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With the continuous development of education informatization, STEM education has become the global trend of education. Project-based learning is widely discussed and applied as a learning method suitable for combination with STEM education concept. Currently, the problem of "how to teach" in STEM education is widely focused on two typical teaching methods, namely problem-based learning and project-based learning. Project-based learning is also learner-centered and tends to comprehensively apply multidisciplinary knowledge, which attracts more attention. Based on the analysis of the impact of combining applied subjects and STEM education with project-based learning on students and other aspects, this paper proposes the connotation of middle school information technology project-based learning under STEM education concept and how to practice the application of project-based learning in junior high school information technology classrooms under STEM education concept in order to promote the further development of STEM education.

Background: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. Methods: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. Results: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. Conclusion: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.

Abstract Background Giardia duodenalis is a common enteric protozoan parasite that is categorized into eight assemblages (A–H). In particular, assemblages A and B are zoonotic, capable of infecting both humans and animals worldwide, resulting in significant economic losses and public health challenges in epidemic regions. Thus, the development of rapid, accurate and non-laboratory-based diagnostic methods for infected animals is crucial for the effective prevention and control of giardiasis. Recent advancements in clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated (Cas) protein (Cas12a) systems allow promising avenues for nucleic acid detection, characterized by their high flexibility, sensitivity and specificity. Methods Combined recombinase polymerase amplification and CRISPR/Cas12a systems were combined and used as end-point diagnostic methods (termed REPORT) to detect G. duodenalis assemblage A and B. The diagnostic results can be observed by fluorescence readouts with the naked eye under blue light or colorimetric signals using a lateral flow strip (LFS). Results The limit of detection (LOD) of the REPORT‑based G. duodenalis assemblage A detection was 2.04 CFU/ml and 10 trophozoites per gram (TPG), and the LOD of assemblage B was 1.1 CFU/ml and 10 cysts per gram (CPG). The REPORT‑based G. duodenalis assemblage A and assemblage B detection methods have strong specificity and no cross-reactivity with other assemblages of G. duodenalis or common enteric parasitic protozoa and have excellent performance in clinical sample detection. Conclusions This study presents a novel strategy for the direct identification of G. duodenalis assemblages A and B, requiring neither highly trained personnel nor costly specialized equipment. Graphical Abstract

Abstract Background Tumor Mutational Burden (TMB) have emerged as pivotal predictive biomarkers in determining prognosis and response to immunotherapy in colorectal cancer (CRC) patients. While Whole Exome Sequencing (WES) stands as the gold standard for TMB assessment, carry substantial costs and demand considerable time commitments. Additionally, the heterogeneity among high-TMB patients remains poorly characterized. Methods We employed eight advanced machine learning algorithms to develop gene-panel-based models for TMB estimation. To rigorously compare and validate these TMB estimation models, four external cohorts, involving 1,956 patients, were used. Furthermore, we computed the Pearson correlation coefficient between the estimated TMB and tumor neoantigen levels to elucidate their association. CD8+ tumor-infiltrating lymphocyte (TIL) density was assessed via immunohistochemistry. Results The TMB estimation model based on the Lasso algorithm, incorporating 20 genes, exhibiting satisfactory performance across multiple independent cohorts (R2 ≥ 0.859). This 20-gene TMB model proved to be an independent prognostic indicator for the progression-free survival (PFS) of CRC patients (p = 0.001). DNAH5 mutations were associated with a more favorable prognosis in high-TMB CRC patients, and correlated strongly with tumor neoantigen levels and CD8+ TIL density. Conclusions The 20-gene model offers a cost-efficient approach to precisely estimating TMB, providing prognosis in patients with CRC. Incorporating DNAH5 within this model further refines the categorization of patients with elevated TMB. Utilizing the 20-gene model facilitates the stratification of patients with CRC, enabling more precise treatment planning.

Abstract To explore the relationship between morphological and hemodynamic parameters, baseline characteristics, and long-term outcomes in patients with moyamoya disease (MMD) using a computational fluid dynamics model. We retrospectively reviewed 129 patients at Beijing Tiantan hospital between July 2020 and December 2021. Perioperative clinical variables and Suzuki stage were recorded. Logistic regression analysis was employed to identify the risk factors for unfavorable long-term outcomes. The association between morphological, CT perfusion parameters, hemodynamic parameters and the Suzuki stage, clinical variables of MMD was also analyzed. Patients with high relative Wall Shear Stress (rWSS) were older and had more cases with higher Suzuki stage and worse follow-up mRS scores (p

Abstract This study aimed to confirm the hypothesis that continuous ACB (CACB) combined with a popliteal plexus block (PPB) can improve posterior knee pain, reduce nalbuphine consumption, and shorten the length of hospital stay. Patients who underwent TKA were allocated to the CACB + sham block (SHAM) or CACB + PPB groups. The primary outcome was the maximum pain score originating from the posterior knee within 4 h after TKA. Secondary outcomes included the maximum pain score originating from the posterior and anterior knees within 72 h after TKA, range of motion on postoperative day (POD) 1–3, postoperative nalbuphine consumption within 72 h of surgery, length of hospital stay, and complications. The maximum pain score of the posterior knee was lower in the CACB + PPB group than in the CACB + SHAM group within 0–12 h after surgery. Nalbuphine consumption within 24 h after surgery was lower in the CACB + PPB group than in the CACB + SHAM group. The range of motion was better in the CACB + PPB group than in the CACB + SHAM group on POD1 and 2. The length of hospital stay was shorter in the CACB + PPB group than in the CACB + SHAM group. The incidence of clinical significant nausea and vomiting was lower in the CACB + PPB group than in the CACB + SHAM group. This study found that PPB combined with CACB could relieve pain in the posterior knee within at least 12 h after TKA, reduce nalbuphine consumption within 24 h after TKA, improve the range of motion on POD1 and 2, and shorten the length of hospital stay for patients who underwent TKA.

Abstract The tectonic of the Middle and Late Ordovician in the western margin of the north China Platform is complex, and the accumulation models of organic matter of the Wulalike Formation formed during this period are still unclear. Total organic carbon (TOC) content, mineral composition, organic carbon isotope composition, as well as the major and trace elements in the shale samples were all measured in this study. The Wulalike Formation was formed during a tectonic transition from a passive continental margin to an active continental margin. Hydrocarbon-forming organisms are mainly algae. Primary productivity, terrigenous input, and sedimentation rates influence input, dilution, and degradation of organic matter. The degree of degradation, redox, and basin restriction control the preservation of organic matter. The TOC of the Wulalike Formation is determined by the input and preservation degree of organic matter at different sedimentary periods. The organic matter accumulation model in the Wulalike Formation is controlled by regional structures, dominated by sedimentation rate and preservation conditions.

Abstract HER2 antagonists remain the cornerstone of therapy for patients with HER2-positive breast cancer. This study introduces a novel small-molecule inhibitor of DNA methyltransferase 1 (DNMT-1), referred to as DI-1, designed to synergize with HER2 antagonists in treating HER2-positive breast cancer cells. Clinical data reveal a negative correlation between DNMT-1 expression and PTEN levels, and a positive correlation with the methylation rates of PTEN's promoter. In experiments with SKBR3 and BT474 cells, DI-1 effectively reduced the methylation of PTEN's promoter region, thereby upregulating PTEN expression. This upregulation, in turn, enhanced the cells' sensitivity to HER2 antagonists, indicating that DI-1’s mechanism involves inhibiting DNMT-1’s recruitment to PTEN's promoter region. Consequently, by increasing PTEN expression, DI-1 amplifies the sensitivity of HER2-positive breast cancer cells to treatment, suggesting its potential as a promising therapeutic strategy in this context.

