A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis.

Chemotherapy typically destroys the tumor mass but rarely eradicates the cancer stem cells (CSCs) that can drive metastatic recurrence. A key current challenge is finding ways to eradicate CSCs and suppress their characteristics. Here, we report a prodrug, Nic-A, created by combining a carbonic anhydrase IX (CAIX) inhibitor, acetazolamide, with a signal transducer and transcriptional activator 3 (STAT3) inhibitor, niclosamide. Nic-A was designed to target triple-negative breast cancer (TNBC) CSCs and was found to inhibit both proliferating TNBC cells and CSCs via STAT3 dysregulation and suppression of CSC-like properties. Its use leads to a decrease in aldehyde dehydrogenase 1 activity, CD44high/CD24low stem-like subpopulations, and tumor spheroid-forming ability. TNBC xenograft tumors treated with Nic-A exhibited decreased angiogenesis and tumor growth, as well as decreased Ki-67 expression and increased apoptosis. In addition, distant metastases were suppressed in TNBC allografts derived from a CSC-enriched population. This study thus highlights a potential strategy for addressing CSC-based cancer recurrence.

TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis.

BACKGROUND: The osteochondrogenic switch of vascular smooth muscle cells (VSMCs) is a pivotal cellular process in atherosclerotic calcification. However, the exact molecular mechanism of the osteochondrogenic transition of VSMCs remains to be elucidated. Here, we explore the regulatory role of TXNIP (thioredoxin-interacting protein) in the phenotypical transitioning of VSMCs toward osteochondrogenic cells responsible for atherosclerotic calcification. METHODS: The atherosclerotic phenotypes of Txnip-/- mice were analyzed in combination with single-cell RNA-sequencing. The atherosclerotic phenotypes of Tagln-Cre; Txnipflox/flox mice (smooth muscle cell-specific Txnip ablation model), and the mice transplanted with the bone marrow of Txnip-/- mice were analyzed. Public single-cell RNA-sequencing dataset (GSE159677) was reanalyzed to define the gene expression of TXNIP in human calcified atherosclerotic plaques. The effect of TXNIP suppression on the osteochondrogenic phenotypic changes in primary aortic VSMCs was analyzed. RESULTS: Atherosclerotic lesions of Txnip-/- mice presented significantly increased calcification and deposition of collagen content. Subsequent single-cell RNA-sequencing analysis identified the modulated VSMC and osteochondrogenic clusters, which were VSMC-derived populations. The osteochondrogenic cluster was markedly expanded in Txnip-/- mice. The pathway analysis of the VSMC-derived cells revealed enrichment of bone- and cartilage-formation-related pathways and bone morphogenetic protein signaling in Txnip-/- mice. Reanalyzing public single-cell RNA-sequencing dataset revealed that TXNIP was downregulated in the modulated VSMC and osteochondrogenic clusters of human calcified atherosclerotic lesions. Tagln-Cre; Txnipflox/flox mice recapitulated the calcification and collagen-rich atherosclerotic phenotypes of Txnip-/- mice, whereas the hematopoietic deficiency of TXNIP did not affect the lesion phenotype. Suppression of TXNIP in cultured VSMCs accelerates osteodifferentiation and upregulates bone morphogenetic protein signaling. Treatment with the bone morphogenetic protein signaling inhibitor K02288 abrogated the effect of TXNIP suppression on osteodifferentiation. CONCLUSIONS: Our results suggest that TXNIP is a novel regulator of atherosclerotic calcification by suppressing bone morphogenetic protein signaling to inhibit the transition of VSMCs toward an osteochondrogenic phenotype.

2D Metal-Organic Framework Nanosheets based on Pd-TCPP as Photocatalysts for Highly Improved Hydrogen Evolution.

