Identification of the differentially expressed activated memory CD4+ T-cells-related genes and ceRNAs in oral lichen planus.

Background: Oral lichen planus (OLP) is a common chronic oral mucosal disease with 1.4 % malignant transformation rate, and its etiology especially immune pathogenesis remains unclear. This study was aimed at investigating the immune cells related molecular underlying the pathophysiology of OLP through bioinformatics analysis. Methods: The dataset GSE52130 obtained from the Gene Expression Omnibus (GEO) database was conducted a comprehensive analysis in this study. The CIBERSORTx was used for investigating immune cells infiltration. The gene set enrichment analysis (GSEA) and gene ontology (GO) enrichment were performed for exploring the biological functions and gene annotation. The protein-protein interactions (PPI) were constructed by STRING database and visualized by Cytoscape software. The cytohubba plugin was utilized for screening hub genes. The receiver operating characteristic (ROC) was performed for evaluating diagnostic value of hub genes. The miRNAs, lncRNAs and drugs were respectively predicted by NetworkAnalyst, miRTarbase, ENCORI, and DGIdb database. Results: This study identified 595 differentially expressed genes (DEGs). The GSEA indicated keratinization, innate immune system and biological oxidation were involved in OLP. GO analysis showed extracellular matrix and keratinocyte were mainly enriched. And we found the activated memory CD4+ T cells were lowly infiltrated in OLP. We identified 101 activated memory CD4+ T-cells-related DEGs. Three hub genes (APP, IL1B, TF) were selected. APP and IL1B were significantly up-regulated, whereas TF was down-regulated in OLP. The three hub genes show high diagnostic value in OLP. Additionally, they were involved in MAPK signal, NF-kappaB signal and iron metabolism in OLP. What's more, NEAT1/XIST - miR - 15a - 5p/miR - 155-5p - APP/IL1B signal axis was focused in competing endogenous RNA (ceRNA) network. In addition, 35 drugs were predicted for OLP. Conclusion: Three activated memory CD4+ T-cells-related DEGs were identified by integrative analysis. It may provide novel insight into the pathogenesis of OLP and suggest potential therapeutic targets for OLP.

Comparison of elastic stable intramedullary nailing versus Kirschner wires in treatment of pediatric radial neck fractures.

Purpose: The aim of the study was to compare the different internal fixations between elastic stable intramedullary nailing and Kirschner wires in treatment of angulated radial neck fractures. Methods: We retrospectively reviewed the patients with radial neck fracture without associated injuries who underwent surgery approach in our department during April 2011-March 2020. There were 62 patients meeting all the criteria with complete clinical data, with median age of 7.5 (IQR 5.8-9.5) years, 34 males and 28 females. The preoperative fracture pattern was assessed according to the Judet classification system. Depending on the materials implanted and fixation strategy, the patients could be divided into a Kirschner wire group and an elastic stable intramedullary nailing group. Final functional outcomes of patients were assessed by the Mayo Elbow Performance Score and Tibone-Stoltz functional evaluation classification. Results: The Kirschner wire group included 37 patients, with 4.8 years median follow-up. The elastic stable intramedullary nailing group included 25 patients with 5.9 years median follow-up. There were no significant differences in gender, age, Judet classification, average operative time, Mayo Elbow Performance Score, Tibone-Stoltz classification, or length of hospital stay between groups. However, the time to union in the Kirschner wire group was significantly shorter than that in the elastic stable intramedullary nailing group (p < 0.05). Both groups achieved satisfactory functional and cosmetic results. Conclusion: In the management of pediatric radial neck fractures, both elastic stable intramedullary nailing and Kirschner wire internal fixation have shown equivalent therapeutic results, leading to satisfactory functional outcomes. The selection of the internal fixation approach can be influenced by the patient's fracture characteristics and the surgeon's preferences. Level of evidence: Level III; Retrospective Comparison; Treatment Study.

The role of the cartilaginous to osseous acetabular angle ratio in children with developmental dysplasia of the hip.

