Advances in Bioinspired Artificial Systems Enabling Biomarker-Driven Therapy.

Bioinspired molecular engineering strategies have emerged as powerful tools that significantly enhance the development of novel therapeutics, improving efficacy, specificity, and safety in disease treatment. Recent advancements have focused on identifying and utilizing disease-associated biomarkers to optimize drug activity and address challenges inherent in traditional therapeutics, such as frequent drug administrations, poor patient adherence, and increased risk of adverse effects. In this review, we provide a comprehensive overview of the latest developments in bioinspired artificial systems (BAS) that use molecular engineering to tailor therapeutic responses to drugs in the presence of disease-specific biomarkers. We examine the transition from open-loop systems, which rely on external cues, to closed-loop feedback systems capable of autonomous self-regulation in response to disease-associated biomarkers. We detail various BAS modalities designed to achieve biomarker-driven therapy, including activatable prodrug molecules, smart drug delivery platforms, autonomous artificial cells, and synthetic receptor-based cell therapies, elucidating their operational principles and practical in vivo applications. Finally, we discuss the current challenges and future perspectives in the advancement of BAS-enabled technology and envision that ongoing advancements toward more programmable and customizable BAS-based therapeutics will significantly enhance precision medicine.

Stability in change: building a stable ecological security pattern in Northeast China under climate and land use changes.

Climate change and land use change caused by human activities have a profound impact on ecological security. Simulating the spatio-temporal changes in ecosystem service value and ecological security patterns under different carbon emission scenarios in the future is of great significance for formulating sustainable development policies. This study quantified the four major ecosystem services (habitat quality, water retention, soil erosion, and carbon storage) in Northeast China (NC), identified ecological source areas, and constructed a stable ecological security pattern. The results show that the spatial patterns of soil erosion, carbon storage, water retention, and habitat quality, the four major ecosystem services in NC, are relatively stable in the next 30 years, and there is no significant difference from the current spatial pattern distribution. The SSP1-2.6 carbon emission scenario is a priority model for the development of NC in the next 30 years. In this carbon emission scenario, the NC has the largest ecological resources (191,177 km2) and the least comprehensive resistance value (850.006 × 10-4). At the same time, the relative resistance of the corridor in this scenario is the smallest, and the area of the mandatory reserve pinch points is the least. The ecological corridors in the SSP1-2.6 scenario form a network distribution among the ecological sources, connecting several large ecological sources as a whole. This study fills the knowledge gap in building a stable ecological security pattern in NC under the background of global change, and provides a scientific basis for the decision-making of regional ecological security and land resource management.

Physiological and molecular mechanism of Populus pseudo-cathayana × Populus deltoides response to Hyphantria cunea.

Populus pseudo-cathayana × Populus deltoides is a crucial artificial forest tree species in Northeast China. The presence of the fall webworm (Hyphantria cunea) poses a significant threat to these poplar trees, causing substantial economic and ecological damage. This study conducted an insect-feeding experiment with fall webworm on P. pseudo-cathayana × P. deltoides, examining poplar's physiological indicators, transcriptome, and metabolome under different lengths of feeding times. Results revealed significant differences in phenylalanine ammonia-lyase activity, total phenolic content, and flavonoids at different feeding durations. Transcriptomic analysis identified numerous differentially expressed genes, including AP2/ERF, MYB, and WRKY transcription factor families exhibiting the highest expression variations. Differential metabolite analysis highlighted flavonoids and phenolic acid compounds of poplar's leaves as the most abundant in our insect-feeding experiment. Enrichment analysis revealed significant enrichment in the plant hormone signal transduction and flavonoid biosynthetic pathways. The contents of jasmonic acid and jasmonoyl-L-isoleucine increased with prolonged fall webworm feeding. Furthermore, the accumulation of dihydrokaempferol, catechin, kaempferol, and naringenin in the flavonoid biosynthesis pathway varied significantly among different samples, suggesting their crucial role in response to pest infestation. These findings provide novel insights into how poplar responds to fall webworm infestation.