Abstract Objectives Allergic rhinitis (AR) is a complex disorder with variable pathogenesis. Increasing evidence suggests that the LRRC8A is involved in maintaining cellular stability, regulating immune cell activation and function, and playing significant roles in inflammation. However, the involvement of LRRC8A in AR inflammation and its underlying mechanisms remain unclear. Methods LRRC8A expression in AR patients, confirmed by qRT-PCR and Western blotting, was analyzed to investigate its relationship with the clinical characteristics of AR patients. In vitro, IL-13 stimulated HNEpCs to establish a Th2 inflammation model, with subsequent LRRC8A knockout or overexpression. NOX1/NOX4 inhibitor (GKT137831) and chloride channel inhibitor (DCPIB) were utilized to investigate AR development mechanisms during LRRC8A overexpression. An OVA-induced AR model with nasal mucosa LRRC8A knockdown confirmed LRRC8A's regulatory role in AR inflammation. Results LRRC8A mRNA and protein levels were significantly elevated in AR patients, positively correlating with NADPH oxidase subunits and Th2 inflammatory markers. In vitro, IL-13 stimulation of HNEpCs resulted in upregulation of LRRC8A and increased expression of NOX1, NOX4, and p22phox, along with mitochondrial dysfunction and NF-κB pathway activation. The knockout of LRRC8A reversed these effects. In nasal mucosal epithelial cells, DCPIB and GKT137831 completely blocked mitochondrial dysfunction caused by the overexpression of LRRC8A, which led to up-regulation of NOX1, NOX4, and p22phox. In vivo, knocking down LRRC8A reduced eosinophil infiltration, downregulated the expression of NOX1, NOX4, p22phox IL-4, IL-5, and IL-13, and decreased NF-κB pathway activation. Conclusion LRRC8A drives the upregulation of NOX1, NOX4, and p22phox, leading to ROS overproduction and mitochondrial dysfunction. It also activates NF-κB, ultimately leading to nasal mucosal epithelial inflammation. LRRC8A may be a potential target for the treatment of AR.

Abstract Background Chronic ethanol exposure (CEE) is recognized as an important risk factor for depression, and the gut-brain axis has emerged as a key mechanism underlying chronic ethanol exposure-induced anxiety and depression-like behaviors. Short-chain fatty acids (SCFAs), which are the key metabolites generated by gut microbiota from insoluble dietary fiber, exert protective roles on the central nervous system, including the reduction of neuroinflammation. However, the link between gut microbial disturbances caused by chronic ethanol exposure, production of SCFAs, and anxiety and depression-like behaviors remains unclear. Methods Initially, a 90-day chronic ethanol exposure model was established, followed by fecal microbiota transplantation model, which was supplemented with SCFAs via gavage. Anxiety and depression-like behaviors were determined by open field test, forced swim test, and elevated plus-maze. Serum and intestinal SCFAs levels were quantified using GC-MS. Changes in related indicators, including the intestinal barrier, intestinal inflammation, neuroinflammation, neurotrophy, and nerve damage, were detected using Western blotting, immunofluorescence, and Nissl staining. Results Chronic ethanol exposure disrupted with gut microbial homeostasis, reduced the production of SCFAs, and led to anxiety and depression-like behaviors. Recipient mice transplanted with fecal microbiota that had been affected by chronic ethanol exposure exhibited impaired intestinal structure and function, low levels of SCFAs, intestinal inflammation, activation of neuroinflammation, a compromised blood-brain barrier, neurotrophic defects, alterations in the GABA system, anxiety and depression-like behaviors. Notably, the negative effects observed in these recipient mice were significantly alleviated through the supplementation of SCFAs. Conclusion SCFAs not only mitigate damage to intestinal structure and function but also alleviate various lesions in the central nervous system, such as neuroinflammation, and reduce anxiety and depression-like behaviors, which were triggered by transplantation with fecal microbiota that had been affected by chronic ethanol exposure, adding more support that SCFAs serve as a bridge between the gut and the brain.

To promote energy savings, high efficiency and miniaturization of power electronic devices, Fe–Si–B–P–Cu nanocrystalline soft magnetic materials with high saturation magnetization (Bs) parallel to that of the 6.5 wt% Si steel and low coercivity (Hc) are desired. In this work, 30 μm-thick Fe84Si3B10P2Cu1 and Fe84.5Si3B9.5P2Cu1 (at.%) amorphous/nanocrystalline precursor ribbons were melt-spun, which has high Fe contents comparable to that of the 6.5 wt% Si steel. These ribbons consist of an amorphous matrix and pre-existing α-Fe of approximately 28–30 nm in size possessed relatively low and similar-value activation energy of nucleation and growth in the range of 224–249 kJ/mol. Which could induce strong crystallization competition and effectively suppress coarsening of the pre-existing α-Fe. The Fe84Si3B10P2Cu1 nanocrystalline alloy obtained by rapid-annealing (∼100 °C/s) the amorphous/nanocrystalline precursor at 480 °C for 30 s (Fe84-480) exhibited a fine and uniform nanostructure containing α-Fe with small average grain size of approximately 23.1 nm and high volume fraction. The Fe84-480 alloy possessed a high Bs of approximately 1.88 T, a low Hc of 8.6 A/m, and good bendability revealed by relatively large bending fracture strain of ∼1.65%, making it a promising soft magnetic material for power electronic devices.

The aim of this paper was to provide a characterization of nonlinear generalized Lie $ n $-higher derivations for a certain class of triangular algebras. It was shown that, under some mild conditions, each component $ G_r $ of a nonlinear generalized Lie $ n $-higher derivation $ \{G_r\}_{r\in N} $ of the triangular algebra $ \mathcal{U} $ could be expressed as the sum of an additive generalized higher derivation and a nonlinear mapping vanishing on all ($ n-1 $)-th commutators on $ \mathcal{U} $.

Abstract Seasonal influenza A virus (IAV), particularly the H1N1 subtype, poses a significant public health threat because of its substantial morbidity and mortality rates worldwide. Understanding the immune response to H1N1 is crucial for developing effective treatments and vaccines. In this study, we deciphered the single-cell transcriptomic landscape of peripheral blood mononuclear cells (PBMCs) from H1N1-infected humans and lung tissue samples from H1N1-infected mice by mining HIN1-related single-cell RNA sequencing data from the GEO database. We observed similar changes in immune cell composition following H1N1 infection, with an increase in macrophages but a decrease in T cells in both species. Moreover, significant transcriptional changes in bystander immune cells upon H1N1 infection were identified, with the upregulation of the chemokine CCL2 in human PBMCs and increased expression of interferon-stimulated genes such as Ifit3, Ifit1 and Isg15 in mouse pulmonary immune cells. Intercellular cross-talk analysis highlighted enhanced interactions among bystander immune cells during H1N1 infection, with neutrophils in humans and macrophages in mice showing the most remarkable increases in interaction intensity. Transcription factor analysis revealed the conserved upregulation of key antiviral regulons, including STAT1 and IRF7, in T cells across both species, highlighting their pivotal roles in antiviral defense. These results suggest that humans and mice exhibit common immune responses to H1N1 infection, underscoring the similarity of vital immune mechanisms across species. The conserved immune mechanisms identified in this study provide potential therapeutic targets for enhancing antiviral immunity. Our research underscores the importance of understanding species-specific and conserved immune responses to H1N1 and offers insights that could inform the development of novel antiviral therapies and improve clinical outcomes for individuals affected by influenza.

