Biological tissues exhibit complex spatial heterogeneity that directs the functions of multicellular organisms. Quantifying protein expression is essential for elucidating processes within complex ...biological assemblies. Imaging mass spectrometry (IMS) is a powerful emerging tool for mapping the spatial distribution of metabolites and lipids across tissue surfaces, but technical challenges have limited the application of IMS to the analysis of proteomes. Methods for probing the spatial distribution of the proteome have generally relied on the use of labels and/or antibodies, which limits multiplexing and requires a priori knowledge of protein targets. Past efforts to make spatially resolved proteome measurements across tissues have had limited spatial resolution and proteome coverage and have relied on manual workflows. Here, we demonstrate an automated approach to imaging that utilizes label-free nanoproteomics to analyze tissue voxels, generating quantitative cell-type-specific images for >2000 proteins with 100-µm spatial resolution across mouse uterine tissue sections preparing for blastocyst implantation.
The rapid clearance of circulating nanocarriers in blood during systemic drug delivery remains a challenging hurdle in cancer chemotherapy. Here, inspired by the unique features of bacterial ...pathogens, an original biodegradable polymer micellar system with a rod‐like shape similar to the morphology of bacterial pathogens is developed. These novel nanocarriers have excellent features such as a great capacity of overcoming the rapid clearance of reticuloendothelial system (RES) with long blood circulation, high cellular internalization, and enhanced therapeutic efficacy against cancers. In vivo pharmacokinetic studies in mice reveal that the rod‐like micelles of ≈40 nm in diameter and 600 nm in length possess a minimal uptake by the RES and excellent blood circulation half‐lives (t1/2β = 24.23 ± 2.87 h) for carrying doxorubicin in contrast to spheres (t1/2β = 8.39 ± 0.53 h). The antitumor activity of the rod‐shaped micelles in Balb/c mice bearing H22 tumor xenograft models reveals that they are promptly internalized by tumor cells, resulting in their superior potency and efficacy against artificial solid tumors. These findings suggest that the bio‐inspired nanocarriers as an emerging drug delivery platform may have considerable benefits for enhancing the delivery efficiency of anticancer drugs and in turn enhancing cancer therapy in future clinical applications.
A novel bio‐inspired rod‐shaped micellar system is developed as a nanoplatform for highly effectively delivering anticancer drugs. The nanoplatform has a great capacity of escaping the rapid clearance of reticuloendothelial system in blood, a high internalization rate of tumor cells, and a significant enhancement of therapeutic agent potency against artificial solid tumors.
Mass-spectrometry-based proteomic analysis is a powerful approach for discovering new disease biomarkers. However, certain critical steps of study design such as cohort selection, evaluation of ...statistical power, sample blinding and randomization, and sample/data quality control are often neglected or underappreciated during experimental design and execution. This tutorial discusses important steps for designing and implementing a liquid-chromatography-mass-spectrometry-based biomarker discovery study. We describe the rationale, considerations and possible failures in each step of such studies, including experimental design, sample collection and processing, and data collection. We also provide guidance for major steps of data processing and final statistical analysis for meaningful biological interpretations along with highlights of several successful biomarker studies. The provided guidelines from study design to implementation to data interpretation serve as a reference for improving rigor and reproducibility of biomarker development studies.
Arrhythmia is characterized by abnormal heartbeat rhythms and frequencies caused by heart pacing and conduction dysfunction. Arrhythmia is the leading cause of death in patients with cardiovascular ...disease, with high morbidity and mortality rates, posing a serious risk to human health. Natural drugs and their active ingredients, such as matrine(MAT), tetrandrine(TET), dehydroevodiamine, tanshinone IIA, and ginsenosides, have been widely used for the treatment of atrial fibrillation, ventricular ectopic beats, sick sinus syndrome, and other arrhythmia-like diseases owing to their unique advantages. This review summarizes the mechanism of action of natural drugs and their active ingredients in the treatment of arrhythmia via the regulation of Ca2+, such as alkaloids, quinones, saponins, terpenoids, flavonoids, polyphenols, and lignan compounds, to provide ideas for the innovative development of natural drugs with potential antiarrhythmic efficacy.
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•The dysfunction of Ca2+ channels are important factors that induce arrhythmias.•Natural drugs maintain calcium homeostasis via calcium channel regulation.•Natural drugs and their active ingredients may be a promising anti-arrhythmic drug.
