Research最新文献

{"title":"Constructing Cell-Specific Causal Networks of Individual Cells for Depicting Dynamical Biological Processes.","authors":"Xinzhe Huang, Luonan Chen, Xiaoping Liu","doi":"10.34133/research.0743","DOIUrl":"10.34133/research.0743","url":null,"abstract":"<p><p>Causal inference is crucial in biological research, as it enables the understanding of complex relationships and dynamic processes that drive cellular behavior, development, and disease. Within this context, gene regulatory network (GRN) inference serves as a key approach for understanding the molecular mechanisms underlying cellular function. Despite substantial advancements, challenges persist in GRN inference, particularly in dynamic rewiring, inferring causality, and context specificity. To tackle these issues, we present single cell-specific causal network (SiCNet), a novel causal network construction method that utilizes single-cell gene expression profiles and a causal inference strategy to construct molecular regulatory networks at a single-cell level. Additionally, SiCNet utilizes cell-specific network information to construct network outdegree matrix (ODM), enhancing the performance of cell clustering. It also enables the construction of context-specific GRNs to identify key regulators of fate transitions for diverse processes such as cellular reprogramming and development. Furthermore, SiCNet can delineate the intricate dynamic regulatory processes involved in development, providing deep insights into the mechanisms governing cellular transitions and the gene regulation across developmental stages.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0743"},"PeriodicalIF":11.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Role of the Microbiota in Cancer Immunotherapy: A New Frontier.","authors":"Shouliang Wang, Shun Li, Mengli Zhang, Ruihan Liu, Xigang Ye, Siyi Mao, Jianwu Yu, Xinhua Xie, Weige Tan","doi":"10.34133/research.0744","DOIUrl":"10.34133/research.0744","url":null,"abstract":"<p><p>Cancer immunotherapy has greatly changed the therapeutic landscape for metastatic malignancies. Nevertheless, due to immune-related adverse events, drug resistance, and other factors, cancer immunotherapy remains largely untapped. Recent research has shown that the microbiota is crucial in shaping immune function and that its modulation can influence antitumor immunity. However, because of the intricate nature of the microbiome and immune system, a comprehensive mechanistic framework for understanding how the microbiota influences antitumor immune responses is still lacking. In this review, we summarize the mechanisms of the microbiota in antitumor immunity. We also comprehensively outline the methods for measuring the microbiota and their limitations. Additionally, we discuss the key challenges facing the targeting of the microbiota as a regulatory strategy for cancer immunotherapy.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0744"},"PeriodicalIF":11.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Processable Bio-Based Polybenzoxazine with Tunable Toughness and Dielectric Properties.","authors":"Jiale Li, Meng Liu, Yuan Liu, Peng Zhao, Yuhan Lou, Zhiqian Meng, Xiaoxue Song, Zhenle Hu, Yongzhuang Liu, Haipeng Yu","doi":"10.34133/research.0745","DOIUrl":"10.34133/research.0745","url":null,"abstract":"<p><p>There is remarkable demand for bio-based specialty resins such as benzoxazine thermosets, but they are brittle and difficult to process. This study reports the synthesis of a processable bio-based polybenzoxazine resin via the copolymerization of rigid and soft benzoxazine dimers synthesized from bio-based phenols. The polybenzoxazine copolymer demonstrated excellent thermoplasticity and a tunable toughness in the range of 9.0 to 24.1 MJ/m³. The incorporation of soft segments and dynamic ester bonds in the polybenzoxazine notably improved its thermoplasticity compared with traditional thermosetting benzoxazine resins. The polybenzoxazine copolymer also demonstrated a dielectric constant of 2.99 and a dielectric loss of 0.019 at 3 GHz, as well as a high breakdown voltage of 27.2 kV/mm. This research highlights the promising mechanical and thermal properties of the resulting bio-based resin, as well as its tunable dielectric properties, making it a competitive candidate for various high-performance applications in the polymer industry.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0745"},"PeriodicalIF":11.