Mice Hepatic Organoids for Modeling Nonalcoholic Fatty Liver Disease and Drug Response.

Nonalcoholic fatty liver disease (NAFLD) is a serious disease. There are no specific drugs for it, in part because of the lack of effective models to aid drug development. However, it has been shown that three-dimensional organoid culture systems can reproduce the organ structure and maintain the gene expression profile of the original tissue. Therefore, we aimed to construct NAFLD models from liver organoids for pharmacological and mechanism studies. We successfully observed morphological changes in normal liver tissue in mouse liver organoids with positive albumin (ALB) expression and potential for differentiation toward hepatocyte-like cells. The mRNA expression of the hepatocyte markers ALB and hepatocyte nuclear factor 4 alpha increased after liver organoid differentiation. We observed free fatty acid (FFA)-induced lipid accumulation in organoids with significant increases in alanine aminotransferase, aspartate aminotransferase, total bilirubin, and triglyceride levels. Moreover, FFA-induced inflammatory cytokines (interleukin-6, tumor necrosis factor-α, and nitric oxide) and fibrosis indicators (collagen type I α1 and laminin α1) were also increased. In addition, RNA sequencing results showed that the expression of key genes [nucleotide oligomerization domain-like receptor (NLR) family apoptosis inhibitory protein, interferon regulatory factor (IRF) 3, and IRF7] involved in NAFLD metabolic abnormalities and insulin resistance in the NLR signaling pathway was altered after FFA induction of the liver organoids. Finally, we found that JC2-11 and lanifibranor limited the FFA-induced increase in oil-red lipid droplets, liver damage, inflammation, and liver fibrosis. In conclusion, tissue structure, gene expression, and the response of mouse liver organoids to drugs can partially mimic in vivo liver tissue. Liver organoids can successfully construct NAFLD models for drug discovery research.

U-type soft tissue lifting: A new composited technique for reversing lower eyelid and midfacial aging.

BACKGROUND: Facial rejuvenation is becoming more and more popular, particularly among middle-aged persons. There are currently many techniques for improving the aforementioned situations, but each has its drawbacks. Our study aimed to discuss the treatment effect of a composited technique for reversing both lower eyelid and midface aging. METHODS: The patient's face was designed and measured before surgery. During surgery, a traditional lower blepharoplasty incision was made. The layer between the orbital septum and the orbicularis oculi muscle was separated to approximately 4-5 mm below the infraorbital, then the orbital septum and orbicularis retaining ligament were found to be released. A self-made suspension curving needle subconsciously passed through the brim of the superficial cheek fat pad via the "U-type" path and raised them to the proper location. Then sutured them to the infraorbital rim periosteum, as well as the suborbicularis oculi fat (SOOF) and the orbital septum fat. Secured the outside canthus to keep the lower lid position stable. RESULTS: From February 2020 to November 2022, 106 patients underwent the new surgical procedure and were successfully followed up for 20 ± 6.5 months postoperatively. The mean GAIS score was 2.42 ± 0.78, patient satisfaction rate was 95%. All of the Barton grades were decreased. The nasal base level suspension points were elevated to a level of 5 ± 2 mm. 3D measurement data revealed significant improvements. CONCLUSIONS: The composited technique is a safe and effective way to reverse the aging of the lower eyelid and midface.

From imaging to clinical outcome: dual-region CT radiomics predicting FOXM1 expression and prognosis in hepatocellular carcinoma.

