Polydopamine-Modified 2D Iron (II) Immobilized MnPS3 Nanosheets for Multimodal Imaging-Guided Cancer Synergistic Photothermal-Chemodynamic Therapy.

Manganese phosphosulphide (MnPS3 ), a newly emerged and promising member of the 2D metal phosphorus trichalcogenides (MPX3 ) family, has aroused abundant interest due to its unique physicochemical properties and applications in energy storage and conversion. However, its potential in the field of biomedicine, particularly as a nanotherapeutic platform for cancer therapy, has remained largely unexplored. Herein, a 2D "all-in-one" theranostic nanoplatform based on MnPS3 is designed and applied for imaging-guided synergistic photothermal-chemodynamic therapy. (Iron) Fe (II) ions are immobilized on the surface of MnPS3 nanosheets to facilitate effective chemodynamic therapy (CDT). Upon surface modification with polydopamine (PDA) and polyethylene glycol (PEG), the obtained Fe-MnPS3 /PDA-PEG nanosheets exhibit exceptional photothermal conversion efficiency (η = 40.7%) and proficient pH/NIR-responsive Fenton catalytic activity, enabling efficient photothermal therapy (PTT) and CDT. Importantly, such nanoplatform can also serve as an efficient theranostic agent for multimodal imaging, facilitating real-time monitoring and guidance of the therapeutic process. After fulfilling the therapeutic functions, the Fe-MnPS3 /PDA-PEG nanosheets can be efficiently excreted from the body, alleviating the concerns of long-term retention and potential toxicity. This work presents an effective, precise, and safe 2D "all-in-one" theranostic nanoplatform based on MnPS3 for high-efficiency tumor-specific theranostics.

Visible Light-Driven Micromotors in Fuel-Free Environment with Promoted Ion Tolerance.

Light-driven electrophoretic micromotors have gained significant attention recently for applications in drug delivery, targeted therapy, biosensing, and environmental remediation. Micromotors that possess good biocompatibility and the ability to adapt to complex external environments are particularly attractive. In this study, we have fabricated visible light-driven micromotors that could swim in an environment with relatively high salinity. To achieve this, we first tuned the energy bandgap of rutile TiO2 that was hydrothermally synthesized, enabling it to generate photogenerated electron-hole pairs under visible light rather than solely under UV. Next, platinum nanoparticles and polyaniline were decorated onto the surface of TiO2 microspheres to facilitate the micromotors swimming in ion-rich environments. Our micromotors exhibited electrophoretic swimming in NaCl solutions with concentrations as high as 0.1 M, achieving a velocity of 0.47 µm/s without the need for additional chemical fuels. The micromotors' propulsion was generated solely by splitting water under visible light illumination, therefore offering several advantages over traditional micromotors, such as biocompatibility and the ability to operate in environments with high ionic strength. These results demonstrated high biocompatibility of photophoretic micromotors and high potential for practical applications in various fields.

Enhanced and Robust Directional Propulsion of Light-Activated Janus Micromotors by Magnetic Spinning and the Magnus Effect.

Advances in the versatile design and synthesis of nanomaterials have imparted diverse functionalities to Janus micromotors as autonomous vehicles. However, a significant challenge remains in maneuvering Janus micromotors by following desired trajectories for on-demand motility and intelligent control due to the inherent rotational Brownian motion. Here, we present the enhanced and robust directional propulsion of light-activated Fe3O4@TiO2/Pt Janus micromotors by magnetic spinning and the Magnus effect. Once exposed to a low-intensity rotating magnetic field, the micromotors become physically actuated, and their rotational Brownian diffusion is quenched by the magnetic rotation. Photocatalytic propulsion can be triggered by unidirectional irradiation based on a self-electrophoretic mechanism. Thus, a transverse Magnus force can be generated due to the rotational motion and ballistic motion (photocatalytic propulsion) of the micromotors. Both the self-electrophoretic propulsion and the Magnus force are periodically changed due to the magnetic rotation, which results in an overall directed motion moving toward a trajectory with a deflection angle from the direction of incident light with enhanced speed, maneuverability, and steering robustness. Our study illustrates the admirable directional motion capabilities of light-driven Janus micromotors based on magnetic spinning and the Magnus effect, which unfolds a new paradigm for addressing the limitations of directionality control in the current asymmetric micromotors.

Enhanced piezotronics by single-crystalline ferroelectrics for uniformly strengthening the piezo-photocatalysis of electrospun BaTiO3@TiO2 nanofibers.

