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Exosomes are vesicles encompassed by a lipid bilayer that are released by various living cells. Exosomal proteins are encapsulated within the membrane or embedded on the surface. As an important type of exosome cargo, exosomal proteins can reflect the physiological status of the parent cell and play an essential role in cell–cell communication. Exosomal proteins can regulate tumor development, including tumor-related immune regulation, microenvironment reconstruction, angiogenesis, epithelial–mesenchymal transition, metastasis, etc. The features of exosomal proteins can provide insight into exosome generation, targeting, and biological function and are potential sources of markers for cancer diagnosis, prognosis, and treatment. Here, we summarize the effects of exosomal proteins on cancer biology, the latest progress in the application of exosomal proteins in cancer diagnosis and prognosis, and the potential contribution of exosomal proteins in cancer therapeutics and vaccines. Cancer: exploring the potential of exosomes Exosomes, membrane-bound vesicles released by some cells, contain a cargo of proteins and other biomolecules that can be analyzed to assist the diagnosis of cancer or predict its likely outcome, and may become useful in treating cancer. Zhihui Li, Jianyong Lei, and colleagues at Sichuan University, Chengdu, China, review progress in cancer-focused exosome research. The proteins in exosomes can act as indicators of the health or disease status of cells. They can also control the development of tumors and wider physiological processes that support tumor growth and spread. The authors consider the specific significance of exosome proteins in each of a wide range of common human cancers, and discuss some technical challenges that must be overcome to fully exploit the potential of exosomes to diagnose, monitor, and perhaps treat cancer.

Abstract Context Teprotumumab, which targets the insulin-like growth factor-1 receptor, is the only drug approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED). Objective This study aimed to identify potential safety signals of teprotumumab by analyzing postmarketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023. Methods The case/noncase approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant 95% CI for adverse events (AEs) that numbered 3 or more. Results A total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders, and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), permanent deafness (ROR [95% CI] = 1552.35 [789.07-3053.98]), bilateral deafness (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]), and amenorrhea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals with teprotumumab. Conclusion This study identified ear and labyrinth disorders, and reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.

Ecosystem services are substantial elements for human society. The central challenge to meet the human needs from ecosystems while sustain the Earth＇s life support systems makes it urgent to enhance efficient natural resource management for sustainable ecological and socioeconomic development. Trade-off analysis of ecosystem services can help to identify optimal decision points to balance the costs and benefits of the diverse human uses of ecosystems. In this sense, the aim of this paper is to provide key insights into ecosystem services trade-off analysis at different scales from a land use perspective, by comprehensively reviewing the trade-offs analysis tools and approaches that addressed in ecology, economics and other fields. The review will significantly contribute to future research on trade-off analysis to avoid inferior management options and offer a win-win solution based on comprehensive and efficient planning for interacting multiple ecosystem services.

The PI3K/AKT/mTOR and RAF/MEK/ERK pathways are commonly activated by mutations and chromosomal translocation in vital targets. The PI3K/AKT/mTOR signaling pathway is dysregulated in nearly all kinds of neoplasms, with the component in this pathway alternations. RAF/MEK/ERK signaling cascades are used to conduct signaling from the cell surface to the nucleus to mediate gene expression, cell cycle processes and apoptosis. RAS, B-Raf, PI3K, and PTEN are frequent upstream alternative sites. These mutations resulted in activated cell growth and downregulated cell apoptosis. The two pathways interact with each other to participate in tumorigenesis. PTEN alterations suppress RAF/MEK/ERK pathway activity via AKT phosphorylation and RAS inhibition. Several inhibitors targeting major components of these two pathways have been supported by the FDA. Dozens of agents in these two pathways have attracted great attention and have been assessed in clinical trials. The combination of small molecular inhibitors with traditional regimens has also been explored. Furthermore, dual inhibitors provide new insight into antitumor activity. This review will further comprehensively describe the genetic alterations in normal patients and tumor patients and discuss the role of targeted inhibitors in malignant neoplasm therapy. We hope this review will promote a comprehensive understanding of the role of the PI3K/AKT/mTOR and RAF/MEK/ERK signaling pathways in facilitating tumors and will help direct drug selection for tumor therapy.

Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP 1 + tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/ . Cancer-associated fibroblasts (CAFs) are a predominant and critical component of the tumour microenvironment. Here, the authors integrate and analyse single-cell RNA-seq data of CAFs across 10 common solid cancer types, identifying their plasticity and interactions with other cell types.

Climate change and rapid urbanization bring natural and anthropogenetic disturbance to the urban ecosystem, damaging the sustainability and resilience of cities. Evaluation of urban ecological resilience and an investigation of its impact mechanisms are of great importance to sustainable urban management. Therefore, taking the Beijing-Tianjin-Hebei Urban Agglomeration (BTHUA) region in China as a study area, this study builds an evaluation index to assess urban ecological resilience and its spatial patterns with the resilience surrogate of net primary production during 2000–2020. The evaluation index is constructed from two dimensions, including the sensitivity and adaptability of urban ecosystems, to capture the two key mechanisms of resilience, namely resistance and recovery. Resilience-influencing factors including biophysical and socio-economic variables are analyzed with the multiple linear regression model. The results show that during 2000–2020, the spatial pattern of urban ecological resilience in the BTHUA is characterized by high resilience in the northwest and relatively low resilience in the southeast. High resilience areas account for 40% of the whole region, mainly contributed by Zhangjiakou and Chengde city in Hebei Province, which is consistent with the function orientation of the BTH region in its coordinated development. Along with urbanization in this region, ecological resilience decreases with increased population and increases with GDP growth; this indicates that, although population expansion uses resources, causes pollution and reduces vegetation coverage, with economic growth and technological progress, the negative ecological impact could be mitigated, and the coordinated development of social economy and ecological environment could eventually be reached. Our findings are consistent with mainstream theories examining the ecological impact of socio-economic development such as the Environmental Kuznets Curve, Porter Hypothesis, and Ecological Modernization theories, and provide significant references for future urbanization, carbon neutrality, resilience building, and urban ecological management in China.

