Valorization of treated swine wastewater and generated biomass by microalgae: Their effects and salt tolerance mechanisms on wheat seedling growth.

The extensive use of mineral fertilizers has a negative impact on the environment, whereas wastewater and microalgal biomass can provide crops with nutrients such as nitrogen, phosphorus, and potassium, and have the potential to be used as a source of fertilizers in circular agriculture. In this study, a step-by-step resource utilization study of algae-containing wastewater generated from microalgae treatment of swine wastewater was carried out. When wheat seedlings were cultivated in the effluent after microalgae separation, the root fresh weight, seedling fresh weight, and total seedling length were increased by 3.44%, 14.45%, and 13.64%, respectively, compared with that of the algae-containing wastewater, and there was no significant difference in seedling fresh weight, total seedling length, maximum quantum yields of PSII photochemistry (Fv/Fm), and performance index (PIABS) from that of the Hogland solution group, which has the potential to be an alternative liquid fertilizer. Under salt stress, microalgae extract increased the contents of GA3, IAA, ABA, and SA in wheat seedlings, antioxidant enzymes maintained high activity, and the PIABS value increased. Low-dose microalgae extract (1 mL/L) increased the root fresh weight, seedling fresh weight, longest seedling length, and total seedling length by 30.73%, 31.28%, 16.43%, and 28.85%, respectively. Algae extract can act as a plant biostimulant to regulate phytohormone levels to attenuate the damage of salt stress and promote growth.

Ultrastable Iodinated Oil-Based Pickering Emulsion Enables Locoregional Sustained Codelivery of Hypoxia Inducible Factor-1 Inhibitor and Anticancer Drugs for Tumor Combination Chemotherapy.

Tumor hypoxia-associated drug resistance presents a major challenge for cancer chemotherapy. However, sustained delivery systems with a high loading capability of hypoxia-inducible factor-1 (HIF-1) inhibitors are still limited. Here, we developed an ultrastable iodinated oil-based Pickering emulsion (PE) to achieve locally sustained codelivery of a HIF-1 inhibitor of acriflavine and an anticancer drug of doxorubicin for tumor synergistic chemotherapy. The PE exhibited facile injectability for intratumoral administration, great radiopacity for in vivo examination, excellent physical stability (>1 mo), and long-term sustained release capability of both hydrophilic drugs (i.e., acriflavine and doxorubicin). We found that the codelivery of acriflavine and doxorubicin from the PE promoted the local accumulation and retention of both drugs using an acellular liver organ model and demonstrated significant inhibition of tumor growth in a 4T1 tumor-bearing mouse model, improving the chemotherapeutic efficacy through the synergistic effects of direct cytotoxicity with the functional suppression of HIF-1 pathways of tumor cells. Such an iodinated oil-based PE provides a great injectable sustained delivery platform of hydrophilic drugs for locoregional chemotherapy.

Cascaded nanozyme-based high-throughput microfluidic device integrating with glucometer and smartphone for point-of-care pheochromocytoma diagnosis.

The development of point-of-care (POC) diagnostics devices for circulating tumor cells (CTCs) detection plays an important role in the early diagnosis of pheochromocytoma (PCC), especially in a low-resource setting. To further realize the rapid, portable, and high-throughput detection of CTCs, an Au@CuMOF cascade enzyme-based microfluidic device for instant point-of-care detection of CTCs was constructed by combining a smartphone application and a commercial portable glucose meter (PGM). In this microfluidic system, DOTA and norepinephrine (NE) modified Au@CuMOF signal probes and Fe3O4@SiO2 capture probes were used for the dual recognition and capture of rare PCC-CTCs. Then, the targeted binding of the Au@CuMOF cascade nanozymes to the CTCs endowed the cellular complexes with multienzyme mimetic activities (i.e., glucose oxidase-like and peroxidase-like activity) to catalyze glucose reduction as signal output for colorimetric and personal glucose meter (PGM) dual-mode detection of CTCs. The developed method has a linear range of 4 to 105 cells mL-1 and a detection limit of 3 cells mL-1. This method allows the simultaneous detection of six samples and demonstrates good applicability for CTCs detection in whole blood samples. More importantly, the combination of PGM, smartphone app and array microfluidic chips enables the rapid, portable, and high-throughput diagnoses of PCC, and providing provide a convenient and reliable alternative to traditional liquid biopsy diagnosis of various cancers.

