BACKGROUND:Integrin β3 orchestrates thrombotic and inflammatory processes through bidirectional signaling, with Src acting as a key downstream effector. OBJECTIVES:To dissect this axis, we generated SrcE97A mice that selectively disrupt the interaction between Src and integrin β3, impairing outside-in signaling while preserving inside-out signaling through integrin β3. METHODS:Platelet function was assessed through clot retraction, irreversible aggregation, thrombus stabilization under flow, and soluble fibrinogen binding. Thrombosis models included FeCl3-induced carotid artery and laser-induced cremaster arteriole injury for arterial thrombosis, and the inferior vena cava ligation for deep vein thrombosis. Hemostasis was evaluated in parallel. The impact on cerebral infarction was measured in vivo. In addition, the biological functions of αvβ3 outside-in signaling were also analyzed. RESULTS:The SrcE97A mutation impaired outside-in signaling while preserving inside-out signaling in platelets. This suppressed αIIbβ3-mediated clot retraction, secondary aggregation, and thrombus stabilization under flow. SrcE97A mice showed reduced arterial and venous thrombosis without hemostatic compromise. These antithrombotic effects were reinforced by protection against cerebral infarction in vivo. Furthermore, the E97A mutation influenced immunologic regulation. Specifically, it promoted pulmonary inflammation by skewing T helper (Th) cell differentiation toward Th1, via disruption of the αvβ3-Src-STAT4/6 signaling axis. CONCLUSIONS:These findings establish integrin β3 as a dual regulator of thrombosis and immune homeostasis. Selective disruption of outside-in signaling attenuates pathologic thrombosis without compromising hemostasis and reshapes Th1/Th2 balance. Targeting the Src E97 interface may offer strategies to inhibit pathologic thrombosis and modulate inflammation.

Platelet spreading and clot retraction, albeit both mediated by integrin outside-in signaling, lead to platelet shape changes in two opposite directions. The mechanisms by which these processes are regulated are not fully understood. Our previous study found that E726Q mutation in β3 integrin caused impaired spreading in Chinese hamster ovary (CHO) cells on immobilized fibrinogen.The current study further utilized knock-in mice bearing the β3E726Q mutation to explore the underlying mechanisms whereby the E726 residue differentially influences platelet spreading and clot retraction.Compared to wild type (WT) platelets, β3E726Q platelets displayed similar level of β3 expression but partially impaired fibrinogen binding associated with attenuated responses in platelet aggregation and P-selectin exposure. Notably, β3E726Q mutation resulted in defective platelet spreading but accelerated clot retraction concomitant with increased clot density. Functionally, β3E726Q mice displayed prolonged bleeding time and defective thrombogenesis in vitro and in vivo. Further mechanistic study showed that in β3E726Q platelets the activities of RhoA and Rac1 were significantly enhanced following thrombin stimulation, possibly due to reduced binding of Gα13 to the β3 cytoplasmic tail.Taken together, the β3E726 is a potential novel regulatory site that influences the direct interaction of β3 cytoplasmic tail with Gα13 and therefore the activity of downstream RhoA, a molecular switch that shifts platelet spreading into clot retraction.

Bone regeneration remains a critical challenge in modern medicine. Recent advancements have focused on incorporating hierarchical microstructures into biomaterials to enhance osteogenesis. Mineralized hydrogels, while promising, face limitations in precise microstructure control due to technical complexities. In this study, we present a biomimetic hierarchical structural mineralized hydrogel featuring a Liesegang pattern. In vitro experiments confirm that it significantly promotes the migration and osteogenic differentiation of bone mesenchymal stem cells (BMSCs). In vivo experiments further demonstrate its ability to significantly promote bone regeneration, with newly formed bone closely replicating the hydrogel's architecture. Notably, this hydrogel synthesis strategy eliminates time-consuming fabrication and extensive post-processing, offering a scalable and efficient route for advanced bone-regenerative materials.

