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This study establishes quantitative relationships between neighborhood layouts, as evaluated by key neighborhood morphological parameters and pedestrian wind environments across China’s five major climate zones. We analyzed 3204 residential neighborhoods using satellite imaging and simulated 281 scenarios by CFD simulations, identifying six typical neighborhood layouts and quantifying their performance in terms of climate specific wind comfort criteria. This work takes an approach that takes into account mechanical wind effects and region-specific criteria for evaluating pedestrian-level wind environment performance, going beyond previous studies that utilize universal evaluation standards. The most influential parameter is building enclosure ratio with sensitivity indices of 0.844 for winter wind proofing. Closed perimeter layout confers 15–20% better winter wind proofing in cold climates and semi-open design enhances summer ventilation by 12–18% in hot climates according to our cross-climate analysis. Quantitative optimization adopting regression technique (R2 = 0.727–0.810) points to an optimal enclosure ratio of 0.25–0.28 or 0.52–0.61 with aspect ratio of 1.75–2.75. The results can provide evidence-based design guidelines for high-rise residential neighborhood planning and pedestrian wind environment, aiming to improve urban livability and support climate adaptation strategies across a broad range of climate zones.

With increasing concerns over climate change and air pollution, sustainable transportation has become a critical component of modern city planning. Bike-sharing systems have emerged as an eco-friendly alternative to motorized transport, contributing to energy conservation and emission reduction. To elaborate on bike-sharing’s contribution to urban sustainable development, this study conducts a quantitative analysis of its environmental benefits through a case study of the Bluebikes program in the Boston area, using a longitudinal dataset of 20.07 million bike trips from January 2015 to December 2024, with data between January 2020 and December 2021 excluded. A combination of Scheiner’s model and Multinomial Logit model was adopted to evaluate the substitution of Bluebikes trips, an optimized Seasonal Autoregressive Integrated Moving Average (SARIMA) model was employed to predict future usage, while energy savings were calculated by estimating reductions in gasoline and diesel consumption. The findings reveal that during the analyzed period, Bluebikes trips saved 2616.44 tons of oil equivalent and reduced CO2 and NOX emissions by 7614.96 and 16.43 tons, respectively. Furthermore, based on the historical trends, it is forecasted that the Bluebikes program will annually save an average of 723.66 tons of oil equivalent and decrease CO2 and NOX emissions by 2422.65 and 4.52 tons between 2025 and 2027. The results highlight the substantial environmental impact of Bluebikes and support policies that encourage their usage.

Cycling significantly contributes to improving metro accessibility; however, the quality of bicycle environments surrounding metro stations remains insufficiently studied. This study develops a criteria–indicators assessment framework that incorporates both objective characteristics of bicycle infrastructure and subjective perceptions of bicycle access to metro stations. The framework consists of four primary criteria—accessibility, convenience, safety, and comfort—along with eighteen sub-level indicators. Taking central Tianjin as the study area, the study evaluated the cycling environment quality around eight representative metro stations by employing information entropy and the analytic hierarchy process, with cosine similarity used to compare the outcomes against human–machine adversarial scoring result to ensure analytical robustness. The findings reveal substantial disparities in cycling infrastructure, with safety and accessibility exhibiting higher scores than convenience and comfort. Additionally, cycling environment quality is higher around comprehensive and public-service stations compared to residential stations, while commercial stations exhibit the lowest quality. The study underscores the necessity of expanding protected bike lanes, enhancing route directness, and improving parking and wayfinding facilities to promote cycling as an effective first- and last-mile metro access mode.

