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Family history (FH) of cancer and polygenic risk scores (PRS) are pivotal for cancer risk assessment, yet their combined impact remains unclear. Participants in the UK Biobank (UKB) were recruited between 2006 and 2010, with complete follow-up data updated until February 2020 for Scotland and January 2021 for England and Wales. Using UKB data (N = 442,399), we constructed PRS and incidence-weighted overall cancer PRS (CPRS). FH was assessed through self-reported standardized questions. Among 202,801 men (34.6% with FH) and 239,598 women (42.0% with FH), Cox regression was used to examine the associations between FH, PRS, and cancer risk. We found a significant dose-response relationship between FH of cancer and corresponding cancer risk (P trend  < .05), with over 10 significant pairs of cross-cancer effects of FH. FH and PRS are positively correlated and independent. Joint effects of FH of cancer (multiple cancers) and PRS (CPRS) on corresponding cancer risk were observed: for instance, compared with participants with no FH of cancer and low PRS, men with FH of cancer and high PRS had the highest risk of colorectal cancer (hazard ratio [HR]: 3.69, 95% confidence interval [CI]: 3.01-4.52). Additive interactions were observed in prostate and overall cancer risk for men and breast cancer for women, with the most significant result being a relative excess risk of interaction (RERI) of 2.98, accounting for ~34% of the prostate cancer risk. In conclusion, FH and PRS collectively contribute to cancer risk, supporting their combined application in personalized risk assessment and early intervention strategies., (© 2024 UICC.)

Lactate and its derivative, lactylation, play pivotal roles in modulating immune responses within the tumor microenvironment (TME), particularly in T-cell-mediated cancer immunotherapy. Elevated lactate levels, a hallmark of the Warburg effect, contribute to immune suppression through CD8 + T cell functionality and by promoting regulatory T cell (Treg) activity. Lactylation, a post-translational modification (PTM), alters histone and non-histone proteins, influencing gene expression and further reinforcing immune suppression. In the complex TME, lactate and its derivative, lactylation, are not only associated with immune suppression but can also, under certain conditions, exert immunostimulatory effects that enhance cytotoxic responses. This review describes the dual roles of lactate and lactylation in T-cell-mediated tumor immunity, analyzing how these factors contribute to immune evasion, therapeutic resistance, and immune activation. Furthermore, the article highlights emerging therapeutic strategies aimed at inhibiting lactate production or disrupting lactylation pathways to achieve a balanced regulation of these dual effects. These strategies offer new insights into overcoming tumor-induced immune suppression and hold the potential to improve the efficacy of cancer immunotherapies.

The tumor secretome comprises the totality of protein factors secreted by various cell components within the tumor microenvironment, serving as the primary medium for signal transduction between tumor cells and between tumor cells and stromal cells. The deletion or mutation of the p53 gene leads to alterations in cellular secretion characteristics, contributing to the construction of the tumor microenvironment in a cell non-autonomous manner. This review discusses the critical roles of mutant p53 in regulating the tumor secretome to remodel the tumor microenvironment, drive tumor progression, and influence the plasticity of cancer-associated fibroblasts (CAFs) as well as the dynamics of tumor immunity by focusing on both secreted protein expression and secretion pathways. The aim is to provide new insights for targeted cancer therapies.

Long non-coding RNAs (lncRNAs), although incapable of encoding proteins, play crucial roles in multiple layers of gene expression regulation, epigenetic modifications, and post-transcriptional regulation. Zinc finger antisense 1 (ZFAS1), a lncRNA located in the 20q13 region of the human genome, exhibits dual functions as an oncogene or tumor suppressor in various human malignancies. ZFAS1 plays a crucial role in cancer progression, metastasis, invasion, apoptosis, cell cycle regulation, and drug resistance through complex molecular mechanisms. Additionally, ZFAS1 has a long half-life of over 16 h, demonstrating exceptional stability, and making it a potential biomarker. This review integrates recent studies on the role and molecular mechanisms of ZFAS1 in malignancies and summarizes its clinical significance. By summarizing the role of ZFAS1 in cancer, we aim to highlight its potential as an anti-cancer biomarker and therapeutic target., Competing Interests: Compliance with Ethical Standards Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Alcohol use is a preventable risk factor for cancer, but public awareness remains low. A promising approach to raising awareness is to include pictorial warning labels (PWLs) on alcohol-containing products, but the typical graphic images used in such warnings can cause inattention. This study investigated whether narrative PWLs (depicting the lived experiences) could lead to greater attention and higher risk perceptions than graphic, non-narrative PWLs (showing graphic health effects)., Methods: Moderate and heavy drinkers participated in an online, webcam-based eye-tracking experiment (N = 649). They were randomized to view an order-randomized stimulus set containing either three narrative PWLs or three non-narrative PWLs. Visual attention was assessed by metrics of participant eye movements, including the visit count and dwell time to separate image and text area of interest (AOI) while viewing each PWL. Risk perceptions were assessed by participant responses to questions presented after viewing all PWLs., Results: Participants paid more attention to the image than the text AOI on both metrics (p's < 0.05). They also spent more time viewing narrative versus non-narrative PWLs (p's < 0.05). However, PWL type had no significant effect on risk perceptions (p's > 0.1), and visual attention did not mediate this relationship., Conclusions: Our findings highlight the potential of narrative PWLs to visually engage alcohol consumers' attention. Further research is needed to understand why narrative PWLs do not outperform non-narrative PWLs in shaping risk perceptions either directly or through attention, the proposed mediator., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

It was previously thought that ncRNA could not encode polypeptides, but recent reports have challenged this notion. As research into ncRNA progresses, it is increasingly clear that it serves roles beyond traditional mechanisms, playing significant regulatory roles in various diseases, notably cancer, which is responsible for 70% of human deaths. Numerous studies have highlighted the diverse regulatory mechanisms of ncRNA that are pivotal in cancer initiation and progression. The role of ncRNA-encoded polypeptides in cancer regulation has gained prominence. This article explores the newly identified regulatory functions of these polypeptides in three types of ncRNA-lncRNA, pri-miRNA, and circRNA. These polypeptides can interact with proteins, influence signaling pathways, enhance miRNA stability, and regulate cancer progression, malignancy, resistance, and other clinical challenges. Furthermore, we discuss the evolutionary significance of these polypeptides in the transition from RNA to protein, examining their emergence and conservation throughout evolution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Sonodynamic therapy (SDT) is gaining popularity in cancer treatment due to its superior controllability and high tissue permeability. Nonetheless, the efficacy of SDT is severely diminished by the transient generation of limited reactive oxygen species (ROS). Herein, we introduce an acid-activated nanosonosensitizer, CaO 2 @PCN, by the controllable coating of porphyrinic metal-organic frameworks (PCN-224) on CaO 2 to induce cascaded oxidative stress in tumors. The PCN-224 doping can generate ROS during SDT to induce intracellular oxidative stress and abnormal calcium channels. Meanwhile, the ultrasound also promotes extracellular calcium influx. In addition, CaO 2 @PCN sequentially degrades in the tumor cell lysosomes, releasing Ca 2+ and H 2 O 2 to induce further abnormal calcium channels and elevate the levels of Ca 2+ . Insufficient catalase (CAT) in tumor cells promotes intracellular calcium overload, which can induce persistent ROS generation and mitochondrial dysfunction through ion interference therapy (IIT). More importantly, PCN-224 also protects CaO 2 against significant degradation under neutral conditions. Hence, the well-designed CaO 2 @PCN produces synergistic SDT/IIT effects and persistent ROS against cancer. More notably, the acidity-responsive biodegradability endows CaO 2 @PCN with excellent biosafety and promising clinical potential.

