Molecular DiversityPub Date : 2025-08-01Epub Date: 2025-03-14DOI: 10.1007/s11030-025-11164-z
Madhavi Kumari, Rohit Chauhan, Prabha Garg
{"title":"MedKG: enabling drug discovery through a unified biomedical knowledge graph.","authors":"Madhavi Kumari, Rohit Chauhan, Prabha Garg","doi":"10.1007/s11030-025-11164-z","DOIUrl":"10.1007/s11030-025-11164-z","url":null,"abstract":"<p><p>Biomedical knowledge graphs have emerged as powerful tools for drug discovery, but existing platforms often suffer from outdated information, limited accessibility, and insufficient integration of complex data. This study presents MedKG, a comprehensive and continuously updated knowledge graph designed to address these challenges in precision medicine and drug discovery. MedKG integrates data from 35 authoritative sources, encompassing 34 node types and 79 relationships. A Continuous Integration/Continuous Update pipeline ensures MedKG remains current, addressing a critical limitation of static knowledge bases. The integration of molecular embeddings enhances semantic analysis capabilities, bridging the gap between chemical structures and biological entities. To demonstrate MedKG's utility, a novel hybrid Relational Graph Convolutional Network for disease-drug link prediction, MedLINK was developed and used in case studies on clinical trial data for disease drug link prediction. Furthermore, a web-based application with user-friendly APIs and visualization tools was built, making MedKG accessible to both technical and non-technical users, which is freely available at http://pitools.niper.ac.in/medkg/.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"3465-3483"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrating deep learning and molecular dynamics simulations for FXR antagonist discovery.","authors":"Yueying Yang, Yuxin Huang, Hanxiao Shen, Ding Wang, Zhen Liu, Wei Zhu, Qing Liu","doi":"10.1007/s11030-025-11145-2","DOIUrl":"10.1007/s11030-025-11145-2","url":null,"abstract":"<p><p>Farnesoid X receptor (FXR) is a key regulator of bile acid, lipid, and glucose homeostasis, making it a promising target for treating metabolic diseases. FXR antagonists have shown therapeutic potential in cholestasis, metabolic disorders, and certain cancers, while clinically approved FXR antagonists remain unavailable and underrepresented in current treatment strategies. To address this, we developed deep learning models for predicting FXR antagonistic activity (ANTCL) and toxicity (TOXCL). Screening 217,345 compounds from the HMDB database identified eleven human metabolite candidates with significant FXR binding potential. Molecular dynamics simulations and binding free energy calculations revealed five more stable complexes compared to the reference compound Gly-MCA, with HMDB0253354 (Fulvestrant) and HMDB0242367 (ZM 189154) standing out for their binding free energies. Hydrophobic interactions, particularly involving residues MET328, PHE329, and ALA291, contributed to their stability. These results demonstrate the effectiveness of deep learning in FXR antagonist discovery and highlight the potential of HMDB0253354 and HMDB0242367 as promising candidates for metabolic disease treatment.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"3391-3409"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patrick Warfield-McAlpine, David F Fletcher, Fiona Zhang, Kiao Inthavong
{"title":"Increasing airflow ventilation in a nasal maxillary ostium using optimised shape and pulsating flows.","authors":"Patrick Warfield-McAlpine, David F Fletcher, Fiona Zhang, Kiao Inthavong","doi":"10.1007/s10237-025-01971-6","DOIUrl":"10.1007/s10237-025-01971-6","url":null,"abstract":"<p><p>Ventilation of the maxillary sinus is essential for regulating pressure, preventing infection and providing mucous to the nasal anatomy. During infection, the pathway between the sinus and the nasal airway (ostia) can become inflamed and restrict ventilation. Surgery is often required to restore airflow. The current surgical standard involves the widening of the ostium. Although this restores fluid flow, it has been linked to post-surgical sequelae. This study examined the effects of pulsating flow and geometric