Triple Sensing Modes for Triggered ß-Galactosidase Activity Assays Based on Kaempferol-Deduced Silicon Nanoparticles and Biological Imaging of MCF-7 Breast Cancer Cells.

ß-Galactosidase (ß-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor ß-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine ß-Gala activity effectively. Via the sensing performance, the catalytic activity of ß-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-ß-d-galactopyranoside (KOßDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing ß-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of ß-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.

[Efficacy and Prognostic Factors of Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia].

OBJECTIVE: To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors. METHODS: Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed. RESULTS: The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34+ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34+ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024). CONCLUSION: Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.

Click Chemoselective Probe with a Photoswitchable Handle for Highly Sensitive Determination of Steroid Hormones in Food Samples.

Residues of endocrine disrupting steroid hormones in food might cause various diseases like cardiovascular diseases and breast and prostate cancers. Monitoring steroid hormone levels plays a vital role in ensuring food safety and exploring the pathogenic mechanism of steroid hormone-related diseases. Based on the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction, a novel chemoselective probe, Azo-N3, which contains a reactive site N3, an imidazolium salt-based MS tag, and an azobenzene-based photoswitchable handle, was designed and synthesized to label ethynyl-bearing steroid hormones. The probe Azo-N3 was applied for the highly selective and sensitive detection of four ethynyl-bearing steroid hormones in food samples (milk, egg, and pork) by using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The ionization efficiency of the labeled analytes could be increased by 6-105-fold, and such a labeled method exhibited satisfactory detection limits (0.04-0.2 µg/L), recovery (80.6-122.4%), and precision (RSDs% lower than 6.9%). Interestingly, the efficient immobilization of the probe Azo-N3 onto α-cyclodextrin (α-CD)-modified magnetic particles to construct a solid supported chemoselective probe Fe3O4-CD-Azo-N3 and UV light-controlled release of the labeled analytes from a magnetic support can be achieved by taking advantage of the photoswitched host-guest inclusion between the azobenzene unit and α-CD. The potential applications of Fe3O4-CD-Azo-N3 for labeling, capturing, and the photocontrolled release of the labeled steroid hormones were fully investigated by mass spectrometry imaging analysis. This work not only provides a sensitive and accurate method to detect steroid hormones in food but also opens a new avenue in designing solid supported chemoselective probes.

A novel "Turn-on" fluorometric assays triggered reaction for ß-glucosidase activity based on quercetin derived silicon nanoparticles and its potential use for cell imaging.

ß-Glucosidase (ß-Gluco) is an enzyme that is crucial to numerous diseases, including cancer, and in sector of industries, it is used in the manufacturing of food. Measuring its enzymatic activity is critical for biomedical studies and other activities. Herein, we have developed a novel and precise fluorescent sensing method for measuring ß-Gluco activity based on the production of yellow-green fluorescent quercetin-silicon nanoparticles (Q-SiNPs) produced from quercetin (QN) as a reducing agent and 3-[2-(2-aminoethyl amino) ethylamino] propyl-trimethoxy silane (AEEA) as a silane molecule. ß-Gluco hydrolyzed quercetin-3-O-ß-d-glucopyranoside (QO-ß-DG) to produce QN, which was then used to produce Q-SiNPs. Reaction parameters, including temperature, time, buffer, pH, and probe concentration, were carefully tuned in this study. Subsequently, the fluorescence intensity was performed, showing good linearity (R2 = 0.989), a broad linear dynamic range between 0.5 and 12 U L-1, and a limit of detection (LOD) as low as 0.428 U L-1, which was proven by fluorescence measurements. Most importantly, various parameters were detected and characterized with or without ß-Gluco. The designed probe was successively used to assess ß-Gluco activity in human serum and moldy bread. However, the mathematical findings revealed recoveries for human serum ranging from 99.3 to 101.66% and for moldy bread from 100.11 to 102.5%. Additionally, Q-SiNPs were well suited to being incubated in vitro with L929 and SiHa living cells, and after using an Olympus microscope, imaging showed good fluorescence cell images, and their viability evinced minimal cytotoxicity of 77% for L929 and 88% for SiHa. The developed fluorescence biosensor showed promise for general use in diagnostic tests. Therefore, due to this outstanding sensing modality, we anticipate that this research can provide a novel schematic project for creating simple nanostructures with a suitable plan and a green synthetic option for enzyme activity and cell imaging.

