Determination of marker residues of quinoxaline-1,4-di-N-oxides and its prototype identification by liquid chromatography tandem mass spectrometry.

Quinoxaline-1,4-di-N-oxides (QdNOs), such as carbadox, olaquindox, mequindox, quinocetone, etc. are a class of antibacterial drugs. Prototype drugs residues can not be detected due to their rapid metabolism in animals. Quinoxaline-2-carboxylic acid (QCA) and 3-methyl-QCA (MQCA) are their common marker residues, so it has been always a challenge to trace the specific QdNOs drug used in food animal production. Herein, a liquid chromatography tandem mass spectrometry method was developed to determine QCA and MQCA, and meanwhile, the prototype drugs were identified by analyzing bis-desoxy QdNOs metabolites in single ion-pair monitoring mode. The method indicated that the average recoveries for QCA and MQCA were from 90 % to 105 % with relative standard deviations below 10 %, and the limits of quantification were 1.0 µg/kg. The limits of detection of five bis-desoxy QdNOs (qualitative markers) reached 0.5 µg/kg. This new analytical strategy can effectively solve the identification problem of QdNOs drugs in animal-derived food.

Mass Spectrometric Analysis of Urinary N-Glycosylation Changes in Patients with Parkinson's Disease.

Urine is thought to provide earlier and more sensitive molecular changes for biomarker discovery than blood. Numerous glycoproteins, peptides, and free glycans are present in urine through glomerular filtration of plasma, cell shedding, apoptosis, proteolytic cleavage, and exosome secretion. Urine biomarkers have enormous diagnostic potential, and the use of these biomarkers is a long-standing practice. The discovery of non-urological disease biomarkers from urine is also gaining attention due to its non-invasive sample collection and ease of analysis. Abnormal protein glycosylation in plasma or cerebrospinal fluid has been associated with Parkinson's disease, however, whether urine with Parkinson's disease has characteristic glycosylation remains to be explored. Here, we use mass spectrometry-based glycomics and glycoproteomics approaches to analyze urine samples for glycans, glycosites, and intact glycopeptides of urine samples. Reduced abundance of N-glycans was detected at the level of total glycans as well as specific glycosites of glycopeptides. The most abundant N-glycan in urine is S(6)1H5N4F1; S(6)2H5N4 and N4H4F1 are highly present in serum and urine, and 10 biantennary galactosylated N-glycans in the urine of PD patients were significantly decreased. The downregulation of sialylation may be due to the reduction of ST3GAL2. Site-specific N-glycosylation analysis revealed that AMBP, UMOD, and RNase1 have PD-specific N-glycosylation sites. GO and KEGG analysis revealed that N-glycosylation changes may provide clues to identify disease-specific glycosylation biomarkers in Parkinson's disease.

The antihelminth drug rafoxanide reverses chromosomal-mediated colistin-resistance in Klebsiella pneumoniae.

