Nanopore discrimination and sensitive plasma detection of multiple natriuretic peptides: The representative biomarker of human heart failure.

Natriuretic peptides can relieve cardiovascular stress and closely related to heart failure. Besides, these peptides also have preferable interactions of binding to cellular protein receptors, and subsequently mediate various physiology actions. Hence, detection of these circulating biomarkers could be evaluated as a predictor ("Gold standard") for rapid, early diagnosis and risk stratification in heart failure. Herein, we proposed a measurement to discriminate multiple natriuretic peptides via the peptide-protein nanopore interaction. The nanopore single-molecular kinetics revealed that the strength of peptide-protein interactions was in the order of ANP > CNP > BNP, which was demonstrated by the simulated peptide structures using SWISS-MODEL. More importantly, the peptide-protein interaction analyzing also allowed us to measure the peptide linear analogs and structure damage in peptide by single-chemical bond breakup. Finally, we presented an ultra-sensitive detection of plasma natriuretic peptide using asymmetric electrolyte assay, obtaining a detection limit of ∼770 fM for BNP. At approximately, it is 1597 times lower than that of using symmetric assay (∼1.23 nM), 8 times lower than normal human level (∼6 pM), and 13 times lower than the diagnostic values (∼10.09 pM) complied in the guideline of European Society of Cardiology. That said, the designed nanopore sensor is benefit for natriuretic peptides measurement at single molecule level and demonstrates its potential for heart failure diagnosis.

Label-free high-precise nanopore detection of endopeptidase activity of anthrax lethal factor regulated by diverse conditions.

Endopeptidase activity of anthrax lethal factor (aLF) prevents the destroy of anthracis spore intracellularly by host macrophages, meanwhile disables the signaling pathways extracellularly that leads to host lethality. Hence, inhibitory of this activity is expected to be an alternative option to cure anthrax infection. Herein, we fabricated a nanopore platform via transmembrane pore construction in vitro, which allows precise mimics, monitoring of intercellular proteinic transport and enables the quantitative detection of aLF endopeptidase activity towards MAPKK signaling protein at single molecule level. Next, we inhibited the aLF activity via screening approaches of protein-metal ion acquisition and other condition controlment (proton/hydroxide strength, adapted temperature, ionizing irradiation), which were identified by nanopore electrokinetic study. Upon the results, we found that Ca2+, Mg2+, Mn2+, Ni2+ collaborating with Zn2+ promote aLF activity efficiently. In contrary, Cd2+, Co2+, Cu2+ have great inhibitory effect. Result further revealed that, the speed of aLF endopeptidase activity with different ions functions as the nanopore signal frequency in linear manner, which enables evident distinction of those divalent ions using this proteinase assay. We also found the higher strength of the proton or hydroxide, the higher the inhibitory to aLF activity. Besides, adapted temperature and γ-ray also play integral roles in inhibiting this activity. Our results lay experimental basis for accurate detection of aLF activity, meanwhile provide new direction to screening novel stimuli-responsive inhibitors specific to aLF.

Ultrahigh Carbon Dioxide-Selective Composite Membrane Containing a γ-CD-MOF Layer.

Mixed matrix membranes (MMMs) for CO2 separation have overcome the trade-off between gas permeability and gas selectivity to some extent. However, most MMMs still are prepared in lab- and pilot-scales since the permeability and selectivity of CO2 are not good enough to reach the economically available requirements. Moreover, the fabrication of few MMMs with good separation performance is time-consuming or need harsh conditions. In this study, a novel MOF-based composite membrane (PAN-γ-CD-MOF-PU membrane) was successfully fabricated by a facile and fast spin-coating method. In the two-step coating process, we applied a uniform selective layer of γ-cyclodextrin-MOF (γ-CD-MOF) on porous polyacrylonitrile and then coated a layer of polyurethane on the γ-CD-MOF layer. The entire membrane formation process was about 30 s. The formation of a unique γ-CD-MOF layer greatly improved the separation ability of CO2 (the CO2 permeability is 70.97 barrers; the selectivity to CO2/N2 and CO2/O2 are 253.46 and 154.28, respectively). The gas separation performance can exceed the Robeson upper limit obviously and the selectivity is better than other MOF-based composite membranes. In addition, the PAN-γ-CD-MOF-PU membrane is strong and flexible. Therefore, the PAN-γ-CD-MOF-PU membrane developed in this study has great potential in large-scale industrial separation of CO2.