Background: Liver cancer, especially hepatocellular carcinoma (HCC), remains a significant global health challenge. Traditional prognostic indicators for HCC often fall short in providing comprehensive insights for individualized treatment. The integration of genomics and radiomics offers a promising avenue for enhancing the precision of HCC diagnosis and prognosis. Methods: From the Cancer Genome Atlas (TCGA) database, we categorized mRNA of HCC patients by Forkhead Box M1 (FOXM1) expression and performed univariate and multivariate studies to pinpoint autonomous HCC risk factors. We deployed subgroup, correlation, and interaction analyses to probe FOXM1's link with clinicopathological elements. The connection between FOXM1 and immune cells was evaluated using the CIBERSORTx database. The functions of FOXM1 were investigated through analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). After filtering through TCGA and the Cancer Imaging Archive (TCIA) database, we employed dual-region computed tomography (CT) radiomics technology to noninvasively predict the mRNA expression of FOXM1 in HCC tissues. Radiomic features were extracted from both tumoral and peritumoral regions, and a radiomics score (RS) was derived. The performance and robustness of the constructed models were evaluated using 10-fold cross-validation. A radiomics nomogram was developed by incorporating RS and clinical variables from the TCGA database. The models' discriminative abilities were assessed using metrics such as the area under the curve (AUC) of the receiver operating characteristic curves (ROC) and precision-recall (PR) curves. Results: Our findings emphasized the overexpression of FOXM1 as a determinant of poor prognosis in HCC and illustrated its impact on immune cell infiltration. After selecting arterial phase CT, we chose 7 whole-tumor features and 3 features covering both the tumor and its surroundings to create WT and WP models for FOXM1 prediction. The WT model showed strong predictive capabilities for FOXM1 expression by PR curve. Conversely, the WP model did not demonstrate the good predictive ability. In our study, the radiomics score (RS) was derived from whole-tumor regions on CT images. The RS was significantly associated with FOXM1 expression, with an AUC of 0.918 in the training cohort and 0.837 in the validation cohort. Furthermore, the RS was correlated with oxidative stress genes and was integrated with clinical variables to develop a nomogram, which demonstrated good calibration and discrimination in predicting 12-, 36-, and 60-month survival probabilities. Additionally, bioinformatics analysis revealed FOXM1's potential role in shaping the immune microenvironment, with its expression linked to immune cell infiltration. Conclusion: This study highlights the potential of integrating FOXM1 expression and radiomics in understanding HCC's complexity. Our approach offers a new perspective in utilizing radiomics for non-invasive tumor characterization and suggests its potential in providing insights into molecular profiles. Further research is needed to validate these findings and explore their clinical implications in HCC management.

CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4.

BACKGROUND: Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. METHODS: Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings. RESULTS: CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo. CONCLUSION: Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer.

Nanoparticles Mediated circROBO1 Silencing to Inhibit Hepatocellular Carcinoma Progression by Modulating miR-130a-5p/CCNT2 Axis.

Background: Circular RNAs (circRNAs) are becoming vital biomarkers and therapeutic targets for malignant tumors due to their high stability and specificity in tissues. However, biological functions of circRNAs in hepatocellular carcinoma (HCC) are still not well studied. Methods: Gene Expression Omnibus (GEO) database and qRT-PCR were used to evaluate expression of circROBO1 (hsa_circ_0066568) in HCC tissues and cell lines. CCK-8, colony formation, EdU staining, flow cytometry for cell cycle analysis, and xenograft model assays were performed to detect the circROBO1 function in vitro and in vivo. RNA pull-down, RNA immunoprecipitation (RIP), and Luciferase reporter assays were used to investigate the relationship among circROBO1, miR-130a-5p, and CCNT2. More importantly, we developed nanoparticles made from poly lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) chains as the delivery system of si-circROBO1 and then applied them to HCC in vitro and in mice. Results: circROBO1 was obviously upregulated in HCC tissues and cell lines, and elevated circROBO1 was closely correlated with worse prognosis for HCC patients. Functionally, knocking down circROBO1 significantly suppressed HCC cells growth in vitro and in mice. Mechanistically, circROBO1 acted as a competing endogenous RNA to downregulate miR-130a-5p, leading to CCNT2 expression upregulation. Furthermore, miR-130a-5p mimic or CCNT2 knockdown reversed the role of circROBO1 overexpression on HCC cells, which demonstrated that circROBO1 promoted HCC development via miR-130a-5p/CCNT2 axis. In addition, we developed nanoparticles loaded with si-circROBO1, named as PLGA-PEG (si-circROBO1) NPs, which significantly prevented the proliferation of HCC cells, and did not exhibit apparent toxicity to major organs in vivo. Conclusion: Our findings firstly demonstrate that circROBO1 overexpression promotes HCC progression by regulating miR-130a-5p/CCNT2 axis, which may serve as an effective nanotherapeutic target for HCC treatment.