Cirrhotic hepatocellular carcinoma-based decellularized liver cancer model for local chemoembolization evaluation.

Transarterial chemoembolization (TACE) is a common treatment for unresectable intermediate stage hepatocellular carcinoma (HCC) and involves the combination of chemotherapy agents and embolic materials to target and block the blood supply to the tumor, leading to localized treatment. However, the selection of clinical chemoembolization agents remains limited, and the effectiveness of various agents is still under investigation. Meanwhile, replicating the complex vasculature and extracellular matrix (ECM) circumstances of HCC in in vitro models for evaluating embolic agents proves to be challenging. Herein, we developed a decellularized cancerous liver model with translucent appearance, a complicated hepatic vascular system and tissue-specific ECM for the evaluation of embolic agents. Inkpad oil and microparticles were used to illustrate different systems of vascular structures between healthy and HCC rats' livers. Quantitative analysis with AngioTool revealed significant differences in vessel density and lacunarity between the two groups. Proteomics showed higher secretion of collagens in the HCC rat liver models than in healthy livers. Utilizing this in vitro model, we investigated the impact of tumor-specific vascular structure and ECM composition on chemoembolization performance, the two key factors inaccessible by currently available drug release testing platforms. Our findings revealed that the presence of an aberrant vascular system and the distorted ECM within the model led to drug retention. This preclinical model holds great promise as a valuable tool for evaluating embolic agents and studying their performance in the tumor microenvironment. STATEMENT OF SIGNIFICANCE: Transarterial chemoembolization (TACE), which employs drug-eluting embolic agents to obstruct the tumor-feeding vessels while locally releasing chemotherapeutic drugs into the tumor, has become the first-line treatment of unresectable liver cancer over past two decades. Nevertheless, the advancement of effective drug-eluting embolic agents has been retarded due to the lack of appropriate in vitro models for assessing the local embolization and chemotherapy performances in TACE. Here we developed a cirrhotic hepatocellular carcinoma-based decellularized liver cancer model, which preserves the aberrant vasculatures and tumor-specific extracellular matrix of liver cancer, for TACE evaluation. This model incorporates a blood flow simulation component to assess the dynamics of drug release behaviors of chemoembolic agents within tumor-mimicking conditions, more accurately replicating the in vivo environment for the locoregional assessments as compared to conventional in vitro models.

Identification of the expression patterns and potential prognostic role of m6A-RNA methylation regulators in Wilms Tumor.

BACKGROUND: To explore the potential role of m6A methylation modification in Wilms Tumor (WT) by m6A-RNA Methylation (m6A) regulators. METHODOLOGY: The association of m6A modification patterns with immune and prognostic characteristics of tumors was systematically evaluated using 19 m6A regulators extracted from Wilms Tumor's samples in public databases. A comprehensive model of "m6Ascore" was constructed using principal component analysis, and its prognostic value was evaluated. RESULTS: Almost all m6A regulators were differentially expressed between WT and normal tissues. Unsupervised clustering identified three distinct m6A clusters that differed in both immune cell infiltration and biological pathways. The m6Ascore was constructed to quantify m6A modifications in individual patients. Our analysis suggests that m6Ascore is an independent prognostic factor for WT and can be used as a novel predictor of WT prognosis. CONCLUSIONS: This study comprehensively explored and systematically characterized m6A modifications in WT. m6A modification patterns play a critical role in the tumor immune microenvironment (TIME) and WT prognosis. m6Ascore provides a more comprehensive understanding of m6A modifications in WT and offers a practical tool for predicting WT prognosis. This study will help clinicians to identify valid indicators of WT to improve the poor prognosis of this disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://www.aliyundrive.com/drive/folder/64be739cd6956a741fb24670baeea53422be6024 .

