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CD8+ T cells play a central role in anti-tumor immunity. Naïve CD8+ T cells are active upon tumor antigen stimulation, and then differentiate into functional cells and migrate towards the tumor sites. Activated CD8+ T cells can directly destroy tumor cells by releasing perforin and granzymes and inducing apoptosis mediated by the death ligand/death receptor. They also secrete cytokines to regulate the immune system against tumor cells. Mitochondria are the central hub of metabolism and signaling, required for polarization, and migration of CD8+ T cells. Many studies have demonstrated that mitochondrial dysfunction impairs the anti-tumor activity of CD8+ T cells through various pathways. Mitochondrial energy metabolism maladjustment will cause a cellular energy crisis in CD8+ T cells. Abnormally high levels of mitochondrial reactive oxygen species will damage the integrity and architecture of biofilms of CD8+ T cells. Disordered mitochondrial dynamics will affect the mitochondrial number and localization within cells, further affecting the function of CD8+ T cells. Increased mitochondria-mediated intrinsic apoptosis will decrease the lifespan and quantity of CD8+ T cells. Excessively low mitochondrial membrane potential will cause the release of cytochrome c and apoptosis of CD8+ T cells, while excessively high will exacerbate oxidative stress. Dysregulation of mitochondrial Ca2+ signaling will affect various physiological pathways in CD8+ T cells. To some extent, mitochondrial abnormality in CD8+ T cells contributes to cancer development. So far, targeting mitochondrial energy metabolism, mitochondrial dynamics, mitochondria-mediated cell apoptosis, and other mitochondrial physiological processes to rebuild the anti-tumor function of CD8+ T cells has proved effective in some cancer models. Thus, mitochondria in CD8+ T cells may be a potential and powerful target for cancer treatment in the future.

Surgery is the common treatment for early lung cancer with multiple pulmonary nodules, but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas. In this study, we found that a combined treatment of local radiofrequency ablation (RFA) and melatonin (MLT) greatly improved clinical outcomes for early lung cancer patients with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas. Mechanically, as demonstrated in an associated mouse lung tumor model, RFA not only effectively remove treated tumors but also stimulate antitumor immunity, which could inhibit tumor growth in non-ablated areas. MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA. Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment, which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT. Analysis of residual tumor further revealed the depressed activity of MAPK, NF-kappa B, Wnt, and Hedgehog pathways and upregulated P53 pathway in tumors, which was in line with the inhibited tumor growth. Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy. These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules. Trial registration: www.chictr.org.cn , identifier ChiCTR2100042695, http://www.chictr.org.cn/showproj.aspx?proj=120931 .

Ethylene oxide (EO) is a reactive epoxide. However, the association between EO exposure and the risk of developing asthma in humans is unknown. The aim of this study was to investigate the relationship between EO exposure and the risk of developing asthma in the general US population. In this cross-sectional study, data of 2542 patients from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016 were obtained and analyzed. Hemoglobin adducts of EO (HbEO) level be used as the main factor for predicting EO exposure. The association between the level of EO exposure and the risk of developing asthma was evaluated with logistic regression models and dose–response analysis curves of restricted cubic spline function. Mediation analysis and linear regression analysis were utilized to evaluate the association between EO exposure and inflammation indicators. According to the quartiles of HbEO level, the patients were divided into four groups. The results indicated that an increased HbEO level was associated with a higher risk of asthma onset. Compared with the lowest quartile, the odds ratio (OR) with the 95% confidence interval (CI) for the highest quartile was 1.960 (95% CI: 1.348–2.849, P  = 0.003). After being adjusted for numerous potential confounders, the OR of quartile 4 relative to quartile 1 was 1.991 (95% CI: 1.359–2.916, P  = 0.001). Consistent results were also obtained in most subgroup analyses and dose–response analysis curves. In addition, EO levels were positively correlated with the inflammatory indicators ( P  = 0.006 for WBC, P  = 0.015 for lymphocyte, and P  = 0.015 for neutrophil). This study revealed a positive correlation between the level of EO exposure and the risk of asthma in a representative US population. In addition, inflammatory response may prove to be a potential biological mechanism underlying EO-induced asthma.

