Smart Target-Initiated Catalytic DNA Junction Circuit Amplification Strategy for the Ultrasensitive Electrochemiluminescence Detection of MicroRNA.

One of the highly attractive research directions in the electrochemiluminescence (ECL) field is how to regulate and improve ECL efficiency. Quantum dots (QDs) are highly promising ECL materials due to their adjustable luminescence size and strong luminous efficiency. MoS2 NSs@QDs, an ECL emitter, is synthesized via hydrothermal methods, and its ECL mechanism is investigated using cyclic voltammetry and ECL-potential curves. Then, a stable and vertical attachment of a triplex DNA (tsDNA) probe to the MoS2 nanosheets (NSs) is applied to the electrode. Next, an innovative ECL sensor is courageously empoldered for precise and ultrasensitive detection of target miRNA-199a through the agency of ECL-resonance energy transfer (RET) strategy and a dextrous target-initiated catalytic three-arm DNA junction assembly (CTDJA) based on a toehold strand displacement reaction (TSDR) signal amplification approach. Impressively, the ingenious system not only precisely regulates the distance between energy donor-acceptor pairs leave energy less loss and more ECL-RET efficiency, but also simplifies the operational procedure and verifies the feasibility of this self-assembly process without human intervention. This study can expand MoS2 NSs@QDs utilization in ECL biosensing applications, and the proposed nucleic acid amplification strategy can become a miracle cure for ultrasensitive detecting diverse biomarkers, which helps researchers to better study the tumor mechanism, thereby unambiguously increasing cancer cure rates and reducing the risk of recurrence.

Metal organic framework-derived transition metal-doped CoSx nanocage for enhanced visible light-assisted methanol electrocatalytic oxidation.

Designing noble metal-free anode catalysts for visible light-assisted direct methanol fuel cells still remains a significant challenge. In this study, combining the photocatalytic and electrocatalytic properties of CoSx, a visible light-assisted methanol electrocatalytic oxidation strategy was provided. Doping engineering was employed to adjust the electronic structure of CoSx and improve their photoassisted methanol electrocatalytic oxidation activity. Using ZIF-67 as precursor, transition metal-doped CoSx (M-CoSx, M = Zn, Cu, Ni, and Cd) nanocage was synthesized by cation exchange and L-cysteine-controlled etching. Cd doping not only widens the light adsorption to the visible region but also enhances the separation efficiency of photogenerated electron-hole pairs. The electrochemical and photochemical results indicated that the strong oxidative photogenerated hole, OH˙, and O2˙- are beneficial for methanol electrocatalytic oxidation. The synergistic electrocatalytic and photocatalytic effect will be a practical strategy for improving the methanol electrocatalytic oxidation activity of noble metal-free semiconductor catalysts.

Injury of photoreceptors and retinal pigment epithelium in macular area of a preterm infant: A case analysis.

RATIONAL: Injury of photoreceptors and retinal pigment epithelium (RPE) in macular area of premature infants is very rare. PATIENT CONCERNS: A preterm infant delivered under general anesthesia. The infant was born at 28 weeks' and 4 days' gestation, with a birth weight of 1.15 kg and a treatment of oxygen inhalation after birth. According to the related protocol formulated by the Ophthalmology Branch of the Chinese Medical Association in 2014, the infant was regularly checked in our hospital. DIAGNOSIS: Optical coherence tomography (OCT) examination showed injuries of the photoreceptors and RPE in macular area. INTERVENTIONS: The fundus screening at 40 weeks' and 4 days' gestation (corrected gestational age) showed retinopathy of prematurity in bilateral eyes, with round yellow-white lesions at the macular area of right eye and sub-temporal macular area. OCT examination showed interrupted signals in the external limiting membrane (ELM), inner segment of the photoreceptors (IS)/outer segment of the photoreceptors (OS) layer, interdigitation zone (IZ), and RPE of the central fovea of macula of the right eye, with the area of defect of approximately 184 µm. Enhanced signal reflection was found under the defect area. Interrupted signals were also found in the IS/OS layer of the central fovea of macula of the left eye, with the area of defect of approximately 222 µm. Fundus fluorescence angiography (FFA) examination showed transmitted fluorescence at the macular area of the right eye and sub-temporal macular area of the left eye, suggesting retinopathy of prematurity in bilateral eyes. OUTCOMES: Several factors, such as photic damage, eye injuries, hyperpyrexia, and underlying diseases, could cause macular retinal injuries. However, the baby had not received any radiation from high energy intense light sources, and had no history of hyperpyrexia or trauma. Fundamental screening was performed 1 year and 4 months of age and no obvious change was found in the round yellow-white lesions of the eyes compared with that in earlier stages. We have contacted with the patient for the follow-up OCT and FFA examinations a month later to check the possible structural changes of the macular area. LESSONS: The retina of a preterm infant is underdeveloped, we speculated that the bilateral retinal injuries in this baby could be caused by various factors.

