Sb/As immobilization and soil function improvement under the combined remediation strategy of modified biochar and Sb-oxidizing bacteria at a smelting site.

Antimony (Sb) and arsenic (As) lead to soil pollution and structural degradation at Sb smelting sites. However, most sites focus solely on Sb/As immobilization, neglecting the restoration of soil functionality. Here, we investigated the effectiveness of Fe/H2O2 modified biochar (Fe@H2O2-BC) and Sb-oxidizing bacteria (Bacillus sp. S3) in immobilizing Sb/As and enhancing soil functional resilience at an Sb smelting site. Over a twelve-month period, the leaching toxicity of As and Sb was reduced to 0.05 and 0.005 mg L-1 (GB3838-2002) respectively, with 1% (w/w) Fe@H2O2-BC and 2% (v/v) Bacillus sp. S3 solution. Compared to CK, the combination of Fe@H2O2-BC and Bacillus sp. S3 significantly reduced the bioavailable As/Sb by 98.00%/93.52%, whilst increasing residual As and reducible Sb fractions by 210.31% and 96.51%, respectively. The combined application generally improved soil aggregate structure, pore characteristics, and water-holding capacity. Fe@H2O2-BC served as a pH buffer and long-term reservoir of organic carbon, changing the availability of carbon substrates to bacteria. The inoculation of Bacillus sp. S3 facilitated the transformation of Sb(III)/As(III) to Sb(V)/As(V) and differentiated the composition and functional roles of bacterial communities in soils. The combination increased the abundance of soil saprotrophs by 164.20%, whilst improving the relative abundance of N- and S-cycling bacteria according to FUNGuild and FAPROTAX analysis. These results revealed that the integrated application was instrumental in As/Sb detoxification/immobilization and soil function restoration, which demonstrating a promising microbially-driven ecological restoration strategy at Sb smelting sites.

Using Fe/H2O2-modified biochar to realize field-scale Sb/As stabilization and soil structure improvement in an Sb smelting site.

Antimony (Sb) and arsenic (As) released from the Sb smelting activities pose a major environmental risk and ecological degradation in Sb smelting sites. Here the effects of Fe/H2O2 modified biochar (Fe@H2O2-BC) on the synchronous stabilization of Sb/As and the improvement of soil structure in a typical Sb smelting site in Southern China based on a 1-year field experiment were studied. Application of ≥1 % (w/w) Fe@H2O2-BC could stably decrease the leaching concentrations of Sb and As of the polluted soils to Environmental quality standards for surface water Chinese Level III (GB3838-2002). Compared to the untreated soils, the stabilization efficiency of soil Sb and As treated by Fe@H2O2-BC reached 90.7 % ~ 95.7 % and 89.6 % ~ 90.8 %, respectively. The residue fractions of Sb/As in the soils increased obviously, and the bio-availability of Sb/As decreased by 65.0-95.6 % and 91.1-96.0 %, respectively. Moreover, Fe@H2O2-BC addition elevated soil organic carbon content, increased soil porosity, and improved water retention capacity, indicating the positive effects on soil structure and functions. Advanced mineral identification and characterization systems showed that Sb/As usually occurred in Fe-bearing minerals and stabilized by surface complexation and co-precipitation. The findings demonstrated that 1 % (w/w) Fe@H2O2-BC was appropriate to Sb/As stabilization and soil function recovery following field conditions, which provided potential application for ecological restoration in Sb smelting sites.

Root architectures differentiate the composition of organic carbon in bauxite residue during natural vegetation.

Understanding plant root architectures induced changes in organic carbon accumulation and conversion is critical to predicting carbon cycling and screening appropriate plant species for ecological restoration on bauxite residue disposal areas. According to the ecological investigation of a weathered bauxite residue disposal area, three plants with different root architectures including Artemisia lavandulaefolia (A. lavandulaefolia), moss, and Zanthoxylum simulans (Z. simulans) were selected to investigate the rhizosphere effects on the composition and structure of organic carbon in bauxite residue. The physic-chemical properties, the contents and structure of different organic carbon fractions, and microbial communities of bauxite residue from rhizosphere and non-rhizosphere were analyzed. Plant growth decreased the saline-alkalinity, increased the contents of total organic carbon, particulate organic carbon and dissolved organic carbon, whilst enhancing the enzymatic activities of bauxite residue. Meanwhile, the rhizosphere effects had significant effects on the accumulation and stabilization of organic carbon in bauxite residue. A. lavandulaefolia had the strongest rhizosphere effects on the composition and structure of total organic carbon and dissolved organic carbon, whilst moss was more effective on the accumulation of particulate organic carbon in bauxite residue. Plant growth and root architecture changed the abundance of specific functional microorganisms and the complexity of microbial co-occurrence networks, thus elevating organic carbon levels in bauxite residue. During natural vegetation encroachment, rhizosphere exciting effects of the salt-tolerated plants could change the composition and structure of organic carbon fractions due to the comprehensive effectiveness of the improvement of physic-chemical properties and microbial communities. The findings improve our understanding of the responses of sequestration and stabilization of organic carbon pools to ecological restoration on bauxite residue disposal areas.

