Integrated Transcriptomics-Proteomics Analysis Identifies Molecular Phenotypic Alterations Associated with Colorectal Cancer.

Understanding the pathogenesis and finding diagnostic markers for colorectal cancer (CRC) are the key to its diagnosis and treatment. Integrated transcriptomics and proteomics analysis can be used to characterize alterations of molecular phenotypes and reveal the hidden pathogenesis of CRC. This study employed a novel strategy integrating transcriptomics and proteomics to identify pathological molecular pathways and diagnostic biomarkers of CRC. First, differentially expressed proteins and coexpressed genes generated from weighted gene coexpression network analysis (WGCNA) were intersected to obtain key genes of the CRC phenotype. In total, 63 key genes were identified, and pathway enrichment analysis showed that the process of coagulation and peptidase regulator activity could both play important roles in the development of CRC. Second, protein-protein interaction analysis was then conducted on these key genes to find the central genes involved in the metabolic pathways underpinning CRC. Finally, Itih3 and Lrg1 were further screened out as diagnostic biomarkers of CRC by applying statistical analysis on central genes combining transcriptomics and proteomics data. The deep involvement of central genes in tumorigenesis demonstrates the accuracy and reliability of this novel transcriptomics-proteomics integration strategy in biomarker discovery. The identified candidate biomarkers and enriched metabolic pathways provide insights for CRC diagnosis and treatment.

Mechanistic insights into hormesis induced by erythromycin in the marine alga Thalassiosira weissflogii.

Erythromycin (ERY) is a typical macrolide antibiotic with large production and extensive use on a global scale. Detection of ERY in both freshwaters and coaster seawaters, as well as relatively high ecotoxicity of ERY have been documented. Notably, hormesis has been reported on several freshwater algae under ERY stress, where growth was promoted at relatively lower exposures but inhibited at higher treatment levels. On the contrary, there is limited information of ERY toxicity in marine algae, hampering the risk assessment on ERY in the coaster waters. The presence of hormesis may challenge the current concept of dose-response adopted in chemical risk assessment. Whether and how exposure to ERY can induce dose-dependent toxicity in marine algae remain virtually unknown, especially at environmentally relevant concentrations. The present study used a model marine diatom Thalassiosira weissflogii (T. weissflogii) to reveal its toxicological responses to ERY at different biological levels and decipher the underlying mechanisms. Assessment of multiple apical endpoints shows an evident growth promotion following ERY exposure at an environmentally relevant concentration (1 µg/L), associated with increased contents reactive oxygen species (ROS) and chlorophyll-a (Chl-a), activated signaling pathways related to ribosome biosynthesis and translation, and production of total soluble protein. By contrast, growth inhibition in the 750 and 2500 µg/L treatments was attributed to reduced viability, increased ROS formation, reduced content of total soluble protein, inhibited photosynthesis, and perturbed signaling pathways involved in xenobiotic metabolism, ribosome, metabolism of amino acid, and nitrogen metabolism. Measurements of multiple apical endpoints coupled with de novo transcriptomics analysis applied in the present study, a systems biology approach, can generate detailed mechanistic information of chemical toxicity including dose-response and species sensitivity difference used in environmental risk assessment.

Cascade C-H-Activated Polyannulations toward Ring-Fused Heteroaromatic Polymers for Intracellular pH Mapping and Cancer Cell Killing.

The development of straightforward and efficient synthetic methods toward ring-fused heteroaromatic polymers with attractive functionalities has great significance in both chemistry and materials science. Herein, we develop a facile cascade C-H-activated polyannulation route that can in situ generate multiple ring-fused aza-heteroaromatic polymers from readily available monomers in an atom-economical manner. A series of complex polybenzimidazole derivatives with high absolute molecular weights of up to 24 000 are efficiently produced in high yields within 2 h. Benefiting from their unique imidazole-containing ring-fused structures with multiple aryl pendants, the obtained polymers show excellent thermal and morphological stability, good solution processability, high refractive index, small chromic dispersion, as well as remarkable acid-base-responsive fluorescence. Taking advantage of the ratiometric fluorescence response of the triphenylamine-substituted heteroaromatic polymer to pH variations, we successfully apply it as a sensitive fluorescence probe for the mapping and quantitative analysis of intracellular pH in live cells. Furthermore, through the simple N-methylation reaction of the ring-fused polybenzimidazoles, diverse azonia-containing polyelectrolytes are readily produced, which can efficiently kill cancer cells via the synergistic effects of dark toxicity and phototoxicity.