In this report, a 2D MOF nanosheet derived Pd single-atom catalyst, denoted as Pd-MOF, was fabricated and examined for visible light photocatalytic hydrogen evolution reaction (HER). This Pd-MOF can provide a remarkable photocatalytic activity (a H2 production rate of 21.3 mmol/gh in the visible range), which outperforms recently reported Pt-MOFs (with a H2 production rate of 6.6 mmol/gh) with a similar noble metal loading. Notably, this high efficiency of Pd-MOF is not due to different chemical environment of the metal center, nor by changes in the spectral light absorption. The higher performance of the Pd-MOF in comparison to the analogue Pt-MOF is attributed to the longer lifetime of the photogenerated electron-hole pairs and higher charge transfer efficiency.

Correction: Post-synthetic modifications in porous organic polymers for biomedical and related applications.

Correction for 'Post-synthetic modifications in porous organic polymers for biomedical and related applications' by Ji Hyeon Kim et al., Chem. Soc. Rev., 2022, 51, 43-56, https://doi.org/10.1039/D1CS00804H.

Post-synthetic modifications in porous organic polymers for biomedical and related applications.

Porous organic polymers (POPs) are prepared by crosslinked polymerization of multidimensional rigid aromatic building blocks. Generally, POPs can be classified into crystalline covalent organic frameworks (COFs) and other poorly crystalline or amorphous porous polymers. Due to their remarkable intrinsic properties, such as high porosity, stability, tunability, and presence of numerous building blocks, several new POPs are being developed for application across various scientific fields. The essential sensitive functional groups needed for specific applications are not sustained under harsh POP preparation conditions. The recently developed post-synthetic modification (PSM) strategies for POPs have enabled their advanced applications that are otherwise restricted. Owing to the advanced PSM strategies POPs have experienced a blossoming resurgence with diverse functions, particularly in biomedical applications, such as bioimaging tools, drugs, enzymes, gene or protein delivery systems, phototherapy, and cancer therapy. This tutorial review focuses on the recently developed PSM strategies for POPs, especially for biomedical applications, and their future perspectives as promising bioapplicable materials.

Gramicidin, a Bactericidal Antibiotic, Is an Antiproliferative Agent for Ovarian Cancer Cells.

Background and Objectives: Gramicidin, a bactericidal antibiotic used in dermatology and ophthalmology, has recently garnered attention for its inhibitory actions against cancer cell growth. However, the effects of gramicidin on ovarian cancer cells and the underlying mechanisms are still poorly understood. We aimed to elucidate the anticancer efficacy of gramicidin against ovarian cancer cells. Materials and Methods: The anticancer effect of gramicidin was investigated through an in vitro experiment. We analyzed cell proliferation, DNA fragmentation, cell cycle arrest and apoptosis in ovarian cancer cells using WST-1 assay, terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL), DNA agarose gel electrophoresis, flow cytometry and western blot. Results: Gramicidin treatment induces dose- and time-dependent decreases in OVCAR8, SKOV3, and A2780 ovarian cancer cell proliferation. TUNEL assay and DNA agarose gel electrophoresis showed that gramicidin caused DNA fragmentation in ovarian cancer cells. Flow cytometry demonstrated that gramicidin induced cell cycle arrest. Furthermore, we confirmed via Western blot that gramicidin triggered apoptosis in ovarian cancer cells. Conclusions: Our results strongly suggest that gramicidin exerts its inhibitory effect on cancer cell growth by triggering apoptosis. Conclusively, this study provides new insights into the previously unexplored anticancer properties of gramicidin against ovarian cancer cells.

Incremental Prognostic Value of Left Ventricular Longitudinal Strain Over Ejection Fraction in Coronary Artery Bypass Grafting.

