High glucose promotes lipopolysaccharide-induced macrophage pyroptosis through GSDME O-GlcNAcylation.

AIM: The high glucose (HG) environment in diabetic periodontitis aggravates the damage of periodontal tissue. Pyroptosis has been shown to be positively correlated with the severity of periodontitis, including macrophage pyroptosis. O-GlcNAcylation is a posttranslational modification that is involved in the pathogenesis of periodontitis. However, whether HG regulates macrophage pyroptosis through O-GlcNAcylation remains uncertain. This study aimed to investigate the effect of HG on the O-GlcNAcylation level of a pyroptosis regulator GSDME in macrophages to further probe the mechanisms of diabetic periodontitis. METHODS: Blood samples were collected from patients with diabetic periodontitis. THP-1 monocytes were induced to differentiate into macrophages by phorbol 12-myristate 13-acetate and then treated with HG to simulate periodontitis in vitro. GSDME expression of blood samples and macrophages was measured by quantitative real-time PCR. Pyroptosis was assessed by propidium iodide staining, measurement of cell viability, cytotoxicity, protein levels of inflammation factors, and pyroptosis-related proteins. O-GlcNAcylation of GSDME was analyzed using co-immunoprecipitation (co-IP), IP, and western blot. RESULTS: The results showed that GSDME expression was elevated in patients with periodontitis and HG-treated macrophages. HG inhibited cell viability but increased LDH content, levels of IL-1ß, IL-18, TNF-α, NLRP3, GSDMD, and Caspase-1, indicating that HG promoted pyroptosis of macrophages, which was reversed by GSDME knockdown. HG treatment increased O-GlcNAcylation in macrophages. Mechanically, GSDME interacted with OGT, and OGT knockdown suppressed O-GlcNAcylation of GSDME at Ser (S)339 site. Knockdown of OGT inhibited pyroptosis in HG-treated macrophages, while GSDME overexpression partially reversed this inhibition. CONCLUSION: HG treatment enhanced OGT-mediated GSDME O-GlcNAcylation, thereby augmenting pyroptosis in LPS-induced macrophages. These results may provide a novel sight for the treatment of periodontitis.

Transcriptome analysis of Schizothorax oconnori (Cypriniformes: Cyprinidae) oocytes: The role of K+ in promoting yolk globule fusion and regulating oocyte maturation.

Schizothorax oconnori (S. oconnori) is an economically important fish in Tibet. Oocyte maturation is a physiological process that is of great significance to reproduction and seed production in S. oconnori, yet little is currently known regarding the molecular mechanisms of oocyte development in this species. To identify candidate genes involved in reproduction of female fish, a combination of PacBio and Illumina HiSeq technologies was employed to provide deep coverage of the oocyte transcriptome. Transcriptome analysis revealed several candidate genes that are potentially involved in the regulation of oocyte maturation in S. oconnori, including GIRK1, CHRM3, NPY2R, GABRA3, GnRH3, mGluR1α, GPER1, GDF9, HSP90, and ESR2. Genes that are significantly expressed during oocyte maturation mainly contribute to the GPCR signaling pathway and the estrogen signaling pathway. Neurotransmitter (Ach, NPY, and GABA) and peptide hormone (GnRH3) binding to G protein-coupled receptors (GPCRs) frees G-protein ßγ subunits to interact with the G protein-gated inward rectifier K+ channel 1 (GIRK1). This process helps release K+ from granulosa cells to maturing oocytes, allowing yolk globule fusion. This mechanism may play an important role in oocyte maturation in S. oconnori. In conclusion, this study provides a valuable basis for deciphering the reproductive system in S. oconnori during the oocyte maturation process.

Unexpected rise of atmospheric secondary aerosols from biomass burning during the COVID-19 lockdown period in Hangzhou, China.

