in osmoregulation.

Comparative genomics analysis reveals sequence characteristics potentially related to host preference in Cryptosporidium xiaoi.

Cryptosporidium spp. are important diarrhea-associated pathogens in humans and livestock. Among the known species, Cryptosporidium xiaoi, which causes cryptosporidiosis in sheep and goats, was previously recognized as a genotype of the bovine-specific Cryptosporidium bovis based on their high sequence identity in the ssrRNA gene. However, the lack of genomic data has limited characterization of the genetic differences between the two closely related species. In this study, we sequenced the genomes of two C. xiaoi isolates and performed comparative genomic analysis to identify the sequence uniqueness of this ovine-adapted species compared with other Cryptosporidium spp. Our results showed that C. xiaoi is genetically related to C. bovis as shown by their 95.8% genomic identity and similar gene content. Consistent with this, both C. xiaoi and C. bovis appear to have fewer genes encoding mitochondrial metabolic enzymes and invasion-related protein families. However, they appear to possess several species-specific genes. Further analysis indicates that the sequence differences between these two Cryptosporidium spp. are mainly in 24 highly polymorphic genes, half of which are located in the subtelomeric regions. Some of these subtelomeric genes encode secretory proteins that have undergone positive selection. In addition, the genomes of two C. xiaoi isolates, identified as subtypes XXIIIf and XXIIIh, share 99.9% nucleotide sequence identity, with six highly divergent genes encoding putative secretory proteins. Therefore, these species-specific genes and sequence polymorphism in subtelomeric genes probably contribute to the different host preference of C. xiaoi and C. bovis.

Identification and evaluation of educational technology trends from 2004 to 2022: Evidence based on computers in human behavior and horizon report.

The increasing influence of technology on education has attracted considerable attention. This study aims to determine the current status and development trends of educational technologies. At first, we used COOC, HistCite, and VOSviewer to systematically review 1562 educational articles published in Computers in Human Behavior (CHB) from 2004 to 2022. Based on bibliometrics, this study identified publication trends, research forces, collaboration, key articles, and research themes. Then, we visualized the technologies predicted by 30 Horizon Reports and combined them with CHB educational research to evaluate the accuracy of the identified trends. The results revealed an immediate influence of AI technology, extended reality and digital resources on education, a moderate influence of educational tools and games, and a delayed influence of data management and maker technology. In addition, human psychology and behavior in technological environment may be important themes in the future. In conclusion, this study not only proposes a comparative analysis of leading reports and representative literature, but also provides guidance for future research and development in educational technology.

A systematic review of studies on stress during the COVID-19 pandemic by visualizing their structure through COOC, VOS viewer, and Cite Space software.

Background: The COVID-19 epidemic generated different forms of stress. From this period, there has been a remarkable increase in the quantity of studies on stress conducted by scholars. However, few used bibliometric analyses to focus on overall trends in the field. Purpose: This study sought to understand the current status and trends in stress development during COVID-19, as well as the main research drives and themes in this field. Methods: 2719 publications from the Web of Science(WOS) core repository on stress during COVID-19 were analyzed by utilizing Co-Occurrence (COOC), VOS viewer, and Cite Space bibliometric software. The overall features of research on stress during COVID-19 were concluded by analyzing the quantity of publications, keywords, countries, and institutions. Results: The results indicated that the United States had the largest number of publications and collaborated closely with other countries with each other. University of Toronto was the most prolific institution worldwide. Visualization and analysis demonstrated that the influence of stress during COVID-19 on the work, life, mental and spiritual dimensions is a hot research topic. Among other things, the frequency of each keyword in research on stress during COVID-19 increased from 2021 to 2022, and the researchers expanded their scope and study population; the range of subjects included children, nurses, and college students, as well as studies focusing on different types of stress, and emphasizing the handling of stress. Conclusion: Our findings reveal that the heat of stress research during COVID-19 has declined, and the main research forces come from the United States and China. Additionally, subsequent research should concern more on coping methods with stress, while using more quantitative and qualitative studies in the future.