Abstract A nomogram to estimate the risk of linezolid-induced thrombocytopenia in patients with renal impairment is not available. The aim of the study is to develop a nomogram for predicting linezolid-induced thrombocytopenia in patients with renal impairment and to investigate the incremental value of PNU-142300 concentration beyond clinical factors and linezolid trough concentration (Cmin) for risk prediction. Logistic regression was used to identify independent risk factors for linezolid-induced thrombocytopenia in patients with renal impairment and nomograms were established. The performance of the nomograms was assessed in terms of area under the receiver operating characteristic curve (AUROC), net reclassification improvement (NRI), integrated discrimination improvement (IDI) , decision curve analysis (DCA) and calibration. Internal validation and external validation of the nomograms were also performed. Four nomograms were created: nomogram A including total bilirubin, creatinine clearance and concomitant mannitol use; nomogram B containing linezolid Cmin additionally; nomogram C containing total bilirubin, concomitant mannitol use, linezolid Cmin, and PNU142300 concentration; nomogram D including total bilirubin, concomitant mannitol use, and PNU142300 concentration. Nomogram C improved the prediction performance than nomogram A (AUROC 0.881 vs. 0.749; NRI 0.290; IDI 0.226) and nomogram B (AUROC 0.881 vs. 0.812; NRI 0.152; IDI 0.130) in the training cohort. DCA analysis showed that nomogram C yielded a greater net benefit. Compared with nomogram A and nomogram B, nomogram C also showed superior discriminatory efficacy, good calibration and clinical usefulness in the external validation cohort. The nomogram containing PNU-142300 concentration and linezolid Cmin had better predictive capability than that containing linezolid Cmin for predicting linezolid-induced thrombocytopenia in patients with renal impairment.

Abstract This study investigates methods to enhance the energy conversion efficiency of electromagnetic repulsion mechanisms. Initially, a model considering the influence of the resistance coefficient on electromagnetic repulsion mechanisms is developed based on electromagnetic principles. Sensitivity analysis of the resistance coefficient is conducted to elucidate its role in energy conversion efficiency. Subsequently, finite element analysis techniques are applied to simulate electromagnetic repulsion mechanisms across varying resistance coefficients to determine the optimal value. Experimental validation of theoretical models and numerical simulation results is then performed, with precise adjustments made to the resistance coefficient during experiments, and energy conversion efficiency accurately measured under diverse conditions. The results indicate a significant improvement in energy conversion efficiency following resistance coefficient optimization. Numerical simulations reveal that setting the resistance coefficient to 0.85Ω yields optimal energy conversion efficiency, with a 23.5% enhancement over the pre-optimized state. Experimental validation corroborates these findings, demonstrating an average 22% increase in energy conversion efficiency compared to the unoptimized state. Comparative analysis with related studies demonstrates an average improvement of 23.5% in energy conversion efficiency, with the maximum enhancement reaching 25.0%. This underscores the effectiveness and superiority of the proposed optimization model. This discovery offers new avenues for designing and enhancing electromagnetic repulsion mechanisms and presents opportunities for improving energy efficiency and performance in associated applications.

Abstract Background Previous studies have suggested an association between low serum bilirubin concentrations and increased risk of cognitive impairment. This study aimed to explore the association and dose-response relationship between serum direct bilirubin (DBIL) concentrations and mild cognitive impairment (MCI) among hemodialysis patients. Methods This is a multicenter cross-sectional study with patients undergoing hemodialysis from 22 dialysis centers in Guizhou Province, China. The outcome was mild cognitive impairment (MCI), measured with a Mini-Mental State Examination. The association and dose-response relationship between serum DBIL and MCI incidence were examined using multivariate logistic regression analysis, restricted cubic spline, and subgroup analysis to explore the association of serum DBIL concentrations with MCI. Results Of the 4223 enrolled patients (mean age 55.2 ± 15.3 years, 60.4% males), 1187 (28.1%) had MCI. Serum DBIL of 0.10-1.67umol/L [multivariable-adjusted odds ratios (OR) 1.32, 95% confidence interval (CI): 1.08–1.60, P = 0.005], 2.31-3.20umol/L (OR = 1.22, 95%CI: 1.00-1.49, P = 0.047), and > 3.21umol/L (OR = 1.32, 95%CI: 1.08–1.61, P = 0.006) had increased risk of MCI compared with 1.68-2.30umol/L. The dose-response analysis between serum DBIL and MCI showed a U-shaped relationship (P for non-linearity = 0.009), and the serum DBIL concentrations with the lowest risk of MCI was 2.01umol/L. As the serum DBIL concentrations were lower than the reference, the risk of MCI decreased by 49% per standard deviation (SD) increase in serum DBIL (OR = 0.51, 95%CI: 0.29–0.89, P

Herba Siegesbeckiae (HS) has been traditionally used for managing cardio- and cerebro-vascular diseases. Our previous study demonstrated that HS ameliorates myocardial ischemia/reperfusion (I/R) injury. Also, the differentially expressed proteins between HS and I/R groups were shown to be displayed as UCHL5 and were mainly enriched in the NLRP3 inflammasome pathway. However, further elucidation is required concerning the effective subfractions, constituents, and HS influence on the UCHL5/NLRP3 pathway. A co-immunoprecipitation assay and UCHL5 overexpression in cardiomyocyte explores were used to determine the interaction between UCHL5 and NLRP3 during myocardial I/R. The water extracts of HS were subjected to column chromatography using a macroporous adsorption resin. Four HS subfractions (HS-A [H 2 O elution], HS-B [20% ethanol elution], HS-C [50% ethanol elution], and HS-D [95% ethanol elution]) were obtained in this study. HS-C exhibited the most significant protective effect against myocardial I/R and improved I/R injury in vivo . HS-C markedly restrained the expression of UCHL5 and NLRP3 and resisted the role of UCHL5/NLRP3 in the pathogenesis of I/R. Eleven main constituents of HS-C were identified, among which kirenol best displayed anti-I/R injury activity and binding energy. Kirenol accounted for 62.4% of HS-C. Thus, HS-C effectively protected against myocardial I/R injury, which was attributed to mitigation of the UCHL5/NLRP3 pathway and kirenol was identified as the core active constituent.

Abstract Parkinson's disease (PD) involves multiple forms of neuronal cell death, but the dominant pathway involved in disease progression remains unclear. This study employed RNA sequencing (RNA-seq) of brain tissue to explore gene expression patterns across different stages of PD. Using the Scaden deep learning algorithm, we predicted neurocyte subtypes and modelled dynamic interactions for five classic cell death pathways to identify the predominant routes of neuronal death during PD progression. Our cell type-specific analysis revealed an increasing shift towards necroptosis, which was strongly correlated with nitric oxide synthase (NOS) expression across most neuronal subtypes. In vitro experiments confirmed that nitric oxide (NO) is a key mediator of necroptosis, leading to nuclear shrinkage and decreased mitochondrial membrane potential via phosphorylation of the PIP1/PIP3/MLKL signalling cascade. Importantly, specific necroptosis inhibitors significantly mitigated neuronal damage in both in vitro and in vivo PD models. Further analysis revealed that NO-mediated necroptosis is prevalent in early-onset Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) and across multiple brain regions but not in brain tumours. Our findings suggest that NO-mediated necroptosis is a critical pathway in PD and other neurodegenerative disorders, providing potential targets for therapeutic intervention.