OBJECTIVES: To evaluate the incremental prognostic value of longitudinal strain over left ventricular ejection fraction (LVEF) after coronary artery bypass grafting (CABG). DESIGN: Retrospective cohort study. SETTING: Single tertiary-care center. PARTICIPANTS: Patients underwent isolated CABG between January 2014 and December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 999 patients (median age, 65 years, 23.5% female) categorized into 3 groups according to their left ventricular (LV) systolic function status: pEF/pS (preserved LVEF and preserved longitudinal strain, n = 490), pEF/iS (preserved LVEF and impaired longitudinal strain, n = 186), and rEF (reduced LVEF, n = 323). During a median follow-up of 2.7 years, 86 (8.6%) patients had died. The 5-year survival significantly differed in patients with preserved LVEF according to the strain status (pEF/pS v pEF/iS, 90.0% v 84.6%; p = 0.002). After adjusting for potential confounders, the pEF/iS group (adjusted hazard ratio [HR], 2.17; 95% CI, 1.10-4.28; p = 0.03) and the rEF group (adjusted HR, 2.96; 95% CI, 1.46-6.00; p = 0.003) had significantly higher risks for all-cause death compared with the pEF/pS group. The addition of longitudinal strain to LVEF in the prediction model significantly improved its performance (global chi-squared, 105.2 v 110.2; p = 0.03). CONCLUSIONS: Left ventricular longitudinal strain could differentiate the prognosis after CABG in patients with preserved LVEF and provide significant incremental prognostic value to LVEF.

DNA-Damage-Response-Targeting Mitochondria-Activated Multifunctional Prodrug Strategy for Self-Defensive Tumor Therapy.

We report a novel multifunctional construct, M1, designed explicitly to target the DNA damage response in cancer cells. M1 contains both a floxuridine (FUDR) and protein phosphatase 2A (PP2A) inhibitor combined with a GSH-sensitive linker. Further conjugation of the triphenylphosphonium moiety allows M1 to undergo specific activation in the mitochondria, where mitochondria-mediated apoptosis is observed. Moreover, M1 has enormous effects on genomic DNA ascribed to FUDR's primary function of impeding DNA/RNA synthesis combined with diminishing PP2A-activated DNA repair pathways. Importantly, mechanistic studies highlight the PP2A obtrusion in FUDR/5-fluorouracil (5-FU) therapy and underscore the importance of its inhibition to harbor therapeutic potential. HCT116 cell xenograft-bearing mice that have a low response rate to 5-FU show a prominent effect with M1, emphasizing the importance of DNA damage response targeting strategies using tumor-specific microenvironment-activatable systems.

A Small Molecule Strategy for Targeting Cancer Stem Cells in Hypoxic Microenvironments and Preventing Tumorigenesis.

Breast cancer consists of heterogenic subpopulations, which determine the prognosis and response to chemotherapy. Among these subpopulations, a very limited number of cancer cells are particularly problematic. These cells, known as breast cancer stem cells (BCSCs), are thought responsible for metastasis and recurrence. They are thus major contributor to the unfavorable outcomes seen for many breast cancer patients. BCSCs are more prevalent in the hypoxic niche. This is an oxygen-deprived environment that is considered crucial to their proliferation, stemness, and self-renewal but also one that makes BCSCs highly refractory to traditional chemotherapeutic regimens. Here we report a small molecule construct, AzCDF, that allows the therapeutic targeting of BCSCs and which is effective in normally refractory hypoxic tumor environments. A related system, AzNap, has been developed that permits CSC imaging. Several design elements are incorporated into AzCDF, including the CAIX inhibitor acetazolamide (Az) to promote localization in MDA-MB-231 CSCs, a dimethylnitrothiophene subunit as a hypoxia trigger, and a 3,4-difluorobenzylidene curcumin (CDF) as a readily released therapeutic payload. This allows AzCDF to serve as a hypoxia-liable molecular platform that targets BCSCs selectively which decreases CSC migration, retards tumor growth, and lowers tumorigenesis rates as evidenced by a combination of in vitro and in vivo studies. To the best of our knowledge, this is the first time a CSC-targeting small molecule has been shown to prevent tumorigenesis in an animal model.