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell RNA Transcriptomics and Multi-omics Analyses Reveal the Clinical Effects of Acupuncture on Methadone Reduction.","authors":"Yiming Chen, Baochao Fan, Jingchun Zeng, Yutian Zou, Chenyang Tao, Chen Chen, Peiming Zhang, Jian Liang, Fangfang Qi, Hailin Tang, Liming Lu","doi":"10.34133/research.0741","DOIUrl":"10.34133/research.0741","url":null,"abstract":"<p><p>Opioid use disorders (OUDs) pose a substantial global health burden, with methadone maintenance treatment (MMT) widely adopted as an intervention; however, MMT is associated with immunosuppression, metabolic disturbances, and dysbiosis of the gut microbiota. Despite the potential of acupuncture in reducing methadone dosages and opioid addiction, the underlying biological mechanisms remain unclear. Therefore, we aimed to integrate clinical trial data with multi-omics analysis, including single-cell sequencing, transcriptomics, metabolomics, and metagenomics, to evaluate the effects of acupuncture in patients undergoing MMT. We collected peripheral blood mononuclear cells, plasma, and fecal samples from 48 MMT participants in a randomized, placebo-controlled trial. Participants were divided into acupuncture (<i>n</i> = 25) and sham-acupuncture (<i>n</i> = 23) groups. After 8 weeks of intervention, 84% of patients in the acupuncture group achieved ≥20% reduction in methadone dosage, compared to 39% in the sham-acupuncture group (<i>P</i> < 0.01). Our findings revealed that acupuncture may activate the defense response to viruses, with altered immune cell functions in classical monocytes correlating with clinical responses to reduced methadone doses. Acupuncture might ameliorate intestinal microbial disruptions caused by OUD by up-regulating <i>Bilophila</i> and modulating bile acid metabolism. Furthermore, acupuncture up-regulated galectin-9 (LGALS9)-mediated intercellular communication between classical monocytes and other immune subsets. To further validate the mechanistic link between bile acid metabolism and immune regulation, we conducted in vitro experiments using THP-1 monocytes treated with cholic acid. The results showed that bile acid exposure suppressed galectin-9 and IFN-γ expression, while low-dose bile acid (simulating acupuncture effects) partially reversed this effect. These findings support a bile acid-galectin-interferon axis that may be modulated by acupuncture in OUD. Collectively, our results provide clinical and mechanistic evidence supporting acupuncture as a potential adjunct therapy to mitigate the adverse effects of long-term opioid use.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0741"},"PeriodicalIF":11.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of Intense Electromagnetic Fields in Heavy-Ion Collisions: Theoretical Predictions and Experimental Results.","authors":"Diyu Shen, Jinhui Chen, Xu-Guang Huang, Yu-Gang Ma, Aihong Tang, Gang Wang","doi":"10.34133/research.0726","DOIUrl":"10.34133/research.0726","url":null,"abstract":"<p><p>In heavy-ion collisions at relativistic energies, the incident nuclei travel at nearly the speed of light. These collisions deposit kinetic energy into the overlap region and create a high-temperature environment where hadrons \"melt\" into deconfined quarks and gluons. The spectator nucleons, which do not undergo scatterings, generate an ultraintense electromagnetic field-on the order of 10¹⁸ G at the Relativistic Heavy Ion Collider and 10¹⁹ G at the Large Hadron Collider. These powerful electromagnetic fields have a substantial impact on the produced particles, not only complicating the study of particle interactions but also inducing novel physical phenomena. To explore the nature of these fields and their interactions with deconfined quarks, we provide a detailed overview, encompassing theoretical estimations of their generation and evolution, as well as experimental efforts to detect them. We also provide physical interpretations of the discovered results and discuss potential directions for future investigations.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0726"},"PeriodicalIF":11.