Overexpression of miR-1225 promotes the progression of breast cancer, resulting in poor prognosis.

Breast cancer is the most common cancer among women, with metastasis as the principal cause of mortality. MiR-1225 has been reported to play roles in the progression of various cancers, but its role in breast cancer was unclear. The expression of miR-1225 was investigated in breast cancer tissues and cells by quantitative real-time PCR. The role of miR-1225 in the cell process of OS was analyzed by CCK-8 assay and Transwell assay. The prognostic value of miR-1225 was evaluated by Kaplan-Meier survival curves and Cox regression analysis. miR-1225 was significantly upregulated in breast cancer tissues, which was associated with the TNM stage of breast cancer patients. The prognosis of patients with high miR-1225 expression was worse than that of patients with low miR-1225 expression, which indicated that miR-1225 acted as an independent factor for the prognosis of breast cancer. Additionally, the upregulation of miR-1225 promoted cell proliferation, migration, and invasion of breast cancer, which suggested miR-1225 might be involved in the progression of breast cancer. JAK1 was identified as the direct target of miR-1225, which was also involved in cell proliferation, migration, and invasion of breast cancer. The overexpression of miR-1225 in breast cancer indicates a poor prognosis of patients and promotes the progression of breast cancer by targeting JAK1. miR-1225 may be a biomarker and therapeutic target for the treatment of breast cancer.

Ultrasound-targeted microbubble destruction-mediated miR-767 inhibition suppresses tumor progression of non-small cell lung cancer.

MicroRNAs (miRNAs/miRs) have important roles in tumor progression in various human cancers. Ultrasound-targeted microbubble destruction (UTMD)-mediated gene transfection has been considered a useful tool for improving cancer treatment. The present study aimed to investigate the role of miR-767 in non-small cell lung cancer (NSCLC) and further analyze the effects of UTMD-mediated miR-767 inhibition on tumor progression. The expression of miR-767 was measured by reverse transcription-quantitative PCR. UTMD-mediated miR-767 inhibition was achieved by the co-transfection of microbubbles and miR-767 inhibitor in NSCLC cells. Cell proliferation was assessed by a CCK-8 assay and cell migration and invasion were examined by a Transwell assay. The expression of miR-767 was increased in NSCLC serum, tissues and cells compared with controls. The reduction of miR-767 in NSCLC cells led to the inhibition of cell proliferation, migration and invasion. UTMD increased the transfection efficiency of the miR-767 inhibitor in NSCLC cells, and UTMD-mediated miR-767 inhibition resulted in a more significant suppressive effect on tumor cell proliferation, migration and invasion. Taken together, the results indicated that miR-767 expression is upregulated in both NSCLC clinical samples and cells. The downregulation of miR-767 can inhibit tumor cell proliferation, migration and invasion, and these effects are further promoted by UTMD-mediated miR-767 inhibition, which indicated the potential of a UTMD-mediated miR-767 inhibition as a novel therapeutic strategy for NSCLC treatment.

Assessment of Deep Brain Stimulation Implantation Surgery: A Practical Scale.

