Multifunctional nano-system for multi-mode targeted imaging and enhanced photothermal therapy of metastatic prostate cancer.

Prostate cancer (PCa) routinely employs magnetic resonance (MR) imaging, while metastatic PCa needs more complicated detection methods for precise localization. The inconvenience of using different methods to detect PCa and its metastases in patients and the limitations of single-mode imaging have brought great challenges to clinicians. Meanwhile, clinical treatments for metastatic PCa are still limited. Herein, we report a targeted theranostic platform of Au/Mn nanodots-luteinising hormone releasing hormone (AMNDs-LHRH) nano-system for multi-mode imaging guided photothermal therapy of PCa. The nano-system not only can simultaneously target Gonadotropin-Releasing Hormone Receptor (GnRH-R) positive PCa and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence (FL) visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. Meanwhile, the AMNDs-LHRH with promising targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic PCa. The AMNDs-LHRH nano-system guarantees the diagnostic accuracy and enhanced therapeutic effect, which provides a promising platform for clinical diagnosis and treatment of metastatic PCa. STATEMENT OF SIGNIFICANCE: Accurate clinical diagnosis and treatment of prostate cancer and its metastases is challenging. A targeted theranostic platform of AMNDs-LHRH nano-system for multi-mode imaging (FL/CT/MR) guided photothermal therapy of metastatic prostate cancer has been reported. The nano-system not only can simultaneously target prostate cancer and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. The nano-system with great targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic prostate cancer. Overall, the AMNDs-LHRH nano-system integrates tumor targeting, multi-mode imaging and enhanced therapeutic effect, which can provide an effective strategy for the clinical diagnosis and treatment of metastatic PCa.

Facile fabrication of an Au/Cu bimetallic nanocluster-based fluorescent composite film for sensitive and selective detection of Cr(VI).

To overcome the disadvantage of simple bimetallic nanocluster solutions being difficult to store and utilize, we prepared and obtained a novel gold and copper bimetallic nanocluster-doped chitosan fluorescent composite film. In this study, gold and copper bimetallic nanoclusters emitting strong red fluorescence were first synthesized by a chemical reduction method. Subsequently, a novel gold and copper bimetallic nanocluster-doped chitosan fluorescent composite film was successfully prepared by a solution casting method. After 60 minutes of UV light irradiation or 30 days at room temperature, the relative fluorescence intensity values of the composite film decreased by 0.9% and 1.2%, respectively. This indicates that its optical properties are stable and that it can be stored for a long time. The composite film has strong and bright red fluorescence and can be used as a fluorescent probe to achieve real-time detection of Cr(VI). It also has a low detection limit for Cr(VI) (0.26 ppb), so it can be applied to the detection of Cr(VI) in actual water samples and get satisfactory detection results. Due to its portability, high selectivity, and high sensitivity, it can also be extended to chemical and food detection.

Au/Mn nanodot platform for in vivo CT/MRI/FI multimodal bioimaging and photothermal therapy against tongue cancer.

Surgical resection is the main method for oral tongue squamous cell carcinoma (OTSCC) treatment. However, the oral physiological function and aesthetics may be seriously damaged during the operation with a high risk of recurrence. Therefore, it is important to develop an alternative strategy with precise guidance for OTSCC treatment. Herein, multifunctional Au/Mn nanodots (NDs) are designed and synthesized. They can perform multimodal bioimaging, including computed tomography (CT) and magnetic resonance imaging (MRI) simultaneously, and exhibit bright near-infrared fluorescence imaging (FI) for navigation, and even integrate photothermal therapy (PTT) property. The localization of OTSCC relies on visual and tactile cues of surgeons while lacking noninvasive pretreament labeling and guidance. Au/Mn NDs provide CT/MRI imaging, giving two means of accurate positioning pretherapy. Meanwhile, the fluorescence of the Au/Mn NDs in the near-infrared region (NIR) is beneficial for noninvasive labeling and intuitive observation with the naked eye to determine the tumor boundary during PTT. Further, Au/Mn NDs showed excellent results in ablating tumors in vivo. Above all, the Au/Mn NDs provide a key platform for multimodal bioimaging and PTT in a single nanoagent, which demonstrated attractive performance for OTSCC treatment.

Ordered Hierarchical Porous Structure of PtSn/3DOMM-Al2O3 Catalyst for Promoting Propane Non-Oxidative Dehydrogenation.