RNA Sequencing Screens the Key Genes and Pathways in a Mouse Model of HFpEF.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with high morbidity and mortality but without available evidence-based therapies. It is essential to investigate changes in gene expression profiles in preclinical HFpEF animal models, with the aim of searching for novel therapeutic targets. METHODS: Wild-type male C57BL/6J mice were administrated with a combination of high-fat diet (HFD) and inhibition of constitutive nitric oxide synthase using N-nitro-l-arginine methyl ester (l-NAME) for 5 and 7 weeks. RNA sequencing was conducted to detect gene expression profiles, and bioinformatic analysis was performed to identify the core genes, pathways, and biological processes involved. RESULTS: A total of 1,347 genes were differentially expressed in the heart at week 5 and 7 post-intervention. Gene Ontology enrichment analysis indicated that these greatly changed genes were involved mainly in cell adhesion, neutrophil chemotaxis, cell communication, and other functions. Using hierarchical cluster analysis, these differentially expressed genes were classified into 16 profiles. Of these, three significant profiles were ultimately identified. Gene co-expression network analysis suggested troponin T type 1 (Tnnt1) directly regulated 31 neighboring genes and was considered to be at the core of the associated gene network. CONCLUSION: The combined application of RNA sequencing, hierarchical cluster analysis, and gene network analysis identified Tnnt1 as the most important gene in the development of HFpEF.

Reduced field-of-view DWI based on deep learning reconstruction improving diagnostic accuracy of VI-RADS for evaluating muscle invasion.

OBJECTIVES: To investigate whether reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with deep learning reconstruction (DLR) can improve the accuracy of evaluating muscle invasion using VI-RADS. METHODS: Eighty-six bladder cancer participants who were evaluated by conventional full field-of-view (fFOV) DWI, standard rFOV (rFOVSTA) DWI, and fast rFOV with DLR (rFOVDLR) DWI were included in this prospective study. Tumors were categorized according to the vesical imaging reporting and data system (VI-RADS). Qualitative image quality scoring, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC value were evaluated. Friedman test with post hoc test revealed the difference across the three DWIs. Receiver operating characteristic analysis was performed to calculate the areas under the curve (AUCs). RESULTS: The AUC of the rFOVSTA DWI and rFOVDLR DWI were higher than that of fFOV DWI. rFOVDLR DWI reduced the acquisition time from 5:02 min to 3:25 min, and showed higher scores in overall image quality with higher CNR and SNR, compared to rFOVSTA DWI (p < 0.05). The mean ADC of all cases of rFOVSTA DWI and rFOVDLR DWI was significantly lower than that of fFOV DWI (all p < 0.05). There was no difference in mean ADC value and the AUC for evaluating muscle invasion between rFOVSTA DWI and rFOVDLR DWI (p > 0.05). CONCLUSIONS: rFOV DWI with DLR can improve the diagnostic accuracy of fFOV DWI for evaluating muscle invasion. Applying DLR to rFOV DWI reduced the acquisition time and improved overall image quality while maintaining ADC value and diagnostic accuracy. CRITICAL RELEVANCE STATEMENT: The diagnostic performance and image quality of full field-of-view DWI, reduced field-of-view (rFOV) DWI with and without DLR were compared. DLR would benefit the wide clinical application of rFOV DWI by reducing the acquisition time and improving the image quality. KEY POINTS: Deep learning reconstruction (DLR) can reduce scan time and improve image quality. Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with DLR showed better diagnostic performances than full field-of-view DWI. There was no difference of diagnostic accuracy between rFOV DWI with DLR and standard rFOV DWI.

People-Oriented Nursing Mode on the Negative Emotions and Psychological Status of Patients with Bladder Cancer.

Background: We aimed to investigate the clinical application effect of people-oriented nursing model on the negative emotions and psychological conditions of patients with bladder cancer. Methods: Eighty patients with bladder cancer were enrolled from January 2020 to January 2022 in the Second Affiliated Hospital of Qiqihar Medical University Heilongjiang, Province, China. The patients were randomly divided into the control group, each group consisted of 40 patients (conventional nursing mode) and the experimental group (people-oriented nursing mode) according to the admission time. The differences of the anxiety, depression and quality of life scores at the time of admission and discharge were compared between the two groups. Results: There was statistically significant differences in the Self-Rating Anxiety Scale (SAS) and Self-rating depression scale (SDS) score within each group of patients and between the two groups at the time of admission and discharge, respectively (P=0.001). In addition, there was a statistically significant difference in the scores at discharge, and the scores of the patients in the experimental group were better than those in the control group. There was a statistically significant difference in the scores at discharge, and the scores of the experimental group were lower than those of the control group P<0.001). After comparing the overall scores of admission and discharge of the two groups of patients, the differences were statistically significant, and the scores at discharge were better improved than those at admission were. Conclusion: The people-oriented nursing model could relieve the negative emotions, relieve pain and improve the life quality of patients with bladder cancer.

