Huangqin Tang Alleviates Colitis-associated Colorectal Cancer via Amino Acids Homeostasisand PI3K/AKT/mTOR Pathway Modulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Tang (HQT), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of inflammatory bowel diseases. It has been reported that HQT exerts antitumor effects on colitis-associated colorectal cancer (CAC). However, the mechanism by which HQT interferes with the inflammation-to-cancer transformation remains unclear. AIMS OF THE STUDY: The purpose of this study was to dynamically evaluate the efficacy of HQT in alleviating or delaying CAC and to reveal the underlying mechanism. METHODS: We established a mouse model of CAC using azoxymethane combined with 1.5% dextran sodium sulphate. The efficacy of HQT was evaluated based on pathological sections and serum biochemical indices. Subsequently, amino acids (AAs) metabolism analyses were performed using ultra-performance liquid chromatography-tandem mass spectrometry, and the phosphatidylinositol 3 kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway was detected by western blotting. RESULTS: The data demonstrated that HQT could alleviate the development of CAC in the animal model. HQT effectively reduced the inflammatory response, particularly interleukin-6 (IL-6), in the inflammation induction stage, as well as in the stages of proliferation initiation and tumorigenesis. During the proliferation initiation and tumorigenesis stages, immunohistochemistry staining showed that the expression of the proliferation marker Ki67 was reduced, while apoptosis was increased in the HQT group. Accordingly, HQT substantially decreased the levels of specific AAs in the colon with CAC, including glutamic acid, glutamine, arginine, and isoleucine. Furthermore, HQT significantly inhibited the activated PI3K/AKT/mTOR pathway, which may contribute to suppression of cell proliferation and enhancement of apoptosis. CONCLUSION: HQT is effective in alleviating and delaying the colon "inflammation-to-cancer". The mechanism of action may involve HQT maintained AAs metabolism homeostasis and regulated PI3K/AKT/mTOR pathway, so as to maintain the balance between proliferation and apoptosis, and then interfere in the occurrence and development of CAC.

Fluid inertia controls mineral precipitation and clogging in pore to network-scale flows.

Mineral precipitation caused by fluid mixing presents complex control and predictability challenges in a variety of natural and engineering processes, including carbon mineralization, geothermal energy, and microfluidics. Precipitation dynamics, particularly under the influence of fluid flow, remain poorly understood. Combining microfluidic experiments and three-dimensional reactive transport simulations, we demonstrate that fluid inertia controls mineral precipitation and clogging at flow intersections, even in laminar flows. We observe distinct precipitation regimes as a function of Reynolds number (Re). At low Reynolds numbers (Re < 10), precipitates form a thin, dense layer along the mixing interface, which shuts precipitation off, while at high Reynolds numbers (Re > 50), strong three-dimensional flows significantly enhance precipitation over the entire intersection, resulting in rapid clogging. When injection rates from two inlets are uneven, flow symmetry-breaking leads to unexpected flow bifurcation phenomena, which result in enhanced concurrent precipitation in both downstream channels. Finally, we extend our findings to rough channel networks and demonstrate that the identified inertial effects on precipitation at the intersection scale are also present and even more dramatic at the network scale. This study sheds light on the fundamental mechanisms underlying mixing-induced mineral precipitation and provides a framework for designing and optimizing processes involving mineral precipitation.