Herein, the hierarchical porous catalyst of 3-dimensional ordered macro-mesoporous (3DOMM) Al2O3 supported active PtSn nanoparticles (NPs) was prepared by the combined synthesized path of evaporation-induced self-assembly with colloid crystal template (EISA-CCT) methods. The hierarchical macro-mesoporous composite structure can markedly increase the specific surface area, accommodate the diffusion of propene, and decrease the number of surface acid sites. In addition, the special surface property and pore structure of 3DOMM-Al2O3 can modify the interaction between metals and substrates, as well as stabilize the metal nanoparticle, which promotes the formation of a highly active and stable PtSn phase. The PtSn/3DOMM-Al2O3 catalyst exhibits higher productivity and stability than PtSn/Al2O3 catalysts with macropore and mesopore structures. The PtSn/3DOMM-Al2O3 catalyst displays the best catalytic performance with propylene selectivity over 95% at a propane conversion of 33.9%. The study of the ordered hierarchical porous structure of PtSn/3DOMM-Al2O3 catalysts can contribute to obtaining improved catalysts in industrial processes.

Electron Delocalization of Au Nanoclusters Triggered by Fe Single Atoms Boosts Alkaline Overall Water Splitting.

The rational design and in-depth understanding of the structure-activity relationship (SAR) of hydrogen and oxygen evolution reaction (HER and OER) bifunctional electrocatalysts are vital to decreasing the energy consumption of hydrogen production by electrochemical water splitting. Herein, we report an inducing electron delocalization method where Fe single atoms as inducers are used to regulate the electron structure of Au nanoclusters by the M-Nx-C substrate to acquire satisfactory intrinsic HER activity. Meanwhile, Fe single atoms also serve as efficient OER active sites to construct bifunctional electrocatalysts. On account of the strong synergistic effect between Au nanoclusters and Fe single atoms, the hybrid catalyst Au-Fe1NC/NF performs an outstanding alkaline HER and OER activity. Only 35.6 mV, 246 mV, and 1.52 V are needed to reach 10 mA cm-2 for alkaline HER, OER, and two-electrode electrolytic cells, respectively. In addition, the bifunctional electrocatalysts also display excellent electrochemical stability. DFT calculations demonstrate that the strong synergistic effect can enhance the O-H bond activation ability of Au nanoclusters and upshift the d-band center of the Fe single atom to promote alkaline electrocatalytic water splitting. The strong synergistic effect is proven to arise from the electron delocalization of Au nanoclusters triggered by Fe single atoms.

Electron-rich ruthenium encapsulated in nitrogen-doped carbon for efficient hydrogen evolution reaction over the whole pH.

The development of a low-cost and high-stability catalyst with Platinum-like electrocatalytic performance is significant for the hydrogen evolution reaction (HER) from water electrolysis. Herein, ultrafine ruthenium nanoparticles encapsulated in Nitrogen(N)-doped carbon anchored on graphene sheets are fabricated and utilized as HER electrocatalysts. Characterization results verify that the strong interaction between the N-doped carbon shell and the Ru core leads to charge redistributions, promoting Ru in a more active electron-rich state. Therefore, the catalyst exhibits excellent activity over a wide pH range, which only needs 16, 23 and 72 mV to drive a current density of 10 mA cm-2 in alkaline, acidic and neutral electrolytes, respectively. In addition, the N-doped carbon shell protects the Ru nanoparticles from aggregation and decomposition in the extreme electrolyte, contributing to the excellent stability.

Molecular Mechanism of HSF1-Upregulated ALDH2 by PKC in Ameliorating Pressure Overload-Induced Heart Failure in Mice.

Evidences abound that HSF1 and ALDH2 are of cardioprotective effect, yet there is still no report on whether HSF1 can regulate ALDH2 to delay the occurrence of heart failure. We first established the pressure overload-induced heart failure model of mice by transverse aortic constriction (TAC) and discovered that, in the forming period of heart failure, changes of HSF1 and ALDH2 expression recorded the consistent trend. When HSF1 was upregulated/downregulated to delay/promote the occurrence of heart failure, PKC and ALDH2 also showed increased/decreased expression. And when ALDH2 was upregulated/downregulated, the role of HSF1 in delaying the occurrence of heart failure strengthened/weakened. Next, we used mechanical stretch to establish a pressure-stimulated myocardial hypertrophy model and discovered an increased expression of both HSF1 and ALDH2. When HSF1 was upregulated/downregulated to increase/decrease the expression of myocardial hypertrophy gene beta-MHC, PKC and ALDH2 recorded an increased/decreased expression. When an inhibitor was used to downregulate the expression of PKC in cardiomyocytes, we found that the role of HSF1 in upregulating ALDH2 beta-MHC weakened. These findings suggest that HSF1 can upregulate the expression of ALDH2 via PKC to promote pressure-stimulated myocardial compensatory hypertrophy, which is an important molecular pathway for HSF1 to ameliorate heart failure.

