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Background: Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics., Methods: In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata , and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo., Results: The results indicated that MC-CDs with a uniform spherical particle size of 1-5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in normal rats. UPLC-MS analysis indicated that the area under the maximum blood concentration of MA from mangiferin-MC-CDs (MA-MC-CDs) was 1.6-fold higher than that from the MA suspension liquid (MA control) after oral administration at a dose of 20 mg/kg., Conclusion: Moutan Cortex -derived novel CDs exhibited superior performance in improving the solubility and bioavailability of MA. This study not only opens new possibilities for the future clinical application of MA but also provides evidence for the development of green biological carbon dots as a drug delivery system to improve the biopharmaceutical properties of insoluble drugs., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2024 Kong et al.)

Fluorescent carbon dots (CDs) are potential tools for the labeling of cells with many advantages such as photostability, multicolor emission, small size, rapid uptake, biocompatibility, and easy preparation. Affinity towards organelles can be influenced by the surface properties of CDs which affect the interaction with the cell and cytoplasmic distribution. Organelle targeting by carbon dots is promising for anticancer treatment; thus, intracellular trafficking and cytotoxicity of cationic CDs was investigated. Based on our previous study, we used quaternized carbon dots (QCDs) for treatment and monitoring the behavior of two human cancer cell MCF-7 and HeLa lines. We found similarities between human cancer cells and mouse fibroblasts in the case of QCDs uptake. Time lapse microscopy of QCDs-labeled MCF-7 cells showed that cells are dying during the first two hours, faster at lower doses than at higher ones. QCDs at a concentration of 100 µg/mL entered into the nucleus before cellular death; however, at a dose of 200 µg/mL, blebbing of the cellular membrane occurred, with a subsequent penetration of QCDs into the nuclear area. In the case of HeLa cells, the dose-depended effect did not happen; however, the labeled cells were also dying in mitosis and genotoxicity occurred nearly at all doses. Moreover, contrasted intracellular compartments, probably mitochondria, were obvious after 24 h incubation with 100 µg/mL of QCDs. The levels of reactive oxygen species (ROS) slightly increased after 24 h, depending on the concentration, thus the genotoxicity was likely evoked by the nanomaterial. A decrease in viability did not reach IC 50 as the DNA damage was probably partly repaired in the prolonged G0/G1 phase of the cell cycle. Thus, the defects in the G2/M phase may have allowed a damaged cell to enter mitosis and undergo apoptosis. The anticancer effect in both cell lines was manifested mainly through genotoxicity.

We disclose for the first time a facile synthetic methodology for the preparation of multicolor carbon dots (CDs) from a single source barring any chromatographic separations. This was achieved via sequential intraparticle cross-linking of surface abundant carboxylic acid groups on the CDs synthesized from a precursor to control their photoluminescence (PL) spectra as well as affect their degree of cellular internalization in cancer cells. The change in PL spectra with sequential cross-linking was projected by theoretical density functional theory (DFT) studies and validated by multiple characterization tools such as X-ray photoelectron spectroscopy (XPS), PL spectroscopy, ninhydrin assay, etc. The variation in cellular internalization of these cross-linked CDs was demonstrated using inhibitor assays, confocal microscopy, and flow cytometry. We supplemented our findings with high-resolution dark-field imaging to visualize and confirm the colocalization of these CDs into distinct intracellular compartments. Finally, to prove the surface-state controlled PL mechanisms of these cross-linked CDs, we fabricated a triple-channel sensor array for the identification of different analytes including metal ions and biologically relevant proteins.

Current treatments for osteoporosis and other bone degenerative diseases predominately rely on preventing further bone erosion rather than restoring bone mass, as the latter treatments can unintentionally trigger cancer development by undiscriminatingly promoting cell proliferation. One approach to circumvent this problem is through the development of novel chemical carriers to deliver drug agents specifically to bones. We have recently shown that carbon nanodots (C-dots) synthesized from carbon nanopowder can bind with high affinity and specificity to developing bones in the larval zebrafish. Larval bones, however, are physiologically different from adult bones in their growth, repair, and regeneration properties. Here we report that C-dots can bind to adult zebrafish bones and that this binding is highly specific to areas of appositional growth. C-dots deposition occurred within 30 minutes after delivery and was highly selective, with bones undergoing regeneration and repair showing higher levels of C-dots deposition than bones undergoing normal homeostatic turnover. Importantly, C-dots deposition did not interfere with bone regeneration or the animal's health. Together, our results establish C-dots as a potential novel vehicle for the targeted delivery of drugs to treat adult bone disease.

Ulcerative colitis (UC) is a modern refractory disease with steadily increasing incidence worldwide that urgently requires effective and safe therapies. Therapeutic peptides delivered using nanocarriers have shown promising developments for the treatment of UC. We developed a novel colon-accumulating oral drug delivery nanoplatform consisting of Musca domestica cecropin (MDC) and mesoporous carbon nanoparticles (MCNs) and investigated its effects and mechanism of action for the treatment of UC. Methods: An optimized one-step soft templating method was developed to synthesize MCNs, into which MDC was loaded to fabricate MDC@MCNs. MCNs and MDC@MCNs were characterized by BET, XRD, and TEM. MDC and MDC@MCNs resistance to trypsin degradation was measured through Oxford cup antibacterial experiments using Salmonella typhimurium as the indicator. Uptake of MDC and MDC@MCNs by NCM460 cells was observed by fluorescence microscopy. The biocompatibility of MDC, MCNs, and MDC@MCNs was evaluated in three cell lines (NCM460, L02, and NIH3T3) and C57BL/6 mice. Dextran sulphate sodium was used to establish models of NCM460 cell injury and UC in mice. MTT assay, flow cytometry, and mitochondrial membrane potential assay were applied to determine the effects of MDC@MCNs on NCM460 cells injury. Additionally, a variety of biological methods such as H&E staining, TEM, ELISA, qPCR, Western blotting, and 16s rDNA sequencing were performed to explore the effects and underlying mechanism of MDC@MCN on UC in vivo . Colonic adhesion of MCNs was compared in normal and UC mice. The oral biodistributions of MDC and MDC@MCNs in the gastrointestinal tract of mice were also determined. Results: MDC@MCNs were successfully developed and exhibited excellent ability to resist destruction by trypsin and were taken up by NCM460 cells more readily than MDC. In vitro studies showed that MDC@MCNs better inhibited DSS-induced NCM460 cells damage with lower toxicity to L02 and NIH3T3 cells compared with MDC. In vivo results indicated that MDC@MCNs have good biocompatibility and significantly improved colonic injury in UC mice by effectively inhibiting inflammation and oxidative stress, maintaining colonic tight junctions, and regulating intestinal flora. Moreover, MDC@MCNs were strongly retained in the intestines, which was attributed to intestinal adhesion and aggregation of MCNs, serving as one of the important reasons for its enhanced efficacy after oral administration compared with MDC. Conclusion: MDC@MCNs alleviated DSS-induced UC by ameliorating colonic epithelial cells damage, inhibiting inflammation and oxidative stress, enhancing colonic tight junctions, and regulating intestinal flora. This colon-accumulating oral drug delivery nanoplatform may provide a novel and precise therapeutic strategy for UC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Boronic acids have been successfully employed as inhibitors of hydrolytic enzymes. Typically, an enzymatic nucleophile catalyzing hydrolysis adds to the electrophilic boron atom forming a tetrahedral species that mimics the intermediate(s)/transition state(s) for the hydrolysis reaction. We show that para -substituted phenylboronic acids (PBAs) are potent competitive inhibitors of mandelate racemase (MR), an enzyme that catalyzes a 1,1-proton transfer rather than a hydrolysis reaction. The K i value for PBA was 1.8 ± 0.1 μM, and p -Cl-PBA exhibited the most potent inhibition ( K i = 81 ± 4 nM), exceeding the binding affinity of the substrate by ∼4 orders of magnitude. Isothermal titration calorimetric studies with the wild-type, K166M, and H297N MR variants indicated that, of the two Brønsted acid-base catalysts Lys 166 and His 297, the former made the greater contribution to inhibitor binding. The X-ray crystal structure of the MR·PBA complex revealed the presence of multiple H-bonds between the boronic acid hydroxyl groups and the side chains of active site residues, as well as formation of a His 297 N ε2 -B dative bond. The dramatic upfield change in chemical shift of 27.2 ppm in the solution-phase 11 B nuclear magnetic resonance spectrum accompanying binding of PBA by MR was consistent with an sp 3 -hybridized boron, which was also supported by density-functional theory calculations. These unprecedented findings suggest that, beyond substituting boron at carbon centers participating in hydrolysis reactions, substitution of boron at the acidic carbon center of a substrate furnishes a new approach for generating inhibitors of enzymes catalyzing the deprotonation of carbon acid substrates.

