Liang Xie

Oral submucous fibrosis (OSF) is a chronic, progressive, premalignant disorder with expanding epidemiology, rising annual incidence, and increasing malignant transformation rates. Therefore, elucidating its pathogenesis and establishing early intervention strategies remain urgent priorities. In this study, we evaluated the interplay between USP10 and IL‐6 and its potential influence on the development of oral submucous fibrosis. Immunohistochemistry and immunofluorescence were used to examine the correlation among IL‐6, USP10, and pathological angiogenesis in OSF clinical samples and mouse models, revealing high IL‐6 expression in the inflammatory microvasculature alongside downregulated USP10. Functional experiments on human umbilical vein endothelial cells (HUVECs) in vitro, including administration of recombinant human IL‐6, demonstrated that USP10 inhibited angiogenesis, cell migration, and cell proliferation, and that targeting USP10 reversed IL‐6‐mediated pathological angiogenesis. RNA sequencing further identified differentially expressed genes in HUVECs, while mass spectrometry, western blotting, and co‐immunoprecipitation uncovered that USP10 interacts with vascular endothelial growth factor receptor 1 (VEGFR1) and inhibits its ubiquitination, thereby suppressing angiogenesis. Collectively, these findings indicate that IL‐6 promotes pathological angiogenesis by suppressing USP10 and its interaction with VEGFR1, thus accelerating OSF progression, and suggest that targeting USP10 may represent a promising mechanism for further investigation in OSF therapy.

Periodontitis has emerged as one of the most critical oral diseases, and research on this condition holds great importance for the advancement of stomatology. As the most authoritative national scientific research funding institution in China, the National Natural Science Foundation of China (NSFC) has played a pivotal role in driving the progress of periodontal science by supporting research on periodontitis. This article provides a comprehensive review of the research and development progress related to periodontitis in China from 2014 to 2023, highlighting the significant contributions of the NSFC to this field. We have summarized the detailed funding information from the NSFC, including the number of applicant codes, funded programs and the distribution of funded scholars. These data illustrate the efforts of the NSFC in cultivating young scientists and building research groups to address key challenges in national scientific research. This study offers an overview of the current hot topics, recent breakthroughs and future research prospects related to periodontitis in China.

Supramolecular hydrogels derived from nucleosides have been gaining significant attention in the biomedical field due to their unique properties and excellent biocompatibility. However, a major challenge in this field is that there is no model for predicting whether nucleoside derivative will form a hydrogel. Here, we successfully develop a machine learning model to predict the hydrogel-forming ability of nucleoside derivatives. The optimal model with a 71% (95% Confidence Interval, 0.69−0.73) accuracy is established based on a dataset of 71 reported nucleoside derivatives. 24 molecules are selected via the optimal model external application and the hydrogel-forming ability is experimentally verified. Among these, two rarely reported cation-independent nucleoside hydrogels are found. Based on their self-assemble mechanisms, the cation-independent hydrogel is found to have potential applications in rapid visual detection of Ag⁺ and cysteine. Here, we show the machine learning model may provide a tool to predict nucleoside derivatives with hydrogel-forming ability.

Proteasome activator subunit 3 (PA28γ) is a member of the proteasome activator family, which mainly regulates the degradation and stability of proteins. Studies have shown that it plays crucial roles in lipid formation, stemness maintenance, and blood vessel formation. However, few studies have clarified the association between PA28γ and bone diseases. Herein, we identified PA28γ as a previously unknown regulator of bone homeostasis that coordinates bone formation and lipid accumulation. PA28γ-knockout mice presented with the characteristics of low bone mass and accumulation of lipids. Suppressed expression of PA28γ restrained the osteogenic differentiation and enhanced the adipogenic differentiation of bone marrow stromal cells (BMSCs). Overexpression of PA28γ promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs. Mechanistically, PA28γ interacted with Wnt5α, and the two interactors appeared to be positively correlated. PA28γ mainly activated the downstream Wnt/β-catenin signaling pathway, which affects BMSCs differentiation homeostasis. Deletion of Wnt5α significantly delayed the promotion of osteogenic differentiation and partially alleviated the inhibitory effect of adipogenic differentiation of BMSCs in the PA28γ-overexpressing group. Furthermore, we demonstrated that PA28γ-knockout mice had an inhibited rate of bone healing in a drill-hole femoral bone defect model in vivo. Therefore, our results confirm the effects of PA28γ on bone formation and bone defect repair, indicating that PA28γ mainly interacts with Wnt5α to activate the Wnt/β-catenin signaling pathway regulating BMSCs differentiation homeostasis. Our results reveal the function of PA28γ in bone diseases and provide a new theoretical basis for expanding the treatment of bone diseases.