Overexpression of histone demethylase gene SlJMJ18 and SlJMJ23 from tomato confers cadmium tolerance by regulating metal transport and hormone content in Arabidopsis.

A lower concentration of cadmium (Cd), a hazardous and non-essential element for plant growth, will have deleterious effects on plants and endanger human health. Histone demethylase (JHDM) is important for plants' ability to withstand abiotic stress, according to an increasing number of studies. The degree of expression of the SlJMJ18 and SlJMJ23 genes in different tomato tissues was confirmed by this study. These two genes were responsive to the heavy metals Cd, Hg, Pb, and Cu stress, according to fluorescence quantification and GUS staining. Interestingly, the overexpression transgenic Arabidopsis plants of two genes have different responses to Cd stress. While SlJMJ18-OE lines consistently display Cd resistance but an early-flowering phenotype, SlJMJ23-OE plants have sensitivity during the post-germination stage and then greater tolerance to Cd stress. It was discovered that these two genes may affect cadmium tolerance of plants by regulating the expression of hormone synthesis related genes and hormone contents (BRs and ABA). Moreover, SlJMJ23 may resist cadmium stress by increasing the total phenol content in plants. The functional significance of JMJs is better understood in this study, which also offers a theoretical foundation for the use of molecular technology to develop plants resistant to Cd and an experimental basis for the efficient use of land resources.

Structural Optimization of Marine Natural Product Pretrichodermamide B for the Treatment of Colon Cancer by Targeting the JAK/STAT3 Signaling Pathway.

Marine natural product (MNP) pretrichodermamide B (Pre B, 9) was identified as a novel STAT3 inhibitor in our previous work, while its metabolic instability hindered its further development. To address this drawback, ligand structure-based drug design was adopted leading to a series of Pre B derivatives. Among them, MNP trichodermamide B (tri B, 24) obtained by skeletal rearrangement exhibited more potent antiproliferative activity with an IC50 value of 0.12 µM against HCT116. Notably, 24 stood out with improved metabolic stability (T1/2 = 31 min) and more favorable oral bioavailability (F = 37.5%). Further studies indicated that 24 blocked JAK/STAT3 signaling in dose- and time-dependent manner. In vivo, 24 suppressed tumor growth (TGI = 65%) at a dose of 20 mg/kg in a HCT116-derived xenograft mouse model. Overall, 24 might be a promising lead compound for colon cancer and is worthy of further investigation.

Electrical Stimulation Induces Activation of Mitochondrial Apoptotic Pathway and Down-Regulates Heat Shock Proteins in Pork: An Innovative Strategy for Enhancing the Ripening Process and Quality of Dry-Cured Loin Ham.

A fundamental regulatory framework to elucidate the role of electrical stimulation (ES) in reducing long production cycles, enhancing protein utilization, and boosting product quality of dry-cured ham is essential. However, how mitochondria and enzymes in meat fibers are altered by ES during post-processing, curing, and fermentation procedures remains elusive. This study sought to explore the impact of ES on the regulation of heat shock proteins (HSP27, HSP70), apoptotic pathways, and subsequent influences on dry-cured pork loin quality. The gathered data validated the hypothesis that ES notably escalates mitochondrial oxidative stress and accelerates mitochondrial degradation along the ripening process. The proapoptotic response in ES-treated samples was increased by 120.7%, with a cellular apoptosis rate 5-fold higher than that in control samples. This mitochondrial degradation is marked by increased ratios of Bax/Bcl-2 protein along the time course, indicating that apoptosis could contribute to the dry-cured ham processing. ES was shown to further down-regulate HSP27 and HSP70, establishing a direct correlation with the activation of mitochondrial apoptosis pathways, accompanied by dry-cured ham quality improvements. The findings show that ES plays a crucial role in facilitating the ripening of dry-cured ham by inducing mitochondrial apoptosis to reduce HSP expression. This knowledge not only explains the fundamental mechanisms behind myofibril degradation in dry-cured ham production but also offers a promising approach to enhance quality and consistency.

ROS-scavenging lipid-based liquid crystalline as a favorable stem cell extracellular vesicles delivery vector to promote wound healing.

