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The MnO2-based aqueous Zn cell can meet the requirements of safety, flexibility, and low cost for portable/wearable electronics; however, its low intrinsic conductivity, weak kinetics, and poor high-loading capacity restrict its practical performance. In this study, the synergistic architecture of MoS2-loaded, oxygen-defect-rich MnO2-x nanocrystals with a carbon coating (M-PM2-x-H2 aerogel) was prepared. As corevealed by various characterizations, this synergistic design not only improves the electronic/ionic conductivity but also motivates the conversion kinetics of the surficial electrochemical reaction. As a result, the M-PM2-x-H2 cathode delivers a much improved capacity of 567 mA h·g-1 at 0.1 A·g-1 and shows a high capacity retention of 176% after 150 cycles at 0.5 A·g-1. More impressively, the high areal loading (3.97 mg·cm-1) of the M-PM2-x-H2 electrode also displays a high capacity of 367 mA h·g-1 at 0.1 A·g-1. In addition, the derived all-solid-state cell exhibits excellent flexibility and safety under the conditions of weight loading, cutting, and bending.

Radioactive iodine, one type of nuclear waste, is harmful to the environment and human health due to its long half-life and volatility. Therefore, designing and synthesizing low-cost and easily-made materials for the effective adsorption of radioiodine is widely concerned. Herein, a biscuit-shaped new material was synthesized by a grinding-mixing coupled with sonication protocol through self-assembly interactions between citrazinic acid (CA) and cytosine (CY) aiming to achieve the iodine capture from both vapor and solution. Electronic structure calculations were used to reveal the adsorption mechanism. The results showed that the high uptake of iodine by CACY originates from the charge transfer via CACY to the antibonding molecular orbital (σ∗) of I2. Meanwhile, trouble-free entry pore sizes of CACY also contribute to the physisorption of molecular iodine. Besides, the iodine molecule is preferentially perpendicularly adsorbed on the carbon atom of the CA ring. Moreover, CACY exhibits a high capture for iodine in hexane following pseudo-second-order kinetics and fitting the Langmuir isotherm model. This work presents a facile and inexpensive synthesis approach for radioiodine adsorption materials and provides new insights into the interaction mechanism between the self-assembled materials and the adsorbates.

Jingzhaotoxin-I, -III, -IV, -XIII, and −35 (JZTX-I, -III, -IV, -XIII, and −35), gating modifier toxins isolated from the venom of the Chinese tarantula Chilobrachys Jingzhao, were reported to act on cardiac sodium channels and Kv channels. JZTX-I and JZTX-XIII inhibited the hERG channel with the IC50 value of 626.9 nM and 612.6 nM, respectively. JZTX-III, -IV, and −35 share high sequence similarity with JZTX-I and JZTX–XIII, but they showed much lower affinity on the hERG channel compared with JZTX-I and JZTX-XIII. The inhibitory potency of the above five toxins on the hERG channel was not in accordance with their affinity on the Nav1.5 and Kv2.1 channels, indicating that the bioactive surfaces of the five toxins interacting with hERG, Nav1.5 and Kv2.1 are at least in part different. Structure-function analysis of the gating modifier toxins suggested that the functional bioactive surface binding to the hERG channel consists of a conserved hydrophobic patch, surrounding acidic residues (Glu10 in JZTX-XIII, Glu11 in JZTX-I), and basic residues which may be different from residues binding to the Kv2.1 channel.

The memristor has been regarded as a promising candidate for constructing a neuromorphic computing platform that is capable of confronting the bottleneck of the traditional von Neumann architecture. Here, inspired by the working mechanism of the G-protein-linked receptor of biological cells, a novel double-layer memristive device with reduced graphene oxide (rGO) nanosheets covered by chitosan (an ionic conductive polymer) as the channel material is constructed. The protons in chitosan and the functional groups in rGO nanosheets imitate the functions of the ligands and receptors of biological cells, respectively. Smooth changes in the response current depending on the historical applied voltages are observed, offering a promising pathway toward biorealistic synaptic emulation. The memristive behavior is mainly a result of the interaction between protons provided by chitosan and the defects and functional groups in the rGO nanosheets. The channel current is due to the hopping of protons through functional groups and is limited by the traps in the rGO nanosheets. The transition from short-term to long-term potentiation is achieved, and learning-forgetting behaviors of the memristor mimicking those of the human brain are demonstrated. Overall, the bioinspired memristor-type artificial synaptic device shows great potential in neuromorphic networks.

Objective Electroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients. Methods A total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted. Results SOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05). Conclusions Our study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD.

Jiayi Li, 1,* Qiao Chen, 1,* Bao Jin, 1 Yue Shi, 1 Xiangan Wu, 1 Haifeng Xu, 1 Yongchang Zheng, 1 Yingyi Wang, 2 Shunda Du, 1 Xin Lu, 1 Yilei Mao, 1 Xinting Sang 1 1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of China; 2Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shunda DuDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1# Shuai-Fu-Yuan, Wang-Fu-Jing, Beijing 100730, People’s Republic of ChinaTel +86-139 1183 2900Fax +86-10-69156043Email dushd@pumch.cnPurpose: The aims of our study were to investigate the prognostic impact of the rate of preoperative serum carbohydrate antigen 19-9/bilirubin (CA19-9/BR) on patients with extrahepatic bile duct cancer.Patients and Methods: We collected clinical data from 89 patients who underwent surgery for extrahepatic cholangiocarcinoma (ECC) at Peking Union Medical College Hospital between January 2012 and December 2017. The Kaplan–Meier analysis for univariate analysis and the Cox proportional hazards models for multivariate analysis were used to determine possible independent prognostic factors.Results: CA19-9/BR was classified as elevated compared with normal based on the upper serum normal values of CA19-9 (37 U/mL) and bilirubin (1.5 mg/dL), which gives a cut-off at 25 U/mL/mg/dL. Univariate analysis showed that the overall survival of patients with a high CA19-9/BR ratio was significantly worse compared with patients with a low CA19-9/BR ratio (Hazard Ratio [HR] 2.149; 95% Confidence Interval [95% CI] 1.027– 4.495; P=0.042). Multivariate analysis revealed that a high CA19-9/BR ratio (HR 3.250; 95% CI 1.165– 9.067; P=0.024), low differentiation (HR 3.551; 95% CI 1.231– 10.244; P=0.019), and positive margin (HR 2.555; 95% CI 1.111– 5.875; P=0.027) remained independent prognostic factors after adjusting for age at diagnosis, maximal diameters, and other possible factors.Conclusion: The preoperative CA19-9/BR ratio is a good prognostic factor in predicting survival in ECC patients and closer follow-up is recommended in patients with a higher CA19-9/BR ratio before surgery.Keywords: prognosis, preoperative bilirubin-adjusted carbohydrate antigen 19-9, extrahepatic cholangiocarcinoma

