A new magnetic molecularly imprinted polymers (MMIPs) for quercetagetin was prepared by surface molecular imprinting method using super paramagnetic core-shell nanoparticle as the supporter. ...Acrylamide as the functional monomer, ethyleneglycol dimethacrylate as the crosslinker and acetonitrile as the porogen were applied in the preparation process. Fourier transform infrared spectrometer (FT-IR), X-ray diffraction (XRD) and Vibrating sample magnetometer (VSM) were applied to characterize the MMIPs, and High performance liquid chromatography (HPLC) was utilized to analyze the target analytes. The selectivity of quercetagetin MMIPs was evaluated according to their recognition to template and its analogues. Excellent binding for quercetagetin was observed in MMIPs adsorption experiment, and the adsorption isotherm models analysis showed that the homogeneous binding sites were distributed on the surface of the MMIPs. The MMIPs were employed as adsorbents in solid phase extraction for the determination of quercetagetin in Calendula officinalis extracts. Furthermore, this method is fast, simple and could fulfill the determination and extraction of quercetagetin from herbal extract.
Quercetagetin imprinted polymer shell layer were coated on the surface of the super-paramagnetic Fe3O4 nanoparticles through surface imprinting method, so novel magnetic molecularly imprinted polymers (MMIPs) for quercetagetin were prepared. The MMIPs were applied in the determination and extraction of quercetagein in Calendula officinalis extracts followed by high-performance liquid chromatography. Display omitted
•Quercetagetin imprinted polymer shell layer were prepared by surface imprinting.•The obtained MMIPs served as sorbents were used to recognize quercetagetin in TCM.•The prepared MMIPs were investigated by FT-IR, XRD and VSM.•The MMIPs were proved to be highly selective, easy to collect and low cost.
A colorimetric method based on TMB/H2O2/HRP and AA-2 G/α-Glu systems was developed for AGIs screening.
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•A colorimetric method is developed for AGIs screening.•The colorimetric method ...is based on the AA-2 G/α-Glu and TMB/H2O2/HRP systems.•AA released from the AA-2 G/α-Glu system suppresses the oxidation of TMB to oxTMB.•The existence of AGIs can be easily observed by color variation of blue oxTMB.•AGIs are screened from 7 flavonoids based on this colorimetric method.
A facile and novel colorimetric method for screening of α-glucosidase inhibitors (AGIs) from flavonoids using 3,3’,5,5’-tetramethylbenzidine (TMB) as a chromogenic probe is proposed. This method is based on the colorimetric detection of ascorbic acid (AA) through the TMB oxidation reaction catalyzed by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2). In the TMB/H2O2/HRP system, HRP catalyzes the oxidation of H2O2 to ‧OH radical which oxidizes TMB to blue-colored oxidized TMB (oxTMB). In the presence of AA, the production of ‧OH radical is suppressed and causes the decrease of oxTMB, resulting in the fading of the blue color and the decrease of absorbance at 652 nm. Based on this, the existence of AA can be facilely identified. In the 2-O-α-d-glucopyranosyl-l-ascorbic acid (AA-2 G)/α-glucosidase (α-Glu) system, the produced AA inhibits the oxidation of TMB to blue-colored oxTMB. In the presence of AGIs, the production of AA is inhibited, which inhibits the reduction of oxTMB, resulting in a blue color recovery and an increase of the absorbance at 652 nm. Based on this, the colorimetric method is developed for screening of AGIs from 7 flavonoids.
•Fe3O4@TiO2 nanoparticle was fabricated as magnetic support of immobilized lipase.•A capillary electrophoresis method was established for screening lipase inhibitors.•Oxytropis falcate and its ...compounds were firstly reported as lipase inhibitors.With the increasing demand for lipase inhibitors and new drugs used in the clinical treatment of obesity, it is of great significance to screen lipase inhibitors from traditional Chinese medicines (TCMs) via capillary electrophoresis. In this work, Fe3O4@TiO2 nanoparticles was fabricated by solvothermal method and employed as an improved magnetic support to immobilize lipase through electrostatic interaction. By the method of transmission electron microscopy, fourier transform infrared spectroscopy and X-ray diffraction, the magnetic nanoparticles were characterized. The immobilized enzyme possessed advantages of a wider range for pH and temperature endurance, better storage stability and reusability. The kinetics performances of the immobilized lipase were studied. When p-Nitrophenyl palmitate (pNPP) was used as enzyme substrate, the Michaelis-Menten constant was calculated to be 2.51 mM and its inhibition constant for Orlistat was ascertained to be 13.41 μM. Ultimately, the established method was applied to lipase inhibitors screening from 6 Tibetan medicines with lipase inhibitory activity and Oxytropis falcate Bunge was screened out for its supreme lipase inhibitory activity. 11 compounds in the Oxytropis falcate Bunge were further screened, five compounds exhibited similar inhibitory activity to Orlistat, and one compound (kaempferol) presented better inhibitory activity than Orlistat, which is the most commonly used drugs to treat obesity in clinic. This work not only developed a method for new anti-obesity drugs discovery, but also provided inspiration for exploring new medicinal value of the TCMs.