Abstract Background Diarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites. Methods The new borne rats were procured from SPF facility and separated as healthy (1 group) and IBS-D model ( 3 groups) rats were prepared articially using mother’s separation and senna leaf treatment. 2 groups of IBS-D models were further treated with TCM- shenling Baizhu decoction and FMT. The efficacy was evaluated by defecation frequency, bristol stool score, and intestinal tight junction proteins (occludin-1 and claudin-1) expression. Microbiomic analysis was conducted using 16 S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database. Results Significant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P

Abstract This study aimed to investigate the potential correlation between the perfusion parameters of brain arteriovenous malformations (bAVMs) as determined by multiphase CT angiography and bAVM rupture. Based on the occurrence of bAVM-related hemorrhage, 480 diagnosed bAVM patients were divided into hemorrhage (n = 220) and non-hemorrhage (n = 260) groups in this retrospective multi-center study spanning 2010 to 2020. On initial rupture CT images, the bAVM nidus and major draining vein were segmented, and time-density curves were extracted to compute perfusion parameters including mean transit time (MTT), time to peak (TTP), blood volume (BV), and blood flow (BF). To examine the potential correlation between these parameters and bAVM rupture, logistic regression was utilized to analyze multifactorial data and compare differences between the two groups. The ruptured group demonstrated a bAVM nidus characterized by an increased BF, a shorter TTP and MTT, and a higher peak density. The veins that were draining exhibited a reduced TTP, MTT, and peak density. A nidus TTP of less than 4s was identified by the multifactorial analysis as a critical risk factor for bAVM rupture. The statistical results highlight the noteworthy correlation between nidus TTP and bAVM rupture, presenting an original framework for assessing the risk of rupture.

Abstract Background In patients undergoing breast-conserving therapy without surgical clip implantation, the accuracy of tumor bed identification and the consistency of clinical target volume (CTV) delineation under computed tomography (CT) simulation remain suboptimal. This study aimed to investigate the feasibility of implementing preoperative magnetic resonance (MR) simulation on delineations by assessing interobserver variability (IOV). Methods Preoperative MR and postoperative CT simulations were performed in patients who underwent breast-conserving surgery with no surgical clips implanted. Custom immobilization pads were used to ensure the same supine position. Three radiation oncologists independently delineated the CTV of tumor bed on the images acquired from MR and CT simulation registration and CT simulation alone. Cavity visualization score (CVS) was assigned to each patient based on the clarity of the tumor bed on CT simulation images. IOV was indicated by generalized conformity index (CIgen), denoted as CIgen−CT and CIgen−MR/CT, and the distance between the centroid of mass (dCOM), denoted as dCOMCT and dCOMMR/CT. The variation of IOV in different CVS subgroups was analyzed. Results A total of 10 patients were enrolled in this study. The median and interquartile range (IQR) of maximum pathological diameter of the tumors in all patients were 1.55 (0.80–1.92) cm. No statistical significance was found between the volumes of CTVs on CT simulation and on MR/CT simulation registration images (p = 0.387). CIgen−MR/CT was significantly larger than CIgen−CT (p = 0.005). dCOMMR/CT was significantly smaller than dCOMCT (p = 0.037). The median and IQR of CVS in all patients were 2.34 (2.00–3.08). The difference of CIgen between CIgen−MR/CT and CIgen−CT was larger in the low CVS group (p = 0.016). The difference of dCOM showed a decreasing trend when CVS was lower, although it did not reach statistical significance (p = 0.095). Conclusions For patients who underwent breast-conserving surgery without surgical clip implantation, the use of preoperative MR simulation in delineating the CTV of tumor bed decreased the IOV among observers. The consistency of tumor bed identification was improved especially in cases where the margins of tumor bed were challenging to visualize on CT simulation images. The study findings offer potential benefits in reducing local recurrence and minimizing tissue irritation in the surrounding areas. Future investigation in a larger patient cohort to validate our results is warranted.

Abstract Background Postoperative pain management remains a significant challenge for patients undergoing posterior urethroplasty (PU). In a previous study, we proposed a novel technique of combined pudendal nerve (PN) and spermatic cord (SC) block to manage pain after PU. The present trial was conducted to test the hypothesis that this technique is effective for pain control after PU and provides longer-lasting analgesia than caudal epidural block (CB). Methods Sixty patients undergoing PU were randomized into two groups: Group NB received combined PN and SC block, and Group CB received CB. General anesthesia with a laryngeal mask was performed. The primary outcome was the postoperative analgesic duration, and the secondary outcomes included the Numeric Rating Scale (NRS) scores for pain and the number of patients with different motor scores of the lower limb at 3, 6, 12, and 24 h postoperatively. Results Two patients in Group CB were withdrawn due to block failure. The postoperative analgesic duration was statistically longer in Group NB compared with Group CB (mean difference [95% confidence interval], 115.78 min [17.80, 213.75]; P = 0.021). The NRS scores for pain at 12 and 24 h after surgery were statistically lower in Group NB compared with Group CB. Group NB had statistically more patients with motor score 0 at 3 h postoperatively than Group CB. Conclusions PN combined with SC block is an effective technique for postoperative analgesia in PU. This technique can achieve a longer duration of analgesia and lower pain scores, especially 12 h after surgery, than a CB. Trial registration This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2100042971, registration date on 2/2/2021).

Abstract Aiming at the problem that the mobility characteristics of electric vehicles (EVs) lead to the complexity of optimal scheduling among multiple decision‐making subjects, the authors propose a multi‐microgrid bi‐layer economic scheduling strategy considering evolutionary‐stackelberg hybrid game of EVs. Firstly, in order to accurately analyse the influence of interaction among EVs, an electric vehicle aggregator (EVA) selection strategy for EV users based on evolutionary game among microgrids and a reconciliation strategy of EVA service fee are established. Secondly, a two‐layer economic scheduling strategy for microgrids is proposed based on the Stackelberg game. The microgrid operator, as a leader, sets the internal price of microgrid based on the supply‐demand balance; aggregators, as followers, adjust their electricity consumption and EVA choices based on the internal price and the evolutionary game model. Then, a multi‐microgrid electricity‐sharing trading strategy is constructed using the supply‐demand ratio to encourage sub‐microgrids to participate in internal transactions. Finally, the case shows that the proposed strategy can optimise the distribution of EVs among microgrids. Combining the across‐time‐and‐space energy transmission potential of EVs and the flexible complementary capability of multi‐microgrid, it can improve the operating economy of each microgrid.