Infected skin wounds represent a significant healthcare challenge, affecting millions of patients worldwide and imposing substantial economic burden on healthcare systems. Traditional wound dressings and systemic antibiotics face critical limitations including lack of tissue adhesion in wet environments, increasing antibiotic resistance, and inability to promote tissue regeneration, resulting in suboptimal healing outcomes. In this research, we formulated an injectable composite hydrogel comprising dopamine-modified sodium alginate, chondroitin sulfate, and silk fibroin as the primary matrix, with magnesium oxide (MgO) nanoparticles and human umbilical mesenchymal stem cells (hUMSCs)-derived exosomes (Exo) as functional components. The resultant ACS/MgO/Exo hydrogel exhibits effective tissue adhesion, superior hemostatic capability, mild-photothermal therapy (M-PTT)-mediated antibacterial activity, and enhanced angiogenesis. In vitro studies demonstrated that the hydrogel effectively reduced bleeding time, eliminated bacteria through M-PTT, and significantly enhanced endothelial tip cell activation, proliferation, motility, and vascularization through activation of the PI3K-AKT-NF-κB-VEGF signaling cascade. In vivo experiments with infected full-thickness defect model confirmed the composite hydrogel’s ability to accelerate wound closure, eliminate bacterial infection, enhance collagen deposition, and promote vascularization while simultaneously modulating the inflammatory response. This multifunctional hydrogel represents a promising therapeutic platform for complex infected wound management, addressing the critical clinical need for integrated solutions that simultaneously achieve adhesion, hemostasis, infection control, and tissue regeneration.

In this work, a highly sensitive electrochemiluminescence (ECL) biosensor was successfully developed for the detection of CYFRA21-1, in which a metal-organic gel (Zr-MOG) was introduced as a novel co-reaction promoter for amplifying the ECL signal of the silver nanoparticle-modified silver sulfide/potassium persulfate (Ag-Ag2S/K2S2O8) system. Specifically, the incorporation of Ag nanoparticles narrowed the bandgap and enhanced the ECL signals of the composites. As a co-reaction promoter, Zr-MOG accelerated the reduction of S2O82- to produce abundant sulfate radicals (SO4˙-) while increasing the electrode active surface area, which led to a significant enhancement of the Ag-Ag2S ECL emission. The biosensor constructed based on the dual-signal amplification strategy demonstrated excellent sensitivity, selectivity, and stability, with a wide linear detection range of 0.00005-100 ng mL-1 and a detection limit as low as 17.66 fg mL-1 (S/N = 3).

Background:Antiplatelet and anticoagulation are the cornerstones for arterial and venous thrombosis, respectively; however, hemorrhage remains a significant clinical challenge. Platelets are crucial for arterial thrombosis and contribute to venous thrombosis. Integrin β3 mediates outside-in signaling, which is critical for thrombosis, while inside-out signaling maintains hemostasis. Targeting the β3/Src interactions to selectively inhibit outside-in signaling offers a promising antithrombotic strategy without compromising hemostasis. Objectives:To develop more potent small molecules that selectively disrupt the β3/Src interaction, thereby inhibiting arterial and venous thrombogenesis without increasing bleeding risk. Methods:Building on the previously identified compound DCDBS84, we developed the structurally modified small molecules C109 and C116, with enhanced affinity for the Src SH3 domain. Their antithrombotic effects on both arterial and venous thrombosis were systematically evaluated through in vitro and in vivo studies. The impact on hemostatic function was assessed using a tail-bleeding model. Additionally, the drug developability of C109 was assessed via pharmacokinetic (PK) and metabolite analysis. Results:C109 and C116 exhibited superior efficacy in disrupting the β3/Src interaction. In vitro and in vivo studies demonstrated that C109 and C116 effectively suppress thrombosis at levels comparable to high doses of the αIIbβ3 antagonist integrilin, without elevating bleeding risk. In the Stenosis Model, C109 and C116 significantly reduced venous thrombogenesis by suppressing platelet activation and neutrophil extracellular trap formation. Additionally, C109 displayed favorable PK properties and robust metabolic stability. Conclusion:These findings identify promising small molecules that inhibit thrombosis while maintaining hemostasis, providing new avenues for safer and more effective clinical management.