With the increasing demand for lipase inhibitors and new drugs used in the clinical treatment of obesity, it is of great significance to screen lipase inhibitors from traditional Chinese medicines (TCMs) via capillary electrophoresis. In this work, Fe3O4@TiO2 nanoparticles was fabricated by solvothermal method and employed as an improved magnetic support to immobilize lipase through electrostatic interaction. By the method of transmission electron microscopy, fourier transform infrared spectroscopy and X-ray diffraction, the magnetic nanoparticles were characterized. The immobilized enzyme possessed advantages of a wider range for pH and temperature endurance, better storage stability and reusability. The kinetics performances of the immobilized lipase were studied. When p-Nitrophenyl palmitate (pNPP) was used as enzyme substrate, the Michaelis-Menten constant was calculated to be 2.51 mM and its inhibition constant for Orlistat was ascertained to be 13.41 μM. Ultimately, the established method was applied to lipase inhibitors screening from 6 Tibetan medicines with lipase inhibitory activity and Oxytropis falcate Bunge was screened out for its supreme lipase inhibitory activity. 11 compounds in the Oxytropis falcate Bunge were further screened, five compounds exhibited similar inhibitory activity to Orlistat, and one compound (kaempferol) presented better inhibitory activity than Orlistat, which is the most commonly used drugs to treat obesity in clinic. This work not only developed a method for new anti-obesity drugs discovery, but also provided inspiration for exploring new medicinal value of the TCMs.
Objective
Our study was performed to evaluate the significance of countable and treatable metastatic liver disease (CTMLD) in patients with gallbladder carcinoma (GBC) after curative‐intent surgery.
...Methods
Resected GBC patients between September 2010 and January 2021 were reviewed. Comparative analyses between patients with CTMLD and those without it were performed. A propensity score matching analysis was conducted for further validation.
Results
A total of 326 resected GBC patients were identified (33 with CTMLD). A significantly higher preoperative CA199 level was detected in those with CTMLD (p = 0.0160). Significantly higher incidences of major hepatectomy (p = 0.0010), lymph node metastasis (p < 0.0001), direct liver invasion (p < 0.0001), moderate to poor differentiation status (p < 0.0001), and T3–4 disease (p < 0.0001) were detected in patients with CTMLD. Even sharing comparable surgical margin status, patients with CTMLD still shared a significantly higher recurrence rate (93.9% vs. 57.3%, p < 0.0001) as well as a significantly higher recurrence rate within 6 months after surgery (63.6% vs. 14.7%, p < 0.0001). A significantly worse overall survival (median survival time: 12 vs. 33 months, p < 0.0001) or disease‐free survival (median recurrence‐free time: 6 vs. 30 months, p < 0.0001) was acquired in patients with CTMLD. After matching, a significantly higher early recurrence rate was still detected. Adjuvant chemotherapy seemed to have survival benefit for patients with CTMLD.
Conclusion
CTMLD was an indicator of advanced disease and served as an independent predictor of early recurrence among resected GBC patients. Whether curative‐intent surgery is superior to nonsurgical treatment among GBC patients with CTMLD remains to be explored in future prospective studies.
Developing highly sensitive and selective methods for Cu
2+
detection in living systems is of great significance in clinical copper-related disease diagnosis. In this work, a near infrared (NIR) ...fluorescent probe, CySBH, with a salicylaldehyde benzoyl hydrazone group as a selective and sensitive receptor for Cu
2+
was designed and synthesized. The specific coordination of the salicylaldehyde benzoyl hydrazone group in CySBH with Cu
2+
can induce a distinct quench of the fluorescence intensity, allowing for real-time tracking of Cu
2+
. We have demonstrated that CySBH could rapidly recognize Cu
2+
with good selectivity and high sensitivity. Moreover, on the basis of low cell cytotoxicity, the probe was used to visualize Cu
2+
in two cell lines by fluorescence imaging. Furthermore, CySBH can also be used to monitor Cu
2+
in vivo
due to its NIR emission properties. These overall results illustrate that the NIR fluorescent probe CySBH provides a novel approach for the selective and sensitive monitoring of Cu
2+
in living systems.
A near infrared fluorescent probe utilizing the salicylaldehyde benzoyl hydrazone group as the Cu
2+
receptor was developed and used to selectively and sensitively monitor Cu
2+
in living systems.
Peri-neural invasion (PNI) in gallbladder carcinoma (GBC) has been demonstrated as a vital prognostic factor. However, whether PNI in patients with GBC can be regarded as a surgical indication of ...bile duct resection (BDR) remains controversial.
GBC patients with pathologically-confirmed PNI between September 2010 and September 2020 were retrospectively reviewed. Comparative analyses were performed in patients with PNI according to the performance of BDR. SPSS 25.0 software and Graph pad PRISMA 7.0 software were used for statistical analyses.