modifications on airflow distribution in a T-junction model analogous to a nasal maxillary ostium. A circular T-junction with variable anterior and posterior radius of curvature ( <math><msub><mi>R</mi> <mi>c</mi></msub> </math> ) was used to simulate airflow through the nasal maxillary ostium, investigating flow behaviour under oscillatory inlet velocities at frequencies of 30, 45, 60, and 75 Hz. Computational fluid dynamics (CFD) simulations assessed how flow distribution through the nasal cavity and maxillary ostium (represented by the x- and y-branches) is affected by curvature and oscillatory frequency, focusing on implications for respiratory airflow, particle delivery and inhalation toxicology. Results indicated that increasing the anterior <math><msub><mi>R</mi> <mi>c</mi></msub> </math> enhanced airflow into the y-branch (analogous to the maxillary ostium), while posterior curvature had minimal impact. Higher oscillatory frequencies increased reverse flow, which may improve ventilation but could interfere with consistent drug delivery. These insights are valuable for optimising respiratory therapies and inhalation toxicology.</p>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":" ","pages":"1343-1362"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bioinformatic Analysis of the Significance of the KIR2DL4 Gene in Recurrent Implantation Failure.","authors":"Xin-Xian Zhang, Zhi-Chao Zhang, Yu-Shan Liu, Li Zhou, Yu-Qin Hu, Cai-Hong Zhang, Wen-Hui Song, Xiao-Hua Wu","doi":"10.1007/s10528-024-10857-8","DOIUrl":"10.1007/s10528-024-10857-8","url":null,"abstract":"<p><p>Related studies have pointed out that Killer immunoglobulin-like receptor 2DL4 (KIR2DL4) was associated with vascular remodeling in early pregnancy, and it might play an important role in immunity. In this study, recurrent implantation failure (RIF)-related GSE58144 dataset was extracted from the Gene Expression Omnibus (GEO) database. Firstly, the immune micro-environment analyses were conducted to analyze the pathogenesis of KIR2DL4 in RIF. Then, the gene set enrichment analysis (GSEA) was performed to investigate the function of KIR2DL4. Moreover, the TF-mRNA-miRNA and the co-expression networks were constructed to reveal the potential regulation of KIR2DL4. Furthermore, the genes that were associated with KIR2DL4 and differentially expressed in RIF were obtained and defined as key genes, and the functions of these genes were further explored. KIR2DL4 could be used for clinical diagnosis of RIF, and it was correlated with the changes in the immune micro-environment in RIF. From the perspective of function, KIR2DL4 was associated with complement and coagulation cascades, natural killer cell-mediated cytotoxicity, etc. Moreover, the TF-mRNA-miRNA regulatory network was constructed with KIR2DL4, 9 TFs, and 29 miRNAs. Furthermore, KIR2DL4, ACSM1, IL2RB, and PTPN11 were screened as key genes, which were associated with immune-related functions. This study deeply analyzed the function of KIR2DL4 and its role in RIF, and we found that STAT1 might up-regulate KIR2DL4 by INF-γ/JAK2/STAT1 signaling pathway. Besides, over-expressed KIR2DL4 in the mid-luteal endometrium might influence embryo implantation by affecting the embryo implantation microenvironment, which might help deepen the understanding of the molecular mechanism of RIF.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"2893-2911"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biochemical GeneticsPub Date : 2025-08-01Epub Date: 2024-06-12DOI: 10.1007/s10528-024-10854-x
Peng Zhang, Dapeng Song, Zhidong Fang, Dekang Sun, Lin Wang, Lei Shi, Liang Gao, Xudong Jiang