Abstract The carboamination of unsaturated molecules using bifunctional reagents is considered an attractive approach for the synthesis of nitrogen-containing compounds. However, bifunctional C–N reagents have never been employed in the carboamination of cyclopropane. In this study, we use an N-heterocyclic carbene (NHC), N-benzoyl saccharin, as a bifunctional reagent and a photoredox catalyst for a dual-catalyzed 1,3-aminoacylation of cyclopropane. NHCs play multiple roles, functioning as Lewis base catalysts to activate C–N bonds, promoting the oxidative quenching process of PC*, and acting as efficient acyl radical transfer catalysts for the formation of C–C bonds. The oxidative quenching process between the excited-state PC* and acyl NHC adduct is the key to the photooxidation generality of aryl cyclopropanes.

Abstract Morphogens play a critical role in coordinating stress adaptation and aging across tissues, yet their involvement in neuronal mitochondrial stress responses and systemic effects remains unclear. In this study, we reveal that the transforming growth factor beta (TGF-β) DAF-7 is pivotal in mediating the intestinal mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans under neuronal mitochondrial stress. Two ASI sensory neurons produce DAF-7, which targets DAF-1/TGF-β receptors on RIM interneurons to orchestrate a systemic UPRmt response. Remarkably, inducing mitochondrial stress specifically in ASI neurons activates intestinal UPRmt, extends lifespan, enhances pathogen resistance, and reduces both brood size and body fat levels. Furthermore, dopamine positively regulates this UPRmt activation, while GABA acts as a systemic suppressor. This study uncovers the intricate mechanisms of systemic mitochondrial stress regulation, emphasizing the vital role of TGF-β in metabolic adaptations that are crucial for organismal fitness and aging during neuronal mitochondrial stress.

Manganese is an important alloying element in iron and steel. Adding the appropriate amount of manganese can enhance the properties of steel. The manganese content directly influences steel quality in the converter steelmaking process. Too little manganese results in insufficient hardness and strength of steel products, whereas excessive manganese leads to increased embrittlement and production costs. Therefore, determining the appropriate amount of manganese is crucial for improving steel quality and reducing smelting costs. The quantity of manganese added during converter steelmaking primarily depends on the predicted final manganese content. However, this content is influenced by various factors, such as the oxidation reaction process and the addition of other alloying elements. These factors exhibit nonlinear effects on the manganese content, and the factors are highly interconnected, making accurate prediction of manganese content at the end point challenging. In response to the challenges posed by noise and strong coupling in predicting manganese content at the end point of converter steelmaking, a research framework was developed to address these issues and facilitate accurate predictions. Key influencing factors in the smelting process were identified through Pearson correlation coefficient analysis and mechanistic analysis. Subsequently, the relationship between these influencing factors and end-point manganese content was modeled using the long short-term memory network (LSTM). To mitigate the effects of high-frequency noise in nonlinear and nonstationary sequences, singular spectral analysis (SSA) was employed during the prediction process. This led to the development of a method known as SSA−LSTM for predicting end-point manganese content. The effects of different test sets and the number of neurons on the prediction results were investigated using converter steelmaking production data from Hebei Jingye Iron & Steel Co., Ltd. The proposed method achieved minimal prediction error when the test set comprised 10% of the data and the number of neurons was set to 85. At these parameters, the mean absolute error of the prediction method for end-point manganese was 1.19%, with a root-mean-square error of 1.48%. These results demonstrate that the proposed method effectively addresses issues related to large noise and nonlinear data. Moreover, compared with existing time series prediction methods, the proposed method, particularly after SSA treatment, showed reduced prediction errors. This validates the effectiveness of the method and provides a basis for accurate alloy addition in actual production processes.

Abstract Background SHR-1707 is a novel humanized anti-Aβ IgG1 monoclonal antibody that binds to Aβ fibrils and monomers to block the formation of Aβ plaques or to promote the microglial phagocytosis of Aβ. Preclinical studies showed that SHR-1707 reduced brain Aβ deposition in 5xFAD transgenic mice. Herein, we conducted two phase 1 studies to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single intravenous dose of SHR-1707 in healthy adult subjects. Methods Two randomized, double-blind, single-ascending-dose, phase 1 studies were conducted in China (Study CHN) and Australia (Study AUS). Study CHN consisted of 2 parts. In Part 1, eligible healthy young adults (18–45 years) were sequentially randomized 8:2 to receive SHR-1707 (five cohorts: 2, 6, 20, 40, and 60 mg/kg) or placebo in each cohort; in Part 2, elderly subjects (55–80 years) were randomized 8:4 to receive SHR-1707 (20 mg/kg) or placebo. A similar design was used in Study AUS, but with only healthy young adults enrolled across three dosing cohorts (2, 20, and 60 mg/kg). Results Sixty-two (part 1/2, n = 50/12; age range, 18–42/55–63 years) and 30 subjects (age range, 18–42 years) received SHR-1707 or placebo in Study CHN and Study AUS, respectively. In Study CHN, all treatment-related adverse events (TRAEs) were mild, with the most common being transient laboratory abnormalities. In Study AUS, TRAEs were mostly mild (1 moderate event each with SHR-1707/placebo); the most common TRAEs with SHR-1707 were dysgeusia and fatigue (8.3% each). In both studies, the exposure of SHR-1707 increased in a slightly greater than dose-proportional manner over the dose range of 2–60 mg/kg in young adults; there was a dose-dependent increase in plasma Aβ42 concentration following SHR-1707 administration compared with the placebo group. The safety and PK and PD profiles of SHR-1707 in the elderly subjects were consistent with the younger counterpart at the same dose level. No ethnic difference in safety, PK and PD of SHR-1707 was observed. Conclusions A single intravenous dose of SHR-1707 at 2–60 mg/kg was safe and well tolerated in healthy young adult and elderly subjects. The PK and PD profiles are supportive for further clinical development. Trial registration NCT04973189 (retrospectively registered on Jul.21, 2021) and NCT04745104 (registered on Feb.6, 2021) on clinicaltrials.gov.

Abstract Urolithiasis, a common and recurrent condition, imposes a significant global health burden. This study investigates the causal relationship between various types of fluid intake and urolithiasis using univariable and multivariable Mendelian randomization (MR) approaches. Genetic data for urolithiasis were obtained from the FinnGen Consortium (n = 400,681), while genetic measures for nine fluid types were sourced from meta-analyses of genome-wide association studies (GWAS). The analysis revealed that genetically predicted coffee intake (OR: 0.571, 95% confidence interval (CI): 0.341–0.958, p = 0.034) and ground coffee intake (OR: 0.219, 95% CI: 0.005–0.923, p = 0.038) were protective factors for upper urinary calculi. Additionally, a standard deviation (SD) increase in tea intake was associated with a 53% reduction in risk (OR: 0.473, 95% CI: 0.320–0.700, p

Abstract Museums, which are among the most popular science institutions outside schools, are usually used to display and introduce historical culture and cultural relics to tourists. Text and audio explanations are used by traditional museums to popularize historical knowledge and science for tourists, and general interactive systems are based on desktops. This learning method is relatively boring in terms of experience. As a result, tourists have no desire or interest in actively exploring and learning about bronze ware, so they only have a basic understanding about bronze ware. Since most tourists are familiar with games, they are more likely to be attracted by game content and will actively explore and interact with it. In addition, a certain degree of reality is created by virtual reality technology and an immersive experience through head-mounted devices is provided to users. In this paper, we take Chinese bronzes as the research objects. We first use 3D laser scanners to obtain bronze models ; then, we build a virtual museum environment, and we finally design a virtual reality curation game based on this bronze digital museum. This game offers visitors an immersive museum roaming and bronze ware interactive experience. Through a combination of text, video learning, and games, visitors’ curiosity and desire to explore bronze ware are stimulated, and their understanding and ability to remember bronze ware knowledge can be deepened. In terms of cultural heritage, this game is also conducive to the spread of traditional Chinese bronze culture throughout the world.

