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Huperzine A (Hup A), an extract from Huperzia serrata, exerted its anti-inflammation and anti-oxidation effect to protect against neurodegenerative disorders and organ injury. Ferroptosis was indicated to involve in the development of acute lung injury (ALI) accompanying by lipid reactive oxygen species (ROS) overexpressed. However, there is little research focused on the protective effect of Hup A on ALI, and the underlying molecular mechanism remains elusive. This study aims to determine the therapeutic effect of Hup A on ALI in vivo and in vitro. Hup A attenuated lung injury and cellular damage in lipopolysaccharide-induced ALI (LPS-ALI) models, both in vivo and in vitro, accompanied by the upregulation of ferroptosis-associated proteins (SLC7A11 and GPX4). Furthermore, the pretreatment with Hup A decreased the abundance of inflammation factors (IL-6, TNF-α), MDA, lipid ROS, and Fe2+ in the LPS-ALI model, while it also promoted the secretion of SOD and GSH to antagonize peroxidation. Mechanistically, RNA sequencing and network pharmacological analysis synergistically revealed the PI3K/Akt signaling pathway as a potential target of Hup A. In vitro experiments demonstrated that Hup A effectively activated GPX4 through the PI3K/Akt signaling pathway, which was subsequently reversed by LY294002, an inhibitor of the PI3K/Akt signaling pathway. Consequently, our results revealed that Hup A inhibited ferroptosis in LPS-ALI by activating the PI3K-Akt signaling pathway which indicated the potential therapeutical effect of Hup A and further emphasized the pivotal role of ferroptosis in ALI.

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Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a "liquid biopsy" that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.

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Triple-negative breast cancer (TNBC) could benefit from PARP inhibitors (PARPi) for their frequent defective homologous recombination repair (HR). However, the efficacy of PARPi is limited by their lower bioavailability and high susceptibility to drug resistance, so it often needs to be combined with other treatments. Herein, polydopamine nanoparticles (PDMN) were constructed to load Olaparib (AZD) as two-channel therapeutic nanoplatforms. The PDMN has a homogeneous spherical structure around 100 nm and exhibits a good photothermal conversion efficiency of 62.4%. The obtained AZD-loaded nanoplatform (PDMN-AZD) showed enhanced antitumor effects through the combination of photothermal therapy (PTT) and PARPi. By western blot and flow cytometry, we found that PTT and PARPi could exert synergistic antitumor effects by further increasing DNA double-strand damage (DSBs) and enhancing HR defects. The strongest therapeutic effect of PDMN-AZD was observed in a BRCA-deficient mouse tumor model. In conclusion, the PDMN-AZD nanoplatform designed in this study demonstrated the effectiveness of PTT and PARPi for synergistic treatment of TNBC and preliminarily explained the mechanism.

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Objective.Electroencephalogram (EEG) signals are promising biometrics owning to their invisibility, adapting to the application scenarios with high-security requirements. However, It is challenging to explore EEG identity features without the interference of device and state differences of the subject across sessions. Existing methods treat training sessions as a single domain, affected by the different data distribution among sessions. Although most multi-source unsupervised domain adaptation (MUDA) methods bridge the domain gap between multiple source and target domains individually, relationships among the domain-invariant features of each distribution alignment are neglected.Approach.In this paper, we propose a MUDA method, Tensorized Spatial-Frequency Attention Network (TSFAN), to assist the performance of the target domain for EEG-based biometric recognition. Specifically, significant relationships of domain-invariant features are modeled via a tensorized attention mechanism. It jointly incorporates appropriate common spatial-frequency representations of pairwise source and target but also cross-source domains, without the effect of distribution discrepancy among source domains. Additionally, considering the curse of dimensionality, our TSFAN is approximately represented in Tucker format. Benefiting the low-rank Tucker Network, the TSFAN can scale linearly in the number of domains, providing us the great flexibility to extend TSFAN to the case associated with an arbitrary number of sessions.Main results.Extensive experiments on the representative benchmarks demonstrate the effectiveness of TSFAN in EEG-based biometric recognition, outperforming state-of-the-art approaches, as verified by cross-session validation.Significance.The proposed TSFAN aims to investigate the presence of consistent EEG identity features across sessions. It is achieved by utilizing a novel tensorized attention mechanism that collaborates intra-source transferable information with inter-source interactions, while remaining unaffected by domain shifts in multiple source domains. Furthermore, the electrode selection shows that EEG-based identity features across sessions are distributed across brain regions, and 20 electrodes based on 10-20 standard system are able to extract stable identity information.