{"title":"Cardamomin Inhibits the Proliferation and Tumorigenesis of Bladder Cancer by ESR1 in PI3K/AKT Pathway.","authors":"Peng Zhang, Dapeng Song, Zhidong Fang, Dekang Sun, Lin Wang, Lei Shi, Liang Gao, Xudong Jiang","doi":"10.1007/s10528-024-10854-x","DOIUrl":"10.1007/s10528-024-10854-x","url":null,"abstract":"<p><p>Cardamomin has been widely studied in cancer, but its role in cancer bladder cancer has not been mentioned. In this study, we validated the anti-cancer effect of cardamom and whether its potential mechanism is related to the PI3K/AKT pathway. After treating with different doses of cardamomin, the cytotoxicity was studied by CCK8. Secondly, we analyzed the effect of cardamomin on the proliferation, apoptosis and cell movement. Next, we analyzed the regulation of ESR1 by western blot and its impact on the PI3K/AKT pathway. We also transfected ESR1 overexpression and silencing vectors, and verified the transfection efficiency through RT-qPCR. Further, the specific mechanism of the drug's inhibitory effect on bladder cancer was also determined. We constructed the subcutaneous tumor model in vivo. After cardamomin administration, we mainly analyzed the positive expression of KI67 in tumor tissues by immunohistochemistry, and the apoptotic cells in tumor tissues by TUNEL, and related proteins in PI3K/AKT pathway by western blot. In this paper, cardamomin inhibited cell proliferation and invasion ability, blocked the transition of G0/G1 phase to S phase, and increased apoptotic rate of 5637 and HT1376 cells, as well as raised ESR1 expression. Cardamomin exerted anti-tumor effect through PI3K/AKT pathway. In vivo animal experiments indicated the inhibitory effect of cardamomin on subcutaneous implanted tumor. Cardamomin inhibited the positive expression of KI67 and promoted the TUNEL-positive cells in tumor tissues. Consistent with in vitro assay, cardamomin increased the expression of ESR1 and downregulated the PI3K/AKT pathway. Cardamomin has a significant inhibitory effect on bladder cancer, and upregulate the expression of ESR1 in bladder cancer through PI3K/AKT.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"2946-2966"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular Mechanism of WWOX Inhibiting the Development of Esophageal Cancer by Inhibiting Hippo Signaling Pathway.","authors":"Zihan Chen, Jingyu Sun, Lili Zhang, Yanglin Sun, Qingqing Ni, Hongkun Zhu, Miao Hui, Longzhen Zhang, Qiang Wang","doi":"10.1007/s10528-024-10856-9","DOIUrl":"10.1007/s10528-024-10856-9","url":null,"abstract":"<p><p>With the emergence of combined surgical treatments, complemented by radiotherapy and chemotherapy, survival rates for esophageal cancer patients have improved, but the overall 5-year survival rate remains low. Therefore, there is an urgent need for further research into the pathogenesis of esophageal cancer and the development of effective prevention, diagnosis, and treatment methods. We initially utilized the GeneCards and DisGeNET databases to identify the esophageal cancer-associated gene WWOX (WW domain containing oxidoreductase). Subsequently, we employed RT-qPCR (Reverse transcription-quantitative PCR) and WB (western blot) to investigate the differential expression of WWOX in HEEC (human esophageal endotheliocytes) and various ESCC (esophageal squamous cell carcinoma) cell lines. We further evaluated alterations in cell proliferation, migration and apoptosis via CCK8 (cell counting kit-8) and clonal formation, Transwell assays and flow cytometry. Additionally, we investigated changes in protein expressions related to the Hippo signaling pathway (YAP/TEAD) through RT-qPCR and WB. Lastly, to further elucidate the regulatory mechanism of WWOX in ESCC, we performed exogenous YAP rescue experiments in ESCC cells with WWOX overexpression to investigate the alterations in apoptosis and proliferation. Results indicated that the expression of WWOX in ESCC was significantly downregulated. Subsequently, upon overexpression of WWOX, ESCC cell proliferation and migration decreased, while apoptosis increased. Additionally, the expression of YAP and TEAD were reduced. However, the sustained overexpression of YAP attenuated the inhibitory effects of WWOX on ESCC cell malignancy. In conclusion, WWOX exerts inhibitory effects on the proliferation and migration of ESCC and promotes apoptosis by suppressing the Hippo signaling pathway. These findings highlight the potential of WWOX as a novel target for the diagnosis and treatment of esophageal cancer.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"3157-3169"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biochemical GeneticsPub Date : 2025-08-01Epub Date: 2024-07-31DOI: 10.1007/s10528-024-10890-7