Chemo-Phototherapy with Carfilzomib-Encapsulated TiN Nanoshells Suppressing Tumor Growth and Lymphatic Metastasis.

The design of nanomedicine for cancer therapy, especially the treatment of tumor metastasis has received great attention. Proteasome inhibition is accepted as a new strategy for cancer therapy. Despite being a big breakthrough in multiple myeloma therapy, carfilzomib (CFZ), a second-in-class proteasome inhibitor is still unsatisfactory for solid tumor and metastasis therapy. In this study, hollow titanium nitride (TiN) nanoshells are synthesized as a drug carrier of CFZ. The TiN nanoshells have a high loading capacity of CFZ, and their intrinsic inhibitory effect on autophagy synergistically enhances the activity of CFZ. Due to an excellent photothermal conversion efficiency in the second near-infrared (NIR-II) region, TiN nanoshell-based photothermal therapy further induces a synergistic anticancer effect. In vivo study demonstrates that TiN nanoshells readily drain into the lymph nodes, which are responsible for tumor lymphatic metastasis. The CFZ-loaded TiN nanoshell-based chemo-photothermal therapy combined with surgery offers a remarkable therapeutic outcome in greatly inhibiting further metastatic spread of cancer cells. These findings suggest that TiN nanoshells act as an efficient carrier of CFZ for realizing enhanced outcomes for proteasome inhibitor-based cancer therapy, and this work also presents a "combined chemo-phototherapy assisted surgery" strategy, promising for future cancer treatment.

Novel Imaging of Silver Nanoparticle Uptake by a Unicellular Alga and Trophic Transfer to Daphnia magna.

Widely applied silver nanoparticles (AgNPs) can have potentially detrimental impacts on aquatic organisms. Unicellular algae as primary producers can interact with AgNPs and initiate their transfer along food chains. Herein, we demonstrate that AgNPs were internalized in a freshwater phytoplankton species Chlamydomonas reinhardtii, but the entrance pathways varied with their surface coatings. Citrate-coated AgNPs (Cit-AgNPs) were internalized mainly through the apical zone of the cell near the flagella, whereas the aggregation-induced emission fluorogen (AIEgen)-coated AgNPs (AIE-AgNPs) were internalized through endocytosis. The internalized AgNPs were dissolved intracellularly and the released Ag+ was distributed heterogeneously in the cytoplasm, in contrast to the directly accumulated Ag+ which displayed a diffuse cytoplasmic distribution pattern. We then further visualized and quantified the trophic transfer of AgNPs from the alga C. reinhardtii to the zooplanktonic species Daphnia magna. Both trophically transferred Ag+ and AgNPs were concentrated in the gut regions of D. magna as a result of the direct ingestion of food particles. After ingestion, about 95% of the trophically transferred Ag+ was eliminated. Retention of AIE-AgNPs by daphnids was relatively higher than that of Cit-AgNPs due to their lower dissolution of Ag+. The present study provides direct evidence for the internalization of AgNPs in unicellular algae and demonstrates that the biological transport of trophically transferred of AgNPs is related to the different surface coatings of NPs.

Direct Visualization and Quantification of Maternal Transfer of Silver Nanoparticles in Zooplankton.