[Clinical research of acupuncture therapy combined with domperidone in treatment of diabetic gastroparesis of liver stagnation and spleen deficiency].

OBJECTIVE: To observe the clinical efficacy of shuanggu yitong acupuncture therapy (the therapy for both replenishment and unblocking) combined with domperidone on diabetic gastroparesis (DGP) of liver stagnation and spleen deficiency pattern and explore its effect mechanism. METHODS: DGP patients differentiated as liver stagnation and spleen deficiency pattern were divided into a control group (n=42) and an observation group (n=42) according to the random number table. The patients in the control group took domperidone tablets orally, 10 mg each time, 3 times a day for 28 days. In the observation group, on the base of the treatment as the control group, shuanggu yitong acupuncture therapy was applied to Baihui (GV20), Shenting (GV24), Zhongwan (CV12), bilateral Zusanli (ST36), Hegu (LI4)and Taichong (LR3), stimulated for 30 min in each treatment. Acupuncture was given once daily, 3 times a weeks for 28 days consecutively. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG) and glycosylated hemoglobin (HbA1c) were detected before and after treatment in the patients of two groups separately. The score of symptom severity index of gastroparesis (GCSI), traditional Chinese medicine (TCM) syndrome score and gastric emptying rate were assessed in the patients of two groups. Using ELISA, radioimmunoassay and colorimentry methods, the contents of motilin in plasma, gastrin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and interferon-gamma (INF-γ) in serum, as well as the activity of superoxide dismutase (SOD), reactive oxygen species (ROS) and malondialdehyde (MDA) in the serum were determined in the two groups. The clinical curative effect was evaluated. RESULTS: After treatment, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM syndrome, the contents of motilin in plasma, gastrin, TNF-α and MDA, as well as the activity of ROS in serum were all reduced when compared with those before treatment in each group (P<0.05, P<0.01), while gastric emptying rate and SOD activity in the serum were higher than those before treatment (P<0.05, P<0.01). After treatment, the serological content of INF-γ was lower than that before treatment in the control group (P<0.05), and the contents of IL-6 and IL-1ß were reduced than those before treatment in the observation group (P<0.05). Compared with the control group, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM symptoms, the contents of motilin in plasma, gastrin, TNF-α, MDA, IL-6 and IL-1ß, and the activity of ROS in serum in the observation group were all lower significantly (P<0.05, P<0.01), while the SOD activity and gastric emptying rate in the observation group were higher than those in the control group (P<0.05, P<0.01). The total effective rate was 90.5% (38/42) in the observation group, better than the control group (73.8%, 31/42, P<0.05). CONCLUSION: Shuanggu yitong acupuncture therapy combined with domperidone remarkably relieves the clinical symptoms and improves the gastric emptying rate, effectively reduces motilin and gastrin and regulates oxidative stress and inflammatory responses in the patients with DGP of liver stagnation and spleen deficiency.

Antibacterial metal-phenolic nanosheets as smart carriers for the controlled release of epirubicin hydrochloride.

Bacterial infections can cause serious complications in cancer treatment and have been proven to weaken therapeutic benefits. Recently, antibacterial nanomaterials that serve as carriers for anticancer drug delivery have been attracting extensive interest due to their combined antimicrobial and anticancer activities. In this study, antibacterial metal-phenolic nanosheets (Cu-TA) were successfully prepared via the self-assembly of the metal-phenolic coordination complexes formed between copper ions and tannic acid, and the structure, morphology, and formation mechanism of Cu-TA nanosheets were explored. The antibacterial activity of Cu-TA nanosheets against both Gram-positive and Gram-negative bacteria was detected using the minimum inhibitory concentration (MIC), zone of inhibition and plate counting methods. The MIC values of both bacterial strains were about 0.4 mg mL-1, and the killing rates of Cu-TA samples were close to 100% at the concentration of 2 and 0.2 mg mL-1 after 12-hour incubation. Epirubicin hydrochloride (EPI) molecules were successfully loaded on the porous Cu-TA nanosheets mainly through the formation of the Cu-EPI chelate complex and strong electrostatic interactions. The Cu-EPI complex and Cu-TA nanosheets could be disassembled under acidic conditions or in the presence of high levels of glutathione (GSH) after uptake by cancer cells, which triggered the unique pH and GSH-responsive controlled release behaviors of EPI and copper ions. The MTT assay results revealed that the presence of bacteria in Hep G2 cells can greatly impair the cell death rate induced by free EPI, but the resultant EPI-loaded Cu-TA nanosheets can significantly enhance cell death both in the presence and absence of bacteria.

