Research最新文献

{"title":"Transcriptional Patterns of Nodal Entropy Abnormalities in Major Depressive Disorder Patients with and without Suicidal Ideation.","authors":"Minxin Guo, Heng Zhang, Yuanyuan Huang, Yunheng Diao, Wei Wang, Zhaobo Li, Shixuan Feng, Jing Zhou, Yuping Ning, Fengchun Wu, Kai Wu","doi":"10.34133/research.0659","DOIUrl":"10.34133/research.0659","url":null,"abstract":"<p><p>Previous studies have indicated that major depressive disorder (MDD) patients with suicidal ideation (SI) present abnormal functional connectivity (FC) and network organization in node-centric brain networks, ignoring the interactions among FCs. Whether the abnormalities of edge interactions affect the emergence of SI and are related to the gene expression remains largely unknown. In this study, resting-state functional magnetic resonance imaging (fMRI) data were collected from 90 first-episode, drug-naive MDD with suicidal ideation (MDDSI) patients, 60 first-episode, drug-naive MDD without suicidal ideation (MDDNSI) patients, and 98 healthy controls (HCs). We applied the methodology of edge-centric network analysis to construct the functional brain networks and calculate the nodal entropy. Furthermore, we examined the relationships between nodal entropy alterations and gene expression. The MDDSI group exhibited significantly lower subnetwork entropy in the dorsal attention network (DAN) and significantly greater subnetwork entropy in the default mode network than the MDDNSI group. The visual learning score of the measurement and treatment research to improve cognition in schizophrenia (MATRICS) consensus cognitive battery was negatively correlated with the subnetwork entropy of DAN in the MDDSI group. The support vector machine model based on nodal entropy achieved an accuracy of 81.87% when distinguishing the MDDNSI and MDDSI. Additionally, the changes in SI-related nodal entropy were associated with the expression of genes in cell signaling and interactions, as well as immune and inflammatory responses. These findings reveal the abnormalities in nodal entropy between the MDDSI and MDDNSI groups, demonstrated their association with molecular functions, and provided novel insights into the neurobiological underpinnings and potential markers for the prediction and prevention of suicide.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0659"},"PeriodicalIF":11.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773193","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 Self-Assembled Metabolic Regulator Reprograms Macrophages to Combat Cytokine Storm and Boost Sepsis Immunotherapy.","authors":"Junyan Zhuang, Yongrui Hai, Xintong Lu, Borui Sun, Renming Fan, Bingjie Zhang, Wenhui Wang, Bingxue Han, Li Luo, Le Yang, Chun Zhang, Minggao Zhao, Gaofei Wei","doi":"10.34133/research.0663","DOIUrl":"10.34133/research.0663","url":null,"abstract":"<p><p>Sepsis, a life-threatening inflammatory disorder characterized by multiorgan failure, arises from a dysregulated immune response to infection. Modulating macrophage polarization has emerged as a promising strategy to control sepsis-associated inflammation. The endogenous metabolite itaconate has shown anti-inflammatory potential by suppressing the stimulator of interferon genes (STING) pathway, but its efficacy is inhibited by hyperactive glycolysis, which sustains macrophage overactivation. Here, we revealed a critical crosstalk between the itaconate-STING axis and glycolysis in macrophage-mediated inflammation. Building on this interplay, we developed a novel nanoparticle LDO (lonidamine disulfide 4-octyl-itaconate), a self-assembled metabolic regulator integrating an itaconate derivative with the glycolysis inhibitor Lonidamine. By concurrently targeting glycolysis and STING pathways, LDO reprograms macrophages to restore balanced polarization. In sepsis models, LDO effectively attenuates CCL2-driven cytokine storms, alleviates acute lung injury, and significantly enhances survival via metabolic reprogramming. This study offers a cytokine-regulatory strategy rooted in immunometabolism, providing a foundation for the translational development of immune metabolite-based sepsis therapies.