Mendelian randomization based on genome-wide association studies and expression quantitative trait loci, predicting gene targets for the complexity of osteoarthritis as well as the clinical prognosis of the condition.

Background: Osteoarthritis (OA) entails a prevalent chronic ailment, marked by the widespread involvement of entire joints. Prolonged low-grade synovial inflammation serves as the key instigator for a cascade of pathological alterations in the joints. Objective: The study seeks to explore potential therapeutic targets for OA and investigate the associated mechanistic pathways. Methods: Summary-level data for OA were downloaded from the genome-wide association studies (GWAS) database, expression quantitative trait loci (eQTL) data were acquired from the eQTLGen consortium, and synovial chip data for OA were obtained from the GEO database. Following the integration of data and subsequent Mendelian randomization analysis, differential analysis, and weighted gene co-expression network analysis (WGCNA) analysis, core genes that exhibit a significant causal relationship with OA traits were pinpointed. Subsequently, by employing three machine learning algorithms, additional identification of gene targets for the complexity of OA was achieved. Additionally, corresponding ROC curves and nomogram models were established for the assessment of clinical prognosis in patients. Finally, western blotting analysis and ELISA methodology were employed for the initial validation of marker genes and their linked pathways. Results: Twenty-two core genes with a significant causal relationship to OA traits were obtained. Through the application of distinct machine learning algorithms, MAT2A and RBM6 emerged as diagnostic marker genes. ROC curves and nomogram models were utilized for evaluating both the effectiveness of the two identified marker genes associated with OA in diagnosis. MAT2A governs the synthesis of SAM within synovial cells, thereby thwarting synovial fibrosis induced by the TGF-ß1-activated Smad3/4 signaling pathway. Conclusion: The first evidence that MAT2A and RBM6 serve as robust diagnostic for OA is presented in this study. MAT2A, through its involvement in regulating the synthesis of SAM, inhibits the activation of the TGF-ß1-induced Smad3/4 signaling pathway, thereby effectively averting the possibility of synovial fibrosis. Concurrently, the development of a prognostic risk model facilitates early OA diagnosis, functional recovery evaluation, and offers direction for further therapy.

Fe(III)-Triggered Radical Arylation of Arene Moieties from Cyclopropanols to Construct Dibenzocyclohepta/octanones: Synthesis of N-Acetylcolchinol-O-methyl ether.

Tricyclic 6-7-6 and 6-8-6 carbon ring systems are present in numerous biologically active natural molecules. However, simple and efficient synthetic approaches to these scaffolds remain challenging. Herein, we report a versatile strategy for constructing these ring systems via Fe(NO3)3-triggered radical arylation of arenes starting from cyclopropanols. This synthetic utility has been demonstrated in the synthesis of the natural product N-acetylcolchinol-O-methyl ether.

Causal associations between chronic heart failure and the cerebral cortex: results from Mendelian randomization study and integrated bioinformatics analysis.

Background: Chronic heart failure (CHF) patients exhibit alterations in cerebral cortical structure and cognitive function. However, the mechanisms by which CHF affects cortical structure and functional regions remain unknown. This study aims to investigate potential causal relationship between CHF and cerebral cortical structure through Mendelian randomization (MR). Methods: The research utilized genome-wide association studies (GWAS) to explore the causal association between CHF and cerebral cortical structure. The results were primarily analyzed using the inverse-variance weighted (IVW). The reliability of the data was verified through horizontal pleiotropy and heterogeneity analysis by MR-Egger intercept test and Cochran's Q-test, respectively. Replication analysis was conducted in the Integrative Epidemiology Unit (IEU) OpenGWAS project for further validation. In addition, we collected mediator genes that mediate causality to reveal potential mechanisms. Integrated bioinformatics analysis was conducted using the Open Target Genetics platform, the STRING database, and Cytoscape software. Results: The IVW results did not reveal any significant causal association between genetically predicted CHF and the overall structure of the cerebral cortex or the surface area (SA) of the 34 functional regions of the cerebral cortex (P > 0.05). However, the results revealed that CHF increased the thickness (TH) of pars opercularis (IVW: ß = 0.015, 95% CI: 0.005-0.025, P = 3.16E-03). Replication analysis supported the causal association between CHF and pars opercularis TH (IVW: ß = 0.02, 95% CI: 0.010-0.033, P = 1.84E-04). We examined the degree centrality values of the top 10 mediator genes, namely CDKN1A, CELSR2, NME5, SURF4, PSMA5, TSC1, RPL7A, SURF6, PRDX3, and FTO. Conclusion: Genetic evidence indicates a positive correlation between CHF and pars opercularis TH.