Identification and functional analysis of the hub Ferroptosis-Related gene EZH2 in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a common microvascular complication and one of the main causes of death in diabetes. Ferroptosis, an iron-dependent mode of cell death characterized by lipid ROS accumulation, was found to be associated with a number of diseases and has great potential for kidney diseases. It has great value to identify potential ferroptosis-related genes and their biological mechanisms in DKD. METHODS: We obtained the GSE30122 dataset from Gene Expression Omnibus (GEO) database and ferroptosis-related genes from the Ferrdb database. After differential expression analysis, and three machine learning algorithms, the hub ferroptosis-related gene EZH2 was identified. In order to investigate the function of EZH2, Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA) and single cell analysis were conducted. The expression of EZH2 was validated in DKD patients, HK-2 cell models and DKD mouse models. EZH2 knockdown HK-2 cells and HK-2 cells treated with GSK126 were performed to verify whether EZH2 affected ferroptosis in DKD. CHIP assay was used to detect whether EZH2 regulated ferroptosis by suppressing SLC7A11. Molecular docking was performed to explore EZH2 and four traditional Chinese medicine (Sennoside A, Berberine, Umbelliferone, Platycodin D) related to ferroptosis in DKD treatment. RESULTS: According to the GSE30122 dataset in GEO and ferroptosis-related genes from the Ferrb database, we obtained the hub ferroptosis-related gene EZH2 in DKD via diversified machine learning methods. The increasing of EZH2 expression was shown in single cell analysis, DKD patients, DKD mouse models and high glucose induced DKD cell models. Further study showed that EZH2 knockdown and inhibition can alleviate HG-induced ferroptosis in vitro. CHIP assay showed EZH2-mediated epigenetic silencing regulated the expression of SLC7A11. Molecular docking results showed that EZH2 had strong binding stability with Sennoside A, Berberine, Umbelliferone, and Platycodin D. CONCLUSION: Overall, our data shouwed that histone H3K27 methyltransferase EZH2 could regulate the renal tubular epithelial cell ferroptosis by suppressing SLC7A11 in DKD, which may serve as a credible reliable indicator for diagnosing DKD and a potential target for treatment.

Altered metabolome and microbiome features provide clues in predicting recurrence of ulcerative colitis.

PURPOSE: Many studies have shown that the imbalance of the intestinal flora and metabolite can lead to the development of ulcerative colitis (UC), but their role in recurrent-UC is still unclear. We studied the intestinal flora and metabolites associated with recurrent-UC to elucidate the mechanism and biomarkers of recurrent-UC. METHODS: Ulcerative colitis (UC) models in active, remission, and recurrence stages were established, and the abundance of intestinal flora was determined by 16 S rRNA sequencing. The changes in the metabolites present in feces and serum were analyzed by UPLC-MS/MS. RESULTS: We identified 24 metabolites in feces and serum, which might be used as diagnostic and predictive biomarkers of recurrent-UC. The dominant flora of recurrent-UC included Romboutsia, UCG-005, etc. The results of a network analysis found that long-chain fatty acids and phenylalanine were strongly correlated with Firmicutes and Proteobacteria, which indicated that the recurrence of UC might be closely related to metabolites and microorganisms. CONCLUSION: The changes in intestinal microbiota and metabolites are closely related to the development of UC. Microbiota is an important inducer of UC, which can regulate metabolites through the 'microorganism-gut-metabolite' axis. It may provide a new method for the prediction and treatment of UC.

Corrigendum: Teaching programming and computational thinking in early childhood education: a case study of content knowledge and pedagogical knowledge.

[This corrects the article DOI: 10.3389/fpsyg.2023.1252718.].

Teaching programming and computational thinking in early childhood education: a case study of content knowledge and pedagogical knowledge.

Programming and computational thinking (CT) have been progressively incorporated into early childhood education to prepare children for the digital age. However, little is known about the content knowledge (CK) and pedagogical knowledge (PK) possessed by early childhood teachers in this domain. To address this gap, we conducted a case study of an early childhood teacher in China who had experience developing and implementing an unplugged programming and CT curriculum. The triangulation of data sources was established to collect evidence from videotaped observations, interviews, and lesson plans. For the CK, analysis of these findings revealed that the teacher had a more robust understanding of CT concepts (e.g., sequences, conditionals, and loops) compared to CT practices (e.g., decomposition, debugging) and CT perspectives (e.g., perseverance, choices of conduct). In terms of PK, the teacher could apply the general pedagogical knowledge but was relatively weak in using content-specific pedagogical knowledge. As the first endeavor to investigate an early childhood teacher's CK and PK in teaching programming and CT, this study provides significant implications for improving teachers' professional knowledge and teaching effectiveness in this burgeoning area.