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0663"},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764771","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":"Progressive Deactivation of Hydroxylases Controls Hypoxia-Inducible Factor-1α-Coordinated Cellular Adaptation to Graded Hypoxia.","authors":"Ping Wang, Xiao-Peng Zhang, Feng Liu, Wei Wang","doi":"10.34133/research.0651","DOIUrl":"10.34133/research.0651","url":null,"abstract":"<p><p>Graded hypoxia is a common microenvironment in malignant solid tumors. As a central regulator in the hypoxic response, hypoxia-inducible factor-1 (HIF-1) can induce multiple cellular processes including glycolysis, angiogenesis, and necroptosis. How cells exploit the HIF-1 pathway to coordinate different processes to survive hypoxia remains unclear. We developed an integrated model of the HIF-1α network to elucidate the mechanism of cellular adaptation to hypoxia. By numerical simulations and bifurcation analysis, we found that HIF-1α is progressively activated with worsening hypoxia due to the sequential deactivation of the hydroxylases prolyl hydroxylase domain enzymes and factor inhibiting HIF (FIH). Bistable switches control the activation and deactivation processes. As a result, glycolysis, immunosuppression, angiogenesis, and necroptosis are orderly elicited in aggravating hypoxia. To avoid the excessive accumulation of lactic acid during glycolysis, HIF-1α induces monocarboxylate transporter and carbonic anhydrase 9 sequentially to export intracellular hydrogen ions, facilitating tumor cell survival. HIF-1α-induced miR-182 facilitates vascular endothelial growth factor production to promote angiogenesis under moderate hypoxia. The imbalance between accumulation and removal of lactic acid in severe hypoxia may result in acidosis and induce cell necroptosis. In addition, the deactivation of FIH results in the destabilization of HIF-1α in anoxia. Collectively, HIF-1α orchestrates the adaptation of tumor cells to hypoxia by selectively inducing its targets according to the severity of hypoxia. Our work may provide clues for tumor therapy by targeting the HIF-1 pathway.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0651"},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764775","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 Noninvasive Menstrual Blood-Based Diagnostic Platform for Endometriosis Using Digital Droplet Enzyme-Linked Immunosorbent Assay and Single-Cell RNA Sequencing.","authors":"Han Wang, Zhouyi Gan, Yueyue Wang, Dingmeng Hu, Lexiang Zhang, Fangfu Ye, Ping Duan","doi":"10.34133/research.0652","DOIUrl":"10.34133/research.0652","url":null,"abstract":"<p><p>Endometriosis is marked by the ectopic growth, spread, and invasion of endometrial tissue beyond the uterus, resulting in recurrent bleeding, pain, reproductive challenges, and the formation of nodules or masses. Despite advancements in detection methods like ultrasound and laparoscopy, these techniques remain limited by low specificity and invasiveness, underscoring the need for a highly specific, noninvasive in vitro diagnostic method. This study investigates the potential of using menstrual blood as a noninvasive diagnostic sample for endometriosis by targeting genetic and inflammatory markers associated with endometriosis lesions. A novel digital droplet enzyme-linked immunosorbent assay (ddELISA) was developed, leveraging SiO₂ nanoparticles for the femtomolar-sensitive detection of inflammatory cytokines (OPN, IL-10, IL-6) in menstrual blood. Single-cell RNA sequencing revealed differentiation patterns across endometrial tissues and menstrual blood, affirming that menstrual blood replicates key inflammatory and immune properties of endometriosis. Furthermore, endometriosis menstrual blood endometrial cells derived from human menstrual blood displayed similar properties to endometrial stromal cells in endometriosis lesions, validating menstrual blood as a suitable in vitro diagnostic sample. In contrast to traditional ELISA, ddELISA supports multi-target detection with enhanced sensitivity and reduced processing time, allowing precise biomarker analysis from minimal sample volumes. Our ddELISA-based approach shows promise as a rapid, accessible, and accurate diagnostic tool for endometriosis, with potential for practical clinical application.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0652"},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764837","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":"Youthful Brain-Derived Extracellular Vesicle-Loaded GelMA Hydrogel Promotes Scarless Wound Healing in Aged Skin by Modulating Senescence and Mitochondrial Function.","authors":"Yuzhu Wu, Jiajie Mao, Yanyan Zhou, Gaoying Hong, Haiyan Wu, Zihe Hu, Xiaoyuan Huang, Jue Shi, Zhijian Xie, Yanhua Lan","doi":"10.34133/research.0644","DOIUrl":"10.34133/research.0644","url":null,"abstract":"<p><p>Slow wound healing in the elderly has attracted much attention recently due to the associated infection risks and decreased longevity. The \"brain-skin axis\" theory suggests that abnormalities in the brain and nervous system can lead to skin degeneration because abnormal mental states, like chronic stress, can