BACKGROUND: Patients requiring deep brain stimulation (DBS) will undergo extensive preoperative and postoperative evaluations. However, the field lacks a robust scoring system for quantifying the outcomes of DBS surgery. We sought to determine whether a practical scale could assess the outcomes of DBS surgery and the clinical significance. METHODS: A retrospective study was performed of the data from 150 patients who had undergone DBS from February 2017 to February 2019. An independence analysis and multivariate testing were used to identify significant independent predictors. The scale scores were computed by summing across the weighted predictors. The correlation between the scale scores and the intraoperative electrophysiological signal length (IESL), DBS power-on voltage, improvement rate in the unified Parkinson disease rating scale (UPDRS) and UPDRS part III (UPDRS III) scores was analyzed. Receiver operating characteristics curve analysis was used to quantify the discriminative capacity of the scale for predicting the prognosis. RESULTS: Listwise exclusion of patients with incomplete data sets yielded a final sample of 130 patients with Parkinson disease who had undergone bilateral DBS. Multivariate testing identified 3 independent predictors of the prognosis, including electrode implantation duration, postoperative pneumocephalus volume, and electrode fusion error. The scale scores correlated significantly with the subthalamic nucleus DBS power-on voltage (r = -0.4063; P < 0.0001), globus pallidus internus DBS power-on voltage (r = -0.4723; P = 0.0014), and improvement rate of the UPDRS (r = 0.3490; P < 0.0001) and UPDRS III (r = 0.6623; P < 0.0001) scores. However, the scale scores did not significantly correlate with the subthalamic nucleus IESL and globus pallidus internus IESL. Receiver operating characteristics curve analysis revealed impressive outcome discrimination for the UPDRS and UPDRS III scores (UPDRS: area under the curve, 0.62, P = 0.0219; UPDRS III: area under the curve, 0.85, P < 0.0001). CONCLUSIONS: We have introduced a novel practical scale capable of assessing the outcomes of DBS surgery and predicting the prognosis of patients after DBS surgery.

Comparison of Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation Surgery on Parkinson Disease-Related Pain.

OBJECTIVE: To analyze and compare the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) and globus pallidus internus (GPi)-DBS on Parkinson disease (PD)-related pain. METHODS: A retrospective study was performed of 64 patients (28 who underwent GPi-DBS and 36 who underwent STN-DBS) with PD-related pain in our hospital between January 2017 and July 2019. A numerical rating scale (NRS) was used to evaluate the degree of pain preoperatively and 4 months after operation, and the unified PD scale III (UPDRS-III) was completed simultaneously to assess motor symptoms. RESULTS: The average NRS score of all 64 patients after surgery was 1.09 ± 1.39, which was significantly lower than that before operation (4.44 ± 1.67; P < 0.0001). The improvement rate of NRS was 75 ± 27% in the 28 GPi-DBS patients and 79 ± 27% in the 36 STN-DBS patients, with no significant difference (P = 0.577). The improvements in NRS and UPDRS-III were significantly correlated in the STN-DBS group (r = 0.3707, P = 0.026) but not significantly correlated in the GPi-DBS group (P = 0.516). CONCLUSIONS: Both GPi-DBS and STN-DBS were effective for analyzing PD-related pain and seemed to have similar efficacy. This study provides an important first-step toward determining different DBS targets for controlling PD-related pain. Follow-up prospective research is an appropriate next step on the path to multicenter clinical trials.

Efficacy Analysis of Robot-Assisted Minimally Invasive Surgery for Small-Volume Spontaneous Thalamic Hemorrhage.

OBJECTIVE: To test whether robot-assisted surgery can improve prognosis of small-volume thalamic hemorrhage and to provide a surgical basis for treatment of small-volume thalamic hemorrhage. METHODS: This retrospective study included patients with thalamic hemorrhage and hematoma volume of 5-15 mL treated from December 2015 to December 2018. Patients were divided into an operation group and a nonoperation group. General data, types of hematoma, incidence of complications, Scandinavian Stroke Scale score, and modified Rankin Scale score were recorded and analyzed. RESULTS: Retrospectively, 84 cases met inclusion criteria: 35 cases in operation group and 49 cases in nonoperation group. At 90 days after onset, mortality was 11.4% in the operation group and 4.1% in the nonoperation group (P > 0.05). The Scandinavian Stroke Scale score in the operation group (43.3 ± 8.5) was higher than in the nonoperation group (36.1 ± 10.0) (P < 0.05). The modified Rankin Scale score in the operation group (2.9 ± 0.3) was lower than in the nonoperation group (3.7 ± 0.2) (P < 0.05). The incidence of pneumonia (8.6%) and renal dysfunction (14.3%) was lower in the operation group than in the nonoperation group (28.6% and 34.7%, respectively) (P < 0.05). There was no significant difference between the 2 groups in the incidence of central fever (5.7% vs. 12.2%), stress ulcer (11.4% vs. 16.3%), and ion balance disturbance (20.0% vs. 26.5%) (P > 0.05). CONCLUSIONS: Robot-assisted drainage of thalamic hemorrhage can improve prognosis and reduce the incidence of pneumonia and renal dysfunction.