Noncovalent Dual-Locked Near-Infrared Fluorescent Probe for Precise Imaging of Tumor via Hypoxia/Glutathione Activation.

Stimulus-responsive fluorescent probes have broad applications in the early detection and treatment of tumors and thus promote the personalized treatment of tumors and improve patient survival. Among the repertoires of probes, dual-locked near-infrared (NIR) fluorescent probes are of great significance due to their improved specificity and multiplex detection in tumor imaging but remain to be explored. In this work, a facile noncovalent strategy for constructing dual-locked probes was proposed. A glutathione (GSH)-activatable single-locked probe CySS (first lock) was preloaded into a hypoxia-responsive molecular container CF3C4A (second lock) through a host-guest interaction to form the dual-locked probe CF3C4A-CySS. Under physiological conditions, CF3C4A-CySS binds strongly to avoid undesired leakage in normal tissues. We have proven that CF3C4A-CySS can be activated and "turn on" its NIR fluorescent signal under the dual key stimulation of hypoxia and GSH in the tumor microenvironment, which enables precise tumor imaging with enhanced accuracy and specificity. Both in vitro and in vivo results indicated the superiority of CF3C4A-CySS in tumor imaging. This work not only provides an effective tool for tumor imaging but also proposes a promising strategy for dual-locked imaging agent construction.

A porous boron nitride nanorods-based QuEChERS analysis method for detection of five neonicotinoid pesticide residues in goji berries.

To accurately determine neonicotinoid pesticide residues in goji berries, porous boron nitride nanorods (p-BNNRs) were prepared and used as a new QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) clean-up sorbent. Combined with ultrahigh-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), a modified QuEChERS method was developed to determine five neonicotinoid pesticide residues in goji berries. In goji berries, the p-BNNRs were shown to have a greater clean-up ability than typical clean-up materials (C18, PSA) The recoveries of the five targets ranged from 78.1 to 117.3% at three fortified levels, and the LODs ranged from 2.2 to 3.7 µg kg-1. The results indicate that this approach could be successfully used to quickly determine of the five neonicotinoid insecticide residues in goji berries for risk assessment purposes, demonstrating the applicability and suitability of p-BNNRs for the routine evaluation of neonicotinoid insecticide residues in goji berries.

Noncovalent Theranostic Prodrug for Hypoxia-Activated Drug Delivery and Real-Time Tracking.

Real-time tracking of hypoxia-activated prodrugs (HAPs) delivery and the release process is of great significance for innovative medical treatments and drug development. Existing theranostic methods for HAPs activation imaging are based on the covalent approach, which suffered from complicated molecular design and tedious synthesis. In this work, a facile noncovalent strategy for constructing an hypoxia-activated theranostic prodrug has been proposed. An hypoxia-activated prodrug, NMAC4A, has been synthesized and bound with an NIR fluorophore CyNH2 through host-guest interaction to form the theranostic prodrug NMAC4A-CyNH2. Interestingly, the NIR fluorescence signal of CyNH2 can be effectively "turned off" after the formation of the stable theranostic prodrug NMAC4A-CyNH2. Because of the selective response to a tumor hypoxic microenvironment, NMAC4A-CyNH2 can realize the tumor-targeted drug delivery, accompanied by its NIR fluorescence "turn on". The synchronization of drug release and fluorescence "turn on" properties of NMAC4A-CyNH2 in an hypoxic microenvironment makes the fluorescence signal an effective tool for a precise tracing of the drug release process. Notably, NMAC4A-CyNH2 has been successfully applied to real-time image tracking of the drug delivery in vitro and in vivo. More importantly, the biodistribution of the theranostic prodrug's metabolites in a tumor and some major tissues have been mapped by mass spectrometry imaging at the molecular level, which further validated the effectiveness of NMAC4A-CyNH2 as a tumor-targeted drug delivery platform and NIR probe. This work will not only provide a promising tool for an hypoxia-activated drug delivery and real-time image tracking but also propose an effective design strategy for noncovalent theranostic prodrug construction.