Comprehensive analysis and experimental verification of the mechanism of action of T cell-mediated tumor-killing related genes in Colon adenocarcinoma.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy of the digestive tract. A new prognostic scoring model for colon adenocarcinoma (COAD) is developed in this study based on the genes involved in tumor cell-mediated killing of T cells (GSTTKs), accurately stratifying COAD patients, thus improving the current status of personalized treatment. METHOD: The GEO and TCGA databases served as the sources of the data for the COAD cohort. This study identified GSTTKs-related genes in COAD through single-factor Cox analysis. These genes were used to categorize COAD patients into several subtypes via unsupervised clustering analysis. The biological pathways and tumor microenvironments of different subgroups were compared. We performed intersection analysis between different subtypes to obtain intersection genes. Single-factor Cox regression analysis and Lasso-Cox analysis were conducted to establish clinical prognostic models. Two methods are used to assess the accuracy of model predictions: ROC and Kaplan-Meier analysis. Next, the prediction model was further validated in the validation cohort. Differential immune cell infiltration between various risk categories was identified via single sample gene set enrichment analysis (ssGSEA). The COAD model's gene expression was validated via single-cell data analysis and experiments. RESULT: We established two distinct GSTTKs-related subtypes. Biological processes and immune cell tumor invasion differed significantly between various subtypes. Clinical prognostic models were created using five GSTTKs-related genes. The model's risk score independently served as a prognostic factor. COAD patients were classified as low- or high-risk depending on their risk scores. Patients in the low-risk category recorded a greater chance of surviving. The outcomes from the validation cohort match those from the training set. Risk scores and several tumor-infiltrating immune cells were strongly correlated, according to ssGSEA. Single-cell data illustrated that the model's genes were linked to several immune cells. The experimental results demonstrated a significant increase in the expression of HOXC6 in colon cancer tissue. CONCLUSION: Our research findings established a new gene signature for COAD. This gene signature helps to accurately stratify the risk of COAD patients and improve the current status of individualized care.

Co-delivery of oxaliplatin prodrug liposomes with Bacillus Calmette-Guérin for chemo-immunotherapy of orthotopic bladder cancer.

To reduce recurrence rate after transurethral resection of bladder tumor, long-term intravesical instillations of Bacillus Calmette-Guérin (BCG) and/or chemotherapeutic drugs is the standard treatment for non-muscle invasive bladder carcinoma. However, the main challenges of intravesical therapy, such as short retention time and poor permeability of drugs in the bladder, often require frequent and high-dose administrations, leading to significant adverse effects and financial burden for patients. Aiming at addressing these challenges, we developed a novel approach, in which the cell-penetrating peptide modified oxaliplatin prodrug liposomes and a low-dose BCG were co-delivered via a viscous chitosan solution (LRO-BCG/CS). LRO-BCG/CS addressed these challenges by significantly improving the retention capability and permeability of chemotherapy agents across the bladder wall. Then, oxaliplatin triggered the immunogenic cell death, and the combination of BCG simultaneously further activated the systemic anti-tumor immune response in the MB49 orthotopic bladder tumor model. As a result, LRO-BCG/CS demonstrated superior anti-tumor efficacy and prolonged the survival time of tumor-bearing mice significantly, even at relatively low doses of oxaliplatin and BCG. Importantly, this combinational chemo-immunotherapy showed negligible side effects, offering a promising and well-tolerated therapeutic strategy for bladder cancer patients.

Transdermal Microneedles Alleviated Rheumatoid Arthritis by Inducing Immune Tolerance via Skin-Resident Antigen Presenting Cells.

Restoring immune tolerance is the ultimate goal for rheumatoid arthritis (RA) treatment. The most reported oral or intravenous injection routes for the immunization of autoantigens cause gastrointestinal side effects, low patient compliance, and unsatisfied immune tolerance induction. Herein, the use of a transdermal microneedle patch is for the first time investigated to codeliver CII peptide autoantigen and rapamycin for reversing immune disorders of RA. The immunized microneedles efficiently recruit antigen-presenting cells particularly Langerhans cells, and induce tolerogenic dendritic cells at the administration skin site. The tolerogenic dendritic cells further homing to lymph nodes to activate systemic Treg cell differentiation, which upregulates the expression of anti-inflammatory mediators while inhibiting the polarization of Th1/2 and Th17 T cell phenotypes and the expression of inflammatory profiles. As a result, the optimized microneedles nearly completely eliminate RA symptoms and inflammatory infiltrations. Furthermore, it is demonstrated that a low dose of rapamycin is crucial for the successful induction of immune tolerance. The results indicate that a rationally designed microneedle patch is a promising strategy for immune balance restoration with increased immune tolerance induction efficiency and patient compliance.

