Exploration探索
Exploration(英文缩写 EXPLORATION-PRC),ISSN 2766-8509,eISSN 2766-2098,中文译名:探索 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-10-01 至 2026-09-30，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2024 | 22.500 | Q1 |
| 2025 | 30.400 | Q1 |
Exploration 最新收录文献
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1. {"_":"ER-Localized Deadenylase Suppresses Colorectal Cancer Progression by Targeting the mRNA Decay of .","i":["PNLDC1","TUBB4B"]}
PMID:日期:2026-09-21Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, highlighting the urgent need for novel therapeutic strategies. In this study, we find that PARN-like Domain Containing protein-1 (PNLDC1), an endoplasmic reticulum-localized deadenylase, lower expresses in 91 clinical CRC tissues. Using both in vitro and in vivo models, we identify PNLDC1 as a key tumor suppressor by modulating cell cycle progression in CRC. RNA-immunoprecipitation and sequencing analyses reveal that PNLDC1 binds cell cycle-associated mRNAs, with emerging as a critical target. PNLDC1 downregulates mRNA, whose regulated degradation is essential for PNLDC1's tumor-suppressive function. Restoration of TUBB4B expression counteracts PNLDC1-mediated suppression of CRC cell proliferation, underscoring its pivotal role in CRC pathogenesis. Importantly, we demonstrate that the TUBB4B inhibitor, mebendazole, effectively suppresses the enhanced proliferation in lower-expression PNLDC1 models, including cell, mouse xenografts, and patient-derived tumor-like cell clusters, positioning it as a promising therapeutic agent. These findings establish PNLDC1 as a valuable biomarker and therapeutic target, paving the way for developing novel CRC treatments.
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2. Electrochemical Valence-Regulated Biomimetic Nanozymes for Breast Cancer Metabolism Inhibition and Potentiated Catalytic Immunotherapy.
PMID:日期:2026-09-17Manganese oxide (MnO) nanozymes have garnered significant attention for their ability to respond to the tumor microenvironment (TME) and stimulator of interferon genes (STING) pathway activation. However, they often suffer from a weak direct tumor-killing capacity due to low enzymatic activity and from attenuated anti-tumor immunity resulting from STING activation-induced excessive programmed death-ligand 1 (PD-L1) expression. In this study, we fabricated MnO nanozymes with precisely controllable valence states via electrochemical valence regulation to modulate their oxidase-like activity. Notably, M-MnOx, with a bulk Mn oxidation state of +3.62, a near-surface Mn oxidation state of approximately +3.23, 19.1% oxygen vacancies, and a reduced Mn-O coordination number of 4.7, exhibited the highest oxidase-like activity and was therefore selected for cancer therapy. This nanozyme was subsequently wrapped with a T lymphocyte membrane (TCM) to form biomimetic nanozymes (TMO). TMO efficiently targets tumors and induces immunogenic cell death via oxidase catalytic therapy, while also activating the cGAS-STING pathway and T cells for tumor killing. Furthermore, TMO competitively binds to tumor cell highly expressed PD-L1 to alleviate T cell immune suppression. Consequently, TMO demonstrates excellent tumor-killing efficacy and inhibits recurrence in vivo. This research offers a new perspective for the construction of manganese-based nanomaterials.
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3. Probiotic Spore Inspired Oral Drug Delivery System With Multiple-Barriers-Crossing Ability Modulates Gut-Brain Axis for Parkinson's Disease Therapy.