Wound management is a critical clinical challenge due to the dynamic and complex pathological characteristics of inflammation, proliferation, and matrix remodeling. To address this challenge, the regulation and management of this multi-stage pathological microenvironment may provide a feasible approach to wound healing. In this work, we synthesized a new lipid material (DA) with reactive oxygen species (ROS) scavenging effect to prepare DA-based liquid crystalline (DALC). Then, DALC was incorporated with adipose mesenchymal stem cells-derived extracellular vesicles (AMSC-EVs) to fabricate a novel scaffold dressing (EVs@DALC) for the treatment of the wound. DALC not only endowed EVs@DALC with ROS scavenging sites for relieving the oxidative stress and inflammation in the microenvironment of the wound site, but also facilitated cellular uptake and transfection of microRNA and growth factors contained in AMSC-EVs. Benefiting from DALC, AMSC-EVs effectively transferred microRNA and growth factors into the skin cells to induce cell proliferation and migration and accelerate angiogenesis. The results of wound healing effect in vivo indicate EVs@DALC achieved multi-stage pathological modulation for accelerating wound healing through alleviating inflammation, promoting cell proliferation and migration, and angiogenesis. Taken together, this work provides an effective strategy based on antioxidant lipid liquid crystalline delivering extracellular vesicles in treating skin wounds and paves a way for stem cell extracellular vesicles clinical translation.

Cerium oxide /Co-Co Prussian blue analogue composite catalyst for enhanced peroxymonosulfate activation for effective removal of tetracycline hydrochloride from water.

In this paper, a novel CeO2/Co3[Co(CN)6]2 (CeO2/PBACo-Co) composite was prepared with co-precipitation and utilized to activate peroxymonosulfate (PMS) to eliminate tetracycline hydrochloride (TCH). Catalyst screening showed that the composite with a CeO2:PBACo-Co mass ratio of 1:5 (namely, 0.2-CeO2/PBACo-Co) had the best performance. The degradation efficiency of TCH in 0.2-CeO2/PBACo-Co/Oxone system was investigated. The experimental results illustrated that 98% of 50 mg/L TCH and 48.5% of TOC were degraded by 50 mg/L 0.2-CeO2/PBACo-Co and 400 mg/L Oxone within 120 min at 25 °C and initial pH 5.3. Recycling studies showed that the elimination rate of TCH can still achieve 85.8% after five cycles, suggesting that 0.2-CeO2/PBACo-Co composite processes good reusability. Trapping experiments and EPR tests revealed that the reaction system produced multiple active species (1O2, O2•-, SO4•-, and •OH). We proposed the catalytic mechanism of 0.2-CeO2/PBACo-Co for PMS activation, which mainly involves the promoted Co3+/Co2+ cycle by Ce3+ donated electrons. These results indicate that CeO2/PBACo-Co composite is an effective catalyst for wastewater remediation.

Multiplex-genome-editing based rapid directional improvement of complex traits in rice.

Although thousands of genes have been identified or cloned in rice (Oryza sativa) in the last two decades, the majority of them have only been separately characterized in specific varieties or single-gene modified backgrounds, thus limiting their practical application. We developed an optimized multiplex genome editing (MGE) toolbox that can efficiently assemble and stably express up to twelve sgRNA targets in a single plant expression vector. In this study, we established the MGE-based Rapid Directional Improvement (MRDI) strategy for directional improvement of complex agronomic traits in one small-scale rice transformation. This approach provides a rapid and practical procedure, encompassing sgRNA assembly, transgene-free screening and the creation of promising germplasm, by combining the precision of gene editing with phenotype-based field breeding. The MRDI strategy was used to generate the full diversity of twelve main agronomic genes in rice cultivar FXZ for the directional improvement of its growth duration and plant architecture. After applying the MRDI to FXZ, ideal plants with the desired traits of early heading date reduced plant height, and more effective panicles were generated without compromising yield, blast resistance and grain quality. Furthermore, the results of whole-genome sequencing (WGS), including the analysis of structural variations (SVs) and single nucleotide variations (SNVs) in the MGE plants, confirmed the high specificity and low frequency of unwanted mutations associated with this strategy. The MRDI breeding strategy would be a robust approach for exploring and applying crucial agronomic genes, as well as for generating novel elite germplasm in the future.

Organoids derived from metastatic cancers: Present and future.