Exploring the mediating effect of creativity on the relationship between family capital and academic achievement in geography.

This study examined the relationship between family capital (FC) and academic achievement in geography along with the mediating role of creativity. The main objective was to determine if FC is a positive predictor of creativity and geographic achievement, and whether creativity completely or partially mediates the relationship between FC and geographic achievement. 1268 high school students participated in this study using the Family Capital Questionnaire (FCQ), the Innovative Behavior Scale (IBS), and students' class geography scores. SPSS 26 and Amos software were used to analyze the descriptive statistics and the correlation between the main variables. The mediating role of creativity was tested using PROCESS version 4. The correlation analyses showed that FC positively affected academic achievement in geography (ß = 0.382, SE = 0.019). Creativity also demonstrated a positive effect on geography academic achievement (ß = 0.376, SE = 0.022). The mediation analysis showed that creativity mediated and buffered the relationship between FC and academic achievement in geography. Thus, FC directly affected students' academic achievement in geography and indirectly affected their creativity. This clearly demonstrates that student characteristics and the external environment should be emphasized in geography education, while placing a strong focus on cultivating individual creativity.

hsa-miR-1301-3p Promotes the Proliferation and Migration of Nonsmall Cell Lung Cancer Cells and Reduces Radiosensitivity via Targeting Homeodomain-Only Protein Homeobox.

Background: There is increasing evidence that abnormal expression of microRNAs is involved in the occurrence and progression of tumors. In previous experiments, we found that the content of hsa-miR-1301-3p in tumor tissues of patients with nonsmall cell lung cancer (NSCLC) showed an obvious upward trend compared with that in normal tissues. We performed a detailed study on the impact and underlying mechanism of hsa-miR-1301-3p in NSCLC cells. Methods: The impact of hsa-miR-1301-3p on NSCLC cell proliferation, apoptosis, migration, and invasion was examined using colony formation, flow cytometry, modified Boyden chamber, and wound healing assays. Different doses of radiation were applied to NSCLC cells to investigate their sensitivity to radiotherapy. The potential target gene of hsa-miR-1301-3p was determined by dual-luciferase reporter assay and immunoblotting. Result: hsa-miR-1301-3p was upregulated in NSCLC tissues and cells. hsa-miR-1301-3p effectively promoted the rapid proliferation, migration, and invasion of NSCLC cells, while inhibiting apoptosis. It also induced radioresistance in NSCLC cells. hsa-miR-1301-3p targeted the homeodomain-only protein homeobox (HOPX) mRNA 3' untranslated region and inhibited its transcription in NSCLC cells. Exogenous HOPX overexpression antagonized the mechanism by which hsa-miR-1301-3p regulates NSCLC cell proliferation, metastasis, and apoptosis. Conclusions: hsa-miR-1301-3p plays an oncogenic role in the occurrence and development of NSCLC. By targeting HOPX, hsa-miR-1301-3p can not only promote the proliferation and metastasis of NSCLC cells, but also alleviate apoptosis and reduce radiosensitivity.

Clinical, biochemical characteristics and genotype-phenotype analysis of congenital hypothyroidism diagnosed by newborn screening in China.