The emergence and rapid spread of multi-drug-resistant (MDR) bacteria pose a serious threat to global healthcare. Although the synergistic effect of rafoxanide and colistin was reported, little is known regarding the potential mechanism of this synergy, particularly against chromosomal-mediated colistin-resistant Klebsiella pneumoniae. In the present study, we elucidated the synergistic effect of rafoxanide and colistin against chromosomal-mediated colistin-resistant Klebsiella pneumoniae isolates from human (KP-9) and swine (KP-1) infections. Treatment with 1 mg/L rafoxanide overtly reversed the MIC max to 512-fold. Time-kill assays indicated that rafoxanide acted synergistically with colistin against the growth of KP-1 and KP-9. Mechanistically, we unexpectedly found that the combination destroys the inner-membrane integrity, and ATP synthesis was also quenched, albeit, not via F1F0-ATPase; thereby also inhibiting the activity of efflux pumps. Excessive production of reactive oxygen species (ROS) was also an underlying factor contributing to the bacterial-killing effect of the combination. Transcriptomic analysis unraveled overt heterogeneous expression as treated with both administrations compared with monotherapy. Functional analysis of these differentially expressed genes (DEGs) targeted to the plasma membrane and ATP-binding corroborated phenotypic screening results. These novel findings highlight the synergistic mechanism of rafoxanide in combination with colistin which effectively eradicates chromosomal-mediated colistin-resistant Klebsiella pneumoniae. IMPORTANCE The antimicrobial resistance of Klebsiella pneumoniae caused by the abuse of colistin has increased the difficulty of clinical treatment. A promising combination (i.e., rafoxanide+ colistin) has successfully rescued the antibacterial effect of colistin. However, we still failed to know the potential effect of this combination on chromosome-mediated Klebsiella pneumoniae. Through a series of in vitro experiments, as well as transcriptomic profiling, we confirmed that the MIC of colistin was reduced by rafoxanide by destroying the inner-membrane integrity, quenching ATP synthesis, inhibiting the activity of the efflux pump, and increasing the production of reactive oxygen species. In turn, the expression of relevant colistin resistance genes was down-regulated. Collectively, our study revealed rafoxanide as a promising colistin adjuvant against chromosome-mediated Klebsiella pneumoniae.

Effects of Cu ratios on the C1-C6 growth mechanism on copper-nickel bimetallic surfaces.

The adsorption and growth mechanisms of Cn (n = 1-6) on different Cu-Ni surfaces are calculated by density functional theory (DFT). The results demonstrate that Cu doping affects the growth mechanism of the deposited carbon on the catalyst surface. Firstly, the addition of Cu weakens the interaction between Cn and the adsorbed surface, which is proved by the results of density of states (DOS) and partial density of states (PDOS). The weakening of the interaction allows Cn to perform at higher proportions of Cu-doped surfaces with a behavior consistent with that in the gas phase. A comparison of the growth energies of the different pathways of Cn in the gas phase shows that the main pathway for the Cn growth is chain-to-chain (CC). The CC reaction is also the main pathway for the growth of Cn on the surfaces, which is enhanced by the doping of Cu. In addition, analysis of the growth energy revealed that C2-C3 is the rate-determining step in the growth process of Cn. The doping of Cu enhances the growth energy of this step, contributing to the suppression of the growth of the deposited carbon on the adsorbed surface. Moreover, an average carbon binding energy shows that the doping of Cu on the Ni surface could weaken the structural stability of Cn, favoring the elimination of carbon deposited on the catalyst surface.

Hyaluronic acid modified carbon nanotubes using for photothermal therapy by promoting apoptosis of nasopharyngeal carcinoma cells.

Background: The present work illustrates the role of multi-walled carbon nanotubes in photothermal therapy. Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck with significant ethnic and geographic differences, and conventional treatment options are no longer suitable to improve the prognosis and survival of patients. Photothermal therapy (PTT) has emerged as a new strategy for oncology treatment in recent years and is now used in the treatment of many common cancers. Multi-walled carbon nanotubes (MWCNT) have been used to advantage in several fields due to their excellent thermal conductivity. The aim of this paper is to investigate the promotion of apoptosis of nasopharyngeal cancer cells by multi-walled carbon nanotubes as an adjuvant nanomaterial for nasopharyngeal cancer photothermal therapy. Methods: Carboxylated multi-walled carbon nanotubes and prepared multi-walled carbon nanotube-hyaluronic acid (MWCNT-HA) composites were used for cell proliferation-related experiments such as CCK-8 assay, live-dead staining and flow cytometric analysis and inverted fluorescence microscopy to determine the expression level of apoptotic factors and confocal microscopy cell morphology analysis on nasopharyngeal carcinoma CNE-1 cells under near-infrared laser irradiation. The effects of multi-walled carbon nanotubes on the proliferation and apoptosis of tumor cells under NIR response were elucidated, and the mechanism of apoptosis was explored. Results: TEM and SEM demonstrated that MWCNT had good appearance morphology and the temperature rise curve indicated excellent photothermal stability. And MWCNT and MWCNT-HA could significantly inhibit the proliferation of tumor cells and change the normal morphology of cells under NIR laser irradiation. Cellular immunofluorescence analysis confirmed that MWCNT-HA significantly upregulated the expression level of apoptosis factor Caspase-3 and significantly downregulated the expression level of anti-apoptosis factor Bcl-2. Conclusion: In this study, MWCNT inhibited the proliferation of tumor cells and promoted apoptosis through the use of multi-walled carbon nanotubes as an adjuvant nanomaterial for photothermal therapy. In addition, multi-walled carbon nanotubes could inhibit the mitochondrial pathway of CNE-1 cells to cause cell death. These studies suggest that multi-walled carbon nanotubes can function as efficient photothermal conversion materials for tumor photothermal therapy.