Red fluorescent AuNDs with conjugation of cholera toxin subunit B (CTB) for extended-distance retro-nerve transporting and long-time neural tracing.

A retrograde transportation nerve probe, Au nanodots-cholera toxin B subunit (AuNDs-CTB), are prepared and fully characterized, which emit bright red fluorescence and show high quantum yield (7.2%) and good stability. The fluorescence emitted by the AuNDs is constant across a wide pH range (4-10) and after prolonged UV irradiation (>4 h). Previously, CTB has shown targeting characteristic for nerve cells with high sensitivity and effectiveness. After linking CTB to AuNDs through amidation reactions, AuNDs-CTB are obtained with excellent fluorescence property, nerve target characteristic, and, particularly, neural retrograde transportation feature. The red emission of the AuNDs-CTB is well distinguished from the blue autofluorescence of normal tissues, which provides potential for detection by naked eyes. Further, the fluorescence emission intensity maintains for 10 days in vivo, suggesting great utility for long-time monitoring and sensing of the nerve tissue. Furthermore, the AuNDs-CTB with bright red fluorescence can travel through the peripheral nerve to the spinal cord rapidly by retrograde transportation. The transportation occurs for a long distance (>5 cm) within only 2 days after injection of the AuNDs-CTB into the sciatic nerve. The present study exhibits a novel method for nerve visualization and drug delivery. STATEMENT OF SIGNIFICANCE: Au nanodots (AuNDs) conjugated with cholera toxin subunit B (CTB) have been developed for nerve labeling and neural retro-transporting. The red fluorescence from AuNDs-CTB is stable in vitro (pH 4-10 and 4 h UV irradiation) and in vivo (for a long time, more than 10 days). When injecting AuNDs-CTB into the sciatic nerve located at the midpiece of the thigh, the targeted nerve emits bright red fluorescence under UV light. Furthermore, the nerve can retrograde transport the AuNDs-CTB to the spinal cord for a distance of more than 5 cm just in 2 days. This work exhibits a novel method for nerve visualization by naked eyes and demonstrates the potential for intraoperative navigation.

Red emitting and highly stable carbon dots with dual response to pH values and ferric ions.

The authors describe strongly red-emitting carbon dots (CDs) which were obtained via microwave synthesis using phenylenediamine as the carbon source. The structural and optical properties of the resultant CDs are studied in some detail. The CDs possess (a) longwave emission (peaking at 620 nm under 470 nm excitation), (b) a quantum yield of ~15%, (c) a size of typically 3.8 nm; and (d) good photostability. The CDs have a pH-dependet response that covers the pH 5 to 10 range, and their fluorescence is quenched by ferric ions. The CDs can detect ferric ions in aqueous samples in the 0 to 30 µM concentration range with a lower detection limit of 15 nM. The CDs were also used to image pH values and ferric ions in E. coli bacteria. Graphical abstract The red-emitting carbon dots with high stability are synthesized which show dual response to pH-values and ferric ions in aqueous solution and biological media simultaneously.

A facile strategy for the synthesis of ferroferric oxide/titanium dioxide/molybdenum disulfide heterostructures as a magnetically separable photocatalyst under visible-light.

Semiconductor photocatalysts is a promising approach to combat both environmental pollution and global energy shortage despite the challenges of recycling and stability. In this paper, magnetic Fe3O4 particle is introduced in the system and Fe3O4/TiO2/MoS2 heterostructures can be formed in a facile strategy. The morphology and structure of Fe3O4/TiO2/MoS2 can be controlled by adjusting the hydrolysis rate of the titanium source. MoS2 is designed to fill in the mesoporous of TiO2 core, forming heterojunction on the surface and near-surface of TiO2 under solvothermal conditions. With respect to the decomposition of a rhodamine B (RhB) solution under visible light, the Fe3O4/TiO2/MoS2 heterostructures display highly photocatalytic activities in aqueous solutions, and they can be easily recovered to realize cyclic utilization by applying an external magnetic field. Thus, the effective magnetic recycle of the catalyst is achieved, and high visible light catalytic activity is ensured simultaneously. Since the current method is simple and flexible to create recyclable catalysts with high stability in this way, it could promote the practicability of semiconductor photocatalysts in water treatment, degradation of dye pollutants, and environmental cleaning.