BACKGROUND: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder worldwide. However, the underlying etiology remains unclear in most patients. METHODS: The newborn screening was performed for TSH in dried blood spots. Serum TSH, T3, T4, free T3(FT3) and free T4 (FT4) were detected for the recalled children. High-throughput sequencing were applied to detect 29 known CH genes. The statistical analyses were performed to analyze the differences between biochemical data, thyroid volume, clinical prognosis and genetic results for 97 patients who had one or more variants in CH related genes. RESULTS: DUOX2 gene had the highest variant rate, followed by TG, TPO and TSHR gene. The "DUOX2 biallelic variants" group was associated with "Goiter", while "DUOX2 monoallelic variants" group was associated with "Agenesis". In addition, the TSH levels and initial L-T4 dose were significantly higher in "TPO biallelic variants" group than those in "DUOX2 and TSHR biallelic variants" groups. CONCLUSIONS: Our study showed dyshormonogenesis (DH) might be the leading pathophysiology of CH in Chinese populations. DUOX2 gene mostly caused goiter, but also could be associated with hypoplasia. TPO might play a more irreplaceable role than DUOX2. The digenic variants combination indicated the complexity of genetic etiology in CH.

Luteolin Alleviates Liver Fibrosis in Rat Hepatic Stellate Cell HSC-T6: A Proteomic Analysis.

Background: Traditional Chinese medicine (TCM) with single or compound materials is an effective cure for liver fibrosis. Hepatic stellate cells (HSCs) play a key role in liver fibrosis pathology and have become a novel drug target for this condition. Methods: CCK-8 assay was used to determine the cytotoxicity of four components, SYPA, HSYPA, Apigenin, and Luteolin, from Deduhonghua-7 powder on HSC-T6 cells. Transforming Growth Factor ß 1 (TGFß1)-induced fibrotic cell model and CCI4-induced fibrotic rat model were constructed, the expression of fibrosis-related genes, the pathological changes and serum biochemical markers were evaluated. Proteomic analysis was performed to determine the mechanism by which luteolin attenuated liver fibrosis, which were further confirmed by Western blot. Results: Luteolin attenuates liver fibrosis in HSC-T6 cells and luteolin decreases the liver fibrosis index level in vivo. A total of 5000 differentially expressed proteins (DEPs) were obtained using proteomic analysis. KEGG analysis found that DEPs were concentrated in various metabolic pathways, including DNA replication and repair and lysosomal signaling. GO analysis showed that molecular functions included the activity and binding of various enzymes, related cellular components included the extracellular space, lysosomal lumen, mitochondrial matrix, and nucleus, and biological processes included collagen organization and biosynthesis and the positive regulation of cell migration. Western blot results showed that CCR1, CD59, and NAGA were downregulated in TGFß1 treatment, while upregulated both in Lut2 and Lut10 treatment. Meanwhile, eight proteins, ITIH3, MKI67, KIF23, DNMT1, P4HA3, CCDC80, APOB, FBLN2, that were upregulated in TGFß1 treatment, while downregulated both in Lut2 and Lut10 treatment. Conclusion: Luteolin was shown to have a strong protective effect on liver fibrosis. CCR1, CD59, and NAGA may promote liver fibrosis while ITIH3, MKI67, KIF23, DNMT1, P4HA3, CCDC80, APOB, and FBLN2 may facilitate protection against fibrosis.

A MnAl double adjuvant nanovaccine to induce strong humoral and cellular immune responses.

At present, the most widely used aluminum adjuvants have poor ability to induce effective Th1 type immune responses. Existing evidence suggests that manganese is a potential metal adjuvant by activating cyclic guanosine phospho-adenosine synthase (cGAS)-interferon gene stimulator protein (STING) signaling pathway to enhance humoral and cellular immune response. Hence, the effective modulation of metal components is expected to be a new strategy to improve the efficiency of vaccine immunization. Here, we constructed a manganese and aluminum dual-adjuvant antigen co-delivery system (MnO2-Al-OVA) to enhance the immune responses of subunit vaccines. Namely, the aluminum hydroxide was first fused on the surface of the pre-prepared MnO2 nanoparticles, which were synthesized by a simple redox reaction with potassium permanganate (KMnO4) and oleic acid (OA). The engineered MnO2-Al-OVA could remarkably promote cellular internalization and maturation of dendritic cells. After subcutaneous vaccination, MnO2-Al-OVA rapidly migrated into the lymph nodes (LNs) and efficiently activate the cGAS-STING pathway, greatly induced humoral and cellular immune responses. Of note, our findings underscore the importance of coordination manganese adjuvants in vaccine design by promoting the activation of the cGAS-STING-IFN-I pathway. With a good safety profile and facile preparation process, this dual-adjuvant antigen co-delivery nanovaccine has great potential for clinical translation prospects.