Background Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two key protein-bound uremic toxins that accumulate in patients with end-stage renal disease. IS and pCS cannot be efficiently removed by conventional hemodialysis because they are highly bound to proteins. One promising means to optimize the removal of protein-bound uremic toxins involves using binding competitors to liberate uremic toxins from protein-binding partners. Purpose In this study, we try to identify potential binding competitors that can enhance the dialysis removal of IS and pCS in natural compounds of phytomedicine. Methods We employed microdialysis to evaluate whether Danhong injection (DHI) and its salvianolic acids can increase the free fractions of IS and pCS and thus improve their dialysis efficiency in vitro. Furthermore, we confirmed the positive effects of DHI and salvianolic acids in vivo on chronic kidney disease model rats in which IS and pCS had heavily accumulated. Results DHI significantly increased the dialysis efficiency of IS and pCS by 99.13% and 142.00% in vitro (10-fold dilution), respectively, and by 135.61% and 272.13% in vivo (4.16 ml/kg). Salvianolic acids including lithospermic acid (LA), salvianolic acid A (SaA), tanshinol (DSS), caffeic acid (CA), salvianolic acid B (SaB), protocatechuic aldehyde (PA) and rosmarinic acid (RA) significantly enhanced the dialysis removal of IS and pCS in a concentration-dependent manner. LA, the best competitor of the tested salvianolic acids, increased dialysis efficiency levels of IS and pCS by 197.23% and 198.31% in vitro (400 μM), respectively, and by 119.55% and 127.56% in vivo (24.69 mg/kg). Conclusion The removal of protein-bound uremic toxins IS and pCS using DHI or salvianolic acids as protein-bound competitors is superior to previously reported strategies and drugs and may contribute to clinical hemodialysis therapeutic practice.

This study reported a novel humidity-insensitive nitrogen dioxide (NO2) gas sensor based on tin dioxide (SnO2)/reduced graphene oxide (rGO) composites through the sol-gel method. The sensor demonstrated ppb-level NO2 detection in p-type sensing behaviors (13.6% response to 750 ppb). Because of the synergistic effect on SnO2/rGO p-n heterojunction, the sensing performance was greatly enhanced compared to that of bare rGO. The limit of detection of sensors was as low as 6.7 ppb under dry air. Moreover, benefited from the formed superhydrophobic structure of the SnO2/rGO composites (contact angle: 149.0°), the humidity showed a negligible influence on the dynamic response (Sg) of the sensor to different concentration of NO2 when increasing the relative humidity (RH) from 0 to 70% at 116°C. The relative conductivity of the sensor to 83% relative humidity was 0.11%. In addition, the response ratio (Sg/SRH) between 750 ppb NO2 and 83% RH was 649.0, indicating the negligible impaction of high-level ambient humidity on the sensor. The as-fabricated humidity-insensitive gas sensor can promise NO2 detection in real-world applications such as safety alarm, chemical engineering, and so on.

Designing of fast, inexpensive and sensitive furfural determination methods for dairy milk is crucial in analytical and food chemistry. In this study, an electrochemical sensor was developed for the cathodic determination of furfural using a one-step electrochemically reduced graphene oxide (ErGO) modified glassy carbon electrode (GCE). The morphology and chemical constituents of the obtained ErGO/GCE were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman and X-ray photoelectron spectroscopy (XPS). The results showed that the fast and green electrochemical reduction process effectively eliminated the oxygen-containing groups in GO and produced reduced graphene with a high surface area and improved electron transfer kinetics. In addition, the ErGO based sensor displayed excellent responses for furfural in a Na2HPO4-NaH2PO4 solution (pH = 9.18) with a wide linear range from 2 to 2015 μM and a low detection limit of 0.4 μM (S/N = 3). The reduction mechanism of furfural was also discussed. Furthermore, the feasibility of the sensor was confirmed by the determination of furfural in three milk samples which generated acceptable outputs.

Uremic toxins are a class of toxins that accumulate in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS), a typical uremic toxin, is not efficiently removed by hemodialysis. Modulation of IS production in the gut microbiota may be a promising strategy for decreasing IS concentration, thus, delaying CKD progression. In the present study, we identified isoquercitrin (ISO) as a natural product that can perturb microbiota-mediated indole production without directly inhibiting the growth of microbes or the indole-synthesizing enzyme TnaA. ISO inhibits the establishment of H proton potential by regulating the gut bacteria electron transport chain, thereby inhibiting the transport of tryptophan and further reducing indole biosynthesis. This non-microbiocidal mechanism may enable ISO to be used as a therapeutic tool, specifically against pathologies triggered by the accumulation of the microbial-produced toxin IS, as in CKD. Herein, we have shown that it is possible to inhibit gut microbial indole production using natural components. Therefore, targeting the uremic toxin metabolic pathway in gut bacteria may be a promising strategy to control host uremic toxin production., Graphical abstract

Flammulina velutipes polysaccharides (FVP) can improve gut health through gut microbiota and metabolism regulation. In this study, the 28-days fed experiment was used to investigate gut microbime and metabolic profiling induced by FVP. After treatment, intestinal tissue section showed the higher villus height and villus height/crypt depth (V/C) value in FVP-treated group. The 16 s rRNA gene sequencing revealed microbiota composition alteration caused by FVP, as the Firmicutes phylum increased while Bacteroidetes phylum slightly decreased. The metabolic profiling was detected by LC/MS and results showed 56 and 99 compounds were dramatically changed after FVP treatment in positive and negative ion mode, respectively. Annotation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways displayed the adjustment of energy metabolism, amino acid metabolism, nucleotide metabolism and other related basic pathways after FVP treatment. Our study suggested that FVP can be developed as a dietary supplement for intestine health promotion.