Electrocoalescence Behavior of Droplets Dispersed with Na2CO3 in Oil under the Electromagnetic Synergy Field.

Electromagnetic synergy is a more effective physical method than a single AC electric field (ACEF) to enhance oil-water separation. However, the electrocoalescence behavior of droplets dispersed with salt ions in oil under the synergistic electromagnetic field (EMSF) still lacks research. Herein, the evolution coefficient of liquid bridge diameter (C1) characterizes the growth rate of the liquid bridge diameter, a series of Na2CO3-dispersed droplets with different ionic strengths were prepared, and C1 values of droplets under ACEF and EMSF were compared. Micro high-speed experiments revealed that C1 under ACEF is larger than C1 under EMSF. In particular, when σ = 100 µS·cm-1and E = 629.73 kV·m-1, C1 under the ACEF is 15% larger than C1 under EMSF. Additionally, the theory of ion enrichment is put forward, which explains the influence of salt ions on ζ potential and total surface potential in EMSF. This study provides guidance for designing high-performance devices by introducing electromagnetic synergy in water-in-oil emulsion treatment.

Near Infrared-Absorbing Nanoparticle-Mediated Endovascular Photothermal Precision Embolization of Tumor Feeding Vessels for Starvation Treatment.

Photothermal therapy has attracted enormous attention as an efficient treatment modality in cancer ablation but still encounters a major bottleneck due to the limited penetration depth of light inside tissues. To overcome the challenge of deep tissue penetration, we present a strategy of endovascular photothermal precision embolization (EPPE), which employs an endovascular optical fiber to induce local embolization only in the entrance of feeding vessels through photothermal heating for the purpose of fully blocking the blood supply of the whole tumor. In EPPE, we apply a highly efficient and biocompatible photothermal agent, i.e., near-infrared (NIR)-light-absorbing diketopyrrolopyrrole-dithiophene-based nanoparticle, which exhibits a high cell-killing efficacy at a concentration of 200 µg/mL using 808 nm laser irradiation of 0.5 W/cm2 within 5 min in both 2D cell culture and a 3D tumor spheroid model. We verify the feasibility of EPPE in an ex vivo organ-structured recellularized liver model and further confirm the in vivo efficacy of the photothermal treatment in a rat liver model. The photothermal treatment combined with the embolization effect holds promise to serve as an effective starvation therapy to treat tumors of varying sizes and locations.

A 3D Tumor-Mimicking In Vitro Drug Release Model of Locoregional Chemoembolization Using Deep Learning-Based Quantitative Analyses.

Primary liver cancer, with the predominant form as hepatocellular carcinoma (HCC), remains a worldwide health problem due to its aggressive and lethal nature. Transarterial chemoembolization, the first-line treatment option of unresectable HCC that employs drug-loaded embolic agents to occlude tumor-feeding arteries and concomitantly delivers chemotherapeutic drugs into the tumor, is still under fierce debate in terms of the treatment parameters. The models that can produce in-depth knowledge of the overall intratumoral drug release behavior are lacking. This study engineers a 3D tumor-mimicking drug release model, which successfully overcomes the substantial limitations of conventional in vitro models through utilizing decellularized liver organ as a drug-testing platform that uniquely incorporates three key features, i.e., complex vasculature systems, drug-diffusible electronegative extracellular matrix, and controlled drug depletion. This drug release model combining with deep learning-based computational analyses for the first time permits quantitative evaluation of all important parameters associated with locoregional drug release, including endovascular embolization distribution, intravascular drug retention, and extravascular drug diffusion, and establishes long-term in vitro-in vivo correlations with in-human results up to 80 d. This model offers a versatile platform incorporating both tumor-specific drug diffusion and elimination settings for quantitative evaluation of spatiotemporal drug release kinetics within solid tumors.