Purpose: This study aims to demonstrate the use of the cartilaginous to osseous acetabular angle ratio (AAR) in surgical decision-making for hip dysplasia. Methods: Data were collected from patients who underwent an MRI of the hip after conservative treatment for developmental dysplasia of the hip between August 2019 and 2022. The data included demographic information as well as an anteroposterior pelvic radiograph. The osseous acetabular index (OAI) was measured using x-ray, while the cartilaginous acetabular index (CAI) and the cartilaginous acetabulum head index (CAHI) were measured using MRI. The square of the CAI to OAI, AAR, was calculated. The patients in the residual hip dysplasia (RHD) group were categorized as having an OAI above 20°. During the postoperative follow-up, we evaluated the patients in this group who underwent Bernese triple pelvic osteotomy. Data on surgical patients with an observation period that exceeded 1 year were collected and analyzed. The distribution of the AAR among the different groups was analyzed. A receiver operating characteristic (ROC) predictive model was constructed using the AAR of the patients in the normal and surgical groups to evaluate the need for surgery. Results: It was found that there was a significant difference in the OAI, CAI, CAHI, and AAR between the RHD group (OAI 26.15 ± 3.90°, CAI 11.71 ± 4.70°, CAHI 79.75 ± 6.27%, and AAR 5.88 ± 4.24) and the control group patients (OAI 16.77 ± 5.39°, CAI 6.16 ± 3.13°, CAHI 85.05 ± 4.91%, and AAR 2.71 ± 2.08) (p < 0.001). A total of 93.5% of the control group patients had an AAR ≤5, while only 6.5% had an AAR >5. The results of postoperative imaging follow-up were "excellent" in 52 patients and "good" in 3, while the functional follow-up results were excellent in 53 and good in 2. In 15 patients, the observation period exceeded 1 year. The mean observation period was 633.1 ± 259.6 days and the preoperative CAHI was 71.7 ± 4.8%. Of the patients with an AAR >5, a substantial 94.8% (55/58) of them were reported to have undergone surgery, while all patients with an AAR less than or equal to 5 did not undergo surgery (91/91). Based on the ROC, a cutoff value of 5.09 was identified for the need for surgery in children with RHD. Conclusions: A surgical decision for residual hip dysplasia can be based on the AAR. An AAR >5 may be a potential indicator for surgical intervention in patients with RHD.

Characterization of novel PHEX variants in X-linked hypophosphatemic rickets and genotype-PHEX activity correlation.

BACKGROUND: X-linked hypophosphatemia (XLHR) is the most common genetic form of hypophosphatemic rickets (HR), which is caused by phosphate regulating endopeptidase homolog X-linked (PHEX) gene mutation. At present, the genotype-phenotype relationship of XLHR and the pathogenic role of PHEX have not been fully understood. METHODS: In this study, we summarized clinical features in a new cohort of 49 HR patients and detected 16 novel PHEX and 5 novel non-PHEX variants. Subsequently, we studied the pathogenesis of new variants by protein expression, glycosylation analysis, subcellular localization and endopeptidase activity. RESULTS: The results showed that missense variants (Q189H and X750R) slightly reduced protein expression without obviously altering protein length and localization, whereas truncating variants significantly impaired the synthesis of PHEX and produced a shorter immature protein in cells. Interestingly, no evident correlation was observed between mutation types and clinical phenotypes. However, when we analyzed the relationship between PHEX activity and serum phosphorus level, we found that patients with low PHEX activity tended to have severe hypophosphatemia and high rickets severity score (RSS). Following this observation, we established two new knock-in XLHR mouse models with two novel Phex variants (c.T1349C and c.C426G, respectively) using CRISPR/Cas9 technology. Both mouse models demonstrated clinical manifestations of XLHR seen in patients and PhexC426G mice showed more severe phenotype than PhexT1349C mice, which further confirmed the rationality of genotype-PHEX enzymatic activity correlation analysis. CONCLUSION: Therefore, our findings demonstrated that novel PHEX variants could disrupt protein function via affecting protein synthesis, post-translational modification, cellular trafficking and catalytic activity. Our study facilitates a better understanding of XLHR pathogenic mechanism and PHEX activity-phenotype correlation, which is of crucial importance for future diagnosis and treatment of XLHR.

Investigating the interconnectedness of carbon, fossil energy, and financial markets: A dynamic spillover index approach.