Background Our previous studies have indicated that miR-198 reduces cellular methylguanine DNA methyltransferase (MGMT) levels to enhance temozolomide sensitivity. Transforming growth factor beta 1 (TGF-β1) switches off miR-198 expression by repressing K-homology splicing regulatory protein (KSRP) expression in epidermal keratinocytes. However, the underlying role of TGF-β1 in temozolomide resistance has remained unknown. Methods The distribution of KSRP was detected by western blotting and immunofluorescence. Microarray analysis was used to compare the levels of long noncoding RNAs (lncRNAs) between TGF-β1–treated and untreated cells. RNA immunoprecipitation was performed to verify the relationship between RNAs and KSRP. Flow cytometry and orthotopic and subcutaneous xenograft tumor models were used to determine the function of TGF-β1 in temozolomide resistance. Results Overexpression of TGF-β1 contributed to temozolomide resistance in MGMT promoter hypomethylated glioblastoma cells in vitro and in vivo. TGF-β1 treatment reduced cellular MGMT levels through suppressing the expression of miR-198. However, TGF-β1 upregulation did not affect KSRP expression in glioma cells. We identified and characterized 2 lncRNAs (H19 and HOXD-AS2) that were upregulated by TGF-β1 through Smad signaling. H19 and HOXD-AS2 exhibited competitive binding to KSRP and prevented KSRP from binding to primary miR-198, thus decreasing miR-198 expression. HOXD-AS2 or H19 upregulation strongly promoted temozolomide resistance and MGMT expression. Moreover, KSRP depletion abrogated the effects of TGF-β1 and lncRNAs on miR-198 and MGMT. Finally, we found that patients with low levels of TGF-β1 or lncRNA expression benefited from temozolomide therapy. Conclusions Our results reveal an underlying mechanism by which TGF-β1 confers temozolomide resistance. Furthermore, our findings suggest that a novel combination of temozolomide with a TGF-β inhibitor may serve as an effective therapy for glioblastomas.

Concussion is a widely recognized environmental risk factor for neurodegenerative diseases, including Parkinson's disease (PD). Small-vessel disease of the brain has been reported to contribute to neurodegenerative diseases. In this study, we observed BBB disruption in wild-type (WT) mice, but not in matrix metalloproteinase 9 (MMP-9) knockout mice, subjected to single severe traumatic brain injury (ssTBI). Furthermore, treating ssTBI mice with the MMP-9 inhibitor GM6001 effectively maintained BBB integrity, promoted the elimination of damaged mitochondria via mitophagy, and then prevented neuronal death and progressive neurodegeneration. However, we did not observe this neuroprotective effect of MMP-9 inhibition in beclin-1-/+ mice. Collectively, these findings revealed that concussion led to BBB disruption via MMP-9, and that GM6001 prevented the development of PD via the autophagy pathway.

Considering the urgent demands of consumers for more all-natural food alternatives and the development trend of healthy times, seeking for new types foam and foam-forming healthcare food biomacromolecules is highly required to food valorization and industry. Herein, the enhanced foaming properties of bovine lactoferrin (LF) after forming complexes with ginsenoside Re (Re) and ginsenoside Rb1 (Rb1) was confirmed, while the interaction mechanism between LF and Re/Rb1 was also revealed. Detailly, multi-spectroscopy (absorption, fluorescence/3D fluorescence, CD spectroscopy), thermodynamic analysis and molecular docking results indicated that the interaction between LF and Re/Rb1 is mainly driven by hydrogen bonds and van der Walls forces accompanied by a conformational change of LF, forming LF-Re and LF-Rb1 complexes with a ratio of 1:1. Moreover, the foamability of LF (141%, LF: Re = 1 : 0, molar ratio) increased to be 172% (LF: Re = 1 : 10) and 200.67% (LF: Re = 1 : 20) after forming complexes with Re, while the foamability of LF (150%, LF: Rb1 = 1 : 0) increased to be 171.67% (LF: Rb1 = 1 : 10) and 189.5% (LF: Rb1 = 1 : 20) after forming complexes with Rb1. This work laid the groundwork for promoting the development of all-natural foam agents, also provided a feasible strategy to improve the applications of functional molecules in food valorization and industry.

The glioma-astrocyte interaction plays an important role in tumor microenvironment remodeling; however, the underlying mechanism has not been completely clarified. In this study, we show that glioma cells stimulate normal human astrocyte (NHA) into reactive astrocyte (RAS) in a non-contact manner. Additionally, the amount of O6-alkylguanine DNA alkyltransferase (MGMT) mRNA in exosomes (EXOs) released by RAS was significantly increased compared with that in non-reactive NHA. Importantly, MGMT-negative glioma cells can take up RAS-EXOs and acquire a temozolomide (TMZ)-resistant phenotype via the translation of exogenous exosomal MGMT mRNA both in vitro and in vivo. Our findings illuminate a novel phenomenon that may be a potent mechanism underlying glioma recurrence in which glioma-associated NHAs protect MGMT-negative glioma cells from TMZ-induced apoptosis by the functional intercellular transfer of exosomal MGMT mRNA.