Recent Advances in Graphitic Carbon Nitride Based Electro-Catalysts for CO2 Reduction Reactions.

The electrocatalytic carbon dioxide reduction reaction is an effective means of combating the greenhouse effect caused by massive carbon dioxide emissions. Carbon nitride in the graphitic phase (g-C3N4) has excellent chemical stability and unique structural properties that allow it to be widely used in energy and materials fields. However, due to its relatively low electrical conductivity, to date, little effort has been made to summarize the application of g-C3N4 in the electrocatalytic reduction of CO2. This review focuses on the synthesis and functionalization of g-C3N4 and the recent advances of its application as a catalyst and a catalyst support in the electrocatalytic reduction of CO2. The modification of g-C3N4-based catalysts for enhanced CO2 reduction is critically reviewed. In addition, opportunities for future research on g-C3N4-based catalysts for electrocatalytic CO2 reduction are discussed.

Exploiting RIG-I-like receptor pathway for cancer immunotherapy.

RIG-I-like receptors (RLRs) are intracellular pattern recognition receptors that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2) that have distinctive features. These receptors not only recognize RNA intermediates from viruses and bacteria, but also interact with endogenous RNA such as the mislocalized mitochondrial RNA, the aberrantly reactivated repetitive or transposable elements in the human genome. Evasion of RLRs-mediated immune response may lead to sustained infection, defective host immunity and carcinogenesis. Therapeutic targeting RLRs may not only provoke anti-infection effects, but also induce anticancer immunity or sensitize "immune-cold" tumors to immune checkpoint blockade. In this review, we summarize the current knowledge of RLRs signaling and discuss the rationale for therapeutic targeting RLRs in cancer. We describe how RLRs can be activated by synthetic RNA, oncolytic viruses, viral mimicry and radio-chemotherapy, and how the RNA agonists of RLRs can be systemically delivered in vivo. The integration of RLRs agonism with RNA interference or CAR-T cells provides new dimensions that complement cancer immunotherapy. Moreover, we update the progress of recent clinical trials for cancer therapy involving RLRs activation and immune modulation. Further studies of the mechanisms underlying RLRs signaling will shed new light on the development of cancer therapeutics. Manipulation of RLRs signaling represents an opportunity for clinically relevant cancer therapy. Addressing the challenges in this field will help develop future generations of cancer immunotherapy.

Potential health benefits of lowering gas production and bifidogenic effect of the blends of polydextrose with inulin in a human gut model.