Detection of ion cyclotron emission by using an ion cyclotron range of frequency antennas-based diagnostic system in experimental advanced superconducting tokamak.

In the experimental advanced superconducting tokamak (EAST), a novel ion cyclotron range of frequency (ICRF) antenna-based diagnostic system is designed to measure ion cyclotron emission (ICE) driven by high-energy ions. The diagnostic system includes ICRF antenna straps, a three-tune impedance matching system, a coaxial switching system, a direct current block, and a data acquisition and storage system. Using the coaxial switching system, the ICRF antenna can be switched from the heating mode to the coupling mode between two discharges. In the 2023 EAST experiment campaign, core ICE was observed using the ICRF antenna-based diagnostic system during neutron beam injection heating, and the obtained results agreed well with the signal detected by the previous high-frequency B-dot probe-based diagnostic system.

The longevity evaluation of multi-metal stabilization by MgO in Pb/Zn smelter-contaminated soils.

The re-mobilization risks of potentially toxic elements (PTEs) during stabilization deserve to be considered. In this study, artificial simulation evaluation methods based on the environmental stress of freeze-thaw (F-T), acidification and variable pH were conducted to assess the long-term effectiveness of PTEs stabilized by MgO in Pb/Zn smelter contaminated soils. Among common stabilizing materials, MgO was considered as the best remediation material, since PTEs bioavailability reduced by 55.48% for As, 19.58% for Cd, 10.57% for Cu, and 26.33% for Mn, respectively. The stabilization effects of PTEs by MgO were best at the dosage of 5 wt%, but these studied PTEs would re-mobilize after 30 times F-T cycles. Acid and base buffering capacity results indicated that the basicity of contaminated soils with MgO treatment reduced under F-T action, and the leached PTEs concentrations would exceed the safety limits of surface water quality standard in China (GB3838-2002) after acidification of 2325 years. No significant changes were found in the pH-dependent patterns of PTEs before and after F-T cycles. However, after F-T cycles, the leaching concentrations of PTEs increased due to the destruction of soil microstructure and the functionality of hydration products formed by MgO, as indicated by scanning electron microscopy (SEM) coupled with energydispersive Xray spectroscopy (EDS) results. Hence, these findings would provide beneficial references for soil remediation assessments of contaminated soils under multi-environmental stress.

Enhancement of Repeat-Mediated Deletion Rearrangement Induced by Particle Irradiation in a RecA-Dependent Manner in Escherichia coli.

Repeat-mediated deletion (RMD) rearrangement is a major source of genome instability and can be deleterious to the organism, whereby the intervening sequence between two repeats is deleted along with one of the repeats. RMD rearrangement is likely induced by DNA double-strand breaks (DSBs); however, it is unclear how the complexity of DSBs influences RMD rearrangement. Here, a transgenic Escherichia coli strain K12 MG1655 with a lacI repeat-controlled amp activation was used while taking advantage of particle irradiation, such as proton and carbon irradiation, to generate different complexities of DSBs. Our research confirmed the enhancement of RMD under proton and carbon irradiation and revealed a positive correlation between RMD enhancement and LET. In addition, RMD enhancement could be suppressed by an intermolecular homologous sequence, which was regulated by its composition and length. Meanwhile, RMD enhancement was significantly stimulated by exogenous λ-Red recombinase. Further results investigating its mechanisms showed that the enhancement of RMD, induced by particle irradiation, occurred in a RecA-dependent manner. Our finding has a significant impact on the understanding of RMD rearrangement and provides some clues for elucidating the repair process and possible outcomes of complex DNA damage.