Increased Tim-3 expression on TILs during treatment with the Anchored GM-CSF vaccine and anti-PD-1 antibodies is inversely correlated with response in prostate cancer.

Programmed death receptor-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) play important roles in tumor immune evasion. PD-1 blockade could produce an effective antitumor effect in many solid tumors except prostate cancer (PCa) because of rare programmed death ligand-1 (PD-L1) expression on PCa cells. Streptavidin (SA)-GM-CSF surface-anchored tumor cell (Anchored GM-CSF) vaccines could increase the number of tumor-infiltrating lymphocytes (TILs) and induce specific antitumor immune responses. The Anchored-GM-CSF vaccine and anti-PD-1 antibodies exerted synergistic effects in mouse models of PCa metastasis. However, the response rate was low due to the presence of other negative regulatory pathways. Tim-3 expression could be upregulated at resistance to combination therapy with anti-PD-1 antibodies and the Anchored GM-CSF vaccine. Sequential administration of anti-PD-1 and anti-Tim-3 antibodies could further improve the efficacy of the Anchored GM-CSF vaccine therapy, and tumor regression was noted in over 60% of animals. This triple therapy improved the specific cytotoxic activity, proliferation and secretion of CD8+ TILs and reduced the production of tumor-promoting cytokines. These findings indicated that this triple therapy could induce a robust antitumor immune response in mouse models of PCa.

Effect of glucocorticoid on cytokines TLR9 and TLR7 in peripheral blood for patients with uveitis.

The effect of glucocorticoid on cytokines Toll-like receptor (TLR)9 and TLR7 in peripheral blood of patients with uveitis was explored. Forty-six patients with uveitis admitted to our hospital from April 2014 to April 2015 were selected as the research observational group. Thirty-five able-bodied individuals in the same period were selected as the control group. To treat uveitis, the observational group was injected with glucocorticoid (1-2 mg/kg/day) daily, while the control group did not receive any treatment. The quantity of expression of peripheral blood cytokines TLR9 and TLR7 were detected by the methods of fluorescence quantitative PCR, enzyme-linked immunosorbent assay and western blotting. The content of peripheral blood TLR9 and TLR7 (0.21±0.01, 0.19±0.01) decreased significantly (P<0.05) in observational group after glucocorticoid treatment. Compared with data of control group (0.21±0.01, 0.19±0.01), TLR9 and TLR7 content in peripheral blood after glucocorticoid treatment on the patients with uveitis from observation group (0.19±0.01, 0.17±0.01) did not show any significant difference, for correlation between TLR9 and TLR7 in observation group before and after treatment. It was observed that the cytokine content of TLR9 was associated with TLR7 positively (r=0.653, P=0.012). In conclusion, glucocorticoid can improve uveitis by reducing the content of cytokines TLR9 and TLR7 in peripheral blood.

Cholinergic activation of the murine trachealis muscle via non-vesicular acetylcholine release involving low-affinity choline transporters.

In addition to quantal, vesicular release of acetylcholine (ACh), there is also non-quantal release at the motor endplate which is insufficient to evoke postsynaptic responses unless acetylcholinesterase (AChE) is inhibited. We here addressed potential non-quantal release in the mouse trachea by organ bath experiments and (immuno)histochemical methods. Electrical field stimulation (EFS) of nerve terminals elicited tracheal constriction that is largely due to ACh release. Classical enzyme histochemistry demonstrated acetylcholinesterase (AChE) activity in nerve fibers in the muscle and butyrylcholinesterase (BChE) activity in the smooth muscle cells. Acute inhibition of both esterases by eserine significantly raised tracheal tone which was fully sensitive to atropine. This effect was reduced, but not abolished, in AChE, but not in BChE gene-deficient mice. The eserine-induced increase in tracheal tone was unaffected by vesamicol (10(-5)M), an inhibitor of the vesicular acetylcholine transporter, and by corticosterone (10(-4)M), an inhibitor of organic cation transporters. Hemicholinium-3, in low concentrations an inhibitor of the high-affinity choline transporter-1 (CHT1), completely abrogated the eserine effects when applied in high concentrations (10(-4)M) pointing towards an involvement of low-affinity choline transporters. To evaluate the cellular sources of non-quantal ACh release in the trachea, expression of low-affinity choline transporter-like family (CTL1-5) was evaluated by RT-PCR analysis. Even though these transporters were largely abundant in the epithelium, denudation of airway epithelial cells had no effect on eserine-induced tracheal contraction, indicating a non-quantal release of ACh from non-epithelial sources in the airways. These data provide evidence for an epithelium-independent non-vesicular, non-quantal ACh release in the mouse trachea involving low-affinity choline transporters.