The immense application of silver nanoparticles (AgNPs) in biomedical fields is likely to increase the exposure of humans. However, little is known about whether these nanoparticles can be maternally transferred, especially regarding their biodistribution in the younger generation, maternal transfer efficiency, and toxic effects. In the present study, maternal transfer of AgNPs in model zooplankton (Daphnia magna) was for the first time visualized and quantified. We found that AgNPs were transferred from mother to offspring and mainly accumulated in the lipids due to the strong colocalization with lipid droplets, which were the major energy sources of Daphnia embryos. In contrast, Ag+ was irregularly distributed in different sites, probably due to the mobility and reactivity of Ag+. The maternal transfer efficiency quantified by the radiolabeling methodology was 2.37 ± 0.25 and 6.05 ± 0.89% for 110mAgNPs and 110mAg, respectively. Furthermore, AgNPs and Ag+ significantly inhibited the reproduction capability of F0 and F1 generations, but such maternal toxic effect inhibition was only found within the first two broods of F0 and F1 generations. Our bioimaging findings demonstrated that AgNPs could be maternally transferred to the next generation; thus, it is critical to produce AgNPs with lower toxic effects, higher delivery efficacy, and more precise targeting.

Differentiating Silver Nanoparticles and Ions in Medaka Larvae by Coupling Two Aggregation-Induced Emission Fluorophores.

Although numerous studies have been conducted on the toxicity and biodistribution of AgNPs and corresponding ionic counterparts, it is still debatable whether the toxicity originates from the accumulation of particles within specific organs or is mediated by the dissolved Ag ions. To gain a better insight into the toxic mechanisms of AgNPs, two aggregation-induced emission fluorogens (AIEgens; AIEgens-coated AgNPs and a fluorogenic Ag+ sensor) were employed for the in situ visualization and quantitative analysis of distribution patterns of AIE-AgNPs and corresponding Ag ions in different organs of medaka larvae. The 96 h LC50 of AIEgens-coated AgNPs (AIE-AgNPs) was 10-20 mg/L, which was much higher than that of the citrate-coated AgNPs (Cit-AgNPs, 2.39-3.24 mg/L) and AgNO3 (0.23 mg/L), suggesting that the AIE-AgNPs were much more biocompability than Cit-AgNPs or AgNO3. The LC50 of AgNO3 was approximately 10% of the LC50 of Cit-AgNPs, which was comparable to the percentage of Ag+ released from Cit-AgNPs. The novel AIE method for the first time simultaneously analyzed the quantitative distribution patterns of AIE-AgNPs and corresponding Ag ions in different organs of medaka larvae. AIE-AgNPs and Ag ions showed distinct distribution patterns, in which AIE-AgNPs were concentrated in intestine and liver, accounting for 53.4% and 32.1% of the total AIE-AgNPs accumulated in medaka larvae, respectively. In contrast, Ag ions were accumulated mainly (92.5%) in the intestine of medaka larvae. The toxicity of AgNPs toward medaka larvae was attributed mainly to the released Ag ions which could potentially disrupt the absorptive capacity of the intestinal epithelium and induce digestive dysfunction. Our study provided a new technique for simultaneous monitoring of the AgNPs and corresponding Ag ions in the biological systems.

Quantitative Characterization of Gold Nanoparticles by Coupling Thin Layer Chromatography with Laser Ablation Inductively Coupled Plasma Mass Spectrometry.

Metal nanoparticles (NPs) determination has recently attracted considerable attention because of the continuing boom of nanotechnology. In this study, a novel method for separation and quantitative characterization of NPs in aqueous suspension was established by coupling thin layer chromatography (TLC) with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Gold nanoparticles (AuNPs) of various sizes were used as the model system. It was demonstrated that TLC not only allowed separation of gold nanoparticles from ionic gold species by using acetyl acetone/butyl alcohol/triethylamine (6:3:1, v/v) as the mobile phase, but it also achieved the separation of differently sized gold nanoparticles (13, 34, and 47 nm) by using phosphate buffer (0.2 M, pH = 6.8), Triton X-114 (0.4%, w/v), and EDTA (10 mM) as the mobile phase. Various experimental parameters that affecting TLC separation of AuNPs, such as the pH of the phosphate buffer, the coating of AuNPs, the concentrations of EDTA and Triton X-114, were investigated and optimized. It was found that separations of AuNPs by TLC displayed size dependent retention behavior with good reproducibility, and the retardation factors (R(f) value) increased linearly with decreasing nanoparticle size. The analytical performance of the present method was evaluated under optimized conditions. The limits of detection were in the tens of pg range, and repeatability (RSD, n = 7) was 6.3%, 5.9%, and 8.3% for 30 ng of 13 nm AuNPs, 34 nm AuNPs, and 47 nm AuNPs, respectively. The developed TLC-LA-ICP-MS method has also been applied to the analysis of spiked AuNPs in lake water, river water, and tap water samples.