Polycyclic aromatic hydrocarbons (PAHs) were measured in 342 daily PM 10 samples collected in four seasons at a site in Bengbu, China. This study was a qualitative and quantitative investigation of the emission sources of atmospheric PAHs in Bengbu and the spatial distribution of regional PAH sources in PM 10 samples. The annual concentrations of the 16 EPA priority PAHs ranged from 1.45 to 62.16 ng/m 3 , with an annual mean of 7.63 ± 7.38 ng/m 3 . The seasonal trends during the year were: winter (6.13-62.16 ng/m 3 , median = 14.99 ng/m 3 ) > autumn (2.01-18.78 ng/m 3 , median = 4.90 ng/m 3 ) > spring (1.45-19.34 ng/m 3 , median = 3.32 ng/m 3 ) > summer (1.57-4.27 ng/m 3 , median = 2.12 ng/m 3 ). The PAHs over the year were dominated by medium-molecular-weight PAHs (39.81%), followed by high-molecular-weight PAHs (35.77%), and low-molecular-weight PAHs (24.42%). The diagnostic ratio method and positive matrix factorization revealed that the PAH sources in Bengbu in spring and summer were industrial emissions, coal and biomass combustion, and traffic emissions; while the sources in autumn and winter were coal and biomass combustion and traffic emissions. According to a backward trajectory clustering analysis and potential source contribution function analysis, Bengbu City was mainly affected by pollution from the northern and northwestern regions in spring, autumn, and winter, while it was more affected by the coastal monsoon in summer. The PAH pollution in Bengbu was most severe in spring, autumn, and winter, and the health risk to the population was also most severe at that time. The health risk to adult males (3.35 × 10 -4 ) was greater than the risk to adult females (3.14 × 10 -4 ), and the health risk to adults was greater than the risk to children (2.52 × 10 -4 )., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Ma, Diao, Wang, Chen, Zhou, Yang and Zhen.)

Metabolic dysregulation constitutes a pivotal feature of cancer progression. Enzymes with multiple metal active sites play a major role in this process. Here we report the first metabolic-enzyme-like FeMoO 4 nanocatalyst, dubbed 'artificial metabzyme'. It showcases dual active centres, namely, Fe 2+ and tetrahedral Mo 4+ , that mirror the characteristic architecture of the archetypal metabolic enzyme xanthine oxidoreductase. Employing spatially dynamic metabolomics in conjunction with the assessments of tumour-associated metabolites, we demonstrate that FeMoO 4 metabzyme catalyses the metabolic conversion of tumour-abundant xanthine into uric acid. Subsequent metabolic adjustments orchestrate crosstalk with immune cells, suggesting a potential therapeutic pathway for cancer. Our study introduces an innovative paradigm in cancer therapy, where tumour cells are metabolically reprogrammed to autonomously modulate and directly interface with immune cells through the intervention of an artificial metabzyme, for tumour-cell-specific metabolic therapy., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The interplay between immune checkpoints KLRB1 and CLEC2D is crucial for tumor progression and immune evasion, yet the interaction dynamics are not fully understood. This study aims to elucidate the interaction across various cancers and identify small molecule inhibitors that can disrupt it. We perform a comprehensive pan-cancer analysis of the KLRB1-CLEC2D pair, including mRNA expression patterns, pathological stages, survival outcomes, and single-cell omics, immune infiltration, copy number variations, and DNA methylation profiles. Our findings reveal a consistently higher CLEC2D/KLRB1 ratio in most cancer types compared to normal tissues, and this ratio also increased with advancing pathological stages. Lower KLRB1 expression correlated with higher mortality in most cancers, opposite to CLEC2D. Expression variations were attributed to differential lymphocyte infiltration, CNV, and DNA methylation. Structure-based virtual screening analysis identified compounds including forsythiaside A and RGD peptides as effective inhibitors of the KLRB1-CLEC2D interaction, validated through microscale thermophoresis. This research advances understanding of the KLRB1-CLEC2D interaction within the tumor microenvironment and introduces novel therapeutic strategies to modulate this interaction., (Copyright © 2024. Published by Elsevier B.V.)

Background: We conducted a systematic review and meta-analysis to assess the risk of respiratory adverse effects in patients with solid tumors treated with immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors) in combination with radiation therapy., Methods: We selected eligible studies through the following databases: PubMed, Embase, Cochrane Library, and Clinicaltrials ( https://clinicaltrials.gov/ ). The data was analyzed by using Rstudio., Results: Among 3737 studies, 26 clinical trials, including 2670 patients, were qualified for the meta-analysis. We evaluated the incidence rates of adverse respiratory events, including cough, pneumonia, upper respiratory tract infections, and others: grades 1-5 cough, 0.176 (95%CI: 0.113-0.274, I2 = 92.36%); grades 1-5 pneumonitis, 0.118 (95%CI: 0.067-0.198, I2 = 88.64%); grades 1-5 upper respiratory tract infection, 0.064 (95%CI: 0.049-0.080, I2 = 0.98%); grades 3-5 cough, 0.050 (95%CI: 0.012-0.204, I2 = 8.90%); grades 3-5 pneumonitis, 0.052 (95%CI: 0.031-0.078, I2 = 83.86%); grades 3-5 upper respiratory tract infection, 0.040 (95%CI: 0.007-0.249, I2 = 45.31%)., Conclusions: Our meta-analysis demonstrated that ICI combined with radiotherapy for solid tumors can produce respiratory adverse effects. ICIs combination treatment, a tumor located in the chest, is more likely to cause adverse reactions, and SBRT treatment and synchronous treatment will bring less incidence of adverse reactions. This study provide insights for clinicians to balance the risks of radiotherapy in the course of treating oncology patients., (© 2024. The Author(s).)