The integrative role of parenting styles and parental involvement in young children's science problem-solving skills.

Introduction: How parents encourage and engage young children to learn science and solve scientific problems remains an understudied issue. Parenting styles have been widely studied and found to be associated with children's various developmental outcomes. However, there is a dearth of research linking parenting styles to early science skills which build from both cognitive and social abilities. This cross-sectional study intended to pilot test a mediation model of parental involvement in the relationship between parenting styles and children's science problem-solving skills. Methods: A total of 226 children (M = 62.10 months, SD = 4.14, 108 girls) and their parents was recruited from five kindergartens in Fuzhou in China by adopting stratified random sampling. All parents completed the Demographics Questionnaire, the Parenting Style and Dimension Questionnaire, and the Chinese Early Parental Involvement Scale. Each child was tested with the Picture Problem Solving Task. Pearson's correlation analysis and intermediary effect analysis were conducted using IBM SPSS 25 in data analysis. Results and discussion: Parental involvement had a significant mediating effect in the bidirectional associations between parenting styles and children's science problem-solving skills. The findings suggested that children with higher science problem-solving skills were likely to be raised by parents who were employing a flexible (i.e., authoritative) parenting style and had more involvement in children's formal and informal learning environments, while children's higher levels of science problem-solving skills predicted a higher level of parental involvement and a more flexible parenting style.

Stem cell-derived exosomal MicroRNAs: Potential therapies in diabetic kidney disease.

The diabetic kidney disease (DKD) is chronic kidney disease caused by diabetes and one of the most common comorbidities. It is often more difficult to treat end-stage renal disease once it develops because of its complex metabolic disorders, so early prevention and treatment are important. However, currently available DKD therapies are not ideal, and novel therapeutic strategies are urgently needed. The potential of stem cell therapies partly depends on their ability to secrete exosomes. More and more studies have shown that stem cell-derived exosomes take part in the DKD pathophysiological process, which may offer an effective therapy for DKD treatment. Herein, we mainly review potential therapies of stem cell-derived exosomes mainly stem cell-derived exosomal microRNAs in DKD, including their protective effects on mesangial cells, podocytes and renal tubular epithelial cells. Using this secretome as possible therapeutic drugs without potential carcinogenicity should be the focus of further research.

Transcriptomics and experimental validation-based approach to understand the effect and mechanism of Huangqin tang interfeience with colitis associated colorectal cancer.

Context: Chronic inflammation is usually caused by persistent irritation or uncontrolled infection and is characterized by ongoing tissue damage, injury-induced cellular proliferation and tissue repair. Colitis-associated colorectal cancer (CAC) isone of the classic examples of tumors that are tightly related to chronic inflammation. Background: To investigated the key pharmacodynamic genes of HQT interventions in CAC by using transcriptome predictions and experiments.Materials & Methods: We used the azoxymethane/dextran sodium sulfate method to induce the mice CAC model. After preventive administration of HQT to the mice model, colonic tissues were taken for transcriptome sequencing and the transcriptome results were then experimentally validated using quantitative Real-Time PCR technique. Results: Transcriptome sequencing revealed that the effect of the mechanism of HQT on the CAC mice model maybe related to its inhibition of accelerated epithelial mesenchymal transition and induction of pyroptosis. The levels of Matrix-metalloproteinases such as MMP-2, MMP-9 were significantly reduced in CAC mice treated with HQT; The mRNA expression for Krt17, App, CD44 and WNT pathway related sites such as Lrrc15, Cldn-1, Mpc1, Agr2 which are related factors affecting the epithelial mesenchymal transition were significantly reduced in CAC mice treated with HQT; the aberrant mRNA expression of inflammasome components that drive pyroptosis, including Nlrp3, Caspase-1, ASC, GSDMD and its mediated product IL-18 have been improved. Conclusions: Our findings provide preliminary clarification that inhibiting the progression of CAC by using HQT is effective, the mechanism of action may be relatedto the inhibition of epithelial mesenchymal transition and induction of pyroptosis during tumorigenesis.