MiR-509-5p improves the proliferative and invasive abilities of papillary thyroid carcinoma cells by inhibiting SFRP1.

INTRODUCTION: Our study was conducted to prove that miR-509-5p improved the proliferative and invasive abilities of papillary thyroid carcinoma (PTC) cells through inhibiting SFRP1 expression. MATERIAL AND METHODS: QRT-PCR was conducted in order to detect the miR-509-5p expression levels in PTC and normal tissues. The miR-509-5p and SFRP1 mRNA expression levels in PTC cell lines K1, TPC-1, BCPAP and the human normal thyroid cell line HT-ori3 were also detected by qRT-PCR. The transfection was performed using Lipofectamine and lentiviral vectors. Pgcsil-008 was used as the SFRP1 gene vector. Western blot and dual luciferase reporter gene assay were conducted to investigate miR-509-5p's direct regulation on SFRP1. MTT, clone formation, and Transwell assays were adopted to investigate the biological behaviors of PTC cells. TCF/LEF luciferase assays were used to prove that miR-509-5p influenced the Wnt/ß-catenin signaling pathway by regulating SFRP1. RESULTS: MiR-509-5p was overexpressed in PTC cells and tissues in which SFRP1 was down-regulated. MiR-509-5p bound to the 3'-UTR of SFRP1 and therefore partially weakened the proliferative, migrating and invasive activities of PTC cells. MiR-509-5p promoted activation of the Wnt/ß-catenin signaling pathway through down-regulating SFRP1. CONCLUSIONS: MiR-509-5p improved the proliferative, migrating and invasive abilities of PTC cells through inhibiting SFRP1 expression.

Improved accuracy using a modified registration method of ROSA in deep brain stimulation surgery.

OBJECTIVE The aim of this study was to determine whether a modified registration method could reduce registration error and postoperative electrode vector error and to analyze the method's clinical significance in deep brain stimulation (DBS) surgery. METHODS The first part of the study involved a skull model, in which three registration methods were tested using the ROSA (robotic stereotactic assistance) system. In the second part, four registration methods were clinically tested in patients undergoing DBS surgery using the ROSA system. Thirty-three patients (65 sides, group I) underwent the conventional registration method 2E, and registration errors were recorded. Thirty-eight patients (75 sides, group II) underwent four types of modified registration methods including 2A, 2B, 2C, and 2D. Registration and electrode vector errors, intraoperative electrophysiological signal length (IESL), and DBS power-on voltage were recorded. The primary measure of efficacy was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) and UPDRS Part III scores from baseline to 10 weeks after surgery. RESULTS In the skull model, the registration error (mean ± SD) was 0.56 ± 0.11 mm for method 1A, 0.35 ± 0.11 mm for method 1B (vs. 1A, p < 0.001), and 0.90 ± 0.15 mm for method 1C (vs. 1A, p < 0.001). In the clinical study, method 2C was selected for DBS surgery in group II since it had the smallest registration error among the four methods tested. The registration error was 0.62 ± 0.22 mm (mean ± SD) for group I and 0.27 ± 0.07 mm for group II (p < 0.001). Postoperative electrode vector error was 0.97 ± 0.31 mm for group I and 0.65 ± 0.23 mm for group II (p < 0.001). There was a positive correlation between registration error and electrode vector error in both groups (group I: r = 0.69, p < 0.001; group II: r = 0.71, p < 0.001). The mean IESL was 5.0 ± 0.9 mm in group I and 5.8 ± 0.7 mm in group II (p < 0.001). The mean DBS power-on voltage was 1.63 ± 0.44 V in group I and 1.48 ± 0.38 V in group II (p = 0.027). In the UPDRS score, group I showed 50% ± 16% improvement and group II showed 52% ± 18% improvement (p = 0.724); there was no statistically significant difference in improvement on the UPDRS. CONCLUSIONS In DBS surgery assisted by the ROSA system, registration error and electrode vector error showed a positive correlation. The modified registration method could reduce the registration error and electrode vector error, but the long-term effects need to be further observed and evaluated.

Colorimetric aptasensing of ochratoxin A using Au@Fe3O4 nanoparticles as signal indicator and magnetic separator.