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CBX7 is a key component of PRC1 complex. Cbx7C is an uncharacterized Cbx7 splicing isoform specifically expressed in mouse embryonic stem cells (mESCs). We demonstrate that CBX7C functions as an epigenetic repressor at the classic PRC1 targets in mESCs, and its preferential interaction to PHC2 facilitates PRC1 assembly. Both Cbx7C and Phc2 are significantly upregulated during cell differentiation, and knockdown of Cbx7C abolishes the differentiation of mESCs to embryoid bodies. Interestingly, CBX7C⋅PHC2 interaction at low levels efficiently undergoes the formation of functional Polycomb bodies with high mobility, whereas the coordination of the two factors at high doses results in the formation of large, low-mobility, chromatin-free aggregates. Overall, these findings uncover the unique roles and molecular basis of the CBX7C⋅PHC2 interaction in PRC1 assembly on chromatin and Pc body formation and open a new avenue of controlling PRC1 activities via modulation of its phase separation properties.

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Acute respiratory distress syndrome (ARDS), a progressive status of acute lung injury (ALI), is primarily caused by an immune-mediated inflammatory disorder, which can be an acute pulmonary complication of rheumatoid arthritis (RA). As a chronic inflammatory disease regulated by the immune system, RA is closely associated with the occurrence and progression of respiratory diseases. However, it remains elusive whether there are shared genes between the molecular mechanisms underlying RA and ARDS. The objective of this study is to identify potential shared genes for further clinical drug discovery through integrated analysis of bulk RNA sequencing datasets obtained from the Gene Expression Omnibus database, employing differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA). The hub genes were identified through the intersection of common DEGs and WGCNA-derived genes. The Random Forest (RF) and least absolute shrinkage and selection operator (LASSO) algorithms were subsequently employed to identify key shared target genes associated with two diseases. Additionally, RA immune infiltration analysis and COVID-19 single-cell transcriptome analysis revealed the correlation between these key genes and immune cells. A total of 59 shared genes were identified from the intersection of DEGs and gene clusters obtained through WGCNA, which analyzed the integrated gene matrix of ALI/ARDS and RA. The RF and LASSO algorithms were employed to screen for target genes specific to ALI/ARDS and RA, respectively. The final set of overlapping genes (FCMR, ADAM28, HK3, GRB10, UBE2J1, HPSE, DDX24, BATF, and CST7) all exhibited a strong predictive effect with an area under the curve (AUC) value greater than 0.8. Then, the immune infiltration analysis revealed a strong correlation between UBE2J1 and plasma cells in RA. Furthermore, scRNA-seq analysis demonstrated differential expression of these nine target genes primarily in T cells and NK cells, with CST7 showing a significant positive correlation specifically with NK cells. Beyond that, transcriptome sequencing was conducted on lung tissue collected from ALI mice, confirming the substantial differential expression of FCMR, HK3, UBE2J1, and BATF. This study provides unprecedented evidence linking the pathophysiological mechanisms of ALI/ARDS and RA to immune regulation, which offers novel understanding for future clinical treatment and experimental research.

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Zinc-ion batteries (ZIBs) are rapidly emerging as safe, cost-effective, nontoxic, and environmentally friendly energy storage systems. However, mildly acidic electrolytes with depleted protons cannot satisfy the huge demand for proton reactions in MnO2 electrodes and also cause several issues in ZIBs, such as rapidly decaying cycling stability and low reaction kinetics. Herein, we propose a pH-buffering strategy in which KH2PO4 is added to the electrolyte to overcome the problems caused by low proton concentrations. This strategy significantly improves the rate and cycle stability performance of zinc-manganese batteries, delivering a high capacity of 122.5 mAh/g at a high current density of 5 A/g and enabling 9000 cycles at this current density, with a remaining capacity of 70 mAh/g. Ex-situ X-ray diffraction and scanning electron microscopy analyses confirmed the generation/dissolution of Zn3PO4·4H2O and Zn4(OH)6(SO4)·5H2O, byproducts of buffer products and proton reactions. In-situ pH measurements and chemical titration revealed that the pH change during the electrochemical process can be adjusted to a low range of 2.2-2.8, and the phosphate distribution varies with the pH range. Those results reveal that H2PO4- provides protons to the cathode through the chemical balance of HPO42-, HPO42-, and Zn3PO4·4H2O. This study serves as a guide for studying the influences and mechanisms of buffering additives in Zn-MnO2 batteries.