The occurrence and development of tumors are accompanied by the abnormal expression of specific microRNAs (miRNAs). Therefore, miRNAs are considered as an important biomarker. The establishment of efficient, simple and sensitive miRNA imaging methods in living cells will contribute to the early diagnosis, treatment and drug development of diseases. In this study, we developed an endogenous enzyme-initiated AND logic circuit using gold nanocubes (AuNCs) as carriers for simultaneous detection of miRNA-21 and miRNA-210 in cells. Apurinic/apyrimidinic endonuclease 1 (APE1) and telomerase (TE), which are overexpressed in cancer cells, act as control switches in a logic circuit that enables sensitive in situ analysis of intracellular miRNAs without additional external intervention. At the same time, due to the lack of necessary enzymes as activation switches, the DNA circuit in normal cells remains in an inactive state. This strategy effectively reduces the risk of false positive signal generation. Our research results show that the logic circuit can not only distinguish between cancer cells and normal cells, and able to distinguish between different types of cancer cells. This finding provides a promising approach to accurately identify cell types.

Improving insights into current research and literature on melanoma enables healthcare providers to offer patients better care by applying the latest advancements. This bibliometric study analyzed the characteristics and trends in melanoma research through the top-cited articles. The top 100 most-cited articles on melanoma were published between 1969 and 2020, and the average number of citations was 36.8-893.9 (mean 176.8). Notably, the frequencies of the main key words, including antineoplastic agents, genetics, randomized controlled trials, metastatic melanoma, BRAF, and monoclonal antibodies, during 2010-2020 were significantly higher than during 1969-2009. Specifically, the main study topics after 2010 were drug research aspects, such as drug safety, drug efficacy, drug resistance, drug withdrawal, cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1), ipilimumab, nivolumab, trametinib, dabrafenib, vemurafenib, and various drug adverse effects. The emergence of immunotherapy caused a burst of citations and substantially changed the distribution of top-cited articles.