Spatial distribution analysis of phospholipids in rice by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging.

Phospholipids are one of the main nutrients in rice, which have a positive effect on cancer, coronary heart disease and inflammation. However, phospholipids will become small molecular volatile substances during the aging process of rice, resulting in change the flavor of rice. Therefore, mapping the concentration and the spatial distribution of phospholipids in rice are of tremendous significance in its function research. In this work, we established a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) imaging method for the spatial distribution analysis of phospholipids in rice. A total of 12 phospholipid compounds were found in the range of m/z 500-1000 through a series of conditions optimization. According to the results, lysophosphatidylcholine (LPC) species spread throughout the rice tissue sections and phosphatidylcholine (PC) species distributed in the bran and embryo (particularly in the scutellum). We also compared the signal intensities of phospholipids in different parts of white rice and brown rice by region of interest (ROI) analysis, which showed the relative content of PC species was higher in the embryo and gradually decreased until disappeared with the increase of processing degree during the processing of brown rice to white rice. The PC species on the surface of rice could be used as an important indicator to identify the processing degree of rice. Our work not only establish a MALDI-TOF-MS imaging method for spatial distribution analysis of rice, but also provide the necessary reference for ensuring food security, improving the eating quality of rice and the health benefits of consumers.

A colon-targeted podophyllotoxin nanoprodrug: synthesis, characterization, and supramolecular hydrogel formation for the drug combination.

Making full use of the undeveloped bioactive natural product derivatives by selectively delivering them to target sites can effectively increase their druggability and reduce the wastage of resources. Azo-based prodrugs are widely regarded as an effective targeted delivery means for colon-related disease treatment. Herein, we report a new-type of azo-based nanoprodrug obtained from bioactive natural products, in which the readily available podophyllotoxin natural products are connected with methoxy polyethylene glycol (mPEG) via a multifunctional azobenzene group. The amphiphilic prodrug can form nanosized micelles in water and will be highly selectively activated by azoreductases, leading to the in situ generation of anticancer podophyllotoxin derivatives (AdP) in the colon after the cleavage of the azo bond. To satisfy the demand of drug carriers for cancer combination therapy in clinics, α-CD is further introduced into this nanoprodrug micelle system to form a supramolecular hydrogel via a cascade self-assembly strategy. Using imaging mass spectrometry (IMS), the colon-specific drug release ability of the hydrogel after oral administration is demonstrated at the molecular level. Finally, the nanoprodrug hydrogel is further used as a carrier to load a hydrophilic anti-cancer drug 5-FU during the hierarchical self-assembly process and to co-deliver AdP and 5-FU for the drug combination. The combination use of AdP and 5-FU provides enhanced cytotoxicity which indicates a significant synergistic interaction. This work offers a new way to enhance the therapeutic effect of nanoprodrugs via drug combination, and provides a new strategy for reusing bioactive natural products and their derivatives.

Analysis of the Relevance of the Ultrasonographic Features of Papillary Thyroid Carcinoma and Cervical Lymph Node Metastasis on Conventional and Contrast-Enhanced Ultrasonography.