The alpine meadow is highly sensitive to global climate change due to its high elevation and cold environment. To understand the dynamics of ecosystem carbon cycling, CO2 fluxes were measured over the Suli alpine meadow, which is located at the upper reach of the Shule River basin at the northeastern edge of the Qinghai-Tibet Plateau (QTP), China. The measurements were taken from October 2008 to September 2012 using the eddy covariance technique. Obvious seasonal and inter-annual variations were observed in the CO2 flux. The annual net carbon exchange ranged from -195.28 g·CO2·m-2 to -118.49 g·CO2·m-2, indicating that the alpine meadow ecosystem in this area played a role as a carbon sink. The inter-annual variability in the net carbon exchange was significantly related to the length of the growing season for the alpine meadow. The results showed that the months of June, July and August were the strongest CO2 absorption periods, while April, May and October were the strongest CO2 release periods. The annual net exchanges of CO2 in the four years were -118.49 g·CO2·m-2, -130.75 g·CO2·m-2, -195.83 g·CO2·m-2 and -160.65 g·CO2·m-2, and the average value was -151.43 g·CO2·m-2. On a seasonal scale, the monthly CO2 fluxes were largely controlled by temperature. At the annual scale, there was no dominant factor that influenced the interannual variations in the CO2 flux., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Carbon dots (CDs), as a fascinating class of fluorescent carbon nanomaterials, have been proven to be powerful tools in the field of bioimaging and biosensing due to their small size, suitable photostability and favourable biocompatibility. However, the cellular uptake of free CDs lacks selectivity and the same negative charges as cell membranes may cause inefficient cell internalization. In this study, an efficient detecting and targeting nanosystem was developed based on the DNA aptamer AS1411 modified CDs with polyethyleneimine (PEI) as connecting bridge., Materials and Methods: Hydrothermally prepared CDs were assembled with positive-charged PEI, followed by conjugation with AS1411 through electrostatic interaction to form CDs-PEI-AS1411 nanocomplexes. The CDs, CDs-PEI and CDs-PEI-AS1411 were characterized by transmission electron microscopy (TEM), fourier transform infrared (FTIR) spectra, UV-vis spectra, zeta potential measurements and capillary electrophoresis characterizations. The cytotoxicity investigation of the CDs-PEI-AS1411 and CDs-PEI in both MCF-7 and L929 cells was carried out by the CCK-8 assay. The cellular uptake of the CDs-PEI-AS1411 was studied with confocal microscopy and flow cytometry., Results: The as-prepared nanosystem possessed good photostability and no obvious cytotoxicity. On the basis of the confocal laser scanning microscope observation and the flow cytometry studies, the cellular uptake of CDs-PEI-AS1411 nanosystem in MCF-7 cells was significantly higher than that of L929 cells, which revealed the highly selective detection ability of nucleolin-positive cells., Conclusions: The results of this study indicated that the CDs-PEI-AS1411 nanosystem had a potential value in cancer cell targeted imaging., (© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

A green and simple process for preparing the polyethylene glycol passivated fluorescent carbon dots (CDs-PEG) have been studied by a microwave pyrolysis method, using gelatin and PEG as starting materials. This method is very effective for development of carbon-based quantum dots from gelatin with high quantum yield (QY). The synthesized CDs-PEG were found to emit blue photoluminescence (PL) with a maximum QY of 34%. At the following research, we investigated the effect of the presence of PEG on PL intensity, and the result showed that CDs-PEG becomes stronger PL properties than pure CDs from gelatin. The synthesized CDs-PEG were characterized by FTIR, TEM, UV-vis, PL, zeta potential and XRD analyses. The anticancer performance of developed CDs-PEG was evaluated by in vitro tests such as MTT assay and fluorescence microscopy analyses. The examination of CDs-PEG as an anti-cancer drug nanocarrier for methotrexate (MTX) illustrated a better antitumor efficacy than free MTX due to its enhanced nuclear delivery in vitro, which resulting in highly effective tumour growth inhibition and improving targeted cancer therapy in clinical medicine.

p-Nitrophenol (p-NP) pollutants are widely present in soil and aquatic environments and can seriously impair the health of living beings. Hence, a rapid, sensitive, and selective method for p-NP detection is urgently needed. Herein, for the first time, we successfully synthesized fluorescent carbon dots (CDs) from Bacillus cereus (BC) via a one-step hydrothermal process. The obtained CDs-BC can be applied as a rapid, highly selective, and sensitive sensor for p-NP detection. The fluorescence quenching efficiency of the CD-BC sensor exhibited excellent linear responses with p-NP concentrations at both 0.3-6.5 μM and 6.5-30 μM, with a detection limit of 0.11 μM. The mechanism of p-NP detection is based on the inner filter effect (IFE). Preliminary bacteria, cell, and animal studies showed that the as-prepared CDs-BC possess high photostability, excellent biocompatibility, low or no biotoxicity, and multicolor fluorescence emission properties; furthermore, they can be rapidly excreted from the body of mice, which suggests their potential for applications in the biomedical field.

Study Objective: To evaluate the detection rate and accuracy of sentinel lymph node (SLN) mapping using cervical and fundal injections of carbon nanoparticles (CNPs) in laparoscopic surgery of endometrioid endometrial cancer (EC) and to identify uterine lymphatic drainage pathways validated by mapping., Design: A prospective consecutive study (Canadian Task Force classification II-2)., Setting: An academic research center., Patients: Consecutive patients with a pathologic diagnosis of early-stage EC scheduled for primary laparoscopic-assisted staging surgery (laparoscopic hysterectomy, bilateral salpingo-oophorectomy, or comprehensive lymphadenectomy)., Interventions: Enrolled patients underwent laparoscopic SLN mapping with a 50-mg CNP tracer injection. Fifty patients received fundal subserosal injections at 4 sites (the fundal group), whereas 65 patients received cervical submucosal injections at 2 sites (the cervical group). After SLN mapping, all patients underwent laparoscopic staging surgery., Measurements and Main Results: No allergic reactions to CNPs were observed in either group. The overall SLN detection rates were 100% and 92% in the cervical and fundal groups, and the bilateral SLN detection rates were 97% and 68% (p < .001), respectively. A total of 12 metastatic SLNs were accurately detected in 5 patients. The sensitivity of metastatic lymph node detection was 100% in the cervical group, which is higher than that in the fundal group (80%). The false-negative rates were 0% and 20%, respectively, in the cervical and fundal groups. Furthermore, we verified 3 uterine lymphatic pathways using the 2 injection methods. The upper paracervical pathway was the most common drainage pathway in both groups (91.4% in the cervical group vs 80.24% in the fundal group), whereas the infundibulopelvic pathway was observed only in the fundal group (15.11%)., Conclusion: SLN mapping by CNPs in laparoscopic surgery for EC is a safe and effective alternative, with a higher detection rate and better accuracy with cervical injections than fundal injections. The upper paracervical pathway was the most common lymphatic pathway, whereas the infundibulopelvic pathway was only displayed in fundal injections., (Copyright © 2018 AAGL. Published by Elsevier Inc. All rights reserved.)