Introduction: Bromodomain-containing protein 4 (BRD4), an important epigenetic reader, is closely associated with the pathogenesis and development of many diseases, including various cancers, inflammation, and infectious diseases. Targeting BRD4 inhibition or protein elimination with small molecules represents a promising therapeutic strategy, particularly for cancer therapy., Areas Covered: The recent advances of patented BRD4 degraders were summarized. The challenges, opportunities, and future directions for developing novel potent and selective BRD4 degraders are also discussed. The patents of BRD4 degraders were searched using the SciFinder and Cortellis Drug Discovery Intelligence database., Expert Opinion: BRD4 degraders exhibit superior efficacy and selectivity to BRD4 inhibitors, given their unique mechanism of protein degradation instead of protein inhibition. Excitingly, RNK05047 is now in phase I/II clinical trials, indicating that selective BRD4 protein degradation may offer a viable therapeutic strategy, particularly for cancer. Targeting BRD4 with small-molecule degraders provides a promising approach with the potential to overcome therapeutic resistance for treating various BRD4-associated diseases.

Copper-induced cell death is a novel mechanism of cell death, which is defined as cuproptosis. The increasing level of copper can produce toxicity in cells and may cause the occurrence of cell death. Several previous studies have proved that cuproptosis has a tight association with various cancers. Thus, the discovery of relationships between cuproptosis-related genes (CRGs) and human cancers is of great importance. Pan-cancer analysis can efficiently help researchers find out the relationship between multiple cancers and target genes precisely and make various prognostic analyses on cancers and cancer patients. Pan-cancer web servers can provide researchers with direct results of pan-cancer prognostic analyses, which can greatly improve the efficiency of their work. However, to date, no web server provides pan-cancer analysis about CRGs. Therefore, we introduce the cuproptosis pan-cancer analysis database (CuPCA), the first database for various analysis results of CRGs through 33 cancer types. CuPCA is a user-friendly resource for cancer researchers to gain various prognostic analyses between cuproptosis and cancers. It provides single CRG pan-cancer analysis, multi-CRGs pan-cancer analysis, multi-CRlncRNA pan-cancer analysis, and mRNA-circRNA-lncRNA conjoint analysis. These analysis results can not only indicate the relationship between cancers and cuproptosis at both gene level and protein level, but also predict the conditions of different cancer patients, which include their clinical condition, survival condition, and their immunological condition. CuPCA procures the delivery of analyzed data to end users, which improves the efficiency of wide research as well as releases the value of data resources. Database URL: http://cupca.cn/., (© The Author(s) 2024. Published by Oxford University Press.)

Accurate screening of cancer types is crucial for effective cancer detection and precise treatment selection. However, the association between gene expression profiles and tumors is often limited to a small number of biomarker genes. While computational methods using nature-inspired algorithms have shown promise in selecting predictive genes, existing techniques are limited by inefficient search and poor generalization across diverse datasets. This study presents a framework termed Evolutionary Optimized Diverse Ensemble Learning (EODE) to improve ensemble learning for cancer classification from gene expression data. The EODE methodology combines an intelligent grey wolf optimization algorithm for selective feature space reduction, guided random injection modeling for ensemble diversity enhancement, and subset model optimization for synergistic classifier combinations. Extensive experiments were conducted across 35 gene expression benchmark datasets encompassing varied cancer types. Results demonstrated that EODE obtained significantly improved screening accuracy over individual and conventionally aggregated models. The integrated optimization of advanced feature selection, directed specialized modeling, and cooperative classifier ensembles helps address key challenges in current nature-inspired approaches. This provides an effective framework for robust and generalized ensemble learning with gene expression biomarkers.

Chemotherapy, radiotherapy, and immunotherapy represent key tumour treatment strategies. Notably, immune checkpoint inhibitors (ICIs), particularly anti-programmed cell death 1 (PD1) and anti-programmed cell death ligand 1 (PD-L1), have shown clinical efficacy in clinical tumour immunotherapy. However, the limited effectiveness of ICIs is evident due to many cancers exhibiting poor responses to this treatment. An emerging avenue involves triggering non-apoptotic regulated cell death (RCD), a significant mechanism driving cancer cell death in diverse cancer treatments. Recent research demonstrates that combining RCD inducers with ICIs significantly enhances their antitumor efficacy across various cancer types. The use of anti-PD-1/PD-L1 immunotherapy activates CD8 + T cells, prompting the initiation of novel RCD forms, such as ferroptosis, pyroptosis, and necroptosis. However, the functions and mechanisms of non-apoptotic RCD in anti-PD1/PD-L1 therapy remain insufficiently explored. This review summarises the emerging roles of ferroptosis, pyroptosis, and necroptosis in anti-PD1/PD-L1 immunotherapy. It emphasises the synergy between nanomaterials and PD-1/PD-L1 inhibitors to induce non-apoptotic RCD in different cancer types. Furthermore, targeting cell death signalling pathways in combination with anti-PD1/PD-L1 therapies holds promise as a prospective immunotherapy strategy for tumour treatment., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

The rapid growth of research on enzyme-mimetic catalysts (Enz-Cats) is expected to promote further advances in nanomedicine for biological detection, diagnosis and treatment of disease, especially tumors. ROS-based nanomedicines present fascinating potential in antitumor therapy owing to the rapid development of nanotechnology. In this review, we focus on the applications of Enz-Cats based on ROS in antitumor therapy. Firstly, the definition and category of ROS are introduced, and the key factors enhancing ROS levels are carefully elucidated. Then, the rationally engineered Enz-Cats via different synthetic approaches with high ROS-producing efficiencies are comprehensively discussed. Subsequently, oncotherapy application of Enz-Cats is comprehensively discussed, which integrates diverse synergistic treatment modalities and exhibits high efficiency in ROS generation. Finally, the challenges and future research direction of this field are presented. This review is dedicated to unraveling the enigmas surrounding the interplay of nanomedicine and organisms.

Copper, an indispensable micronutrient, is implicated in numerous vital biological processes and is essential for all physiological activities. Recently, the discovery of a novel type of copper-dependent cell death, known as cuproptosis, has shed light on its role in cancer development. Extensive research is currently underway to unravel the mechanisms underlying cuproptosis and its correlation with various cancer types. In this review, we summarize the findings regarding the roles and mechanisms of cuproptosis in various cancer types, including colorectal cancer, lung cancer, gastric cancer, breast cancer, liver cancer and cutaneous melanoma. Furthermore, the effects of copper-related agents such as copper chelators and copper ionophores on cell proliferation, apoptosis, angiogenesis, tumor immunity, and chemotherapy resistance have been explored in cancer preclinical and clinical trials. These insights provide promising avenues for the development of prospective anticancer drugs aimed at inducing cuproptosis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The reciprocal modulation between the CXCL12/CXCR4/ACKR3 axis and the STAT3 signaling pathway plays a crucial role in the progression of various diseases and neoplasms. Activation of the CXCL12/CXCR4/ACKR3 axis triggers the STAT3 pathway through multiple mechanisms, while the STAT3 pathway also regulates the expression of CXCL12. This review offers a thorough and systematic analysis of the reciprocal regulatory mechanisms between the CXCL12/CXCR4/ACKR3 signaling axis and the STAT3 signaling pathway in the context of diseases, particularly tumors. It explores the potential clinical applications in tumor treatment, highlighting possible therapeutic targets and novel strategies for targeted tumor therapy.