[Effects of sevoflurane on the migration of vascular endothelial cells].

PURPOSE: To evaluate the effects of sevoflurane on cell migration and expression of VE-cadherin mRNA in human umbilical vein endothelial cells(HUVECs). METHODS: HUVECs were allocated to 4 groups randomly (each group contained 4 culture dishes with a diameter of 10 cm), and were exposed to 2% sevoflurane (refer to 1.6 MAC) respectively for 0 h (control group which exposed to the same environment as the other 3 groups but without sevoflurane), 0.5 h, 1 h, 2 h. After sevoflurane exposure, HUVECs were subjected to scratch assay to observe the migration distance; RT-PCR was used to detect the expression of vascular endothelial-cadherin mRNA(VE-cadherin mRNA). Statistical analysis of the data was conducted using SPSS 13.0 software package. RESULTS: Scratch assay results suggested that the migration ability of HUVECs exposed to 2% sevoflurane for 2 h were significantly inhibited during 12 h after scratch compared with the control group(P<0.01), and RT-PCR results suggested that HUVECs exposed to 2% sevoflurane for 2 h expressed greater VE-cadherin mRNA than the control group(P<0.05). CONCLUSIONS: Sevoflurane exposure for 2 h can inhibit HUVECs migration and the mechanism may be up-regulating VE-cadherin expression.

Sevoflurane induces cognitive impairments via the MiR-27b/LIMK1-signaling pathway in developing rats.

Exposure to sevoflurane in neonatal rats could induce learning deficits and abnormal social behaviors, but the specific molecular mechanism is unknown. Postnatal day-7 SD rats were treated with 3% sevoflurane plus 30% oxygen/air or 30% oxygen/air. As the rats grew, the Morris water maze (MWM) and fear conditioning tests were performed to evaluate cognitive function, while the expression of LIMK1 was analyzed by western blot. Luciferase reporter assay was performed to investigate the interaction between LIMK1 and miR-27b. The expression of miR-27b was measured by real-time polymerase chain reaction (PCR) after exposure to sevoflurane. Once the miR-27b inhibitor was transfected into the neurons, the expression of LIMK1 was analyzed by real-time PCR and western blot. Exposure to sevoflurane in neonatal rats induced memory and learning impairments according to the MWM and fear conditioning tests. Sevoflurane increased the expression of miR-27b and reduced the expression of LIMK1 in the brain tissues of rats compared to the control group. The results of the luciferase reporter assay showed that LIMK1 was a direct target of miR-27b. In the primary neurons, the inhibition of miR-27b could reverse the down-regulating effects of sevoflurane on LIMK1 expression. We suggest that sevoflurane-induced learning and memory impairments in rats might be mediated via the miR-27b-LIMK1-signaling pathway.

Fluorescence-Magnetism Functional EuS Nanocrystals with Controllable Morphologies for Dual Bioimaging.

Multiple functions incorporated in one single component material offer important applications in biosystems. Here we prepared a divalent state of rare earth EuS nanocrystals (NCs), which provides luminescent and magnetic properties, using both 1-Dodecanethiol (DT) and oleylamine (OLA) as reducing agents. The resultant EuS NCs exhibit controllable shapes, uniform size, and bright luminescence with a quantum yield as high as 3.5%. OLA as a surface ligand plays an important role in tunable morphologies, such as nanowires, nanorods, nanospheres et al. Another attractive nature of the EuS NCs is their paramagnetism at room temperature. In order to expand the biological applications, the resultant EuS NCs were modified with amphiphilic block copolymer F127 and transferred from oil to water phase. The excellent biocompatibility of EuS NCs is demonstrated as well as preservation of their luminescence and paramagnetic properties. The EuS NCs offer multifunction and great advantages of bright luminescence, paramagnetic, controllable morphologies, and good biocompatibility promising applications in the field of simultaneous magnetic resonance and fluorescence bioimaging.

pH- and Temperature-Sensitive Hydrogel Nanoparticles with Dual Photoluminescence for Bioprobes.