have negative physiological and functional effects on the skin through a variety of processes, resulting in delayed wound healing and accelerated skin aging. However, it remains unclear whether maintaining a youthful brain has beneficial effects on aged skin healing. In light of this, we identified youthful brain-derived extracellular vesicles (YBEVs) and created a composite GelMA hydrogel material that encourages scarless wound healing in aged skin. We found that YBEVs reduce the expression of senescence, senescence-associated secretory phenotypes, and inflammation-associated proteins, and even restore dysfunction in senescent cells. Furthermore, by encouraging collagen deposition, angiogenesis, epidermal and dermal regeneration, and folliculogenesis, we demonstrated that YBEV-containing composite hydrogels accelerated scarless wound healing in skin wounds of aged rats. The pro-repairing speed and effect of this composite hydrogel even matched that of young rats. Subsequent proteomic analysis revealed the presence of numerous proteins within YBEVs, some of which may play a role in the regulation of skin energy intake, particularly through oxidative phosphorylation and mitochondrial function. In conclusion, the findings suggest that maintaining a youthful brain could potentially alleviate skin aging, and the proposed YBEVs-GelMA hydrogel emerges as a promising strategy for addressing age-related impairments in skin healing.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0644"},"PeriodicalIF":11.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754422","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":"Transport of Volatiles in Agglutinates from Lunar Regolith of Chang'e-5 Mission.","authors":"Long Li, Guang Zhang, Hui Zhang, Yuan Xiao, Shaofan Zhao, Jian Song, Wei Yao, Weihua Wang, Zhigang Zou, Mengfei Yang","doi":"10.34133/research.0638","DOIUrl":"10.34133/research.0638","url":null,"abstract":"<p><p>Agglutinate particles, an important component resulting from micrometeoroids impacts, account for about 13.4% to 84.7% of the volume of lunar regolith depending on its maturity. They are crucial in the soil's evolution and the migration of volatile substances. Here, we examined a representative agglutinate particle from Chang'e-5 samples and modeled how volatiles move through its porous framework. Our analysis revealed that the agglutinate's surface features a patchy distribution of smooth, open pores, as shown by both surface and 3-dimensional structural assessments. By integrating elemental distribution data, we propose that the formation of these smooth, open pores is primarily due to the flow of gaseous volatiles, byproducts of intricate physiochemical reactions occurring in the lunar surface layer during impacts by micrometeoroids. Numerical models of volatile transport in the porous agglutinate have been developed for different flow regimes. These models demonstrate that under the intense conditions of impacts, the transport of volatiles occurs at a remarkably high velocity. Consequently, it is improbable that water would accumulate within the porous structure of lunar soil agglutinates. Nevertheless, understanding this process is valuable for gaining a deeper understanding of the lunar regolith's development and for potential future endeavors in extracting water from the lunar surface.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0638"},"PeriodicalIF":11.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731153","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":"When Large Language Models Meet Evolutionary Algorithms: Potential Enhancements and Challenges.","authors":"Chao Wang, Jiaxuan Zhao, Licheng Jiao, Lingling Li, Fang Liu, Shuyuan Yang","doi":"10.34133/research.0646","DOIUrl":"10.34133/research.0646","url":null,"abstract":"<p><p>Pre-trained large language models (LLMs) exhibit powerful capabilities for generating natural text. Evolutionary algorithms (EAs) can discover diverse solutions to complex real-world problems. Motivated by the common collective and directionality of text generation and evolution, this paper first illustrates the conceptual parallels between LLMs and EAs at a micro level, which includes multiple one-to-one key characteristics: token representation and individual representation, position encoding and fitness shaping, position embedding and selection, Transformers block and reproduction, and model training and parameter adaptation. These parallels highlight potential opportunities for technical advancements in both LLMs and EAs. Subsequently, we analyze existing interdisciplinary research from a macro perspective to uncover critical challenges, with a particular focus on evolutionary fine-tuning and LLM-enhanced EAs. These analyses not only provide insights into the evolutionary mechanisms behind LLMs but also offer potential directions for enhancing the capabilities of artificial agents.