Turning the built-in electric field by modulating the morphology and microstructure of ferroelectric materials is considered a viable approach to enhancing the piezo-photocatalytic activity of the ferroelectric/oxide semiconductor heterojunctions. Here, hydrothermally synthesized single-crystalline BaTiO3 nanoparticles are employed to construct BaTiO3@TiO2 hybrid nanofibers by sol-gel assisted electrospinning of TiO2 nanofibers and annealing. Because of the obvious enhancement of the synergetic piezo-photocatalytic effect under both ultrasonic and ultraviolet (UV) light irradiation, the piezo-photocatalytic degradation rate constant (k) of BaTiO3@TiO2 hybrid nanofibers on methyl orange (MO) reaches 14.84 × 10-2 min-1, which is approximately seven fold that for piezocatalysis and six fold that for photocatalysis. Moreover, BaTiO3@TiO2 core-shell nanoparticles are also synthesized for comparison purposes to assess the influence of microstructure on the piezo-photocatalysis by a wet-chemical coating of TiO2 on BaTiO3 nanoparticles. Such a high piezo-photocatalytic activity is attributed to the enhancement of the piezotronic effect by the single-crystalline ferroelectric nanoparticles and the nanoconfinement effect caused by the one-dimensional boundary of nanofibers with high specific surface areas. The mechanically induced uniform local built-in electric fields originated from the single-crystalline ferroelectric nanoparticles can enhance the separation of photogenerated electron and hole pairs and promote the formation of free hydroxyl radicals, resulting in a strong piezotronic effect boosted photochemical degradation of organic dye. This work introduces the single-crystalline ferroelectrics to construct ferroelectric/oxide semiconductor heterojunctions, and the enhanced local piezotronic effect uniformly strengthens the photochemical reactivity, which offers a new option to design high-efficiency piezo-photocatalysts for pollutant treatment.

EVALUATION OF THE INHIBITORY EFFECTS OF SIX NATURAL PRODUCT EXTRACTS AGAINST BABESIA GIBSONI IN VITRO AND IN VIVO.

New antibabesial drugs are required to fight resistant parasites, and plant-derived natural products are a robust source. Six kinds of natural product extracts derived from herbal medicines that are traditionally used for the treatment of malaria were selected to test the antibabesial effect on Babesia gibsoni in vitro and in vivo. Parasitized blood was collected from dogs infected with B. gibsoni to evaluate the inhibitory effect of verbenalin, catechin hydrate, dihydrolycorine, embelin, ursolic acid, agrimol B, and bruceine H in vitro. The expression levels of the 18S rRNA gene in all drug-treated groups were determined by relative quantification using a real-time PCR method. Significant inhibition of the in vitro growth of B. gibsoni was observed after treatment by those natural product extracts (200 nM concentration) (P < 0.05). Catechin hydrate showed the highest activity in vitro due to the lowest expression levels of the 18S rRNA gene. The IC50 value of catechin hydrate against B. gibsoni was 273 nM. In B. gibsoni infected dogs, intravenous administrations of catechin hydrate and diminazene aceturate showed significant (P < 0.05) inhibition of B. gibsoni growth at a dose of 11 mg/kg and 10 mg/kg, respectively, compared to the control group. The results of our study may suggest that catechin hydrate may be a promising alternative to treat canine babesiosis caused by B. gibsoni.

Physical Surface Modification of Carbon-Nanotube/Polydimethylsiloxane Composite Electrodes for High-Sensitivity DNA Detection.

The chemical modification of electrode surfaces has attracted significant attention for lowering the limit of detection or for improving the recognition of biomolecules; however, the chemical processes are complex, dangerous, and difficult to control. Therefore, instead of the chemical process, we physically modified the surface of carbon-nanotube/polydimethylsiloxane composite electrodes by dip coating them with functionalized multi-walled carbon nanotubes (F-MWCNTs). These electrodes are used as working electrodes in electrochemistry, where they act as a recognition layer for sequence-specific DNA sensing through π-π interactions. The F-MWCNT-modified electrodes showed a limit of detection of 19.9 fM, which was 1250 times lower than that of pristine carbon/polydimethylsiloxane electrodes in a previous study, with a broad linear range of 1-1000 pM. The physically modified electrode was very stable during the electrode regeneration process after DNA detection. Our method paves the way for utilizing physical modification to significantly lower the limit of detection of a biosensor system as an alternative to chemical processes.

Dipole-Moment Induced Phototaxis and Fuel-Free Propulsion of ZnO/Pt Janus Micromotors.