Suppressing circIDE/miR-19b-3p/RBMS1 axis exhibits promoting-tumour activity through upregulating GPX4 to diminish ferroptosis in hepatocellular carcinoma.

Ferroptosis is a newly characterized form of iron-dependent non-apoptotic cell death, which is closely associated with cancer progression. However, the functions and mechanisms in regulation of escaping from ferroptosis during hepatocellular carcinoma (HCC) progression remain unknown. In this study, we reported that the RNA binding motif single stranded interacting protein 1 (RBMS1) participated in HCC development，and functioned as a regulator of ferroptosis. Clinically, the downregulation of RBMS1 occurred in HCC tissues, and low RBMS1 expression was associated with worse HCC patients survival. Mechanistically, RBMS1 overexpression inhibited HCC cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. Collectively, our findings established circIDE/miR-19b-3p/RBMS1 axis as a regulator of ferroptosis, which could be a promising therapeutic target and prognostic factor.

Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜠B-IL-6 axis of tumor-associated macrophages.

BACKGROUND: Circular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs in the tumor microenvironment (TME) remains unclear. Moreover, we also explore the effects of si-circRNAs loaded in nanoparticles as therapeutic agent for anti-tumor in vivo. METHODS: We conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell assays, co-culture system and multiple orthotopic xenograft models to investigate the expression and function of circRNAs. Additionally, PLGA-based nanoparticles loaded with si-circRNAs were used to evaluate the potential of nanotherapeutic strategy in anti-tumor response. RESULTS: We identified oncogene SERPINE2 derived circRNA, named as cSERPINE2, which was notably elevated in breast cancer and was closely related to poor clinical outcome. Functionally, tumor exosomal cSERPINE2 was shuttled to tumor associated macrophages (TAMs) and enhanced the secretion of Interleukin-6 (IL-6), leading to increased proliferation and invasion of breast cancer cells. Furthermore, IL-6 in turn increased the EIF4A3 and CCL2 levels within tumor cells in a positive feedback mechanism, further enhancing tumor cSERPINE2 biogenesis and promoting the recruitment of TAMs. More importantly, we developed a PLGA-based nanoparticle loaded with si-cSERPINE2, which effectively attenuated breast cancer progression in vivo. CONCLUSIONS: Our study illustrates a novel mechanism that tumor exosomal cSERPINE2 mediates a positive feedback loop between tumor cells and TAMs to promote cancer progression, which may serve as a promising nanotherapeutic strategy for the treatment of breast cancer.

Splicing factor SNRPA associated with microvascular invasion promotes hepatocellular carcinoma metastasis through activating NOTCH1/Snail pathway and is mediated by circSEC62/miR-625-5p axis.

Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC. SNRPA was overexpressed in MVI-HCC and correlated with poor patient survival. Mechanistically, SNRPA promoted the epithelial-mesenchymal transition (EMT)-like process for HCC cells to accelerate metastasis by activating the NOTCH1/Snail pathway in vitro and in vivo. Importantly, circSEC62 upregulated SNRPA expression in HCC cells via miR-625-5p sponging. Taking these results together, our study identified a novel regulatory mechanism among SNRPA, miR-625-5p, circSEC62 and the NOTCH1/Snail pathway in HCC, which promoted metastasis of HCC and may provide effective suggestions for improving the prognosis of HCC patients with metastasis.

The anti-alcoholism drug disulfiram effectively ameliorates ulcerative colitis through suppressing oxidative stresses-associated pyroptotic cell death and cellular inflammation in colonic cells.