BACKGROUND: Preoperative prediction of lymph node metastases has a major impact on prognosis and recurrence for patients with papillary thyroid carcinoma (PTC). Thyroid ultrasonography is the preferred inspection to guide the appropriate diagnostic procedure. PURPOSE: To investigate the relationship between PTC and cervical lymph node metastasis (CLNM, including central and lateral LNM) using both conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). MATERIAL AND METHODS: Our study retrospectively analyzed 379 patients diagnosed with PTC confirmed by surgical pathology at our hospital who underwent US and CEUS examinations from October 2016 to March 2021. Individuals were divided into two groups: the lymph node metastasis group and the nonmetastasis group. The relationship between US and CEUS characteristics of PTC and CLNM was analyzed. Univariate and multivariable logistic regression methods were used to identify the high-risk factors and established a nomogram to predict CLNM in PTC. Furthermore, we explore the frequency of CLNM at each nodal level in PTC patients. RESULTS: Univariate analysis indicated that there were significant differences in gender, age, tumor size, microcalcification, contact with the adjacent capsule, multifocality, capsule integrity and enhancement patterns in CEUS between the lymph node metastasis group and the nonmetastasis group (all P<0.05). Multivariate regression analysis showed that tumor size ≥1 cm, age ≤45 years, multifocality, and contact range of the adjacent capsule >50% were independent risk factors for CLNM in PTC, which determined the nomogram. The diagnostic model had an area under the curve (AUC) of 0.756 (95% confidence interval, 0.707-0.805). And calibration plot analysis shown that clinical utility of the nomogram. In 162 PTC patients, the metastatic rates of cervical lymph nodes at levels I-VI were 1.9%, 15.4%, 35.2%, 34.6%, 15.4%, 82.1%, and the difference was statistically significant (P<0.001). CONCLUSION: Our study indicated that the characteristics of PTC on ultrasonography and CEUS can be used to predict CLNM as a useful tool. Preoperative analysis of ultrasonographical features has important value for predicting CLNM in PTCs. The risk of CLNM is greater when tumor size ≥1 cm, age ≤45 years, multifocality, contact range of the adjacent capsule >50% are present.

PEGylated NALC-functionalized gold nanoparticles for colorimetric discrimination of chiral tyrosine.

In this work, acid and matrix-tolerant multifunctionalized gold nanoparticles (AuNPs) with an integrated chiral selector towards tyrosine (Tyr) and polyethylenglycol (PEG) chains were developed for visual chiral discrimination of Tyr in biological samples under acid conditions. In brief, AuNPs multifunctionalized with N-acetyl-l-cysteine (NALC) and PEG (PEG/NALC-AuNPs) were prepared via a simple strategy. In the presence of l-Tyr, the color of PEG/NALC-AuNP solution changed from red to gray, while no obvious color change was observed with the introduction of d-Tyr, which indicated that the introduction of PEG onto the surface of AuNPs has no effect on the chiral recognition between l-Tyr and NALC. A computer-aided molecular model was used to clarify the chiral recognition mechanism between NALC and Tyr enantiomers and to further guide the optimization of sensitivity. The resultant PEG/NALC-AuNP sensor presented a significantly improved stability under acid and alkali conditions compared with conventional NALC-AuNPs, resulting in a wider dynamic range (500 nM-100 µM) and a 50 times reduced detection limit by simply adjusting the pH of the sensor system under acid conditions (pH 2-2.5). More importantly, the PEG/NALC-AuNPs can realize the visual chiral discrimination of Tyr enantiomers in biological samples due to their significantly improved long-term stability and reduced interaction towards non-target species.

Bungsteroid A: One Unusual C34 Pentacyclic Steroid Analogue from Zanthoxylum bungeanum Maxim.

Bungsteroid A (1), possessing an unreported carbon skeleton, was isolated from the pericarps of Zanthoxylum bungeanum Maxim. It represents the first carbon skeleton of a C34 steroid analogue featuring a unique 6/6/6/6/5-fused pentacyclic skeleton, which has been determined by spectroscopic methods, quantum-chemical 13C NMR, ECD calculations, and calculations of optical rotations. Bungsteroid A showed the antiproliferative effects against HepG2, MCF-7, and HeLa cell lines with the IC50 values of 56.3 ± 1.1, 64.2 ± 0.9, and 74.2 ± 1.3 µM, respectively.

Precisely Traceable Drug Delivery of Azoreductase-Responsive Prodrug for Colon Targeting via Multimodal Imaging.