Gold nanoparticles (Au NPs) doped Fe3O4 (Au@Fe3O4) NPs have been synthesized by a facile one-step solvothermal method. The peroxidase-like activity of Au@Fe3O4 NPs was effectively enhanced due to the synergistic effect between the Fe3O4 NPs and Au NPs. On this basis, an efficient colorimetric aptasensor has been developed using the intrinsic dual functionality of the Au@Fe3O4 NPs as signal indicator and magnetic separator. Initially, the amino-modified aptamer specific for a typical mycotoxin, ochratoxin A (OTA), was surface confined on the amino-terminated glass beads surafce using glutaraldehyde as a linker. Subsequently, the amino-modified capture DNA (cDNA) was labeled with the amino-functionalized Au@Fe3O4 NPs and the aptasensor was thus fabricated through the hybridization reaction between cDNA and the aptamers. While upon OTA addition, aptamers preferred to form the OTA-aptamer complex and the Au@Fe3O4 NPs linked on the cDNA were released into the bulk solution. Through a simple magnetic separation, the collected Au@Fe3O4 NPs can produce a blue colored solution in the presence of 3,3',5,5'-tetramethylbenzidine and H2O2. When the reaction was terminated by addition of H(+) ions, the blue product could be changed into a yellow one with higher absorption intensity. This colorimetric aptasensor can detect as low as 30 pgmL(-1) OTA with high specificity. To the best of our knowledge, the present colorimetric aptasensor is the first attempt to use the peroxidase-like activity of nanomaterial for OTA detection, which may provide an acttractive path toward routine quality control of food safety.

Safflower Yellow regulates microglial polarization and inhibits inflammatory response in LPS-stimulated Bv2 cells.

Activated microglia, especially polarized M1 cells, produce pro-inflammatory cytokines and free radicals, thereby contributing directly to neuroinflammation and various brain disorders. Given that excessive or chronic neuroinflammation within the central nervous system (CNS) exacerbates neuronal damage, molecules that modulate neuroinflammation are candidates as neuroprotective agents. In this study, we provide evidence that Safflor yellow (SY), the main active component in the traditional Chinese medicine safflower, modulates inflammatory responses by acting directly on BV2 microglia. LPS stimulated BV2 cells to upregulate expression of TLR4-Myd88 and MAPK-NF-κB signaling pathways and to release IL-1ß, IL-6, TNF-α, and COX-2. However, SY treatment inhibited expression of TLR4-Myd88 and p-38/p-JNK-NF-κB, downregulated expression of iNOS, CD16/32, and IL-12, and upregulated CD206 and IL-10. In conclusion, our results demonstrate that SY exerts an anti-inflammatory effect on BV2 microglia, possibly through TLR-4/p-38/p-JNK/NF-κB signaling pathways and the conversion of microglia from inflammatory M1 to an anti-inflammatory M2 phenotype.

A distinct three-helix centipede toxin SSD609 inhibits I(ks) channels by interacting with the KCNE1 auxiliary subunit.

KCNE1 is a single-span transmembrane auxiliary protein that modulates the voltage-gated potassium channel KCNQ1. The KCNQ1/KCNE1 complex in cardiomyocytes exhibited slow activated potassium (I(ks)) currents. Recently, a novel 47-residue polypeptide toxin SSD609 was purified from Scolopendra subspinipes dehaani venom and showed I(ks) current inhibition. Here, chemically synthesized SSD609 was shown to exert I(ks) inhibition in extracted guinea pig cardiomyocytes and KCNQ1/KCNE1 current attenuation in CHO cells. The K(+) current attenuation of SSD609 showed decent selectivity among different auxiliary subunits. Solution nuclear magnetic resonance analysis of SSD609 revealed a distinctive three-helix conformation that was stabilized by a new disulfide bonding pattern as well as segregated surface charge distribution. Structure-activity studies demonstrated that negatively charged Glu19 in the amphipathic extracellular helix of KCNE1 was the key residue that interacted with SSD609. The distinctive three-helix centipede toxin SSD609 is known to be the first polypeptide toxin acting on channel auxiliary subunit KCNE1, which suggests a new type of pharmacological regulation for ion channels in cardiomyocytes.

The expression patterns of tight junction protein claudin-1, -3, and -4 in human gastric neoplasms and adjacent non-neoplastic tissues.

