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Radiotherapy is one of the most common treatments for oral cancer. However, in the clinic, recurrence and metastasis of oral cancer occur after radiotherapy, and the underlying mechanism remains unclear. Cancer stem cells (CSCs), considered the “seeds” of cancer, have been confirmed to be in a quiescent state in most established tumours, with their innate radioresistance helping them survive more easily when exposed to radiation than differentiated cancer cells. There is increasing evidence that CSCs play an important role in recurrence and metastasis post-radiotherapy in many cancers. However, little is known about how oral CSCs cause tumour recurrence and metastasis post-radiotherapy. In this review article, we will first summarise methods for the identification of oral CSCs and then focus on the characteristics of a CSC subpopulation induced by radiation, hereafter referred to as “awakened” CSCs, to highlight their response to radiotherapy and potential role in tumour recurrence and metastasis post-radiotherapy as well as potential therapeutics targeting CSCs. In addition, we explore potential therapeutic strategies targeting these “awakened” CSCs to solve the serious clinical challenges of recurrence and metastasis in oral cancer after radiotherapy.

Silver nanoparticles (Ag NPs) have accumulated significant interest due to their exceptional physicochemical properties and remarkable applications in biomedicine, electronics, and catalysis sensing. This comprehensive review provides an in-depth study of synthetic approaches such as biological synthesis, chemical synthesis, and physical synthesis with a detailed overview of their sub-methodologies, highlighting advantages and disadvantages. Additionally, structural properties affected by synthesis methods are discussed in detail by examining the dimensions and surface morphology. The review explores the distinctive properties of Ag NPs, including optical, electrical, catalytic, and antimicrobial properties, which render them beneficial for a range of applications. Furthermore, this review describes the diverse applications in several fields, such as medicine, environmental science, electronics, and optoelectronics. However, with numerous applications, several kinds of issues still exist. Future attempts need to address difficulties regarding synthetic techniques, environmental friendliness, and affordability. In order to ensure the secure utilization of Ag NPs, it is necessary to establish sustainability in synthetic techniques and eco-friendly production methods. This review aims to give a comprehensive overview of the synthesis, structural analysis, properties, and multifaceted applications of Ag NPs.

Human serum albumin (HSA) based drug delivery platforms that feature desirable biocompatibility and pharmacokinetic property are rapidly developed for tumor-targeted drug delivery. Even though various HSA-based platforms have been established, it is still of great significance to develop more efficient preparation technology to broaden the therapeutic applications of HSA-based nano-carriers. Here we report a bridging strategy that unfastens HSA to polypeptide chains and subsequently crosslinks these chains by a bridge-like molecule (BPY-Mal 2 ) to afford the HSA reassemblies formulation (BPY@HSA) with enhanced loading capacity, endowing the BPY@HSA with uniformed size, high photothermal efficacy, and favorable therapeutic features. Both in vitro and in vivo studies demonstrate that the BPY@HSA presents higher delivery efficacy and more prominent photothermal therapeutic performance than that of the conventionally prepared formulation. The feasibility in preparation, stability, high photothermal conversion efficacy, and biocompatibility of BPY@HSA may facilitate it as an efficient photothermal agents (PTAs) for tumor photothermal therapy (PTT). This work provides a facile strategy to enhance the loading capacity of HSA-based crosslinking platforms in order to improve delivery efficacy and therapeutic effect. Human serum albumin (HSA) can be used as a drug delivery material for cancer therapy. Here, the authors report an HSA-based photothermal platform that improves drug loading and photothermal therapeutic performance in breast cancer mouse models.

Hypoxic tumors present a significant challenge in cancer therapy due to their ability to adaptation in low-oxygen environments, which supports tumor survival and resistance to treatment. Enhanced mitophagy, the selective degradation of mitochondria by autophagy, is a crucial mechanism that helps sustain cellular homeostasis in hypoxic tumors. In this study, we develop an azocalix[4]arene-modified supramolecular albumin nanoparticle, that co-delivers hydroxychloroquine and a mitochondria-targeting photosensitizer, designed to induce cascaded oxidative stress by regulating mitophagy for the treatment of hypoxic tumors. These nanoparticles are hypoxia-responsive and release loaded guest molecules in hypoxic tumor cells. The released hydroxychloroquine disrupts the mitophagy process, thereby increasing oxidative stress and further weakening the tumor cells. Additionally, upon laser irradiation, the photosensitizer generates reactive oxygen species independent of oxygen, inducing mitochondria damage and mitophagy activation. The dual action of simultaneous spatiotemporal mitophagy activation and mitophagy flux blockade results in enhanced autophagic and oxidative stress, ultimately driving tumor cell death. Our work highlights the effectiveness of hydroxychloroquine-mediated mitophagy blockade combined with mitochondria-targeted photosensitizer for cascade-amplified oxidative stress against hypoxic tumors. Enhanced mitophagy has been recognized as crucial mechanism to sustain cellular homeostasis in hypoxic tumors. Here, this group fabricates an azocalix[4]arene-modified supramolecular albumin nanoparticle codelivering hydroxychloroquine (HCQ) and sulfur-substituted methylated nile blue analog, capable of inducing cascaded oxidative stress via regulating mitophagy for hypoxic tumors treatment.