Light-driven micromotors have stimulated considerate interests due to their potentials in biomedicine, environmental remediation, or serving as the model system for non-equilibrium physics of active matter. Simultaneous control over the motion direction and speed of micro/nanomotors is crucial for their functionality but still difficult since Brownian motion always randomizes the orientations. Here, a highly efficient light-driven ZnO/Pt Janus micromotor capable of aligning itself to illumination direction and exhibiting negative phototaxis at high speeds (up to 32 µm s-1 ) without the addition of any chemical fuels is developed. A light-triggered self-built electric field parallel to the light illumination exists due to asymmetrical surface chemical reactions induced by the limited penetration depth of light along the illumination. The phototactic motion of the motor is achieved through electrophoretic rotation induced by the asymmetrical distribution of zeta potential on the two hemispheres of the Janus micromotor, into alignment with the electric field. Notably, similar phototactic propulsion is also achieved on TiO2 /Pt and CdS/Pt micromotors, which presents explicit proof of extending the mechanism of dipole-moment induced phototactic propulsion in other light-driven Janus micromotors. Finally, active transportation of yeast cells are achieved by the motor, proving its capability in performing complex tasks.

Isotropic Hedgehog-Shaped-TiO2/Functional-Multiwall-Carbon-Nanotube Micromotors with Phototactic Motility in Fuel-Free Environments.

Directional motion in response to specific signals is critically important for micro/nanomotors in precise cargo transport, obstacle avoidance, collective control, and complex maneuvers. In this work, a kind of isotropic light-driven micromotor that is made of hedgehog-shaped TiO2 and functional multiwall carbon nanotubes (Hs-TiO2@FCNTs) has been developed. The FCNTs are closely entangled with Hs-TiO2 and form a close-knit matrix on the surface of Hs-TiO2, which facilitates the transfer of electrons from Hs-TiO2 to FCNTs. Due to the high redox potential of Hs-TiO2, excellent electron-hole separation efficiency by the addition of FCNTs, and isotropic morphology of the micromotor, these Hs-TiO2@FCNT micromotors show phototactic and fuel-free propulsion under unidirectional irradiation of UV light. It is the first time to demonstrate isotropic micromotors that are propelled by self-electrophoresis. The isotropy of Hs-TiO2@FCNT micromotors makes them immune to the rotational Brownian diffusion and local flows, exhibiting superior directionality. The motion direction of our micromotors can be precisely tuned by light and a velocity of 8.9 µm/s is achieved under 160 mW/cm2 UV light illumination. Photodegradation of methylene blue and active transportation of polystyrene beads are demonstrated for a proof-of-concept application of our micromotors. The isotropic design of the Hs-TiO2@FCNT micromotors with enhanced photocatalytic properties unfolds a new paradigm for addressing the limitations of directionality control and chemical fuels in the current asymmetric light-driven micromotors.

Highly selective, reusable electrochemical impedimetric DNA sensors based on carbon nanotube/polymer composite electrode without surface modification.

We fabricated a composite of multi-walled carbon nanotube and polydimethylsiloxane and utilized it as an electrode for DNA sensing using electrochemical impedance spectroscopy. Without any surface modification or probe immobilization, often necessary for other electrodes, this electrode also acts as a recognition layer for DNA via π-π interactions between the multi-walled carbon nanotube and DNA. This electrode is easily reusable via a simple cleansing process, because there are no covalently bonded adsorbates on the electrode. Compared to previous DNA detection based on differential pulse voltammetry using a similar electrode, the measurement time was reduced from 1 h to less than 30 min, and the limit of detection (25 pM) was reduced by a factor of more than five. In addition, our system can detect the single-base mismatch between the target and probe. Our results indicate that electrochemical impedance spectroscopy is promising for utilizing the multi-walled carbon nanotube and polydimethylsiloxane electrode as a DNA sensor.

Effects of Baicalin on Diabetic Cardiac Autonomic Neuropathy Mediated by the P2Y12 Receptor in Rat Stellate Ganglia.