Harnessing matrix stiffness to engineer a bone marrow niche for hematopoietic stem cell rejuvenation.

Hematopoietic stem cell (HSC) self-renewal and aging are tightly regulated by paracrine factors from the bone marrow niche. However, whether HSC rejuvenation could be achieved by engineering a bone marrow niche ex vivo remains unknown. Here, we show that matrix stiffness fine-tunes HSC niche factor expression by bone marrow stromal cells (BMSCs). Increased stiffness activates Yap/Taz signaling to promote BMSC expansion upon 2D culture, which is largely reversed by 3D culture in soft gelatin methacrylate hydrogels. Notably, 3D co-culture with BMSCs promotes HSC maintenance and lymphopoiesis, reverses aging hallmarks of HSCs, and restores their long-term multilineage reconstitution capacity. In situ atomic force microscopy analysis reveals that mouse bone marrow stiffens with age, which correlates with a compromised HSC niche. Taken together, this study highlights the biomechanical regulation of the HSC niche by BMSCs, which could be harnessed to engineer a soft bone marrow niche for HSC rejuvenation.

The mediating effect of geospatial thinking on the relationship between family capital and academic achievement in geography.

Purpose: Family environment has the major impact on children's academic development. The aim of this study was to research the relationship between family capital and academic achievement in geography. Further, geospatial thinking, as a form of spatial thinking focusing on the scale of the geographical environment, is closely related to family environment and academic achievement in geography. Thus, the study was more specifically to apply a mediation model to explore the potential mediating role of geospatial thinking. Methods: A total of 1,037 upper-secondary-school students in Western China were surveyed using t the Family Capital Questionnaire and the Geospatial Thinking Test Questionnaire. SPSS (version 26.0) was used for descriptive statistical analysis and correlation analysis. The PROCESS plug-in (version 4.0) was used to test the mediating effect of geospatial thinking. Results: (1) The correlation analysis showed that family capital has a positive effect on academic achievement in geography and is related to geospatial thinking. Moreover, geospatial thinking exerts a positive effect on academic achievement in geography. (2) The results of mediation analysis indicated that geospatial thinking plays mediating and buffering roles in the relationship between family capital and academic achievement in geography after controlling for family residence and gender. The direct and indirect effects accounted for 75.32% and 24.68% of the total effect, respectively. Conclusion: The results indicated that family capital not only affected academic achievement in geography directly but also indirectly through geospatial thinking. This finding provides some ideas for the development of geography education, which suggests that geography educators need to pay more attention to the influence of the family environment on students' geography learning in curriculum design and teaching processes. Also, the mediating role of geospatial thinking further uncovers the mechanisms underlying the academic achievement in geography. Therefore, it is necessary to focus on both students' family capital and geospatial thinking in the process of geography learning, and carry out more geospatial thinking training to improve academic achievement in geography.

Degradation of Aflatoxin B1 in Moldy Maize by Pseudomonas aeruginosa and Safety Evaluation of the Degradation Products.

Aflatoxin B1 (AFB1) is the most harmful mycotoxin commonly found in food and feed. Pollution from AFB1 causes serious economic and health issues worldwide because it causes strong mutagenicity and carcinogenicity in humans and animals. In this study, Pseudomonas aeruginosa was used to degrade AFB1 in moldy maize, and the safety of this biological method was investigated using genotoxicity and cytotoxicity tests. Using response surface methodology, we established the optimal conditions for degrading AFB1 by the fermentation supernatant of P. aeruginosa. Under these conditions, the degradation rate of AFB1 reached 99.67%. Furthermore, the Ames mutagenicity test showed that AFB1 treated with P. aeruginosa fermentation supernatant for 72 h was not mutagenic. CCK-8 cell assay showed that AFB1 cytotoxicity was significantly reduced after degradation. Overall, our findings show that the fermentation supernatant of P. aeruginosa may be a good candidate for biodegradation of AFB1.