Engineering orthotopic tumor spheroids with organ-specific vasculatures for local chemoembolization evaluation.

Developing a three-dimensional (3D) in vitro tumor model with vasculature systems suitable for testing endovascular interventional therapies remains a challenge. Here we develop an orthotopic liver tumor spheroid model that captures the organ-level complexity of vasculature systems and the extracellular matrix to evaluate transcatheter arterial chemoembolization (TACE) treatment. The orthotopic tumor spheroids are derived by seeding HepG2 cell colonies with controlled size and location surrounding the portal triads in a decellularized rat liver matrix and are treated by clinically relevant drug-eluting beads embolized in a portal vein vasculature while maintaining dynamic physiological conditions with nutrient and oxygen supplies through the hepatic vein vasculature. The orthotopic tumor model exhibits strong drug retention inside the spheroids and embolization location-dependent cellular apoptosis responses in an analogous manner to in vivo conditions. Such a tumor spheroid model built in a decellularized scaffold containing organ-specific vasculatures, which closely resembles the unique tumor microenvironment, holds the promise to efficiently assess various diagnostic and therapeutic strategies for endovascular therapies.

Molecular characterization of hexokinase (HK) in Haemaphysalis longicornis and evaluation of HK protein- and DNA-based vaccines against adult ticks.

BACKGROUND: Haemaphysalis longicornis is an obligate hematophagous ectoparasite, which transmits various pathogens to humans, livestock and wild animals. Hexokinase (HK) is a key regulatory enzyme of the glycolytic pathway in the organisms. However, little is known about hexokinase and its functions in ticks. RESULTS: The open reading frame of the H. longicornis HK (HlHK) gene was 1425 bp and encoded a protein of 474 amino acids, containing conserved domains for glucose, glucose 6-phosphate, and adenosine triphosphate. The expression of HlHK gene was detected at different developmental stages and in different tissues of unfed female ticks. Enzyme-linked immunosorbent assay revealed that both HK protein- and DNA-based vaccines increased the antibody levels of the immunized animals. A vaccination trail on rabbits against H. longicornis infestation indicated that the rHlHK protein and HlHK DNA vaccines reduced the number of attached female ticks by 9% and 12%, egg mass weight by 36% and 34%, and egg hatching rate by 41% and 17%, respectively. Overall, protein vaccination conferred 65.6% protection against adult female ticks, whereas the DNA vaccine conferred 51.8% protection. CONCLUSION: This is the first report of the molecular characterization of the HK protein and sequencing of the HK gene from H. longicornis. Positive results from vaccination trials on rabbits of the recombinant HK protein and HK DNA suggest that these novel anti-tick vaccines potentially can be used as viable tick control tools for the management of the Asian longhorned tick. Additionally, inhibition of glucose metabolism may be a new strategy for tick control. © 2023 Society of Chemical Industry.

miR-449a ameliorates acute rejection after liver transplantation via targeting procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 in macrophages.

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.

Accurate detection of lung cancer-related microRNA through CRISPR/Cas9-assisted garland rolling circle amplification.