Abstract Background Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. Methods We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. Results A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband’s parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. Conclusions WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.

Abstract Heterosis, recognized for improving crop performance, especially in the first filial (F1) generation, remains an area of significant study in the tobacco industry. The low utilization of leaf veins in tobacco contributes to economic inefficiency and resource waste. Despite the positive impacts of heterosis on crop genetics, investigations into leaf-vein ratio heterosis in tobacco have been lacking. Understanding the mechanisms underlying negative heterosis in leaf vein ratio at the molecular level is crucial for advancing low vein ratio leaf breeding research. This study involved 12 hybrid combinations and their parental lines to explore heterosis associated with leaf vein ratios. The hybrids displayed diverse patterns of positive or negative leaf vein ratio heterosis across different developmental stages. Notably, the F1 hybrid (G70 × Qinggeng) consistently exhibited substantial negative heterosis, reaching a maximum of -19.79% 80 days after transplanting. A comparative transcriptome analysis revealed that a significant proportion of differentially expressed genes (DEGs), approximately 39.04% and 23.73%, exhibited dominant and over-dominant expression patterns, respectively. These findings highlight the critical role of non-additive gene expression, particularly the dominance pattern, in governing leaf vein ratio heterosis. The non-additive genes, largely associated with various GO terms such as response to abiotic stimuli, galactose metabolic process, plant-type cell wall organization, auxin-activated signaling pathway, hydrolase activity, and UDP-glycosyltransferase activity, were identified. Furthermore, KEGG enrichment analysis unveiled their involvement in phenylpropanoid biosynthesis, galactose metabolism, plant hormone signal transduction, glutathione metabolism, MAPK signaling pathway, starch, and sucrose metabolism. Among the non-additive genes, we identified some genes related to leaf development, leaf size, leaf senescence, and cell wall extensibility that showed significantly lower expression in F1 than in its parents. These results indicate that the non-additive expression of genes plays a key role in the heterosis of the leaf vein ratio in tobacco. This study marks the first exploration into the molecular mechanisms governing leaf vein ratio heterosis at the transcriptome level. These findings significantly contribute to understanding leaf vein ratios in tobacco breeding strategies.

Abstract Periodontitis is a chronic inflammatory disease involving plaque biofilm as a pathogenic factor. Potassium ion plays an important role in cellular homeostasis; a large outflow of potassium may lead to local inflammation progression. In this work, the multifunctional short peptide molecule BmKTX-33 was designed by modifying the BmKTX, a Kv1.3 potassium channel inhibitor. This was to explore its antibacterial properties, capability of maintaining cell ion homeostasis, and bone-forming capacity. The results showed that BmKTX-33 had inhibitory effects on S. gordonii, F. nucleatum, and P. gingivalis. Moreover, BmKTX-33 also inhibited excessive potassium outflow in inflammatory environments. Finally, BmKTX-33 promoted MC3T3-E1 early osteogenesis while suppressing the NLRP3 inflammasome's production. In conclusion, BmKTX-33 not only has antibacterial properties, but also can inhibit the expression of NLRP3 inflammasome and play an anti-inflammatory role.

Some core designs integrate high-enriched fuel and moderator materials to enhance neutron utilization. This combination results in a broad spectrum within the system, posing challenges in resonance calculation. This paper introduces a general framework to realize resonance self-shielding treatment in broad-spectrum fuel lattice problems. The framework consists of three components. First, a new energy group structure is devised to support resonance calculation in the entire energy range and capture spectral transition and thermalization effects during eigenvalue calculation. Second, the subgroup method based on narrow approximation is selected as a universal method to perform resonance calculation. Finally, transport equations for each fissionable region are solved for neutron flux to collapse the fission spectrum. The proposed method is verified against fast, intermediate, and thermal spectrum pin cell problems and an assembly problem featuring a fast-thermal coupled spectrum. Numerical results affirm the accuracy of the proposed method in handling these scenarios, with eigenvalue errors below 154 pcm for pin cell problems and 106 pcm for the assembly problem. The verification results revealed that the proposed method enables accurate resonance self-shielding treatment for broad-spectrum problems.

Breast cancer is the most common cancer among women worldwide, and adjuvant radiotherapy (RT) following tumor removal is one of the most commonly used treatments for breast cancer. However, the high risk of tumor recurrence and inevitable radiation skin injury after RT remain fatal problems, seriously challenging the patient's postoperative rehabilitation. Herein, a multifunctional poly (lipoic acid)-based hydrogel is constructed through one-step heating the mixture of α-lipoic acid (LA)/arginine (Arg)/silk fibroin (SF), without introducing any non-natural molecules. The multiple synergistic interactions among LA, Arg, and SF not only enhance the solubilization of LA in aqueous systems but also stabilize poly(lipoic acid) through strong salt bridge hydrogen bonds and ionic hydrogen bonds. Intriguingly, the LA-based surfactant induced β-sheet transformation of SF can further modulate the bulk strength of the hydrogel. Regulating the content of LA in hydrogels not only allows efficient control of hydrogel bioactivity but also enables the evolution of hydrogels from injectable forms to adhesive patches. Based on the different biological activities and forms of hydrogels, they can be implanted internally or applied externally on the mice's skin, achieving simultaneous prevention of tumor recurrence post-surgery and assistance in treating radiation-induced skin damage after radiotherapy.

Objective In the gentle slope zone of the Dongying Depression, the first member of the Kongdian Formation and the lower part of the fourth member of the Shahejie Formation can be split by a distinctive assemblage of reddish sediments, which originated from both fluvial and lacustrine processes. Extensive research has substantiated the significant exploration potential of the Palaeogene red bed in the Dongying Depression. Nevertheless, the sedimentary facies type of the red bed remains a subject of debate among researchers. Methods To address this issue, we present a comprehensive analysis of wells W1, W2, and W3, which are located in the Wangjiagang area within the southern gentle slope zone of the Dongying Depression. This analysis mainly focused on evaluating the grain size distribution, grain size parameters, and grain size probability accumulation curves of the red bed. Results This study revealed the distinctive characteristics of the red sandstone reservoirs in the study area. These include thin single sand body thicknesses ranging from 1 to 7.7 m and fine particle sizes, changing from 2.24ϕ to 4.73ϕ. The grain size distribution is mainly characterized by unimodal positive skewness curves, suggesting the dominance of the relatively coarse fraction. The grain-size parameter discriminant function and bivariate grain-size parameter plots suggest a fluvial environment. The grain size accumulation probability curves of most samples exhibit a significant transition component (over 50%), and the graphs in the C-M bivariate plot are parallel to the C=M baseline, reflecting the characteristics of density flow. Moreover, the logging curves mainly exhibit box and bell shapes with medium to high amplitudes, indicating that the sedimentary processes primarily involved vertical accretion and lateral accretion. The core analysis revealed the presence of blocky bedding indicative of rapid sediment accumulation, parallel bedding characteristic of unidirectional flow, and small cross-bedding suggestive of weak flow. Conclusion In conclusion, it is believed that the red sandstone resulted from distributive fluvial systems deposited with both palaeo-geomorphic features and hot-arid palaeo-climate factors in the study area. From upstream to downstream, the hydrodynamic conditions gradually weakened, the bifurcation of river channels strengthened, the flood erosion ability decreased, the single sand body thickness and sediment grain size decreased progressively, and the fluid properties transitioned from density flow to traction flow. The novel insights of this study offer a fresh perspective for the exploration of petroleum in the red sandstone of the study area. In forecasting such reservoirs, particular emphasis should be placed on analyzing palaeo-provenance and paleo-current while enhancing the identification and characterization of individual-stage flood channels.