Recently, there is growing evidence that tight junction proteins are often abnormally regulated in human tumors. The function of tight junction proteins in the maintenance of normal epithelial physiology has been well discussed, but their role in the tumorigenesis of gastric cancer is less well defined. To explore the expression distinction of the tight junction proteins claudin-1, -3, and -4 expression in the gastric cancer, the expression of claudin-1, -3, and -4 in 92 gastric cancer tissues and the non-neoplastic tissues adjacent to the tumors were examined by immunohistochemistry. Compared with adjacent non-neoplastic tissues, the expression of claudin-1 was down regulated. However, the expression of claudin-3 and claudin-4 were up-regulated in gastric cancer tissue. In addition, the expression of claudin-3 is correlated with claudin-4 expression in gastric cancer. Our present study reveals that claudin-1, -3, and -4 protein expression altered between human gastric cancers and adjacent non-neoplastic tissues.

Combination of miR-21 with Circulating Tumor Cells Markers Improve Diagnostic Specificity of Metastatic Breast Cancer.

Circulating miR-21 is upregulated in breast cancer. However, correlation of miR-21 expression with clinic pathologic characteristics remains questionable. In this study, we investigate whether combination of circulation miR-21 with circulating tumor cells (CTCs) marker (EpCAM, MUS1, HER2) could improve diagnostic specificity of metastatic breast cancer. Total 223 breast cancer patients were included. 89 % patients were associated with upregulation of miR-21 compared with health control. 20 % patients were detected for CTCs marker positive. For higher specificity purpose, triple marker positive samples were selected as true CTCs positive, which only occupied 59.5 % of total metastatic breast cancer patients. Specificity of detection of CTCs was 96.7 %. Furthermore, 59.5 % metastatic breast cancer patients were shown both abnormal miR-21 and true CTCs positive according to distribution of true CTCs positive and abnormal miR-21; Combination of miR-21 and CTCs was increased specificity of metastatic detection to 100 %. Our findings suggested that combination of miR-21 with CTCs marker could be used for better diagnosis of metastatic breast cancer in the future.

The therapeutic potential of Rho kinase inhibitor fasudil derivative FaD-1 in experimental autoimmune encephalomyelitis.

Although therapeutic potential of fasudil in EAE is promising, action mechanism and clinical limitations are still not fully understood and resolved. In this study, we observed the therapeutic potential of a novel Rho kinase (ROCK) inhibitor FaD-1, a fasudil derivative, and explored possible mechanism in MOG35-55-induced EAE. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG35-55) immunization. The pathology of spinal cord was measured by immunohistochemistry and neurological impairment was evaluated using clinical scores. FaD-1, as a novel ROCK inhibitor, inhibited the expression of ROCK II that is mainly expressed in the CNS. We show here that FaD-1 ameliorates the neurological defects and the severity of MOG-induced EAE in mice, accompanied by the protection of demyelination and the inhibition of neuroinflammation in spinal cord of EAE. In addition, FaD-1 dampened TLR2 and TLR4 signaling as well as Th1 (IFN-γ) and Th17 (IL-17) responses in spinal cord of EAE. FaD-1 also prevented the expression of iNOS and production of inflammatory cytokine IL-1ß, IL-6, and TNF-α which are specific markers for M1 inflammatory microglia/macrophages. This study highlights the therapeutic potential of FaD-1 as a ROCK inhibitor for the treatment of human autoimmune diseases with both inflammatory and autoimmune components.

Metformin inhibits angiogenesis induced by interaction of hepatocellular carcinoma with hepatic stellate cells.

Accumulated evidences indicate metformin is associated with reduced risk of hepatocellular carcinoma (HCC) in diabetic patients, which inspired researchers to explore its therapeutic potentials in HCC. Since Hepatic stellate cells (HSCs) are believed to be the key contributors to tumor microenvironment in HCC and promotes tumor development, here, we explored the effect of metformin on tumor angiogenesis induced by interplay of HCC and HSCs. Our results showed that conditional medium from co-culture of HCC/HSCs induced VEGF secretions and stimulated human umbilical vein endothelial cells (HUVEC) tube formation. However, 25 µM metformin could inhibit this angiogenesis effect. Furthermore, knockdown AMPK of HSCs, not HCC, could abolish inhibition caused by metformin. Our finding suggested that metformin could inhibit HCC angiogenesis through targeting on HSCs through AMPK pathway.