A total of 70 patients GBC patients with PNI were incorporated. The results of comparative analyses indicated that patients who received BDR were generally in a more advanced stage and often required a more extended radical cholecystectomy. Higher incidences of preoperative jaundice (48.6% vs 2.9%, P < 0.0001), major hepatectomy (25.7% vs 8.6%, P = 0.055), combined multi-visceral resections (48.6% vs 5.7%, P < 0.0001), combined major vascular reconstruction (22.9% vs 2.9%, P = 0.014), and a lower R0 rate (68.6% vs 88.6%, P = 0.039) were detected in patients who received BDR. Even after propensity score matching (PSM), BDR still had no significant survival advantage but only increased the length of postoperative stay and the frequency of postoperative morbidities.
BDR seemed to have no significant survival advantage in GBC patients with PNI and was only correlated with a longer postoperative hospital stay and a higher rate of morbidities. PNI should not be regarded as a surgical indication of BDR in patients with GBC.
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•The Janus AuNPs based on controllable aggregation improve the dynamic range and enhance the long-term stability of sensor.•The large Janus AuNPs detect aspartic acid with low ...detection limit while maintaining the stability toward complex matrix.•The PEG chains increase steric hindrance, improve the anti-interference of sensor for direct Asp detection in CSF of rat.
We report a colorimetric assay based on oriented Janus gold nanoparticles (AuNPs) aggregation for highly selective and sensitive detection of aspartic acid (Asp) in rat brain. Initially, the Janus AuNPs with relatively large size was prepared, during which the stabilizing agent polyethylene glycol (PEG) and highly selective recognition agent cysteine (Cys) were attached to the selected area at the surface. The addition of Asp causes the oriented and controllable aggregation due to the specific recognition between Cys and Asp. Such a way of aggregation leads to significantly improved long-term stability and an at least 2 orders of magnitude wider dynamic range (1.8 nM–180 μM) compared with conventional colorimetric sensors. In addition, the strategy to increase the size of AuNPs (13–45 nm) enables to efficiently increase the limit of detection (18 μM–1.8 nM). Surprisingly, such a sensor can be applied to direct sensing of cerebral Asp in rat brain, which is determined round 33.9 ± 1.3 μM with satisfactory spiked recovery (86.5 ± 7.5%) due to the excellent anti-interference ability. This work provides a direct and reliable method to evaluate the Asp involved physiological and pathological process and opens a new avenue for real sample detection.
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely ...understood.
To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue.
Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs.
This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.
Magnetic molecularly imprinted nanoparticles (MMIPs) with improved dispersity and an increased number of adsorption sites are described. Uniform silica layers were first deposited on the surface of ...Fe
3
O
4
nanoparticles (Fe
3
O
4
NPs) in order to improve the dispersity of magnetic nanoparticles. Then, 4-formylphenylboronic acid (FPBA) as functional monomer was immobilized on the magnetic carriers to improve the efficiency of template eluting and rebinding. A thin layer of polyaniline imprinted with horseradish peroxidase (HRP) as a model glycoprotein was then placed on the magnetic nanoparticles to enhance the dispersity of the resultant MMIPs. These exhibit high adsorption capacity (62 mg g
−1
), a satisfactory imprinting factor ( 3.78) and short adsorption equilibrium time (40 min) toward HRP, and the limit of detection is 18.7 μg L
−1
. This kind of MMIPs, therefore, is deemed being a useful tool for extracting low-abundance glycoproteins from even complex samples.
Graphical abstract
Schematic of the preparation of magnetic molecular imprinted nanoparticles using Fe
3
O
4
nanoparticles as carriers, 4-formylphenylboronic acid as functional monomer, aniline as cross linker and horseradish peroxidase as template. TEOS: tetraethyl orthosilicate; APTES: 3-aminopropyltriethoxysilane; FPBA: 4-formylphenylboronic acid; HRP: horseradish peroxidase.
The significance of peri-neural invasion (PNI) in resected patients with hilar cholangiocarcinoma (HCCA) has been rarely explored. Our study was performed to evaluate the significance of PNI in ...resected HCCA patients in terms of tumor biological features and long-term survival.
We retrospectively reviewed surgically-treated HCCA patients between June, 2000 and June 2018. SPSS 25.0 software was used for statistical analysis.
A total of 239 resected HCCA patients were included (No. PNI: 138). PNI indicated more aggressive tumor biological features. Major vascular reconstruction was more frequently performed in patients with PNI (34.8% vs 24.8%, P = 0.064). Patients with PNI shared a significantly higher percentage of surgical margin width <5 mm (29.0% vs 16.8%, P = 0.02). The proportion of patients with T1-2 disease (31.2% vs 40.6%, P = 0.085) or I-II disease (21% vs 34.7%, P = 0.014) was significantly lower in patients with PNI. The overall morbidity rate was significantly higher in patients with PNI (P = 0.042). A much worse overall survival (OS) (P = 0.0003) or disease-free survival (DFS) (P = 0.0011) in patients with PNI. Even after matching vital prognostic factors, a significantly worse OS (P = 0.0003) or DFS (P = 0.0002) was still observed in patients with PNI. PNI was an independent prognostic factor in both OS (P = 0.011) and DFS (P = 0.024).
PNI indicated more aggressive tumor biological features and more advanced tumor stage in patients with resected HCCA. PNI can be an independent prognostic factor in both OS and DFS. Future multi-center studies covering various races or populations are required for further validation.
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