Ban Adnan Hatem, Ferdous A Jabir
{"title":"The Role of ACE2 Receptor and Its Polymorphisms in COVID-19 Infection and Severity and Its Association with Lipid Profile, Thrombin, and D-Dimer Levels in Iraqi Patients: A Cross-Sectional Study.","authors":"Ban Adnan Hatem, Ferdous A Jabir","doi":"10.1007/s10528-024-10890-7","DOIUrl":"10.1007/s10528-024-10890-7","url":null,"abstract":"<p><p>COVID-19 patients experience a complex interplay involving ACE2, thrombin, D-dimer, and lipid profile, yet its full understanding remains elusive. ACE2, a pivotal regulator of the renin-angiotensin system and the primary receptor for SARS-CoV-2 undergoes downregulation upon viral binding, potentially leading to severe cases with acute respiratory distress syndrome (ARDS). A specific ACE2 gene polymorphism (rs2285666) may be associated with COVID-19 susceptibility, with the A allele potentially increasing infection risk. COVID-19 disease progression is linked to coagulation abnormalities, but the exact connection with thrombin and D-dimer remains uncertain. A study examining coagulation parameters in COVID-19 patients admitted to Al-Diwania Educational Hospital from February to May 2022 found that thrombin and D-dimer levels were directly related to disease severity. Severe cases exhibited significantly altered coagulation function compared to mild and recovered cases, with notably higher D-dimer levels and elevated thrombin serum concentrations. Moreover, dyslipidemia, particularly low HDL cholesterol, is a prevalent comorbidity in COVID-19 patients and may be linked to worse outcomes. In conclusion, COVID-19 is associated with a prothrombotic state and dysregulation of the renin-angiotensin system due to ACE2 downregulation following viral binding. The intricate interplay between ACE2, thrombin, D-dimer, and lipid profile necessitates further investigation. The multifaceted nature of the disease demands continued research to unravel its pathogenesis and identify potential therapeutic targets.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"3657-3675"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AmbioPub Date : 2025-08-01Epub Date: 2025-04-10DOI: 10.1007/s13280-025-02154-4
Sinéad O'Keeffe, Sophie Stein, Michael Curran, Lukas Baumgart, Sabine Zikeli, Marianna Siegmund-Schultze
{"title":"How to square the circle? A conceptual framework synergising strategies for circular agriculture to tackle climate change and enhance overall on-farm sustainability.","authors":"Sinéad O'Keeffe, Sophie Stein, Michael Curran, Lukas Baumgart, Sabine Zikeli, Marianna Siegmund-Schultze","doi":"10.1007/s13280-025-02154-4","DOIUrl":"10.1007/s13280-025-02154-4","url":null,"abstract":"<p><p>There is an urgent need to change the current extractive and resource-intensive agricultural practices. Adopting circular practices within the agricultural system could provide multiple benefits of slowing global climate change, reducing extractive practices and helping farmers to adapt to a changing climate. However, there are still many barriers for farmers to adopt these desired circular agriculture (CA) practices, among others, a lack of information about on-farm circular practices. There is a need to support farmers in recognising which strategies can increase the circularity of their farm and what this means in terms of their farms' climate neutrality and its long-term sustainability. Therefore, the aim of this paper is to develop a novel conceptual framework to facilitate a broader and integrated understanding of how on-farm CA strategies and practices contribute to the goals of climate change mitigation and on-farm sustainability, thus supporting farmers in transitioning their farms towards greater circularity.</p>","PeriodicalId":461,"journal":{"name":"Ambio","volume":" ","pages":"1334-1352"},"PeriodicalIF":5.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biochemical GeneticsPub Date : 2025-08-01Epub Date: 2024-08-07DOI: 10.1007/s10528-024-10899-y
Melis Tuncer, Muhammed Erkan Karabekmez, Filiz Kisaayak Collak