Carbon dots (CDots) for their excellent optical and other properties have been widely pursued for potential biomedical applications, in which a more comprehensive understanding on the cellular behaviors and mechanisms of CDots is required. For such a purpose, two kinds of CDots with surface passivation by 3-ethoxypropylamine (EPA-CDots) and oligomeric polyethylenimine (PEI-CDots) were selected for evaluations on their uptakes by human cervical carcinoma HeLa cells at three cell cycle phases (G 0 /G 1 , S and G 2 /M), and on their different internalization pathways and translocations in cells. The results show that HeLa cells could internalize both CDots by different pathways, with an overall slightly higher internalization efficiency for PEI-CDots. The presence of serum in culture media could have major effects, significantly enhancing the cellular uptake of EPA-CDots, yet markedly inhibiting that of PEI-CDots. The HeLa cells at different cell cycle phases have different behaviors in taking up the CDots, which are also affected by the different dot surface moieties and serum in culture media. Mechanistic implications of the results and the opportunities associated with an improved understanding on the cellular behaviors of CDots for potentially the manipulation and control of their cellular uptakes and translocations are discussed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The anterograde neuroanatomical tracing technique plays a crucial role in studying and charting the complex interconnections of the nervous system. But there are several major limitations for traditional neural tracers, such as complex immunohistochemical staining procedures, low fluorescence intensity and quick fluorescence quenching. Carbon dots (CDs) as fluorescent bio-probes have been widely used in the biological studies due to their superior optical properties, excellent chemical stability, low toxicity, and easy modifications. In this study, biotinylated dextran amine (BDA) and red fluorescent carbonized polymer dots (CPDs) are successfully conjugated to develop a brand-new generation of fluorescent nano-neural tracers: BDA-CPDs. They are successfully applied as fluorescent probes for in vitro and in vivo bioimaging. In vitro biodistribution of BDA-CPDs shows that they distribute mainly in lysosomes and endoplasmic reticulum. Moreover, two metabolic pathways of BDA-CPDs are found through the investigation of in vivo biodistribution of BDA-CPDs. Furthermore, they can be taken up and anterogradely transported by neurons within the peripheral nervous system of rats. Our results suggest that BDA-CPDs have many advantages over traditional tracers, such as low toxicity, high photoluminescence intensity, excellent photostability and easy procedures. Anterograde pathway tracing with BDA-CPDs is a simple, direct and economical way of studying the connections in the nervous system. Therefore, BDA-CPDs are reliable and valuable fluorescent anterograde neural tracers.

Carbon dots (CDs) with low biotoxicity, high photostability, and well-controlled size are highly desirable imaging agents for optical bioimaging. However, most of the CDs triggered by ultraviolet/blue light present visible/first near-infrared emissions shorter than 820 nm, impairing their imaging applications in vivo by low penetration depth. Hence, developing novel CD-based materials with second near-infrared (NIR-II) emission located in 1000-1700 nm region is an urgent task. Here, a novel NIR-II-emitting CD-based nanoprobe triggered by 808 nm laser is developed. The designed CDs with 900-1200 nm luminescence possess high quantum yield (QY-0.4%) and high biocompatibility, which have proven to be effective probes for in vivo NIR-II bioimaging. Notably, nearly 65% CDs are excreted from mouse urine within 6 h, demonstrating the rapid renal clearance of CDs. Furthermore, the designed CDs also exhibit high photothermal efficiency (30.6%), making them ideal materials for thermal ablation of cancer. Our findings pave the way of designing a multifunctional CD-based theranostic platform for simultaneously integrating the advanced NIR-II bioimaging and photothermal therapy of cancer.

Nanoparticle-based theranostics combines tumor imaging and cancer therapy in one platform, but the synthesis of theranostic agents is impeded by chemical groups on the surface and the size and morphology of the components. Strategies to construct a multifunctional platform for bioimaging and photothermal therapy (PTT) are urgently needed. A new upconversion-magnetic agent (FeCUPs) based on hollow carbon spheres, which is both a photothermal agent and a dual carrier of luminescent and magnetic nanoparticles, provides an effective approach for tumor elimination. Methods: The morphology of FeCUPs was characterized for the construction and size adjustment of the theranostic agent using transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy and high angle annular dark field scanning transmission electron microscopy. The distribution of FeCUPs was tracked under in-situ upconversion luminescence (UCL) imaging and magnetic resonance imaging (MRI) in vivo . Photothermal therapy was carried out on tumor-bearing mice, after which the toxicity of PTT was evaluated by a blood biochemistry test and histological section analysis. Results: Stable and uniform loading of luminescent nanocomposites on three-dimensional carbon materials is reported for the first time. Based on the mechanism of synthesis, the size of the hybrid particles was adjusted from micrometers to nanometers. External magnetic field-enhanced photothermal therapy with multi-model imaging was accomplished using FeCUPs. Moreover, no cancer recurrence was found during 14 days of recovery without PTT. Conclusions: Hollow carbon spheres, photothermal agents loaded with upconversion nanoparticles inside and magnetic nanoparticles outside were prepared for photothermal therapy. The aggregation of FeCUPs in tumors by the local magnetic field was verified by MRI and UCL imaging, and PTT was enhanced., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

In this work, we presented ternary nanoparticles [poly(carboxybetaine methacrylate) (pCBMA)(peptide dendrimer-modified carbon dots (CD-D)/doxorubicin (DOX))] based on peptide dendritic carbon dots (CDs) to realize tumor-specific drug delivery and highly efficient cancer therapy. The versatile nanoparticles could achieve "stealth" delivery in blood due to the antifouling zwitterion coating. Meanwhile, charge changes of the zwitterions could be moderated during their transportation toward/inside tumor cells, where subtle environmental pH variations acted as potent stimuli to actualize desired functions. In particular, the detachment of the zwitterionic "coat" at the tumor site resulted in the exposure of abundant peripheral guanidine groups on peptide dendritic carbon dots (CD-D/DOX) owing to the extracellular pH environment (pH 6.8)-induced charge conversion. Consequently, the positively charged CD-D/DOX (+7.02 mV) interacted with the negatively charged cancer cell membrane to enhance cellular uptake. After endocytosis, tumor intracellular microenvironments (acidic conditions and high glutathione (GSH) levels) could lead to effective disintegration of the CD-D/DOX entities due to acid-induced protonation of guanidine groups and glutathione-induced cleavage of peptide dendritic components on CDs, and then effective endosomal escape and fast doxorubicin hydrochloride (DOX·HCl) release (73.2% accumulative release within 4 h) were achieved successively. This strategy enabled a 9.19-fold drug release rate at tumor sites in comparison with the one in the physiological environment. Moreover, the excellent fluorescence properties of CDs endowed the pCBMA(CD-D/DOX) with fluorescence bioimaging function. In view of the above-mentioned advantages, pCBMA(CD-D/DOX) exhibited outstanding antitumor activities both in vitro and in vivo, demonstrating much higher antitumor efficacy and less side effects than the free DOX·HCl.

Drug delivery systems for doxorubicin (DOX) have attracted tremendous interest nowadays for the improved efficacy and/or reduced toxicity. Due to the aromatic structures and hydrophobic domains, carbon nanoparticle suspension injection (CNSI), a clinical applied reagent for lymph node mapping, strongly adsorbs DOX and holds great potential in cancer therapy. Herein, we evaluated the therapeutic effects of CNSI-DOX to establish its delivery applications for cancer drugs. CNSI adsorbed DOX from solution quickly after the mixing, and the release of DOX from CNSI followed a pH-dependent way. CNSI-DOX and free DOX had nearly identical inhibitive effects on cancer cells, while the vehicle CNSI was nontoxic. CNSI-DOX largely prolonged the life span of ascites tumor bearing mice after the intraperitoneally injection and the ascites weights showed significant decreases. CNSI-DOX also inhibited the growth of subcutaneous xenografts following the same administration route. The therapeutic efficacy of CNSI-DOX was similar to that of free DOX in ascites tumor model, but slightly lower in subcutaneous xenografts model. The advantage of using CNSI was majorly reflected by the reduced toxicity of DOX according to the bodyweight changes, serum biochemical indicators and histopathological observations. The LD 50 (median lethal dose) value of CNSI-DOX was 43.8 mg/kg bodyweight, nearly three times of that of free DOX (15.2 mg/kg bodyweight). Our results suggested that CNSI might be used for DOX delivery through "off label" use to benefit the patients immediately., (Copyright © 2018. Published by Elsevier B.V.)