The increasing density of cities poses a huge threat to public health, so pocket parks with high accessibility and flexibility have become potential resources to promote public health. In this context, the ways in which pocket parks can improve public health have become the focus and challenge of current research. This study selected 10 different types of pocket parks in Fuzhou, China, as the research subjects and collected real-time psychological and physiological data of participants by watching videos of the sample plots. The aim was to explore the impact of the environmental characteristics of pocket parks on the psychological and physiological responses of recreational users. The results of the study showed that: (1) the environmental characteristics of pocket parks significantly affect the psychological and physiological responses of recreationists. Different environmental characteristics can affect recreationists’ emotional state, attention recovery, environmental preferences, and the indicators of IBI, HR, SDNN, RMSSD, pNN50, SCL, and EMG to varying degrees. (2) The environment of pocket parks may encourage recreationists to generate positive psychological benefits when the site is larger and has a higher degree of scenic beauty, and when the space is not effectively confined. A pocket park environment with a low paving ratio, open view, cultural elements, topographic changes, special vegetation and distributing space can also have a positive effect on the psychological benefits of recreationists to a certain extent. Low canopy density and high green visibility can also play a role in suppressing negative emotions. (3) Pocket parks with high levels of depression and off-site disturbance are not conducive to positive physiological responses from recreationists, while pocket parks with high levels of green visibility and beauty and specialized vegetation are more likely to provide health benefits to them.

With the increasing requirements of healthy habitat environments, landscape microclimates have been widely concerned. To comprehensively grasp the development history and research status of the landscape microclimates in China and other countries, CiteSpace software was used to comparatively analyze and visually present the literature related to landscape microclimates in CNKI and WOS databases for the past 20 years. The results show that: (1) The number of publications on landscape microclimate research shows an increasing trend in China and other countries, and the number of publications increased significantly after 2016. Although the number of publications by Chinese scholars is less than that of foreign scholars, they have developed rapidly in recent years, and their international influence has increased significantly. (2) A positive exchange has been formed among international scholars, and the number of collaborative studies has been increasing. China’s microclimate research has formed relatively stable teams that have conducted numerous studies in the fields of urban communities, street greening, and plant communities, respectively. Although the links between research teams and institutions in China and other countries are relatively close, they still need to be further strengthened. (3) In the past decade, the theoretical system of landscape microclimates has been improved, and the research themes have become more concentrated, but it still has remained close to the early basic research. (4) Future research will remain centered on “mitigating the urban heat island effect” and “optimizing human heat perception”. New topics such as “biodiversity”, “carbon cycle”, and “climate change” have been added. In conclusion, the research needs to continue to explore the evaluation system of microclimates and verify the evaluation index of outdoor thermal comfort for human thermal adaptation in different regions. The standards and systems of human habitat adapted to different regional characteristics should be formed.

Epidermal growth factor receptor (EGFR) is one of the most important and therapeutically significant targets in most cancer treatments, and EGFR-targeted therapy is widely performed to treat various tumors, such as non-small cell lung cancer. Although EGFR-targeted therapy has fewer side effects than conventional chemotherapy, they have limited applications and are prone to drug resistance. Traditional Chinese medicine (TCM), are promising solutions to address these challenges because of their biological activities, such as inhibition of EGFR-related signaling pathways, reversal of drug resistance, and mitigation of side effects of targeted therapy. Moreover, TCM is characterized by multiple targets, few side effects and good therapeutic effect Here, we summarized several typical traditional Chinese medicine monomers derived from traditional Chinese medicine that can be used along with EGFR inhibitors, as well as herbal plants with potential for natural product development and TCM. We focused on their mechanisms of action underlying the reversal of drug resistance, enhancement of drug efficacy, and mitigation of side effects; we also assessed relevant clinical studies that are available. However, the potential adverse effects (e.g., drug-drug interactions, hepatotoxicity, and immune-related side effects) of TCMs along with EGFR inhibitors need to be further investigated. This article provided new perspectives on the use of TCMs in EGFR-targeted therapy and emphasized the importance of safety assessment in future studies.