PMID:日期:2026-09-09For Parkinson's disease (PD), the development of oral brain-targeted drug delivery is challenging due to various physiological barriers. Besides the brain, the effect of the gut on the microbiome-gut-brain axis should not be ignored. Therefore, developing a gut-brain dual-targeted delivery system with multiple-barriers-crossing ability is meaningful. During the germination of probiotic spores, we find that spore coat proteins (SP) shed from their surface possess excellent characteristics (re-assembling into nanoparticles, multiple-barriers penetration ability, antioxidant property, etc.), offering potential for brain-targeted drug delivery. Inspired by this, we propose a probiotic spore based oral drug delivery system to dual-regulate the gut-brain. After oral administration, the spore system crosses the harsh gastrointestinal chemical barrier. Spores germinate in the intestine into probiotics to modulate the gut-brain axis. Meanwhile, the SP-derived reassembled nanosystems cross multiple barriers (intestinal mucus barrier, enterocyte barrier, blood-brain barrier) to reach brain and further reduce oxidative stress. Notably, neurodegeneration and behavioral deficits are alleviated in PD mice. Such gut-brain dual-regulation strategy emphasizes a comprehensive and promising technique for central nervous system disease treatment, which may be an alternative to traditional single-targeted methods. Furthermore, the probiotic spore-based oral biotherapeutics with multiple-barriers-crossing efficiency provide new insight into other brain diseases.
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4. Engineering mRNA-LNP Medicines for the Ageing Brain: Opportunities and Challenges for Neurodegenerative Diseases.
PMID:日期:2026-09-08Messenger RNA (mRNA) therapeutics delivered by lipid nanoparticles (LNPs) have advanced from concept to clinic at unprecedented speed, yet their promise for neurodegenerative diseases remains largely untapped. Currently intractable age-related proteinopathies such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis demand new therapies that combine molecular precision with scalable manufacturing. This review surveys recent advances in engineering LNPs that traverse the blood-brain barrier (BBB), evade innate immune surveillance, and achieve cell-selective expression in the ageing brain. We highlight emerging chemistries, including BBB-shuttling ionizable lipids, peptide-functionalized shells, and liver-detargeted formulations that enable systemic or minimally invasive delivery to the central nervous system (CNS) in animal models. Although no CNS-directed mRNA-LNP has yet reached clinical trials, first-in-human studies for rare metabolic disorders demonstrate favourable safety, manufacturability, and durable protein replacement. Drawing lessons from COVID-19 mRNA vaccines and ongoing liver-targeted programmes, we outline a translational roadmap for brain applications. Major hurdles that are critically assessed include efficient endosomal escape in aged neurons, heterogeneity of the senescent BBB, chronic-dose immunogenicity, and large-scale synthesis of next-generation lipids. Finally, we propose design rules and analytical standards to address outstanding knowledge gaps in expression durability and age-related BBB alterations. Together, these insights chart a path for engineering mRNA-LNP therapeutics capable of meeting the rising burden of neurodegenerative diseases in an ageing global population.
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5. The Needle-Free Frontier: Redefining the Limits of Transdermal Insulin Delivery.
PMID:日期:2026-08-26Wei and colleagues reported a pH-responsive, charge-switchable polyzwitterionic polymer carrier that achieves non-invasive transdermal insulin delivery without external energy input. The approach leverages adaptive compatibility with the cutaneous microenvironment to shuttle functional macromolecules across intact skin and achieve definitive systemic therapeutic outcomes.
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6. Targeting eEF1A1 With Baicalein to Block eEF1A1/Prdx4 Interaction for Treating Sepsis-Mediated Lung Injury.