Background: MicroRNA (miRNA) is reported to be closely related to a variety of pathophysiological processes for carcinoma and considered a potential biomarker for the diagnosis of lung cancer with brain metastasis. However, developing an accurate and sensitive miRNA detection method has proven to be a challenge. The aim of the present study was to integrate the advantages of rolling circle amplification (RCA), clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nucleases 9 (Cas9), and catalytic hairpin assembly (CHA) technologies to develop an miRNA detection method. Methods: In the present study, we developed a novel approach for the sensitive and accurate detection of miRNA through integrating garland RCA and CRISPR/Cas9-assisted signal generation. In this method, target miRNA cyclized dumbbell padlock and triggered the RCA process to form long single-stranded DNA products with a repeated hairpin structure. Double-stranded DNA sequences (dsDNA) were formed with the addition of complementary sequences. With the assistance of the Cas9 enzyme for specific recognition and cleavage of formed dsDNA, RCA products were disassembled into hairpin probes. The generated hairpin probe could be unfolded by target miRNA to initiate the CHA process for signal generation. Results: Through integration of the RCA and CHA processes, the method demonstrated favorable detection performance. The correlation equation between the signal and concentration of target miRNA was determined to be Y=312.3 × lgC + 2108, with a high correlation coefficient of 0.9786. The approach also exhibited high selectivity to the mismatched miRNAs. Conclusions: Our method could be used in the screening, diagnosis, and prognosis of multiple diseases without complicated thermal cycling instrumentation.

An exploration into the application of specialty-orientated CBL pedagogy in undergraduate teaching in pediatric surgery.

Objective: This study aims to identify whether the specialty-oriented case-based learning (CBL) pedagogy contributes to the teaching of basic theory and practical operation in undergraduate clinical teaching in pediatric surgery, and to assess the satisfaction of undergraduates. Methods: A total of 72 undergraduates in Grade 2016 who interned at Qilu Hospital of Shandong University were enrolled in this study. All these undergraduates voluntarily participated in this experimental study. They were randomly divided into the experimental group (the CBL group, n = 36) and the control group [the traditional lecture-based learning (LBL) group, n = 36] with the assistance of random number tables. In the control group, a traditional pedagogy was adopted and the knowledge in the textbook was explained according to the syllabus. In the experimental group, a specialty-oriented CBL pedagogy was adopted under the guidance of clinical instructors. After the teaching, a comparison was drawn between both groups in respect of the theoretical exam and practical exam scores. In addition, the teaching results were evaluated by a questionnaire survey. Results: The average theoretical exam scores and comprehensive scores of undergraduates in the CBL group were higher than those in the LBL group (P < 0.05). There was no significant difference in the practical exam scores between the CBL group and the LBL group (P > 0.05). However, those undergraduates in the CBL group attained higher scores in doctor-patient communication and perioperative diagnosis and treatment (P < 0.05). According to the questionnaire survey, the undergraduates in the CBL group had higher satisfaction than those in the LBL group. Besides, this specialty-oriented CBL pedagogy had higher performance in improving their ability to solve problems independently and cultivating and expanding their knowledge compared with the traditional pedagogy. Meanwhile, this specialty-oriented CBL pedagogy can cultivate the critical thinking of undergraduates, which could increase their learning efficiency and improve their interest in learning. Conclusion: This specialty-oriented CBL pedagogy could improve the mastery of professional knowledge, course satisfaction, doctor-patient communication ability in clinical practice, and perioperative diagnosis and treatment ability of these undergraduates. Therefore, it is worthwhile to recommend and popularize this pedagogy in undergraduate clinical teaching in pediatric surgery.

Hypofunction of directed brain network within alpha frequency band in depressive patients: a graph-theoretic analysis.

Directed brain networks may provide new insights into exploring physiological mechanism and neuromarkers for depression. This study aims to investigate the abnormalities of directed brain networks in depressive patients. We constructed the directed brain network based on resting electroencephalogram for 19 depressive patients and 20 healthy controls with eyes closed and eyes open. The weighted directed brain connectivity was measured by partial directed coherence for α, ß, γ frequency band. Furthermore, topological parameters (clustering coefficient, characteristic path length, and et al.) were computed based on graph theory. The correlation between network metrics and clinical symptom was also examined. Depressive patients had a significantly weaker value of partial directed coherence at alpha frequency band in eyes-closed state. Clustering coefficient and characteristic path length were significantly lower in depressive patients (both p < .01). More importantly, in depressive patients, disruption of directed connectivity was noted in left-to-left (p < .05), right-to-left (p < .01) hemispheres and frontal-to-central (p < .01), parietal-to-central (p < .05), occipital-to-central (p < .05) regions. Furthermore, connectivity in LL and RL hemispheres was negatively correlated with depression scale scores (both p < .05). Depressive patients showed a more randomized network structure, disturbed directed interaction of left-to-left, right-to-left hemispheric information and between different cerebral regions. Specifically, left-to-left, right-to-left hemispheric connectivity was negatively correlated with the severity of depression. Our analysis may serve as a potential neuromarker of depression.

