In recent years, natural polysaccharides have been considered as the ideal candidates for novel drug delivery systems because of their good biocompatibility, biodegradation, low immunogenicity, ...renewable source and easy modification. These natural polymers are widely used in the designing of nanocarriers, which possess wide applications in therapeutics, diagnostics, delivery and protection of bioactive compounds or drugs. A great deal of studies could be focused on developing polysaccharide nanoparticles and promoting their application in various fields, especially in biomedicine. In this review, a variety of polysaccharide-based nanocarriers were introduced, including nanoliposomes, nanoparticles, nanomicelles, nanoemulsions and nanohydrogels, focusing on the latest research progress of these nanocarriers in the treatment of diabetes and the possible strategies for further study of polysaccharide nanocarriers.
Inhibition of the epidermal growth factor receptor (EGFR) has been proved to be one of the most promising strategies for the treatment of non-small cell lung cancers. A series of 2-aryl-4-amino ...substituted quinazoline derivatives were designed and synthesized with the purpose to overcome L858R/T790M/C797S (CTL) triple mutant drug resistance and the biological activity for inhibition of CTL kinases and EGFR wild type (WT) were evaluated. Three compounds (20, 24 and 27) showed excellent inhibitory activities against EGFR kinases triple mutant CTL (IC50 < 1 µM) and high selectivity (IC50: WT/CTL >10000). Cell line evaluation showed that the most potent compound 27 was significantly potent against H1975-EGFR L858R/T790M (IC50 = 3.3 µM) and H1975-EGFR L858R/T790M/C797S (IC50 = 1.2 µM). Compound 27 also exhibited good microsomes stabilities in human, rat and mouse liver species, but low bioavailability. This work would be very useful for discovering new quinazoline derivatives as tyrosine kinase inhibitors targeting triple mutant L858R/T790M/C797S.
Though semi-supervised classification learning has attracted great attention over past decades, semi-supervised classification methods may show worse performance than their supervised counterparts in ...some cases, consequently reducing their confidence in real applications. Naturally, it is desired to develop a safe semi-supervised classification method that never performs worse than the supervised counterparts. However, to the best of our knowledge, few researches have been devoted to safe semi-supervised classification. To address this problem, in this paper, we invent a safety-control mechanism for safe semi-supervised classification by adaptive tradeoff between semi-supervised and supervised classification in terms of unlabeled data. In implementation, based on our recent semi-supervised classification method based on class memberships (SSCCM), we develop a safety-aware SSCCM (SA-SSCCM). SA-SSCCM, on the one hand, exploits the unlabeled data to help learning (as SSCCM does) under the assumption that unlabeled data can help learning, and on the other hand, restricts its prediction to approach that of its supervised counterpart least-square support vector machine (LS-SVM) under the assumption that unlabeled data can hurt learning. Therefore, prediction by SA-SSCCM becomes a tradeoff between those by semi-supervised SSCCM and supervised LS-SVM, respectively, in terms of the unlabeled data. As in SSCCM, the optimization problem in SA-SSCCM can be efficiently solved by the alternating iterative strategy, and the iteration convergence can theoretically be guaranteed. Experiments over several real datasets show the promising performance of SA-SSCCM compared with LS-SVM, SSCCM, and off-the-shelf safe semi-supervised classification methods.
A series of novel pinanyl pyrimidine amine derivatives (
~
) and camphoryl pyrimidine amine derivatives (
~
) bearing bicyclic monoterpene moieties were designed and synthesized from natural and ...renewable nopinone and camphor. All chemical structures of target compounds were characterized by
H NMR,
C NMR and HRMS spectra analyses, and the antimicrobial activities were evaluated. The results indicated that most compounds showed considerable antibacterial and antifungal activities against
,
,
,
,
,
(MRSA),
and
Among them,
showed potent antibacterial activity against all tested bacteria,
exhibited excellent inhibition against
(1 μg/mL) and
(1 μg/mL), which was better than the control drug amikacin (2 μg/mL). As to antifungal activity against
(
), compound
showed comparable activity (16 μg/mL) to the control drug ketoconazole. Furthermore, five active compounds with better antimicrobial activities also showed anti-inflammatory potencies against mouse mononuclear macrophages leukemia cells (RAW). Especially,
(IC
= 1.37 μM) and
(IC
= 1.87μM) are more potent than the control drug aspirin (IC
= 1.91 μM).
Supersaturated total dissolved gas (TDG) generation in rivers poses great harm to aquatic organisms. In this paper, 30 groups of supersaturated TDG dissipation experiments with aeration were carried ...out. These results showed that aeration actively promoted the dissipation of supersaturated TDG. The aeration rate decreased by 34.94% from 1.0 m
/h to 5.0 m
/h, the reduced proportion of aeration aperture was 35.51% from 215 mm to 260 mm, whereas the aeration depth increased by 16.93% from 0.4 m to 1.2 m for the TDG dissipation time required, resulting in corresponding the variation of TDG dissipation coefficients were 86.26%, 23.74% and -5.39%, respectively. In general, the effect on TDG dissipation is that the aeration rate is the largest, followed by the aeration aperture, and the aeration depth is the smallest. A quantitative relationship was established between TDG dissipation coefficient and aeration conditions, and followed a power function, while the aeration depth inhibited its dissipation. Moreover, what matters was that a numerical model was presented for predicting the TDG dissipation in Eulerian-Eulerian. When the parameter was β = 10.52, the error between the original experimental data and the simulated of a multiphase TDG dissipation model was 0.2%. The study provides essential scientific data for mitigating the harms of supersaturated TDG.