Development and validation of the STEM Teaching Self-efficacy Scale (STSS) for early childhood teachers.

The preparation of STEM (science, technology, engineering, and mathematics) teachers for early childhood education (ECE) has clearly become an important issue in recent years. Teacher efficacy can lead to changes in professional beliefs toward and teaching practices in STEM. In this study, we developed the STEM Teaching Self-efficacy Scale (STSS) and validated it in a sample of 225 pre-service and 193 in-service early childhood teachers in Zhejiang, China. Results indicated preliminary evidence of reliability and validity of the two factors of STSS: Pedagogy Self-efficacy and Content Self-efficacy. Items were constructed based on literature and selected through factor analysis to cover the scope of self-efficacy on the behaviors of STEM teaching and ensure the content and construct validity of the scale. Scores on the STSS subscales were positively correlated with early childhood teachers' working status, age, occupational commitment, and interest in ECE, showing evidence of its criterion validity. The STSS provides a professionally and psychologically meaningful tool for evaluating early childhood teachers' efficacy beliefs about teaching STEM, which would help obtain evidence for the optimal design of STEM teacher training programs.

Infection Microenvironment-Sensitive Photothermal Nanotherapeutic Platform to Inhibit Methicillin-Resistant Staphylococcus aureus Infection.

Methicillin-resistant Staphylococcus aureus (MRSA) can induce multiple inflammations. The biofilm formed by MRSA is resistant to a variety of antibiotics and is extremely difficult to cure, which seriously threatens human health. Herein, a nanoparticle encapsulating berberine with polypyrrole core and pH-sensitive shell to provide chemo-photothermal dual therapy for MRSA infection is reported. By integrating photothermal agent polypyrrole, berberine, acid-degradable crosslinker, and acid-induced charge reversal polymer, the nanoparticle exhibited highly efficient MRSA infection treatment. In normal uninfected areas and bloodstream, nanoparticles showed negatively charged, demonstrating high biocompatibility and excellent hemocompatibility. However, once arriving at the MRSA infection site, the nanoparticle can penetrate and accumulate in the biofilm within 2 h. Simultaneously, berberine can be released into biofilm rapidly. Under the combined effect of photothermal response and berberine inhibition, 88.7% of the biofilm is removed at 1000 µg mL-1 . Moreover, the nanoparticles have an excellent inhibitory effect on biofilm formation, the biofilm inhibition capacity can reach up to 90.3%. Taken together, this pH-tunable nanoparticle can be employed as a new generation treatment strategy to fight against the fast-growing MRSA infection.

School and Teacher Information, Communication and Technology (ICT) readiness across 57 countries: The alignment optimization method.

This study investigated the measurement invariance of school and teacher Information, Communication and Technology (ICT) readiness among 57 countries that participated in the Program in International Student Assessment (PISA) 2018 assessment. School and teacher ICT readiness scale is 11-item scale with two subfactors: school ICT readiness and teacher ICT readiness subscales (Bozkus, International Online Journal of Education and Teaching, 8(3), 1560-1579, 2021). With the novel alignment optimization method, we revealed that the school ICT readiness subscale was invariant for unbiased country comparisons but overall noninvariance was identified for the teacher ICT readiness subscale. Additionally, the rank of the school ICT readiness factor means indicated that Singapore, Sweden, B-S-J-Z (regions of China), United Arab Emirates and United States were among the top league, while countries like Indonesia, Poland, Ireland in between, and Japan, Mexico, Colombia, Argentina and Brazil ranked comparatively the lowest. Measures of school location, school type and class size further confirmed the validity of the school ICT readiness subscale. It was expected that the study would enhance our understanding of school and teacher ICT readiness across countries with the application of an alternative alignment optimization approach in examining ICT related scales.

Interfacial Microstructure and Mechanical Properties of 1Cr18Ni9Ti/1Cr21Ni5Ti Stainless Steel Joints Brazed with Mn-Based Brazing Filler.