Oral DiseasesEarly View LETTER TO THE EDITOR Reappraisal of the association between oral lichen planus and Hashimoto thyroiditis Wei Liu, Wei Liu orcid.org/0000-0002-4841-8356 Department of Oral and Maxillofacial-Head and Neck Oncology, Fengcheng Hospital of Fengxian District, Shanghai Ninth People's Hospital Fengcheng Branch Hospital, Shanghai, China Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, Shanghai, China Contribution: Data curation, Writing - original draftSearch for more papers by this authorYun Wang, Yun Wang Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Contribution: ​Investigation, Validation, Formal analysisSearch for more papers by this authorXuemin Shen, Corresponding Author Xuemin Shen [email protected] orcid.org/0000-0002-9646-5237 College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, Shanghai, China Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Correspondence Xuemin Shen and Zhenhu Ren, College of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai 200011, China. Email: [email protected] and [email protected] Contribution: Supervision, Project administration, Funding acquisitionSearch for more papers by this authorZhenhu Ren, Corresponding Author Zhenhu Ren [email protected] Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, Shanghai, China Correspondence Xuemin Shen and Zhenhu Ren, College of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai 200011, China. Email: [email protected] and [email protected] Contribution: Conceptualization, Writing - review & editingSearch for more papers by this author Wei Liu, Wei Liu orcid.org/0000-0002-4841-8356 Department of Oral and Maxillofacial-Head and Neck Oncology, Fengcheng Hospital of Fengxian District, Shanghai Ninth People's Hospital Fengcheng Branch Hospital, Shanghai, China Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, Shanghai, China Contribution: Data curation, Writing - original draftSearch for more papers by this authorYun Wang, Yun Wang Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Contribution: ​Investigation, Validation, Formal analysisSearch for more papers by this authorXuemin Shen, Corresponding Author Xuemin Shen [email protected] orcid.org/0000-0002-9646-5237 College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, Shanghai, China Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Correspondence Xuemin Shen and Zhenhu Ren, College of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai 200011, China. Email: [email protected] and [email protected] Contribution: Supervision, Project administration, Funding acquisitionSearch for more papers by this authorZhenhu Ren, Corresponding Author Zhenhu Ren [email protected] Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, Shanghai, China Correspondence Xuemin Shen and Zhenhu Ren, College of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai 200011, China. Email: [email protected] and [email protected] Contribution: Conceptualization, Writing - review & editingSearch for more papers by this author First published: 26 December 2023 https://doi.org/10.1111/odi.14842 Wei Liu and Yun Wang contributed equally to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Open Research DATA AVAILABILITY STATEMENT Data from this study are available from the corresponding author upon pertinent request. Supporting Information Filename Description odi14842-sup-0001-TableS1.docxWord 2007 document , 18.4 KB Table S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. REFERENCES Alikhani, M., Ghalaiani, P., Askariyan, E., Khunsaraki, Z. A., Tavangar, A., & Naderi, A. (2017). Association between the clinical severity of oral lichen planus and anti-TPO level in thyroid patients. Brazilian Oral Research, 31, e10. 10.1590/1807-3107bor-2017.vol31.0010 PubMedWeb of Science®Google Scholar Bouquot, J. E. (2022). When systematic reviews are not done by experts. Oral Diseases, 28(4), 1294–1295. 10.1111/odi.13970 PubMedWeb of Science®Google Scholar Brzak, B. L., Skrinjar, I., Sumilin, L., Zuzul, I., Spiljak, B., Brailo, V., & Rogulj, A. A. (2020). Oral lichen planus and thyroid disease: Is there a possible connection? Research Journal of Pharmaceutical, Biological and Chemical Sciences, 11(6), 70–74. Google Scholar Cankovic, M., Bokor-Bratic, M., Tesic, M., & Marinoski, J. (2016). Association of oral lichen planus with autoimmune diseases in a northern Serbia population: Matched case-control study and literature review. Journal of Dental Science and Therapy, 1(2), 15–21. 10.24218/jdst.2016.08 Google Scholar Dave, A., Shariff, J., & Philipone, E. (2021). Association between oral lichen planus and systemic conditions and medications: Case-control study. Oral Diseases, 27(3), 515–524. 10.1111/odi.13572 PubMedWeb of Science®Google Scholar De Porras-Carrique, T., Ramos-Garcia, P., Aguilar-Diosdado, M., Warnakulasuriya, S., & González-Moles, M. A. (2022). Autoimmune disorders in oral lichen planus: A systematic review and meta- analysis. Oral Diseases, 29(4), 1382–1394. 10.1111/odi.14127 PubMedWeb of Science®Google Scholar Družijanić, A., Glavina, A., Draganja, M., Biočina-Lukenda, D., & Cigić, L. (2019). Inflammatory markers and incidence of other autoimmune diseases in patients with oral lichen planus. Acta Stomatologica Croatica, 53(4), 363–370. 10.15644/asc53/4/7 CASPubMedWeb of Science®Google Scholar Liu, W., Deng, Y., Shi, H., & Shen, X. (2023). Clinical investigation on oral lichen planus and associated comorbidities needs a holistic concept. Oral Diseases, 29(1), 327–329. 10.1111/odi.14181 PubMedWeb of Science®Google Scholar Piloni, S., Ferragina, F., Barca, I., Kallaverja, E., & Cristofaro, M. G. (2023). The correlation between oral lichen planus and thyroid pathologies: A retrospective study in a sample of Italian population. European Journal of Dentistry. https://doi.org/10.1055/s-0043-1772247 10.1055/s?0043?1772247 PubMedGoogle Scholar Serni, L., Barbato, L., Nieri, M., Mallardi, M., Noce, D., & Cairo, F. (2023). Association between oral lichen planus and Hashimoto thyroiditis: A systematic review. Oral Diseases. https://doi.org/10.1111/odi.14591 10.1111/odi.14591 Web of Science®Google Scholar Tang, Y., Shi, L., Jiang, B., Zhou, Z., & Shen, X. (2020). A cross-sectional study of oral lichen planus associated with thyroid diseases in East China. Frontiers in Endocrinology, 10, 928. 10.3389/fendo.2019.00928 PubMedWeb of Science®Google Scholar Zhou, T., Li, D., Chen, Q., Hua, H., & Li, C. (2018). Correlation between oral lichen planus and thyroid disease in China: A case-control study. Frontiers in Endocrinology, 9, 330. 10.3389/fendo.2018.00330 PubMedWeb of Science®Google Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Depression is one of the most common mental illnesses and is a well-known risk factor for suicide, characterized by low overall efficacy (<50%) and high relapse rate (40%). A rapid and objective approach for screening and prognosis of depression is highly desirable but still awaits further development. Herein, a high-performance metabolite-based assay to aid the diagnosis and therapeutic evaluation of depression by developing a vacancy-engineered cobalt oxide (Vo-Co3O4) assisted laser desorption/ionization mass spectrometer platform is presented. The easy-prepared nanoparticles with optimal vacancy achieve a considerable signal enhancement, characterized by favorable charge transfer and increased photothermal conversion. The optimized Vo-Co3O4 allows for a direct and robust record of plasma metabolic fingerprints (PMFs). Through machine learning of PMFs, high-performance depression diagnosis is achieved, with the areas under the curve (AUC) of 0.941-0.980 and an accuracy of over 92%. Furthermore, a simplified diagnostic panel for depression is established, with a desirable AUC value of 0.933. Finally, proline levels are quantified in a follow-up cohort of depressive patients, highlighting the potential of metabolite quantification in the therapeutic evaluation of depression. This work promotes the progression of advanced matrixes and brings insights into the management of depression.