PMID:日期:2026-08-24Sepsis is a systemic inflammatory response syndrome triggered by an uncontrolled host response to infection, which causes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Baicalein (Bai) is one of the major active components of for treating pulmonary diseases. However, its specific underlying molecular mechanism is unknown for treating sepsis-mediated ALI. Herein, we found that Bai inhibited the nuclear factor kappa B (NF-κB) pathway to suppress inflammation and oxidative stress in vitro and in vivo, alleviating the course of lung injury. Affinity chromatography revealed that Bai directly bound to eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) through hydrogen bond interaction with Q108 and D110, exhibiting a dissociation constant ( ) of 336 nM. Mechanistically, Bai blocked the interaction between eEF1A1 and peroxiredoxin 4 (Prdx4) to inhibit ring finger protein 14 (RNF14)-mediated ubiquitin-dependent degradation of Prdx4 based on APEX2 and Co-IP experiments. Moreover, eEF1A1 knockdown could repress inflammation, whereas its overexpression exerted an opposite effect in the in vitro experiments. Notably, Bai did not display any additional protective effect in LPS-mediated eEF1A1 knockdown cells, while its effect was weakened in LPS-mediated eEF1A1 overexpression cells. In addition, our study revealed that the course of sepsis-mediated lung injury was alleviated in vivo by eEF1A1 knockdown, and no extra effects were exhibited by Bai in sepsis-mediated eEF1A1 knockdown mice. These findings collectively suggested that targeting eEF1A1 represented a promising therapeutic strategy against sepsis-associated lung injury through dual anti-inflammatory and antioxidant mechanisms, particularly via Bai's role as a direct blocker disrupting eEF1A1-Prdx4 interactions.
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7. M2 Macrophage-Mimetic and ROS-Sensitive Hybrid Nanoplatform for Targeted Alleviation of Rheumatoid Arthritis.
PMID:日期:2026-08-19Rheumatoid arthritis (RA) constitutes the most prevalent inflammatory arthropathy globally, which is typically marked by synovitis and deteriorating joint damage. Regrettably, RA remains incurable owing to insufficient therapeutic response along with severe side reactions of available treatments. To overcome these formidable obstacles, an M2 macrophage membrane-cloaked, ROS-sensitive lipid-gated, and herbal anti-arthritic agent celastrol (Cel)-loaded hybrid silica nanosystem (Cel@M2-L-MSN) was established to reshape the intricate RA microenvironment. Benefiting from cell membrane camouflaging, Cel@M2-L-MSN inherited the inflammation-homing capability of M2 macrophages and selectively accumulated in the inflamed joints, where excessive ROS triggered Cel release from the mesopores to exert anti-inflammatory and antioxidative effects for joint protection. Moreover, Cel@M2-L-MSN demonstrated strengthened anti-inflammatory capability by robustly sponging multiple pro-arthritogenic factors including TNF-α, IL-1β, and CCL-2. In adjuvant-induced arthritis (AIA) rats, Cel@M2-L-MSN tremendously alleviated arthritis symptoms, mitigated cartilage and bone degeneration, and attenuated major organ injuries by playing multiple roles including inflammation downregulation, ROS clearance, and macrophage repolarization. Furthermore, Cel@M2-L-MSN substantially enhanced the cyto/hemocompatibility of free Cel and manifested good biosafety in vivo. Collectively, this study presents a biohybrid and stimuli-responsive nanomedicine for targeted RA remission, which also holds great promise for the clinical intervention of a wide spectrum of refractory inflammatory diseases.
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8. Hepatic Mechanisms and Therapeutic Target Underpinning Hypercoagulation in Obesity: Insights From Genetic and Transcriptomic Analyses.
PMID:日期:2026-08-13Obesity predisposes individuals to hypercoagulation, a key factor in life-threatening complications like stroke and cardiovascular disease. While clotting factors are primarily secreted by the liver, the mechanisms linking obesity to hypercoagulation remain unclear. In this study, we established an obesity cohort and conducted genetic analyses, single-nucleus and bulk RNA sequencing of human liver tissues, and in vitro experiments to elucidate the underlying mechanisms. Genetic analysis identified a causal relationship between body mass index (BMI) and coagulation parameters, specifically elevated fibrinogen levels. Clinical cohort data demonstrated a significant association between BMI and plasma fibrinogen levels and fibrinogen function. Hepatic transcriptomic data revealed a significant link between BMI and hepatic fibrinogen expression. snRNA-seq data and deconvolution analysis of bulk RNA-seq uncovered a specific hepatocyte subpopulation (Hep5) that was significantly increased and responsible for aberrant coagulation factor secretion in obesity. Pseudotime trajectory analysis indicated that increased interleukin 6 (IL6) signaling in obese patients contributed to the activation of the hepatocyte identity-related transcription factor CEBPB, promoting the differentiation of other hepatocyte subpopulations into Hep5. Further analysis in an independent obesity cohort confirmed serum IL6 as a critical mediator of the BMI-fibrinogen relationship, supporting the potential value of IL6 antibodies, which are currently in Phase 2b trials, for improving coagulation abnormalities. In vitro experiments demonstrated that the CEBPB inhibitor helenalin acetate reversed the aberrant expression of hepatocyte differentiation-related genes induced by IL6. This study defines the hepatic transcriptomic landscape in obesity, elucidates mechanisms of fibrinogen elevation, and highlights therapeutic targets for managing hypercoagulation in obesity.