BACKGROUND/AIMS: Chronic diabetic hyperglycemia can damage various of organ systems and cause serious complications. Although diabetic cardiac autonomic neuropathy (DCAN) is the primary cause of death in diabetic patients, its pathogenesis remains to be fully elucidated. Baicalin is a flavonoid extracted from Scutellaria baicalensis root and has antibacterial, diuretic, anti-inflammatory, anti- metamorphotic, and antispasmodic effects. Our study explored the effects of baicalin on enhancing sympathoexcitatory response induced by DCAN via the P2Y12 receptor. METHODS: A type 2 diabetes mellitus rat model was induced by a combination of diet and streptozotocin. Serum epinephrine was measured by enzyme-linked immunosorbent assay. Blood pressure and heart rate were measured using the indirect tail-cuff method. Heart rate variability was analyzed using the frequency-domain of electrocardiogram recordings. The expression levels of P2Y12, interleukin-1beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and connexin 43 (Cx43) were determined by quantitative real-time reverse transcription-polymerase chain reaction and western blotting. The interaction between baicalin and P2Y12 determined using by molecular docking. RESULTS: Baicalin alleviated elevated blood pressure and heart rate, improved heart rate variability, and decreased the elevated expression levels of P2Y12, IL-1ß, TNF-α, and Cx43 in the stellate ganglia of diabetic rats. Baicalin also reduced the elevated concentration of serum epinephrine and the phosphorylation of p38 mitogen-activated protein kinase in diabetic rats. CONCLUSION: Baicalin decreases sympathetic activity by inhibiting the P2Y12 receptor in stellate ganglia satellite glial cells to maintain the balance between sympathetic and parasympathetic nerves and relieves DCAN in the rat.

Chronic lead exposure enhances the sympathoexcitatory response associated with P2X4 receptor in rat stellate ganglia.

Chronic lead exposure causes peripheral sympathetic nerve stimulation, including increased blood pressure and heart rate. Purinergic receptors are involved in the sympathoexcitatory response induced by myocardial ischemia injury. However, whether P2X4 receptor participates in sympathoexcitatory response induced by chronic lead exposure and the possible mechanisms are still unknown. The aim of this study was to explore the change of the sympathoexcitatory response induced by chronic lead exposure via the P2X4 receptor in the stellate ganglion (SG). Rats were given lead acetate through drinking water freely at doses of 0 g/L (control group), 0.5 g/L (low lead group), and 2 g/L (high lead group) for 1 year. Our results demonstrated that lead exposure caused autonomic nervous dysfunction, including blood pressure and heart rate increased and heart rate variability (HRV) decreased. Western blotting results indicated that after lead exposure, the protein expression levels in the SG of P2X4 receptor, IL-1ß and Cx43 were up-regulated, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was activated. Real-time PCR results showed that the mRNA expression of P2X4 receptor in the SG was higher in lead exposure group than that in the control group. Double-labeled immunofluorescence results showed that P2X4 receptor was co-expressed with glutamine synthetase (GS), the marker of satellite glial cells (SGCs). These changes were positively correlated with the dose of lead exposure. The up-regulated expression of P2X4 receptor in SGCs of the SG maybe enhance the sympathoexcitatory response induced by chronic lead exposure.

The P2X7 receptor in dorsal root ganglia is involved in HIV gp120-associated neuropathic pain.

Human immunodeficiency virus (HIV)-associated neuropathic pain is common, and studies have shown that HIV envelope glycoprotein 120 (gp120) can directly stimulate primary sensory afferent neurons causing hyperalgesia. The P2X7 receptor in the dorsal root ganglia (DRG) is involved in pain transmission and is closely related to the inflammatory and immune response. In this study, we aimed to explore the role of the P2X7 receptor in gp120-induced neuropathic pain using a rat model specific for this type of pain. The results showed that mechanical hyperalgesia, thermal hyperalgesia and P2X7 expression levels were increased in rats treated with gp120. The P2X7 antagonist, brilliant blue G (BBG), decreased hyperalgesia and P2X7 expression levels in rats treated with gp120. BBG also decreased IL-1ß and TNF-α receptor expression and ERK1/2 phosphorylation levels and increased IL-10 expression in the gp120-treated rat DRG. In addition, P2X7 agonist (BzATP)-activated currents in DRG neurons cultured with gp120 were larger than those in control neurons, and the inhibitory effect of BBG on BzATP-induced currents in gp120-treated DRG neurons was larger than that in control neurons. Therefore, inhibition of the P2X7 receptor in rat DRG relieved gp120-induced mechanical hyperalgesia and thermal hyperalgesia.

Naringin Protects Against High Glucose-Induced Human Endothelial Cell Injury Via Antioxidation and CX3CL1 Downregulation.