Bioavailable dissolved organic carbon (B DOC ), nitrogen (B DON ) and their degradation rate constants were measured for the Chilika Lagoon, India. Long-term laboratory incubation experiments (90 days) were conducted at a constant temperature (25 °C) to quantify the bioavailable dissolved organic matter (DOM) and the possible degradation rate coefficients. The results showed that 41 ± 12% of dissolved organic carbon (DOC) and 47 ± 17% of dissolved organic nitrogen (DON) were B DOC and B DON respectively, with their stoichiometry found to be higher than the Redfield ratio. A first order exponential non-linear fitting routine was used to estimate pool sizes. The degradation rate constant (k) for the B DOC varied from 0.127-0.329 d -1 and B DON from 0.043-0.306 d -1 during the study period. Half-lives of the B DOC and B DON ranged from 2.1-5.4 and 2.2-15.9 days, respectively. Overall, the results showed that a fraction of the labile DON was transported from the lagoon to the adjacent coastal sea., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ultrasmall clearable nanoparticles possess enormous potential as cancer imaging agents. In particular, biocompatible silicon nanoparticles (Si NPs) and carbon quantum dots (CQDs) hold great potential in this regard. Their facile surface functionalization easily allows the introduction of different labels for in vivo imaging. However, to date, a thorough biodistribution study by in vivo positron emission tomography (PET) and a comparative study of Si vs. C particles of similar size are missing. In this contribution, ultrasmall (size <5 nm) Si NPs and CQDs were synthesized and characterized by high-resolution transmission electron microscopy (HR-TEM), Fourier-transform infrared (FTIR), absorption and steady-state emission spectroscopy. Subsequent functionalization of NPs with a near-infrared dye (Kodak-XS-670) or a radiolabel (64Cu) enabled a detailed in vitro and in vivo study of the particles. For radiolabeling experiments, the bifunctional chelating agent S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) was conjugated to the amino surface groups of the respective NPs. Efficient radiolabeling of NOTA-functionalized NPs with the positron emitter 64Cu was found. The biodistribution and PET studies showed a rapid renal clearance from the in vivo systems for both variants of the nanoparticles. Interestingly, the different derivatives investigated exhibited significant differences in the biodistribution and pharmacokinetic properties. This can mostly be attributed to different surface charge and hydrophilicity of the NPs, arising from the synthetic strategy used to prepare the particles.

The distribution of surface modified carbon dots (CDs) in the pumpkin seedlings was studied by visualization techniques and their potential phytotoxicity was investigated at both the physiological and biochemical levels. The average size of carbon dots was approximately 4 nm. The fluorescent peaks of bared CDs, CD-PEI and CD-PAA were between 420 nm and 500 nm, indicating CDs could emit blue and green fluorescence. Fluorescent images showed that all three types of CDs could accumulate in the pumpkin roots and translocate to the shoots, although the distribution pattern of each CDs was obviously different. At the biochemical level, the elevated antioxidant enzymes in pumpkin roots suggest that all the CDs could potentially trigger the antioxidant defense systems in pumpkin seedlings. Additionally, such alteration was greater in the roots than in the shoots. Our study represents a new perspective on CD visualization in plant tissues and provide useful information for the potential toxicity of different types of CDs to terrestrial plants, which is of importance to agricultural application.

Samples collected from 12 rivers with typical vegetation types in the permafrost regions on the Qinghai-Tibetan Plateau were incubated in the laboratory, and the relationships among the vegetation types, river discharges, the compositions of dissolved organic carbon (DOC), permafrost areas, riverine DOC concentration, biodegradability of dissolved organic carbon (BDOC), and the biodegradation kinetics were examined. The results showed that the DOC concentrations of typical vegetation types in the basin, such as alpine meadow (AM), alpine swamp meadow-alpine meadow (ASM-AM), alpine meadow-alpine steppe (AM-AS), and alpine meadow-alpine steppe-bare soil (AM-AS-BL), were (5.17±0.21), (5.02±0.50), (3.55±0.25), and (2.79±0.41) mg ·L -1 , respectively. The values for the bioavailability of river DOC of different vegetation types were (23.54±2.62)%, (23.66±3.31)%, (18.17±5.26)%, and (11.72±15.56)%, respectively. Correspondingly, the riverine DOC aromaticity increased along with the vegetation cover, while the biodegradation and degradation rates decreased gradually. During the incubation, the reaction of BDOC was in accordance with the first-order kinetics equation. Furthermore, the BDOC in continuous permafrost regions of the rivers was greater than that in the non-continuous permafrost regions. The BDOC in higher discharges were lower than those with lower discharges. Taken together, the results suggested that the vegetation types were the main controlling factors for the BDOC, and BDOC was also related to the discharge and permafrost.

This study investigated the simultaneous carbon and nitrogen removal from anaerobic effluent of cassava stillage using a lab-scale integrated system consisting of an upflow anaerobic sludge blanket (UASB) reactor and an activated sludge (AS) process. Simultaneous denitrification and methanogenesis (SDM) was observed in the UASB with nitrate recirculation. Compared with the blank reactor without recirculation, the overall chemical oxygen demand (COD) removal efficiencies in the combined system with nitrate recirculation were similar (80-90%), while the TN removal efficiencies were significantly improved from 4.7% to 71.0%. Additionally, the anaerobic COD removal efficiencies increased from 21% to 40% as the recirculation ratio decreased from 3 to 1. Although the influent nitrate concentrations fluctuated (60-140 mg N/L), the nitrate removal efficiencies could be maintained at about 97% under different recirculation conditions. With the decreasing recirculation ratio from 3 to 1, the CH 4 content in biogas improved from 2% to 40% while the N 2 content reduced from 95.8% to 50.6%. The 16S rDNA sequencing results indicated that bacteria diversity in anaerobic SDM granular sludge was much higher than archaea. The effect of recirculation ratios on the bacterial and archaeal communities in SDM granular sludge could be further confirmed by the relative abundance of denitrifying bacteria., (Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

In this manuscript, the effect of the particle size of polymer-functionalized mesoporous carbon (MPP) nanoparticles on enhancing oral absorption of a water-insoluble drug is first investigated. The insoluble drug, fenofibrate (Fen), was selected as the model drug loaded in the MPP nanoparticles. MPP nanoparticles with different particle sizes were designed for improving the oral bioavailability of drugs, in which the branched polyethyleneimine (PEI) and polyacrylic acid (PAA) were modified on the surfaces of mesoporous carbon nanoparticles (MCNs) with amide bonds. In addition, PEI-functionalized carbon quantum dots (PCA) and radioisotope 125 I were applied to label the MPP nanoparticles to trace in the vivo process. According to the data, the MPP nanoparticles could markedly improve the dissolution rate and oral bioavailability of Fen. Interestingly, the MPP nanoparticle size had a notable effect on Fen oral absorption, and intermediate sized MPP nanoparticles were expected to be more ideal oral drug carriers. The nanoparticles were safe and easily excreted. These findings present the prospect of MPP nanoparticles for oral application, and guides the rational design of an oral delivery system with respect to particle size., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Lower cellular adhesion and dense fibrous capsule formation around silicone breast implants caused by lower biocompatibility is a serious clinical problem. Preliminary work has shown that ion implantation enhances cell adhesion. Whether the biocompatibility is further enhanced by higher doses of carbon ion implantation and the mechanism by which ion implantation enhances biocompatibility remain unclear. In this study, five doses of carbon ions, which gradually increase, were implanted on the surface of silicone rubber and then the surface characteristics were surveyed. Then, cell adhesion, proliferation and migration were investigated. Furthermore, the vitronectin (VN) protein was used as a model protein to investigate whether the ion implantation affected the adsorbed protein on the surface. The obtained results indicate that enhanced cytocompatibility is dose dependent when the doses of ion implantation are less than 1 × 10 16  ions/cm 2 . However, when the doses of ion implantation are more than 1 × 10 16  ions/cm 2 , enhanced cytocompatibility is not significant. In addition, surface physicochemical changes by ion implantation induced a conformational change of the adsorbed vitronectin protein that enhanced cytocompatibility. Together, these results suggest that the optimum value of carbon ion implantation in silicone rubber to enhance biocompatibility is 1 × 10 16  ions/cm 2 , and ion implantation regulates conformational changes of adsorbed ECM proteins, such as VN, and mediates the expression of intracellular signals that enhance the biocompatibility of silicone rubber. The results herein provide new insights into the surface modification of implant polymer materials to enhance biocompatibility. It has potentially broad applications in the biomedical field.