Cardiovascular (CV) diseases and tumors are best known for its high morbidity and mortality worldwide. There is a growing recognition of the association between CV diseases and tumorigenesis. In addition to CV damage caused by anti-tumor drugs and tumor-induced organ dysfunction, CV events themselves and their treatment may also have a role in promoting tumorigenesis. Therefore, Therefore, the diagnosis and treatment of the two kinds of diseases have entered the era of clinical convergence. Emerging evidence indicates significant biologic overlap between cancer and CV diseases, with the recognition of shared biologic mechanisms. Neutrophil extracellular traps (NETs) represent an immune mechanism of neutrophils promoting the development of tumors and their metastasis. It has been recently demonstrated that NETs exist in various stages of hypertension and heart failure, exacerbating disease progression. At present, most studies focus on the biological role of NETs in CV diseases and tumor respectively, and there are relatively few studies on the specific regulatory mechanisms and effects of NETs in cardiovascular diseases associated with tumors. In this narrative review, we summarize some recent basic and clinical findings on how NETs are involved in the pathogenesis of cardiovascular diseases associated with tumors. We also highlight that the development of treatments targeting NETs may be one of the effective ways to prevent and treat cardiovascular diseases associated with tumors., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Triclocarban (TCC), a novel antimicrobial agent found in personal care products, has been extensively detected in marine environments. However, research on the toxic effects of TCC on marine organisms remains inadequate. This study delved into the subchronic toxic effects of TCC on the early life stages of marine medaka (Oryzias melastigma, O. melastigma), revealing that TCC could reduce embryo heart rate and hatching rate while diminishing the survival rate of larvae. Biomarker assays indicated that TCC could inflict damage on the embryos' antioxidant and nervous systems. Transcriptomic analysis suggested that TCC could impact cell growth, reproduction, and various life processes, activating cancer signaling pathways, increasing the likelihood of cancer, and exerting toxic effects on the immune and osmoregulatory systems. To validate and enhance our understanding of TCC's unique toxic impact on the osmoregulatory system of O. melastigma, we conducted homology modeling and molecular docking analyses on the protein involved in osmoregulation. The study intuitively revealed the potential binding affinity of TCC to sodium/potassium-transporting ATPase subunit alph (ATP1A1), indicating its ability to disrupt osmotic balance in marine fish by affecting this target protein. In summary, the results of this study will further enhance our comprehension of the potential toxic effects and mechanisms of TCC on the early stages of marine fish, with a specific focus on its unique toxic effects in osmoregulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer., Methods: Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs)., Results: Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18-1.27) in men, and 1.26 (1.22-1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10-2.51) for men and 1.94 (1.78-2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = -1.01 in men, p<0.001; Beta = -0.98 in women, p<0.001)., Conclusions: Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle., Funding: This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ)., Competing Interests: LB, ZM, XF, CJ, TW, CY, JD, HM, ZH, HS, LW, MZ, GJ No competing interests declared, (© 2024, Bian, Ma et al.)

Sonodynamic therapy (SDT) has garnered growing interest owing to its high tissue penetration depth and minimal side effects. However, the lack of efficient sonosensitizers remains the primary limiting factor for the clinical application of this treatment method. Here, defect-repaired graphene phase carbon nitride (g-C 3 N 4 ) nanosheets are prepared and utilized for enhanced SDT in anti-tumor treatment. After defect engineering optimization, the bulk defects of g-C 3 N 4 are significantly reduced, resulting in higher crystallinity and exhibiting a polyheptazine imide (PHI) structure. Due to the more extended conjugated structure of PHI, facilitating faster charge transfer on the surface, it exhibits superior SDT performance for inducing apoptosis in tumor cells. This work focuses on introducing a novel carbon nitride nanomaterial as a sonosensitizer and a strategy for optimizing sonosensitizer performance by reducing bulk defects., (© 2024 Wiley‐VCH GmbH.)

In order to establish a set of perfect heterojunction designs and characterization schemes, step-scheme (S-scheme) BiOBr@Bi 2 S 3 nanoheterojunctions that enable the charge separation and expand the scope of catalytic reactions, aiming to promote the development and improvement of heterojunction engineering is developed. In this kind of heterojunction system, the Fermi levels mediate the formation of the internal electric field at the interface and guide the recombination of the weak redox carriers, while the strong redox carriers are retained. Thus, these high-energy electrons and holes are able to catalyze a variety of substrates in the tumor microenvironment, such as the reduction of oxygen and carbon dioxide to superoxide radicals and carbon monoxide (CO), and the oxidation of H 2 O to hydroxyl radicals, thus achieving sonodynamic therapy and CO combined therapy. Mechanistically, the generated reactive oxygen species and CO damage DNA and inhibit cancer cell energy levels, respectively, to synergistically induce tumor cell apoptosis. This study provides new insights into the realization of high efficiency and low toxicity in catalytic therapy from a unique perspective of materials design. It is anticipated that this catalytic therapeutic method will garner significant interest in the sonocatalytic nanomedicine field., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The crucial role of cancer-associated fibroblasts (CAFs) in promoting T-cell exclusion has a significant impact on tumor immune evasion and resistance to immunotherapy. Therefore, enhancing T-cell infiltration into solid tumors has emerged as a pivotal area of research. We achieved a conventional knockout of Shcbp1 (Shcbp1 -/- ) through CRISPR/Cas9 gene editing and crossed these mice with spontaneous breast cancer MMTV-PyMT mice, resulting in PyMT Shcbp1 -/- mice. The different CAF subtypes were detected by flow cytometry analysis (FCA). We evaluated collagen and CAFs levels using Sirius red staining, immunohistochemistry (IHC), and immunofluorescence (IF). Primary tumor cells and CAFs were isolated from both PyMT Shcbp1 +/+ and PyMT Shcbp1 -/- mice. We analyzed CAFs' proliferation, invasion, migration, apoptosis, and cell cycle. Transwell coculture experiments were performed with primary tumor cells and CAFs to evaluate the role of CAFs in increasing the sensitivity of tumor cells to Erdafitinib. Tumors from PyMT Shcbp1 +/+ and PyMT Shcbp1 -/- mice were orthotopically transplanted to assess the therapeutic effect of the Erdafitinib and PD-1 combination. CAFs and T-cell infiltration in these tumors were assessed using FCA and IF. Knockout of Shcbp1 leads to a significant reduction in tumor burden, promotes longer survival, and decreases CAFs in MMTV-PyMT. Moreover, knockout of Shcbp1 enhances the sensitivity of Erdafitinib, leading to effective inhibition of CAFs' proliferation and invasion, as well as the induction of apoptosis. Additionally, it results in cell cycle arrest at the G2/M phase in vitro. Meanwhile, Shcbp1 -/- CAFs change the sensitivity of Shcbp1 -/- tumor cells to Erdafitinib compared to Shcbp1 +/+ CAFs. Importantly, knockout of Shcbp1 boosts the effectiveness of Erdafitinib in combination with immune checkpoint blockade therapy by augmenting T-cell infiltration through CAFs regulation in vivo. Our findings demonstrate that knockout of Shcbp1 holds significant potential in enhancing the therapeutic response of Erdafitinib combined with PD-1 antibody treatment, offering promising prospects for future breast cancer therapies., (© 2024 Wiley Periodicals LLC.)