BACKGROUND/AIMS: The induction of endothelial injury by hyperglycemia in diabetes has been widely accepted. Naringin is a bio-flavonoid. Some studies showed that naringin alleviates diabetic complications, but the exact mechanisms by which naringin improves diabetic anomalies are not yet fully understood. The aim of this research was to study the protective effect of naringin on high glucose-induced injury of human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were cultured with or without high glucose in the absence or presence of naringin for 5 days. The expression of CX3CL1 was determined by quantitative real-time RT-PCR (qPCR) and western blot. The cellular bioenergetic analysis oxygen consumption rate (OCR) was measured with a Seahorse Bioscience XF analyzer. RESULTS: The production of reactive oxygen species (ROS), the expression of CX3CL1 and the level of AKT phosphorylation were increased in HUVECs cultured with high glucose compared with controls. However, naringin rescued these increases in ROS production, CX3CL1 expression and AKT phosphorylation. Nitric oxide (NO) production and OCR were lower in the high glucose group, and naringin restored the changes induced by high glucose. Molecular docking results suggested that Naringin might interact with the CX3CL1 protein. CONCLUSION: Naringin protects HUVECs from high-glucose-induced damage through its antioxidant properties by downregulating CX3CL1 and by improving mitochondrial function.

Long noncoding RNA MRAK009713 is a novel regulator of neuropathic pain in rats.

Long noncoding RNAs have been implicated in neuropathy. Here, we identify and validate a long noncoding RNA, MRAK009713, as the primary regulator of neuropathic pain in chronic constriction injury (CCI) rats. MRAK009713 expression was markedly increased in CCI rats associated with enhanced pain behaviors, and small interfering RNA against MRAK009713 significantly reduced both mechanical and thermal hyperalgesia in the CCI rats. MRAK009713 is predicted to interact with the nociceptive P2X3 receptor by CatRAPID, a bioinformatics technology. Overexpression of MRAK009713 markedly increased expression of P2X3 in the dorsal root ganglia of the control rats, and MRAK009713 small interfering RNA significantly inhibited the P2X3 expression in the dorsal root ganglia of the CCI rats. MRAK009713 directly interacted with the P2X3 protein heterologously expressed in the human embryonic kidney (HEK) 293 cells and potentiated P2X3 receptor function. Thus, MRAK009713 is a novel positive regulator of neuropathic pain in rats through regulating the expression and function of the P2X3 receptor.

Co-expression changes of lncRNAs and mRNAs in the cervical sympathetic ganglia in diabetic cardiac autonomic neuropathic rats.

Cardiac autonomic neuropathy in Type 2 diabetes (T2D) is often a devastating complication. Long non-coding RNAs (lncRNAs) have important effects on both normal development and disease pathogenesis. In this study, we explored the expression profiles of some lncRNAs involved in inflammation which may be co-expressed with messenger RNA (mRNA) in superior cervical and stellate ganglia after type 2 diabetic injuries. Total RNA isolated from 10 pairs of superior cervical and stellate ganglia in diabetic and normal male rats was hybridized to lncRNA arrays for detections. Pathway analysis indicated that the most significant gene ontology (GO) processes that were upregulated in diabetes were associated with immune response, cell migration, defense response, taxis, and chemotaxis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed that most of the target genes of the lncRNAs were located in cytokine-cytokine receptor interactions, the chemokine signaling pathway and cell adhesion molecules, which were involved in T2D. Gene co-expression network construction showed that the co-expression network in the experimental rats consisted of 268 regulation edges among 105 lncRNAs and 11 mRNAs. Our studies demonstrated the co-expression profile of lncRNAs and mRNAs in diabetic cardiac autonomic ganglia, suggesting possible roles for multiple lncRNAs as potential targets for the development of therapeutic strategies or biomarkers for diabetic cardiac autonomic neuropathy. © 2016 Wiley Periodicals, Inc.

The role of adrenergic activation on murine luteal cell viability and progesterone production.

Sympathetic innervations exist in mammalian CL. The action of catecholaminergic system on luteal cells has been the focus of a variety of studies. Norepinephrine (NE) increased progesterone secretion of cattle luteal cells by activating ß-adrenoceptors. In this study, murine luteal cells were treated with NE and isoprenaline (ISO). We found that NE increased the viability of murine luteal cells and ISO decreased the viability of luteal cells. Both NE and ISO promoted the progesterone production. Nonselective ß-adrenergic antagonist, propranolol reversed the effect of ISO on cell viability but did not reverse the effect of NE on cell viability. Propranolol blocked the influence of NE and ISO on progesterone production. These results reveal that the increase of luteal cell viability induced by NE is not dependent on ß-adrenergic activation. α-Adrenergic activation possibly contributes to it. Both NE and ISO increased progesterone production through activating ß-adrenergic receptor. Further study showed that CyclinD2 is involved in the increase of luteal cell induced by NE. 3ß-Hydroxysteroid dehydrogenase, LHR, steroidogenic acute regulatory protein (StAR), and PGF2α contribute to the progesterone production induced by NE and ISO.