Primary liver cancer has consistently exhibited a high prevalence and fatality rate, necessitating the investigation of associated diagnostic markers and inhibition mechanisms to effectively mitigate its impact. The significance of apolipoprotein M (ApoM) in impeding the progression of neoplastic ailments is progressively gaining recognition. However, a comprehensive understanding of its underlying mechanism in liver cancer advancement remains to be elucidated. Recent evidence indicates a potential association between ApoM and polyunsaturated fatty acids (PUFAs), with the peroxidation of phospholipids (PLs) containing PUFAs being recognized as a crucial element in the occurrence of ferroptosis. This prompts us to investigate the impact of the APOM gene on the progression of liver cancer through the ferroptosis pathway and elucidate its underlying mechanisms. The findings of this study indicate that the liver cancer cell model, which was genetically modified to overexpress the APOM gene, demonstrated a heightened ferroptosis effect. Moreover, the observed inhibition of the GSH (Glutathione) - GPX4 (Glutathione Peroxidase 4) regulatory axis suggests that the role of this axis in inhibiting ferroptosis is weakened. Through intersection screening and validation, we found that Mucin 1,cell surface associated ( MUC1 ) can inhibit ferroptosis and is regulated by the APOM gene. Bioinformatics analysis and screening identified miR-4489 as a mediator between the two. Experimental results using the dual luciferase reporter gene confirmed that has-miR-4489 targets MUC1 ' s 3 ' -UTR and inhibits its expression. In conclusion, this study provides evidence that the APOM gene induces a down-regulation in the expression of the ferroptosisinhibiting gene MUC1 , mediated by miR-4489, thereby impeding the advancement of liver cancer cells through the facilitation of ferroptosis.