Background Tumor-associated dendritic cells (TADCs) can interact with tumor cells to suppress anti-tumor T cell immunity. However, there is no information on whether and how TADCs can modulate programmed death-ligand 1 (PD-L1) expression by cancer cells. Methods Human peripheral blood monocytes were induced for DCs and immature DCs were cultured alone, or co-cultured with bladder cancer T24 or control SV-HUC-1 cells, followed by stimulating with LPS for DC activation. The activation status of DCs was characterized by flow cytometry and allogenic T cell proliferation. The levels of chemokines in the supernatants of co-cultured DCs were measured by CBA-based flow cytometry. The impacts of CXCL9 on PD-L1, STAT3 and Akt expression and STAT3 and Akt phosphorylation in T24 cells were determined by flow cytometry and Western blot. Results Compared with the control DCs, TADCs exhibited immature phenotype and had significantly lower capacity to stimulate allogenic T cell proliferation, particularly in the presence of recombinant CXCL9. TADCs produced significantly higher levels of CXCL9, which enhanced PD-L1 expression in T24 cells. Pre-treatment with AMG487 abrogated the CXCL9-increased PD-L1 expression in T24 cells. Treatment with CXCL9 significantly enhanced STAT3 and Akt activation in T24 cells. Conclusions TADCs produced high levels of CXCL9 that increased PD-L1 expression in bladder cancer T24 cells by activating the CXCR3-related signaling. Our findings may shed new lights in understanding the regulatory roles of TADCs in inhibiting antitumor T cell responses and promoting tumor growth.

Little is known regarding the association between adverse experiences and cognitive frailty, and the role of social support in this relationship. This study aimed to investigate the association between adverse experiences and cognitive frailty, as well as determine how social support affects this relationship among rural older adults in China. Data were obtained from two waves of follow-up surveys (2020 and 2022) conducted by the Shandong Rural Elderly Health Cohort (SREHC), including 2,572 participants aged 60 years or above. The primary outcome was cognitive frailty, defined as the co-existence of physical frailty (≥3 Fried criteria) and cognitive impairment (educationally adjusted Mini-Mental Status Examination). Self-reported adverse experiences were categorised as no adversity, only childhood adversity (≥1 of 12 events before age 17), only current adversity (≥1 of 7 events past year), and dual adversity (experiencing both childhood and current adversity). The Generalized Estimating Equation (GEE) analyses and the margins plot were performed to estimate our hypothetical models. In fully adjusted models, older adults with dual adversity were significantly associated with a higher risk of cognitive frailty (OR = 1.64, 95% CI: 1.02-2.63), not significant in only childhood or only current adversity. Social support alleviated the risk of cognitive frailty among rural older adults with only childhood adversity (OR = 0.41, 95% CI: 0.21-0.79) or dual adversity (OR = 0.26, 95% CI: 0.09-0.72), but not among those with only current adversity. Our results underscore the relationship between dual adversity and cognitive frailty, not significant in only childhood or only current adversity, with social support serving as a pivotal moderating factor. Governmental authorities should elevate their awareness of adverse experiences, and enhancing social support is crucial to preventing cognitive frailty and promoting healthy aging.

