Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease.

INTRODUCTION: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers. METHODS: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts. RESULTS: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aß)42, Aß42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement. DISCUSSION: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aß and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD. HIGHLIGHTS: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

Alternative Oxidase: From Molecule and Function to Future Inhibitors.

In the respiratory chain of the majority of aerobic organisms, the enzyme alternative oxidase (AOX) functions as the terminal oxidase and has important roles in maintaining metabolic and signaling homeostasis in mitochondria. AOX endows the respiratory system with flexibility in the coupling among the carbon metabolism pathway, electron transport chain (ETC) activity, and ATP turnover. AOX allows electrons to bypass the main cytochrome pathway to restrict the generation of reactive oxygen species (ROS). The inhibition of AOX leads to oxidative damage and contributes to the loss of adaptability and viability in some pathogenic organisms. Although AOXs have recently been identified in several organisms, crystal structures and major functions still need to be explored. Recent work on the trypanosome alternative oxidase has provided a crystal structure of an AOX protein, which contributes to the structure-activity relationship of the inhibitors of AOX. Here, we review the current knowledge on the development, structure, and properties of AOXs, as well as their roles and mechanisms in plants, animals, algae, protists, fungi, and bacteria, with a special emphasis on the development of AOX inhibitors, which will improve the understanding of respiratory regulation in many organisms and provide references for subsequent studies of AOX-targeted inhibitors.

Simultaneous removal of Cd(II) and As(III) by graphene-like biochar-supported zero-valent iron from irrigation waters under aerobic conditions: Synergistic effects and mechanisms.

Irrigation water is commonly contaminated with cadmium and arsenic near mining regions, which significantly contributes to excessive heavy metals in rice grains. Herein, we have developed a novel graphene-like biochar (GB)-supported nanoscale zero-valent iron (nZVI) and the underlying mechanisms of synergistic effects between GB and nZVI for the simultaneous removal of Cd(II) and As(III) under aerobic conditions. The results show that GB/nZVI has a high removal capacity of 363 mg/g (nZVI) for As(III) at pH 4 and 92.8 mg/g (nZVI) for Cd(II) at pH 7. These values are significantly higher than GB and nZVI (1.7 times for Cd(II); 1.4 times for As(III)) alone, suggesting strong synergistic effects between GB and nZVI. GB promotes nZVI oxidation to form iron oxyhydroxides and causing 35 % of As(III) converting to As(V). Importantly, As(III) significantly enhance Cd(II) removal by GB/nZVI (i.e., 131.8 mg/g as nZVI). Coexisting ions such as phosphate and humic acid have a stronger inhibitory effect on the simultaneous removal of Cd(II) and As(III). Our results indicate that oxidation and surface complexation are the dominant mechanisms and electrostatic binding exists for As(III) removal, while surface complexation predominates for Cd(II) removal. These findings provide insight into developing an effective solution for removing Cd(II)/As(III) from irrigation waters.

Peritumoral implantation of hydrogel-containing nanoparticles and losartan for enhanced nanoparticle penetration and antitumor effect.