A Gallic Acid-Doped Polypyrrole Coating with Anticorrosion and Antibacterial Properties on Magnesium Alloy.

Magnesium (Mg) and its alloys exhibit great potential as biomedical implants due to their excellent biological performance and mechanical properties. However, their clinical applications are limited by their rapid corrosion rate in physiological media and the risk of implant-associated infections. Herein, a multifunctional polypyrrole/gallic acid (PPy/GA) coating was deposited on an AZ31 Mg alloy substrate by electrochemical polymerization to enhance simultaneously the corrosion resistance and antibacterial properties of the Mg alloy. Electrochemical and in vitro immersion tests demonstrated that the anticorrosion performance of the Mg alloy was significantly improved with the PPy/GA coating. The thiazolyl blue tetrazolium bromide (MTT) assay and live-dead staining of L929 cells indicated the acceptable cytocompatibility of the PPy/GA coating. In vitro antibacterial tests revealed a remarkable enhancement in the antibacterial activity of the PPy/GA-coated Mg alloy compared with the PPy-coated material and the bare Mg alloy.

Electrochemical/visual microfluidic detection with a covalent organic framework supported platinum nanozyme-based device for early diagnosis of pheochromocytoma.

The development of smart, portable, and sensitive devices for the monitoring of circulating tumor cells (CTCs) is essential to diagnose several diseases, including pheochromocytoma (PCC). Therefore, in this study, a dual-mode (electrochemical/visual) microfluidic device was designed for the rapid and sensitive detection of PCC-CTCs using a microfluidic chip for automatic cell sampling and detection and a smartphone-based three-dimensional-printed accessory for signal output analysis. The device was employed to capture and identify PCC-CTCs via specific immunogenic binding to the norepinephrine transporter and somatostatin receptor, which are overexpressed on the surface of PCC cells. Specifically, targeted-modified magnetic particles were used to capture and separate PCC-CTCs from peripheral blood; then, similarly modified covalent organic framework based nanozymes (COF@Pt) were used as peroxidase mimics to amplify the electrochemical response from H2O2 reduction and catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine by hydroxyl radicals in the presence of the PCC cells to enable visual quantification. Using the prepared microfluidic device, a low detection limit of 1 cell mL-1 at a signal-to-noise ratio of 3 and a wide linear range of 2 to 105 cells mL-1 were achieved. Overall, this work demonstrates a portable, sensitive, and visual platform for PCC diagnostics that meets the requirement for quick and precise point-of-care diagnostics.

Fabrication of dual anti-corrosive polyaniline microcapsules via Pickering emulsion for active corrosion protection of steel.

A novel kind of inhibitor-loaded polyaniline (PANI) microcapsule was prepared by Pickering emulsion photopolymerization using polyaniline particles as the Pickering emulsifier. In our strategy, water-dispersible polyaniline nanoparticles were firstly synthesized using a micelle template method and used to stabilize oil-in-water emulsions, in which the oil phase contained photo-crosslinkable and pH sensitive monomers and a photo-initiator. Under UV light, the pH-responsive monomers underwent photo-polymerization and crosslinking and converted to microcapsule shells. During this process, polyaniline nanoparticles were trapped in the microcapsule shells, leading to the formation of PANI microcapsules. The structure and morphology of the synthesized PANI microcapsules were analyzed using FTIR spectroscopy, SEM, and EDX mapping. The inhibitor (mercaptobenzothiazole, MBT) was subsequently incorporated into the PANI microcapsule as a functional core and demonstrated pH-sensitive releasing behavior. With the anti-corrosive PANI as the microcapsule wall and the inhibitor MBT as the core, the as-prepared MBT loaded PANI (MBT@PANI) microcapsule could afford dual corrosion protection, allowing smart protection of metals when exposed to corrosive conditions. The MBT@PANI microcapsules were embedded in UV-cured coating for protecting steel. The corrosion protection performance of the coating with MBT@PANI microcapsules was evaluated using the electrochemical impedance spectroscopy technique and salt spray test, which demonstrated the synergistic inhibition effect of the PANI wall and the loaded MBT in improving anti-corrosion performance of the coating.

