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Background Exposure to aflatoxin, a mycotoxin produced by fungi that commonly contaminates cereal crops across sub-Saharan Africa, has been associated with impaired child growth. We investigated the impact of aflatoxin exposure on the growth of Gambian infants from birth to two years of age, and the impact on insulin-like growth factor (IGF)-axis proteins. Methods A subsample ( N  = 374) of infants from the Early Nutrition and Immune Development (ENID) trial (ISRCTN49285450) were included in this study. Aflatoxin-albumin adducts (AF-alb) were measured in blood collected from infants at 6, 12 and 18 months of age. IGF-1 and IGFBP-3 were measured in blood collected at 12 and 18 months. Anthropometric measurements taken at 6, 12, 18 and 24 months of age were converted to z-scores against the WHO reference. The relationship between aflatoxin exposure and growth was analysed using multi-level modelling. Results Inverse relationships were observed between lnAF-alb and length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores from 6 to 18 months of age (β = − 0·04, P  = 0·015; β = − 0·05, P  = 0.003; β = − 0·06, P  = 0·007; respectively). There was an inverse relationship between lnAF-alb at 6 months and change in WLZ between 6 and 12 months (β = − 0·01; P  = 0·013). LnAF-alb at 12 months was associated with changes in LAZ and infant length between 12 and 18 months of age (β = − 0·01, P  = 0·003; β = − 0·003, P  = 0·02; respectively). LnAF-alb at 6 months was associated with IGFBP-3 at 12 months ( r  = − 0·12; P  = 0·043). Conclusions This study found a small but significant effect of aflatoxin exposure on the growth of Gambian infants. This relationship is not apparently explained by aflatoxin induced changes in the IGF-axis.

BackgroundChronic aflatoxin (AF) exposure has been shown to occur at high levels in children from sub-Saharan Africa (SSA), and has been associated with growth retardation and immune dysfunction. Our objective was to investigate the impact of AF exposure on immune development in early infancy using thymic size and antibody (Ab) response to vaccination as indicators of immune function.MethodsA total of 374 infants born between May 2011 and December 2012 were enrolled into the current study. These infants were recruited from a larger, randomised trial examining the impact of nutritional supplementation of mothers and infants on infant immune development (the Early Nutrition and Immune Development Trial). Thymic size (Thymic Index, TI) was measured by sonography at 1 week, 8 weeks, 24 weeks and 52 weeks of infant age. Infants were given the diphtheria–tetanus–pertussis (DTP) vaccine at 8 weeks, 12 weeks and 16 weeks of age, and Ab responses to each vaccine measured at 12 weeks and 24 weeks of age. AF-albumin (AF-alb) adduct levels in infant blood were measured by ELISA as the biomarker of AF exposure.ResultsThe geometric mean (GM) level of AF-alb increased with age. Only half of infants had detectable AF-alb with a GM of 3.52 pg/mg at 24 weeks, increasing to 25.39 pg/mg at 52 weeks, when 98% of infants had AF-alb >limit of detection. Significant negative association of AF-alb level with TI was seen in infants during the first 24 weeks, especially at 8 weeks of age (p<0.001), which is the time point of fastest thymus growth. There were no associations between AF exposure level and Ab response to pertussis and tetanus, but a significant positive correlation was observed between AF-alb level and Ab titre to diphtheria (p<0.005).ConclusionsHigh levels of AF exposure during early infancy may impact on infant immune development.Trial registration numberISRCTN49285450.

Background Information about how newspapers portray antidiabetic medicines to readers is lacking. This study investigated the reporting on antidiabetic medicines in the most widely circulated newspapers published in the United Kingdom (UK) and the United States (US) over a 10-year period. Methods The Nexis UK database was used to identify and select relevant articles. Systematic content analysis of the articles which met the inclusion criteria (articles of any format that contained reference to antidiabetic medicines) within the highest circulated newspapers in the UK and US between 2009 and 2018 was conducted. Inter-rater reliability of coding was established using a 10% sample of the identified articles. Results A total of 560 (369 UK and 191 US) relevant newspaper articles were retrieved. In the UK, the number of relevant articles showed a slightly increasing trend over the study period, while in the US, article numbers declined over the study period. Safety/risk of antidiabetic medicines was the most frequent theme covered by the articles (34.6%). Over one-third of the newspaper articles were written from a clinical perspective (37.7%). Insulin was the most commonly discussed class of antidiabetic medicine (23.1%). Control of blood sugar levels (53.1%) and side effects/toxicity (92.7%) were the most frequently reported benefit and risk of antidiabetic medicines, respectively. The most frequently reported organ systems harmed by antidiabetic medicines were the cardiovascular, endocrine and gastrointestinal systems. The UK newspapers were more likely to report the benefits of antidiabetic medicines ( p  = 0.005), while the US articles were more likely to report on harms/risks ( p  = 0.001). The majority of relevant articles (91.8%) were judged as having a balanced judgement, while 8.2% of the articles were rated as exaggerated. Conclusions This study has revealed that antidiabetic medicines are indeed reported on by UK and US newspapers. As media portrayal has the potential to negatively or positively influence patients’ views of their medication for diabetes, healthcare professionals should check on patients’ beliefs and knowledge about their medication and proactively provide objective and balanced information (including promotion of medication adherence).