Accelerated decomposition of Bi2S3 nanorods in water under an electron beam: a liquid phase transmission electron microscopy study.

Evaluating the stability of semiconductor photocatalysts is critical in the development of efficient catalysts. The morphological and microstructural behaviors of nanorod-shaped Bi2S3 semiconductors in aqueous solution were studied using a liquid cell transmission electron microscopy (TEM) technique. The rapid decomposition of Bi2S3 in water was observed under electron beam irradiation during TEM. Rounded bright spots due to a reduction in thickness were observed on the Bi2S3 nanorods at the initial stage of the decomposition, and rounded dark particles appeared outside of the nanorods in the solution, continuing the decomposition. This was confirmed by analyzing the atomic structure of the newly formed small particles, which consisted of an orthorhombic Bi2S3 phase. The stability-related decomposition of the Bi2S3 nanorods was demonstrated by considering the reduction and oxidation potentials of Bi2S3 in an aqueous solution. The effect of water radiolysis by the incident electron during TEM observations on the decomposition process was also determined by considering the time-dependent concentration behavior of the chemical species. Our study therefore reflects a novel route to evaluate the stabilities of semiconductor photocatalysts, which could ultimately solve a range of energy and environmental pollution problems.

Cancer stem cell-targeted bio-imaging and chemotherapeutic perspective.

Cancer stem cells (CSCs), also called tumor-initiating cells (TICs), have been studied intensively due to their rapid proliferation, migration, and role in the recurrence of cancer. In general, CSC marker-positive cells [CD133, CD44, CD166, aldehyde dehydrogenase (ALDH), and epithelial cell adhesion molecule (EpCAM)] exhibit a 100-fold increased capacity to initiate cancer. Within a heterogeneous tumor mass, only approximately 0.05-3% of cells are suspected to be CSCs and able to proliferate under hypoxia. Interestingly, CSCs, cancer cells, and normal stem cells share many cytochemical properties, such as inhibition of the redox system for reactive oxygen species (ROS) production and high expression of drug resistance transporters. However, compared to normal stem cells, CSCs develop unique metabolic flexibility, which involves switching between oxidative phosphorylation (OXPHOS) and glycolysis as their main source of energy. Due to the similarities between CSCs and other cancer cells and normal stem cells, limited chemotherapeutic and bio-imaging reagents specific for CSCs have been developed. In this short review, we address the current knowledge regarding CSCs with a focus on designing chemotherapeutic and bio-imaging reagents that target CSCs.

Multifunctional sonosensitizers in sonodynamic cancer therapy.

Phototherapy, including photodynamic therapy and photothermal therapy, has the potential to treat several types of cancer. However, to be an effective anticancer treatment, it has to overcome limitations, such as low penetration depth, low target specificity, and resistance conferred by the local tumor microenvironment. As a non-invasive technique, low-intensity ultrasound has been widely used in clinical diagnosis as it exhibits deeper penetration into the body compared to light. Recently, sonodynamic therapy (SDT), a combination of low-intensity ultrasound with a chemotherapeutic agent (sonosensitizer), has been explored as a promising alternative for cancer therapy. As all known cancer treatments such as chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, and drug delivery have been advanced independently enough to complement others substantially, the combination of these therapeutic modalities with SDT is opportune. This review article highlights the recent advances in SDT in terms of sonosensitizers and their formulations and anticancer therapeutic efficacy. Also discussed is the potential of SDT in combination with other modalities to address unmet needs in precision medicine.

"Turn on" Fluorescence Sensor of Glutathione Based on Inner Filter Effect of Co-Doped Carbon Dot/Gold Nanoparticle Composites.