An impressive pristine biochar from food waste digestate for arsenic(V) removal from water: Performance, optimization, and mechanism.

Anaerobic digestion has become a global practice for valorizing food waste, but the recycling of the digestate (FWD) remains challenging. This study aimed to address this issue by utilizing FWD as a low-cost feedstock for Ca-rich biochar production. The results demonstrated that biochar pyrolyzed at 900 °C exhibited impressive As(V) adsorption performance without any modifications. Kinetic analysis suggested As(V) was chemisorbed onto CDBC9, while isotherm data conformed well to Langmuir model, indicating monolayer adsorption with a maximum capacity of 76.764 mg/g. Further analysis using response surface methodology revealed that pH value and adsorbent dosage were significant influencing factors, and density functional theory (DFT) calculation visualized the formation of ionic bonds between HAsO42- and CaO(110) and Ca(OH)2(101) surfaces. This work demonstrated the potential of using FWD for producing Ca-rich biochar, providing an effective solution for As(V) removal and highlighting the importance of waste material utilization in sustainable environmental remediation.

The occurrence of "yellowing" phenomenon and its main driving factors after the remediation of chromium (Cr)-contaminated soils: A literature review.

Chromium (Cr) is a highly toxic element, which is widely present in environment due to industrial activities. One of most applicable technique to clean up Cr pollution is chemical reduction. However, the Cr(VI) concentration in soil increases again after remediation, and meanwhile the yellow soil would appear, which is commonly called as "yellowing" phenomenon. To date, the reason behind the phenomenon has been disputed for decades. This study aimed to introduce the possible "yellowing" mechanism and the influencing factors based on the extensive literature review. In this work, the concept of "yellowing" phenomenon was explained, and the most potential reasons include the reoxidation of manganese (Mn) oxides and mass transfer were summarized. Based on the reported finding and results, the large area of "yellowing" is likely to be caused by the re-migration of Cr(VI), since it could not sufficiently contact with the reductant under the effects of the mass transfer. In addition, other driving factors also control the occurrence of "yellowing" phenomenon. This review provides valuable reference for the academic peers participating in the Cr-contaminated sites remediation.

Epidemiology and a Predictive Model of Prognosis Index Based on Machine Learning in Primary Breast Lymphoma: Population-Based Study.

BACKGROUND: Primary breast lymphoma (PBL) is a rare disease whose epidemiological features, treatment principles, and factors used for the patients' prognosis remain controversial. OBJECTIVE: The aim of this study was to explore the epidemiology of PBL and to develop a better model based on machine learning to predict the prognosis for patients with primary breast lymphoma. METHODS: The annual incidence of PBL was extracted from the surveillance, epidemiology, and end results database between 1975 and 2019 to examine disease occurrence trends using Joinpoint software (version 4.9; National Cancer Institute). We enrolled data from 1251 female patients with primary breast lymphoma from the surveillance, epidemiology, and end results database for survival analysis. Univariable and multivariable analyses were performed to explore independent prognostic factors for overall survival and disease-specific survival of patients with primary breast lymphoma. Eight machine learning algorithms were developed to predict the 5-year survival of patients with primary breast lymphoma. RESULTS: The overall incidence of PBL increased drastically between 1975 and 2004, followed by a significant downward trend in incidence around 2004, with an average annual percent change (AAPC) of -0.8 (95% CI -1.1 to -0.6). Disparities in trends of PBL exist by age and race. The AAPC of the 65 years or older cohort was about 1.2 higher than that for the younger than 65 years cohort. The AAPC of White patients is 0.9 (95% CI 0.0-1.8), while that of Black patients was significantly higher at 2.1 (95% CI -2.5 to 6.9). We also identified that the risk of death from PBL is multifactorial and includes patient factors and treatment factors. Survival analysis revealed that the patients diagnosed between 2007 and 2015 had a significant risk reduction of mortality compared to those diagnosed between 1983 and 1990. The gradient booster model outperforms other models, with 0.752 for sensitivity and 0.817 for area under the curve. The important features established with the gradient booster model were the year of diagnosis, age, histologic type, and primary site, which were the 4 most relevant variables to explain 5-year survival status. CONCLUSIONS: The incidence of PBL started demonstrating a tendency to decrease after 2004, which varied by age and race. In recent years, the prognosis of patients with primary breast lymphoma has been remarkably improved. The gradient booster model had a promising performance. This model can help clinicians identify the early prognosis of patients with primary breast lymphoma and therefore improve the clinical outcome by changing management strategies and patient health care.