Osteosarcoma (OS) is a "cold" tumor enriched in noninflammatory M2 phenotype tumor-associated macrophages (TAMs), which limits the efficacy of immunotherapy. The acidic tumor microenvironment (TME), generated by factors such as excess hydrogen (H+) ions and high lactate levels, activates immunosuppressive cells, further promoting a suppressive tumor immune microenvironment (TIME). Therefore, a multitarget synergistic combination strategy that neutralizes the acidic TME and reprograms TAMs can be beneficial for OS therapy. Here, a calcium carbonate (CaCO3)/polydopamine (PDA)-based nanosystem (A-NPs@(SHK+Ce6)) is developed. CaCO3 nanoparticles are used to neutralize H+ ions and alleviate the suppressive TIME, and the loaded SHK not only synergizes with photodynamic therapy (PDT) but also inhibits lactate production, further reversing the acidic TME and repolarizing TAMs to consequently lead to enhanced PDT-induced tumor suppression and comprehensive beneficial effects on antitumor immune responses. Importantly, A-NPs@(SHK+Ce6), in combination with programmed cell death protein 1 (PD-1) checkpoint blockade, shows a remarkable ability to eliminate distant tumors and promote long-term immune memory function to protect against rechallenged tumors. This work presents a novel multiple-component combination strategy that coregulates the acidic TME and TAM polarization to reprogram the TIME.

The existence of a comorbidity between diabetes mellitus (DM) as well as between thyroid diseases (TD) and oral lichen planus (OLP), respectively, was substantially demonstrated. However, there is not enough attention to the concurrent status of both TD and DM in OLP patients. Herein, this short communication aimed to compare 1) the prevalence of DM when TD was concurrently investigated and that of DM when TD status was ignored; 2) the prevalence of TD when DM was concurrently investigated and that of TD when DM status was ignored in the studies. The pooled prevalence (9.86 %; 95 % confidence intervals [CI], 9.22-10.53 %) of DM when TD was concurrently investigated was significantly higher than that (8.13 %; 95%CI, 8.03-9.12 %) when TD status was not investigated in OLP patients. The pooled prevalence (12.48 %; 95%CI, 11.77-13.22 %) of TD when DM was concurrently investigated was significantly higher than that (10.45 %; 95%CI, 9.52-11.46 %) when DM status was not investigated in OLP patients. Thus, it is logical to presume for the first time that there is possible interplay of DM and TD in OLP occurrence. TD and DM should serve as important confounding factors each other in clinical investigation on OLP and associated comorbidities. 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Background Although the disturbance of circadian rhythms represents a significant clinical feature of major depressive disorder (MDD), the relationship between biological rhythm disturbances and the severity of suicidal ideation in individuals with MDD remains unclear. We aimed to explore the characteristics of different biological rhythm dimensions in MDD and their association with the severity of depressive symptoms and suicidal ideation. Methods A total of 50 MDD patients and 50 healthy controls were recruited and their general information was collected. The severity of depressive symptoms was assessed with the 17-item Hamilton Depression Rating Scale (HDRS 17 ). The intensity of suicidal ideation was evaluated with the Beck Scale for Suicide Ideation (BSS). The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) scale was utilized to assess the participants’ biological rhythm dysregulation. Multiple logistic regression analysis was conducted to explore the relationship between biological rhythm and the risk of MDD. Multiple linear regression analysis was performed in the MDD group to investigate the relationship between different biological rhythm dimensions and suicide ideation. Results Significant differences were observed between the MDD group and the control group in total BRIAN score (Z=-5.41, P < 0.001) as well as scores for each dimension. After adjusting for confounding factors, multiple logistic regression analysis revealed a significant association between total BRIAN score and the presence of MDD (OR = 1.20, 95% CI = 1.10–1.29, P < 0.001), as well as between scores in different BRIAN dimensions and the presence of MDD (activity: OR = 1.47, 95% CI = 1.24–1.74, P < 0.001; sleep: OR = 1.52, 95% CI = 1.28–1.79, P < 0.001; social: OR = 1.80, 95% CI = 1.32–2.46, P < 0.001; eating pattern: OR = 1.34, 95% CI = 1.12–1.60, P = 0.001). In patients with MDD, linear regression analysis demonstrated a positive relationship between BSS scores and BRIAN eating pattern scores (β = 0.34, P = 0.022), even after adjusting for demographic factors and the severity of depression. Conclusions Patients with MDD exhibited significantly higher levels of dysregulation in all four biological rhythm dimensions compared to healthy controls and the degree of dysregulation was associated with the severity of depression. More importantly, dysregulation of eating pattern may increase the intensity of suicidal ideation in MDD, thus elevating the risk of suicide.