Glutathione (GSH) is a thiol that plays a significant role in nutrient metabolism, antioxidant defense and the regulation of cellular events. GSH deficiency is related to variety of diseases, so it is useful to develop novel approaches for GSH evaluation and detection. In this study we used nitrogen and phosphorus co-doped carbon dot-gold nanoparticle (NPCD-AuNP) composites to fabricate a simple and selective fluorescence sensor for GSH detection. We employed the reductant potential of the nitrogen and phosphorus co-doped carbon dots (NPCDs) themselves to form AuNPs, and subsequently NPCD-AuNP composites from Au3+. The composites were characterized by using a range of spectroscopic and electron microscopic techniques, including electrophoretic light scattering and X-ray diffraction. The overlap of the fluorescence emission spectrum of NPCDs and the absorption spectrum of AuNPs resulted in an effective inner filter effect (IFE) in the composite material, leading to a quenching of the fluorescence intensity. In the presence of GSH, the fluorescence intensity of the composite was recovered, which increased proportionally to increasing the GSH concentration. In addition, our GSH sensing method showed good selectivity and sensing potential in human serum with a limit of detection of 0.1 µM and acceptable results.

Unimolecular Photodynamic O2-Economizer To Overcome Hypoxia Resistance in Phototherapeutics.

Tumor hypoxia has proven to be the major bottleneck of photodynamic therapy (PDT) to clinical transformation. Different from traditional O2 delivery approaches, here we describe an innovative binary photodynamic O2-economizer (PDOE) tactic to reverse hypoxia-driven resistance by designing a superoxide radical (O2•-) generator targeting mitochondria respiration, termed SORgenTAM. This PDOE system is able to block intracellular O2 consumption and down-regulate HIF-1α expression, which successfully rescues cancer cells from becoming hypoxic and relieves the intrinsic hypoxia burden of tumors in vivo, thereby sparing sufficient endogenous O2 for the PDT process. Photosensitization mechanism studies demonstrate that SORgenTAM has an ideal intersystem crossing rate and triplet excited state lifetime for generating O2•- through type-I photochemistry, and the generated O2•- can further trigger a biocascade to reduce the PDT's demand for O2 in an O2-recycble manner. Furthermore, SORgenTAM also serves to activate the AMPK metabolism signaling pathway to inhibit cell repair and promote cell death. Consequently, using this two-step O2-economical strategy, under relatively low light dose irradiation, excellent therapeutic responses toward hypoxic tumors are achieved. This study offers a conceptual while practical paradigm for overcoming the pitfalls of phototherapeutics.

Pulmonary alveolar proteinosis in Korea: analysis of prevalence and incidence via a nationwide population-based study.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a very rare lung disease and its prevalence and incidence remain unclear. The prevalence and incidence of PAP were investigated by using nationwide claims data from the Korean Health Insurance Review and Assessment service. METHODS: Data were extracted for adults who visited any secondary or tertiary medical institute between 2010 and 2016 with the PAP-related Korean Classification of Disease, 7th edition code J84.0 and the Rare Intractable Disease exempted calculation code V222. To robust case definition, a narrow case definition was made when all following factors were met: 1) more than two PAP-coded visits within 1 year of the first claim, and 2) more than one claim for both chest computed tomography and diagnostic procedures (bronchoscopy or surgical lung biopsy) within 90 days before or after the first claim. RESULTS: A total of 182 patients (narrow, n = 82) with PAP-related codes were identified from 2010 to 2016 and 89 new patients (narrow, n = 66) visited medical institutes between 2012 and 2015. The prevalence of PAP was 4.44 (narrow: 2.27) per 106 population, with a peak age of 60-69 years. The incidence of PAP was 0.56 (narrow: 0.41) per 106 population at risk, with a peak age of 50-59 years. Among incident cases, the male-to-female ratio was 1.52 and about two-thirds had comorbidities, dyslipidaemia being the most common. CONCLUSIONS: The prevalence and incidence of PAP in Korea are low, similar to those in other countries; however, Korean patients with PAP are characterized by older diagnostic age and a lower male-to-female ratio.