After the global outbreak of COVID-19, the Chinese government took many measures to control the spread of the virus. The measures led to a reduction in anthropogenic emissions nationwide. Data from a single particle aerosol mass spectrometer in an eastern Chinese megacity (Hangzhou) before, during, and after the COVID-19 lockdown (5 January to February 29, 2020) was used to understand the effect lockdown had on atmospheric particles. The collected single particle mass spectra were clustered into eight categories. Before the lockdown, the proportions of particles ranked in order of: EC (57.9%) < K-SN (13.6%) < Fe-rich (10.2%) < ECOC (6.7%) < K-Na (6.6%) < OC (3.4%) < K-Pb (1.0%) < K-Al (0.7%). During the lockdown period, the EC and Fe-rich particles decreased by 42.8% and 93.2% compared to before lockdown due to reduced vehicle exhaust and industrial activity. By contrast, the K-SN and K-Na particles containing biomass burning tracers increased by 155.2% and 45.2% during the same time, respectively. During the lockdown, the proportions of particles ranked in order of: K-SN (39.7%) < EC (38.1%) < K-Na (11.0%) < ECOC (7.7%) < OC (1.2%) < K-Pb (0.9%) < Fe-rich (0.8%) < K-Al (0.6%). Back trajectory analysis indicated that both inland (Anhui and Shandong provinces) and marine transported air masses may have contributed to the increase in K-SN and K-Na particles during the lockdown, and that increased number of fugitive combustion points (i.e., household fuel, biomass combustion) was a contributing factor. Therefore, the results imply that regional synergistic control measures on fugitive combustion emissions are needed to ensure good air quality.

A simple enzyme-catalyzed reaction induced "switch" type fluorescence biosensor based on carbon nitride nanosheets for the assay of alkaline phosphatase activity.

An enzyme-catalyzed fluorescence "switch" type sensor was constructed for the determination of alkaline phosphatase (ALP) activity by combining the fluorescence quenching effect of Ag+ on ultrathin g-C3N4 nanosheets (CNNSs) with the simple redox reaction of AA and Ag+. Briefly, Ag+ exhibits a significant quenching effect on the fluorescence of CNNSs. Thus the fluorescence signal of the CNNS-Ag+ system is extremely weak even in the presence of l-ascorbic acid-2-phosphate (AAP) ("off" state). When ALP coexists in the system, the enzyme can specifically catalyze the hydrolysis of AAP to form ascorbic acid (AA), which reduces Ag+ to Ag0. In this case, the fluorescence signal of the system is recovered ("on" state). Based on this principle, a signal-enhanced CNNS fluorescence sensor was developed to determine the activity of alkaline phosphatase. The experimental results show that the detection range of alkaline phosphatase is 0.5-20 U L-1, and the detection limit is 0.05 U L-1 (S/N = 3). Meanwhile, this method was used to assay ALP in serum samples.

Target-responsive ratiometric fluorescent aptasensor for OTA based on energy transfer between [Ru(bpy)3]2+ and silica quantum dots.

A ratiometric fluorescent aptasensor based on energy transfer between [Ru(bpy)3]2+ and silica quantum dots (silica QDs) for assaying OTA was fabricated. The aptamer for OTA was used as the gate to shield the fluorescent reagent [Ru(bpy)3]2+ into mesoporous silica nanoparticle (MSN). In the presence of OTA, the constrained [Ru(bpy)3]2+ was released from MSN due to a target-induced aptamer conformational change. The released [Ru(bpy)3]2+ adsorbed onto the negatively charged silica QDs through electrostatic interaction. This creates appearance of fluorescence from [Ru(bpy)3]2+ at 625 nm and decrease of the fluorescence from silica QDs at 442 nm owing to the energy transfer. The value of FL625nm/FL442nm was in proportion to the concentration of OTA in the range 0.5~100 ng mL-1 with a LOD of 0.08 ng mL-1. Practical applicability of this method was validated by the determination of OTA in flour samples. Graphical abstract The sensing principle of this sensor.

Electrochemiluminescent functional nucleic acids-based sensors for food analysis.

Foodborne contaminants widely exist in foods, which can lead to various foodborne diseases and food safety issues. The development of quick, sensitive and universal analytical approaches for foodborne contaminants is imperative. Electrochemiluminescent functional nucleic acids (ECL FNAs)-based sensors are a series of sensing devices using FNAs as the recognition elements and ECL as the transducer. Contributing to the specific recognition ability of FNA and the high sensitivity of ECL, ECL FNA-based sensors are considered to be of great application potential for foodborne contaminants monitoring. This review mainly presents the applications of ECL FNA-based sensors for foodborne contaminants (including microorganisms, mycotoxins, allergens, antibiotics, heavy metal ions, pesticides and some illegal additives). In general, the application of ECL FNA-based sensors in the field of food analysis is just in its infancy. Although there are several limitations and challenges, it is envisaged that ECL FNA-based sensors will have broad prospects for food analysis in the future.

Signal-on fluorescence assay for pyrophosphate ions based on DNA-stabilized silver nanoclusters.