The excellent performance of semiconductor nanocrystals as sensitizers for photothermal therapy (PTT) has attracted the attention of many researchers; however, they are hindered by limited bandwidth and complex synthesis. To overcome these limitations, starting with an initial determination of photothermal conductivity, we synthesized and designed molybdenum and Cys-MoO_3−x nanoparticles (NPs) for use in the minimally invasive treatment of papillary thyroid carcinoma (PTC), as the NPs are coated only with cysteine molecules. The obtained Cys-MoO₂ NPs were used as a PTT reaction drug for topical application to PTC cells. The use of near-infrared photoconductive PTT in combination with low-toxicity biological chemotherapy reached a 90% efficacy for cancer treatment in vitro. The conducted experiments intuitively demonstrate that non-toxic Cys-MoO₂ NPs are lethal to the cancer cells under visual (VL, 405 nm) and near-infrared (NIR, 808 nm) laser irradiation and can be precisely controlled. Therefore, this study provides a powerful, safe, and easily modified NP platform for photo-triggered PTC elimination with broad application prospects. Assessment of the ideal damage range indicates a high degree of controllability, allowing the tumor to be precisely targeted while minimizing damage to the surrounding healthy tissue. In conclusion, this study provides a convenient, safe, and powerful NP platform for the near-infrared photo-controlled PTT of PTC cells, which has broad application prospects for the elimination of PTC and other types of cancer.

To compare and investigate the differences and characteristics of pulmonary vascular remodeling in three mouse models of pulmonary arterial hypertension (PAH) constructed by left pneumonectomy, jugular vein injection of monocrotaline pyrrole, and left pneumonectomy combined with jugular vein injection of monocrotaline pyrrole, to explore for a PAH animal model that approximates the clinical pathogenesis of PAH, and to create a model that will provide sound basis for thorough investigation into the pathogenesis of severe PAH. 59 male C57/BL mice (10-12 weeks, 24-30 g) were randomized into four groups, a control group ( n=9), a group that had left pneumonectomy (PE, n=15), a group that had jugular vein injection of monocrotaline pyrrole (MCTP, n=15), and the last group that had left pneumonectomy combined with jugular injection of monocrotaline pyrrole (P+M, n=20). To evaluate the effect of modeling and the characteristics of pulmonary vascular remodeling, hemodynamic and morphological parameters, including right ventricular systolic pressure (RVSP), right ventricle/(left ventricle plus septum) (RV/LV+S), percent of wall thickness in the pulmonary artery (WT%), muscularization of non-muscular arteries, neointima formation, and vascular obstruction score (VOS), were measured in each group. 1) Compared with those of the control group, the RVSP, RV/LV+S, WT%, and the degree of small pulmonary arteries muscularization in the P+M group were significantly increased ( PP0.05). 2) Neointima formation in the acinus pulmonary arteries, which caused obvious stenosis of the lumen, was observed in the P+M group, the VOS being 1.25±0.80 points ( P0.05). Left pneumonectomy combined with jugular intravenous injection of MCTP could induce severe PAH formation in mouse. The model provides a good simulation of neointima formation, the characteristic pathological change of clinical severe PAH.

Purpose: The present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario.Materials and Methods: In this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared.Results: One hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery.Conclusion: Our results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

Background: Damaged and dead cells release cell-free DNA (cfDNA) that activates cyclic GMP–AMP (cGAMP) synthase (cGAS), which leads to the activation of stimulator of interferon genes (STING) via the second messenger cGAMP. STING promotes the production of inflammatory cytokines and type I interferons to induce an inflammatory response. Oral lichen planus (OLP), a chronic autoimmune disease involving oral mucosa characterized by the apoptosis of keratinocytes mediated by T-lymphocytes, is related to the activation of multiple inflammatory signaling pathways. Currently, the relationship between cfDNA and OLP has not been confirmed. We hypothesized that cfDNA may be a potential therapeutic target for OLP.Methods: cfDNA was extracted from the saliva and plasma of OLP patients; its concentration was measured using the Quanti-iT-PicoGree kit and its relationship with OLP inflammation was assessed. cfDNA of OLP patients (cfDNA-OLP) was transfected into THP-1 macrophages and the expression of inflammatory factors was investigated by performing quantitative real time PCR (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA). STING expression was analyzed in the tissues of OLP patients and healthy controls using immunohistochemical staining and western blotting. siRNA was used to knockdown STING expression in THP-1 macrophages, and the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secreted by cells following cfDNA-OLP transfection were detected using ELISA. Finally, the effect of the cationic polymer PAMAM-G3 was evaluated on the treatment of inflammation induced by cfDNA-OLP.Results: The concentration of cfDNA in the saliva and plasma of OLP patients was considerably higher than that of healthy controls, and it positively correlated with the levels of inflammatory cytokines and clinical characteristics. cfDNA-OLP induced an inflammatory response in THP-1 macrophages. STING expression was significantly higher in OLP tissues than in the gingival tissues of healthy controls. STING knockdown suppressed cfDNA-OLP-induced inflammation in THP-1 macrophages. PAMAM-G3 inhibited the inflammatory response caused by cfDNA-OLP.Conclusion: The cfDNA level is increased in OLP patients, and the STING pathway activated by cfDNA-OLP might play a critical role in OLP pathogenesis. Treatment with PAMAM-G3 reduced the inflammation induced by cfDNA-OLP, and therefore, may be a potential treatment strategy for OLP.