Polydextrose is a nutrient supplement, which is widely applied in the food industry. The use of polydextrose in combination with prebiotics and probiotics has recently increased, whereas the fermentation properties of its blend have not yet been fully revealed. We evaluated the metabolic profile of polydextrose, inulin, and their blends by a batch in vitro fermentation of fifteen human fecal inocula. After 24 h of fermentation, polydextrose increased the production of gas, ammonia, and several short chain fatty acids, including propionate and butyrate, when compared to its blends, inulin, and fructo-oligosaccharides. Furthermore, polydextrose had the slowest degradation rate of all the carbohydrates tested, consistent with its partial fermentation in the distal colon. The 16S rRNA gene sequencing analysis of the gut microbiome exhibited significantly increased relative abundance of Clostridium_XVIII, Megamonas, Mitsuokella, and Erysipelotrichaceae_incertae_sedis in polydextrose compared to other carbohydrates. On the other hand, the blends of polydextrose and inulin (1:1 or 2:1) showed reduced gas production and similar bifidogenicity to inulin alone. The blends not only had similar alpha-diversity and PCoA to inulin but also had a similar abundance of beneficial bacteria, such as Faecalibacterium and Roseburia, suggesting potential health benefits. Also their low gas production was likely due to the abundance of Faecalibacterium and Anaerostipes, which were negatively correlated with gas production. Additionally, our in vitro fermentation model shows advantages in the large-scale assessment of fermentation performance.

Bond Properties of Magnesium Phosphate Cement-Based Engineered Cementitious Composite with Ordinary Concrete.

A magnesium phosphate cement-based engineered cementitious composite (MPC-ECC) was developed using polyvinyl alcohol (PVA) fibers and fly ash. In this study, the bond behavior of MPC-ECC with ordinary concrete was evaluated through single and double shear bond strength tests. The effects of the water to solid mass ratio (W/S), the sand to binder mass ratio (S/B), the molar ratio of MgO to KH2PO4 (M/P), the fly ash content (F), the borax dosage (B), the volume fraction of PVA fibers (Vf), and curing age on the bond behavior of MPC-ECC with ordinary concrete were examined. The results showed that as the W/S increased, the single and double shear bond strengths were gradually reduced. As the S/B increased, the double shear bond strength increased; the single shear bond strength first decreased up to an S/B of 0.1 and then increased. With the increase of M/P, the single and double shear bond strengths increased. With the increase of F, the single shear bond strength first increased up to an F of 30% and then decreased; the double shear bond strength decreased. With the increase of B, the single and double shear bond strengths increased first and then decreased, and their strength reached its maximum at a B of 6%. The increase of Vf improved the single and double shear bond strengths. The research results can provide some technical guidance for repairing concrete structures with MPC-ECC.

Hydroxypropylmethyl Cellulose Modified with Carbon Dots Exhibits Light-Responsive and Reversible Optical Switching.

A light-responsive optical switching material is reported, which was obtained by incorporating carbon dots (CDs) into thermochromic hydroxypropylmethyl cellulose (HPMC). The ultrasmall size of CDs guarantees the considerable transparency of CDs/HPMC. Under illumination, CDs/HPMC shows rapid and reversible optical switching between transparent and opaque states due to the remarkable photothermal effect of CDs. Moreover, the interaction between CDs and HPMC enhances the light absorption and boosts the nonradiative recombination of photoexcited charge carriers that further promote the photothermal conversion of CDs, and also ensures the structural stability of the composite. The obtained CDs/HPMC with good reversibility and high sensitivity which can dynamically switch their transparency in response to weather conditions exhibits excellent solar modulation ability.

Fluorescent Supramolecular Assembly with Coronene Centers for Controlled DNA Condensation and Drug Delivery.

A multifunctional supramolecular assembly was successfully constructed by the host-guest complexation of doubly positively charged adamantane (ADA) with ß-CD-modified hexabenzocoronene and the π-stacking of coronene with mitoxantrone, which was characterized by transmission electron microscopy, scanning electron microscopy, dynamic light-scattering, and zeta potential experiments. Possessing a small size and rigid backbone coronene center, the water-soluble biocompatible supramolecular assembly has intracellular imaging abilities. Moreover, after the ester group of ADA was hydrolyzed into a carboxyl group, the positively charged quaternary amine strand converted into a zwitterion structure, which realized the controlled plasmid DNA binding and release. Besides, the cytotoxicity experiments showed that the supramolecular assembly possesses slightly lower toxicity and a slightly higher anticancer activity than free drug. We believe that this work might present a convenient method for synergetic cancer treatment.