Clinical value of the high expression of corticosteroid receptor-beta mRNA in the nasal mucosa of steroid-resistant patients with allergic rhinitis.

PURPOSE: This study investigated clinical values of corticosteroid (CS) receptor α and ß in the nasal mucosa of patients with allergic rhinitis (AR) by determining CS receptor α and ß mRNA expression following steroid treatment. PROCEDURES: Among 120 outpatients, 65 had persistent AR, including 36 being sensitive to steroid treatment (steroid-sensitive group) and 29 being resistant to steroid treatment (steroid-resistant group). In addition, 30 patients with deflection of the nasal septum alone, which was corrected by surgery, were recruited as controls. Fluorescent quantitative reverse transcription-PCR was used to quantify CS receptor α and ß mRNA expression in the nasal mucosa of patients. RESULTS: Results showed that CS receptor ß mRNA expression in the nasal mucosa was significantly higher in the steroid-resistant group [(5.62 ± 1.28) × 102 copies/µg] compared with the steroid-sensitive [(4.62 ± 0.48) × 102 copies/µg, t = -6.67, p < 0.01] and control [(5.32 ± 0.55) × 102 copies/µg, t = -8.29, p < 0.01] groups. There were significant differences in the mRNA expression ratio of CS receptor α to ß between the steroid-sensitive (658.32 ± 65.16) and steroid-resistant (525.70 ± 68.10) groups (t = 10.16, p < 0.01). CONCLUSION: A high level of CS receptor ß mRNA but a low level of CS receptor α mRNA expression in patients with steroid-resistant AR indicates steroid resistance. CS receptor ß plays a role in evaluating the effects of steroid therapy for AR.

Bioprospecting of Chlamydomonas reinhardtii for boosting biofuel-related products production based on novel aggregation-induced emission active extracellular polymeric substances nanoprobes.

Biofuel production from microalgae has been greatly restricted by low biomass productivity and long-term photosynthetic efficacy. Here, a novel strategy for selecting high-growing, stress-resistant algal strains with high photosynthetic capacity was proposed based on biocompatible extracellular polymeric substances (EPS) probes with aggregation-induced emission (AIE) properties. Specifically, AIE active EPS probes were synthesized for in-situ long-term monitoring of the EPS productivity at different algal growth stages. By coupling the AIE-based fluorescent techniques, algal cells were classified into four diverse populations based on their chlorophyll and EPS signals. Mechanistic studies on the sorted algal cells revealed their remarkable stress resistance and high expression of cell division, biopolymer production and photosynthesis-related genes. The sorted and subcultured algal cells consistently exhibited relatively higher growth rates and photosynthetic capacities, resulting in an increased (1.2 to 1.8-fold) algal biomass production, chlorophyll, and lipids. This study can potentially open new strategies to boost microalgal-based biofuel production.

Smart Delivery Systems Responsive to Cathepsin B Activity for Cancer Treatment.

Cathepsin B is a lysosomal cysteine protease, contributing to vital cellular homeostatic processes including protein turnover, macroautophagy of damaged organelles, antigen presentation, and in the extracellular space, it takes part in tissue remodeling, prohormone processing, and activation. However, aberrant overexpression of cathepsin B and its enzymatic activity is associated with different pathological conditions, including cancer. Cathepsin B overexpression in tumor tissues makes this enzyme an important target for smart delivery systems, responsive to the activity of this enzyme. The generation of technologies which therapeutic effect is activated as a result of cathepsin B cleavage provides an opportunity for tumor-targeted therapy and controlled drug release. In this review, we summarized different technologies designed to improve current cancer treatments responsive to the activity of this enzyme that were shown to play a key role in disease progression and response to the treatment.