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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a profoundly aggressive and fatal cancer. One of the key factors defining its aggressiveness and resilience against chemotherapy is the existence of cancer stem cells (CSCs). The important task of discovering upstream regulators of stemness that are amenable for targeting in PDAC is essential for the advancement of more potent therapeutic approaches. In this study, we sought to elucidate the function of the nuclear receptor subfamily 5, group A, member 2 (NR5A2) in the context of pancreatic CSCs. METHODS: We modeled human PDAC using primary PDAC cells and CSC-enriched sphere cultures. NR5A2 was genetically silenced or inhibited with Cpd3. Assays included RNA-seq, sphere/colony formation, cell viability/toxicity, real-time PCR, western blot, immunofluorescence, ChIP, CUT&Tag, XF Analysis, lactate production, and in vivo tumorigenicity assays. PDAC models from 18 patients were treated with Cpd3-loaded nanocarriers. RESULTS: Our findings demonstrate that NR5A2 plays a dual role in PDAC. In differentiated cancer cells, NR5A2 promotes cell proliferation by inhibiting CDKN1A. On the other hand, in the CSC population, NR5A2 enhances stemness by upregulating SOX2 through direct binding to its promotor/enhancer region. Additionally, NR5A2 suppresses MYC, leading to the activation of the mitochondrial biogenesis factor PPARGC1A and a shift in metabolism towards oxidative phosphorylation, which is a crucial feature of stemness in PDAC. Importantly, our study shows that the specific NR5A2 inhibitor, Cpd3, sensitizes a significant fraction of PDAC models derived from 18 patients to standard chemotherapy. This treatment approach results in durable remissions and long-term survival. Furthermore, we demonstrate that the expression levels of NR5A2/SOX2 can predict the response to treatment. CONCLUSIONS: The findings of our study highlight the cell context-dependent effects of NR5A2 in PDAC. We have identified a novel pharmacological strategy to modulate SOX2 and MYC levels, which disrupts stemness and prevents relapse in this deadly disease. These insights provide valuable information for the development of targeted therapies for PDAC, offering new hope for improved patient outcomes. A Schematic illustration of the role of NR5A2 in cancer stem cells versus differentiated cancer cells, along with the action of the NR5A2 inhibitor Cpd3. B Overall survival of tumor-bearing mice following allocated treatment. A total of 18 PDX models were treated using a 2 x 1 x 1 approach (two animals per model per treatment); n=36 per group (illustration created with biorender.com ).

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Bladder cancer (BC) is a common form of urinary tract tumor, and its incidence is increasing annually. Unfortunately, an increasing number of newly diagnosed BC patients are found to have advanced or metastatic BC. Although current treatment options for BC are diverse and standardized, it is still challenging to achieve ideal curative results. However, Sulforaphane, an isothiocyanate present in cruciferous plants, has emerged as a promising anticancer agent that has shown significant efficacy against various cancers, including bladder cancer. Recent studies have demonstrated that Sulforaphane not only induces apoptosis and cell cycle arrest in BC cells, but also inhibits the growth, invasion, and metastasis of BC cells. Additionally, it can inhibit BC gluconeogenesis and demonstrate definite effects when combined with chemotherapeutic drugs/carcinogens. Sulforaphane has also been found to exert anticancer activity and inhibit bladder cancer stem cells by mediating multiple pathways in BC, including phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), nuclear factor kappa-B (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), zonula occludens-1 (ZO-1)/beta-catenin (ß-Catenin), miR-124/cytokines interleukin-6 receptor (IL-6R)/transcription 3 (STAT3). This article provides a comprehensive review of the current evidence and molecular mechanisms of Sulforaphane against BC. Furthermore, we explore the effects of Sulforaphane on potential risk factors for BC, such as bladder outlet obstruction, and investigate the possible targets of Sulforaphane against BC using network pharmacological analysis. This review is expected to provide a new theoretical basis for future research and the development of new drugs to treat BC.