Against the background of the global active pursuit of carbon neutrality, this paper uses the DY spillover index method to analyze the spillover network effects between carbon, fossil energy and financial markets. The research results show that the spillover effects between these three markets change over time, with an average spillover index of 25.30%, showing a significant mutual influence. Further analysis found that the EU carbon market plays an important role in spillover effects. Especially under the influence of extreme events, the spillover effects reach their peak. At this time, the degree of mutual influence between markets is as high as 60.01%. In addition, during the COVID-19 epidemic, the spillover effect of the EU carbon market on other markets also reached its maximum, indicating that the epidemic increased the contagion of cross-market risks and caused the carbon market to bear greater risks. The research results of this article have important guiding significance for environmental protection investment and emphasize the importance of formulating differentiated environmental protection policies in different time frames. Facing the dual challenges of global climate change and promoting the goal of carbon neutrality, governments and relevant institutions should pay close attention to changes in spillover effects between markets and timely adjust environmental protection policies to achieve maximum results.

Modeling collision avoidance maneuvers for micromobility vehicles.

INTRODUCTION: In recent years, as novel micromobility vehicles (MMVs) have hit the market and rapidly gained popularity, new challenges in road safety have also arisen. There is an urgent need for validated models that comprehensively describe the behavior of such novel MMVs. This study aims to compare the longitudinal and lateral control of bicycles and e-scooters in a collision-avoidance scenario from a top-down perspective, and to propose appropriate quantitative models for parameterizing and predicting the trajectories of the avoidance-braking and steering-maneuvers. METHOD: We compared a large e-scooter and a light e-scooter with a bicycle (in assisted and non-assisted modes) in field trials to determine whether these new vehicles have different maneuverability constraints when avoiding a rear-end collision by braking and/or steering. RESULTS: Braking performance in terms of deceleration and jerk varies among the different types of vehicles; specifically, e-scooters are not as effective at braking as bicycles, but the large e-scooter demonstrated better braking performance than the light one. No statistically significant difference was observed in the steering performance of the vehicles. Bicycles were perceived as more stable, maneuverable, and safe than e-scooters. The study also presents arctangent kinematic models for braking and steering, which demonstrate better accuracy and informativeness than linear models. CONCLUSIONS: This study demonstrates that the new micromobility solutions have some maneuverability characteristics that differ significantly from those of bicycles, and even within their own kind. Steering could be a more efficient collision-avoidance strategy for MMVs than braking under certain circumstances, such as in a rear-end collision. More complicated modeling for MMV kinematics can be beneficial but needs validation. PRACTICAL APPLICATIONS: The proposed arctangent models could be used in new advanced driving assistance systems to prevent crashes between cars and MMV users. Micromobility safety could be improved by educating MMV riders to adapt their behavior accordingly. Further, knowledge about the differences in maneuverability between e-scooters and bicycles could inform infrastructure design, and traffic regulations.

An augmented diffusion algorithm with bidirectional communication for a distributed active noise control system.

Recent studies on diffusion adaptation for distributed active noise control (DANC) systems have attracted significant research interest due to their balance between computational burden and stability compared to conventional centralized and decentralized adaptation schemes. The conventional multitask diffusion FxLMS algorithm assumes that the converged solutions of all control filters are consistent to each other, which is unrealistic in practice hence results in inferior performance in noise reduction. An augmented diffusion FxLMS algorithm has been proposed to overcome this problem, which adopts a neighborhood-wide adaptation and node-based combination approach to mitigate the bias in the converged solution of the multitask diffusion algorithms. However, the improvement comes at the expense of a higher computational burden and communication cost. All existing DANC systems, including the multitask and augmented diffusion algorithms, assume one-way communication between nodes. By contrast, this paper proposes a bidirectional communication scheme for the augmented diffusion algorithm to further reduce the memory requirement, computational burden, and communication cost. Simulation results in the free field and with measured room impulse responses both demonstrate that the proposed augmented diffusion algorithm with bidirectional communication can achieve a faster convergence speed than that based on one-way communication with a lower memory, computation, and communication burden.

A Risk Model for Prognosis and Treatment Response Prediction in Colon Adenocarcinoma Based on Genes Associated with the Characteristics of the Epithelial-Mesenchymal Transition.