Tumor microenvironments (TMEs) have received increasing attention in recent years as they play pivotal roles in tumorigenesis, progression, metastases, and resistance to the traditional modalities of cancer therapy like chemotherapy. With the rapid development of nanotechnology, effective antineoplastic nanotherapeutics targeting the aberrant hallmarks of TMEs have been proposed. The appropriate design and fabrication endow nanomedicines with the abilities for active targeting, TMEs-responsiveness, and optimization of physicochemical properties of tumors, thereby overcoming transport barriers and significantly improving antineoplastic therapeutic benefits. This review begins with the origins and characteristics of TMEs and discusses the latest strategies for modulating the TMEs by focusing on the regulation of biochemical microenvironments, such as tumor acidosis, hypoxia, and dysregulated metabolism. Finally, this review summarizes the challenges in the development of smart anti-cancer nanotherapeutics for TME modulation and examines the promising strategies for combination therapies with traditional treatments for further clinical translation.

IL-34 involves in host immunity regulated carcinogenesis. Alpha-fetoprotein (AFP) is related to the development of HCC. We explored if combination of IL-34 and APF could improve the diagnostic value in HBV related hepatocellular carcinoma (HBV-HCC). Serum was obtained from HBV patients or healthy control. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBV-HCC patients. Serum IL-34 and MCSF, or intrahepatic IL-34, MCSF and CD68+ tumor associate macrophages (TAMs) were determined using ELISA or immunohistochemistry. Serum IL-34 was 1.7, 1.3 or 2.3-fold higher in HBV-HCC than that of CHB, HBV related cirrhosis or healthy control, which was inhibited following trans-hepatic arterial chemoembolization (TACE) in HBV-HCC patients. Intra-hepatic IL-34 was higher in HBV-HCC than that of the other three groups. Intra-hepatic IL-34 was associated with high HBV-DNA, HBeAg-, poor differentiation and small tumor size of HBV-HCC patients. Intra-hepatic TAMs in HBV-HCC were increased 1.7 or 1.3-fold, compared to that from CHB or HBV-cirrhosis patients. Intra-hepatic TAMs were associated with high HBV-DNA, high tumor differentiation, small tumor size, abnormal AFP and more tumor number. AFP plus serum IL-34, showed the highest AUC (0.837) with sensitivity (0.632) and highest specificity (0.931), suggesting that AFP plus IL-34 enhances the reliability for prediction of the development of HBV-HCC among CHB patients. Circulating and intra-hepatic IL-34 was upregulated gradually in HBV disease progression from CHB, cirrhosis and HCC. IL-34 may be used as a diagnostic biomarker and potential therapeutic target for the management of HBV-HCC.

The localization of invisible and impalpable small pulmonary nodules has become an important concern during surgery, since current widely used techniques for localization have a number of limitations, such as invasive features of hookwires and microcoils, and rapid diffusion after injection of indocyanine green (ICG). Lanthanide-based metal-organic frameworks (MOFs) have been proven as potential fluorescent agents because of their prominent luminescent characteristics, including large Stokes shifts, high quantum yields, long decay lifetimes, and undisturbed emissive energies. In addition, lanthanides, such as Eu, can efficiently absorb X-rays for CT imaging. In this study, we synthesized Eu-UiO-67-bpy (UiO = University of Oslo, bpy = 2,2'-bipyridyl) as a fluorescent dye with a gelatin-methacryloyl (GelMA) hydrogel as a liquid carrier. The prepared complex exhibits constant fluorescence emission owing to the luminescent characteristics of Eu and the stable structure of UiO-67-bpy with restricted fluorescence diffusion attributed to the photocured GelMA. Furthermore, the hydrogel provides stiffness to make the injection site tactile and improve the accuracy of localization and excision. Finally, our complex enables fluorescence-CT dual-modal imaging of the localization site.