An axisymmetric mirror device for studying confinement and instability.

We describe a magnetic mirror device, namely, the Keda Mirror with AXisymmetricity (KMAX), which aims to study new approaches to confine and stabilize the mirror plasma as well as basic plasma research. KMAX consists of one central cell, two side cells, and two end chambers at two ends of the device. For the central cell, the mirror-to-mirror distance is 5.2 m, while the central cylinder is 2.5 m in length and 1.2 m in diameter. The plasmas are generated by two washer guns located in the end chambers, which subsequently flow into the central cell and merge there. The density in the central cell is usually adjusted by changing the magnetic field strength inside the side cell, and it ranges from 1017 to 1019 m-3, depending on the experimental requirement. Ion cyclotron frequency heating with two 100 kW transmitters is routinely used to heat up the ions. Plasma controls mainly rely on configuring the magnetic geometry and rotating magnetic fields to improve the confinement and suppress instability. Routine diagnostics, such as probes, interferometers, spectrometers, diamagnetic loops, and bolometers, are also reported in this paper.

Analog soil organo-ferrihydrite composites as suitable amendments for cadmium and arsenic stabilization in co-contaminated soils.

Remediation of CdAs co-contaminated soils has long been considered a difficult problem to solve, as Cd and As have distinctly different metallic characters. Amending contaminated soils with traditional single passivation materials may not always work well in the stabilization of both Cd and As. Here, we reported that analog soil organo-ferrihydrite composites made with either living or non-living organics (bacterial cells or humic acid) could achieve stabilization of both Cd and As in contaminated soils. BCR and Wenzel sequential extractions showed that organo-ferrihydrite, particularly at 1 wt% loading, shifted liable Cd and As to more stable phases. Organo-ferrihydrite amendments significantly (p < 0.05) increased soil urease, alkaline phosphatase and catalase enzyme activities. With organo-ferrihydrite amendments, the bioavailable fraction of Cd decreased to 35.3 % compared with the control (65.1 %), while the bioavailable As declined from 29.4 % to 12.4%. Soil pH, microbial community abundance and diversity were almost unaffected by organo-ferrihydrite. Ferrihydrite and organo fractions both contributed to direct Cd-binding, while the organo fraction probably maintained the Fe-bound As via lowering ferrihydrite phase transformation. Compared to pure ferrihydrite, organo-ferrihydrite composites performed better not only in reducing liable Cd and As, but also in maintaining soil quality and ecosystem functions. This study demonstrates the applications of organo-ferrihydrite composites in eco-friendly remediation of CdAs contaminated soils, and provides a new direction in selecting appropriate soil amendments.

Polyimide-Based Solid-State Gel Polymer Electrolyte for Lithium-Oxygen Batteries with a Long-Cycling Life.