The epithelial-mesenchymal transition (EMT) is an important process during metastasis in various tumors, including colorectal cancer (CRC). Thus, the study of its characteristics and related genes is of great significance for CRC treatment. In this study, 26 EMT-related gene sets were used to score each sample from The Cancer Genome Atlas program (TCGA) colon adenocarcinoma (COAD) database. Based on the 26 EMT enrichment scores for each sample, we performed unsupervised cluster analysis and classified the TCGA-COAD samples into three EMT clusters. Then, weighted gene co-expression network analysis (WGCNA) was used to investigate the gene modules that were significantly associated with these three EMT clusters. Two gene modules that were strongly positively correlated with the EMT cluster 2 (worst prognosis) were subjected to Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. Then, a prognosis-related risk model composed of three hub genes GPRC5B, LSAMP, and PDGFRA was established. The TCGA rectal adenocarcinoma (READ) dataset and a CRC dataset from the Gene Expression Omnibus (GEO) were used as the validation sets. A novel nomogram that incorporated the risk model and clinicopathological features was developed to predict the clinical outcomes of the COAD patients. The risk model served as an independent prognostic factor. It showed good predictive power for overall survival (OS), immunotherapy efficacy, and drug sensitivity in the COAD patients. Our study provides a comprehensive evaluation of the clinical relevance of this three-gene risk model for COAD patients and a deeper understanding of the role of EMT-related genes in COAD.

Research on Photoacoustic Synthetic Aperture Focusing Technology Imaging Method of Internal Defects in Cylindrical Components.

Cylindrical components are parts with curved surfaces, and their high-precision defect testing is of great significance to industrial production. This paper proposes a noncontact internal defect imaging method for cylindrical components, and an automatic photoacoustic testing platform is built. A synthetic aperture focusing technology in the polar coordinate system based on laser ultrasonic (LU-pSAFT) is established, and the relationship between the imaging quality and position of discrete points is analyzed. In order to verify the validity of this method, small holes of Φ0.5 mm in the aluminum alloy rod are tested. During the imaging process, since a variety of waveforms can be excited by the pulsed laser synchronously, the masked longitudinal waves reflected by small holes need to be filtered and windowed to achieve high-quality imaging. In addition, the influence of ultrasonic beam angle and signal array spacing on imaging quality is analyzed. The results show that the method can accurately present the outline of the small hole, the circumferential resolution of the small hole is less than 1° and the dimensional accuracy and position error are less than 0.1 mm.

Sulforaphane Inhibits Exhaustive Exercise-Induced Liver Injury and Transcriptome-Based Mechanism Analysis.

Exhaustive exercise (EE) induces liver injury and has recently gained much attention. Sulforaphane (SFN) can protect the liver from inflammation and oxidative stress. However, the effects of SFN on EE-induced liver injury and its underlying mechanisms are still unclear. C57BL/6J mice swimming to exhaustion for seven days were used to simulate the liver injury caused by EE. Different doses of SFN (10, 30, 90 mg/kg body weight) were gavage-fed one week before and during the exercise. SFN intervention significantly reduced the EE-induced lactate dehydrogenase (LDH), creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum, as well as attenuating liver tissue morphological abnormality, oxidative stress injury, and inflammation. Liver transcriptomic analysis showed that the differentially expressed genes altered by SFN intervention in the exercise model were mainly enriched in glucose and lipid metabolism pathways. The most altered gene by SFN intervention screened by RNA-seq and validated by qRT-PCR is Ppp1r3g, a gene involved in regulating hepatic glycogenesis, which may play a vital role in the protective effects of SFN in EE-induced liver damage. SFN can protect the liver from EE-induced damage, and glucose and lipid metabolism may be involved in the mechanism of the protective effects.

Object Detection of Flexible Objects with Arbitrary Orientation Based on Rotation-Adaptive YOLOv5.

