The purpose of our study is to assess the diagnostic performance of quantitative evaluation of tissue stiffness around lesion by Sound Touch Elastography (STE) in distinguishing between benign and malignant breast lesions. A total number of 160 breast lesions from 160 female patients were examined by STE. Resona 7 was equipped with "shell" function to measure elastic modulus values of tissue in the region of surrounding lesion quantitatively. The contours of the lesion were required to be delineated. The elastic modulus values of tissue in the region of 1mm, 2mm, and 3mm outside the boundary were acquired. The elastic modulus values included maximum elastic modulus (E max), mean elastic modulus (E mean), minimum elastic modulus (E min), and elastic modulus standard deviation (E sd). All lesions were confirmed by histopathology. We compared the differences of the above elastic modulus values between benign and malignant groups. Receiver operating characteristic (ROC) curve was drawn with the histological diagnostic results as the gold standard. Sensitivity and specificity were calculated to evaluate the diagnostic performance of STE. Operator consistency was also analyzed. Among the 160 lesions, 100 (62.5%) were benign and 60 (37.5%) were malignant. In the region of 1mm, 2mm, and 3mm surrounding the lesion, E max , E mean , and E sd of malignant group were significantly higher than those of the benign group (all P<0.05). When the "shell" was 3mm, E max had the highest AUROC value (AUROC = 0.998). Regarding the measurement of elastic modulus values, all the intra-class correlation coefficient (ICC) values of the inter-operator consistency were greater than 0.75 for E max , E mean , and E sd. Therefore, quantitative evaluation of tissue stiffness around lesion by STE has the potential to distinguish between benign and malignant breast lesions.
Intelligent drug delivery systems (DDSs) that can improve therapeutic outcomes of antitumor agents and decrease their side effects are urgently needed to satisfy special requirements of treatment of malignant tumors in clinics. Here, the fabrication of supramolecular self-assembled amphiphiles based on the host−guest recognition between a cationic water-soluble pillar[6]arene (WP6A) host and a sodium decanesulfonate guest (G) is reported. The chemotherapeutic agent doxorubicin hydrochloride (DOX) can be encapsulated into the formed vesicle (G/WP6A) to construct supramolecular DDS (DOX@G/WP6A). WP6A affords strong affinities to G to avoid undesirable off-target leakage during delivery. Nanoscaled DOX@G/WP6A is capable of preferentially accumulating in tumor tissue via enhanced permeability and retention (EPR) effect. After internalization by tumor cells, the abundant adenosine triphosphate (ATP) binds competitively with WP6A to trigger the disintegration of self-assembled vesicles with the ensuing release of DOX. In vitro and in vivo research confirmed that DOX@G/WP6A is not only able to promote antitumor efficacy but also reduce DOX-related systemic toxicity. The above favorable findings are ascribed to the formation of ternary selfassembly, which profits from the combination of the factors of the EPR effect and the ATP-triggered release.
Biotoxins are diverse, complex, and hypertoxic, ultimately serving as grave and lasting menaces to humanity. Here, it is aimed to introduce a new detoxification methodology for macromolecular biotoxin through complexation by a very large macrocycle. A 25‐mer peptide isolated from Lycosa erythrognatha spider venom (LyeTxI) is selected as the model macromolecular biotoxin. Quaterphen[4]arene, with a side length of ≈1.6 nm, has a sufficient cavity to bind LyeTxI. Hence, the water‐soluble derivative of Quaterphen[4]arene (H) is designed and synthesized. H exhibits an overall host–guest complexation toward LyeTxI, resulting in a considerably high association constant of (7.01 ± 0.18) × 107 m−1. This encapsulation of peptide is interesting as traditional macrocycles can only engulf the amino acid residues of peptides due to their limited cavity size. In vitro assay verifies that complexation by H inhibits the interactions of LyeTxI with cell membranes, thereby reducing its cytotoxicity, suppressing hemolysis, and decreasing the release of lactate dehydrogenase. Notably, the intravenous administration of H has a significant therapeutic effect on LyeTxI‐poisoned mice, alleviating inflammation and tissue damage, and markedly improving the survival rate from 10% to 80%. An efficient and potentially versatile approach is provided to detoxify macromolecular biotoxins, with giant macrocycle serving as an antidote.
Since bacteria in biofilms are inherently resistant to antibiotics and biofilm‐associated infections pose a serious threat to global public health, new therapeutic agents and schemes are urgently needed to meet clinical requirements. Here two quaternary ammonium‐functionalized biphen[n]arenes (WBPn, n=4, 5) were designed and synthesized with excellent anti‐biofilm potency. Not only could they inhibit the assembly of biofilms, but also eradicate intractable mature biofilms formed by Gram‐positive S. aureus and Gram‐negative E. coli bacterial strains. Moreover, they could strongly complex a conventional antibiotic, cefazolin sodium (CFZ) with complex stability constants of (7.41±0.29)×104 M−1 for CFZ/WBP4 and (4.98±0.49)×103 M−1 for CFZ/WBP5. Combination of CFZ by WBP4 and WBP5 synergistically enhanced biofilm eradication performance in vitro and statistically improved healing efficacy on E. coli‐infected mice models, providing a novel supramolecular strategy for combating biofilm‐associated infections.
Sleep deprivation impairs cognitive functions, including attention, memory, and decision-making. Studies on the neuro-electro-physiological mechanisms underlying total sleep deprivation (TSD) that impairs spatial cognition are limited. Based on electroencephalogram (EEG) and Exact Low Resolution Brain Electromagnetic Tomography (eLORETA), this study focused on the effects of TSD on mental rotation and the cognitive neural mechanisms underlying its damage. Twenty-four healthy college students completed mental rotation tasks while resting and after 36 h of TSD; their EEG data were simultaneously recorded. The amplitude of P300 component associated with mental rotation was observed and localized through source reconstruction, while changes in effective connectivity between multiple brain regions associated with mental rotation cognitive processing were calculated using isolated effective coherence (iCoh) of eLORETA. Compared with the baseline before TSD, the amplitude of the P300 component related to mental rotation decreased. The task-state data of P300 were localized to the source of the difference in ERP current density, and it was found that the brain regions related to the difference in the decrease in P300 amplitude included the superior parietal lobule, precuneus, prefrontal lobe, and other related regions. Effective connectivity analysis found that TSD enhanced the effective connectivity from the left middle frontal gyrus to the left superior parietal lobule, left inferior parietal lobule, and left precuneus under the identical condition. Pearson correlation analysis showed a positive correlation between the decrease in accuracy of mental rotation and increase in effective connectivity. Thus, our study suggests that TSD impairs the ability of the mental rotation, showing a decrease in P300 amplitude and an enhanced effective connectivity between the middle frontal gyrus and the parietal lobe in the task state.
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