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiomic Model Associated with Tumor Microenvironment Predicts Immunotherapy Response and Prognosis in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.","authors":"Jie Sun, Xuewei Wu, Xiao Zhang, Weiyuan Huang, Xi Zhong, Xueyan Li, Kaiming Xue, Shuyi Liu, Xianjie Chen, Wenzhu Li, Xin Liu, Hui Shen, Jingjing You, Wenle He, Zhe Jin, Lijuan Yu, Yuange Li, Shuixing Zhang, Bin Zhang","doi":"10.34133/research.0749","DOIUrl":"10.34133/research.0749","url":null,"abstract":"<p><p><b>Background:</b> No robust biomarkers have been identified to predict the efficacy of programmed cell death protein 1 (PD-1) inhibitors in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). We aimed to develop radiomic models using pre-immunotherapy MRI to predict the response to PD-1 inhibitors and the patient prognosis. <b>Methods:</b> This study included 246 LANPC patients (training cohort, <i>n</i> = 117; external test cohort, <i>n</i> = 129) from 10 centers. The best-performing machine learning classifier was employed to create the radiomic models. A combined model was constructed by integrating clinical and radiomic data. A radiomic interpretability study was performed with whole slide images (WSIs) stained with hematoxylin and eosin (H&E) and immunohistochemistry (IHC). A total of 150 patient-level nuclear morphological features (NMFs) and 12 cell spatial distribution features (CSDFs) were extracted from WSIs. The correlation between the radiomic and pathological features was assessed using Spearman correlation analysis. <b>Results:</b> The radiomic model outperformed the clinical and combined models in predicting treatment response (area under the curve: 0.760 vs. 0.559 vs. 0.652). For overall survival estimation, the combined model performed comparably to the radiomic model but outperformed the clinical model (concordance index: 0.858 vs. 0.812 vs. 0.664). Six treatment response-related radiomic features correlated with 50 H&E-derived (146 pairs, |<i>r</i>|= 0.31 to 0.46) and 2 to 26 IHC-derived NMF, particularly for CD45RO (69 pairs, |<i>r</i>|= 0.31 to 0.48), CD8 (84, |<i>r</i>|= 0.30 to 0.59), PD-L1 (73, |<i>r</i>|= 0.32 to 0.48), and CD163 (53, |<i>r</i>| = 0.32 to 0.59). Eight prognostic radiomic features correlated with 11 H&E-derived (16 pairs, |<i>r</i>|= 0.48 to 0.61) and 2 to 31 IHC-derived NMF, particularly for PD-L1 (80 pairs, |<i>r</i>|= 0.44 to 0.64), CD45RO (65, |<i>r</i>|= 0.42 to 0.67), CD19 (35, |<i>r</i>|= 0.44 to 0.58), CD66b (61, |<i>r</i>| = 0.42 to 0.67), and FOXP3 (21, |<i>r</i>| = 0.41 to 0.71). In contrast, fewer CSDFs exhibited correlations with specific radiomic features. <b>Conclusion:</b> The radiomic model and combined model are feasible in predicting immunotherapy response and outcomes in LANPC patients. The radiology-pathology correlation suggests a potential biological basis for the predictive models.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0749"},"PeriodicalIF":11.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vision Gaze-Driven Micro-Electro-Mechanical Systems Light Detection and Ranging Optimization.","authors":"Shaotang Wei, Bo Gao, Junya Wang, Zheng You","doi":"10.34133/research.0756","DOIUrl":"10.34133/research.0756","url":null,"abstract":"<p><p>Micro-electro-mechanical systems (MEMS) light detection and ranging (LiDAR) systems are widely employed in diverse applications for their precise ranging and high-resolution imaging capabilities. However, conventional Lissajous scanning patterns, despite their design flexibility, are increasingly limited in meeting the growing demands for image quality. In this study, we propose a novel programmable scanning method that enhances angular resolution within defined regions of interest (ROIs). By applying parameter modulation techniques, we establish a direct, analytical link between the scanning trajectory and ROI placement, enabling precise resolution control. The proposed method increases point cloud density by 2 to 6 times across any ROI within a Lissajous scan, achieving localized improvements of up to 650%, independent of frequency constraints. Moreover, it reduces the design complexity of MEMS scanning mirrors by half, while maintaining comparable high-resolution performance. Incorporating a gaze-inspired trajectory modulation strategy and random modulation continuous wave ranging, we develop a MEMS LiDAR prototype that greatly enhances point cloud fidelity and enables accurate 3-dimensional imaging within ROIs-achieving a ranging accuracy of 2.4 cm (3σ). This approach not only improves angular resolution in targeted regions but also extends the practical applicability of MEMS LiDAR to multitarget tracking and recognition scenarios. Furthermore, the study establishes a robust theoretical framework for ROI-based trajectory control, contributing to the advancement of next-generation high-resolution imaging systems.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0756"},"PeriodicalIF":11.