Comparative proteomic analysis reveals the different hepatotoxic mechanisms of human hepatocytes exposed to silver nanoparticles.

Silver nanoparticles (AgNPs), which have been used extensively in consuming products and eventually released into the natural environment, have aroused concerns recently because of their potentially harmful effects on human beings following various routes of exposure. As the liver is one of the largest accumulation and deposition sites of circulatory AgNPs, it is important to evaluate the hepatotoxicity induced by AgNPs. However, the acting mechanisms of AgNPs-induced hepatotoxicity are still elusive to a great extent. Herein, we investigated the hepatotoxic effects of AgNPs using a comparative proteomics approach. First, we evaluated the cytotoxicity of different-sized AgNPs and found that the cancerous liver cells were generally more sensitive than the normal liver cells. Next, proteomics results suggested that HepG2 and L02 cells showed distinct adaptive responses upon AgNPs exposure. HepG2 cells respond to stresses by adapting energy metabolism, upregulating metallothionein expression and increasing the expression of antioxidants, while L02 cells protect themselves by increasing DNA repair and macro-autophagy. Besides, mitochondrial ROS has been identified as one of the causes of AgNPs-induced hepatotoxicity. Collectively, our results revealed that hepatic cancer cells and normal cells cope with AgNPs in notably different pathways, providing new insights into mechanisms underlying AgNPs-induced hepatotoxicity. DATA AVAILABILITY: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (Deutsch et al. (2020)) via the PRIDE (Perez-Riverol et al. (2019)) partner repository with the dataset identifier PXD029511.

Imaging and pathological diagnosis of primary intracranial malignant melanoma: A case report and literature review.

RATIONALE: Primary intracranial malignant melanoma (PIMM) is a rare malignant tumor that lacks specific clinical manifestations. Preoperative diagnosis is difficult to differentiate from meningiomas on computed tomography (CT) scans. Magnetic resonance imaging (MRI) usually shows typical characteristics with high signal intensity on T1WI and low signal intensity on T2WI. PIMM is highly invasive, insensitive to chemoradiotherapy, and has a poor prognosis. PATIENT CONCERNS: A 27-year-old woman was admitted to the hospital with a headache for 10 days. She did not experience nausea, vomiting, dizziness, or any other discomfort. A computerized tomography (CT) scan demonstrated a high-density mass in the left cerebellum with patchy calcification at the posterior edge, and heterogeneous enhancement was observed on a contrast-enhanced scan. MRI revealed typical characteristics of high signal intensity on T1WI and low signal intensity on T2WI. The signal characteristics of FLAIR were similar to those of T2WI, and diffusion-weighted imaging (DWI) sequence showed limited diffusion of the tumor. Magnetic resonance spectroscopy revealed increased choline (Cho) and decreased creatine (Cr) and N-acetyl aspartate (Naa) in the tumor. INTERVENTIONS: The patient underwent tumor resection and postoperative chemoradiotherapy and immunotherapy. PATHOLOGICAL DIAGNOSIS: Histological and Immunohistochemistry (IHC) tests confirmed the diagnosis of PIMM. In addition, genetic testing revealed GNAQ gene variation. OUTCOMES: No recurrence or complications were observed during the follow-up for 6 months. LESSONS: PIMM is rare, and its pathological diagnosis should be closely combined with clinical and medical history. GNAQ is a common variant of PIMM and is expected to be a therapeutic target.

Maternal transfer and biodistribution of citrate and luminogens coated silver nanoparticles in medaka fish.