BACKGROUND: Oxidative stress, cell pyroptosis and inflammation are considered as important pathogenic factors for ulcerative colitis (UC) development, and the traditional anti-alcoholism drug disulfiram (DSF) has recently been reported to exert its regulating effects on all the above cellular functions, which makes DSF as ideal therapeutic agent for UC treatment, but this issue has not been fully studied. METHODS: Dextran sulfate sodium (DSS)-induced animal models in C57BL/6J mice and lipopolysaccharide (LPS)-induced cellular models in colonic cell lines (HT-29 and Caco-2) for UC were respectively established. Cytokine secretion was determined by ELISA. Cell viability and proliferation were evaluated by MTT assay and EdU assay. Real-Time qPCR, Western Blot, immunofluorescent staining assay and immunohistochemistry (IHC) were employed to evaluate gene expressions. The correlations of the genes in the clinical tissues were analyzed by using the Pearson Correlation analysis. RESULTS: DSF restrained oxidative stress, pyroptotic cell death and cellular inflammation in UC models in vitro and in vivo, and elimination of Reactive Oxygen Species (ROS) by N-acetyl-l-cysteine (NAC) rescued cell viability in LPS-treated colonic cells (HT-29 and Caco-2). Further experiments suggested that a glycogen synthase kinase-3ß (GSK-3ß)/Nrf2/NLRP3 signaling cascade played critical role in this process. Mechanistically, DSF downregulated GSK-3ß and NLRP3, whereas upregulated Nrf2 in LPS-treated colonic cells. Also, the regulating effects of DSF on Nrf2 and NLRP3 were abrogated by upregulating GSK-3ß. Moreover, upregulation of GSK-3ß abolished the protective effects of DSF on LPS-treated colonic cells. CONCLUSIONS: Taken together, data of this study indicated that DSF restrained oxidative damages-related pyroptotic cell death and inflammation via regulating the GSK-3ß/Nrf2/NLRP3 pathway, leading to the suppression of LPS-induced UC development.

Adrenal pheochromocytoma: is it all or the tip of the iceberg?

Adrenal pheochromocytoma is not always a simple retroperitoneal tumor but may be part of a more complicated condition. It often has a spectrum of complex and variable imaging features, may present as a collision tumor and composite tumor, and is associated with a variety of clinical syndromes. A comprehensive understanding of the clinical, pathological, and variable imaging manifestations of pheochromocytoma can help radiologists make an accurate diagnosis. This article reviews various special imaging features of pheochromocytoma and pheochromocytoma-related diseases.

Icaritin Attenuates Lipid Accumulation by Increasing Energy Expenditure and Autophagy Regulated by Phosphorylating AMPK.

BACKGROUND AND AIMS: Lipid accumulation is the major characteristic of non-alcoholic fatty liver disease, the prevalence of which continues to rise. We aimed to investigate the effects and mechanisms of icaritin on lipid accumulation. METHODS: Cells were treated with icaritin at 0.7, 2.2, 6.7, or 20 µM for 24 h. The effects on lipid accumulation in L02 and Huh-7 cells were detected by Bodipy and oil red O staining, respectively. Mitochondria biogenesis of L02 cells was detected by MitoTracker Orange staining. Glucose uptake and adenosine triphosphate content of 3T3-L1 adipocytes and C2C12 myotubes were detected. The expression levels of proteins in the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway, biomarkers of autophagy, and mitochondria biogenesis were measured by western blotting. LC3 puncta were detected by immunofluorescence. RESULTS: Icaritin significantly attenuated lipid accumulation in L02 and Huh-7 cells and boosted the mitochondria biogenesis of L02 cells. Icaritin enhanced glucose uptake, decreased adenosine triphosphate content, and activated the AMPK signaling pathway in 3T3-L1 adipocytes and C2C12 myotubes. Icaritin boosted autophagy and also enhanced the initiation of autophagic flux in 3T3-L1 preadipocytes and C2C12 myoblasts. However, icaritin decreased autophagy and promoted mitochondria biogenesis in 3T3-L1 adipocytes and C2C12 myotubes. CONCLUSIONS: Icaritin attenuates lipid accumulation by increasing energy expenditure and regulating autophagy by activating the AMPK pathway.

Identification of Tumor Tissue of Origin with RNA-Seq Data and Using Gradient Boosting Strategy.