Walking is the primary mode of reaching metro stations, yet the quality of pedestrian networks around these stations has not been well researched. Considering the objective physical characteristics of pedestrian networks and the subjective assessments of walkers on the routes, this study developed an evaluation model that integrated the Analytic Hierarchy Process and Entropy Weight Method with human–machine adversarial scoring and cosine similarity to validate the reliability. Nineteen indicators concerning four fundamental criteria, including accessibility, convenience, safety, and comfort, were applied with data acquired from eight stations in Tianjin, China. Results reveal that accessibility and safety indicators weigh more than convenience and comfort indicators. The quality of pedestrian networks around the public-service and comprehensive stations scores higher than that around residential stations, while walking environment quality near commercial stations shows significant disparities. These findings highlight the importance of prioritizing accessibility and safety while enhancing convenience and comfort in the renewal of the pedestrian network in Tianjin. The assessment model provides a valuable tool for urban policymakers and planners, enabling the formulation of sound pedestrian-network policies, facilitating higher-quality walking access and egress trips to stations, and encouraging transit-oriented development.

Understanding the intricate relationship between the built environment and living street vitality is crucial for guiding the revitalization of street life. Traditional linear models often oversimplify this relationship, while machine learning models fail to account for spatial heterogeneity. To overcome these limitations, this study proposes a hybrid framework, geographically weighted-gradient boosting decision trees (GW-GBDT), which integrates geographically weighted regression (GWR) with gradient boosting decision trees (GBDT). Using Xiamen Island as a case study, we examined the nonlinear effects of built environment features on both the intensity and stability of living street vitality across four dimensions, including transport accessibility, built environment quality, daily service facilities, and morphological features. Results reveal that daily service facility density and floor area ratio are the most significant characteristics shaping intensity of vitality, while daily service facility diversity and green view ratio play dominant roles in stability of vitality. Furthermore, built environment features exhibit spatially varying threshold effects across different functional zones. These findings offer actionable insights for urban planners, emphasizing the need for localized, context-specific strategies to enhance living street vitality.

The tumor microenvironment (TME) in gastric cancer (GC) has been shown to be important for tumor control but the specific characteristics for GC are not fully appreciated. We generated an atlas of 166,533 cells from 10 GC patients with matched paratumor tissues and blood. Our results show tumor-associated stromal cells (TASCs) have upregulated activity of Wnt signaling and angiogenesis, and are negatively correlated with survival. Tumor-associated macrophages and LAMP3 + DCs are involved in mediating T cell activity and form intercellular interaction hubs with TASCs. Clonotype and trajectory analysis demonstrates that Tc17 ( IL-17 + CD8 + T cells) originate from tissue-resident memory T cells and can subsequently differentiate into exhausted T cells, suggesting an alternative pathway for T cell exhaustion. Our results indicate that IL17 + cells may promote tumor progression through IL17 , IL22 , and IL26 signaling, highlighting the possibility of targeting IL17 + cells and associated signaling pathways as a therapeutic strategy to treat GC. Gastric cancer can vary in tumour stage and immune cell involvement. Here the authors compare gene expression in immune cell types from the blood and the tumour site from GC patients using single cell and TCR sequencing and show that IL17 + CD8 + T cells have a phenotype related to that seen with exhausted cells.

Cervical cancer is the second leading cause of morbidity and mortality in women worldwide. Traditional treatment methods have become limited. Naringenin, a flavonoid abundant in various fruits and herbal medicines, has demonstrated anti-tumor properties among other effects. This research undertook to elucidate the mechanism of naringenin in the context of cervical cancer treatment by leveraging network pharmacology and performing experimental validation. Initial steps involved predicting potential naringenin targets and subsequently screening for overlaps between these targets and those related to cervical cancer, followed by analysis of their interrelationships. Molecular docking was subsequently utilized to verify the binding effect of the central target. Within the framework of network pharmacology, it was discovered that naringenin might possess anti-cancer properties specific to cervical cancer. Following this, the anti-tumor effects of naringenin on Hela cell viability, migration, and invasion were assessed employing CCK-8, transwell, wound healing assays, and western blotting. Experimental data indicated that naringenin attenuates the migration and invasion of Hela cells via downregulation EGFR/PI3K/AKT signaling pathway. Thus, our findings suggest that naringenin has therapeutic impacts on cervical cancer via multiple mechanisms, primarily by inhibiting the migration and invasion through the EGFR/PI3K/AKT/mTOR pathway. This study offers fresh insights for future clinical studies.