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9. {"_":"Architecture-Interface Co-Design of g-CN Driven Dry Thick Cathodes Enabling Fast Li-Ion Transport.","sub":["3","4"]}
PMID:日期:2026-08-11Overcoming ionic transport limitations in thick-film electrodes is a central challenge for next-generation high-energy-density lithium-ion batteries. Here, we report an architecture-interface co-design strategy for solvent-free dry thick cathodes, introducing nanostructured graphitic carbon nitride (g-CN) as a multifunctional ion-transport promoter, representing the first demonstration of its application as a cathode additive. Mechanistic studies reveal that g-CN operates via a dual mechanism, simultaneously enhancing electrolyte wettability and accelerating Li transport kinetics through transient Li-N coordination that effectively lowers the desolvation energy barrier. High-resolution 3D X-ray nanotomography and pore network modeling quantitatively map the ionic-mechanical trade-off arising from compressive spring-back in the dry process, directly guiding the optimization of electrode architecture. The resulting single-layer dry electrode (∼21.5 mg cm, ∼68 µm thick) delivers a 165.9% capacity increase at 3C and a 2.85-fold enhancement in power density, while achieving markedly improved cyclic stability with 81.3% capacity retention after 600 cycles. Furthermore, a functionally graded dual-layer design (∼42.2 mg cm, ∼113 µm thick) yields a 62.5% capacity gain at 1C. This work establishes a generalizable, scalable, and sustainable pathway for engineering high-performance dense electrodes.
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10. Zero-Valent Ruthenium-Anchored Nanozymes Remodel Tumor Microenvironment for Malignant Tumor Treatment in Combination With αPD-L1 Immunotherapy.
PMID:日期:2026-08-10The complex tumor microenvironment (TME) includes high concentrations of hydrogen peroxide, high expression of reduced glutathione (GSH), hypoxia, and the resulting immunosuppression from the combination of these features, posing major challenges in tumor therapy. Although nanozymes have demonstrated remarkable potential in treating malignant tumors, nanozymes with zero-valent metal doping that can simultaneously catalyze the above three indicators to reverse the TME are still limited. Herein, zero-valent ruthenium was anchored on iron-based materials to obtain FeRu nanozymes with ruthenium as the "electron bridge" and iron as the "REDOX center" to enhance the electron transfer efficiency. Its hollow structure significantly exposes more catalytic active sites. Density functional theory calculations theoretically explain the potential triple catalytic and electron transfer mechanisms of the nanozyme. The catalase-like, peroxidase-like, and GSHOx-like activities of FeRu nanozymes rapidly generate a large amount of oxygen and hydroxyl radicals, significantly consume GSH, and disrupt the redox balance in tumor cells. These in situ catalytic reactions lead to cell damage, necrosis in malignant tumors, release of damage-associated molecular patterns, and activation of the adaptive immune response. This work also performs a combined application of anti-programmed cell death-ligand 1 and FeRu nanozymes to further enhance the efficacy of immunotherapy, thus providing a new perspective for future cancer therapy.