The problem of stainless steel brazing is still the focus of scientific research. In this work, the Mn-based brazing filler was used to braze 1Cr18Ni9Ti and 1Cr21Ni5Ti stainless steel. The typical microstructure of the 1Cr18Ni9Ti/1Cr21Ni5Ti joint was analyzed in detail, and the interface structure of the joint was determined to be 1Cr18Ni9Ti/Mn(s, s)/1Cr21Ni5Ti. The brazing temperature and holding time were shown to have a great influence on the microstructure of the brazed joint. The tensile strength of brazed joints first increased and then decreased with the rising of the brazing temperature and the holding time. The maximum tensile strength was 566 MPa when the joints were brazed at 1125 °C for 15 min. The diffusion of Mn and Cr was an important factor affecting the quality of the joints. The diffusion distances of Mn and Cr at different brazing temperatures and holding times were measured, and the diffusion activation energy and diffusion coefficient were achieved by the Arrhenius equation.

Pharmacokinetics and metabolites of glycosides and lignans of the stem bark of Magnolia officinalis in functional dyspepsia and normal rats using liquid chromatography-tandem mass spectrometry.

The stem bark of Magnolia officinalis is a traditional Chinese medicine for the treatment of abdominal distention and functional dyspepsia. The pharmacokinetics of three glycosides (magnoloside A, magnoloside B, and syringin) and two lignans (honokiol and magnolol) in both normal and functional dyspepsia rats were firstly investigated by ultra-performance liquid chromatography-triple quadrupole mass spectrometry method and the influences of the coexisting compounds on the pharmacokinetic parameters of honokiol and magnolol were also studied. It was found that all of the five target compounds were quickly absorbed and eliminated in both normal and functional dyspepsia rats, while, their residence time was significantly decreased in pathological states except magnoloside A. The coexisting compounds in the stem bark of M. officinalis significantly reduced absorption and increased elimination of honokiol in vivo. It's worth noticing that the volume of distribution of lignan was quite lower than that of a glycoside. Moreover, the metabolic profiling of magnoloside A, honokiol, and magnolol in vivo was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method, from which three prototypes were identified and 35 metabolites were putatively characterized, and 18 unknown metabolites were reasonably characterized for the first time. The results indicated that sulfation and glucuronidation were the main metabolic pathways of honokiol and magnolol.

Huangqin Tang Interference With Colitis Associated Colorectal Cancer Through Regulation of Epithelial Mesenchymal Transition and Cell Cycle.

Background: Although the exact molecular mechanisms of colitis-associated colorectal cancer are not fully understood, the chronic inflammation was positively correlated with tumorigenesis. The traditional Chinese medicine botanical formulation Huangqin Tang has significant anti-inflammatory effects. We investigated whether HQT can ameliorate the progression of inflammation to cancer through its anti-inflammatory effects by using relevant predictions and experiments. Methods: We used the azoxymethane/dextran sodium sulfate method to induce the mice colitis-associated colorectal cancer model. After preventive administration of Huangqin Tang to the mice model, colonic tissues were taken for quantitative proteomic analysis of tandem mass tags, and the proteomic results were then experimentally validated using the molecular biology approach. Results: Proteomic screening revealed that the effect of the mechanism of Huangqin-Tang on the colitis-associated colorectal cancer mice model may be related to infinite replication which demonstrated abnormal G1/S checkpoint and epithelial mesenchymal transition acceleration. The levels of inflammatory factors such as interleukin-1α, interleukin-1ß, interleukin-6, and tumor necrosis factor-α were significantly reduced in colitis-associated colorectal cancer mice treated with Huangqin Tang; the aberrant expression of G1/S checkpoint-associated sites of cell cycle protein-dependent kinase 4, D1-type cyclins, and dysregulation of related sites of the WNT pathway which are most related to the acceleration of the epithelial mesenchymal transition process including WNT3A, ß-catenin, E-cadherin, and glycogen synthase kinase 3ß has been improved. Conclusion: Reducing inflammation and thus inhibiting the progression of colitis-associated colorectal cancer by using Huangqin-Tang is effective, and the mechanism of action may be related to the inhibition of uncontrolled proliferation during tumorigenesis. In the follow-up, we will conduct a more in-depth study on the relevant mechanism of action.