Background Medication adherence, one of the most important aspects in the process of optimal medicines use, is unfortunately still a major challenge in modern healthcare, and further research is required into how adherence can be assessed and optimised. The aim of this study was to use a combined method approach of self-report and dried blood spot (DBS) sampling coupled with population pharmacokinetic (PopPK) modelling, to assess adherence to metformin in adult patients with type 2 diabetes. Further aims were to assess metformin exposure levels in patients, determine factors associated with non-adherence with prescribed metformin, and to explore the relationship between adherence and therapeutic outcomes. Methods A combined method approach was used to evaluate metformin adherence in patients with type 2 diabetes who had been prescribed metformin for a minimum period of 6 months. Patients were recruited from consultant-led diabetic outpatient clinics at three hospitals in Northern Ireland, UK. Data collection involved self-reported questionnaires [Medication Adherence Report Scale (MARS), Beliefs about Medicines Questionnaire and Centre for Epidemiologic Studies Depression Scale], direct measurement of metformin concentration in DBS samples, and researcher-led patient interviews. The DBS sampling approach was coupled with population pharmacokinetic (PopPK) modelling, which took account of patient characteristics, metformin dosage and type of formulation prescribed (immediate or sustained release). Results The proportion of patients considered to be adherent to their prescribed metformin, derived from self-reported MARS scores and metformin concentration in DBS samples, was 61.2% (74 out of 121 patients). The majority ( n  = 103, 85.1%) of recruited patients had metformin exposure levels that fell within the therapeutic range. However, 17 patients (14.1%) had low exposure to metformin and one patient (0.8%) had undetectable metformin level in their blood sample (non-exposure). Metformin self-administration and use of a purchased adherence pill box significantly increased the probability of a patient being classified as adherent based on logistic regression analysis. Both HbA1c and random glucose levels (representing poor glycaemic control) in the present research were, however, not statistically linked to non-adherence to metformin ( P  > 0.05). Conclusions A significant proportion of participating patients were not fully adherent with their therapy. DBS sampling together with the use of a published PopPK model was a useful, novel, direct, objective approach to estimate levels of adherence in adult patients with type 2 diabetes (61.2%).

Organophosphorus hydrolase can effectively degrade organic phosphorus compounds such as sarin. In this study, we constructed a recombinant Bacillus subtilis mutant expressing organophosphorus hydrolase, measured the effect of the mutant on the degradation rate of nerve agent sarin, and selected the optimal mutation scheme. Three different hydrolase mutant genes, 257L, 257Y and 303T, were ligated to PMA0911 vector and transferred into Bacillus subtilis WB800 to construct the target recombinant strain successfully. The recombinant bacteria secreted the target protein by fermentation. The effect of enzyme protein on the degradation of sarin was determined by the benzidine method. The optimal mutant was screened, and its enzymatic performance was explored. The effects of three organophosphorus hydrolase mutants on the hydrolysis rate of sarin were detected. The results showed that the 257Y mutant accelerated the hydrolysis of sarin significantly. Point mutation can improve the enzyme activity of wild-type organophosphorus hydrolase to a certain extent, laying the foundation for subsequent in-depth research.

Due to the abuse of antibiotics, more and more bacteria are resistant to antibiotics. Non antibiotic nano antibacterial materials emerge as the times require. Carbon based nano enzyme is an efficient and environmentally friendly antibacterial material with certain antibacterial effect. It has simple structure and good compatibility. It can be combined with a variety of antibacterial substances to form composite antibacterial materials, expand the scope of antibacterial and improve the antibacterial ability. This paper summarizes the research progress of three kinds of carbon based nanoenzymes including carbon nanotubes, graphene, carbon quantum dots and their composites in the field of antibacterial.

The biodegradation of organophosphorus pesticides is characterized by high efficiency, mild reaction conditions, no stimulation, environmental friendliness and no secondary pollution, however, the hydrolysis activity, expression level and thermal stability of wild-type enzymes restrict the practical application of biodegradation seriously. Using protein engineering methods, researchers have made many achievements in improving the properties of enzymes.