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BACKGROUND: Thyroid nodules are increasingly treated with minimally invasive surgery. Thermal ablation could efficiently treat patients with benign thyroid nodules, recurrent thyroid cancer, and low-risk papillary thyroid carcinoma. This research aims to explore the research field of thermal ablation for thyroid nodules using bibliometric analysis. METHODS: The web of science core collection (WoSCC) database was utilized from its inception to 1 October 2022, to collect research articles and reviews on ultrasound-guided thermal ablation for thyroid nodules. We applied the R package 'bibliometrix' to summarize the main findings, calculate the occurrences of the top keywords and visualize the international collaboration networks. The co-authorship and co-occurrence analyses were conducted with VOSviewer software. CiteSpace was used to identify the top references and keywords with the highest citation bursts. RESULTS: A total of 820 publications from 32 countries were retrieved. The annual number of related publications showed an increasing trend. China, Italy, and Korea were the most contributing countries. The University of Ulsan College of Medicine in Korea was the most productive institution, and Jung Hwan Baek published the maximum number of articles. The International Journal of Hyperthermia was the most productive journal. 'Papillary thyroid micro-carcinoma (PTMC)' and 'association guideline' were the most frequently used keywords in the field of thermal ablation for thyroid nodules, which indicated the potential hot research topics and frontiers in the future. CONCLUSION: This bibliometric study conducts a comprehensive analysis of publications on thermal ablation for thyroid nodules, which aids investigators in discovering potential research directions.

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The enriched collagens in the extracellular matrix (ECM) of breast cancer substantially impede drug delivery. Halofuginone (HF), a potent antifibrotic agent, was effective to deplete the collagens and remodel the ECM by inhibiting the TGFß pathway. However, the application of HF was hindered by its strong liver toxicity. Herein, mesoporous platinum (mPt) nanoparticles were constructed to load HF as theranostic nanoplatforms. mPt had a uniform spherical structure with a diameter of 79.83 ± 6.97 nm and an average pore diameter of 20 nm and exhibited good photothermal conversion efficiency of 62.4%. The obtained HF-loaded nanoplatform (PEG@mPt-HF) showed enhanced cytotoxicity through the combination of photothermal therapy and the anti-TGFß effect induced by HF. The animal imaging and histochemical assays confirmed the PEG@mPt-HF could efficiently deliver HF to tumors (monitored by CT) and remodel the ECM by TGFß pathway inhibition, which resulted in increased anti-cancer efficacy. Importantly, the liver toxicity observed in HF-treated mice was negligible in those treated by PEG@mPt-HF. Overall, this study designed a theranostic nanoplatform to remodel the ECM with remarkably reduced systematic toxicity and enhance the therapeutic efficacy through combination treatment.

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Pancreatic cancer is one of the most lethal cancers, mostly due to late diagnosis and limited treatment options. Early detection of pancreatic cancer in high-risk populations bears the potential to greatly improve outcomes, but current screening approaches remain of limited value despite recent technological advances. This review explores the possible advantages of liquid biopsies for this application, particularly focusing on circulating tumour cells (CTCs) and their subsequent single-cell omics analysis. Originating from both primary and metastatic tumour sites, CTCs provide important information for diagnosis, prognosis and tailoring of treatment strategies. Notably, CTCs have even been detected in the blood of subjects with pancreatic precursor lesions, suggesting their suitability as a non-invasive tool for the early detection of malignant transformation in the pancreas. As intact cells, CTCs offer comprehensive genomic, transcriptomic, epigenetic and proteomic information that can be explored using rapidly developing techniques for analysing individual cells at the molecular level. Studying CTCs during serial sampling and at single-cell resolution will help to dissect tumour heterogeneity for individual patients and among different patients, providing new insights into cancer evolution during disease progression and in response to treatment. Using CTCs for non-invasive tracking of cancer features, including stemness, metastatic potential and expression of immune targets, provides important and readily accessible molecular insights. Finally, the emerging technology of ex vivo culturing of CTCs could create new opportunities to study the functionality of individual cancers at any stage and develop personalised and more effective treatment approaches for this lethal disease.