A facile label-free colorimetric aptasensor for acetamiprid based on the peroxidase-like activity of hemin-functionalized reduced graphene oxide.

A facile aptasensor has been developed for the colorimetric detection of acetamiprid by using the hemin-functionalized reduced graphene oxide (hemin-rGO) composites. The as-prepared hemin-rGO composites possessed both the ability of rGO to physically adsorb the aptamers and the peroxidase-like activity of hemin that could catalyse 3,3,5,5-tetramethylbenzidine (TMB) in the presence of H2O2, to produce a solution with blue color. The well-dispersed hemin-rGO composites coagulated completely at the proper salt concentration; however, the coagulation of hemin-rGO was vanished when abundant aptamers were adsorbed on its surface because the attached negatively charged DNA backbone increased individual hemin-rGO electrostatic repulsion. In the detection scheme, acetamiprid with different concentrations was firstly incubated with the same amount of aptamer. The more acetamiprid in the tested solution, the less free aptamers were absorbed on the hemin-rGO surface, making the composites coagulate to a higher degree in the presence of the optimum NaCl concentration. As a consequence, the content of hemin-rGO in the supernatant was decreased after centrifugation, which catalysed oxidation of TMB in the presence of H2O2 to produce light blue color with a low absorbance. The color variation relavant to the acetamiprid concentration can be judged by the naked eyes and easily monitored by the inexpensive UV-vis spectrometer. Such designed aptasensor displayed a linear response for acetamiprid in the range from 100nM to 10µM with a detection limit of 40nM (S/N=3). This colorimetric aptasensing platform offers great advantages including the simple operation process, low-cost portable instrument, and user-friendly applications.

Multiwalled carbon nanotube@reduced graphene oxide nanoribbon heterostructure: synthesis, intrinsic peroxidase-like catalytic activity, and its application in colorimetric biosensing.

In this study, multiwalled carbon nanotube@reduced graphene oxide nanoribbon (MWCNT@rGONR) core-shell heterostructures have been synthesized by the facile unzipping of MWCNTs and subsequent chemical reduction with hydrazine. MWCNTs with diameter <10 nm were selected as the starting material to maintain narrow ribbons <30 nm wide with a few-layer structure. The most important discovery is that the resulting MWCNT@rGONR heterostructures possess intrinsic peroxidase-like activity, 15.9 times higher than that of MWCNTs and 8.4 times higher than that of their unreduced form. The nature of the peroxidase-like activity of the MWCNT@rGONR heterostructures can be attributed to the acceleration of their electron-transfer process and the consequent facilitation of ˙OH radical generation. Kinetic analysis demonstrates that the catalytic behavior is in accordance with typical Michaelis-Menten kinetics and the obtained kinetic parameters indicate that the MWCNT@rGONR heterostructures display a higher affinity for both H2O2 and 3,3,5,5-tetramethylbenzidine than that of horseradish peroxidase. On this basis, we have employed the MWCNT@rGONR heterostructures as novel biosensing platforms to develop a simple, sensitive, and selective colorimetric biosensor for free cholesterol determination. This work will facilitate the formation of MWCNT@rGONR heterostructures with narrow ribbons and the utilization of their intrinsic peroxidase-like activity in biotechnology and medical diagnostics.

Highly sensitive impedimetric aptasensor based on covalent binding of gold nanoparticles on reduced graphene oxide with good dispersity and high density.

A series of gold nanoparticles (AuNPs) that were covalently bound to 2-aminothiophenol-functionalized reduced graphene oxide (Au-ATP-rGO) composites have been synthesized with well-dispersed and controllable surface coverage of AuNPs. Aptamer immobilization capacity studies demonstrated that the surface density of AuNPs played a key role in increasing the amount of anchoring aptamers to enhance the sensitivity of affinity based detection. With the composites possessing dense surface coverage of AuNPs as a versatile signal amplified platform, a label-free aptasensor for the sensitive and selective detection of small molecules (ochratoxin A in this case) has been developed using electrochemical impedance spectroscopy (EIS). A wide linear range of 0.1-200 ng mL(-1) was obtained with a low detection limit of 0.03 ng mL(-1) (S/N = 3). This work provides a universal strategy for the sensitive detection of a variety of targets in a truly label-free manner by means of changing the corresponding aptamer. The promising platform based on the combination of Au-ATP-rGO composites, EIS technique, and aptamers would have great potential applications in clinical diagnosis, environmental analysis, and food safety monitoring.