Fresh and dehydrated banana peels were used as biomass feedstock to produce highly effective sorbent biochars through a facile one-step hydrothermal carbonization approach with 20%vol phosphoric acid as the reaction medium. The elemental ratio of oxygen content of the two as-prepared biochars were about 20%, and the FT-IR analysis confirmed the existence of abundant surface functional groups such as hydroxyl and carboxyl which greatly enhanced the adsorption performance. The sorbents showed excellent lead clarification capability of 359mg·g -1 and 193mg·g -1 for dehydrated and fresh banana peels based biochars, respectively. The change of the CO/OCO and the appearance of PbO/PbOC on the surface after adsorption confirmed that the ion exchange might be the dominant mechanism. The dehydration and pulverization pre-treatment and the addition of phosphoric acid can benefit the formation of those functional groups and hydrothermal carbonization can be a promising method to transfer biomass like fruit peels into biochars with excellent adsorption performance., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A spiral fiber based biofilm reactor was developed to remove nitrate and chromate simultaneously. The denitrification and Cr(VI) removal efficiency was evaluated with synthetic groundwater (NO 3 - -N=50mg/L) under different Cr(VI) concentrations (0-1.0mg/L), carbon nitrogen ratios (C/N) (0.8-1.2), hydraulic retention times (HRT) (2-16h) and initial pHs (4-10). Nitrate and Cr(VI) were completely removed without nitrite accumulation when the Cr(VI) concentration was lower than 0.4mg/L. As Cr(VI) up to 1.0mg/L, the system was obviously inhibited, but it recovered rapidly within 6days due to the strong adaption and domestication of microorganisms in the biofilm reactor. The results demonstrated that high removal efficiency of nitrate (≥99%) and Cr(VI) (≥95%) were achieved at lower C/N=0.9, HRT=8h, initial pH=7, and Cr(VI)=1.0mg/L. The technology proposed in present study can be alternative for simultaneous removal of co-contaminants in groundwater., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Carbon-based nanoparticles (CBNs) are largely distributed worldwide due to fossil fuel combustion and their presence in many consumer products. In addition to their proven toxicological effects in several biological models, attention in recent years has focussed on the role played by CBNs as Trojan-horse carriers for adsorbed environmental pollutants. This role has not been conclusively determined to date because CBNs can decrease the bioavailability of contaminants or represent an additional source of intake. Herein, we evaluated the intake, transport and distribution of one of the carbon-based powders, the so-called carbon nanopowder (CNPW), and benzo(α)pyrene, when administered alone and in co-exposure to Danio rerio embryos. Data obtained by means of advanced microscopic techniques illustrated that the "particle-specific" effect induced a modification in the accumulation of benzo(α)pyrene, which is forced to follow the distribution of the physical pollutant instead of its natural bioaccumulation. The combined results from functional proteomics and gene transcription analysis highlighted the different biochemical pathways involved in the action of the two different contaminants administered alone and when bound together. In particular, we observed a clear change in several proteins involved in the homeostatic response to hypoxia only after exposure to the CNPW or co-exposure to the mixture, whereas exposure to benzo(α)pyrene alone mainly modified structural proteins. The entire dataset suggested a Trojan-horse mechanism involved in the biological impacts on Danio rerio embryos especially due to different bioaccumulation pathways and cellular targets.

A novel heterotrophic nitrifying fungus, defined as Penicillium sp. L1, can form mycelial pellets in liquid medium in this study. The effects of inoculation method, C/N ratio, initial pH, and temperature were gradually evaluated to improve the simultaneous removal of total nitrogen (TN) and chemical oxygen demand (COD) in wastewater by Penicillium sp. L1. Results showed that compared with spore inoculation, 48 h pellet inoculum could significantly increase the pellet size (from about 1.5 mm to 3.2 mm) and improve the removal capability, particularly for COD removal (from less than 50-86.20%). The removal efficiencies of TN and COD reached 98.38% (from 136.01 mg/L to 2.20 mg/L) and 92.40% (from 10,720 mg/L to 815 mg/L) under the following conditions: C/N 36, pH 3, 30°C, and inoculation with 48 h pellets. The pellet diameter reached 4.8 mm after 4-day cultivation. In this case, Penicillium sp. L1 removed TN from 415.93 mg/L to 43.39 mg/L, as well as COD from 29,533 mg/L to 8850 mg/L. Overall, the results indicated that the pellet size was closely related to the pollutant-removal ability of Penicillium sp. L1. Furthermore, mycelial pellets (4.8 mm, dead) only adsorbed 38.08% TN (from 125.45 mg/L to 77.78 mg/L), which indicated that adsorption did not play a major role in the nitrogen-removal process., (Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Purpose: 11 C-Acetate is radiotracer being considered an alternative to 18 F-fluorodeoxyglucose. Evaluation of 11 C-acetate biodistribution in human parenchymal organs is described., Methods and Materials: 60 consecutive patients referred to 11 C-acetate PET CT suspected of renal or prostate cancer relapse with negative results (no recurrent tumor) were included in the study. Acquisition from the base of skull to upper thigh was made 20 min after i.v. injection of 720 MBq of 11 C-acetate. The distribution was evaluated by measuring the uptake in pancreas (uncinate process and body separately), liver, spleen, and left suprarenal gland. Clinical data of included patients showed no abnormalities in these organs., Results: Biodistributions of 11 C-acetate radiotracer were compared in different organs. Standardized uptake values of 11 C-acetate were significantly higher in pancreatic parenchyma (SUV mean 6,4) than in liver (SUV mean 3,3), spleen (SUV mean 4,5), or suprarenal gland (SUV mean 2,7) tissues. No significant difference was found between pancreatic head (SUV mean 6,4) and body (SUV mean 5,9) uptake. In case of all aforementioned organs, there were no differences either between both sexes or between formerly diagnosed tumors (renal and prostate)., Conclusions: Evaluation of 11 C-acetate uptake differences in parenchymal organs will allow establishing normal patterns of distribution. High pancreatic uptake may be used in quantitative assessment of organ function in diffuse nonneoplastic pathology.

The distribution of iron-carbon nanoparticles in FeC-DSPE-PEG-2000 modification (micellar particles with structure (Fe) core-carbon shell; PEG-based coating) is studied. The greater part of the nanoparticles accumulated in the spleen and liver, a small amount in the lungs, and the minimum amount in the thymus. The structural changes in the lymphoid organs were minor and involved only the microcirculatory bed. Analysis of the peripheral blood showed manifest anemia, thrombocytopenia, and leukocytosis.