BACKGROUND: Cancer of unknown primary (CUP) is a type of malignant tumor, which is histologically diagnosed as a metastatic carcinoma while the tissue-of-origin cannot be identified. CUP accounts for roughly 5% of all cancers. Traditional treatment for CUP is primarily broad-spectrum chemotherapy; however, the prognosis is relatively poor. Thus, it is of clinical importance to accurately infer the tissue-of-origin of CUP. METHODS: We developed a gradient boosting framework to trace tissue-of-origin of 20 types of solid tumors. Specifically, we downloaded the expression profiles of 20,501 genes for 7713 samples from The Cancer Genome Atlas (TCGA), which were used as the training data set. The RNA-seq data of 79 tumor samples from 6 cancer types with known origins were also downloaded from the Gene Expression Omnibus (GEO) for an independent data set. RESULTS: 400 genes were selected to train a gradient boosting model for identification of the primary site of the tumor. The overall 10-fold cross-validation accuracy of our method was 96.1% across 20 types of cancer, while the accuracy for the independent data set reached 83.5%. CONCLUSION: Our gradient boosting framework was proven to be accurate in identifying tumor tissue-of-origin on both training data and independent testing data, which might be of practical usage.

Development of photosensitizer-loaded lipid droplets for photothermal therapy based on thiophene analogs.

Photothermal therapy (PTT) was considered as one of the most promising cancer therapies to overcome the severe side effects caused by chemotherapy. Hence, four thiophene analogs were developed to construct novel organic photothermal agents (PTAs) for many biomedical applications in cancer biosensing and photothermal therapies. The efficacy of four compounds was demonstrated by studies of photothermal properties as well as photothermal therapeutic effects. Besides, tumor ablation experiments indicated that HTN2 can effectively suppress tumors in vivo and in vitro as a novel PTA. Hence, PTAs that we designed and synthesized with their advantage of good biocompatibility and facile structural design could be candidates for PTT.

A Machine Learning Approach for Tracing Tumor Original Sites With Gene Expression Profiles.

Some carcinomas show that one or more metastatic sites appear with unknown origins. The identification of primary or metastatic tumor tissues is crucial for physicians to develop precise treatment plans for patients. With unknown primary origin sites, it is challenging to design specific plans for patients. Usually, those patients receive broad-spectrum chemotherapy, while still having poor prognosis though. Machine learning has been widely used and already achieved significant advantages in clinical practices. In this study, we classify and predict a large number of tumor samples with uncertain origins by applying the random forest and Naive Bayesian algorithms. We use the precision, recall, and other measurements to evaluate the performance of our approach. The results have showed that the prediction accuracy of this method was 90.4 for 7,713 samples. The accuracy was 80% for 20 metastatic tumors samples. In addition, the 10-fold cross-validation is used to evaluate the accuracy of classification, which reaches 91%.

A visible and near-infrared dual-fluorescent probe for discrimination between Cys/Hcy and GSH and its application in bioimaging.

Biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) play important roles in various physiological and pathological processes, and due to their similar structures and reaction activities, it is still challenging to simultaneously discriminate between GSH and Cys/Hcy in vivo. Hence, a novel fluorescent probe for simultaneously discriminating GSH and Cys/Hcy in biological samples is highly desirable. Herein, we presented two enhanced fluorescent probes (Cy1 and Cy2) with doubly-activated dual emission for sensitive and discriminative detection of Cys/Hcy and GSH. The probes were constructed with IR-780 and NBD linked via an ether bond, which responds to GSH with near infrared (NIR) emission at 810 nm (λex = 720 nm) and Cys/Hcy with visible green emission at 550 nm (λex = 470 nm). The probe Cy2 is operable in human serum samples, thus holding promise for its diagnosis-related application. Notably, the results of fluorescence microscopy imaging indicated that Cy2 is suitable for visualization of exogenous and endogenous biothiols in living cells. Furthermore, desirable results were obtained when the probe Cy2 was applied for bioimaging in tumor-bearing mice and acute liver injury (ALI) mice models, which revealed encouraging clinical values of this probe.

A Bioresponsive Near-Infrared Fluorescent Probe for Facile and Persistent Live-Cell Tracking.