It is challenging to accurately detect flexible objects with arbitrary orientation from monitoring images in power grid maintenance and inspection sites. This is because these images exhibit a significant imbalance between the foreground and background, which can lead to low detection accuracy when using a horizontal bounding box (HBB) as the detector in general object detection algorithms. Existing multi-oriented detection algorithms that use irregular polygons as the detector can improve accuracy to some extent, but their accuracy is limited due to boundary problems during the training process. This paper proposes a rotation-adaptive YOLOv5 (R_YOLOv5) with a rotated bounding box (RBB) to detect flexible objects with arbitrary orientation, effectively addressing the above issues and achieving high accuracy. Firstly, a long-side representation method is used to add the degree of freedom (DOF) for bounding boxes, enabling accurate detection of flexible objects with large spans, deformable shapes, and small foreground-to-background ratios. Furthermore, the further boundary problem induced by the proposed bounding box strategy is overcome by using classification discretization and symmetric function mapping methods. Finally, the loss function is optimized to ensure training convergence for the new bounding box. To meet various practical requirements, we propose four models with different scales based on YOLOv5, namely R_YOLOv5s, R_YOLOv5m, R_YOLOv5l, and R_YOLOv5x. Experimental results demonstrate that these four models achieve mean average precision (mAP) values of 0.712, 0.731, 0.736, and 0.745 on the DOTA-v1.5 dataset and 0.579, 0.629, 0.689, and 0.713 on our self-built FO dataset, exhibiting higher recognition accuracy and a stronger generalization ability. Among them, R_YOLOv5x achieves a mAP that is about 6.84% higher than ReDet on the DOTAv-1.5 dataset and at least 2% higher than the original YOLOv5 model on the FO dataset.

Environmental impact assessment of multi-source solid waste based on a life cycle assessment, principal component analysis, and random forest algorithm.

As a national pilot city for solid waste disposal and resource reuse, Dongguan in Guangdong Province aims to vigorously promote the high-value utilization of solid waste and contribute to the sustainable development of the Greater Bay Area. In this study, life cycle assessment (LCA) coupled with principal component analysis (PCA) and the random forest (RF) algorithm was applied to assess the environmental impact of multi-source solid waste disposal technologies to guide the environmental protection direction. In order to improve the technical efficiency and reduce pollution emissions, some advanced technologies including carbothermal reduction‒oxygen-enriched side blowing, directional depolymerization‒flocculation demulsification, anaerobic digestion and incineration power generation, were applied for treating inorganic waste, organic waste, kitchen waste and household waste in the park. Based on the improved techniques, we proposed a cyclic model for multi-source solid waste disposal. Results of the combined LCA-PCA-RF calculation indicated that the key environmental load type was human toxicity potential (HTP), came from the technical units of carbothermal reduction and oxygen-enriched side blowing. Compared to the improved one, the cyclic model was proved to reduce material and energy inputs by 66%-85% and the pollution emissions by 15%-88%. To sum up, the environmental impact assessment and systematic comparison suggest a cyclic mode for multi-source solid waste treatments in the park, which could be promoted and contributed to the green and low-carbon development of the city.

How do different micro-mobility vehicles affect longitudinal control? Results from a field experiment.

INTRODUCTION: While micromobility vehicles offer new transport opportunities and may decrease fuel emissions, the extent to which these benefits outweigh the safety costs is still uncertain. For instance, e-scooterists have been reported to experience a tenfold crash risk compared to ordinary cyclists. Today, we still do not know whether the real safety problem is the vehicle, the human, or the infrastructure. In other words, the new vehicles may not necessarily be unsafe; the behavior of their riders, in combination with an infrastructure that was not designed to accommodate micromobility, may be the real issue. METHOD: In this paper, we compared e-scooters and Segways with bicycles in field trials to determine whether these new vehicles create different constraints for longitudinal control (e.g., in braking avoidance maneuvers). RESULTS: The results show that acceleration and deceleration performance changes across vehicles; specifically, e-scooters and Segways that we tested cannot brake as efficiently as bicycles. Further, bicycles are experienced as more stable, maneuverable, and safe than Segways and e-scooters. We also derived kinematic models for acceleration and braking that can be used to predict rider trajectories in active safety systems. PRACTICAL APPLICATIONS: The results from this study suggest that, while new micromobility solutions may not be intrinsically unsafe, they may require some behavior and/or infrastructure adaptations to improve their safety. We also discuss how policy making, safety system design, and traffic education may use our results to support the safe integration of micromobility into the transport system.

Integrated Metabolomics and Network Pharmacology Investigation of Cardioprotective Effects of Myricetin after 1-Week High-Intensity Exercise.