Self-Regeneration Performance and Characterization of Silver-Containing Activated Carbon Fibers Coated by Titanium Dioxide.

In this study, wood-based activated carbon fibers (WACF) were modified by Ag nanoparticles (AgNPs) and TiO2 films. The coating of TiO2 films decreased the AgNPs agglomeration and exfoliation on WACF. As the soaking concentration of AgNO3 solution (Sconc) increased, AgNPs size and content increased, while the pore volume (especially micropore volume) of fibers reduced. However, at higher Sconc in the range of 0.2 to0.4 mol/L, only slight variations in AgNPs content and pore structure were observable for WACF/TiO2/Ag (Ag-containing WACF coated by TiO2 film). WACF/TiO2/Ag-0.1 (0.1 was the soaking concentration of AgNO3 solution, mol/L) represented the best self-regeneration performance under the visible light irradiation. The self-regeneration performance of WACF/TiO2/Ag was determined by the synergistic effects of two factors: adsorption and photodegradation. The abundant pores of WACF/TiO2/Ag-0.1 increased the methylene blue (MB) concentration of TiO2 surrounding and facilitated the MB photodegradation. Meanwhile, their suitable Ag content enhanced MB photodegradation. Furthermore, the principal pathway of a chemical reaction between Ag+ and WACF was interpreted based on the data of surface elemental constituents and surface functional groups.

Flexible C-Mo2C fiber film with self-fused junctions as a long cyclability anode material for sodium-ion battery.

Electrospun carbon fiber films have high contact resistance at the fiber junctions, which causes poor cycling stability and limits their further improvement in energy storage performances. To eliminate the contact resistance of the film, we provide a new strategy to fuse the fiber junctions by introducing MoO2 in the fibers, which replaces the C-C interface by a more active C-MoO2-C interface at the fiber junction to promote mass transfer. MoO2 reacts with C matrix to generate Mo2C and form self-fused junctions during the carbonization process. Due to much lower charge transfer and sodium diffusion resistance, the C-Mo2C fiber film with self-fused junctions shows much better cyclability with capacity retention of 90% after 2000 cycles at a constant current density of 1 A g-1. Moreover, the Mo2C particles provide many electrochemically active sites, leading to additional improvement in sodium storage. The C-Mo2C fiber film has a capacity of 134 mA h g-1 at 1 A g-1 and a high capacity of 99 mA h g-1 even at 5 A g-1.

[Analysis on main factors for successful quitting--study on the one-year follow-up for Chinese 'Quit and Win' in 2002].

OBJECTIVE: China took part in the fifth 'Quit & Win in 2002 which was held by WHO and KTL in Finland. 27398 participants from eleven cities in China took part in the contest. Then we had a one-year follow-up research from May to June in 2003. METHODS: A random sample of 1298 was surveyed by mailing, telephone and visiting. RESULTS: One year were 27.71%. Main factors for successful quitting in one year included "intention to stop smoking completely by participating the contest", "age", "marriage", et al. But some factors had no effect on the successful quitting, such as cessation measures, helping from others, et al. CONCLUSION: It is important for smokers to make a decision and perseverance to stop smoking.

The effect of glucose levels on fetal birth weight: a study of Chinese gravidas in Tianjin, China.