In this work, a near-infrared emissive photosensitizer of 3,3-dimethyl-N,N-diphenyl-2-(thiophen-2-yl)-3H-indol-6-amine functionlized benzothiazolium (DPITT) was developed. DPITT exhibited aggregation-induced emission effect and potent type I and II reactive oxygen species generation capacities after white light irradiation. Taking advantage of the cationic feature, DPITT penetrated the cell membrane and selectively accumulated in the mitochondria in living cells. Upon white light irradiation, the photosensitized DPITT was able to induce mitochondrial dysfunction, leading to cell death. Photosensitized DPITT was further applied to disrupt the multicellular tumour spheroids, demonstrating its potential application in inhibiting hypoxic solid tumours., (© 2024 John Wiley & Sons Ltd.)

Innate immune cells can undergo long-term functional reprogramming after certain infections, a process called trained immunity (TI). Here, we focus on antigens of Leishmania braziliensis, which induced anti-tumor effects via trained immunity in human monocytes. We reveal that monocytes exposed to promastigote antigens of L. braziliensis develop an enhanced response to subsequent exposure to Toll-like receptor (TLR)2 or TLR4 ligands. Mechanistically, the induction of TI in monocytes by L. braziliensis is mediated by multiple pattern recognition receptors, changes in metabolism, and increased deposition of H3K4me3 at the promoter regions of immune genes. The administration of L. braziliensis exerts potent anti-tumor capabilities by delaying tumor growth and prolonging survival of mice with non-Hodgkin lymphoma. Our work reveals mechanisms of TI induced by L. braziliensis in vitro and identifies its potential for cancer immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

FBXW7 is an E3 ubiquitin ligase that targets proteins for proteasome-mediated degradation and is mutated in various cancer types. Here, we use CRISPR base editors to introduce different FBXW7 hotspot mutations in human colon organoids. Functionally, FBXW7 mutation reduces EGF dependency of organoid growth by ~10,000-fold. Combined transcriptomic and proteomic analyses revealed increased EGFR protein stability in FBXW7 mutants. Two distinct phosphodegron motifs reside in the cytoplasmic tail of EGFR. Mutations in these phosphodegron motifs occur in human cancer. CRISPR-mediated disruption of the phosphodegron motif at T693 reduced EGFR degradation and EGF growth factor dependency. FBXW7 mutant organoids showed reduced sensitivity to EGFR-MAPK inhibitors. These observations were further strengthened in CRC-derived organoid lines and validated in a cohort of patients treated with panitumumab. Our data imply that FBXW7 mutations reduce EGF dependency by disabling EGFR turnover., Competing Interests: Competing interests statement:H.C. is inventor of several patents related to organoid technology, is cofounder of Xilis Inc. and is currently employee of Roche, Basel (CH) Switzerland. His full disclosure is given at https://www.uu.nl/staff/JCClevers/.

Phototherapy provides a noninvasive and spatiotemporal controllable paradigm to inhibit the evasion of the programmed cell death (PCD) of tumors. However, conventional photosensitizers (PSs) often induce a single PCD process, resulting in insufficient photodamage and severely impeding their application scopes. In this study, molecular engineering is conducted by adjusting electron donors to develop an aggregation-induced NIR-II emissive PS (DPITQ) for plasma membrane and mitochondria dual-targeted tumor therapy by evoking synergetic pyroptosis and apoptosis. DPITQ displays boosted type I and II reactive oxygen species generation as well as a high photothermal conversion efficacy (43%) after laser irradiation of 635 nm. The excellent biocompatibility and appropriate lipophilicity help the DPITQ to specifically anchor in the plasma membrane and mitochondria of cancer cells. Furthermore, the photosensitized DPITQ can disrupt the intact plasma membrane and cause mitochondrial dysfunction, ultimately causing concurrent pyroptosis and apoptosis to suppress cancer cell proliferation even under hypoxia. It is noteworthy that the DPITQ nanoparticles (NPs) present clear NIR-II fluorescence imaging capability on the venous vessels of nude mice. Notably, the DPITQ NPs exert efficient NIR-II fluorescence imaging-guided phototherapy both in multicellular tumor spheroids and in vivo, causing maximum destruction to tumors but minimum adverse effects to normal tissue., (© 2023 Wiley-VCH GmbH.)

Male infertility, age-related changes, and tumors have been increasingly studied in the field of male reproductive health due to the emergence of environmental stressors, declining fertility rates, and aging populations. Numerous studies have demonstrated that the ERK1/2 signaling pathway plays a significant role in male reproduction. The ERK1/2 pathway is associated with several signaling pathways and has a complex interplay that influences the spermatogenic microenvironment, sperm viability, gonadal axis regulation, as well as resistance to testicular aging and tumors. Moreover, the ERK1/2 pathway directly or indirectly regulates testicular somatic cells, which are crucial for maintaining spermatogenesis and microenvironment regulation. Given the critical role of the ERK1/2 signaling pathway in male reproductive health, comprehensive exploration of its multifaceted effects on male reproduction and underlying mechanisms is necessary. This study aims to provide a solid foundation for in-depth research in the field of male reproduction and further enhance the reproductive health of males., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu 2+ -to-Cu + photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu + . Bb mediates photogeneration of hydroxyl radicals (•OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of •OH based on Bb and the Cu + species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model., (© 2023 Wiley-VCH GmbH.)