Cardiovascular adverse effects caused by high-intensity exercise (HIE) have become a public health problem of widespread concern. The therapeutic effect and metabolic regulation mechanism of myricetin, a phytochemical with potential therapeutic effects, have rarely been studied. In this study, we established mice models of different doses of myricetin intervention with 1 week of HIE after intervention. Cardiac function tests, serology, and pathological examinations were used to evaluate the protective effect of myricetin on the myocardium. The possible therapeutic targets of myricetin were obtained using an integrated analysis of metabolomics and network pharmacology and verified using molecular docking and RT-qPCR experiments. Different concentrations of myricetin improved cardiac function, significantly reduced the levels of myocardial injury markers, alleviated myocardial ultrastructural damage, reduced the area of ischemia/hypoxia, and increased the content of CX43. We obtained the potential targets and regulated metabolic network of myricetin by combined network pharmacology and metabolomics analysis and validated them by molecular docking and RT-qPCR. In conclusion, our findings suggest that myricetin exerts anti-cardiac injury effects of HIE through the downregulation of PTGS2 and MAOB and the upregulation of MAP2K1 and EGFR while regulating the complicated myocardial metabolic network.

Expanding the valorization of waste mushroom substrates in agricultural production: progress and challenges.

Waste mushroom substrate (WMS) generated in large quantities from mushroom production process has caused severe environmental pollution. As a sustainable resource, the valorization of WMS in the agricultural field has attracted attention due to the abundant active components. A comprehensive review of valorization of WMS in agricultural production is meaningful to promote the further utilization of this resource. This paper provided an overview of the valorization in sustainable agricultural production using WMS, including animal and crop farming improvement, and agricultural environmental restoration. Moreover, the limitations and the possible development directions of WMS in agricultural production were discussed. Different sustainable cycle models for WMS in agricultural production were proposed. The aim of this review is to provide a feasible solution for the favorable treatment of WMS and improvement of agricultural production quality.

Failure to achieve reduction on developmental dysplasia of hip: an ultrasound evaluation.

BACKGROUND: Ultrasound examination of the medial side of the hip joint has been rarely used to evaluate the status of developmental dysplasia of the hip (DDH) in Pavlik harness treatment according to the literature. PURPOSE: To analyze the effects of cartilaginous acetabulum, hip joint labrum, and acetabular tissue on the reduction of DDH. MATERIAL AND METHODS: A total of 50 cases (100 hips) were detected by the Graf method with a high-frequency linear transducer (L 5-12), and there were 59 dislocated hips and 41 non-dislocated hips. Patients were treated with a Pavlik harness. Ultrasound examination of the medial side of the hip joint was performed for follow-up. The hip joints were divided into three groups: the non-dislocated group; the reducible group; and the non-reducible group. RESULTS: The success rate of reduction was significantly higher when the acetabulum cartilage was located on the cephalic side (chi-square = 28.12, P < 0.001). The success rate was also significantly higher when the hip joint labrum was located on the cephalic side (chi-square = 17.21, P < 0.001). Type III and D had a higher success rate of reduction than type IV (P < 0.001). The pairwise comparison of the measurements of acetabular tissue between the non-dislocated group, the reducible group, and the non-reducible group showed statistical differences (P < 0.001). CONCLUSION: The present study confirmed that the location of acetabulum cartilage and hip joint labrum affected the outcome of treatment. The degree of dislocation and the amount of acetabular tissue were correlated with the success rate of treatment.

Inhibition of the dopamine transporter promotes lysosome biogenesis and ameliorates Alzheimer's disease-like symptoms in mice.

INTRODUCTION: Lysosomes are degradative organelles that maintain cellular homeostasis and protein quality control. Transcription factor EB (TFEB)-mediated lysosome biogenesis enhances lysosome-dependent degradation and alleviates neurodegenerative diseases, but the mechanisms underlying TFEB regulation and modification are still poorly understood. METHODS: By screening novel small-molecule compounds, we identified a group of lysosome-enhancing compounds (LYECs) that promote TFEB activation and lysosome biogenesis. RESULTS: One of these compounds, LH2-051, significantly inhibited the function of the dopamine transporter (DAT) and subsequently promoted lysosome biogenesis. We uncovered cyclin-dependent kinase 9 (CDK9) as a novel regulator of DAT-mediated lysosome biogenesis and identified six novel CDK9-phosphorylated sites on TFEB. We observed that signal transduction by the DAT-CDK9-TFEB axis occurs on lysosomes. Finally, we found that LH2-051 enhanced the degradation of amyloid beta plaques and improved the memory of amyloid precursor protein (APP)/Presenilin 1 (PS1) mice. DISCUSSION: We identified the DAT-CDK9-TFEB signaling axis as a novel regulator of lysosome biogenesis. Our study sheds light on the mechanisms of protein quality control under pathophysiological conditions.