Purpose: AST-120 is used to decrease the abundance of serum uremic toxins in treatment of chronic kidney disease; however, it could also adsorb concomitantly administered drugs. This study aimed to develop a prediction method for drug interaction between AST-120 and concomitantly administered drugs based on in vitro dissolution and in vivo absorption behavior., Methods: Sixty-eight drugs were selected for the analysis. For each drug, theoretical dissolution (R d ) and absorption (R a ) rates at estimated dosing intervals (1, 30, 60, 90, 120, and 240 min) were calculated using the Noyes-Whitney formula and compartment analysis, respectively. The optimal thresholds for R d and R a (R dth and R ath ) were estimated by comparing the results with those of previous drug interaction studies for six drugs. Four drug interaction risk categories for 68 drugs at each dose interval were defined according to the indices of dissolution and absorption against their thresholds., Results: The in vitro dissolution and in vivo absorption behavior of the selected drugs were well fitted to the Noyes-Whitney formula and one- or two-compartment models. The optimal R dth and R ath that gave the highest value of consistency with the equivalence of drug interaction studies were 90 and 30 %, respectively. As the dosing intervals were lengthened, the number of drugs classified into the low-risk categories increased., Conclusion: A new drug interaction prediction method based on the pharmacokinetic parameters of drugs was developed. The new model is useful for estimating the risk of drug interaction in clinical practice when AST-120 is used in combination with other drugs., Competing Interests: Shinya Uchida and Tsutomu Kotegawa have received advisory fees from KUREHA CORPORATION.

In this article, we will first describe the metabolic fate of 11 C-acetate; then discuss its biodistribution in health and disease; and subsequently focus on its key clinical applications, the detection and localization of prostate cancer tissue in patients with primary or recurrent disease. Finally, we will discuss the potential role of 11 C-acetate in the context of other prostate cancer imaging probes and non-radionuclide-based imaging approaches., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Domestic combustion of biomass fuels, such as wood, charcoal, crop residue and dung causes Household Air Pollution (HAP). These inhaled particulates affect more than half of the world's population, causing respiratory problems such as infection and inflammatory lung disease. We examined whether the presence of black carbon in alveolar macrophages was associated with alterations in the lung microbiome in a Malawi population., Methods: Bronchoalveolar lavage samples from 44 healthy adults were sequenced using 16S rDNA amplification to assess microbial diversity, richness and relative taxa abundance. Individuals were classified as high or low particulate exposure as determined by questionnaire and the percentage of black carbon within their alveolar macrophages., Results: Subjects in the low and high particulate groups did not differ in terms of source of fuels used for cooking or lighting. There was no difference in alpha or beta diversity by particulate group. Neisseria and Streptococcus were significantly more abundant in samples from high particulate exposed individuals, and Tropheryma was found less abundant. Petrobacter abundance was higher in people using biomass fuel for household cooking and lighting, compared with exclusive use of electricity., Conclusions: Healthy adults in Malawi exposed to higher levels of particulates have higher abundances of potentially pathogenic bacteria (Streptococcus, Neisseria) within their lung microbiome. Domestic biomass fuel use was associated with an uncommon environmental bacterium (Petrobacter) associated with oil-rich niches.

In this work, we report that the biodistribution and excretion of carbon nanohorns (CNHs) in mice are dependent on their size and functionalization. Small-sized CNHs (30-50 nm; S-CNHs) and large-sized CNHs (80-100 nm; L-CNHs) were chemically functionalized and radiolabeled with [(111)In]-diethylenetriaminepentaacetic acid and intravenously injected into mice. Their tissue distribution profiles at different time points were determined by single photon emission computed tomography/computed tomography. The results showed that the S-CNHs circulated longer in blood, while the L-CNHs accumulated faster in major organs like the liver and spleen. Small amounts of S-CNHs- and L-CNHs were excreted in urine within the first few hours postinjection, followed by excretion of smaller quantities within the next 48 hours in both urine and feces. The kinetics of excretion for S-CNHs were more rapid than for L-CNHs. Both S-CNH and L-CNH material accumulated mainly in the liver and spleen; however, S-CNH accumulation in the spleen was more prominent than in the liver.

For children, ingestion of soils and house dusts can be an important exposure pathway for regulated organic compounds. Following ingestion, the extent to which compounds desorb and become bioaccessible is a critical determinant of systemic adsorption. We characterized the physicochemical properties of 37 soil and house dust pairs collected during a national survey of United States homes. For each sample, we measured the bioaccessibility of fipronil, a phenylpyrazole insecticide using an in vitro, three- compartment digestive system, then modeled the physicochemical predictors of fipronil bioaccessibility. The properties of the soils and dusts were not correlated and percent carbon was the only significant predictor of bioaccessibility for both soils (p<0.001) and dusts (p<0.001). The carbon content of the soils (3.1±2.4%) was lower than that of the dusts (18.6±6.9%) Due to the lower carbon content, soil sorbed fipronil was more bioaccessible than dust sorbed fipronil. However, the slope of the bioaccessibility carbon regression line was steeper for the soils than for the house dusts. This suggested that, for soils having carbon percentages greater than those in this study, fipronil bioaccessibility may be less than that of house dusts having equal carbon content., (Published by Elsevier B.V.)

The effects of dissolved inorganic carbon (DIC) availability on photosynthesis were studied in two estuarine intertidal microphytobenthos (MPB) communities and in the model diatom species Phaeodactylum tricornutum. Kinetics of DIC acquisition, measured with a liquid-phase oxygen electrode, showed higher K(1/2)(DIC) (0.31 mM) and Vm (7.78 nmol min(-1) µg (Chl a)(-1)) for MPB suspensions than for P. tricornutum (K(1/2)(DIC) = 0.23 mM; Vm = 4.64 nmol min(-1) µg (Chl a)(-1)), suggesting the predominance of species with lower affinity for DIC and higher photosynthetic capacity in the MPB. The net photosynthetic rate of the MPB suspensions reached saturation at a DIC concentration of 1-1.5 mM. This range was lower than the concentrations found in the interstitial water of the top 5-mm sediment layer, suggesting no limitation of photosynthesis by DIC in the MPB communities. Accordingly, carbon isotope discrimination revealed a moderate activity of CO2-concentrating mechanisms in the MPB. However, addition of NaHCO3 to intact MPB biofilms caused a significant increase in the relative maximum photosynthetic electron transport rate (rETR max) measured by imaging pulse-amplitude modulated chlorophyll a fluorescence. These results suggest local depletion of DIC at the photic layer of the sediment (the first few hundred µm), where MPB cells accumulate during diurnal low tides. This work provides the first direct experimental evidence of DIC limitation of photosynthesis in highly productive intertidal MPB communities.

Background: While carbon-encapsulated iron carbide nanoparticles exhibit strong magnetic properties appealing for biomedical applications, potential side effects of such materials remain comparatively poorly understood. Here, we assess the effects of iron-based nanoparticles in an in vivo long-term study in mice with observation windows between 1 week and 1 year., Materials & Methods: Functionalized (PEG or IgG) carbon-encapsulated platinum-spiked iron carbide nanoparticles were injected intravenously in mice (single or repeated dose administration)., Results: One week after administration, magnetic nanoparticles were predominantly localized in organs of the reticuloendothelial system, particularly the lung and liver. After 1 year, particles were still present in these organs, however, without any evident tissue alterations, such as inflammation, fibrosis, necrosis or carcinogenesis. Importantly, reticuloendothelial system organs presented with normal function., Conclusion: This long-term exposure study shows high in vivo compatibility of intravenously applied carbon-encapsulated iron nanoparticles suggesting continuing investigations on such materials for biomedical applications.