Osteoarthritis drugs are often short-acting; therefore, to enhance their efficacy, long-term, stable-release, drug-delivery systems are urgently needed. Mesoporous polydopamine (MPDA), a natural nanoparticle with excellent biocompatibility and a high loading capacity, synthesized via a self-aggregation-based method, is frequently used in tumor photothermal therapy. Here, we evaluated its efficiency as a sustained and controlled-release drug carrier and investigated its effectiveness in retarding drug clearance. To this end, we used MPDA as a controlled-release vector to design a drug-loaded microsphere system (RCGD423@MPDA) for osteoarthritis treatment, and thereafter, tested the efficacy of the system in a rat model of osteoarthritis. The results indicated that at an intermediate drug-loading dose, MPDA showed high drug retention. Furthermore, the microsphere system maintained controlled drug release for over 28 days. Our in vitro experiments also showed that drug delivery using this microsphere system inhibited apoptosis-related cartilage degeneration, whereas MPDA-only administration did not show obvious cartilage degradation improvement effect. Results from an in vivo osteoarthritis model also confirmed that drug delivery via this microsphere system inhibited cartilage damage and proteoglycan loss more effectively than the non-vectored drug treatment. These findings suggest that MPDA may be effective as a controlled-release carrier for inhibiting the overall progression of osteoarthritis. Moreover, they provide insights into the selection of drug-clearance retarding vectors, highlighting the applicability of MPDA in this regard.

Most preventable deaths after trauma are related to hemorrhage and occur early after injury. Timely hemostatic treatment is essential to minimize blood loss and improve survival. Among the various treatment methods, the most economical and effective is to use a hemostatic agent. A powdered hemostatic agent can be used for wounds of any shape or depth with high compactness and excellent accumulation effect. Herein, we chose the natural, hydrophilic polymer poly(γ-glutamic acid) (γ-PGA) to form composite hemostatic microspheres with sodium alginate (SA), which show good biocompatibility, water absorptivity, and viscosity. The morphology and structure of the hemostatic microspheres were determined using Fourier transform infrared spectroscopy and scanning electron microscopy. The overall safety, hemolysis, pyrogenic, and intradermal irritation tests were examined. The relationship between hemostatic pressure and hemostatic time during microsphere use was also measured. The hemostatic effect was analyzed with a liver, spleen, and femoral artery bleeding model. The composite microspheres were well tolerated in vivo and exhibited better hemostatic effects in animal experiments than a microporous polysaccharide powder compound. Research results showed that SA/γ-PGA microspheres are materials with good hemostatic effect, high safety, and great potential in clinical applications.

The use of an artificial bone substitute is a potential strategy for repairing bone defects; however, the inadequate consideration of repair-immune system interactions, resulting in significant pathological changes in the microenvironment, is a major barrier to achieving effective regenerative outcomes. Here, we evaluated a biomimetic baicalin (BAI)-incorporating graphene oxide-demineralized bone matrix (GO-BAI/DBM) hybrid scaffold, which was beneficial for bone regeneration. First, by considering that bone is a kind of organic-inorganic composite, a biomimetic GO/DBM bone substitute with enhanced physiochemical and osteoinductive properties was fabricated. Furthermore, inherently therapeutic GO was also used as a drug delivery carrier to achieve the sustained and prolonged release of BAI. Notably, a series of experiments showed that the GO-BAI nanocomposites could transform inflammatory M1 macrophages into pro-healing M2 macrophages, which was beneficial for in vitro angiogenesis and osteogenesis. By using a rat subcutaneous model, it was revealed that the GO-BAI nanocomposites proactively ameliorated the inflammatory response, which was coupled with decreased fibrous encapsulation. Notably, obvious in situ calvarial bone regeneration was achieved using the GO-BAI/DBM hybrid scaffold. These findings demonstrated that the bifunctional GO-BAI/DBM scaffold, by enhancing beneficial cross-talk among bone cells and inflammatory cells, might be utilized as an effective strategy for bone regeneration.