Although there have existed kinds of gold nanoclusters (AuNCs) employed for various sensing purposes, scarce studies were proposed for systematically exploring their multiple routes of the sensing mechanism since that plays the critical role for broadening their analysis applications. Herein, casein-directed gold nanoclusters (AuNCs@casein) have been successfully raised for identifying their multiple routes towards the sensing mechanism. Initially, the current nanoclusters were synthesized in aqueous solution with a quantum yield of nearly 2.1%, which obviously showed the red fluorescence at 600 nm. Subsequently, we have explored three routes of quenching the fluorescence of AuNCs@casein by introducing thiourea, bromelain, and graphene oxide with amino groups (GO-NH2) as the representatives. To be specific, the formed bonds of Au-S between thiourea and AuNCs@casein achieved to quench their fluorescence, and the templates of AuNCs@casein destroyed by bromelain also showed the dramatically decreased fluorescence, and the energy transferring from the current AuNCs to GO-NH2 indeed lead to the fluorescent variations of AuNCs@casein. On the basis of these phenomena, AuNCs@casein was further applied for simply sensing thiourea, bromelain and GO-NH2 through the standard formats. Significantly, this study elaborated three quenching routes of AuNCs@casein and may provide more sensing strategies for other types of nanoclusters.

Malignant tumors posed severe threat to human health, and various efforts have been contributed towards assaying tumor markers, howbeit, achieving to identify the multiple targets by one single analytical mode is in demand. Hereby, three kinds of aptamer-functionalized silver and silver/gold nanoclusters (DNA-AgNCs and DNA-Ag/AuNCs) were originally synthesized, and possessed the specific recognition ability for their corresponding targets. Specifically, the fluorescence of AgNCs or Ag/AuNCs was quenched by introducing graphene oxide (GO), and more competitive interactions between tumor markers and their aptamers occurred with the targets added, thus facilitating their fluorescence recovered. Based on AgNCs or Ag/AuNCs cooperating with GO, this sensing mode was subsequently employed for detecting mucin 1 in a linear range of 1.33–200 ng/mL with a detection limit of 0.18 ng/mL. Meanwhile, this method was also applied to examine carcinoembryonic antigen and cancer antigen 125, and showed the linear range of 6.7 ng/mL–13.3 μg/mL with a detection limit of 3.18 ng/mL for CEA, while CA125 sensing acquired a linear range of 2 ng/mL–6.7 μg/mL accompanied by a detection limit of 1.26 ng/mL. Besides, this strategy provided the potential ways to identify other tumor markers by designing their corresponding nanoclusters with the aptamers.

Hereby, one type of facile-green copper nanoclusters (CuNCs) derived from ovalbumin (CuNCs@OVA) has been innovatively synthesized with a quantum yield of 5.8%. Meaningfully, this nanoclusters exhibited the multiple advantages including satisfactory photostability, low-toxicity and satisfactory stability. By the characterizations in detail, there existed –COOH, –OH, –NH2 and C˭O groups on their surfaces of the prepared CuNCs@OVA, providing their possible applications for sensing. Significantly, the fluorescence of the as-prepared CuNCs@OVA could be quenched by introducing Vitamin B1, while they exhibited the enhanced fluorescence by adding into doxycycline. On the basis of both the fluorescence quenching and enhancement, CuNCs were further employed as the fluorescent probe for assaying both Vitamin B1 and doxycycline. Consequently, it displayed a linear range of 1–1000 nM with the detection limit of 380 pM for assaying VB1, as well as a linear range from 1 to 1000 μM with the detection limit of 270 nM for detecting doxycycline, which indicates the potential applications of CuNCs@OVA for the actual-sample detections.

Chronic kidney disease (CKD) is a worldwide public health problem. Uremic retention solutes such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are accumulated in CKD patients and are associated with the incidence of CKD progression. Amino acids are the major precursors of uremic retention solutes in gut. The dynamic change of amino acid metabolism in the gut during CKD progression has not been reported previously. In this paper, we studied the dynamic change of gut IS/PCS precursor and amino acid metabolism profile during CKD progression in 5/6 nephrectomized (5/6Nx) rats model. The related gut microbiota and metagenome profile was also studied. Rat plasma, urine and feces were collected at different time points after nephrectomization. Plasma IS and PCS, fecal indole (the precursor of IS), p-cresol (the precursor of PCS) and 19 kinds of amino acids were analyzed by LC-MS. During CKD progression, 5/6 Nx rats showed increased plasma IS, PCS concentration and increased fecal indole, p-cresol concentration. 5/6 Nx rats also showed disordered gut amino acids metabolism profile which became more significant along with the progession of CKD. The abundance of some specific gut bacteria also changed significantly in 5/6 Nx rats. The 16S rDNA sequencing data of gut microbiota was further analyzed by an online tool PICRUSt, a large-scale computational method for metagenomes prediction with 16S rDNA sequencing data. The content of each gene was compared between the two groups by Mann-Whitney U test, and then the significantly regulated genes in 5/6 Nx group were subjected to KEGG website. The amino acid metabolism related genes were picked out. Most of these genes are more abundant in 5/6 Nx groups. Our study showed that gut amino acids metabolism profile was disordered with CKD progression, which was highly related to the gut microbiota dysbiosis and metagenome change. And that regulation of gut amino acids metabolism pathway may be a possible way to intervene the progression of CKD.

Herein, blue-fluorescence carbon dots (CDs) derived from carboxymethylcellulose have been innovatively synthesized with well-distributed sizes. Subsequently, a sensitive assay of isoniazid and H2O2 has been further proposed based on the hydrogen bond formation between CDs and isoniazid and the further oxidation of isoniazid by H2O2. To be specific, the richness of carboxyl groups and hydroxyl groups on the CDs enables isoniazid to be adsorbed on the surface of CDs, resulting in effective fluorescence quenching through aggregation. Moreover, we have taken the advantage of the oxidation reaction between isoniazid and H2O2 to achieve the immediate recovery of the fluorescence of CDs. Consequently, quantitative evaluation of H2O2 in a linear range from 4 nM to 800 nM has been proposed along with the range from 20 nM to 6 μM for isoniazid, and its practicability is subsequently validated by detecting actual samples, suggesting that the current strategy may broaden the avenues for sensing both isoniazid and H2O2.