Gastric cancer (GC) is a malignant tumor of the gastrointestinal tract with a high mortality rate worldwide, a low early detection rate and a poor prognosis. The rise of metabolomics has facilitated the early detection and treatment of GC. Metabolism in the GC tumor microenvironment (TME) mainly includes glucose metabolism, lipid metabolism and amino acid metabolism, which provide energy and nutrients for GC cell proliferation and migration. Abnormal tumor metabolism can influence tumor progression by regulating the functions of immune cells and immune molecules in the TME, thereby contributing to tumor immune escape. Thus, in this review, we summarize the impact of metabolism on the TME during GC progression. We also propose novel strategies to modulate antitumor immune responses by targeting metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Safety evaluations in preclinical studies are needed to confirm before translating a cell-based product into clinical application. We previously developed a serum-free, xeno-free, and chemically defined media (S&XFM-CD) for the derivation of clinical-grade umbilical cord-derived MSCs (UCMSCs), and demonstrated that intraperitoneal administration of UCMSCs in S&XFM-CD (UCMSC S&XFM-CD ) exhibited better therapeutic effects than UCMSCs in serum-containing media (SCM, UCMSC SCM ). However, a comprehensive investigation of the safety of intraperitoneal UCMSC S&XFM-CD treatment should be performed before clinical applications., Methods: In this study, the toxicity, immunogenicity and biodistribution of intraperitoneally transplanted UCMSC S&XFM-CD were compared with UCMSC SCM in rats via general vital signs, blood routine, blood biochemistry, subsets of T cells, serum cytokines, pathology of vital organs, antibody production and the expression of human-specific gene. The tumorigenicity and tumor-promoting effect of UCMSC S&XFM-CD were compared with UCMSC SCM in nude mice., Results: We confirmed that intraperitoneally transplanted UCMSC S&XFM-CD or UCMSC SCM did not cause significant changes in body weight, temperature, systolic blood pressure, diastolic blood pressure, heart rate, blood routine, T lymphocyte subsets, and serum cytokines, and had no obvious histopathology change on experimental rats. UCMSC S&XFM-CD did not produce antibodies, while UCMSC SCM had very high chance of antibody production to bovine serum albumin (80%) and apolipoprotein B-100 (60%). Furthermore, intraperitoneally injected UCMSC S&XFM-CD were less likely to be blocked by the lungs and migrated more easily to the kidneys and colon tissue than UCMSC SCM . In addition, UCMSC S&XFM-CD or UCMSC SCM showed no obvious tumorigenic activity. Finally, UCMSC S&XFM-CD extended the time of tumor formation of KM12SM cells, and decreased tumor incidence than that of UCMSC SCM ., Conclusions: Taken together, our data indicate that UCMSC S&XFM-CD display an improved safety performance and are encouraged to use in future clinical trials., (© 2023. The Author(s).)

Somatic copy number gains are pervasive across cancer types, yet their roles in oncogenesis are insufficiently evaluated. This inadequacy is partly due to copy gains spanning large chromosomal regions, obscuring causal loci. Here, we employed organoid modeling to evaluate candidate oncogenic loci identified via integrative computational analysis of extreme copy gains overlapping with extreme expression dysregulation in The Cancer Genome Atlas. Subsets of "outlier" candidates were contextually screened as tissue-specific cDNA lentiviral libraries within cognate esophagus, oral cavity, colon, stomach, pancreas, and lung organoids bearing initial oncogenic mutations. Iterative analysis nominated the kinase DYRK2 at 12q15 as an amplified head and neck squamous carcinoma oncogene in p53 -/- oral mucosal organoids. Similarly, FGF3, amplified at 11q13 in 41% of esophageal squamous carcinomas, promoted p53 -/- esophageal organoid growth reversible by small molecule and soluble receptor antagonism of FGFRs. Our studies establish organoid-based contextual screening of candidate genomic drivers, enabling functional evaluation during early tumorigenesis., Competing Interests: Declaration of interests A.A.S. has served as a consultant for Boehringer Ingelheim and Pharmacosmos and is a former employee of Tempus Labs. C.J.K. is a scientific advisory board member for Surrozen, Inc., Mozart Therapeutics, and NextVivo. C.C. has served as a scientific advisory board member/consultant for Genentech, Grail, DeepCell, Nanostring, and Viosera. W.C.H. is a consultant for Thermo Fisher, Solasta Ventures, MPM Capital, KSQ Therapeutics, Tyra Biosciences, Frontier Medicine, Jubilant Therapeutics, RAPPTA Therapeutics, Hexagon Bio, Serinus Biosciences, Function Oncology, and Calyx., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In oncolytic virus (OV) therapy, a critical component of tumor immunotherapy, viruses selectively infect, replicate within, and eventually destroy tumor cells. Simultaneously, this therapy activates immune responses and mobilizes immune cells, thereby eliminating residual or distant cancer cells. However, because of OVs' high immunogenicity and immune clearance during circulation, their clinical applications are currently limited to intratumoral injections, and their use is severely restricted. In recent years, numerous studies have used nanomaterials to modify OVs to decrease virulence and increase safety for intravenous injection. The most commonly used nanomaterials for modifying OVs are liposomes, polymers, and albumin, because of their biosafety, practicability, and effectiveness. The aim of this review is to summarize progress in the use of these nanomaterials in preclinical experiments to modify OVs and to discuss the challenges encountered from basic research to clinical application., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2023 Cancer Biology & Medicine.)

Exosomes are a kind of extracellular vesicles, which play a significant role in intercellular communication and molecular exchange. Cancer-derived exosomes are potential and ideal biomarkers for the early diagnosis and treatment monitoring of cancers because of their abundant biological information and contribution to the interaction between cancer cells and the tumor microenvironment. However, there are a number of drawbacks, such as low sensitivity and tedious steps, in conventional detection techniques. Furthermore, exosome quantification is not enough to accurately distinguish cancer patients from healthy individuals. Therefore, developing efficient, accurate, and inexpensive exosome surface protein analysis techniques is necessary and critical. In recent years, a considerable number of researchers have presented novel detection strategies in this field. This review summarizes the recent progress in quantitative technologies for the analysis of cancer-related exosome proteins, mainly including the detection methods based on aptamers, nanomaterials, and antibodies, discusses a roadmap for future developments, and aims to offer an innovative perspective of exosome research.

Purpose: To introduce the clinical outcomes of adductor longus and sartorius muscle transfer alone and combined application for reconstruction of the inguinal region., Methods: This is a retrospective study of patients between January 2019 and December 2022 who underwent adductor longus flap transfer, sartorius muscle flap transfer, and combined transfer of adductor longus and sartorius muscle. The demographic data and surgical details were recorded., Results: Sixteen patients were included, with a mean age of 57.5 years. Nine patients performed adductor longus flap transfers, three patients performed sartorius muscle flap transfers, and four patients performed combined transfers. The average operation time was 238 min. The average length of stay was 6.7 days. The average follow-up period was 9.6 months (range 6-16). The overall early postoperative complication rate was 12.5% (one patient had excessive wound exudation and one patient had a wound infection). No delayed postoperative complications occurred during the follow-up., Conclusion: The sartorius muscle flap, the adductor longus flap, and the combined application are suitable techniques for inguinal region reconstruction under different conditions. The combined application of the two flaps can fill the dead space and cover the neurovascular bundle efficaciously., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2023. Published by Elsevier Ltd.)