First Report of Fusarium Wilt Caused by Fusarium equiseti on Cabbage (Brassica oleracea var. capitate L.) in Korea.

Cabbage (Brassica oleracea var. capitate L.) is an important vegetable crop that is widely cultivated throughout the world. In August 2019, wilting symptoms on cabbage (stunted growth, withered leaves, and wilted plants) were observed in a cabbage field of Pyeongchang, Gangwon Province, with an incidence of 5 to 10%. To identify the cause, symptomatic root tissue was excised, surface-sterilized with 70% ethanol, and rinsed thrice with sterile distilled water. The samples were dried on blotter paper, placed onto potato dextrose agar (PDA), and incubated at 25°C for 1 week. Five morphologically similar fungal isolates were sub-cultured and purified using the single spore isolation method (Choi et al. 1999). The fungus produced colonies with abundant, loosely floccose, whitish-brown aerial mycelia and pale-orange pigmentation on PDA. Macroconidia had four 4 to six 6 septa, a foot-shaped basal cell, an elongated apical cell, and a size of 20.2 to 31.8 × 2.2 to 4.1 µm (n = 30). No microconidia were observed. Chlamydospores were produced from hyphae and were most often intercalary, in pairs or solitary, globose, and frequently formed chains (6.2? to 11.7 µm, n = 10). Based on these morphological characteristics, the fungus was identified as Fusarium equiseti (Leslie and Summerell 2006). A representative isolate was deposited in the Korean Agricultural Culture Collection (KACC48935). For molecular characterization, portions of the translation elongation factor 1-alpha (TEF-1α) and second largest subunit of RNA polymerase II (RPB2) genes were amplified from the representative isolate using the primers pair of TEF-1α (O'Donnell et al. 2000) and GQ505815 (Fusarium MLST database), and sequenced. Searched BLASTn of the RPB2 sequence (MT576587) to the Fusarium MLST database showed 99.94% similarity to the F. incarnatum-equiseti species complex (GQ505850) and 98.85 % identity to both F. equiseti (GQ505599) and F. equiseti (GQ505772). Further, the TEF-1α sequence (MT084815) showed 100% identity to F. equiseti (KT224215) and 99.85% identity to F. equiseti (GQ505599), respectively. Therefore, the fungus was identified as F. equiseti based on morphological and molecular identification. For pathogenicity testing, a conidial suspension (1 × 106 conidia/ml) was prepared by harvesting macroconidia from 2-week-old cultures on PDA. Fifteen 4-week-old cabbage seedlings (cv. 12-Aadrika) were inoculated by dipping roots into the conidial suspension for 30 min. The inoculated plants were transplanted into a 50-hole plastic tray containing sterilized soil and maintained in a growth chamber at 25°C, with a relative humidity of >80%, and a 12-h/12-h light/dark cycle. After 4 days, the first wilt symptoms were observed on inoculated seedlings, and the infected plants eventually died within 1 to 2 weeks after inoculation. No symptoms were observed in plants inoculated with sterilized distilled water. The fungus was re-isolated from symptomatic tissues of inoculated plants and its colony and spore morphology were identical to those of the original isolate, thus confirming Koch's postulates. Fusarium wilt caused by F. equiseti has been reported in various crops, such as cauliflower in China, cumin in India, and Vitis vinifera in Spain (Farr and Rossman 2020). To our knowledge, this is the first report of F. equiseti causing Fusarium wilt on cabbage in Korea. It This disease poses a threat to cabbage production in Korea, and effective disease management strategies need to be developed.

Detection of Ferric Ions and Catecholamine Neurotransmitters via Highly Fluorescent Heteroatom Co-Doped Carbon Dots.