A dual channel optical sensing composite for the detection of picric acid (PA) was constructed, using luminescent lanthanide MOF as supporting substrate and a rhodamine-based dye as sensing probe, ...respectively. These rod-liked composite nanocrystals had dual sensing channels towards PA, including colorimetric sensing and ratiometric fluorescent sensing. A linear working curve with limit of detection as low as 10μM was obtained. Good selectivity towards PA was confirmed.
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•A dual channel optical sensing composite for the detection of picric acid was constructed.•Colorimetric sensing and ratiometric fluorescent sensing were realized.•A linear working curve with limit of detection as low as 10μM was obtained.•Sensing mechanism was the combination of rhodamine emission increase and nitrophenyl-triggered Eu emission quenching.
For the present work, a dual channel optical sensing composite for the detection of picric acid (PA) was constructed, using luminescent lanthanide MOF as supporting substrate and a rhodamine-based dye as sensing probe, respectively. This composite material was discussed in detail by means of electron microscopy images, XRD, IR, TGA, absorption and emission spectra. These rod-liked composite nanocrystals had dual sensing channels towards PA, including colorimetric sensing and ratiometric fluorescent sensing. A linear working curve with limit of detection as low as 10μM was obtained. Good selectivity towards PA was confirmed. Their sensing mechanism was discussed and found as the combination of proton-triggered rhodamine structural transformation and nitrophenyl-triggered Eu emission quenching. This composite material showed a superior sensing performance over literature ones owing to its dual sensing channels and the possibility of naked eye detection.
The illustrated azomethine ylide, produced through a Schiff base condensation of the corresponding aldehyde-containing C3a-arylhexahydroindole with ethyl l-leucinate, engages in a stereoselective ...intramolecular cycloaddition reaction to give adduct 23 that has been elaborated, over eight steps, into the racemic modification of the alkaloid derivative gracilamine (1). The formation of this ylide and its conversion into isomer 23 mimics the proposed biogenesis of the pentacyclic framework of compound 1.
A new sheathless transient capillary isotachophoresis (CITP)/capillary zone electrophoresis (CZE)-MS interface, based on a commercially available capillary with an integrated metal-coated ESI ...emitter, was developed in this study aiming at overcoming the reproducibility and ruggedness problems suffered to a certain degree by almost all the available CE-MS interfaces, and pushing the CE-MS technology suitable for routine sample analysis with high sensitivity. The new CITP/CZE-MS interface allows the electric contact between ESI voltage power supply and the CE separation liquid by using a conductive liquid that comes in contact with the metal-coated surface of the ESI emitter, making it a true sheathless CE-MS interface. Stable electrospray was established by avoiding the formation of gas bubbles from electrochemical reaction inside the CE capillary. Crucial operating parameters, such as sample loading volume, flow rate, and separation voltage, were systematically evaluated for their effects on both CITP/CZE separation efficiency and MS detection sensitivity. Around one hundred CITP/CZE-MS analyses can be easily achieved by using the new sheathless CITP/CZE interface without a noticeable loss of metal coating on the ESI emitter surface, or degrading of the ESI emitter performance. The reproducibility in analyte migration time and quantitative performance of the new interface was experimentally evaluated to demonstrate a LOQ below 5 attomole.
The onset of Alzheimer's disease is related to neuron damage caused by massive deposition of Aβ in the brain. Recent studies suggest that excessive Aβ in the brain mainly comes from peripheral blood, ...and BBB is the key to regulate Aβ in and out of the brain. In this study, we explored the pathogenesis of AD from the perspective of Aβ transport through the BBB and the effect of QKL injection in AD mice. The results showed that QKL could improve the cognitive dysfunction of AD mice, decrease the level of Aβ and Aβ transporter—RAGE, which was supported by the results of network pharmacology, molecular docking and molecular dynamics simulation. In conclusion, RAGE is a potential target for QKL's therapeutic effect on AD.
•QKL injection decreased the Aβ level, and finally improved cognitive impairment in AD mice.•QKL injection inhibited the transport of Aβ by inhibiting the expression of RAGE.•RAGE may be the therapeutic target of QKL, which is proved by the network pharmacology, molecular docking and MDS.
Context:
Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, ...considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD.
Objectives:
Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD.
Design:
This study used a cross-sectional design.
Setting:
The general community in the United States, United Kingdom, and The Gambia were included in this study.
Participants:
Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included.
Exposures:
Total 25OHD concentration, race, and DBP (GC) genotype exposures were included.
Outcome Measures:
Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures.
Results:
Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80–0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites.
Conclusions:
Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population.
We found no racial or genetic differences in serum vitamin D binding protein. Free 25OHD, directly measured or calculated from DBP (using polyclonal antibodies), was low in Afro-Americans, compared to US whites or blacks from The Gambia.
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