{"title":"Multi-Omics Analysis of Primary Prostate Cancer Datasets Reveals Novel Biomarkers.","authors":"Melis Tuncer, Muhammed Erkan Karabekmez, Filiz Kisaayak Collak","doi":"10.1007/s10528-024-10899-y","DOIUrl":"10.1007/s10528-024-10899-y","url":null,"abstract":"<p><p>Prostate cancer (PCa) ranks second in cancer-related deaths in men. Current screenings used in the diagnosis are not sufficient enough in the early stages therefore, more diagnostic biomarker studies are needed. We performed a meta-analysis on the biomarker potential of miRNAs, mRNAs, and methylation for the early stages of PCa by searching available microarrays from the GEO dataset for PCa tissue and benign prostatic hyperplasia (BPH) or normal adjacent to PCa. Target genes of miRNAs were determined using the miRWalk and miRDB datasets. The results were visualized using network analysis. qPCR quantification of potential miRNA and genes was performed in human prostate epithelial cell line (RWPE-1) and human prostate carcinoma epithelial cell line (22RV1). Our meta-analysis of potential biomarkers for the diagnosis of PCa identified several candidates. It was shown that miR-7-5p is overexpressed. CAMKK2, TMEM97 expression were upregulated and CLIP1 expression was downregulated and these genes were shown to be targets of miR-7-5p. CAMKK2, TMEM97, and CLIP1 genes were found to be hypermethylated. Although the changes in the expression levels of miR-7-5p and CAMKK2, TMEM97, and CLIP1 in the two cell lines used in our study were not consistent with the significant expression differences observed in the meta-analysis, our meta-analysis results would be promising in human prostate tissue or different human tumor cell line studies. This highlights the importance of our meta-analysis results in prostate cancer biomarker research, given the difficulty of experimental validation of our large-scale data meta-analysis results using a specific cell line.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":"3676-3693"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ignacio Requena-Ruiz, Xenia Stavropulos-Laffaille, Thomas Leduc, Daniel Siret
{"title":"Unveiling thermal diversity in urban coolspots through microclimate mobile-measurements.","authors":"Ignacio Requena-Ruiz, Xenia Stavropulos-Laffaille, Thomas Leduc, Daniel Siret","doi":"10.1007/s00484-025-02926-3","DOIUrl":"10.1007/s00484-025-02926-3","url":null,"abstract":"<p><p>Urban environments amplify the effects of global warming, increasing thermal stress and endangering public health and social life. Among heat adaptation strategies, \"urban coolspots\" have emerged as an urban design practice that integrates adaptive comfort behaviours with spatial features. This study evaluates the impact of coolspots on pedestrians' thermal environments using high-resolution in-situ microclimate mobile-measurements from four sites in Nantes and Paris, France. A pedestrian-carried human-biometeorological station was employed across the study areas to record at 0.5 Hz the variables of air temperature, relative humidity, wind speed, and shortwave and longwave radiation. The findings highlight the influence of coolspots' spatial features, such as shading and flooring materials, on measured variables and relative thermal metrics. Results show that coolspots provide localized cooling effects within warmer environments, enhancing thermal diversity. Measurements spatial variability is particularly high (> 50%) in short distances in wind speed and radiative variables (shortwave and longwave radiation) but remains very low in air temperature and humidity. Radiative variables emerge as the primary drivers of thermal environments, with mean radiant temperature reductions of up to -20.0 °C in some coolspots areas. Ultimately, this study provides a spatiotemporal perspective on the role of coolspots in the public space, highlighting their contribution to thermal diversity and challenging the \"one-size-fits-all\" approach in urban design guidelines. Furthermore, it underscores the significance of designing thermal sequences to foster a more human-centric and adaptive approach to urban design.</p>","PeriodicalId":588,"journal":{"name":"International Journal of Biometeorology","volume":" ","pages":"1867-1883"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"地球科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}