The relationship between maternal glucose intolerance and fetal birth weight remains, to a large extent, unknown in Chinese gravidas. From December 1998 to December 1999, 9471[corrected] women in six urban districts of Tianjin, China, underwent an initial screening using a 50-g, 1-h glucose load at 26-30 gestational weeks. Women with a serum glucose reading >or=7.8 mmol/l, were followed up for a 75-g, 2-h glucose tolerance test, which was interpreted using the 1998 World Health Organization's (WHO) criteria for diabetes. A total of 174 women had gestational diabetes mellitus. Complete data was collected in 170 women. Among them, 56 accepted diabetes management including self-home glucose monitoring, diet, and physical activity advice, and others received no treatment. The comparison group was 302 women with normal glucose tolerance (NGT). Glucose levels at the initial screening (partial R(2)=.0343, P<.0001), maternal weight gain during pregnancy (partial R(2)=.0915, P<.0001), and gestational week at delivery (partial R(2)=.0432, P<.0001) were determinants of fetal birth weight, controlling for maternal age, pregravid BMI, maternal stature, and other confounders. Both gestational diabetes mellitus (GDM) status and a positive screening but normal oral glucose tolerance test (OGTT) result were predictors of macrosomia (birth weight >or=4000 g). It concludes that maternal glucose levels correlate with fetal birth weight and a glucose level of 7.8 mmol/l or more at the initial screening is predictive of macrosomia in Chinese gravidas regardless of GDM status.

Commuting, leisure-time physical activity, and cardiovascular risk factors in China.

PURPOSE: The relationship between both commuting and leisure-time physical activity and selected cardiovascular risk factors was analyzed. METHODS: A cross-sectional survey was carried out in 1996 in urban Tianjin, China. A total of 2002 male and 1974 female subjects aged 15-69 yr completed the survey. Commuting, leisure-time physical activity, body mass index, blood pressure, and cigarette smoking were determined. RESULTS: Doing more than 60 min of commuting physical activity or combined commuting and leisure-time physical activity was related to the highest mean blood pressure and the highest prevalence of hypertension among both genders compared with going to and from work by bus; 31-60 min commuting only or commuting plus leisure-time physical activity was associated with the lowest mean blood pressure in women and the lowest prevalence of hypertension in both genders. Daily time on commuting or leisure-time physical activity was inversely related to mean body mass index and prevalence of overweight among men and prevalence of smoking among both genders. CONCLUSION: The present study suggests that commuting and leisure-time physical activity were favorably associated with cardiovascular risk factors in this Chinese population, except that more than 60 min of physical activity was associated with high blood pressure.

Socio-economic status and serum lipids: a cross-sectional study in a Chinese urban population.

Socio-economic status and serum lipids are important factors in the progression of cardiovascular disease. We studied the association between socio-economic status and serum lipids in a Chinese urban population. In all, 4,541 respondents (2,231 men and 2,310 women) between 25-64 years of age participated in a cross-sectional population survey carried out in Tianjin, China, and provided blood samples. Three socio-economic indicators (education, occupation, and income), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were determined. People in higher socio-economic groups had a more unfavorable serum lipid profile compared with those in lower socio-economic groups. This significant association was especially apparent in men. Education seemed to be the most important predictor of serum lipids in the three socio-economic indicators. The direction of the association between high socio-economic status and poor serum lipid profiles appears to be opposite to those observed in the developed countries.

Physical activity during leisure and commuting in Tianjin, China.

OBJECTIVE: To investigate physical activity during leisure time and commuting among persons aged 15-69 years in the urban population of Tianjin, China, and to assess its associations with demographic and health-related characteristics. METHODS: In 1996 a cross-sectional survey of 2002 males and 1974 females provided information on physical activity during leisure time and commuting and on demographics and health behaviours. FINDINGS: No leisure-time physical activity was engaged in by 67% of females and 61% of males. However, only 4% of females and 9% of males reported an absence of physical activity during commuting. The mean duration of leisure-time physical activity for the whole population was about 10 min per day. The average commuting time on foot or by bicycle was about 30 min. Leisure-time physical activity was more frequent among highly educated people, people with high incomes, white-collar workers, married people, non-smokers, or people commuting on foot or by bicycle than among other people. Persons with low incomes, male blue-collar workers and married people were more likely than others to engage in 30 min or more per day of physical activity on foot or by bicycle when commuting. CONCLUSION: People in Tianjin engaged in a high level of physical activity when commuting and a low level of leisure-time physical activity.