Alcohol is a known carcinogen. However, public awareness of cancer risk associated with alcohol use is low. A promising approach to raising awareness is to include cancer warning labels on alcohol-containing products, but there is limited knowledge of the design and effect of such warnings. The present study investigated the impact of visual elements on the effectiveness of cancer warning labels. In a randomized online experiment, alcohol consumers ( N = 1,190) were randomly assigned to one of three conditions: exposure to (a) text-only warning labels, (b) pictorial warning labels showing graphic health effects (e.g., diseased organs), and (c) pictorial warning labels showing lived experience (e.g., cancer patients in a medical setting). The results showed that whereas the three warning types did not differ significantly in behavioral intentions, pictorial warnings featuring health effects led to greater disgust and anger than text-only warnings and pictorial warnings featuring lived experience. Moreover, anger predicted lower intentions to reduce alcohol use and was a significant mediator of the effects of warning type on behavioral intentions. The findings highlight the role of emotions in responses to health warning labels with different visual elements and suggest that text-only warnings and pictorial warnings with lived experience may be useful in preventing boomerang effects.

Background: Although sleep quality is known to be associated with mortality, how poor sleep quality contributes to an increased risk of mortality is still unknown. We aimed to examine whether lifestyle, psychosocial and biological factors mediate the association., Methods: 205,654 participants from UK Biobank were used for the analysis. The outcome was all-cause, cardiovascular disease (CVD) and cancer mortality by February 2022. Exposure was assessed by a sleep score consisting of five sleep behaviors at baseline. Lifestyle, psychosocial, and biological factors are regarded as potential mediators. Mediation analysis based on Cox proportional hazards models was performed., Results: Poor sleep quality was associated with a higher risk of all-cause (Hazard Ratio [HR] = 1.098; 95% CI: 1.058-1.140), CVD (HR = 1.139; 95% CI: 1.045-1.243) and cancer mortality (HR = 1.095; 95% CI: 1.040-1.152). Lifestyle mediators (smoking, physical activity, sedentary, BMI and diet) could explain between 2.6% and 34.0% of the increased risk of all-cause mortality in individuals with poor sleep quality. Self-reported health, frailty, depression, and loneliness were significant psychosocial mediators of this association pathway. About one-fifth of the association can be explained by the biological role of CRP. Similar mediating patterns were observed for CVD and cancer mortality., Limitations: Both exposure and mediators were measured at baseline, so the possibility of reverse causality cannot be ruled out., Conclusions: Poor sleep quality is associated with an increased risk of death through a combination of lifestyle, psychosocial and biological pathways. Adopting healthy lifestyles and staying psychosocial well-being are cost-effective interventions to lower the risk of death., Competing Interests: Declaration of Competing Interest All authors have declared that no competing interest exists., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Telomeres are unique structures located at the ends of linear chromosomes, responsible for stabilizing chromosomal structures. They are synthesized by telomerase, a reverse transcriptase ribonucleoprotein complex. Telomerase activity is generally absent in human somatic cells, except in stem cells and germ cells. Every time a cell divides, the telomere sequence is shortened, eventually leading to replicative senescence and cell apoptosis when the telomeres reach a critical limit. However, most human cancer cells exhibit increased telomerase activity, allowing them to divide continuously. The importance of telomerase in cancer and aging has made developing drugs targeting telomerase a focus of research. Such drugs can inhibit cancer cell growth and delay aging by enhancing telomerase activity in telomere-related syndromes or diseases. This review provides an overview of telomeres, telomerase, and their regulation in cancer and aging, and highlights small-molecule drugs targeting telomerase in these fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nuclear receptor binding SET domain proteins (NSDs) catalyze the mono- or dimethylation of histone 3 lysine 36 (H3K36me1 and H3K36me2), using S -adenosyl-l-methionine (SAM) as a methyl donor. As a key member of the NSD family of proteins, NSD2 plays an important role in the pathogenesis and progression of various diseases such as cancers, inflammations, and infectious diseases, serving as a promising drug target. Developing potent and specific NSD2 inhibitors may provide potential novel therapeutics. Several NSD2 inhibitors and degraders have been discovered while remaining in the early stage of drug development. Excitingly, KTX-1001, a selective NSD2 inhibitor, has entered clinical trials. In this Perspective, the structures and functions of NSD2, its roles in various human diseases, and the recent advances in drug discovery strategies targeting NSD2 have been summarized. The challenges, opportunities, and future directions for developing NSD2 inhibitors and degraders are also discussed.

In 1971, Folkman proposed that tumors could be limited to very small sizes by blocking angiogenesis. Angiogenesis is the generation of new blood vessels from pre-existing vessels, considered to be one of the important processes in tumor growth and metastasis. Angiogenesis is a complex process regulated by various factors and involves many secreted factors and signaling pathways. Angiogenesis is important in the transport of oxygen and nutrients to the tumor during tumor development. Therefore, inhibition of angiogenesis has become an important strategy in the clinical management of many solid tumors. Combination therapies of angiogenesis inhibitors with radiotherapy and chemotherapy are often used in clinical practice. In this article, we will review common targets against angiogenesis, the most common and up-to-date anti-angiogenic drugs and clinical treatments in recent years, including active ingredients from chemical and herbal medicines., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Masson SAS.)

Cancer is a malignant disease that endangers human life, especially owing to its high fatality rate; therefore, rapid and accurate early screening is needed to effectively improve the survival rate. Compared with traditional cancer detection methods, electrochemical biosensors that recognize cancer biomarkers in blood have the advantages of low invasiveness, fast diagnosis, and low cost. However, there is always a trade-off between sensitivity and selectivity, which limits the detection of trace amounts of biomarkers produced in the early stages. To address this issue, an increasing number of nanomaterials with simultaneous improvements in both sensitivity and selectivity have recently been reported. In this review, different categories of state-of-the-art electrochemical biosensors and their operating principles are introduced, and their respective advantages and disadvantages are described. Furthermore, the review discusses the existing detection strategies and performance of nanomaterial-based cancer biosensors for biomarker recognition, providing overall guidance for the material selection of different biomarkers. Finally, the main challenges involving existing electrochemical cancer biosensors are evaluated to present the future development prospects of nanomaterials and detection strategies., (© 2023 Wiley-VCH GmbH.)

Cancer is a severe threat to human life and health and represents the main cause of death globally. Drug therapy is one of the primary means of treating cancer; however, most anticancer medications do not proceed beyond preclinical testing because the conditions of actual human tumors are not effectively mimicked by traditional tumor models. Hence, bionic in vitro tumor models must be developed to screen for anticancer drugs. Three-dimensional (3D) bioprinting technology can produce structures with built-in spatial and chemical complexity and models with accurately controlled structures, a homogeneous size and morphology, less variation across batches, and a more realistic tumor microenvironment (TME). This technology can also rapidly produce such models for high-throughput anticancer medication testing. This review describes 3D bioprinting methods, the use of bioinks in tumor models, and in vitro tumor model design strategies for building complex tumor microenvironment features using biological 3D printing technology. Moreover, the application of 3D bioprinting in vitro tumor models in drug screening is also discussed.