Carbon-based nanomaterials including carbon nanotubes, graphene oxide, fullerenes and nanodiamonds are potential candidates for various applications in medicine such as drug delivery and imaging. However, the successful translation of nanomaterials for biomedical applications is predicated on a detailed understanding of the biological interactions of these materials. Indeed, the potential impact of the so-called bio-corona of proteins, lipids, and other biomolecules on the fate of nanomaterials in the body should not be ignored. Enzymatic degradation of carbon-based nanomaterials by immune-competent cells serves as a special case of bio-corona interactions with important implications for the medical use of such nanomaterials. In the present review, we highlight emerging biomedical applications of carbon-based nanomaterials. We also discuss recent studies on nanomaterial 'coronation' and how this impacts on biodistribution and targeting along with studies on the enzymatic degradation of carbon-based nanomaterials, and the role of surface modification of nanomaterials for these biological interactions., From the Clinical Editor: Advances in technology have produced many carbon-based nanomaterials. These are increasingly being investigated for the use in diagnostics and therapeutics. Nonetheless, there remains a knowledge gap in terms of the understanding of the biological interactions of these materials. In this paper, the authors provided a comprehensive review on the recent biomedical applications and the interactions of various carbon-based nanomaterials., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to their excellent biocompatibility, carbon nanoparticles have been widely investigated for prospective biomedical applications. However, their impact on an organism with prolonged exposure is still not well understood. Here, we performed an experiment investigating diamond, graphene oxide and graphite nanoparticles, which were repeatedly administrated intraperitoneally into Wistar rats for four weeks. Some of the animals was sacrificed after the last injection, whereas the rest were sacrificed twelve weeks after the last exposure. We evaluated blood morphology and biochemistry, as well as the redox and inflammatory state of the liver. The results show the retention of nanoparticles within the peritoneal cavity in the form of prominent aggregates in proximity to the injection site, as well as the presence of some nanoparticles in the mesentery. Small aggregates were also visible in the liver serosa, suggesting possible transportation to the liver. However, none of the tested nanoparticles affected the health of animals. This lack of toxic effect may suggest the potential applicability of nanoparticles as drug carriers for local therapies, ensuring accumulation and slow release of drugs into a targeted tissue without harmful systemic side effects.

Fluorescent carbonaceous nanospheres (CDs) have gained significant attention because of their promising applications, especially in biology and medicine, due to their unique properties. However, the application of CDs in the noninvasive imaging of diseased tissues has been restricted by the poor targeting efficiency of CDs. In this study, CDs were prepared from sucrose and glutamic acid with a particle size of 122.5 nm. Due to quantum confinement in the nanoparticles, CDs exhibited emission from 450 to 600 nm upon excitation at approximately 400 nm. This feature made it possible to use the CDs for low-background bioimaging of deep diseased tissues. RGD, a ligand that can target α(v)β3, which is highly expressed on most tumor and neovascular cells, was decorated onto the CDs after PEGylation. The product, RGD-PEG-CDs, possessed low cytotoxicity, as determined by MTT assay. In vitro, RGD-PEG-CDs targeted U87 (a human brain glioma cell line) cells with a higher cellular uptake intensity than CDs and PEGylated CDs (PEG-CDs), and endosomes were involved in the uptake procedure. The internalization of RGD-PEG-CDs, PEG-CDs and CDs all were primarily mediated by macropinocytosis and a clathrin-mediated pathway, which were energy-dependent. Additionally, the uptake of RGD-PEG-CDs could be significantly inhibited by free RGD, indicating that the uptake was mediated by the receptor of RGD. In vivo, RGD-PEG-CDs accumulated in U87 glioma at high intensity, at values that were 1.67- and 1.64-fold higher than those of PEG-CDs and CDs. Furthermore, RGD-PEG-CDs exhibited good colocalization with neovasculature. In conclusion, RGD-PEG-CDs could be successfully used for noninvasive U87 glioma imaging.

Polymer-functionalized carbon nanoparticles hold great promise for their use in enhancing the oral absorption of drugs with poor oral bioavailability. And since the abundant expression of folate receptors in intestinal tract, folic acid (FA) modified uniform mesoporous carbon spheres (UMCS) was used to improve oral absorption of paclitaxel, a chemotherapeutic drug with poor oral bioavailability. In this research, folate-polyethyleneimine (FA-PEI) was grafted onto acid-treated uniform mesoporous carbon spheres through one-step electrostatic attraction. PTX was loaded into mesopores of nanoparticles through solvent evaporation, present as amorphous. The release of PTX from the FA-PEI-UMCS nanoparticles exhibited an initial rapid release, followed by a sustained release. And release rate could be regulated by changing amount of FA-PEI complex on the UMCS. The uptake of PTX-encapsulated nanoparticles was studied exploiting Caco-2 cells as an in vitro model. The results of confocal microscopy and flow cytometry demonstrated that folate functionalization enhanced internalization of nanoparticles by the cells. Moreover, PTX loaded in FA-PEI-UMCS nanoparticles resulted in a 5.37-fold increase in apparent permeability (Papp) across Caco-2 cell monolayers compared to Taxol(®). And the in vivo results showed that FA-PEI-UMCS nanoparticles did not only improve the oral bioavailability of PTX, but also decrease the gastrointestinal toxicity of PTX. In conclusion, the FA-PEI-UMCS nanoparticles might be a potentially applicable system to improve oral absorption of drugs with poor oral bioavailability., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Carbon nanotubes (CNTs) are biologically non-toxic and long-circulating nanostructures that have special physical properties. This study was focused on developing alternative methods that track carbon nanotubes, like FR-IR to classical tissue histological procedure. FT-IR absorption spectra were used to confirm the carboxylation of carbon nanotubes and to evaluate the presence of carbon nanotubes from bulk spleen samples and histologically prepared samples (control spleen and spleen with SWCNT-COOH). FT-IR spectrum of spleen sample from animals injected with CNTs shows major spectral differences consisting in infrared bands located at ~1173 cm(-1), ~ 1410 cm(-1); ~1658 cm(-1), ~1737 cm(-1) and around 1720 cm(-1) respectively. In terms of localization of carbon nanotubes, selective accumulation of marginal zone macrophages and splenic red pulp is observed for all treated groups, indicating the presence of carbon nanotubes even at 3, 4 and 7 days after treatment. In summary, we believe that histological evaluation and FT-IR can provide more characteristic information about the pharmacokinetcis and the clearance of carbon nanotubes.

Around the world, peatland degradation and soil subsidence is occurring where these soils have been converted to agriculture. Since initial drainage in the mid-1800s, continuous farming of such soils in the California Sacramento-San Joaquin Delta (the Delta) has led to subsidence of up to 8 meters in places, primarily due to soil organic matter (SOM) oxidation and physical compaction. Rice (Oryza sativa) production has been proposed as an alternative cropping system to limit SOM oxidation. Preliminary research on these soils revealed high N uptake by rice in N fertilizer omission plots, which we hypothesized was the result of SOM oxidation releasing N. Testing this hypothesis, we developed a novel N budgeting approach to assess annual soil C and N loss based on plant N uptake and fallow season N mineralization. Through field experiments examining N dynamics during growing season and winter fallow periods, a complete annual N budget was developed. Soil C loss was calculated from SOM-N mineralization using the soil C:N ratio. Surface water and crop residue were negligible in the total N uptake budget (3 - 4 % combined). Shallow groundwater contributed 24 - 33 %, likely representing subsurface SOM-N mineralization. Assuming 6 and 25 kg N ha-1 from atmospheric deposition and biological N2 fixation, respectively, our results suggest 77 - 81 % of plant N uptake (129 - 149 kg N ha-1) was supplied by SOM mineralization. Considering a range of N uptake efficiency from 50 - 70 %, estimated net C loss ranged from 1149 - 2473 kg C ha-1. These findings suggest that rice systems, as currently managed, reduce the rate of C loss from organic delta soils relative to other agricultural practices.