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Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

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Objective To investigate the influencing factors and establish a model predicting the performance of needle visualization in fine-needle aspiration (FNA) of thyroid nodules. Methods This study prospectively included 175 patients who underwent FNA of thyroid nodules in the Department of Ultrasound in China-Japan Friendship Hospital and compared the display of the needle tips in the examination of 199 thyroid nodules before and after the application of needle visualization.We recorded the location,the positional relationship with thyroid capsule,ultrasonic characteristics,and the distribution of the soft tissue strip structure at the puncture site of the nodules with unclear needle tips display before using needle visualization.Furthermore,according to the thyroid imaging reporting and data system proposed by the American College of Radiology,we graded the risk of the nodules.Lasso-Logistic regression was employed to screen out the factors influencing the performance of needle visualization and establish a nomogram for prediction. Results The needle tips were not clearly displayed in the examination of 135 (67.8%) and 53 (26.6%) nodules before and after the application of needle visualization,respectively,which showed a significant difference (P<0.001).Based on the positional relationship between the nodule and capsule,anteroposterior/transverse diameter (A/T) ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site,a nomogram was established to predict the probability of unclear display of the needle tips after application of needle visualization.The C-index of the prediction model was 0.75 (95%CI=0.67-0.84) and the area under the receiver operating characteristic curve was 0.72.The calibration curve confirmed the appreciable reliability of the prediction model,with the C-index of 0.70 in internal validation. Conclusions Needle visualization can improve the display of the needle tip in ultrasound-guided FNA of thyroid nodules.The nomogram established based on ultrasound features such as the positional relationship between the nodule and capsule,A/T ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site can predict whether needle visualization is suitable for the examination of nodules.

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Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease. In this study, we generated an induced pluripotent stem cell (iPSC) line from the dermal fibroblasts of a 69-year-old female patient carrying APOEε3/ε4 allele and diagnosed with sporadic AD. The iPSC line will be a useful tool for investigating the pathogenesis mechanisms and for drug tests in AD.

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In recent years, emotion recognition using physiological signals has become a popular research topic. Physiological signal can reflect the real emotional state for individual which is widely applied to emotion recognition. Multimodal signals provide more discriminative information compared with single modal which arose the interest of related researchers. However, current studies on multimodal emotion recognition normally adopt one-stage fusion method which results in the overlook of cross-modal interaction. To solve this problem, we proposed a multi-stage multimodal dynamical fusion network (MSMDFN). Through the MSMDFN, the joint representation based on cross-modal correlation is obtained. Initially, the latent and essential interactions among various features extracted independently from multiple modalities are explored based on specific manner. Subsequently, the multi-stage fusion network is designed to split the fusion procedure into multi-stages using the correlation observed before. This allows us to exploit much more fine-grained unimodal, bimodal and trimodal intercorrelations. For evaluation, the MSMDFN was verified on multimodal benchmark DEAP. The experiments indicate that our method outperforms the related one-stage multi-modal emotion recognition works.

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Background: To report the occurrence of abdominal symptoms in patients who presented with prolonged heterogeneous liver enhancement (PHLE) after injecting contrast agent SonoVue®. Methods: A total of 105 patients who indicated to have contrast-enhanced ultrasound (CEUS) examinations were consecutively observed. The liver scanning under ultrasound was performed before and after the contrast agent injection. Patients' basic information, clinical manifestations, and ultrasound images under B-mode and CEUS mode were respectively recorded. For patients exhibiting abdominal symptoms, the occurrence and last time of symptoms were recorded in detail. We subsequently compared the difference in clinical characteristics between patients with and without the PHLE phenomenon. Results: In 20 patients with the PHLE phenomenon, 13 showed abdominal symptoms. Eight patients (61.5%) appeared to have mild defecation sensation, and 5 (38.5%) showed apparent abdominal pain. The PHLE phenomenon began to appear within 15 minutes to 1.5 hours after the intravenous injection of SonoVue®. This phenomenon lasted for 30 minutes to 5 hours in ultrasound. Patients with severe abdominal symptoms showed large-area and diffuse PHLE patterns. Only sparse hyperechoic spots in the liver were detected in patients with mild discomfort. Abdominal discomfort resolved spontaneously in all patients. Meanwhile, the PHLE gradually disappeared without any medical treatment. In the PHLE-positive group, the proportion of patients with a history of gastrointestinal disease was significantly higher (P=0.02). Conclusions: Patients with the PHLE phenomenon can exhibit abdominal symptoms. We suggest gastrointestinal disorders may contribute to PHLE, which can be considered a harmless phenomenon that does not affect the safety profile of SonoVue®.