Organoids are three-dimensional structures derived from primary tissue or tumors that closely mimic the architecture, histology, and function of the parental tissue. In recent years, patient-derived organoids (PDOs) have emerged as powerful tools for modeling tumor heterogeneity, drug screening, and personalized medicine. Although most cancer organoids are derived from primary tumors, the ability of organoids from metastatic cancer to serve as a model for studying tumor biology and predicting the therapeutic response is an area of active investigation. Recent studies have shown that organoids derived from metastatic sites can provide valuable insights into tumor biology and may be used to validate predictive models of the drug response. In this comprehensive review, we discuss the feasibility of culturing organoids from multiple metastatic cancers and evaluate their potential for advancing basic cancer research, drug development, and personalized therapy. We also explore the limitations and challenges associated with using metastasis organoids for cancer research. Overall, this review provides a comprehensive overview of the current state and future prospects of metastatic cancer-derived organoids.

Sex-specific association of serum dehydroepiandrosterone and its sulfate levels with osteoporosis in type 2 diabetes.

INTRODUCTION: This study is to investigate the relation between serum dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) levels and the risk of osteoporosis in patients with T2DM. MATERIALS AND METHODS: This cross-sectional study involved 938 hospitalized patients with T2DM. Linear regression models were used to explore the relationship between DHEA and DHEAS and the BMD at different skeletal sites. Multinominal logistic regression models and the restricted cubic spline (RCS) were used to evaluate the associations of DHEA and DHEAS with the risks of osteopenia and/or osteoporosis. RESULTS: In postmenopausal women with T2DM, after adjustment for confounders including testosterone and estradiol, DHEA showed a significant positive correlation with lumbar spine BMD (P = 0.013). Moreover, DHEAS exhibited significant positive correlations with BMD at three skeletal sites: including femoral neck, total hip, and lumbar spine (all P < 0.05). Low DHEA and DHEAS levels were associated with increased risk of osteopenia and/or osteoporosis (all P < 0.05) and the risk of osteoporosis gradually decreased with increasing DHEAS levels (P overall = 0.018, P-nonlinear = 0.559). However, DHEA and DHEAS levels in men over the age of 50 with T2DM were not associated with any of above outcomes. CONCLUSION: In patients with T2DM, independent of testosterone and estradiol, higher DHEA and DHEAS levels are associated with higher BMD and lower risk of osteopenia/osteoporosis in postmenopausal women but not men over the age of 50.

Synthesis of ɑ-Aryl-oxindoles via Grignard Reaction with Isatin in the Presence of Diphenyl Phosphite.

A protocol has been developed for the synthesis of α-aryl-oxindoles from isatin and Grignard reagents in the presence of diphenyl phosphite for the first time. This reaction was conveniently carried out under mild conditions in a one-pot fashion with moderate to excellent yields.

EGC enhances tumor antigen presentation and CD8+ T cell-mediated antitumor immunity via targeting oncoprotein SND1.

The Staphylococcal nuclease and Tudor domain containing 1 (SND1) has been identified as an oncoprotein. Our previous study demonstrated that SND1 impedes the major histocompatibility complex class I (MHC-I) assembly by hijacking the nascent heavy chain of MHC-I to endoplasmic reticulum-associated degradation. Herein, we aimed to identify inhibitors to block SND1-MHC-I binding, to facilitate the MHC-I presentation and tumor immunotherapy. Our findings validated the importance of the K490-containing sites in SND1-MHC-I complex. Through structure-based virtual screening and docking analysis, (-)-Epigallocatechin (EGC) exhibited the highest docking score to prevent the binding of MHC-I to SND1 by altering the spatial conformation of SND1. Additionally, EGC treatment resulted in increased expression levels of membrane-presented MHC-I in tumor cells. The C57BL/6J murine orthotopic melanoma model validated that EGC increases infiltration and activity of CD8+ T cells in both the tumor and spleen. Furthermore, the combination of EGC with programmed death-1 (PD-1) antibody demonstrated a superior antitumor effect. In summary, we identified EGC as a novel inhibitor of SND1-MHC-I interaction, prompting MHC-I presentation to improve CD8+ T cell response within the tumor microenvironment. This discovery presents a promising immunotherapeutic candidate for tumors.

Associations of four surrogate insulin resistance indexes with non-alcoholic steatohepatitis in Chinese patients with obesity: a cross-sectional study.