Personalized Preoperative Education Reduces Perioperative Anxiety in Old Men with Benign Prostatic Hyperplasia: A Retrospective Cohort Study.

INTRODUCTION: Psychological health is important to old patients with benign prostatic hyperplasia (BPH) after prostatic surgery. In this retrospective cohort study, we evaluated the effect of personalized preoperative education in the reduction of perioperative anxiety in old BPH patients after prostatic surgery. METHODS: Senior patients (≥65 years) admitted with a diagnosis of BPH and scheduled for initial transurethral resection of the prostate from January 1, 2017 to November 30, 2019 were retrieved. Patients in the preoperatively educated group completed the Chinese version of generalized anxiety disorder 7-item scale (GAD-7) form to evaluate their anxiety level at admission and 14 days clinical visits after individual preoperative education. Patients in the control group completed GAD-7 forms but did not receive personalized preoperative education. Patients in both groups discussed their disease with physicians during clinic visits and after admission, and were given an informed consent about their treatment plans. RESULTS: Seven hundred and twenty-four patients were retrieved, including 312 patients who received preoperative education and 412 patients who did not. There were significantly lower postoperative GAD-7 score and fewer moderate to severe postoperative anxiety patients in the preoperatively educated group (p < 0.01). Patients with education above secondary education level had less perioperative anxiety. CONCLUSION: Personalized education incorporated with shared valuable physiological and psychological experience and expectations dealing with BPH, in comparison to traditional uniformed patient education and informed consent before surgery, may reduce perioperative anxiety more efficiently in BPH patients. A higher educational level helps patients reduce perioperative anxiety before and after their personalized preoperative education.

Facile Fabrication of an AIE-Active Metal-Organic Framework for Sensitive Detection of Explosives in Liquid and Solid Phases.

Nowadays, the practical applications of metal-organic framework (MOF)-based fluorescence detectors are severely hindered because of the complex synthesis process of linkers or heavy metal contamination. The development of a simple, inexpensive, and environmentally friendly fluorescence sensing system remains a huge challenge. In this study, we designed and synthesized a TPE@γ-CD-MOF-K complex using the facile in situ encapsulation method. The unique pore structure of γ-CD-MOF allowed it to effectively include TPE and explosives as guests simultaneously. The TPE@γ-CD-MOF-K showed stronger fluorescence emission than TPE and sensitive fluorescence quenching activities in response to nitro-aromatic compounds in the liquid phase with detection limits as low as 3 ppm. Furthermore, TPE@γ-CD-MOF-K can also effectively detect nitro-aromatic compounds in the solid state, which is very convenient for practical detection of explosives. The unique pore structure of γ-CD-MOF-K and the interaction between K+ and nitro compounds play important roles in solid-state quenching.

miR­96 exerts an oncogenic role in the progression of cervical cancer by targeting CAV­1.

Cervical cancer is the 4th most common malignant tumor type affecting women worldwide; however, its molecular mechanisms are not fully understood. Previous studies have indicated that microRNAs (miRs) serve crucial roles in the cellular functions of tumors. miR­96 is involved in the tumorigenesis of many cancer types. The aim of the present study was to investigate the role and mechanism of miR­96 in the progression of cervical cancer. The present results suggested that overexpression of miR­96 significantly enhanced the proliferative, migratory and invasive abilities of cervical cancer cells, while inhibiting miR­96 had the opposite effects. Additionally, activation of the Akt/mTOR signaling pathway was enhanced by miR­96 overexpression, while it was inhibited by the miR­96 inhibitor. Moreover, it was identified that miR­96 may directly target caveolin­1 (CAV­1) to decrease its expression level. Furthermore, overexpression of CAV­1 could reverse the increase in cell proliferation, migration and invasion induced by miR­96, as well as the upregulation of the Akt/mTOR signaling pathway. In conclusion, the present results suggested that miR­96 may have an oncogenic role in the progression of cervical cancer by targeting CAV­1. Therefore, miR­96 may be a potential target for cervical cancer therapy.