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Accumulating evidence has indicated the vital roles of long noncoding RNA (lncRNA) in the epithelial ovarian cancer (EOC). However, the function of lncRNA HAS2-AS1 in EOC is still ...unclear. This study aims to investigate the expression and role of HAS2-AS1 in EOC. In the cells and tissue of EOC, HAS2-AS1 expression was markedly up-regulated. Besides, the overexpression of HAS2-AS1 indicated the poor clinical outcome of EOC patients. Transcription factor CREB1 could bind with the promoter of HAS2-AS1 and activate its transcriptional expression. Functionally, HAS2-AS1 knockdown suppressed the proliferation, invasion and tumor growth of EOC cells in vitro and in vivo. Mechanical investigation found that HAS2-AS1 could relive the RUNX2 protein expression via sponging the miR-466, acting as miRNA sponge. In conclusion, this finding suggests the CREB1/HAS2-AS1/miR-466/RUNX2 axis in the in the EOC tumorigenesis, providing the novel insight for the molecular mechanism of EOC.
Epidermal growth factor receptor (EGFR) C797S mutation leads to Osimertinib drug resistance by disturbing the covalent biding of Michael acceptor group to the Cys797 residue in the ATP biding cleft. ...In this manuscript, a class of 2-amine-4-oxyphosaniline pyrimidine derivatives were designed, synthesized and evaluated as new noncovalent reversible EGFR inhibitors against L858R/T790M/C797S (CTL) triple mutant. The kinases inhibitiory activity evaluation showed that four compounds exhibited significant inhibitory activities against CTL (IC50 < 30 nM). In particularly, the most promising compound 7a showed excellent enzymatic inhibitory activity against CTL with IC50 value of 9.9 nM, which was more potent than control compound Osimertinib. Moreover, cell proliferation assays indicated that 7a effectively inhibited H1975-EGFR L858R/T790M/C797S with IC50 value of 0.33 µM. Furthermore, compound 7a displayed good metabolic stabilities in human, rat and mouse liver microsomes, and the putative biding mode of compound 7a with ATP was revealed by molecular docking study. These findings strongly indicated that compound 7a was a promising L858R/T790M/C797S mutant EGFR inhibitor.
High-flow nasal cannula (HFNC) oxygen therapy is being increasingly used to prevent post-extubation hypoxemic respiratory failure and reintubation. However, evidence to support the use of HFNC in ...chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure after extubation is limited. This study was conducted to test if HFNC is non-inferior to non-invasive ventilation (NIV) in preventing post-extubation treatment failure in COPD patients previously intubated for hypercapnic respiratory failure.
COPD patients with hypercapnic respiratory failure who were already receiving invasive ventilation were randomized to HFNC or NIV at extubation at two large tertiary academic teaching hospitals. The primary endpoint was treatment failure, defined as either resumption of invasive ventilation or switching to the other study treatment modality (NIV for patients in the NFNC group or vice versa).
Ninety-six patients were randomly assigned to the HFNC group or NIV group. After secondary exclusion, 44 patients in the HFNC group and 42 patients in the NIV group were included in the analysis. The treatment failure rate in the HFNC group was 22.7% and 28.6% in the NIV group-risk difference of - 5.8% (95% CI, - 23.8-12.4%, p = 0.535), which was significantly lower than the non-inferior margin of 9%. Analysis of the causes of treatment failure showed that treatment intolerance in the HFNC group was significantly lower than that in the NIV group, with a risk difference of - 50.0% (95% CI, - 74.6 to - 12.9%, p = 0.015). One hour after extubation, the mean respiratory rates of both groups were faster than their baseline levels before extubation (p < 0.050). Twenty-four hours after extubation, the respiratory rate of the HFNC group had returned to baseline, but the NIV group was still higher than the baseline. Forty-eight hours after extubation, the respiratory rates of both groups were not significantly different from the baseline. The average number of daily airway care interventions in the NIV group was 7 (5-9.3), which was significantly higher than 6 (4-7) times in the HFNC group (p = 0.006). The comfort score and incidence of nasal and facial skin breakdown of the HFNC group was also significantly better than that of the NIV group 7 (6-8) vs 5 (4-7), P < 0.001 and 0 vs 9.6%, p = 0.027, respectively.
Among COPD patients with severe hypercapnic respiratory failure who received invasive ventilation, the use of HFNC after extubation did not result in increased rates of treatment failure compared with NIV. HFNC also had better tolerance and comfort than NIV.
chictr.org ( ChiCTR1800018530 ). Registered on 22 September 2018, http://www.chictr.org.cn/usercenter.aspx.
Metastasis is a critical determinant for the treatment strategy and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). However, the mechanisms underlying SCCHN ...metastasis are poorly understood. Our study sought to determine the key microRNA and their functional mechanisms involved in SCCHN metastasis. For The Cancer Genome Atlas (TCGA) data analysis, quantitative PCR was used to quantify the level of miR‐30e‐5p in SCCHN and its clinical significance was further analyzed. A series of in vitro and in vivo experiments were applied to determine the effects of miR‐30e‐5p and its target AEG‐1 on SCCHN metastasis. A mechanism investigation further revealed that AEG‐1 was implicated in the angiogenesis and metastasis mediated by miR‐30e‐5p. Overall, our study confirms that miR‐30e‐5p is a valuable predictive biomarker and potential therapeutic target in SCCHN metastasis.
Valuable predictive biomarkerPotential therapeutic targetMetastasis related gene
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