Given the wide applications of silver nanoparticles (AgNPs), it is necessary to evaluate their potentially adverse long-term effects. In this study, we performed a 100-day exposure of medaka fish to citrate and luminogens coated AgNPs and investigated the maternal transfer potentials and biodistribution of AgNPs. Following long-term AgNPs exposure, AgNPs were mainly distributed in the liver, followed by gills, intestine, and brain, but were also detected in the ovary and strongly colocalized with the dissolved Ag+. The quantified transfer efficiency of different Ag species was 1.56-5.07%. Long-term exposure of medaka to small size of AgNPs (20 nm) reduced the hatching rate attributable to the accumulation of AgNPs and their dissolved Ag+. The maternally transferred AgNPs were mainly concentrated in the Kupffer's vesicle of embryos, while their dissolved Ag+ was almost homogeneously distributed in the embryos. In contrast, the newly accumulated AgNPs were mainly absorbed at the chorion of embryos. During initial larval development, the maternally transferred AgNPs and their dissolved Ag+ were consistently concentrated in intestine. Significant dissolution of maternally transferred AgNPs occurred during larval development. Our results showed that long-term exposure to AgNPs caused distinct biodistribution in the next generation of medaka, and may have implications for assessing their potential adverse effects.

Aggregation-induced emission luminogens for augmented photosynthesis.

Photosynthesis is promising in sequestrating carbon dioxide and providing food and biofuel. Recent findings have shown that luminescent materials could shift the wavelength of light to a more usable range for augmented photosynthesis. Among them, aggregation-induced emission luminogens (AIEgens) have advantages of efficient light conversion, high biocompatibility, large Stokes' shift, and so on. In this perspective, emerging reports of augmented photosynthesis with luminescent materials, especially the AIEgens are included. We emphasized the spectra shift characteristics, material formation, and sustainable development based on augmented photosynthesis.

Fluorescent Imaging and Sorting of High-Lipid-Content Strains of Green Algae by Using an Aggregation-Induced Emission Luminogen.

Microalgae-based biofuels are receiving attention at the environmental, economic, and social levels because they are clean, renewable, and quickly produced. The green algae Chlorella vulgaris has been extensively studied in research laboratories and the biofuel industry as a model organism to increase lipid production to be cost-effective in commercial production. In this work, we utilized a lipid-droplet-specific luminogen with aggregation-induced emission (AIE) characteristics to increase the lipid production of C. vulgaris by fluorescent imaging and sorting of those algal cells with large and rich lipid droplets for subculturing. The AIE-active TPA-A enabled real-time monitoring of the size and number of lipid droplets in C. vulgaris during their growth period so that we can identify the best time for harvesting. Furthermore, the algae cells with high lipid content were identified and collected for subculturing by the technique of fluorescence-activated cell sorting (FACS). The lipid production in the generation of two successive selections was almost doubled compared to the generation with natural selection. This work demonstrated that the technologies of AIE and FACS could be applied together to improve the production of a third-generation biofuel.

Direct puncture the superior ophthalmic vein guiding by Dyna-CT to obliterating a traumatic carotid-cavernous sinus fistula: A case report and literature review.

RATIONALE: Traumatic carotid-cavernous sinus fistula (TCCF) is a pathological shunt between the carotid arteries and cavernous sinus due to trauma. Imaging-guided (e.g., ultrasonic image and fluoroscopic roadmap image) direct puncture of the superior ophthalmic vein (SOV) for embolization of TCCF has been previously described in other studies. PATIENT CONCERNS AND DIAGNOSIS: We report a case of TCCF in a 58-years-old male patient who was admitted to our hospital with a sustained head injury after falling from a high platform, resulting in rapidly progressive swelling, pain, diminishing vision for more than 6 months, and blindness in his left eye for 1 month. INTERVENTIONS AND OUTCOMES: The patient underwent digital subtraction angiography and endovascular embolization. After the failure of super-selection of the left cavernous sinus, an alternative approach to obliterating the TCCF by puncturing the SOV is directly guided by Dyna-CT. After embolization, the patient's clinical symptoms gradually disappeared and discharged from the hospital 5 days later. No recurrence or complications occurred during follow-up for 1 year. CONCLUSION: This case illustrates that direct puncture of the SOV guided by Dyna-CT as an alternative approach to embolization of TCCF is safe, effective, and feasible.