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Background: Accurate diagnosis of highly aggressive papillary thyroid cancer (PTC) may greatly help avoid overdiagnosis and overtreatment of PTC. However, there is still a lack of a convenient and accurate method. Targeted microbubbles, an emerging ultrasound contrast agent, have the potential to accurately diagnose highly aggressive PTC. Purpose: To design and prepare a targeted microbubble for specific contrast-enhanced ultrasound (CEUS) imaging of highly invasive PTC. Methods: Using ß-galactoside-binding protein galectin-3 (Gal-3) overexpressed on the surface of highly invasive PTC cells as a target, C12 polypeptide (ANTPCGPYTHDCPVKR) with high affinity and specificity for Gal-3 was coupled to the surface of lipid microbubbles to prepare targeted microbubbles (Gal-3-C12@lipo MBs). The targeted microbubbles were prepared by thin-film hydration method and mechanical shaking method. The morphology, diameter, concentration and stability of microbubbles were investigated by fluorescence microscopy and an AccuSizer. The biosafety of microbubbles was studied using BCPAP cells through CCK8 assay. Confocal laser scanning microscope and flow cytometry were applied to research the cellular uptake of microbubbles to investigate the targeting ability to highly aggressive PTC. Finally, the specific contrast-enhanced ultrasound imaging of microbubbles in highly invasive PTC was validated on the mice bearing subcutaneous BCPAP tumor model via a clinically ultrasound imaging system. Results: Gal-3-C12@lipo MBs were successfully prepared which showed a well-defined spherical morphology with an average diameter of 1.598 ± 0.848 µm. Gal-3-C12@lipo MBs showed good stability without rupture within 4 hours after preparation. At the cellular level, Gal-3-C12@lipo MBs exhibited favorable biosafety and superior targeting ability to BCPAP cells, with 2.8-fold higher cellular uptake than non-targeted lipid microbubbles (Lipo MBs). At the animal level, Gal-3-C12@lipo MBs significantly improved the quality of contrast-enhanced ultrasound imaging in highly invasive PTC, with an echo intensity of tumor significantly higher than that of Lipo MBs. Conclusion: We designed and fabricated a novel targeted microbubble for the specific ultrasound imaging diagnosis of highly aggressive PTC. The targeted microbubbles have good stability, superior biosafety and high targeting specificity, which can significantly improve the tumor signal-to-noise ratio of highly invasive PTC, and have the potential to facilitate and accurately diagnose highly invasive PTC.

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Pancreatic cancer is a lethal condition with a rising incidence and often presents at an advanced stage, contributing to abysmal five-year survival rates. Unspecific symptoms and the current lack of biomarkers and screening tools hamper early diagnosis. New technologies for liquid biopsies and their respective evaluation in pancreatic cancer patients have emerged over recent years. The term liquid biopsy summarizes the sampling and analysis of circulating tumor cells (CTCs), small extracellular vesicles (sEVs), and tumor DNA (ctDNA) from body fluids. The major advantages of liquid biopsies rely on their minimal invasiveness and repeatability, allowing serial sampling for dynamic insights to aid diagnosis, particularly early detection, risk stratification, and precision medicine in pancreatic cancer. However, liquid biopsies have not yet developed into a new pillar for clinicians' routine armamentarium. Here, we summarize recent findings on the use of liquid biopsy in pancreatic cancer patients. We discuss current challenges and future perspectives of this potentially powerful alternative to conventional tissue biopsies.

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