Metal-air batteries have attracted wide interest owing to their ultrahigh theoretical energy densities, particularly for lithium-oxygen batteries. One of the challenges inhibiting the practical application of lithium-oxygen batteries is the unavoidable liquid electrolyte evaporation accompanying oxygen fluxion in the semi-open system, which leads to safety issues and poor cyclic performance. To address these issues, we propose a solid-state polyimide based gel polymer electrolyte (PI@GPE), immobilizing and reserving a liquid electrolyte in the gelled polymer substrate. The liquid electrolyte uptake of PI@GPE is measured to be 842%, 6 times higher than that of the commercial glass fiber separator, contributing to a high ionic conductivity of 0.44 mS cm-1. Additionally, PI@GPE possesses an enhanced lithium transference number of 0.596 as well as superior interfacial compatibility with lithium metals. Under 0.1 mA cm-2 and 0.25 mA h cm-2, PI@GPE-based lithium-oxygen batteries demonstrate distinguished long-cycling stability of 366 cycles, 4 times more than that with a glass fiber separator and liquid electrolyte. Our work provides a unique solid-state gel polymer electrolyte to mitigate liquid electrolyte leakage, exhibiting promising potential application in highly safe lithium-oxygen batteries with a long-cycling life.

A Hierarchical Spatial Transformer for Massive Point Samples in Continuous Space.

Transformers are widely used deep learning architectures. Existing transformers are mostly designed for sequences (texts or time series), images or videos, and graphs. This paper proposes a novel transformer model for massive (up to a million) point samples in continuous space. Such data are ubiquitous in environment sciences (e.g., sensor observations), numerical simulations (e.g., particle-laden flow, astrophysics), and location-based services (e.g., POIs and trajectories). However, designing a transformer for massive spatial points is non-trivial due to several challenges, including implicit long-range and multi-scale dependency on irregular points in continuous space, a non-uniform point distribution, the potential high computational costs of calculating all-pair attention across massive points, and the risks of over-confident predictions due to varying point density. To address these challenges, we propose a new hierarchical spatial transformer model, which includes multi-resolution representation learning within a quad-tree hierarchy and efficient spatial attention via coarse approximation. We also design an uncertainty quantification branch to estimate prediction confidence related to input feature noise and point sparsity. We provide a theoretical analysis of computational time complexity and memory costs. Extensive experiments on both real-world and synthetic datasets show that our method outperforms multiple baselines in prediction accuracy and our model can scale up to one million points on one NVIDIA A100 GPU. The code is available at https://github.com/spatialdatasciencegroup/HST.

Nonflammable Localized High-Concentration Electrolytes with Long-Term Cycling Stability for High-Performance Li Metal Batteries.

High-concentration electrolytes (HCEs) can effectively enhance interface stability and cycle performance of Li metal batteries (LMBs). However, HCEs suffer from low ionic conductivity, high viscosity, high cost, and high density. Herein, fluorobenzene (FB) diluted localized high-concentration electrolytes (LHCEs) consisting of lithium bis(fluorosulfonyl)imide (LiFSI)/triethyl phosphate (TEP)/FB are developed. 2.3 M LHCE can reserve concentrated Li+-FSI--TEP solvation structures. Diluent FB possesses low density, low viscosity, low cost, low dielectric constant, low LUMO, and a good fluorine-donating property, which can significantly reduce viscosity, improve ionic conductivity, promote the formation of LiF-rich SEI, and enhance interaction of Li+-TEP and Li+-FSI- ion-pairs of the electrolytes. 2.3 M LHCE is a highly safe nonflammable electrolyte. 2.3 M LHCE can effectively inhibit dendrite growth on Li metal anode. 2.3 M LHCE endows LiFePO4 cells with good rate capability (discharge capacity of 112.7 mAh g-1 at 5 C rate) and excellent cycling performance (capacity retention of 95.4% after 1000 cycles). 2.3 M LHCE also shows good compatibility with LiNi0.8Co0.1Mn0.1O2 and exhibits outstanding cycle stability (capacity retention of 86.4% after 500 cycles). Therefore, 2.3 M LHCE is a promising electrolyte for practical applications in LMBs.