Ecological environment quality and resilience assessment is an important prerequisite for ensuring the coordination and stability of socio-economic development and eco-environment protection. Remote sensing technology has provided new approaches for quantitatively evaluating regional ecological environment quality and resilience rapidly, accurately, and objectively. Taking the middle and lower reaches of the Yangtze River Economic Belt (YREBML) as an example, to assess ecological environment quality, this study calculated the remote sensing ecological index (RSEI) based on the Google Earth Engine using Moderate Resolution Imaging Spectroradiometer (MODIS) data with a spatial resolution of 500 m during 2000–2020. An evaluation index to assess ecological resilience and its spatial pattern based on the RSEI of 2000–2020 was then constructed. The evaluation index was constructed from two dimensions, including the sensitivity and adaptability of the RSEI. Finally, this study identified key factors that affect ecological residence based on a structural equation model. The results showed that the overall RSEI was at moderate and good levels in the YREBML during 2000–2020, accounting for more than 85% of the total area. Its spatial characteristics showed that the RSEI was higher in the middle reaches than in the lower reaches of the YREB, and higher in the south than in the north. The overall RSEI in the YREBML showed a decreasing trend during 2000–2020, with 54.36% of the region improving and 45.64% declining. Areas with declining RSEI were concentrated in Anhui, while the increasing RSEI was observed in Zhejiang. In addition, the spatial pattern of ecological resilience was characterized by high resilience in the north and east, and low resilience in the south and west. High resilience areas accounted for 40.48% of the YREBML, mainly contributed by Jiangxi and Hunan provinces. The driving factors analysis results indicated that economic development, natural disaster risk, and environmental pollution would further affect ecological resilience of urban systems. This study provides more scientific and effective data support for ecological environment monitoring and governance.

Postpartum depression (PPD) is the most common psychological condition following childbirth, and may have a detrimental effect on the social and cognitive health of spouses, infants, and children. The aim of this study was to complete a comprehensive overview of the current literature on the global epidemiology of PPD. A total of 565 studies from 80 different countries or regions were included in the final analysis. Postpartum depression was found in 17.22% (95% CI 16.00–18.51) of the world’s population. Meta-regression analysis showed that study size, country or region development, and country or region income were the causes of heterogeneity. Multivariable meta-regression analysis found that study size and country or area development were the most important predictors. Varied prevalence rates were noted in geographic regions with the highest rate found in Southern Africa (39.96%). Of interested was a significantly lower rate of PPD in developed countries or high-income countries or areas. Furthermore, the findings showed that there was a substantial difference in rates of PPD when marital status, educational level, social support, spouse care, violence, gestational age, breast feeding, child mortality, pregnancy plan, financial difficulties, partnership, life stress, smoking, alcohol intake, and living conditions were considered in the pooled estimates. Our results indicated that one out of every five women experiences PPD which is linked to income and geographic development. It is triggered by a variety of causes that necessitate the attention and committed intervention of primary care providers, clinicians, health authorities, and the general population.

Cancer treatment is currently one of the most critical healthcare issues globally. A well-designed drug delivery system can precisely target tumor tissues, improve efficacy, and reduce damage to normal tissues. Stimuli-responsive drug delivery systems (SRDDSs) have shown promising application prospects. Intelligent nano drug delivery systems responsive to endogenous stimuli such as weak acidity, complex redox characteristics, hypoxia, active energy metabolism, as well as exogenous stimuli like high temperature, light, pressure, and magnetic fields are increasingly being applied in chemotherapy, radiotherapy, photothermal therapy, photodynamic therapy, and various other anticancer approaches. Metal–organic frameworks (MOFs) have become promising candidate materials for constructing SRDDSs due to their large surface area, tunable porosity and structure, ease of synthesis and modification, and good biocompatibility. This paper reviews the application of MOF-based SRDDSs in various modes of cancer therapy. It summarizes the key aspects, including the classification, synthesis, modifications, drug loading modes, stimuli-responsive mechanisms, and their roles in different cancer treatment modalities. Furthermore, we address the current challenges and summarize the potential applications of artificial intelligence in MOF synthesis. Finally, we propose strategies to enhance the efficacy and safety of MOF-based SRDDSs, ultimately aiming at facilitating their clinical translation. Graphical Abstract

Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor metastasis. Primary tumors are shed and released into the bloodstream to form CTCs that are referred to as seeds to colonize and grow in soil-like distant target organs, while EVs of tumor and nontumor origin act as fertilizers in the process of tumor metastasis. There is no previous text that provides a comprehensive review of the role of EVs on CTCs during tumor metastasis. In this paper, we reviewed the mechanisms of EVs on CTCs during tumor metastasis, including the ability of EVs to enhance the shedding of CTCs, protect CTCs in circulation and determine the direction of CTC metastasis, thus affecting the distant metastasis of tumors.