Pyrophosphate anion (P2 O7 4- , PPi) is considered as a potential biomarker for arthritic diseases because high levels of PPi may result in calcium pyrophosphate dehydrate crystal deposition diseases. In this study, a simple fluorescence method for PPi was demonstrated by organic integration of the efficient fluorescence quenching ability of copper ions to DNA-scaffolded silver nanoclusters and the strong affinity of PPi towards copper ions. This simple fluorescence sensor showed a low detection limit (0.28 µM based on signal/noise = 3) towards the detection of PPi. Practical application of this method was also validated by detection of PPi in the synovial fluid.

Water-dispersed silicon quantum dots for on-off-on fluorometric determination of chromium(VI) and ascorbic acid.

Water-dispersed silicon quantum dots (SiQDs) with the quantum yield of 25% was prepared using aminopropyltrimethoxysilane as the silicon source and ascorbic acid (AA) as the reduction reagent. The SiQDs display blue fluorescence with excitation/emission peaks at 350 nm/440 nm. The synthesized SiQDs are shown to be a viable "on-off-on" fluorescent probe for the detection of Cr(VI) and AA. Cr(VI) ions exert an inner filter effect on the fluorescence of the SiQDs which results in a reduction of fluorescence (off-state). On addition of AA, Cr(VI) is chemically reduced to Cr(III) which weakens the inner filter effect and restores fluorescence (on-state). The method has low detection limits for both Cr(VI) and AA (0.16 µM and 0.57 µM, respectively). It was applied to the analysis of spiked lotus seeds and human serum samples. Graphical abstract A simple and facile "on-off-on" fluorometric method for Cr(VI) and ascorbic acid (AA) was developed using water-soluble silicon quantum dots (SiQDs) as the fluorescent probe. The approach was also used to assay Cr(VI) and AA in the lotus seeds and human serum, respectively.

T-cell subsets are associated with serum homocysteine concentration in patients with essential hypertension.

OBJECTIVE: To explore the association between serum homocysteine (Hcy) concentration and T-cell subsets from patients with essential hypertension. PATIENTS AND METHODS: A total of 218 essential hypertension patients were recruited, of which 170 were H-type essential hypertensive and 48 were non-H-type essential hypertensive. H-type essential hypertensive patients were divided into three groups by concentration of serum Hcy. The peripheral blood T-cell subsets (CD3+%, CD4+%, CD8+ T%, CD4+/CD8+) and clinical features including age, sex, serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were recorded and analyzed with T-cell subsets which were counted by fluorescence activated cytometry. RESULTS: Compared with non-H-type hypertensive patients, CD4+ T-cell percentage in peripheral blood was significantly decreased in H-type hypertensive patients. Because of the increase of Hcy level, CD4+ T-cell percentage decreased. Linear regression analysis showed that Hcy level was negatively correlated with CD4+ T-cell percentage; however, it was positively correlated with CD3+ T-cell percentage. CONCLUSION: A direct association between serum Hcy concentrations and T-cell percentage was observed in patients with essential hypertension. This observation indicates that T-cell subsets might play an important role in hypertension.

Leptin is associated with heart rate recovery in Chinese hypertensive patients.

Elevated serum leptin concentrations are closely related to sympathetic nervous system activation in essential hypertension (EH); however, it is not clear whether or not they are associated with parasympathetic nervous system impairment in EH. Heart rate recovery (HRR) is a reproducible method used to assess parasympathetic activity. This study aimed to investigate the relationship between serum leptin and HRR in Chinese untreated EH patients. This was a cross-sectional study enrolling 471 Chinese EH patients (205 men, 266 women; mean age 63.1 years). HRR was calculated during an incremental cardiopulmonary exercise test. Simple and multiple regression analyses were used to assess the correlation between serum leptin level and HRR value. Serum leptin levels elevated with increasing BP values. Moreover, univariate analysis revealed that the HRR value was negatively correlated with serum leptin (r = -0.037, P < 0.01). In multiple regression analysis, the age-adjusted serum leptin level was negatively correlated with HRR (ß = -0.268, P < 0.01). Serum leptin remained negatively associated with HRR (ß = -0.017, P < 0.01) after further adjustments for factors including age, systolic blood pressure, total cholesterol, and several factors that correlated with HRR. Our findings demonstrated that a raised serum leptin concentration is related to HRR blunt, which suggests that the role of leptin in the development of EH might be associated with impairment of the parasympathetic nervous system as well.