Global climate change caused by carbon dioxide emissions has become a hot topic globally. It is of great significance to study how low-carbon landscapes can reduce carbon emissions and improve the ecological environment. In this study, CiteSpace software was used to conduct a bibliometric analysis of the research field. The analysis data were based on 2910 studies published in the research field from 2002 to 2023. By analyzing the number of publications in the research field, cooperation networks, keywords, etc., the research status, processes, and hotspots of low-carbon landscapes were systematically reviewed. The results show the following: (1) Between 2002 and 2023, low-carbon landscape research developed rapidly, gradually becoming a multidisciplinary field. A large number of studies were conducted by relevant institutions and scholars from 106 countries. (2) The research focuses on carbon emission reduction, renewable energy, life cycle assessment, etc. The research mainly goes through the following stages: theoretical research on low-carbon technology, the application of low-carbon technology, and the development of the low-carbon economy. (3) Research frontiers focus on low-carbon landscape emission-reduction technologies, low-carbon landscape research methods, and the development and application of low-carbon materials. This study deeply analyzes the research process of low-carbon landscapes and puts forward a research direction for low-carbon landscapes in future urban development, such as economic benefit assessments, ecosystem restoration and protection, social participation, and policy support, in order to provide a reference for low-carbon landscape research.

As urbanization accelerates, parks, as vital urban public open spaces, and their acoustic and thermal ambience directly impact visitors’ comfort and the sustainability of parks. Selecting Xihu Park in Fuzhou, China located in the subtropical region as a typical example, this study utilizes covert observational experiments with different typical sounds (grass cutting, music, and no sound source) across temperature levels to examine the influence of thermal–acoustic interactions on crowd behaviors in the park. The findings are as follows: (1) melodious music can attract more tourists, while strong stimulating grass cutting noises under high temperatures reduce crowd flow. Excluding unpleasant audio sources, park soundscapes across temperatures have a relatively limited influence on attractiveness to people flow. (2) High temperatures diminish tourists’ interest in landscape experiences and persons staying, especially when the soundscape quality is poorer. Under non-high temperatures, audio environments have a minor impact on the staying time. (3) The soundscape quality plays a role by affecting people’s path choices of approaching or avoiding sound sources, where grass cutting noise has the most negative influence. Music, grass cutting sounds, and natural sounds demonstrate conspicuous differences in their effects under varied temperatures. (4) Comfortable acoustic environments can draw larger crowds and decrease the walking pace. High temperatures make crowds take slower steps. Different sound types have significant influences on crowd movement velocity under three typical temperature levels. This study comprehensively investigates the mechanisms of typical thermal–acoustic environments’ impacts on park crowd behaviors, providing important references for optimizing the acoustic and thermal environments of urban parks, while also enriching related research on landscape design and environmental psychology. Future studies can conduct in-depth explorations by creating more abundant thermal–acoustic combinations and probe differences across diverse populations.

BRD4 is well known for its role in super-enhancer organization and transcription activation of several prominent oncogenes including c-MYC and BCL2. As such, BRD4 inhibitors are being pursued as promising therapeutics for cancer treatment. However, drug resistance also occurs for BRD4-targeted therapies. Here, we report that BRD4 unexpectedly interacts with the LSD1/NuRD complex and colocalizes with this repressive complex on super-enhancers. Integrative genomic and epigenomic analyses indicate that the BRD4/LSD1/NuRD complex restricts the hyperactivation of a cluster of genes that are functionally linked to drug resistance. Intriguingly, treatment of breast cancer cells with a small-molecule inhibitor of BRD4, JQ1, results in no immediate activation of the drug-resistant genes, but long-time treatment or destabilization of LSD1 by PELI1 decommissions the BRD4/LSD1/NuRD complex, leading to resistance to JQ1 as well as to a broad spectrum of therapeutic compounds. Consistently, PELI1 is up-regulated in breast carcinomas, its level is negatively correlated with that of LSD1, and the expression level of the BRD4/LSD1/NuRD complex–restricted genes is strongly correlated with a worse overall survival of breast cancer patients. Together, our study uncovers a functional duality of BRD4 in superenhancer organization of transcription activation and repression linking to oncogenesis and chemoresistance, respectively, supporting the pursuit of a combined targeting of BRD4 and PELI1 in effective treatment of breast cancer.

The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid (TCA) cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus. We report here the identification of a nonclassical TCA cycle in the nucleus (nTCA cycle). We found that all the TCA cycle-associated enzymes including citrate synthase (CS), aconitase 2 (ACO2), isocitrate dehydrogenase 3 (IDH3), oxoglutarate dehydrogenase (OGDH), succinyl-CoA synthetase (SCS), fumarate hydratase (FH), and malate dehydrogenase 2 (MDH2), except for succinate dehydrogenase (SDH), a component of electron transport chain for generating ATP, exist in the nucleus. We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria. We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates, not for energy production. We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation. Together, our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.