Cell Cycle Control of Nanoplastics Internalization in Phytoplankton.

Nanoparticles (NPs) for delivering chemotherapeutic drugs are now in clinical trials, and cellular uptake of NPs plays an important role in determining the drug delivery efficiency. Herein, we reported that the bioaccumulation and internalization of NPs were governed by the cell cycle. Specifically, we found that the bioaccumulation of NPs was more favored in the G2/M stages, followed by the S and G0/G1 stages. We demonstrated that three key parameters-clathrin-mediated endocytosis capacity, algal cell membrane permeability, and exopolymer substance (EPS) thickness-were critical in the bioaccumulation of NPs during the cell cycling process. Over the 24-h average duration of cell cycle, clathrin-mediated endocytosis capacity was much higher at the S stage than that at the G0/G1 and G2/M stages. Besides, cell membrane permeability was measured to be higher in S and G2/M stages while the lowest in G0/G1 stage. We have also identified the change of EPS thickness during the 24-h cell cycle. Transition from G0/G1 to S and G2/M induced the attenuation in EPS thickness, and the thinnest EPS was found at the end of mitosis. The cell cycle control NPs internalization were further verified by exposing Ag nanoparticles to algae at different cell cycle stages, confirming the important roles of EPS thickness and cell cycle control in the dynamic internalization processes. The present study highlights the important roles of cell cycle controlling the NPs bioaccumulation and internalization, with possible implications in maximizing NPs internalization efficiency while reducing the cost.

Real-Time 3D Framework Tracing of Extracellular Polymeric Substances by an AIE-Active Nanoprobe.

Extracellular polymeric substances (EPS) are produced by many microorganisms and play an essential role in physiological systems such as nutrient storage and stress resistance. Besides, EPS show great potential in biomedical and therapeutic applications due to their biocompatibility and biodegradability. In situ noninvasive monitoring of the EPS produced by microorganisms is thus critical but has not yet been achieved. Herein, we developed a novel aggregation-induced emission (AIE) active nanoprobe enabling in situ visualization of the EPS distribution produced by various microorganisms (cyanobacteria, yeast, freshwater, and marine phytoplankton). The synthesized AIE-active nanoprobe displayed excellent specificity and precision for the staining of EPS, as well as strong photostability, showing great advantage in sensing the EPS in living organisms. With the application of this novel probe, the three-dimensional (3D) framework of EPS distribution was visualized under different environmental conditions (temperature, light intensity, nutrition, and pH). The EPS distribution was found to correlate significantly with the metal tolerance and cyanobacterial photosynthesis capability. Collectively, this study proposed an AIE-active nanoprobe for visualizing the EPS distribution and quantifying the EPS thickness/volume, and has significant implications in understanding the physiological functions of microorganisms.

In vivo monitoring of tissue regeneration using a ratiometric lysosomal AIE probe.

Tissue regeneration is a crucial self-renewal capability involving many complex biological processes. Although transgenic techniques and fluorescence immunohistochemical staining have promoted our understanding of tissue regeneration, simultaneous quantification and visualization of tissue regeneration processes is not easy to achieve. Herein, we developed a simple and quantitative method for the real-time and non-invasive observation of the process of tissue regeneration. The synthesized ratiometric aggregation-induced-emission (AIE) probe exhibits high selectivity and reversibility for pH responses, good ability to map lysosomal pH both in vitro and in vivo, good biocompatibility and excellent photostability. The caudal fin regeneration of a fish model (medaka larvae) was monitored by tracking the lysosomal pH change. It was found that the mean lysosomal pH is reduced during 24-48 hpa to promote the autophagic activity for cell debris degradation. Our research can quantify the changes in mean lysosomal pH and also exhibit its distribution during the caudal fin regeneration. We believe that the AIE-active lysosomal pH probe can also be potentially used for long-term tracking of various lysosome-involved biological processes, such as tracking the stress responses of tissue, tracking the inflammatory responses, and so on.