BACKGROUND AND PURPOSE: Nanoparticle-loaded hydrogels - localized drug delivery devices containing a combination of therapeutic nanoparticles and implantable hydrogel - have been recipients of increased focus and interest for cancer treatment. However, it is difficult for the released nanoparticles to penetrate deeply into tumors because of the dense collagen network in the tumor extracellular matrix, which greatly limits their antitumor effect. We hypothesized that the implantation of a hydrogel loaded with both nanoparticles and losartan (Los) might enhance penetration because Los has been proven to effectively reduce collagen levels in various tumors. Herein, we developed a nanoparticle/Los-loaded hydrogel system and evaluated the intratumoral distribution and anticancer effect after peritumoral implantation of nanoparticles. METHODS: Fluorescent polystyrene nanoparticles (FPNPs, size ~100 nm) and Los were simultaneously encapsulated in a polyethylene glycol (PEG) hydrogel to form the FPNP/Los-loaded hydrogel. After peritumoral implantation in 4T1 tumor-bearing mice for 2 weeks, intratumoral distributions of FPNPs and collagen level were determined. Based on the results, liposomal doxorubicin (Doxil, ~100 nm) was subsequently substituted for FPNPs in the hydrogel. The cellular uptake and cytotoxicity of the Doxil/Los-loaded hydrogel were studied, and the in vivo antitumor efficacy after peritumoral implantation was evaluated. RESULTS: Compared with a standard FPNP-loaded hydrogel, the FPNP/Los-loaded hydrogel resulted in enhanced penetration and reduced collagen levels after implantation. Thereafter, the potential of a Doxil/Los-loaded hydrogel for cancer treatment was studied. Doxorubicin was released from the hydrogel and induced effective cytotoxicity against 4T1 cells. The Doxil/Los-loaded hydrogel showed synergistic antitumor effects in 4T1 tumor-bearing mice and was more effective at tumor inhibition than the Doxil-loaded hydrogel. CONCLUSION: This study provides a proof of principle that the implantation of nanoparticles/Los-loaded hydrogel can increase the intratumoral distribution and antitumor efficacy of nanoparticles, owing to collagen depletion by Los. Future studies may build on this strategy for enhanced tumor penetration of nanoparticles.

[Study on the linked samples of methamphetamine identified by the impurity profile].

OBJECTIVE: To compare and classify the samples of MA crystals by using impurity profile to offer methods for identification of linked samples. METHODS: 50 mg samples of MA were dissolved in 1 ml of buffer solution (pH 7.0, four parts of 0.1 mol/L phosphate buffer, and one part of 10% Na2CO3), impurities were extracted with 0.5 ml of ethyl acetate containing four internal standards (n-decane, n-pentadecane, n-eicosane and n-octacosane) and analyzed by gas chromatography with a flame ionization detector on a DB-5 capillary column (30 m x 0.32 mm i.d. x 1.0 microm). Seventeen characteristic peaks on chromatograms were selected for the comparison and classification of samples, and the data were evaluated by the Euclidean distance of the relative peak areas after logarithmic transformation. RESULTS: Eight different batches of MA (six samples from each batch) to be seized by the Beijing Public Security Bureau (BPSB) in 2006-2007 were analyzed. The results indicated that the samples from the same batch were successfully classified into one group. CONCLUSION: The methods could be very useful for identifying the linked samples and could provide technique foundation for MA drug criminal inspection.

[Determination of the synthetic route based on impurity profiling of methamphetamine].

OBJECTIVE: Impurity profiling of seized methamphetamine may play an important role in the determination of the synthetic method employed and the criminal investigations of drug traffic routes. METHODS: A sample of methamphetamine was dissolved in buffer solution. Impurities were extracted with ethyl acetate containing four internal standards (n-decane, n-pentadecane, n-eicosane and n-octacosane) and analyzed by GC-MS. RESULTS: These data are suggestive of ephedrine/pseudoephedrine as the main precursor of the methamphetamine samples seized during 2006-2007. Six samples of selected eight samples were synthesized via the more specific ephedrine/hydriodic acid/red phosphorus method. CONCLUSION: Ephedrine/pseudoephedrine is common material used to synthesize methamphetamine.

[Determination of aconitine in biological samples].

The determination of aconitine in biological samples by using TLC, HPLC and animal tests is described. TLC is simple, easy to manipulate and highly sensitive. The minimum detection limit was 0.3 microgram, so it can be used as a preliminary screening method. While detecting by HPLC, the characteristic UV-absorption spectrum of aconitine and animal tests were used as the qualitative methods. The characteristic UV absorption wavelengths were (228 +/- 2) nm and (275 +/- 2) nm. The linear range of calibration curve was 2 mg/L-50 mg/L. The coefficient of variation was 0.9996. It is suitable for applications in forensic field.