Echocardiographic assessment of hypertensive patients with or without hyperhomocysteinemia.

The study was designed to assess left ventricular (LV) systolic and diastolic function in hypertensive patients with or without Hhcy. The study participants consisted of 40 hypertensive patients with Hhcy, 40 hypertensive patients without Hhcy and 40 age-matched healthy control participants. Cardiac functions were determined using echocardiography and the Tei index was calculated for analysis. LAVI (left atrial volume index), IVST (interventricular septum thickness in diastole), PVST (posterior ventricular septum thickness in diastole), LVMI (left ventricular mass index), E/A (peak early and late diastolic transmitral filling flow velocities ratio), DT (deceleration time of the E wave), IRT (isovolumic relaxation time), and the Tei index were different in the hypertensive patient groups (hypertension with Hhcy and hypertension without Hhcy) compared with the controls. The Tei index was significantly higher in the hypertensive groups compared with the controls (0.62 ± 0.05, 0.51 ± 0.04, and 0.40 ± 0.04, respectively, p < 0.01). Significant differences were also observed between the hypertensive patients with Hhcy and the hypertensive patients without Hhcy regarding LAVI (25.6 ± 4.7 versus 22.9 ± 3.5 ml/m(2)), E/A (0.73 ± 0.22 versus 0.92 ± 0.14), DT (93.1 ± 6.9 versus 84.3 ± 8.1 ms), IRT (93.1 ± 6.9 versus 84.3 ± 8. ms) and the Tei index. Significant correlations were observed between serum homocysteine levels and LV diastolic function parameters (LAVI: r = 0.39, E/A: r = -0.32, DT: r = 0.47, IRT: r = 0.51, p < 0.05). We found that Hhcy had contributory effects on myocardial impairment induced by hypertension. Moreover, there were strong relationships between homocysteine level and LV diastolic dysfunction parameters.

Dual-channel cathodic electrochemiluminescence of luminol induced by injection of hot electrons on a niobate semiconductor modified electrode.

In this paper, a new niobate semiconductor photocatalyst Sr(0.4)H(1.2)Nb(2)O(6)·H(2)O (HSN) nanoparticle was applied to investigate the cathodic electrochemiluminescent (ECL) behavior of luminol for the first time. The results presented here demonstrated that there were two ECL peaks of luminol at the cathodic potential attributed to immobilization of HSN on the electrode surface. It is implied that HSN can be electrically excited and injected electrons into aqueous electrolytes from this electrode under a quite low potential that only excites luminol. A mechanism for this luminol-ECL system on HSN/GCE has been proposed. Additionally, this HSN/GCE has lots of advantages, such as high stability, good anti-interference ability, simple instrumentation, rapid procedure and ultrasensitive ECL response. It is envisioned that this HSN/GCE has further applications in biosensors.

Association between polymorphism of the G-protein ß3 subunit C825T and essential hypertension: an updated meta-analysis involving 36,802 subjects.

PURPOSE: The G-protein ß3-subunit gene C825T polymorphism (GNB3-C825T) has been reported to be associated with essential hypertension (EH), but results from previous studies are conflicting. The present study aimed at investigating the association between this polymorphism and risk of EH using a meta-analysis on the published studies. MATERIALS AND METHODS: PubMed, Embase, CBM (China Biological Medicine Database), Wanfang and VIP databases were searched to identify eligible studies published in English and Chinese before March 2013. Data were extracted using standardized methods. The association was assessed by the odds ratio (OR) with 95% confidence intervals (CI). Begg's test was used to measure publication bias. RESULTS: A total of 40 case-control studies containing 16,518 EH patients and 20,284 controls were involved in this meta-analysis. Overall, a significant association was found between GNB3 C825T polymorphism and risk of EH when all studies were pooled with a random-effects model for T versus C (OR=1.09, 95% CI: 1.04-1.19). In the subgroup analysis, the same association was found in overall Caucasian (T versus C, OR=1.16, 95% CI 1.08-1.24) and Chinese populations (TT versus CC, OR=1.23, 95% CI 1.06-1.57). No associations were detected between GNB3-C825T and the risk of EH overall in Asian and Japanese people. CONCLUSIONS: Meta-analysis results suggest that the GNB3-C825T polymorphism is associated with risk of EH in the overall population, the Caucasians and the Chinese. The effect of the variants on the expression levels and the possible functional role of the variants in EH should be addressed in further studies.