We report the development of an azoreductase-responsive prodrug AP-N═N-Cy in which the precursor compound AP, a readily available podophyllotoxin derivative, is linked with a NIR fluorophore (Cy) via a multifunctional azobenzene group. This type of azo-based prodrug can serve as not only an azoreductase-responsive NIR probe to real-time tracking of the drug delivery process but also a delivery platform for an anticancer compound (AdP). We have shown that cleavage of the multifunctional azobenzene group in AP-N═N-Cy only occurred in the presence of azoreductase, which specifically secretes in the colon, resulting in direct release of AdP through an in situ modification of a phenylamino group on the precursor AP. Moreover, introduction of the azobenzene group endows the prodrug with an unique fluorescence "off-on" property and served as a switch to "turn on" the fluorescence of Cy as consequence of a self-elimination reaction with breakage of an azo bond. Such a prodrug can be administered orally and exhibit high stability and low toxicity before arriving at the colon. In view of the synchronism of drug release and the fluorescence turn-on process, the fluorescence imaging method was utilized to precisely trace drug delivery in vitro, ex vivo, and in vivo. Distinguishingly, the biodistribution of AdP and Cy in various tissues was further precisely mapped at the molecular level using imaging mass spectrometry. To the best of our knowledge, this is the first time that the in vivo real-time precise tracking of the colon-specific drug release and biodistribution was reported via a multimodal imaging method.

Flavonoids as key bioactive components of Oxytropis falcata bunge, a traditional anti-inflammatory and analgesic Tibetan medicine.

The traditional Tibetan medicine Oxytropis falcata Bunge, in the Leguminosae family, is widely used in the west area owing to its significant anti-inflammatory and analgesic activities. O. falcata is rich in flavonoids, which are the main secondary metabolites and key bioactive components of this plant. Up to now, 91 flavonoids have been isolated from O. falcata, including isoflavone, flavone, flavonone, flavonol, homoisoflavonoid, chalcone, dihydrochalcone, chalcone dimers, and pterocarpans. The flavonoids in O. falcata have good anti-inflammatory and analgesic activities, which are comparable to those of a positive drug control (indomethacin). Furthermore, these flavonoids exhibit antibacterial, antioxidant, antitumour, anti-cardiovascular disease, and haemostatic activities. However, to date, O. falcata has not been reviewed comprehensively. Herein, the main secondary metabolites, biosynthetic pathways, and bioactivities of O. falcata are discussed.

Sodium(I)-doped graphitic carbon nitride with appropriate interlayer distance as a highly selective sorbent for strontium(II) prior to its determination by ICP-OES.

Multilayered and porous sodium-doped graphitic carbon nitride (GCN-Na) was prepared and employed to the solid-phase extraction of Sr(II). The sorbent exhibits high adsorption capacity and excellent selectivity for Sr(II). This is due to its small interplanar stacking distance caused by doping with Na(I) which matches the size of Sr(II) better than blank GCN. An original solid-phase extraction method based on GCN-Na coupled with ICP-OES was established for Sr(II), the calibration plots are linear ranging from 0.05-10 mg·kg-1 with the correlation coefficients (R2) above 0.999, the limits of detection are in the range of 0.57-1.52 µg·kg-1 and the preconcentration factor of 80 is achieved using 48 mL sample. It was successfully applied in the extraction and detection of trace Sr(II) in tap water, rice and sea fish. Graphical abstractA multilayer porous sodium(I) doped graphitic carbon nitride nanosheet (GCN-Na) was synthesized and exhibited excellent adsorption capability and selectivity for Sr(II).

A fluorescent molecularly imprinted device for the on-line analysis of AFP in human serum.

MIT is a promising strategy in antibody free analysis for tumour markers. Conventional nanosized MIPs with off-line analysis are beset by tedious operation and unsatisfactory analysis performance. In this work, an on-line analytical device to directly detect AFP, which is a typical tumour marker in cancer screening, was prepared for the first time. A microscope slide was chosen to be the basis of the device. APBA-PA, a polymerizable fluorescent boronic acid monomer, was synthesised and grafted on the surface of the microscope slide to act as the signal transduction pathway between the templates and the device. Along with the hydrolysis of TEOS and the elution of the templates, a portable, stable, easy to operate and low-cost analysis device for AFP with excellent repeatability was successfully prepared. Owing to the excellent selectivity and highly sensitive fluorescence response ability of the device towards the templates, the on-line detection of AFP in human serum was realized. A series of characterizations were applied to the device, and its analysis performance and possible detection mechanism were carefully studied. Furthermore, the device exhibited appropriate application prospects by comparing its analysis results with those of the commercially available ELISA. In our perception, this work is an important step towards MIPs for clinical applications.