Hereby, one kind of facile carbon dots (CDs) from hydroxypropylmethyl cellulose (HPMC) has been successfully provided, which obviously emitted blue fluorescence. With the related characterizations in detail, the CDs prepared here mainly consisted of C and O, owing to the functional groups of -OH and C=O on their surfaces. Likewise, the CDs also showed multiple advantages, including excellent photostability, superior dispersity and desirable stability. Moreover, the CDs were applied for sensing ciprofloxacin due to forming complexes with ciprofloxacin, thus leading to the fluorescence quenching of CDs. This proposed method was permitted to sense ciprofloxacin in a linear range of 10 nM L-1 - 90 μM L-1, suggesting that it may broaden the sensing ways for assaying ciprofloxacin.

Herein, carbon dots (CD@Papain) from papain have been originally synthesized in aqueous solution along with a quantum yield of 6.2%, and showed cyan fluorescence at 435 nm. Meanwhile, papain-templated Au nanoclusters (AuNCs@Papain) were prepared with the same precursor. On the basis of the two types of nanomaterials, CD@Papain and AuNCs@Papain have been designed to assemble as one nanosensor (termed as CD-AuNCs@Papain) through a typical cross-linking reaction. Significantly, it not only emitted the dual-emission fluorescent signals with the same excitation, but also can assay multiple targets through exhibiting cyan, yellow, and red emission respectively. Thereby, H 2 O 2 , doxycycline and I - can be detected by CD-AuNCs@Papain. The mechanism of the fluorescence variations of CD-AuNCs@Papain: Au(0) of CD-AuNCs@Papain oxidized as Au(I) by H 2 O 2 , the formation of hydrogen bonds between the CD-AuNCs@Papain and I - , the inner filter effect (IFE) occurring caused by tetracyclines. Meanwhile, the detection limits of H 2 O 2 , doxycycline and I - were obtained as 0.3 nM, 0.2 nM, and 0.6 nM at a signal-to-ratio of 3, respectively. These results suggested that the nanoprobe here has provided the possibility for rapidly assaying multiple targets with the acceptable selectivity.

We present a novel photovoltaic self-powered gas sensor based on a p-type single-walled carbon nanotube (SWNT) and n-type silicon (n-Si) heterojunction. The energy from visible light suffices to drive the device owing to a built-in electric field (BEF) induced by the differences between the Fermi levels of SWNTs and n-Si.

The natural compound Zerumbone (hereinafter referred to as ZER), a monocyclic sesquiterpenoid, has been reported to possess many pharmacological properties, including antioxidant and anti-inflammatory properties. This study aimed to investigate the underlying mechanism of ZER against acute liver injury (ALI) in CCl4-induced mice models. ICR mice were pretreated intraperitoneally with ZER for five days, then received a CCl4 injection two hours after the last ZER administration and were sacrificed 24 h later. Examination of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the histopathological analysis confirmed the hepatoprotective effect of ZER. Biochemical assays revealed that ZER pretreatment recovered the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), restored the glutathione (GSH) reservoir, and reduced the production of malondialdehyde (MDA), all in a dose-dependent manner. Furthermore, administration of ZER in vivo reduced the release amounts of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-&alpha, ) and inhibited the increased protein levels of Toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-&kappa, B) p-p65, and cyclooxygenase (COX-2). Further studies in lipopolysaccharide (LPS)-induced Raw264.7 inflammatory cellular models verified that ZER could inhibit inflammation via inactivating the TLR4/NF-&kappa, B/COX-2 pathway. Thus, our study indicated that ZER exhibited a hepatoprotective effect against ALI through its antioxidant and anti-inflammatory activities and the possible mechanism might be mediated by the TLR4/NF-&kappa, B/COX-2 pathway. Collectively, our studies indicate ZER could be a potential candidate for chemical liver injury treatment.

Integrating kinds of bactericides as one entirety shows prospect for improving antibacterial efficiency, thus a new type of nanoclusters based on bactericide-directed herein emerged as a combination for achieving a higher antibacterial effect. Specifically, an easily operated approach for preparing bacitracin-directed silver, gold, and copper nanoclusters (AgNCs, AuNCs, and CuNCs, respectively) was proposed. Meanwhile, AgNCs@Bacitracin, AuNCs@Bacitracin, and CuNCs@Bacitracin emitted cyan, yellow, and red colors of fluorescence, respectively, and different sizes and nitrogen contents of these nanoclusters played a critical role for their fluorescence alterations. Significantly, AgNCs@Bacitracin exhibited robust bacteria-killing efficiency than other nanoclusters, owing to its marked damage on the bacterial membrane. Additionally, propidium iodide (PI) staining indicated the bacterial membrane damage of 72.3% to the bacteria population followed by the treatment with AgNCs@Bacitracin, and the introduction of AgNCs@Bacitracin lead to the higher reactive oxygen species (ROS) production, facilitating their attractive antibacterial activity. Moreover, this strategy of developing new nanoclusters broadened the avenues for designing the improved antibacterial materials.