Effects of angiotensin-converting enzyme inhibitory peptide LAP on vascular remodeling.

The aim of this article is to study the efficiency of an angiotensin-converting enzyme (ACE)-inhibitory peptide LAP on the blood pressure (BP) and the vascular remodeling in spontaneously hypertensive rats (SHRs). Ten-week-old male SHRs were divided into four groups with 10 animals in each group and treated for 2 months: blank, pseudo-experimental (NS), enalapril (ENA), and LAP. The alterations of BP, plasma angiotensin II (AngII) levels, and morphological changes of left common carotid artery and the third level of superior mesenteric artery were investigated. After 2 weeks of treatment, LAP and ENA significantly decreased BP and the antihypertensive effects lasted till the end of experiment. After 2 months, LAP and ENA also significantly lowered plasma AngII levels. LAP and enalapril significantly lowered vascular medial thickness, media thickness/lumen diameter, medial cross-sectional area, and mean nuclear area of smooth muscle cells in left common carotid artery. When compared to the blank group, LAP and ENA significantly lowered the percentages of collagen fibers in the vascular area of left common carotid artery with 24.84 ± 0.53, 23.36 ± 0.99 versus 31.82 ± 0.57 (blank), respectively, and those of the third level of superior mesenteric artery with 15.82 ± 0.60, 15.15 ± 0.71 versus 23.42 ± 0.72, respectively. LAP had a beneficial effect on BP and vascular remodeling in SHRs. These findings suggest the potential therapeutic value of LAP in the treatment of hypertension.

[Effect of water extracts from duhuo jisheng decoction on expression of chondrocyte G1 phase regulator mRNA].

OBJECTIVE: To investigate the effect of water extracts from Duhuo Jisheng decoction on chondrocyte G1 phase. METHODS: Chondrocytes were collected from four-week-old SD rats to establish the chondrocyte in vitro culture system. The third generation of chondrocytes was intervened. MTT method was used to measure the effect of water extracts from different concentrations of Duhuo Jisheng decoction on chondrocyte activity. The expressions of Chondrocyte Cyclin D1, CDK4, CDK6 and P21 mRNA in the blank group and low, middle and high-dose groups (100, 200, 400 mg x L(-1)) were detected by RT-PCR method. RESULT: The MTT assay showed that the chondrocyte activity significantly increased within specific drug concentrations (50-800 mg x L(-1)) (P < 0.01); After the intervention for 24 h, the expressions of CyclinD1, CDK4 and CDK6 mRNA in all dose groups notably increased (P < 0.05), with the maximum expressions at the concentration of 200 mg x L(-1); The expression of P21 mRNA decreased, particularly at the concentration of 200 mg x L(-1) (P < 0.01). CONCLUSION: Water extracts from Duhuo Jisheng decoction can promote chondrocyte proliferation by effecting the expression of chondrocyte G1 phase regulator mRNA.

Label-free dual-mode sensing platform based on target-regulated CRISPR-Cas12a activity for ochratoxin A in Morinda officinalis.

Many traditional Chinese herbs are susceptible to ochratoxin A (OTA), a potent mycotoxin, which causes serious effects on the quality of the herb and on people's health. The development of methods to detect OTA is extremely important. Most methods for detecting OTA are based on a single-signal output mode, which might be easily influenced by complex environmental conditions. In this research, by taking advantage of the cleavage of DNA by target-induced CRISPR-Cas12a activity and the difference in electrostatic force of DNA to different charge electrochemiluminescent (ECL) and electrochemical (EC) probes, a biosensor is developed for the detection of OTA. First, the CRISPR-Cas12a system consists of a well-designed crRNA, its complementary strand (also as an aptamer for OTA), and Cas12a. Without the target, this CRISPR-Cas12a system is in the "activated stage", which digests hairpin DNA on the electrode, resulting in a weak ECL signal and strong current response. With the introduction of OTA bound with the aptamer, CRISPR-Cas12a activity is inhibited ("locked stage"). Thus, hairpin DNA remained intact on the electrode, resulting in recovery of the ECL signal and attenuation of the current intensity. As a result, this label-free dual-mode sensing platform realizes an assay for OTA in Morinda officinalis. This target-regulated CRISPR-Cas12a activity-sensing platform with dual-mode output not only provides high sensitivity (due to the CRISPR-Cas12a system), but also has good anti-interference ability against complex substrates (due to dual-mode output), and exhibits a broad range of prospects for application.