Cellulose Acetate-Based High-Electrolyte-Uptake Gel Polymer Electrolyte for Semi-Solid-State Lithium-Oxygen Batteries with Long-Cycling Stability.

Lithium-oxygen batteries have received great research interest owing to their ultrahigh theoretical energy density and are considered as one of the promising secondary batteries. However, there are still some challenges in their practical application, like liquid organic electrolyte evaporation in the semi-open system and instability in the high-voltage oxidizing environment. In this work, a cellulose acetate-based gel polymer electrolyte (CA@GPE) is proposed, whose cross-linked microporous structure ensures the ultrahigh liquid electrolyte uptake of 2391%. The prepared CA@GPE exhibits a high lithium-ion transference number of 0.595, a satisfying ionic conductivity of 0.47 mS cm-1 and a wide electrochemical stability window up to 5.0 V. The Li//Li symmetric cell employing CA@GPE could cycle stably over 1200 h. The lithium-oxygen battery with CA@GPE presents a superb cycling lifetime of 370 cycles at 0.1 mA cm-2 under 0.25 mAh cm-2 . This work offers a possible strategy to realize long-cycling stability lithium-oxygen batteries.

Effects of Enalapril on TLR2/NF-κB Signaling Pathway and Inflammatory Factors in Rabbits with Chronic Heart Failure.

Chronic heart failure (CHF) refers to the state of persistent heart failure, which is a complex clinical syndrome of various advanced heart diseases. The toll-like receptor 2 (TLR2)/nuclear transcription factor-κB (NF-κB) signal transduction pathway is one of the pathological mechanisms of CHF. Adriamycin can significantly induce the upregulation of TLR2 expression. Angiotensin-converting enzyme inhibitors (ACEI) are commonly used drugs for the treatment of CHF. In our study, the CHF model was established by injection of doxorubicin into the rabbit ear vein. The effect of enalapril on the TLR2/NF-κB signaling pathway in CHF rabbits has been analyzed and determined. Our research results showed that enalapril reduced the inflammatory response by inhibiting the activation of the TLR2/NF-κB signaling pathway, thereby improving cardiac structure, myocardial remodeling, and cardiac function.

Effects of the Wenyang Zhenshuai Granule on the Expression of LncRNA-MiR143HG/miR-143 Regulating ERK5 in H9C2 Cardiomyocytes.

Chronic heart failure (CHF) is a complex clinical syndrome caused by a variety of heart problems, with a high incidence. The 5-year survival rate of patients with clinical symptoms is similar to that of malignant tumors. Wenyang Zhenshuai granules are a safe and effective granule of traditional Chinese medicine components, including aconite, dried ginger, licorice, and red ginseng. In contemporary clinical applications, it is widely used in acute and chronic heart insufficiency, coronary heart disease, and arrhythmia. This research cultured H9C2 cardiomyocytes and divided them into the normal control group, LncRNA-MiR143HG overexpression group, LncRNA-MiR143HG silence group, Adriamycin (ADR) group, ADR + medicated serum group, ADR + LncRNA-MiR143HG overexpression + medicated serogroup, and ADR + LncRNA-MiR143HG silence + medicated serogroup. The cells of each group were treated differently, and the survival rate of each group of cells and the expression levels of LncRNA-MiR143HG/miR-143 and ERK5 were detected at the end of the experiment, and the expression of LncRNA-MiR143HG/miR-143 in H9C2 cardiomyocytes was regulated by Wenyang Zhenshuai granules' impact. The results of this study showed that, in the doxorubicin-induced H9C2 cardiomyocyte injury model, the expression of miR-143 was upregulated, and the expression of LncRNA-MiR143HG and ERK5 was significantly downregulated. Wenyang Zhenshuai granules can downregulate the expression of miR-143 to promote ERK5 protein expression and phosphorylation. The process is regulated by LncRNA-MiR143HG/miR-143, which may be one of its important mechanisms for the treatment of chronic heart failure.

Emodin enhances cisplatin sensitivity in non-small cell lung cancer through Pgp downregulation.