Background Epithelial cell transformation sequence 2 (ECT2) is upregulated in glioma and promotes glioma cell proliferation. A preliminary experiment showed a positive correlation between ECT2 and pituitary tumor-transforming gene 1 (PTTG1). The aim of this study was to explore how ECT2 affects PTTG1 to influence the proliferation of glioma cells. Methods The expression of ECT2 in glioma was detected by western blot and reverse transcription PCR. The effect of ECT2 on glioma proliferation was examined using cell proliferation-related assays and in vivo experiments. The effect of ECT2 on the stability of E2F transcription factor 1 (E2F1) and the expression of PTTG1 were examined by western blot, co-immunoprecipitation, and in vivo ubiquitination assays. Results ECT2 was upregulated in gliomas and was negatively correlated with prognosis; its downregulation inhibited glioma cell proliferation. Furthermore, ECT2 regulated PTTG1 expression by affecting the stability of E2F1, thereby affecting the glioma cell proliferation. In addition, the deubiquitinating enzyme proteasome 26S subunit, non-ATPase 14 (PSMD14) affected the degradation of E2F1 and regulated the stability of E2F1. Interestingly, ECT2 regulated the expression of PSMD14. Conclusion In this study, we clarify a new mechanism by which ECT2 regulates the expression of PTTG1 and thus affects the proliferation of glioma cells: ECT2 influences the stability of E2F1 by regulating the expression of the deubiquitinating enzyme PSMD14, thereby affecting the expression of PTTG1. Intensive and extensive understanding of the mechanism of ECT2 in glioma proliferation may provide an opportunity for the development of new molecular therapeutic targets for glioma treatment.

Simultaneous treatment NO and SO2 from industrial flue gas by wet processes, a large number of sulfate ( S O 4 2 - ) ions will be generated in the system, and S O 4 2 - ion is corrosive to concrete buildings used for subsequent sewage treatment. If the generated S O 4 2 - ions can be in-situ reutilization to be converted to sulfate radicals ( S O 4 · - ) with strong oxidizing, then they can continue to oxidize removal NO and SO2 in the flue gas, which will further promote the effect of flue gas treatment. Therefore, a novel strategy with C/C electrodes electro-activated peroxymonosulfate (PMS) is developed, utilizing electrons to activate PMS to generate radicals while carbon electrodes converting S O 4 2 - ions to S O 4 · - radicals via direct electron transfer, and then use the radicals and other active substance generated to remove NO. The effects of current intensity, temperature on NO removal and the types of oxides produced in the electro-activated system are investigated. In addition, the relationships of current intensity and conversion time with the S O 4 · - radical signal intensity detected are discussed respectively. Accordingly, a catalytic mechanism is proposed involving S O 4 · - ⋅OH and 1O2 radicals oxidation and C-PMS* non-radical oxidation.

Currently, the synthesis of carbon dots (CDs) exhibiting long-wavelength emission is still challenging. Herein, we have synthesized for the first time three types of CD with multicolor emission derived from isomers. Importantly, their particle size, nitrogen-doping amount and band gaps collectively regulate the fluorescence emission of the proposed CDs.

Although a number of methods to perform assays of tetracyclines using fluorescent probes have been reported, approaches for discriminating and detecting tetracyclines are few. Herein, bright-blue fluorescent carbon dots (CDs) with a quantum yield (QY) of up to ∼27.9% were hydrothermally synthesized using tobacco as the carbon source. Importantly, the as-prepared carbon dots were employed as a fluorescent probe, enabling selective differentiation of three tetracyclines using a test strip and the related quantitative detection. Towards the mechanism, three kinds of tetracyclines showed different interactions with the CDs, leading to variations in their fluorescence emissions. To be specific, the fluorescence of CDs was quenched by tetracycline (TC) without a fluorescence shift (Em = 440 nm), which was caused by an inner filter effect rather than a change in the energy band gap. Moreover, the introduction of chlorotetracycline (CTC) resulted in a blue shift (Em = 415 nm) of the fluorescence of the CD; this phenomenon was induced by the enlarged energy band gap. The CDs also responded to oxytetracycline (OTC), and their corresponding fluorescence experienced a red shift (Em = 500 nm) due to the narrowed band gap. Consequently, a visual detection strategy for three tetracyclines has been proposed based on the quantitative evaluation of TC, OTC, and CTC concentrations in broad range from 6 × 10-6 to 4 × 10-9 M, 2 × 10-6 to 2 × 10-8 M, and 2 × 10-7 to 2 × 10-8 M, respectively. Moreover, we have successfully applied the current CDs for visually distinguishing the three tetracyclines on a test strip on the basis of CDs exhibiting three types of fluorescence (weak-blue, navy-blue, and chartreuse).

// Dongfeng Han 1, * , Wenjin Wei 1, * , Xincheng Chen 1, * , Yaxuan Zhang 1, * , Yingyi Wang 1 , Junxia Zhang 1 , Xiefeng Wang 1 , Tianfu Yu 1 , Qi Hu 1 , Ning Liu 1 , Yongping You 1 1 Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China * These authors have contributed equally to this work Correspondence to: Yongping You, e-mail: YYPL9@njmu.edu.cn Keywords: fenofibrate, PPARα, RelA, PKM2, Warburg effect Received: February 16, 2015 Accepted: June 19, 2015 Published: June 30, 2015 ABSTRACT Aerobic glycolysis (production of lactate from glucose in the presence of oxygen) is a hallmark of cancer. Fenofibrate is a lipid-lowering drug and an agonist of the peroxisome proliferator-activated receptor alpha (PPARα). We found that FF inhibited glycolysis in a PPARα-dependent manner in glioblastoma cells. Fenofibrate inhibited the transcriptional activity of NF-κB/RelA and also disrupted its association with hypoxia inducible factor1 alpha (HIF1α), which is required for the binding of NF-κB/RelA to the PKM promoter and PKM2 expression. High ratios of PKM2/PKM1 promote glycolysis and inhibit oxidative phosphorylation, thus favoring aerobic glycolysis. Fenofibrate decreased the PKM2/PKM1 ratio and caused mitochondrial damage. Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM).

A series of new A–π–D–π–A molecules including diphenylamine and carbazole had been synthesized and characterized ( T1 – T3 ). T1 and T2 displayed aggregation-induced emission enhancement (AIEE): exhibiting weak fluorescence in pure THF, which a signification AIEE effect was observed in mixture with a water fraction ( f w ) of 90% with a sharp increase in fluorescence intensity. T3 displayed aggregation-caused quenching (ACQ): exhibiting strong fluorescence in pure THF, which a signification ACQ effect was observed in mixture with a water fraction ( f w ) of 90% with a sharp decrease in fluorescence intensity. Their two-photon absorption (2PA) had been investigated using the open-aperture Z-scan technique, and the values of the 2PA cross section at 800 nm for T1 – T3 were 1115, 681, in chloroform, respectively.