This study demonstrates high contrast and sensitivity by designing a dual-emissive hydrogel particle system, whose two emissions respond to pH and temperature strongly and independently. It describes the photoluminescence (PL) response of poly(N-isopropylacrylamide) (PNIPAM)-based core/shell hydrogel nanoparticles with dual emission, which is obtained by emulsion polymerization with potassium persulfate, consisting of the thermo- and pH-responsive copolymers of PNIPAM and poly(acrylic acid) (PAA). A red-emission rare-earth complex and a blue-emission quaternary ammonium tetraphenylethylene derivative (d-TPE) with similar excitation wavelengths are inserted into the core and shell of the hydrogel nanoparticles, respectively. The PL intensities of the nanoparticles exhibit a linear temperature response in the range from 10 to 80 °C with a change as large as a factor of 5. In addition, the blue emission from the shell exhibits a linear pH response between pH 6.5 and 7.6 with a resolution of 0.1 unit, while the red emission from the core is pH-independent. These stimuli-responsive PL nanoparticles have potential applications in biology and chemistry, including bio- and chemosensors, biological imaging, cancer diagnosis, and externally activated release of anticancer drugs.

MiR-134-Mbd3 axis regulates the induction of pluripotency.

MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression and play an important role in reprogramming process; however, relatively little is known about the underlying regulatory mechanism of miRNAs on how they epigenetically modulate reprogramming and pluripotency. Here, we report that the expression level of microRNA-134 (miR-134) was low in mouse embryonic stem cells (mESCs) but significantly up-regulated during neural differentiation, while down-regulated during the induction of induced pluripotent stem cells (iPSCs) from neural progenitor cells (NPCs). Inhibition of miR-134 by miR-134 sponge promoted the efficiency of reprogramming which also was highly similar to mESCs. On the contrary, up-regulation of miR-134 repressed iPSCs induction. We also found that inhibition of miR-134 promoted the maturation of pre-iPSCs and increased its pluripotency. We also showed that miR-134 can directly target to the pluripotency related factor Methyl-CpG-binding domain protein 3 (Mdb3) 3' untranslated regions (3' UTR) to down-regulate its expression. And Mbd3 was found to promote the induction of iPSCs and could block the repression of reprogramming caused by overexpression of miR-134. This work revealed the critical function of miR-134-Mbd3 axis on regulating reprogramming and pluripotency of iPSCs derived from the NPCs, and might provide an insight into the miR-134-Mbd3 axis on regulating the iPSCs quality for further clinical treatment.

[Correlations of plasma concentrations of ß-amyloid peptide and S-100ß with postoperative cognitive dysfunction in patients undergoing oral and maxillofacial cancer surgery].

PURPOSE: To evaluate the changes of perioperative plasma concentrations of Aß1-40 and S-100ß to determine the relationship with postoperative cognitive dysfunction in elderly patients undergoing oral and maxillofacial cancer surgeries. METHODS: One hundred and fifteen patients aged at least 60 years undergoing oral and maxillofacial tumor resection were investigated between May 2014 to December 2014.Neuropsychological tests for detecting postoperative cognitive dysfunction(POCD) were performed one day before surgery and 7 days postoperatively. According to the results of neuropsychological tests on day 7, patients were divided into POCD group and non-POCD group.Plasma values of Aß1-40 and S-100ß were determined with enzyme linked immunosorbent assay (ELISA) before anesthesia induction, 24 h and 7 days after surgery. The data were analyzed using SPSS 19.0 software package. RESULTS: According to the definition, POCD was present in 37 of 115 (32.3%) patients 1 week after surgery. Compared with pre-anesthesia, S-100ß levels in POCD group were significantly increased (P<0.05); the level of Aß1-40 was significantly higher 24 h after surgery (P<0.05). Compared with non-POCD group, S-100ß levels were significantly increased 24 h postoperatively (P<0.05); Aß1-40 levels were significantly higher 24 h and 7 days postoperatively (P<0.05). CONCLUSIONS: POCD was present in 32.2% of patients on day 7 after oral and maxillofacial surgeries with general anesthesia. The increasing levels of Aß1-40, S-100ß may be associated with the occurence of POCD. Patients with long-lasting operation and high concentrations of Aß1-40 and S-100ß after surgeries were at a higher risk of POCD. The clinical values of Aß1-40 and S-100 as predictive measurements of POCD after oral and maxillofacial cancer surgery appear to be reasonable.