Carbon dots (CDs) demonstrate very poor fluorescence quantum yield (QY). In this study, with the help of a hydrothermal method, we combined CDs with nitrogen and phosphorus elements belonging to the VA group (in the periodic table) to form heteroatom co-doped CDs, i.e., nitrogen and phosphorus co-doped carbon dots (NPCDs). These displayed a significant improvement in the QY (up to 84%), which was as much as four times than that of CDs synthesized by the same method. The as-prepared NPCDs could be used as an "off-on" fluorescence detector for the rapid and effective sensing of ferric ions (Fe3+) and catecholamine neurotransmitters (CNs) such as dopamine (DA), adrenaline (AD), and noradrenaline (NAD). The fluorescence of NPCDs was "turned off" and the emission wavelength was slightly red-shifted upon increasing the Fe3+ concentration. However, when CNs were incorporated, the fluorescence of NPCDs was recovered in a short response time; this indicated that CN concentration could be monitored, relying on enhancing the fluorescence signal of NPCDs. As a result, NPCDs are considered as a potential fluorescent bi-sensor for Fe3+ and CN detection. Particularly, in this research, we selected DA as the representative neurotransmitter of the CN group along with Fe3+ to study the sensing system based on NPCDs. The results exhibited good linear ranges with a limit of detection (LOD) of 0.2 and 0.1 µM for Fe3+ and DA, respectively.

Effects of Resveratrol on Thymic Stromal Lymphopoietin Expression in Mast Cells.

Background and objectives: Cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathogenesis of atopic diseases such as atopic dermatitis, allergic rhinitis, and asthma. Resveratrol (RSV) exerts various pharmacological effects such as antioxidant, anti-inflammatory, neuroprotective, and anticancer. Although, it has been verified the beneficial effects of RSV on various subjects, the effect of RSV on thymic stromal lymphopoietin (TSLP) regulation has not been elucidated. Materials and Methods: Here, we examined how RSV regulates TSLP in HMC-1 cells. Enzyme-linked immunosorbent assay, real-time polymerase chain reaction, Western blotting, and calcium assay were performed to evaluate the effect of RSV. Results: TSLP production and mRNA expression were reduced by RSV. RSV down-regulated nuclear factor-κB activation, IκBα phosphorylation as well as activation of receptor-interacting protein2 and caspase-1 in HMC-1 cells. In addition, RSV treatment decreased the up-regulation of intracellular calcium in HMC-1 cells. Conclusions: These results suggest that RSV might be useful for the treatment of atopic diseases through blocking of TSLP.

A pH-Responsive Glycyrrhetinic-Acid-Modified Small-Molecule Conjugate for NIR Imaging of Hepatocellular Carcinoma (HCC).

We report a glycyrrhetinic-acid (GA)-decorated small-molecule conjugate for pH-triggered near-infrared (NIR) fluorescence imaging of hepatocellular carcinoma (HCC). Our in vitro studies demonstrated that the conjugate, referred to as NIR-GA, was efficiently taken up by liver cancer cell lines such as HepG2 and Huh7 through an endocytic pathway mediated by GA receptors. As suggested by co-localization studies, NIR-GA mainly localized in the lysosome, where the acidic pH results in the activation of the fluorescent dye through H+ -triggered spirolactam ring opening to give strong fluorescence in the NIR region.

Celery Stalk-Derived Carbon Dots for Detection of Copper Ions.

Fluorescent carbon dots (CDs) have motivated a significant amount of research because of their properties such as excellent biocompatibility and low toxicity. In this work, water-soluble fluorescent CDs were synthesized from celery stalks by a one-step, low-cost hydrothermal process. The as-prepared CDs had the average size of 3.7 ± 1.1 nm, and they emitted bright blue photoluminescence. The surface functional groups and states were investigated via Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. The blue fluorescence of the as-prepared CDs was effectively quenched by Cu2+ ions compared to other competing metal ions. Therefore, these CDs are promising probes for the fluorescence detection of Cu2+ ions. Moreover, an excellent linear relationship was obtained between the relative fluorescence intensity and the concentration of Cu2+ ions in the linear detection range 0-100 µM, and the limit of detection was 0.132 µM.