By employing the attractive performance of fluorescent carbon dots and the assistant of hairpin structure, an innovative dual-channel biosensor on the basis of gold nanoparticles (AuNPs) for detecting multiple nucleotide sequences has been successfully proposed. In brief, the fluorescence of carbon dots (CDs) was quenched in the absence of the targets, and the hairpin structure was hybridized with the AuNPs-DNA and resulted in recovering the fluorescence. Instead, the presence of breast cancer (BRCA1) RNA/DNA could specifically bind with its contrary sequence to release the CDs from AuNPs, hence leading to the fluorescence recovery as a positive signal. Again, the hairpin structure can be released in the presence of thymidine kinase (TK1) RNA/DNA, thus induced a fluorescence quenching accordingly. Subsequently, the prepared sensing model was applied to detect BRCA1 RNA/DNA respectively accompanied with a linear range of 4-120nM as well as a detection limit of 1.5nM and 2.1nM, and 10-120nM as well as a detection limit of 3.6nM and 4.5nM for TK1 RNA/DNA respectively. More importantly, this sensing model could assay any possible gene sequence or aptamer-substrate complexes by appropriately programming.

H19 expression is elevated in many human tumors including glioblastomas, suggesting an oncogenic role for the long noncoding RNA; yet the upregulation of H19 in glioblastomas remains unclear. Here we report that hypoxia significantly stimulated H19 expression in glioblastoma cell lines, which was related to hypoxia-inducible factors 1α (Hif-1α). Hif-1α promoted H19 expression in U87 and U251 cells. Meanwhile PTEN is an advantageous factor to affect H19 expression, through attenuating Hif-1α stability. Hif-1α also positively correlates with H19 in human glioblastoma samples depending on PTEN status. ChIP and luciferase reporter assays showed that Hif-1α induced H19 transcription through directly binding to the H19 promoter. Furthermore, Hif-1α upregulated specific protein 1 (SP1) expression in glioblastomas cells in vitro and in vivo, and SP1 also strongly interacted with the H19 promoter to promote H19 expression under hypoxia. We also showed that H19 acts as a molecular sponge that binds miR-181d, relieving inhibition of β-catenin expression. Therefore, H19 participates in hypoxia-driven migration and invasion in glioblastoma cells. In summary, our results uncover the mechanisms that stimulate H19 expression under hypoxia to promote malignant effects in glioblastomas and suggest H19 might be a promising therapeutic target.

Objective To evaluate the efficacy of bicyclol in preventing chemotherapy-induced liver damage. Methods Patients ≥60 years of age with cancer were equally randomized into control (chemotherapy alone) or prophylactic (chemotherapy supplemented with 75 mg bicyclol, oral, daily) groups. Liver function indices were assessed immediately before treatment, during each therapy cycle and following treatment. Results Of 306 patients enrolled, 300 patiets completed the study ( n = 147 and n = 153; prophylactic and control groups, respectively). Incidence of grade I–IV elevation of serum transaminase and/or bilirubin was significantly lower in the prophylactic group (17.1%) compared with the control group (47.1%). Incidence of grade II–IV hepatic injury was also significantly lower in the prophylactic group (0.7%) than in the control group (12.4%). Conclusions Prophylactic bicyclol (75 mg daily) could significantly reduce the incidence and degree of chemotherapeutic agent-induced liver damage in elderly patients with cancer. Further studies are recommended with larger sample sizes and long-term follow up.

Two conjugated ethynyl-linked oligomers, oligo(benzodithiophene-ethynylene-benzothiadiazole) (O1) and oligo(benzodithiophene-ethynylene-carbazole) (O2), were synthesized by Sonogashira coupling reaction. Their degrees of polymerization were 7 and 10, respectively. Their photophysical and electrochemical properties were investigated. O1 exhibitd two strong absorption bands at 404 nm and 483 nm, and O2 at 401 nm and 429 nm. The results of UV-Vis, cyclic voltammetry (CV) and theoretical calculations showed that O1 has a narrower band gap than O2. The conductivities of O1 and O2 were 1.05×10−15 and 6.98×10−16 S/cm, respectively, and would increase to 1.23×10−10 and 1.05×10−10 S/cm after doping with iodine.

Mucormycosis is a rare and fatal opportunistic infection occurring in severely immunocompromised patients. Here, we report, for the first time, on a 65-year-old man with idiopathic membranous nephropathy and moderate renal dysfunction who suffered from life-threatening pulmonary mucormycosis during immunosuppressive therapy. After amphotericin B (AmB) administration with a total accumulating dose of 1.5 g, not only has he recovered from this fatal infection, but also his nephrotic syndrome has entered complete and long-term remission without any continued corticosteroid and immunosuppressive therapy during the 6-year follow-up. Serum creatinine levels remained stable by adjusting the tolerable daily dose of AmB during the period of treatment.

Di (2-ethylhexyl) phthalate (DEHP), which is widely used in polyvinyl chloride materials, can be easily accumulated into human body. Lung cancer cells can be directly exposed to DEHP via inhalation, however, the effects and related mechanisms of DEHP on the progression of non small cell lung cancer (NSCLC) were not illustrated. Our present study revealed that DEHP less than 10-4M had no significant effect on the proliferation of A549 or H1299 cells, while nanomolar DEHP can trigger the migration and invasion of NSCLC cells. DEHP treatment also increased the expression of interleukin-6 (IL-6) and IL-8. Silencing of IL-6, while not IL-8, can attenuate DEHP induced migration and invasion of NSCLC cells. This was confirmed by result that neutralization antibody of IL-6, while not anti-IL-8, attenuated DEHP induced invasion of A549 cells. The inhibitor of NF-κB, while not ERK1/2 or Akt, abolished DEHP induced up regulation of IL-6 and invasion of NSCLC cells. DEHP treatment can increase the phosphorylation, nuclear localization, and transcriptional activities of p65, one of the major parts of NF-κB complex. Collectively, our study revealed that DEHP can stimulate NSCLC migration and invasion via NF-κB mediated up regulation of IL-6.

