Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

Traditional Chinese medicine(TCM) solid waste is characterized by widespread availability, renewability, and substantial production volume. In the context of the "dual carbon" goals, the pyrolysis of TCM solid waste for producing fuel gas for recycling in pharmaceutical production has emerged as a crucial strategy for optimizing the energy structure in the TCM industry and developing renewable energy. This paper comprehensively reviews both internal and external factors that influence the pyrolysis of TCM solid waste. Internal factors encompass moisture content, particle size, ash content, and the morphology of the raw materials, while external factors include pyrolysis conditions, equivalence ratios, types of gasifiers, and gasifying agents. Furthermore, this paper details the challenges associated with the pyrolysis of TCM solid waste, such as the dispersion of feedstocks, the diversity of resources, the complexity of the pyrolysis process, and the variations in gasifier performance. Finally, this paper proposes measures to address these challenges. This paper aims to provide insights into the development of a circular economy for TCM resources and the advancement of low-carbon energy utilization in the TCM industry.
Pyrolysis ; Carbon/chemistry* ; Medicine, Chinese Traditional ; Solid Waste/analysis* ; Drugs, Chinese Herbal/chemistry* ; Gases/chemistry*

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology* ; Animals ; Male ; Mice ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Histones/metabolism* ; RNA Interference ; Testis/metabolism* ; Methylation ; Mice, Knockout ; Histone Demethylases

This article reports the clinical characteristics and treatment processes of three cases of mucormycosis occurring after hematopoietic stem cell transplantation in children, along with a review of relevant literature. All three patients presented with chest pain as the initial symptom, and metagenomic next-generation sequencing (mNGS) confirmed the mucycete infection early in all cases. Two patients recovered after treatment, while one succumbed to disseminated infection. mNGS has facilitated early diagnosis and treatment, reducing mortality rates. Additionally, surgical intervention is an important strategy for improving the prognosis of this condition.
Humans ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mucormycosis/etiology* ; Male ; High-Throughput Nucleotide Sequencing/methods* ; Child ; Female ; Metagenomics ; Child, Preschool

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

OBJECTIVES: To explore the therapeutic mechanism of Arctium lappa extract for treatment of Post-Viral Pneumonia Pulmonary Fibrosis (PPF). METHODS: The chemical constituents of Arctium lappa extracts were identified using UHPLC-Q-TOF-MS/MS. Mouse models of pulmonary fibrosis established by tracheal instillation of bleomycin were treated with Arctium lappa extract, and body weight changes were recorded and lung tissue pathology was examined using HE and Masson staining. Metabolomics analysis was used to identify the differential metabolites and the associated metabolic pathways in the treated mice. The common targets of viral pneumonia and pulmonary fibrosis were acquired from the publicly available databases, and the core targets and active constituents were screened using the protein-protein interaction (PPI) network, GO and KEGG enrichment analyses, and molecular docking, and a "gene-metabolite" regulatory network was constructed. The expressions of the core targets were detected in the lung tissues of the treated mice using Western blotting. RESULTS: Fifty-three chemical constituents were identified from Arctium lappa extract. In the mouse models of pulmonary fibrosis, treatment with Arctium lappa extract significantly improved weight loss and ameliorated lung inflammation and fibrosis. The differential metabolites in the treated mice were enriched in energy metabolism pathways involving citrate cycle, pentose phosphate pathway, glycolysis, tryptophan metabolism, glutamate metabolism and glutathione metabolism, which regulated the production of energy metabolism intermediates. Twenty-three key active compounds (mostly lignans and phenolic acids) and 82 core targets were screened, which were associated with the non-canonical Smad signaling pathways (including PI3K/AKT, HIF-1, MAPK, and Foxo) that participated in the regulation of energy metabolism. Arctium lappa extract also regulated the expressions of epithelial-mesenchymal transition (EMT)‑related proteins (fibronectin, vimentim, and Snail, etc.) and inhibited MAPK signaling pathway activation. CONCLUSIONS Preliminary findings suggest that Arctium lappa treats fibrosis by regulating metabolism to inhibit EMT and involves the modulation of non-canonical Smad signaling pathways, such as MAPK providing theoretical support for its clinical application and further research in treating PPF.
Arctium/chemistry* ; Animals ; Pulmonary Fibrosis/metabolism* ; Mice ; Metabolomics ; Network Pharmacology ; Plant Extracts/pharmacology* ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

120 extracted maxillary first premolars were endodontically treated and randomly divided into 5 groups(n=24).The teeth in group A had 4 walls of coronal tooth structure,in group B,C,D and E had only 3 walls,missing the palatal,buccal,mesial and distal wall,respectively.The teeth in group A0-E0(n=6)were restored without post,in group A1-E1(n=6)with buccal post,in group A2-E2(n=6)with palatal post,in group A3-E3(n=6)with buccal and palatal post,respectively.The fracture resistance of group A was higher than that of B,C,D and E groups(P＜0.05).The fracture resistance of fiber posts placed in the buccal root canal was higher than that in the palatal root canal(P＜0.05).The 360° complete ferrule can provide the best fracture resistance,When the ferrule is not complete,it is recommended to place buccal fiber post for repair.