17ß-estradiol preserves right ventricular function in rats with pulmonary arterial hypertension: an echocardiographic and histochemical study.

Pulmonary arterial hypertension (PAH) is more prevalent in females. Paradoxically, female patients have better right ventricular (RV) function and higher survival rates than males. However, the effects of 17ß-estradiol (E2) on RV function in PAH has not been studied. Twenty-four male rats were exposed to monocrotaline (MCT) to induce experimental PAH, while treated with E2 or vehicle respectively. Together with eight control rats, thirty-two rats were examined by echocardiography 4 weeks after drug administration. Echocardiographic measurement of RV function included: tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), RV fractional area change (RVFAC) and tricuspid annular systolic velocity (s'). RV free wall longitudinal strain (RVLSFW) and RV longitudinal shortening fraction (RVLSF) were also used to quantify RV function. RV morphology was determined by echocardiographic and histological analysis. TAPSE, RVFAC and s' were reduced, and RIMP was elevated in the MCT-treated group and vehicle-treated group, when compared with control group (P < 0.01). TAPSE, RVFAC and s' in the E2 group were higher, while RIMP was lower than those in the MCT-treated group and vehicle-treated group (P < 0.01). Myocardial functional parameters (RVLSFW and RVLSF) were also higher in the E2 group. Enhanced serum E2 levels were closely correlated with the improvement in RV functional parameters and enhancement of serum BNP levels (P < 0.01 for all groups). RV function decreased significantly in male rats with MCT-induced PAH, while E2 exhibited a protective effect on RV function, suggesting that E2 is a critical modulator of sex differences in PAH.

Regulatory role of microRNA-320a in the proliferation, migration, invasion, and apoptosis of trophoblasts and endothelial cells by targeting estrogen-related receptor γ.

Recently, microRNAs (miRNAs) have been demonstrated to participate in many physiological and biological processes, especially by acting as circulating biomarkers or modulators in cell differentiation. Therefore, the aim of the current study was to clarify whether microRNA-320a (miR-320a) regulates the proliferation, migration, invasion, and apoptosis of trophoblasts and endothelial cells. In this study, miR-320a mimics and inhibitors were transfected into HTR.8/SVneo cells and human umbilical vein endothelial cells (HUVECs) using liposomes. Subsequently, the expression of miR-320a and estrogen-related receptor γ (ERRγ) mRNA was detected by a reverse transcription quantitative polymerase chain reaction, whereas the protein expression of ERRγ, vascular endothelial growth factor (VEGF), angiogenin 1 (Ang-1), human 3beta-hydroxysteroid dehydrogenase type 1 (HSD3B1), and human chorionic gonadotropin (HCG) was detected by western blot analysis. Furthermore, the proliferation, invasion/migration, and apoptosis of cells were analyzed by the cell counting kit-8 assay, transwell assay, and flow cytometry, respectively. The results showed that overexpression of miR-320a decreased the optical density (OD) values and the proliferation rate of HTR.8/SVneo cells and HUVECs, while inhibiting the expression of VEGF, Ang-1, HSD3B1, and HCG in these cells. Furthermore, miR-320a reduced the ability of cell invasion and migration, while increasing the rate of cell apoptosis. After cotransfecting the cells with miR-320a and ERRγ small (or short) interfering RNA (siRNA), the decreased ERRγ expression led to inhibited proliferation, migration, and invasion, but increased apoptosis of HTR.8/SVneo cells and HUVECs. Our results further revealed that miR-320a induced the apoptosis of trophoblasts and endothelial cells while inhibiting their proliferation, migration, and invasion by decreasing the expression of ERRγ and by indirectly suppressing the expression of VEGF, Ang-1, HSD3B1, and HCG.