Phenolic compounds are a class of important plant secondary metabolites, which are regarded as prime constituents of nutraceuticals and functional foods due to their various bioactivities. Lycium barbarum L., an excellent tonic used for both medicinal and dietary purposes, is rich in phenolic compounds and their derivatives. This article aims to review recent progress in research on phenolic compounds and their derivatives in L. barbarum L. with respect to their extraction, separation, identification, and analysis methods as well as their bioactivities. Furthermore, it summarizes the current knowledge on the contribution of phenolic substances to the flavor and taste of L. barbarum L. along with their synthesis and metabolism and reviews recent progress in their deep processing and application. Finally, possible solutions to the problems existing in the research and development of phenolic compounds from L. barbarum L. and an outlook on future prospects are proposed. It is our expectation that this review will provide a reference for further exploration of phenolic compounds and derivatives in L. barbarum L., and offer theoretical guidance for the development and utilization of this specialty resource.

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA), a rare but life-threatening systemic vasculitis, is distinguished by marked eosinophilia and presents with diverse symptoms, including asthma, cutaneous purpura, ecchymosis, skin necrosis, cardiac lesions, peripheral neuropathy, and necrotizing vasculitis. The etiology of EGPA involves a complex interaction among humoral, adaptive, innate, and allergic immune responses. Standard treatment employs prolonged high-dose glucocorticoid therapy, which is critical for survival; however, some patients’ symptoms cannot be relieved. Case report This case report details the medical management of an 11-year-old patient with EGPA, who was at risk of bilateral lower limb amputation due to differential arterial occlusion and severe, necrotizing vasculitis-induced gangrene in both feet. Treatment modalities administered included systemic infusion of Umbilical Cord Mesenchymal Stem Cells (UC-MSCs), targeted gastrocnemius muscle injections, and application of a Placenta-Derived Mesenchymal Stem Cells (PD-MSCs) hydrogel. Results After receiving a four-month regimen of allogeneic mesenchymal stem cell therapy via intravenous and local administration, the patient showed normalized eosinophil counts, reestablished blood flow in the dorsal arteries, and marked improvement in foot ulcerations. Conclusion Mesenchymal stem cell therapy is a promising option for severe EGPA cases refractory to glucocorticoids.

Herbal plants that contain aristolochic acids (AAs) have been widely used for medicinal purposes for centuries. However, human exposure to AAs via herbal or dietary intake is thought to be a causative factor for aristolochic acid nephropathy (AAN), hepatotoxic effects, and carcinomas. At present, the molecular mechanisms underlying AA-induced hepatotoxicity and carcinogenesis and the corresponding detoxification strategies are unclear. This review summarizes the exposure, absorption, distribution, metabolism, and excretion (ADME) process of AAs. Importantly, to more objectively determine the emerging correlation between AAs and liver cancer, this review summarizes the possible direct and indirect connections between AAs and liver cancer. In brief, this review comprehensively summarizes and analyzes the molecular mechanisms underlying AA-induced hepatotoxicity and carcinogenesis, as well as an assessment of current detoxification strategies. At the same time, a new view on the prevention and detoxification of AA-induced hepatotoxicity is proposed. Chinese medicines that contain AAs might induce liver cancer but this is a controversial notion. This review summarizes relevant views from the past and provides novel insight into AA-induced liver injury or cancer to lay the foundation for AA detoxification.

Abstract Background The transplantation of periodontal ligament stem cells (PDLSCs) has been shown to enhance periodontal regeneration in animal models and clinical trials. However, it is not known whether PDLSCs are antibacterial and whether this affects oral microbiota and periodontal regeneration. Methods We isolated human PDLSCs from periodontal ligament of extracted teeth. Rats’ periodontal fenestration defects were prepared, and treated with PDLSC injections (Cell group), using saline injections (Saline group) as the control. The oral microbiota was explored by 16 S rDNA sequencing and compared with that before surgery (PRE group). The antibacterial property of PDLSCs and its underlying mechanism were tested in vitro. Results Microbiome analyses reveal a decreased biodiversity, a changed community structure, and downregulated community functions of the oral microbiome in the Saline group. PDLSCs injections enhance periodontal regeneration, reverse the decrease in diversity, and increase the abundance of non-pathogenic bacterial Bifidobacterium sp. and Lactobacillus sp., making the oral microbiome similar to that of the PRE group. In vitro, PDLSCs inhibit the growth of Staphylococcus aureus, Escherichia coli, and Fusobacterium nucleatum. The main mechanism of action is postulated to involve production of the cationic antimicrobial peptide LL-37. Conclusions Our findings reveal that PDLSC injections enhance periodontal regeneration and regulate the oral microbiome to foster an oral cavity microenvironment conducive to symbiotic microbiota associated with health.

Abstract To develop new types of dynamic molecular devices with atomic-scale control over electronic function, new types of molecular switches are needed with time-dependent switching probabilities. We report such a molecular switch based on proton-coupled electron transfer (PCET) reaction with giant hysteric negative differential resistance (NDR) with peak-to-valley ratios of 120 ± 6.6 and memory on/off ratios of (2.4 ± 0.6) × 103. The switching dynamics probabilities are modulated by bias voltage sweep rate and can also be controlled by pH and relative humidity, confirmed by kinetic isotope effect measurements. The demonstrated dynamical and environment-specific modulation of giant NDR and memory effects provide new opportunities for bioelectronics and artificial neural networks.

Abstract Cutaneous T-cell lymphoma (CTCL) is a group of primary and secondary cutaneous malignancies characterized by aberrant T-cells in the skin. Diagnosing CTCL in its early stage can be difficult because of CTCL’s ability to mimic benign cutaneous inflammatory skin diseases. CTCL has multiple subtypes with different disease progression and diagnostic parameters despite similar clinical manifestations. The accurate diagnosis and prognosis of a varied range of diseases require the detection of molecular entities to capture the complete footprint of disease physiology. Non-coding RNAs (ncRNAs) have recently been discovered as major regulators of CTCL gene expression. They can affect tumor cell growth, migration, programmed cell death (PCD), and immunoregulation through interactions with the tumor microenvironment (TME), which in turn affect CTCL progression. This review summarizes recent advances in how ncRNAs regulate CTCL cell activity, especially their role in PCD. It also discusses the potential use of ncRNAs as diagnostic and prognostic biomarkers for different subtypes of CTCL. Furthermore, prospective targets and therapeutic approaches influenced by ncRNAs are presented. A better appreciation of the intricate epigenetic landscape of CTCL is expected to facilitate the creation of innovative targeted therapies for the condition.