Extraction and utilization of active substances from edible fungi substrate and residue: A review.

The expansion of the edible fungi industry has resulted in the production of large amounts of edible fungus residues, causing great pressure on environmental protection.Therefore, research on edible fungus residue utilization has become a controversial issue. Thus far, numerous efforts have been devoted to separate active substances from edible fungus substrates and residues for high application value utilization. Building upon this, the main methods for extracting active substances from edible mushroom residues are reviewed, and the mechanisms, influencing factors, and trade-offs of the various methods are analysed. Furthermore, the existing and possible directions of utilization of the extracted active substances are reviewed and discussed. Finally, challenges and prospects for the extraction and utilization of different substances in edible fungus residues are proposed. This review provides an effective strategy for protecting the ecological environment and promoting the sustainable development of human society.

TFEB acetylation promotes lysosome biogenesis and ameliorates Alzheimer's disease-relevant phenotypes in mice.

Lysosomes are one of the major centers for regulating cargo degradation and protein quality control. Transcription factor EB (TFEB)-promoted lysosome biogenesis enhances lysosome-mediated degradation and alleviates neurodegenerative diseases, but the mechanisms underlying TFEB modification and activation are still poorly understood. Here, we report essential roles of TFEB acetylation in TFEB nuclear translocation and lysosome biogenesis, which are independent of TFEB dephosphorylation. By screening small molecules, we find that Trichostatin A (TSA), the pan-inhibitor of histone deacetylases (HDACs), promotes nuclear translocation of TFEB. TSA enhances the staining of cells by LysoTracker Red and increases the expression of lysosomal and autophagic genes. We identify four novel acetylated lysine residues in TFEB, which are important for TFEB nuclear translocation and lysosome biogenesis. We show that TFEB acetylation is regulated by HDACs (HDAC5, HDAC6, and HDAC9) and lysine acetyltransferases (KATs), including ELP3, CREBBP, and HAT1. During TSA-induced cytosol-to-nucleus translocation of TFEB, acetylation is independent of TFEB dephosphorylation, since the mTORC1- or GSK3ß-related phosphorylation sites on TFEB are still phosphorylated. Administration of TSA to APP/PS1 mice increases the expression of lysosomal and autophagic genes in mouse brains and also improves memory. Accordingly, the ß-amyloid plaque burden is decreased. These results show that the acetylation of TFEB, as a novel mechanism of TFEB activation, promotes lysosome biogenesis and alleviates the pathogenesis of Alzheimer's disease. Our results also suggest that HDAC inhibition can promote lysosome biogenesis, and this may be a potential therapeutic approach for the treatment of neurodegenerative diseases and disorders related to HDAC hyperactivation.

Dihydromyricetin Enhances Exercise-Induced GLP-1 Elevation through Stimulating cAMP and Inhibiting DPP-4.

The purpose of this study was to examine whether endogenous GLP-1 (glucagon-like peptide-1) could respond to exercise training in mice, as well as whether dihydromyricetin (DHM) supplementation could enhance GLP-1 levels in response to exercise training. After 2 weeks of exercise intervention, we found that GLP-1 levels were significantly elevated. A reshaped gut microbiota was identified following exercise, as evidenced by the increased abundance of Bifidobacterium, Lactococcus, and Alistipes genus, which are involved in the production of short-chain fatty acids (SCFAs). Antibiotic treatment negated exercise-induced GLP-1 secretion, which could be reversed with gut microbiota transplantation. Additionally, the combined intervention (DHM and exercise) was modeled in mice. Surprisingly, the combined intervention resulted in higher GLP-1 levels than the exercise intervention alone. In exercised mice supplemented with DHM, the gut microbiota composition changed as well, while the amount of SCFAs was unchanged in the stools. Additionally, DHM treatment induced intracellular cAMP in vitro and down-regulated the gene and protein expression of dipeptidyl peptidase-4 (DPP-4) both in vivo and in vitro. Collectively, the auxo-action of exercise on GLP-1 secretion is associated with the gut-microbiota-SCFAs axis. Moreover, our findings suggest that DHM interacts synergistically with exercise to enhance GLP-1 levels by stimulating cAMP and inhibiting DPP-4.