An immobilization-free electrochemical aptamer-based assay for zearalenone based on target-triggered dissociation of DNA from polydopamine nanospheres with strand displacement amplification.

Zearalenone (ZEN), a widespread mycotoxin, can cause great harm to people's health. In order to assay ZEN, an immobilization-free electrochemical sensor has been developed. A multifunctional hairpin DNA has been carefully designed, including three functions: the aptamer for zearalenone (ZEN), primer, and template sequence. This hairpin DNA can anchor on polydopamine nanospheres (PDANSs), which can protect DNA against the digestion of enzymes and prevent the occurrence of strand displacement amplification (SDA). In the presence of ZEN, the hairpin DNA is dissociated from PDANSs due to the interaction between ZEN and the aptamer, and the SDA reaction is initiated with the help of endonuclease and polymerase. During the SDA process, substantial amounts of negatively charged dsDNA are generated. The MB molecules are embedded into the dsDNA grooves to obtain the complex with a negative charge. The confined MB is repelled on the surface of the negatively charged ITO electrode, leading to the decline of the current. This immobilization-free method possesses high sensitivity (LOD of 0.18 pg mL-1) and good selectivity and can be applied to assay ZEN in corn flour.

Effects of sowing date on photosynthetic characteristics, chlorophyll fluorescence and yield of different Echium plantagineum L. cultivars.

The seed oil of Echium plantagineum L. is rich in unsaturated fatty acids. With the gradual development of the value of echium oil in food, medical care and cosmetics, the corresponding market demand has also increased. The selection of suitable cultivars and the increase of yield per unit area has also become one of the main objectives of current breeding and cultivation of E. plantagineum. To effectively use the local photothermal resources, to improve the use of light energy by E. plantagineum, and to enhance the growth and yield of E. plantagineum. E. plantagineum cultivars Blue Bedder and Mixed Bedding were used as research subjects to study the effects of different sowing dates (1 May, 8 May, 15 May, 22 May and 29 May) on the photosynthetic characteristics and yield of E. plantagineum. Under the same cultivar conditions, with the delay in sowing date, the leaf chlorophyll content (SPAD), photosynthetic rate (Pn), transpiration rate (Tr), stomatal limitation value (Ls), photochemical quenching (qP), electron transfer rate (ETR), actual photochemical efficiency (ΦpsII) and yield of Blue Bedder decreased and reached a maximum at T1, while the SPAD, Pn, Tr, water use efficiency (WUE), Ls, initial fluorescence (Fo), maximum fluorescence (Fm), qP, ETR, ΦpsII and yield of Mixed Bedding reached the maximum at T4. Blue Bedder should be sown early at T1 and Mixed Bedding late at T4 during planting, which will help to improve the photosynthetic characteristics and grain yield of E. plantagineum.

Smart Chondroitin Sulfate Micelles for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Metastasis.

Introduction: Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis. Methods: AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balb/c mice. Results: D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity. Conclusion: The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer.

An electrochemiluminescence biosensor for cadmium ion based on target-induced strand displacement amplification and magnetic Fe3O4-GO nanosheets.

Taking advantage of an exquisite hairpin DNA for strand displacement amplification (SDA) and the magnetic Fe3O4-graphene oxide nanosheets (MGN) as the carrier, an immobilization-free ECL biosensor was constructed for ultra-trace detection of Cd2+. Firstly, the ECL probe Ru (phen)32+ easily diffuses in the solution and reaches the electrode surface to induce strong ECL signal. This is because the pre-designed hairpin DNA is constrained by MGN in the absence of Cd2+. The presence of Cd2+ releases cDNA by binding to its corresponding aptamer, leading to removal of hairpin DNA away from the surface of MGN. In this case, SDA amplification was evoked and generated numerous dsDNA which further trapped Ru (phen)32+ in its groove. It is difficult for the embedded ECL probe to touch the electrode surface to generate ECL signal. Therefore, the concentration of Cd2+ was monitored according to the attenuation of ECL signal. This method showed high sensitivity to Cd2+ with a detection limit of 1.1 × 10-4 ppb. Moreover, it not only avoids many condition optimizations required in the conventional SDA method, but also circumvent the modification and immobilization of DNA probe. This sensor is further applied in the detection of Cd2+ in the sample of traditional Chinese medicine.