Abstract Pomacea canaliculata is one of the most successful invader in worldwide, adversely affecting native ecosystem through direct predation or indirect competition, while the mechanism of indirect effects on native species remain poorly understood. To clarify the effects of P. canaliculata on the native near-niche species, Bellamya purificata, a widespread freshwater gastropod in China, was selected as the research subject. The changes of mortality, histology, antioxidant system as well as the intestinal flora diversity of B. purificata were explored in present study. The results showed that the median lethal dose of P. canaliculata culture solution for B. purificata was 23.76 ind/L and a concentration-dependent damage of both the gonad and hepatopancreas were observed, the gonadal villi were dissolved and the hepatopancreas cells were broken at 20 ind/L. Furthermore, different concentrations of P. canaliculata culture solution leading to the antioxidant damage on the enzyme or non-enzyme systems of B. purificata at various degrees. Additionally, a decrease in the diversity of the intestinal flora was observed, accompanied by an increase in the abundance of pathogenic bacteria such as Pseudomonas and Aeromonas after the exposure of the culture solution of P. canaliculata. Last, after being recovered in freshwater for 24 h, the antioxidant damage of B. purificata and the disturbance of intestinal flora diversity were still not recovered especially in the high concentration group. The indirect competitive mechanism of P. canaliculata culture solution on B. purificata were explored from the aspects of tissue, biochemical level and intestinal flora, which enriched the research of P. canaliculata invasion on native snails in China, and provided new insights for the study of the invasion strategy of P. canaliculata.

Abstract The C-terminal domain of RPB1 (CTD) orchestrates transcription by recruiting regulators to RNA Pol II upon phosphorylation. With CTD driving condensate formation on gene loci, the molecular mechanism behind how CTD-mediated recruitment of transcriptional regulators influences condensates formation remains unclear. Our study unveils that phosphorylation reversibly dissolves phase separation induced by the unphosphorylated CTD. Phosphorylated CTD, upon specific association with transcription regulators, forms distinct condensates from unphosphorylated CTD. Functional studies demonstrate CTD variants with diverse condensation properties exhibit differences in promoter binding and mRNA co-processing in cells. Notably, varying CTD lengths influence the assembly of RNA processing machinery and alternative splicing outcomes, which in turn affects cellular growth, linking the evolution of CTD variation/length with the complexity of splicing from yeast to human. These findings provide compelling evidence for a model wherein post-translational modification enables the transition of functionally specialized condensates, highlighting a co-evolution link between CTD condensation and splicing.

Abstract Nowadays, some fracking fluids can enable resourceful extraction of coalbed methane and reduce greenhouse gas emissions. However, their toxicity or corrosiveness will cause harm to downhole workers and pollute groundwater resources. Thus, five kinds of clean composite fracturing fluids were developed in this paper by using starch solution as the matrix and adding various preparations. The change rule of methane adsorption capacity by microstructure changes of coal samples was investigated systematically, and the optimal composite fracturing fluid was determined. The results showed that the new fracturing fluid increased the degree of aromatic ring condensation by 43.3% and the average pore size by 52.1%. Also, the adsorption constants of a value decreased by 11.6% and b value decreased by 23.9%, which can remarkably reduce the methane adsorption. The experimental results provide theoretical support for the clean production of coalbed methane.

Understanding the temporal and spatial variation of hydrochemical components in large freshwater lakes is crucial for effective management and conversation. In this study, we identify the temporal-spatial characteristics and driving factors of the hydrochemical components in Baiyangdian Lake using geochemical methods (Gibbs diagram, Piper diagram and End-element diagram of ion ratio) and multivariate statistical techniques (Principal component analysis and Correlation analysis). 16 sets of samples were collected from Baiyangdian Lake in May (normal season), July (flood season), and December (dry season) of 2022. Results indicate significant spatial variation in Na+, Cl−, SO42− and NO3− , suggesting a strong influence of human activities. Cation concentrations exhibit greater seasonal variation in the dry season compared to the flood season, while the concentrations of the four anions show inconsistent seasonal changes due to the combined effects of river water chemical composition and human activities. The hydrochemical type of Baiyangdian Lake is primarily HCO3·Cl-Na·Ca2+, Mg2+ and HCO3− originate mainly from silicate and carbonate rock dissolution, while K+, Na+ and Cl− originate mainly from sewage and salt dissolution in sediments. SO42− may mainly stem from industrial wastewater, while NO3− primarily originates from animal feces and domestic sewage. Through the use of Principal Component Analysis, it is identified that water-rock interaction (silicate and carbonate rocks dissolution, and dissolution of salt in sediments), carbonate sedimentation, sewage, agricultural fertilizer and manure, and nitrification are the main driving factors of the variation of hydrochemical components of Baiyangdian Lake across three hydrological seasons. These findings suggest the need for effective control of substandard domestic sewage discharge, optimization of agricultural fertilization strategies, and proper management of animal manure to comprehensively improve the water environment in Baiyangdian Lake.

AIM: To observe early clinical outcome with lens position adjustment following the implantable collamer lens (ICL) surgery. METHODS: Sixty patients were selected for this retrospective study. One eye from each patient received Toric ICL for astigmatism correction, and the other received non-astigmatic ICL surgery using horizontal position. Patients with higher postoperative arch height were selected, and their non-astigmatic eye clinical outcome were observed after ICL surgery at 1wk, 1, and 3mo. The clinical measurements included uncorrected visual acuity (UCVA), intraocular pressure (IOP), refractive state, corneal endothelium cell count, and arch height. Three months later, the ICL in each patient's non-astigmatic eye was adjusted to the vertical from the horizontal position. The results were compared before and 1wk, 1, and 3mo after adjustment. RESULTS: UCVA and IOP were significantly reduced 1wk after position adjustment compared to 1wk after ICL implantation (P0.05). CONCLUSION: Early positioning adjustment post-phakic ICL implantation can benefit patients with adjusted arch height or higher IOP. Despite the good clinical effects, the doctors should pay attention to the potential for adverse effects on UCVA and corneal endothelium cells following early position adjustment after posterior chamber phakic ICL implantation.

Objective: This study aims to delineate the characteristics of severe self-injurious behaviors (SIB) in a cohort of children with autism and unspecified intellectual developmental disorder (UIDD) (intellectual disability) and examine potential risk factors for developing SIB. Methods: A retrospective chart review studied characteristics of severe SIB in 30 children with autism spectrum disorder (ASD) and UIDD referred to a tertiary care center. Characteristics examined include genetic syndromes, brain MRI abnormalities, verbal ability, adaptive functioning, SIB frequency and severity, age of onset, number of psychopharmacological agents, irritability, hyperactivity, stereotypy, psychiatric and physical comorbidities, among others. Descriptive and bivariate analysis were applied to explore potential relationships between factors. Results: Children with severe SIB exhibit this behaviour with high frequency, inflicting moderate to severe injury. Most children in the study sample are non-verbal and have ASD (93.3%; n = 28) with psychiatric (96.7%; n = 29) and physical (90%; n = 27) comorbidities. Overall SIB improvement using the Clinical Global Impression, Improvement Score (CGI-I) was 3.0 (minimally improved). A minority were much or very much improved following appropriate intervention. Conclusions: The severity of SIB is much higher in this sample than previously noted in the literature. Severe SIB is associated with ADHD, early onset mood disorders, tics, avoidant restrictive food intake disorder and Obsessive-Compulsive Disorder.