OBJECTIVES: This study was designed to evaluate the association of four surrogate indexes of IR with NASH in patients with obesity. METHODS: A total of 270 patients who underwent bariatric surgery, were included in this cross-sectional study. NASH was diagnosed based on liver biopsies. Binary logistics regression analyses were performed to assess the associations of four surrogate indexes of IR (HOMA-IR, Matsuda index, TyG, and TG/HDL-C) with NASH in patients with obesity. The restricted cubic spline was used to assess the dose-response associations of surrogate indexes of IR with NASH after adjusting for confounding factors. RESULTS: NASH was diagnosed in 136 patients, with a prevalence of 50.37%. Compared with tertile 1, the fully adjusted ORs (95% CIs) of NASH for tertile 3 were 2.711(1.113-6.608) and 0.297 (0.152-0.579) for TyG and Matsuda index. Consistently, per SD increment of TyG were still significantly associated with 64% increased risks of NASH, and per SD increment of Matsuda index were still significantly associated with 38% decreased risks of NASH. In contrast, no significant associations were found between HOMA-IR and TG/HDL-C and the risk of NASH in patients with obesity (all P > 0.05). After adjusting covariates in restricted cubic splines, the risk of NASH decreased with the increment of Matsuda Index levels (P-nonlinear = 0.442, P-overall = 0.007) and with the decrement of TyG levels (P-nonlinear = 0.004, P-overall = 0.001). CONCLUSIONS: In patients with obesity, TyG and Matsuda index were independently related to the risk of NASH after adjustment for traditional risk factors. In addition, compared with HOMA-IR and TG/HDL-C, the Matsuda index and TyG may be more suitable for NASH prediction in patients with obesity.

Employee green behavior: Bibliometric-content analysis.

Purpose: - This research conducted a thorough literature review to analyze current research on Employee Green Behavior (EGB) and its contexts. It identified key areas of emphasis in EGB and provided a precise roadmap for future research. Design/methodology/approach: The research on employee green behavior will be visually represented using bibliometric analysis. Additionally, we provided a comprehensive overview of the correlation between relevant theories and determinants of employee green behavior. We also offered specific suggestions for future research to deepen consumer researchers' understanding of this concept. Findings: A bibliometric analysis was conducted on 275 journal articles regarding employee green behavior sourced from the Web of Science database spanning 2012 to 2023. The study revealed an increasing focus on employee green behavior research across diverse fields such as management, economics, psychology, sociology, and law. China, the United States, and Italy emerged as the top three countries both in publication volume and literature centrality. The academic literature primarily centers on investigating antecedent variables of green employee behavior, broadly categorized into corporate social responsibility, organizational support, green human resource management, transformational and ethical leadership, organizational commitment, job satisfaction, responsible leadership, intentions, values, organizational identification, and organizational climate. To comprehensively analyze prior studies, content analysis was performed, outlining and scrutinizing four empirical areas including antecedents, mediators, moderators, and outcomes of employee green behavior. While research on antecedents and influencing mechanisms of green loyalty was prevalent among the influencing variables, boundary conditions such as moderators received relatively less attention. Originality/value: This comprehensive literature review offers a clear understanding of the conceptual content, organization, and assessment of employee green behavior. Furthermore, it includes a bibliometric analysis of 275 papers on employee green behavior published between 2012 and 2023 in the Web of Science database. The text analysis reveals insights into the theoretical foundation, antecedent and outcome variables, and processes of employee green behavior, providing valuable guidance for future research.

Curvature-mediated rapid extravasation and penetration of nanoparticles against interstitial fluid pressure for improved drug delivery.

Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these tissues, solid tumors present the most challenging scenario. While several strategies through reducing tumor IFP have been devised to enhance nanoparticle delivery, few approaches focus on modulating the intrinsic properties of nanoparticles to effectively counteract IFP during extravasation and penetration, which are precisely the stages obstructed by elevated IFP. Herein, we propose an innovative solution by engineering nanoparticles with a fusiform shape of high curvature, enabling efficient surmounting of IFP barriers during extravasation and penetration within tumor tissues. Through experimental and theoretical analyses, we demonstrate that the elongated nanoparticles with the highest mean curvature outperform spherical and rod-shaped counterparts against elevated IFP, leading to superior intratumoral accumulation and antitumor efficacy. Super-resolution microscopy and molecular dynamics simulations uncover the underlying mechanisms in which the high curvature contributes to diminished drag force in surmounting high-pressure differentials during extravasation. Simultaneously, the facilitated rotational movement augments the hopping frequency during penetration. This study effectively addresses the limitations posed by high-pressure impediments, uncovers the mutual interactions between the physical properties of NPs and their environment, and presents a promising avenue for advancing cancer treatment through nanomedicine.