A Versatile Platform for Sensitive and Label-Free Identification of Biomarkers through an Exo-III-Assisted Cascade Signal Amplification Strategy.

The development of a versatile and sensitive analytical biomarker detection platform is important for both early diagnosis and treatment of diseases. In the present study, we propose a novel fluorescence-based, ultrasensitive, and label-free biomarker detection platform. This platform relies on a flexible probe design compatible for multiple biomarker identification and Exo-III enzyme-triggered cascade signal amplification. We have validated that this label-free platform exhibits high sensitivity and specificity. Indeed, this platform exhibited brilliant analytical performance in qualifying a carcinoembryonic antigen and small extracellular vesicles (sEVs). It also shows excellent capability in multiplexing mapping of surface proteins of various cancer-derived sEVs. Therefore, we believe that the proposed sensing platform has great potential for clinical diagnosis and anticancer drug development.

Generative Adversarial Training with Dual-Attention for Vascular Segmentation and Topological Analysis.

The vascular topology is of vital importance in building a chemotherapy model for the liver cancer in rats. And segmentation of vessels in the liver is an indispensable part of vessels' topological analysis. In this paper, we proposed and validated a novel pipeline for segmenting liver vessels and extracting their skeletons for topological analysis. We employed a dual-attention based U-Net trained in a generative adversarial network (GAN) fashion to obtain precise segmentations of vessels. For subsequent topological analysis, the vessels' skeletons are extracted and classified according to their lengths and bifurcation orders. Based on 40 samples with carefully-annotated ground truth labels, our experiments revealed consistent superiority in terms of both segmentation accuracy and topology correctness, demonstrating the robustness of the proposed pipeline.

Visualization and Evaluation of Chemoembolization on a 3D Decellularized Organ Scaffold.

Transarterial chemoembolization (TACE) has emerged as the mainstay treatment for patients suffering from unresectable intermediate hepatocellular carcinoma and also holds the potential to treat other types of hypervascular cancers such as renal cell carcinoma. However, an in vitro model for evaluating both embolic performance and drug-release kinetics of the TACE embolic agents is still lacking since the current models greatly simplified the in vivo vascular systems as well as the extracellular matrices (ECM) in the organs. Here, we developed a decellularized organ model with preserved ECM and vasculatures as well as a translucent appearance to investigate chemoembolization performances of a clinically widely used embolic agent, i.e., a doxorubicin-loaded ethiodised oil (EO)-based emulsion. We, for the first time, utilized an ex vivo model to evaluate the liquid-based embolic agent in two organs, i.e., liver and kidneys. We found that the EO-based emulsion with enhanced stability by incorporating an emulsifier, i.e., hydrogenated castor oil-40 (HCO), showed an enhanced occlusion level and presented sustained drug release in the ex vivo liver model, suggesting an advantageous therapeutic effect for TACE treatment of hepatocellular carcinoma. In contrast, we observed that drug-release burst happened when applying the same therapy in the kidney model even with the HCO emulsifier, which may be explained by the presence of the specific renal vasculature and calyceal systems, indicating an unfavorable effect in the renal tumor treatment. Such an ex vivo model presents a promising template for chemoembolization evaluation before in vivo experiments for the development of novel embolic agents.