Iron ions-sequestrable and antioxidative carbon dot-based nano-formulation with nitric oxide release for Parkinson's disease treatment.

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp2-hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD.

In Situ Attached Photothermal Immunomodulation-Enhanced Nanozyme for the Inhibition of Postoperative Malignant Glioma Recurrence.

Glioblastoma (GBM) is one of the most challenging malignant brain tumors to treat. Herein, we describe a nanoenzyme hemostatic matrix strategy with the tumor cavity in situ application that simultaneously serves as photothermal agent and induces immunogenic cell death after GBM surgical resection to enhance the antitumor immunity and delay tumor recurrence. The hemostatic matrix system (Surgiflo@PCN) contains Surgiflo, a multispace structure that can be used to penetrate different shapes of tumor cavities to prevent postoperative tumor cavity hemorrhage. As well, porous palladium-copper nanoclusters (PCNs) have adjustable enzyme-like activities (oxidase, peroxidase, and catalase) responsible for formation of reactive oxygen species (ROS) under near-infrared (808 nm) laser irradiation. When the Surgiflo@PCN entered the resected tumor cavity, the first action was the direct killing of glioma cells via ROS and photothermal therapy (PTT). The second action was the induction of immunogenic cell death by PCN-enhanced oxidative stress and PTT, which reversed the immunosuppressive tumor microenvironment and enhanced the antitumor immune response. This eradicated residual glioma cells and prevented recurrence. The collective findings demonstrate that Surgiflo@PCN kills glioma cells directly through ROS and PTT and enhances antiglioma immunity and kills glioma cells indirectly. The "one-stone, two-birds" strategy could become an effective photothermal immunotherapy in GBM patients.

Inorganic Recognizer-Assisted Homogeneous Electrochemiluminescence Determination of Organophosphorus Pesticides via Target-Controlled Emitter Release.

Given the relevance of organophosphorus pesticides (OPs) with food safety, it is highly urgent to develop sensitive and reliable sensors for OPs. However, most of the OP sensors are developed based on colorimetric and fluorescent techniques, which are limited to severe interference of color and fluorescence from pigments and organic acids in agricultural crops. Herein, we develop an inorganic recognizer-based homogeneous electrochemiluminescence (ECL) sensor for the highly sensitive and credible determination of OPs based on manganese dioxide and tris(2,2'-bipyridine)ruthenium [Ru(bpy)3]2+. Through electrostatic interaction, manganese dioxide nanoflakes-[Ru(bpy)3]2+ nanocomposites (MnNFs-Ru) are formed and exhibit a weak ECL signal due to the confinement of [Ru(bpy)3]2+ in MnNFs-Ru. Interestingly, MnNFs-Ru are capable of recognizing thiols due to the analyte-initiated reduction of MnNFs into Mn2+ and release of [Ru(bpy)3]2+ from MnNFs-Ru into solution. Further, MnNFs-Ru are employed for the homogeneous ECL determination of OPs, where acetylcholinesterase (AChE) catalyzes the hydrolysis of acetylthiocholine (ATCh) into thiocholine, which in turn decomposes MnNFs of MnNFs-Ru into Mn2+, and OPs inhibit AChE activity. This study widens the application of inorganic recognizers from colorimetry/fluorescence to homogeneous ECL and effectively avoids the interference of color and fluorescence, opening up a new path to the development of high-performance OP sensors and supplying a promising tool for guaranteed OP-related food safety.

Improved performance of soy protein adhesive with melamine-urea-formaldehyde prepolymer.

In recent years, soy protein adhesive, as an environmentally friendly bio-based adhesive, has attracted extensive attention. In this study, in order to ameliorate the bonding quality of soy protein isolate (SPI) adhesive, the melamine-urea-formaldehyde prepolymer (MUFP) was synthesized, and different amounts of it were introduced into the SPI adhesive as a cross-linking agent. Fourier transform infrared (FT-IR) spectroscopy, gel permeation chromatography (GPC), thermogravimetric analyze (TGA), and scanning electron microscopy (SEM) were used to analysis the mechanism of modification. The results of plywood test indicated that the wet bonding strength of the adhesives was first increased and then decreased with an increase in the amount of MUFP additive. FT-IR, TGA, and SEM tests suggested that the introduction of MUFP could promote the establishment of a cross-linking structure in the cured adhesive layer to improve the bonding quality of adhesives, but presence of excessive MUFP could introduce hydrophilic groups and adversely affect water resistance.

One-Step Synthesis of Methylene Blue-Encapsulated Zeolitic Imidazolate Framework for Dual-Signal Fluorescent and Homogeneous Electrochemical Biosensing.

In vitro diagnosis requires target biomarkers to be reliably detected at an ultralow level. A dual-signal strategy permits self-calibration to overcome the interferences of experimental and environmental factors, and thus is regarded as a promising approach. However, currently reported works mainly concentrated on the same forms of energy of output signals. Herein, we propose a one-step strategy for synthesis of methylene blue-encapsulated zeolitic imidazolate framework-90 (MB@ZIF-90) with high loading, unique dual-signal property, exceptional recognition capability, and good stability, and we further pioneer MB@ZIF-90 as a dual-signal biosensor for label-free, enzyme-free, and ultrasensitive detection of adenosine triphosphate (ATP) by integration of fluorescence and homogeneous electrochemical techniques. The recognition of MB@ZIF-90 by target ATP spurs the decomposition of ZIF-90, subsequently permitting MB to be released into a supernatant. As compared to the case where ATP does not exist, obviously increased intensities in fluorescence and differential pulse voltammetry current are observed and both signals are directly proportional to ATP concentrations. Thus, the MB@ZIF-90-based biosensor achieved dual-signal detection of ATP in an ultrasensitive manner and displayed a more reliable diagnosis result than previously reported ATP biosensors. This dual-signal strategy provides a new opportunity to develop high-performance biosensors for in vitro diagnosis and demonstrates great potential for future applications in bioinformatics and clinical medicine.

PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population.

PARP-1 (poly(ADP-ribose) polymerase-1) plays an important role in tumorigenesis. Since its effects on different populations are varied, this study investigated the impact of PARP-1 on primary hepatocellular carcinoma in a Southern Chinese Zhuang population. We assessed the global PARP-1 messenger RNA expression in patients with hepatocellular carcinoma using The Cancer Genome Atlas dataset. Increased PARP-1 expression, related to alpha-fetoprotein level, was observed. The area under the receiver operating characteristic curve value was 0.833. Kaplan-Meier survival curves indicated that higher PARP-1 expression was not correlated with poorer overall survival and recurrence-free survival. In a Zhuang population, PARP-1 messenger RNA and protein levels were increased in the hepatocellular carcinoma tissue and its adjacent liver tissues as assessed by quantitative polymerase chain reaction, immunohistochemistry, and western blotting. Higher PARP-1 level was associated with a higher tumor stage (p < 0.05), without correlation with age, gender, smoking, drinking, tumor size, serum alpha-fetoprotein level, hepatitis B virus infection, metastasis, and invasion (p > 0.05). Further analysis suggested that H2AX, a PARP-1 protein interaction partner, was coordinated with PARP-1 in hepatocellular carcinoma tumorigenesis. Overall, some new characteristics of PARP-1 expression were noted in the Zhuang population. PARP-1 is a novel promising diagnostic marker for hepatocellular carcinoma in the Southern Chinese Zhuang population.

Cigarette smoking has a positive and independent effect on testosterone levels.

Previous studies have suggested that testosterone levels are linked to a variety of diseases, such as cardiovascular disease, type-2 diabetes, the metabolic syndrome, erectile dysfunction, depression, stroke and osteoporosis. Since cigarette smoking is a major health problem and highly prevalent among men, several groups have studied the effects of cigarette smoking on testosterone levels in men. However, the results have been conflicting. Our objectives were to examine the association of cigarette smoking and serum levels of sex hormone-binding globulin (SHBG), total testosterone (TT) and free testosterone (FT) in a large male population. Data from 2,021 men (989 nonsmokers and 1,032 smokers), aged 20-69, were collected from the Fangchenggang Area Male Health and Examination survey using an in-person interview and self-administered questionnaires from September to December, 2009. We have found the following: (a) smokers had significantly higher TT and FT levels compared to nonsmokers, even after stratification as per age, BMI, triglycerides and alcohol consumption. (b) Both TT (r = -0.083, P <0.001) and FT (r = -0.271, P <0.001) levels were negatively correlated to the amount of tobacco exposure. (c) Smoking was an independent influencing factor for the levels of both TT (unadjusted OR = 1.64, 95% CI: 1.33-2.01, P <0.001; adjusted OR = 1.69, 95% CI: 1.34-2.13, P <0.001) and FT (unadjusted OR = 1.32, 95% CI: 1.08-1.61, P = 0.007; adjusted OR = 1.27, 95% CI: 1-1.61, P = 0.050) levels in multivariate logistic regression models before and after adjusting for age, BMI, fasting blood glucose, triglycerides, alcohol consumption and estradiol. (d) Smoking was not found to be an independent predictor of SHBG level after adjustment for confounders in multivariate regression model (P >0.05), although a positive association between increasing pack-years and SHBG level was observed (r = 0.174, P <0.001). More research is needed to elucidate the biological mechanisms and clinical significance of these associations.

Research of correlation between the amount of leukocyte in EPS and NIH-CPSI: result from 1242 men in Fangchenggang Area in Guangxi Province.

OBJECTIVE: To investigate the correlation between the leukocyte in expressed prostatic secretion (EPS) and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) in a large Chinese male population. MATERIALS AND METHODS: Data were collected from 1242 men who participated in the population-based Fangchenggang Area Male Health and Examination Survey (FAMHES), which was carried out in Guangxi, China from September 2009 to December 2009. The severity and symptoms of chronic prostatitis were accessed by the National Institutes of Health Chronic Prostatitis Symptom Index. Meanwhile, the leukocyte in EPS was counted. Demographic information, lifestyle characteristic, and medical history were also obtained through questionnaire. RESULTS: There was no linear correlation between the leukocyte in EPS and NIH-CPSI scores in all subjects (n=1242) (P>.05). Regardless of whether subjects had prostatitis-like symptoms (n=107), there was no linear correlation between the leukocyte in EPS and NIH-CPSI scores (P>.05). After using chi-square tests linear-by-linear association, there were also no linear correlation between the leukocyte in EPS and NIH-CPSI scores (P>.05). CONCLUSION: The results of this study have demonstrated that either in all subjects or in the subjects with prostatitis-like symptoms, there was no linear correlation between the leukocyte in EPS and the severity symptom. So the amount of leukocyte in EPS was unsuitable to apply as the only index of diagnosis, evaluating and observing curative effect. The index should be taken into account for a variety of factors. The improvement of clinical symptom and quality of life were the key points.