Cisplatin resistance is one of the main causes of chemotherapy failure and tumor progression in non-small cell lung cancer (NSCLC). Emodin has been demonstrated to induce NSCLC cell apoptosis and act as a potential cancer therapeutic agent. However, whether emodin could affect NSCLC cell sensitivity toward cisplatin remains unclear. The present study aimed to determine the effect of emodin and cisplatin combination on the chemosensitivity of NSCLC cells. A549 and H460 cells were treated with different concentrations of cisplatin and/or emodin. Cell Counting Kit-8, fluorescence microscopy, immunofluorescence assays and flow cytometry were used to determine cell proliferation, drug efflux, DNA damage level and cell apoptosis, respectively. P-glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1) expression was detected by western blotting. The results demonstrated that emodin and cisplatin inhibited the proliferation of A549 and H460 cells. Furthermore, emodin inhibited the drug efflux in A549 and H460 cells in a dose-dependent manner. In addition, emodin enhanced cisplatin-induced apoptosis and DNA damage in A549 and H460 cells. Emodin also decreased Pgp expression in A549 and H460 cells in a dose-dependent manner; however, it had no effect on MRP1 expression. Taken together, the results from the present study demonstrated that emodin can increase A549 and H460 cell sensitivity to cisplatin by inhibiting Pgp expression. Emodin may therefore be considered as an effective adjuvant for cisplatin treatment.

Direct nanodrug delivery for tumor targeting subject to shear-augmented diffusion in blood flow.

The advent of multifunctional nanoparticle has enabled numerous innovative strategies in diagnostics, imaging, and cancer therapy. Despite the intense research efforts in developing new nanoparticles and surface bonding ligands, one major obstacle in achieving highly effective treatment, including minimizing detrimental side effects, is the inability to deliver drug-carrying nanoparticles from the injection point directly to the tumor site. The present study seeks to employ a direct nanodrug delivery methodology to feed multifunctional nanoparticles directly to tumor vasculatures, sparing healthy tissue. An important aspect to examine is how the interactions between such nanoparticles and relatively large red blood cells would affect the transport and delivery efficiency of nanodrugs. So, a novel computer simulation model has been developed to study nanoparticle transport in a representative human hepatic artery system, subject to shear-induced diffusion of nanoparticles due to hydrodynamic interactions with red blood cells. The particle-size effect was also evaluated by comparing the dynamics of nanoparticles with microspheres. Results from computer simulations under physiologically realistic conditions indicate that shear-induced diffusion has a significant effect on nanoparticle transport, even in large arteries. Nevertheless, as documented, direct nanodrug delivery to tumor-feeding hepatic artery branches is feasible. Graphical abstract Direct nanodrug delivery from injection point to tumor-feeding artery branch.

Solid Tumor Embolotherapy in Hepatic Arteries with an Anti-reflux Catheter System.

Unresectable hepatoma accounts for the majority of malignant liver tumor cases for which embolization therapy is considered a viable treatment option. However, the potential risk of aberrant particle deposition in non-target regions could cause severe side-effects, alongside diminished efficacy. A computational model has been developed to analyze the particle-hemodynamics before and after deployment of an FDA-approved anti-reflux catheter. The catheter features a retractable, porous cone-like tip designed to allow forward blood flow while preventing microsphere reflux. A patient-specific hepatic artery system, with different daughter branches connected to a liver tumor, was chosen as a representative test bed. In vitro as well as in vivo measurements were used to validate the computer simulation model. The model captures the effect of tip-deployment on blood perfusion and pressure drop in an interactive manner under physiologically realistic conditions. A relationship between the pressure drop and embolization level was established, which can be used to provide clinicians with real-time information on the best infusion-stop point. However, the results show that the present procedure for embolization of downstream vessels which feed a tumor is quite arbitrary. Nevertheless, a method to recycle aberrant particles captured by the deployed tip was proposed to minimize side-effects.