Molecular imaging significantly transforms the field of biomedical science and facilitates the visualization, characterization, and quantification of biologic processes. However, it is still challenging to monitor cell localization in vivo, which is essential to the study of tumor metastasis and in the development of cell-based therapies. While most conventional small-molecule fluorescent probes cannot afford durable cell labeling, transfection of cells with fluorescent proteins is limited by their fixed fluorescence, poor tissue penetration, and interference of autofluorescence background. Here, a bioresponsive near-infrared fluorescent probe is reported as facile and reliable tool for real-time cell tracking in vivo. The design of this probe relies on a new phenomenon observed upon fluorobenzene-conjugated fluorescent dyes, which can form complexes with cytosolic glutathione and actively translocates to lysosomes, exhibiting enhanced and stable cell labeling. Fluorobenzene-coupled hemicyanine, a near-infrared fluorophore manifests to efficiently staining tumor cells without affecting their invasive property and enables persistent monitoring of cell migration in metastatic tumor murine models at high resolution for one week. The method of fluorobenzene functionalization also provides a simple and universal "add-on" strategy to render ordinary fluorescent probes suitable for long-term live-cell tracking, for which currently there is a deficit of suitable molecular tools.

Application of Nitroimidazole-Carbobane-Modified Phenylalanine Derivatives as Dual-Target Boron Carriers in Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) has received extensive attention as noninvasive cell-level oncotherapy for treating solid cancer tumors. However, boron-containing drugs such as l-boronophenylalanine (BPA) and sodium borocaptate have low boron content and/or poor tumor-targeting ability, limiting their application. In this study, we designed and synthesized a series of nontoxic, dual-target boron carriers (B139, B142, and B151) with the ability to accumulate specifically in tumor cells. We found that the B139 uptake into hypoxic tumor regions was high, with a 70-fold boron content compared to BPA. In addition, in vivo observation showed that B139 can be trapped in tumor cells for a prolonged period and maintains an effective therapeutic concentration, with a peak boron concentration of 50.7 µg/g and a high tumor: blood boron ratio of >3, achieving ideal BNCT conditions. Cytotoxicity evaluation in mice further proved that B139 is safe and reliable. Therefore, B139 has great potential for BNCT application as a dual-target, safe, and efficient boron carrier.

A new lysosome-targetable fluorescent probe for detection of endogenous hydrogen polysulfides in living cells and inflamed mouse model.

Hydrogen polysulfides (H2Sn, n > 1) belong to sulfane sulfur in the reactive sulfur species (RSS) family and play significant roles in maintaining biological homeostasis in organisms. The detection of H2Sn in living systems is essential, but further understanding of its "intact" function in living cells has been limited, owing to the lack of appropriate analytical tools. In this work, a new fluorescent probe PP-PS was designed for the detection of endogenous H2Sn. The probe has a large Stokes shift (178 nm), low detection limit (1 nM), and short response time (1 minute). Besides, PP-PS was successfully applied in the imaging of endogenous H2Sn in lysosomes of living cancer cells, xenograft mouse tumor tissues, and LPS-induced mouse inflammation tissues. These results revealed that the probe PP-PS could act as a new fluorescence imaging tool to study the function of intracellular hydropolysulfides.

A family of push-pull bio-probes for tracking lipid droplets in living cells with the detection of heterogeneity and polarity.

Lipid droplets (LDs) are multi-functional organelles with the storage of lipid and participating in a variety of physiological processes, including membrane transport and signal transduction. The dysfunction of LDs has been reported to be associated with multiple diseases such as obesity, diabetes, atherosclerosis, and cancer in research. Herein, we designed and synthesized a family of push-pull bio-probes (LDP1-LDP4) based on thiophene or 3,4-ethylenedioxythiophene, which is also called EDOT. LDP1-LDP4 showed positive solvatochromic effect from toluene to ethanol and the maximum fluorescence wavelength redshifted to 165 nm. It was found that the four probes showed significant increase in fluorescence intensity from PBS to oil. LDP1-LDP4 displayed excellent biocompatibility and good optical properties and had substantially facilitated to track LDs with detecting heterogeneity. LDP4 was also used to expose the difference in the polarity of LDs and cytoplasm.