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0646"},"PeriodicalIF":11.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731265","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":"Essential Regulation of Spermatogonial Stem Cell Fate Decisions and Male Fertility by APBB1 via Interaction with KAT5 and GDF15 in Humans and Mice.","authors":"Dai Zhou, Bang Liu, Lvjun Liu, Guangmin Liu, Fang Zhu, Zenghui Huang, Shusheng Zhang, Zuping He, Liqing Fan","doi":"10.34133/research.0647","DOIUrl":"10.34133/research.0647","url":null,"abstract":"<p><p>Spermatogonial stem cells (SSCs) are essential for initiating and maintaining normal spermatogenesis, and notably, they have important applications in both reproduction and regenerative medicine. Nevertheless, the molecular mechanisms controlling the fate determinations of human SSCs remain elusive. In this study, we identified a selective expression of APBB1 in dormant human SSCs. We demonstrated for the first time that APBB1 interacted with KAT5, which led to the suppression of GDF15 expression and consequent inhibition of human SSC proliferation. Intriguingly, Apbb1^-/- mice assumed the disrupted spermatogenesis and markedly reduced fertility. SSC transplantation assays revealed that Apbb1 silencing enhanced SSC colonization and impeded their differentiation, which resulted in the impaired spermatogenesis. Notably, 4 deleterious <i>APBB1</i> mutation sites were identified in 2,047 patients with non-obstructive azoospermia (NOA), and patients with the c.1940C>G mutation had a similar testicular phenotype with Apbb1^-/- mice. Additionally, we observed lower expression levels of APBB1 in NOA patients with spermatogenic arrest than in obstructive azoospermia patients with normal spermatogenesis. Collectively, our findings highlight an essential role of APBB1/KAT5/GDF15 in governing human SSC fate decisions and maintaining normal spermatogenesis and underscore them as therapeutic targets for treating male infertility.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0647"},"PeriodicalIF":11.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731151","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":"High-Performance Room-Temperature Terahertz Photodetection Using 2-Dimensional Electron Gas Channel Transport.","authors":"Mengjuan Liu, Yongzhen Li, Ziyang Ren, Yao Wang, Haiming Zhu, Qinxi Qiu, Nasir Ali, He Zhu, Jiaqi Zhu, Weien Lai, Zhiming Huang, Huizhen Wu","doi":"10.34133/research.0656","DOIUrl":"10.34133/research.0656","url":null,"abstract":"<p><p>Room-temperature (RT) terahertz (THz) detection finds widespread applications in security inspection, communication, biomedical imaging, and scientific research. However, the state-of-the-art detection strategies are still limited by issues such as low sensitivity, narrow response range, slow response speed, complex fabrication techniques, and difficulties in scaling up to large arrays. Here, we present a high-sensitivity, broadband-response, and high-speed RT THz detection strategy by utilizing a deep subwavelength metal-semiconductor-metal (MSM) structure. The spontaneously formed 2-dimensional electron gas (2DEG) at the CdTe/PbTe interface provides a superior transport channel characterized by high carrier concentration, low scattering, and high mobility. The synergy of the electromagnetic induced well effect formed in the MSM structure, and the efficient and rapid transport capabilities of the 2DEG channel give rise to an impressive performance improvement. The proposed 2DEG photodetector exhibits a broad frequency range from 22 to 519 GHz, an ultralow noise equivalent power of 3.0 × 10^-14 W Hz^-1/2 at 166 GHz, and a short response time of 6.7 μs. This work provides an effective route for the development of high-performance RT THz detection strategies, paving the way for enhanced THz technology applications.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0656"},"PeriodicalIF":11.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721185","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":"Precision Microbiome: A New Era of Targeted Therapy with Core Probiotics.","authors":"Xiuyu Fang, Yuhao Wang, Hong Wei, Yuan Huang","doi":"10.34133/research.0658","DOIUrl":"10.34133/research.0658","url":null,"abstract":"","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0658"},"PeriodicalIF":11.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720646","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}