Recently, several microRNAs (miRNAs) were reported to be involved in the modulation of glioma development. The aim of our study was to determine the effect of miR-181d on the growth of glioma and to investigate whether this growth is modulated by targeting K-ras and Bcl-2. Real-time PCR was used to analyze the expression of miR-181d in human glioma samples and glioma cell lines. Apoptosis, cell cycle, and proliferation (MTT) assays were performed to assess the phenotypic changes in glioma cells. Immunohistochemistry was used to determine the expression of K-ras and Bcl-2 in glioma tissues, and a luciferase reporter assay was carried out to confirm whether K-ras and Bcl-2 are direct targets of miR-181d. Western blotting was used to identify the potential signaling pathways affected glioma cell growth by miR-181d. In vivo, xenograft tumors were examined for an anti-glioma effect of miR-181d. MiR-181d was down-regulated in human glioma samples and up-regulated in transfected glioma cells. Ectopic expression of miR-181d suppressed proliferation and triggered cell cycle arrest and apoptosis in glioma cell lines. K-ras and Bcl-2 were identified as direct targets of miR-181d and were up-regulated in glioma samples. The results showed evidence linking the tumor suppressor activity of miR-181d in glioma cells with the K-ras-related PI3K/AKT and MAPK/ERK pathways. Furthermore, xenograft tumors from miR-181d-treated U251 cells were suppressed in vivo. MiR-181d may act as a glioma suppressor by targeting K-ras and Bcl-2.

Ultrathin free-standing graphene oxide (GO) films were fabricated by vacuum filtration method assisted with Ni(OH)2 nanosheets as the sacrifice layer. The surface of the obtained GO film is very clean as the Ni(OH)2 nanosheets can be thoroughly etched by HCl. The thickness of the GO films can be well-controlled by changing the volume of GO dispersion, and the thinnest GO film reached ~12 nm. As a novel and transparent dielectric material, the GO film has been applied as the dielectric layer for the flexible touchless capacitive sensor which can effectively distinguish the approaching of an insulator or a conductor.

The peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor, which belongs to the super-family of steroid hormone receptor. To date, the biologic function of PPARα in human cancers is still controversial and needs further investigation. In our study, we explored the clinical feature, biological function and potential mechanism of PPARα in glioma. PPARα expression was significant lower in high grade tissues than low grade tissues in whole genome gene profiling of 158 glioma tissues. PPARα activation using fenofibrate inhibited glioma cells proliferation, invasion and aerobic glycolysis. Further, PPARα was a direct target of miR-19a and miR-19a was modulated by E2F1 at transcriptional level. Moreover, PPARα activation repressed E2F1 activation by modulating transcriptional complexes formed with E2F1 and pRB proteins. Finally, we confirmed PPARα/E2F1/ miR-19a feedback loop in vivo using nude mouse glioma xenograft and human glioma tissues. To our knowledge, it is first time to demonstrate that PPARα regulates glioma development by E2F1-induced miR-19a in a feedback loop and provide important clues for understanding the key roles of PPARα functional network in glioma. Note: This abstract was not presented at the meeting. Citation Format: Junxia Zhang, Yan Shi, Yingyi Wang, Wenkang Luan, Yongping You. Peroxisome proliferator-activated receptor α is regulated by E2F1-induced miR-19a in a feedback loop in glioma progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4195. doi:10.1158/1538-7445.AM2014-4195

MiRNAs, are small noncoding RNA molecules of approximately 20-22 nucleotides in length, regulate protein expression by cleaving or repressing the translation of targets mRNA. MiR-21, as an oncogene, has been reported to be dyregulated in a variety of cancer. Our recent data have verified that miR-21 is one of the most frequently over-expressed miRNA in human glioblastoma (GBM) cell lines. However, the mechanism of miR-21 involved in gliomagenesis is still unknown. In this study, reduction of miR-21 by antisense oligonucleotide induced cell apoptosis and inhibited cell growth in U87 and LN229 GBM cells, with a decreased expression of human telomerase reverse transcriptase (hTERT). Knockdown of hTERT expression using lentiviral vector mediated delivery of hTERT-siRNA triggered cell apoptosis and cell cycle G1/G0 arrest in U87 and LN229 cells. In order to explore the molecular regulation of hTERT by miR-21, we found that STAT3 could be an important mediator between miR-21 and hTERT. Reduction of miR-21 repressed STAT3 expression and STAT3 phosphorylation. STAT3 inhibitor WP1066 led to a remarkable depletion of hTERT both at mRNA and protein levels. To determine the functional interaction between STAT3 and hTERT, ChIP showed the presence of STAT3-binding sites in the hTERT gene. Luciferase reporter assay revealed that the hTERT gene promoter was direct bound by STAT3. Furthermore, we evaluated the status of STAT3 in hTERT regulation by miR-21. U87 and LN229 cells that treated with miR-21 antisense oligonucleotide and IL-6 which could elevate the expression of STAT3 showed a significant increase of hTERT expression, whereas cells that treated with miR-21 oligonucleotide and STAT3 inhibitor WP1066 displayed a reduction of hTERT expression. Finally, knockdown of miR-21 considerably inhibited tumor growth and diminished the expression of STAT3, pSTAT3 and hTERT in xenograft model. Taken together, we have demonstrated that miR-21 inhibits cell growth through regulating hTERT expression in a STAT3-dependent pathway in GBM cells. These results suggest that modulation of the mechanism responsible for miR-21 in GBM could be used as a therapeutic strategy for GBM treatment and warrants further investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3973. doi:10.1158/1538-7445.AM2011-3973