We studied the phagocytic-like capacity of human CD34+ stromal cells/telocytes (TCs). For this, we examined segments of the colon after injection of India ink to help surgeons localize lesions identified at endoscopy. Our results demonstrate that CD34+ TCs have endocytic properties (phagocytic-like TCs: phTCs), with the capacity to uptake and store India ink particles. phTCs conserve the characteristics of TCs (long, thin, bipolar or multipolar, moniliform cytoplasmic processes/telopodes, with linear distribution of the pigment) and maintain their typical distribution. Likewise, they are easily distinguished from pigment-loaded macrophages (CD68+ macrophages, with oval morphology and coarse granules of pigment clustered in their cytoplasm). A few c-kit/CD117+ interstitial cells of Cajal also incorporate pigment and may conserve the phagocytic-like property of their probable TC precursors. CD34+ stromal cells in other locations (skin and periodontal tissues) also have the phagocytic-like capacity to uptake and store pigments (hemosiderin, some components of dental amalgam and melanin). This suggests a function of TCs in general, which may be related to the transfer of macromolecules in these cells. Our ultrastructural observation of melanin-storing stromal cells with characteristics of TCs (telopodes with dichotomous branching pattern) favours this possibility. In conclusion, intestinal TCs have a phagocytic-like property, a function that may be generalized to TCs in other locations. This function (the ability to internalize small particles), together with the capacity of these cells to release extracellular vesicles with macromolecules, could close the cellular bidirectional cooperative circle of informative exchange and intercellular interactions., (© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Optimisation of cyanobacterial cell productivity should consider the key factors light cycle and carbon source. We studied the influence of CO2 bubble size on carbon uptake and fixation, on basis of mRNA expression levels in Arthrospira platensis KMMCC CY-007 at 30°C (light intensity: 40μmolm(-2)s(-1); 1% CO2). Growth rate, carbon fixation and lipid accumulation were examined over 7days under fine bubble (FB) (100μm Ø) bulk bubble (BB) (5000μm Ø) and non-CO2 (NB) aeration. The low affinity CO2 uptake mRNA (NDH-I4 complex) was stronger expressed than the high affinity NDH-I3 complex (bicA and sbtA) under 1% CO2 and FB conditions, with no expression of bicA1 and sbtA1 after 4days. The high affinity CO2 uptake mRNA levels corresponded to biomass, carbon content and lipid accumulation, and increase in NDH-I3 complex (9.72-fold), bicA (5.69-fold), and sbtA (10.61-fold), compared to NB, or BB conditions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Given that forests represent the primary terrestrial sink for atmospheric CO2 , projections of future carbon (C) storage hinge on forest responses to climate variation. Models of gross primary production (GPP) responses to water stress are commonly based on remotely sensed changes in canopy 'greenness' (e.g., normalized difference vegetation index; NDVI). However, many forests have low spectral sensitivity to water stress (SSWS) - defined here as drought-induced decline in GPP without a change in greenness. Current satellite-derived estimates of GPP use a vapor pressure deficit (VPD) scalar to account for the low SWSS of forests, but fail to capture their responses to water stress. Our objectives were to characterize differences in SSWS among forested and nonforested ecosystems, and to develop an improved framework for predicting the impacts of water stress on GPP in forests with low SSWS. First, we paired two independent drought indices with NDVI data for the conterminous US from 2000 to 2011, and examined the relationship between water stress and NDVI. We found that forests had lower SSWS than nonforests regardless of drought index or duration. We then compared satellite-derived estimates of GPP with eddy-covariance observations of GPP in two deciduous broadleaf forests with low SSWS: the Missouri Ozark (MO) and Morgan Monroe State Forest (MMSF) AmeriFlux sites. Model estimates of GPP that used VPD scalars were poorly correlated with observations of GPP at MO (r(2) = 0.09) and MMSF (r(2) = 0.38). When we included the NDVI responses to water stress of adjacent ecosystems with high SSWS into a model based solely on temperature and greenness, we substantially improved predictions of GPP at MO (r(2) = 0.83) and for a severe drought year at the MMSF (r(2) = 0.82). Collectively, our results suggest that large-scale estimates of GPP that capture variation in SSWS among ecosystems could improve predictions of C uptake by forests under drought., (© 2014 John Wiley & Sons Ltd.)

Purpose: A novel mesocellular carbon foam (MSU-FC) with a large pore size and a three-dimensional porous structure for the oral delivery of poorly water-soluble drugs was prepared. The goal of this study was to improve in vitro dissolution and in vivo absorption of celecoxib (CEB), a model drug, by means of novel carbon-based nanoparticles prepared from the MSU-FC matrix., Methods: The MSU-FC matrix was synthesized by an inverse replica templating method using mesocellular silica template. A solvent immersion/evaporation method was used to load the drug molecules. The drug-loaded nanoparticles were characterized for morphology, surface area, particle size, mesoporous structure, crystallinity, solubility and dissolution. The effect of MSU-FC on cell viability was measured using the MTT conversion assay. Furthermore, the oral bioavailability of CEB-loaded MSU-FC in fasted rats was compared with that of the marketed product., Results: Our results demonstrate that CEB incorporation into the prepared MSU-FC resulted in an approximately 9-fold increase in aqueous solubility in comparison with crystalline CEB. MSU-FC produced accelerated immediate release of CEB in comparison with crystalline CEB (pure CEB powder or marketed formulation) and the drug-loaded conventional mesoporous carbon particles. The relative bioavailability of CEB for CEB-loaded MSU-FC was 172%. In addition, MSU-FC nanoparticles exhibited very low toxicity., Conclusions: The MSU-FC nanomatrix has been shown to be a promising drug delivery vehicle for improving the dissolution and biopharmaceutical characteristics of poorly water-soluble drugs.

Future climate change and increasing atmospheric CO2 are expected to cause major changes in vegetation structure and function over large fractions of the global land surface. Seven global vegetation models are used to analyze possible responses to future climate simulated by a range of general circulation models run under all four representative concentration pathway scenarios of changing concentrations of greenhouse gases. All 110 simulations predict an increase in global vegetation carbon to 2100, but with substantial variation between vegetation models. For example, at 4 °C of global land surface warming (510-758 ppm of CO2), vegetation carbon increases by 52-477 Pg C (224 Pg C mean), mainly due to CO2 fertilization of photosynthesis. Simulations agree on large regional increases across much of the boreal forest, western Amazonia, central Africa, western China, and southeast Asia, with reductions across southwestern North America, central South America, southern Mediterranean areas, southwestern Africa, and southwestern Australia. Four vegetation models display discontinuities across 4 °C of warming, indicating global thresholds in the balance of positive and negative influences on productivity and biomass. In contrast to previous global vegetation model studies, we emphasize the importance of uncertainties in projected changes in carbon residence times. We find, when all seven models are considered for one representative concentration pathway × general circulation model combination, such uncertainties explain 30% more variation in modeled vegetation carbon change than responses of net primary productivity alone, increasing to 151% for non-HYBRID4 models. A change in research priorities away from production and toward structural dynamics and demographic processes is recommended.

Atmospheric carbon dioxide emissions cause a decrease in the pH and aragonite saturation state of surface ocean water. As a result, calcifying organisms are expected to suffer under future ocean conditions, but their physiological responses may depend on their nutrient status. Because many coral reefs experience high inorganic nutrient loads or seasonal changes in nutrient availability, reef organisms in localized areas will have to cope with elevated carbon dioxide and changes in inorganic nutrients. Halimeda opuntia is a dominant calcifying primary producer on coral reefs that contributes to coral reef accretion. Therefore, we investigated the carbon and nutrient balance of H. opuntia exposed to elevated carbon dioxide and inorganic nutrients. We measured tissue nitrogen, phosphorus and carbon content as well as the activity of enzymes involved in inorganic carbon uptake and nitrogen assimilation (external carbonic anhydrase and nitrate reductase, respectively). Inorganic carbon content was lower in algae exposed to high CO₂, but calcification rates were not significantly affected by CO₂ or inorganic nutrients. Organic carbon was positively correlated to external carbonic anhydrase activity, while inorganic carbon showed the opposite correlation. Carbon dioxide had a significant effect on tissue nitrogen and organic carbon content, while inorganic nutrients affected tissue phosphorus and N:P ratios. Nitrate reductase activity was highest in algae grown under elevated CO₂ and inorganic nutrient conditions and lowest when phosphate was limiting. In general, we found that enzymatic responses were strongly influenced by nutrient availability, indicating its important role in dictating the local responses of the calcifying primary producer H. opuntia to ocean acidification.