Background The faithful maintenance of DNA methylation homeostasis indispensably requires DNA methyltransferase 1 (DNMT1) in cancer progression. We previously identified DNMT1 as a potential candidate target for oral squamous cell carcinoma (OSCC). However, how the DNMT1- associated global DNA methylation is exploited to regulate OSCC remains unclear. Methods The shRNA-specific DNMT1 knockdown was employed to target DNMT1 on oral cancer cells in vitro, as was the use of DNMT1 inhibitors. A xenografted OSCC mouse model was established to determine the effect on tumor suppression. High-throughput microarrays of DNA methylation, bulk and single-cell RNA sequencing analysis, multiplex immunohistochemistry, functional sphere formation and protein immunoblotting were utilized to explore the molecular mechanism involved. Analysis of human samples revealed associations between DNMT1 expression, global DNA methylation and collaborative molecular signaling with oral malignant transformation. Results We investigated DNMT1 expression boosted steadily during oral malignant transformation in human samples, and its inhibition considerably minimized the tumorigenicity in vitro and in a xenografted OSCC model. DNMT1 overexpression was accompanied by the accumulation of cancer-specific DNA hypomethylation during oral carcinogenesis; conversely, DNMT1 knockdown caused atypically extensive genome-wide DNA hypomethylation in cancer cells and xenografted tumors. This novel DNMT1-remodeled DNA hypomethylation pattern hampered the dual activation of PI3K-AKT and CDK2-Rb and inactivated GSK3β collaboratively. When treating OSCC mice, targeting DNMT1 achieved greater anticancer efficacy than the PI3K inhibitor, and reduced the toxicity of blood glucose changes caused by the PI3K inhibitor or combination of PI3K and CDK inhibitors as well as adverse insulin feedback. Conclusions Targeting DNMT1 remodels a novel global DNA hypomethylation pattern to facilitate anticancer efficacy and minimize potential toxic effects via balanced signaling synergia. Our study suggests DNMT1 is a crucial gatekeeper regarding OSCC destiny and treatment outcome.

As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.

Printing technology has revolutionized manufacturing by enabling high-volume, multipurpose, low-cost production with minimal environmental impact. This advancement has led to the integration of flexible electronic devices, such as displays, actuators, and sensors, into various consumer markets. Over the past few decades, printed electronics have garnered significant interest from both academic and industrial communities. Among these, flexible strain sensors stand out due to their adaptability and potential for large-scale applications. However, a comprehensive analysis of their sensing performance, particularly with respect to printability, remains lacking. This review aims to systematically explore the development of flexible strain sensors produced through printing technology, focusing on key aspects such as the formulation of conductive inks, the use of diverse substrate materials, and the challenges associated with printability. Additionally, it delves into the practical applications of these sensors across multiple industries. By providing an in-depth examination of these factors, this review offers valuable insights into the current state of printed electronics and highlights their future potential in advancing flexible sensing technologies.

Acinetobacter baumannii is an increasing important nosocomial pathogen that is difficult to combat due to its ability to survive in harsh environments and the emergence of isolates that are resistant to multiple antibiotics. A better understanding of the mechanism underlying the toughness of A. baumannii may identify its Achilles’ heel, which will facilitate the development of novel preventive and treatment measures. Many Gram-negative bacteria deploy a type VI secretion system (T6SS) to inject toxins into target cells to promote their survival and replication in complex environments. Here, we report that Acinetobacter baumannii uses its T6SS to kill fungi and that the effector TafE ( ACX60_15365 ) is responsible for such killing. Although ectopically expressed TafE is toxic to both Escherichia coli and Saccharomyces cerevisiae , deletion of tafE only affects the antifungal activity of A. baumannii . We demonstrate that TafE is a DNase capable of targeting the nuclei of yeast cells and that an Ntox15 domain is essential for its ability to degrade DNA. Furthermore, our findings show that A. baumannii is protected from the toxicity of TafE by elaborating the immunity protein TaeI ( ACX60_15360 ), which antagonizes the activity of the effector by direct binding. The discovery of A. baumannii T6SS effectors capable of killing multiple taxonomically distinct microbes has shed light on a mechanism of the high-level fitness of this pathogen in environments characterized by scarce nutrients and the potential presence of diverse microorganisms. IMPORTANCE Acinetobacter baumannii is an increasing important nosocomial pathogen that is difficult to combat due to its ability to survive in harsh environments and the emergence of isolates that are resistant to multiple antibiotics. A better understanding of the mechanism underlying the toughness of A. baumannii may identify its Achilles’ heel, which will facilitate the development of novel preventive and treatment measures. In this study, our findings show that A. baumannii kills fungi with the DNase effector TafE injected into competitor cells by its type VI secretion system. A. baumannii is protected from the activity of TafE by the immunity protein TaeI, which inactivates the effector by direct binding. Our results suggest that inactivation of its T6SS or effectors may reduce the fitness of A. baumannii and increase the effectiveness of treatment by means such as antibiotics. Furthermore, our finding suggests that targeted degradation of TaeI may be an effective strategy to kill A. baumannii .