Background Icariin (ICA), an active ingredient extracted from Epimedium species, has shown promising results in the treatment of Alzheimer's disease (AD), although its potential therapeutic mechanism remains largely unknown. This study aimed to investigate the therapeutic effects and the underlying mechanisms of ICA on AD by an integrated analysis of gut microbiota, metabolomics, and network pharmacology (NP). Methods The cognitive impairment of mice was measured using the Morris Water Maze test and the pathological changes were assessed using hematoxylin and eosin staining. 16S rRNA sequencing and multi-metabolomics were performed to analyze the alterations in the gut microbiota and fecal/serum metabolism. Meanwhile, NP was used to determine the putative molecular regulation mechanism of ICA in AD treatment. Results Our results revealed that ICA intervention significantly improved cognitive dysfunction in APP/PS1 mice and typical AD pathologies in the hippocampus of the APP/PS1 mice. Moreover, the gut microbiota analysis showed that ICA administration reversed AD-induced gut microbiota dysbiosis in APP/PS1 mice by elevating the abundance of Akkermansia and reducing the abundance of Alistipe . Furthermore, the metabolomic analysis revealed that ICA reversed the AD-induced metabolic disorder via regulating the glycerophospholipid and sphingolipid metabolism, and correlation analysis revealed that glycerophospholipid and sphingolipid were closely related to Alistipe and Akkermansia . Moreover, NP indicated that ICA might regulate the sphingolipid signaling pathway via the PRKCA/TNF/TP53/AKT1/RELA/NFKB1 axis for the treatment of AD. Conclusion These findings indicated that ICA may serve as a promising therapeutic approach for AD and that the ICA-mediated protective effects were associated with the amelioration of microbiota disturbance and metabolic disorder. Graphical Abstract

Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs, which are covalently closed loop structures formed by precursor mRNAs (pre-mRNAs) through back-splicing. CircRNAs are abnormally expressed in many tumors, and play critical roles in a variety of tumors as oncogenes or tumor suppressor genes by sponging miRNAs, regulating alternative splicing and transcription, cis-regulating host genes, interacting with RNA binding proteins (RBPs) or encoding polypeptides. Among them, the regulation of circRNAs on their corresponding host genes is a critical way for circRNAs to exit their functions. Accumulating evidence suggests that circRNAs are able to regulate the expression of host genes at the transcriptional level, post-transcriptional level, translational level, post-translational level, or by encoding polypeptides. Therefore, this paper mainly summarized the roles and association of circRNAs and their corresponding host genes in tumorigenesis and tumor progression, generalized the circRNAs that function synergistically or antagonistically with their host genes, and elaborated the mechanisms of mutual regulation between circRNAs and their host genes. More importantly, this review provides specific references for revealing the potential application of circRNAs combined with their host genes in tumor diagnosis, treatment and prognosis.

Ischemia-reperfusion injury (IRI) is one of the leading causes of acute kidney injury (AKI), predisposing patients to chronic kidney disease (CKD) due to maladaptive renal repair. Nevertheless, the molecular mechanisms and biomarkers that cause maladaptive repair remain unclear. In this study, we used single-nucleus RNA sequencing data from GEO database (GSE139107) to identify molecular markers during the transition from AKI to CKD caused by IRI. Analysis of intercellular crosstalk, trajectory and machine learning algorithms revealed hub cell clusters and genes. Proximal tubule (PT) cells, especially a new cluster (New PT2), significantly interacted with fibroblasts during the transition. The expression levels of hub genes were validated using the bulk RNA-seq data (GSE98622) and further confirmed through RT-qPCR and immunohistochemical analysis in ischemia-reperfusion injury (uIRI) mice. Ankrd1, a hub gene in New PT2, showed sustained upregulation in the proximal tubule in AKI. Compared to the sham-operated group, the expression of Ankrd1 in mice increased at 0.5 days post-reperfusion, peaked at day 1, and remained significantly elevated up to 60 days. This study indicated that the upregulation of Ankrd1 was positively associated with the progression from AKI to CKD and may potentially serve as a valuable biomarker for this transitional process.