Automatic Real-Time Space Registration Application for Simulating Dental and Maxillofacial Surgery.

ABSTRACT: Real-time surgical navigation systems are important for preoperative planning and intraoperative navigation. Automatic preoperative multimodal data registration and postoperative spatial registration are extremely crucial in such surgical navigation systems. However, existing automatic multimodal data registration methods have extremely limited application scope due to the lack of accuracy and speed. In addition, the registration results obtained by existing methods are practically lacking and are rarely applied in clinics. To address the above issues, this paper proposes a novel real-time teeth registration algorithm with computed tomography (CT) data and optical tracking scanning data. The proposed method is based on the weighted iterative closest point (ICP) algorithm with 3 improvements: (1) the multilayer spherical point set is generated inside the laser scanning marker sphere, (2) the weight decreases from inside to outside layer by layer, and (3) the weight of the voxel center point set is combined with the CT data of the marker sphere. Specifically, the proposed iCP registration method can overcome the limitation of surface point set registration and tackle the problem of high surface deformity of laser scanning marker spheres. For the registration result of CT and scanning data, the authors employ the real-time spatial registration algorithm based on optical tracking to complete the navigation of the simulated surgical instruments on the multimodal fusion image. The experimental results show that the proposed ICP algorithm reduces the mean square error by 1 order of magnitude and that our method has strong practical value.

Developing a Toothbrushing Visual Pedagogy (TBVP) for Preschool Children with Autism Spectrum Disorder.

Visual pedagogy and social stories have been widely used to assist children with Autism Spectrum Disorder (ASD) in learning various skills. A toothbrushing visual pedagogy (TBVP) was developed adapting existing toothbrushing social stories for children with ASD. This TBVP consists of 13 toothbrushing steps with scripts describing the toothbrushing technique. To evaluate its feasibility, a review panel was formed to provide feedback on the TBVP and three other published toothbrushing social stories. Effectiveness of the TBVP was further evaluated among 119 preschool children with ASD with significant improvements in toothbrushing skills observed at 3-month and 6-month follow-ups. It is concluded that TBVP is a feasible and an effective educational means that assists children with ASD in learning toothbrushing skills.

[Research progress on culture technologies,chemical components,and pharmacological activities of Saussurea involucrata cells].

Saussurea involucrata,a traditional Chinese medicinal material,is effective in the treatment of rheumatoid arthritis with cold-dampness blockage syndrome,cold pain in lower abdomen,and menstrual irregularities. However,due to the specific habitat,low natural reproduction rate,slow growth,and overexploitation,it is at the high risk of extinction. S. involucrata cells can be obtained through callus culture,suspension culture,and hairy root culture. This study highlighted the influences of reactor type,culture system,precursor,elicitor type, and light wavelength on the suspension culture of S. involucrate cells. The chemical components of S. involucrata cells mainly include phenylpropanoids,flavonoids,lignans,and steroids,among which phenylpropanoids are the most abundant. S. involucrata cells have multiple pharmacological activities of anti-inflammation,analgesia,activating blood and resolving stasis,immunoregulation,increasing bone density,lowering blood lipids,anti-hypoxia,anti-exercise fatigue,anti-radiation,anti-obesity,and anti-oxidation. Moreover,it has the potential of treating aplastic anemia. This study reviews the cell culture technologies,chemical components,and pharmacological activities of S. involucrata cells,laying a basis for the further research,development,and utilization.

Micromodel Studies of Surfactant Flooding for Enhanced Oil Recovery: A Review.

Micromodels have been widely used to visualize surfactant flooding, which provides new insights into understanding pore-scale events during displacement. In this review, recent advances in micromodel studies of surfactant flooding are briefly summarized. The mechanisms of surfactant flooding as demonstrated by micromodel studies are presented, as well as pore-scale findings that cannot be captured by traditional coreflood methods.