Cancer is one of the leading causes of human death. MicroRNAs have been found to be closely associated with cancer. The miR-183 cluster, comprising miR-183, miR-96, and miR-182, is transcribed as a polycistronic miRNA cluster. Importantly, in most cases, these clusters promote cancer development through different pathways. Exosomes, as extracellular vesicles, play an important role in cellular communication and the regulation of the tissue microenvironment. Interestingly, the miR-183 cluster can be detected in exosomes and plays a functional regulatory role in tumor development. Here, the biogenesis and functions of the miR-183 cluster in highly prevalent cancers and their relationship with other non-coding RNAs are summarized. In addition, the miR-183 cluster in exosomes has also been discussed. Finally, we discuss the miR-183 cluster as a promising target for cancer therapy. This review is expected to provide a new direction for cancer treatment.

Hypercoagulation threatens the lives of cancer patients and cancer progression. Platelet overactivation attributes to the tumor-associated hypercoagulation and maintenance of the tumor endothelial integrity, leading to limited intratumoral perfusion of nanoagents into solid tumors in spite of the enhanced penetration and retention effect (EPR). Therefore, the clinical application of nanotherapeutics in solid cancer still faces great challenges. Herein, this work establishes platelet inhibiting nanoagents based on Fe III -doped C 3 N 4 coloaded with the chemotherapy drug and the antiplatelet drug chlorogenic acid (CA), further opening tumor vascular endothelial junctions, thereby disrupting the tumor vascular endothelial integrity, and enhancing drug perfusion. Moreover, CA not only damages the cancer cells but also potentiates the cytotoxicity induced by the chemotherapy drug doxorubicin, synergistically ablating the tumor tissue. Further, the introduction of CA relieves the original causes of the hypercoagulable state such as tissue factor (TF), thrombin, and matrix metalloproteinases (MMPs) secreted by cancer cells. It is anticipated that the hypercoagulation- and platelet-inhibition strategy by integration of phenolic acid CA into chemotherapy provides insights into platelet inhibition-assisted theranostics based on nanomedicines., (© 2022 Wiley-VCH GmbH.)

Although chemotherapy and photodynamic therapy (PDT) have been developed for fighting cancer, the complex and heterogeneous nature of tumors makes it difficult for a single therapy to completely inhibit tumor growth. In order to reduce multidrug resistance of cancer cells to chemotherapeutic drugs and overcome low PDT efficiency in the hypoxic tumor microenvironment (TME), chemo/PDT synergistic treatment has received much attention in recent years. Depending on the characteristic signals of TME, various drug delivery systems can be constructed to target tumors and improve the therapeutic efficacy and the pharmacokinetic profile of anticancer drugs. This review highlights the synergistic strategies, treatment protocols, and design of chemo/PDT co-therapy in recent years to explore its scope and limitations. Taking advantage of stimuli-responsive materials and active cancer-targeting agents, cancer-targeting synergistic therapy is presented and discussed, providing ideas and suggestions for the construction of chemo/PDT co-therapy "smart" nanocarriers.

Background: Cutaneous adverse effects (AEs) are common following the phosphoinositide-3-kinase (PI3K) inhibitors treatment. We aim to estimate the incidence and risk of PI3K inhibitor-related cutaneous AEs., Methods: The protocol was submitted to the PROSPERO registry. We searched ClinicalTrials.gov and international databases up to July 29, 2022. Meta-analysis was conducted by using risk ratios (RRs) with 95% confidence intervals (CIs)., Results: Fourteen randomized controlled trials (RCTs) comprising 3877 patients were analyzed in this study. Compared with control arms, PI3K inhibitors showed a significant increase in the risk of all-grade rash, high-grade rash, and serious rash events (RR 2.29, 95% CI 1.58-3.31, p < 0.00001; RR 9.34, 95% CI 4.21-20.69, p < 0.00001; RR 5.11, 95% CI 2.11-12.36, p = 0.0003). The overall incidences of all-grade rash and high-grade rash were 26.2% (592/2257) and 4.4% (66/1487). Subgroup analyses of all-grade rash according to cancer types and PI3K inhibitor assignations identified the significant associations. PI3K inhibitors also significantly increased the risk of pruritus and dry skin (RR 1.63, 95% CI 1.14-2.33, p = 0.007; RR 3.34, 95% CI 2.30-4.85, p < 0.00001), with incidences of 13.4% (284/2115) and 9.8% (141/1436) in the treatment group., Conclusion: There is a significantly increased risk of some cutaneous AEs in patients using PI3K inhibitors. Advance intervention is recommended in case of severe and life-threatening events. Further research is required to investigate the risk factors and pathogenesis., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Mitochondria play critical roles in the regulation of the proliferation and apoptosis of cancerous cells. Targeted induction of mitochondrial dysfunction in cancer cells by multifunctional nanosystems for cancer treatment has attracted increasing attention in the past few years. Numerous therapeutic nanosystems have been designed for precise tumor therapy by inducing mitochondrial dysfunction, including reducing adenosine triphosphate, breaking redox homeostasis, inhibiting glycolysis, regulating proteins, membrane potential depolarization, mtDNA damage, mitophagy dysregulation and so on. Understanding the mechanisms of mitochondrial dysfunction would be helpful for efficient treatment of diseases and accelerating the translation of these therapeutic strategies into the clinic. Then, various strategies to construct mitochondria-targeted nanosystems and induce mitochondrial dysfunction are summarized, and the recent research progress regarding precise tumor therapeutics is highlighted. Finally, the major challenges and an outlook in this rapidly developing field are discussed. This review is expected to inspire further development of novel mitochondrial dysfunction-based strategies for precise treatments of cancer and other human diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The purpose of this study was to develop a nano-drug delivery system with intelligent stimuli-responsive drug delivery in tumor microenvironment (TME). Based on chiral mesoporous silica nanoparticles (CMSN) with a chiral recognition function in our previous research, a pH-responsive CMSN (CS-CMSN) was successfully prepared by chemical modification of chitosan (CS), and the related physicochemical properties, drug release performance, potential anti-tumor effect, and biological safety were studied. The results showed that the CS-CMSN were successfully modified by CS. Moreover, CS-CMSN displayed superior encapsulation ability for doxorubicin (DOX) and exhibited controllable pH-responsive drug release properties. In particular, in a physiological environment (pH 7.4/6.5), CS shielded the nanopores, prevented DOX release, and minimized side effects on normal cells. Once the CS-CMSN was exposed to the TME (pH 5.0), the pH-sensitive moiety of CS was cleaved in an acidic environment, along with the rapid release of DOX. In vitro cell experiments further proved that DOX@CS-CMSN was more strongly taken up by 4T1 cells and could enhance the toxicity to 4T1 tumor cells as well as promote cell apoptosis. More importantly, CS-CMSN were shown to have good biosafety in vitro and in vivo. Overall, the delivery of DOX by CS-CMSN nanocarriers is a promising strategy for tumor-targeted therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)