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic IFN-I Synergizes with Topical TLR7/8 Agonists to Suppress Metastatic Tumors.","authors":"Haiting Xu, Chenghui Wang, Bo Xiao","doi":"10.34133/research.0739","DOIUrl":"10.34133/research.0739","url":null,"abstract":"<p><p>Advancing targeted cancer immunotherapy is pivotal for overcoming distant metastasis and tumor relapse. The recent study in <i>Nature Cancer</i> by Sanlorenzo et al. demonstrates a breakthrough strategy combining systemic type I interferon with topical Toll-like receptor 7/8 agonists, where oral imiquimod primes plasmacytoid dendritic cells (DCs) to produce type I interferon, thereby sensitizing conventional DCs in tumors to local Toll-like receptor 7 activation. This approach triggers c-Jun-dependent IL-12 production and CCL2-mediated plasmacytoid DC recruitment, enabling localized and systemic tumor suppression. Importantly, the therapy synergizes with PD-1 blockade to prevent recurrence, representing a significant advance in DC-targeted cancer immunotherapy.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0739"},"PeriodicalIF":11.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications.","authors":"Salem Baldi, Nanbiao Long, Shu Ma, Li Liu, Abdullah Al-Danakh, Qin Yang, Xinpei Deng, Jindong Xie, Hailin Tang","doi":"10.34133/research.0747","DOIUrl":"10.34133/research.0747","url":null,"abstract":"<p><p>Protein kinases are key mediators of cellular signaling and control cell functions through the phosphorylation of target proteins. They have become major targets for therapeutic agents aimed at treating human diseases, particularly cancer. Protein kinase inhibitors (PKIs) have emerged at the forefront of drug development, and their investigations continue to be intense, with several candidates undergoing clinical trials and persistent endeavors to identify new chemical scaffolds. The main focus is still on developing isoform-selective compounds, which are inhibitors designed to target certain protein kinases, specifically isoforms, for more precise treatment. The identification and advancement of versatile inhibitor scaffolds that more effectively target individual kinases is essential for minimizing off-target effects and resistance. This review highlights important progress in PKI therapy, emphasizing the expansion of treatments for cancer, inflammatory diseases, and neurodegenerative diseases. Future efforts should focus on improving the specificity of inhibitors via mechanistic insights, developing combination therapies, establishing novel strategies, such as CRISPR-Cas9 integration with artificial intelligence-driven drug design, and overcoming resistance to enhance clinical treatment outcomes. Clinical case stories show the challenges and possible opportunities in this quickly evolving area.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0747"},"PeriodicalIF":11.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Instant Energy Barrier Modulation in Bistable Robotic Grippers for Compliant Triggering and Powerful Grasping.","authors":"Jie Zhang, Hao Yang, Chenyu He, Hanfei Ma, Yuwen Zhao, Zongyu Zhang, Shengming Li, Wei Wang, Jinzhao Yang, Jianing Wu, Haijun Peng","doi":"10.34133/research.0737","DOIUrl":"10.34133/research.0737","url":null,"abstract":"<p><p>Bistable structures, which leverage mechanical instability, have emerged as a promising paradigm in the development of robotic grippers, providing advantages including rapid response and low energy consumption. A critical limitation of existing bistable grippers, however, lies in their invariable energy barriers, which hinder the balance between compliant triggering and powerful grasping. In this study, we propose a bistable robotic gripper capable of in situ energy barrier modulation, inspired by the adaptive seed dispersal behavior of <i>Impatiens</i> pods. This robotic gripper features an elastic curved beam-based architecture integrated with a motor-driven mechanism, enabling dynamic regulation of its energy landscape. This approach allows the energy barrier to be tuned over an order of magnitude during manipulation. In the low-barrier state, the robotic gripper initiates object interaction with a triggering force as low as 0.66 N, allowing for delicate manipulation. Upon state transition, instant energy barrier modulation (~300 ms) enhances grasping stability, achieving failure forces up to 12.08 N. This adaptive modulation strategy enables our robotic gripper to implement rapid, compliant, and powerful interaction. When incorporated into an unmanned aerial vehicle, the robotic gripper showcases reliable perching across diverse scenarios, highlighting the potential of energy barrier modulation to advance the adaptability and functionality of robotic systems.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0737"},"PeriodicalIF":11.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}