The degradation of oily sludge is an important subject in the field of environmental remediation, especially the degradation of aromaticity in oily sludge, because its harm to human body is immeasurable, it is urgent to find an effective method to degrade oily sludge. Taking the oily sludge of Karamay oil field in Xinjiang as the research object, the chemical composition of the oily sludge was determined through the analysis of the chemical composition of the oily sludge. A strain was isolated from nearby contaminated soil, and was identified by ultraviolet spectroscopy, liquid chromatography, Gas chromatography-mass spectrometry, and other methods, it was found that the strain had a good degradation ability to aromaticity, with a degradation rate of 98.2%.

Molecular sensors and switches have made important contributions to biomedical devices and molecular computational operations. There are numerous molecular designs using a fluorophore linked through a spacer group to a receptor(s), with a wide dynamic range, directional precision, target specificity, and molecular logic capability. Tb(III) and Eu(III) metal ions have natural luminescence lifetimes in the order of milliseconds. As a result they have been used as probes that allow discrimination between probe emission and background fluorescence using timeresolved techniques. Unfortunately the free ions themselves absorb light poorly so cannot provide the sensitivity often required of a probe or a sensor. Their performance however can be improved dramatically by the coordination of the metal ions to organic chelate ligands containing appropriate organic fluorophores.This project is based on the design and synthesis of Tb(III) and Eu(III) complexes of phthalimide and phthalamate derivatives as responsive lanthanide complexes. Phthalimide and phthalamate compounds are organic chromophores. Four acyclic phthalimide derivatives, L1, L3, L5 and L7, were prepared through condensation reaction of phthalic anhydride and the corresponding amine derivatives in glacial acetic acid. These phthalimide derivatives, L1, L3, L5 and L7, were then hydrolysed under basic conditions to yield the desired phthalamate compounds, L2, L4, L6 and L8. The yields of these phthalamate derivatives (L2, L4, L6 and L8)were 50%-70%. They are fully characterised by and 13C NMR spectroscopy, elemental analysis, mass spectrometer, IR and melting point analysis.A series of macrocycles with Ai-substituted phthalimide pendant arm(s) L9_12were synthesised. The macrocyclic phthalimide derivatives were prepared by incorporating A-bromoalkyl phthalimide onto tri-tert-butyl-1,4,7,10- tetraazacyclododecane-1,4,7-triacetate, di-tert-butyl-1,4,7,10- tetraazacyclododecane-1,4-diacetate and mono-tert-butyl-1,4,7,10- tetraazacyclododecane-monoacetate through nucleophilic substitution reactions. Removal of t-butyl functions and retention of phthalimide was achieved in trifluoroacetic acid to yield the final products (6%-14%). 1,4,7,10- Tetraazacyclododecane was alkylated on its 4 nitrogen sites by phthalimide function with a propyl bridge to yield L13 (10%). L913 were fully characterized by : H and 13C NMR spectroscopy, elemental analysis, mass spectrometer, 1R and melting point analysis. Apart from L1, L3, L4, Ls and L10 all the phthalimide and phthalamate derivatives synthesised in this thesis are new.The optimal metal-to-ligand ratio of 1:2 was established for acyclic phthalamatebased terbium complexes, whereby the best antennae effects on the luminescence properties of these complexes were observed. The highest luminescence level of [Tb(L2)2]-, [Tb(L4)2]-, [Tb(L6)2]3- and [Tb(L8)2]- was observed at pH ca. 6, but it was quenched at pH>7. These four terbium complexes exhibited long emission lifetimes of the order of sub-milliseconds.

Background Pulmonary arterial hypertension (PAH) is a progressive and devastating disease characterized by pulmonary vascular remodeling which is associated with the malignant phenotypes of pulmonary vascular cells. Recently, the effects of heat shock protein 110 (Hsp110) in human arterial smooth muscle cells were reported. However, the underlying roles and mechanisms of Hsp110 in human pulmonary arterial endothelial cells (HPAECs) that was disordered firstly at the early stage of PAH remain unknown. Methods In this research, the expression of Hsp110 in PAH human patients and rat models was investigated, and the Hsp110 localization was determined both in vivo and in vitro. The roles and mechanism of elevated Hsp110 in excessive cell proliferation and migration of HPAECs were assessed respectively exposed to hypoxia. Small molecule inhibitors targeting Hsp110-STAT3 interaction were screened via fluorescence polarization, anti-aggregation and western blot assays. Moreover, the effects of compound 6 on HPAECs abnormal phenotypes in vitro and pulmonary vascular remodeling of hypoxia-indued PAH rats in vivo by interrupting Hsp110-STAT3 interaction were evaluated. Results Our studies demonstrated that Hsp110 expression was increased in the serum of patients with PAH, as well as in the lungs and pulmonary arteries of PAH rats, when compared to their respective healthy subjects. Moreover, Hsp110 levels were significantly elevated in HPAECs under hypoxia and mediated its aberrant phenotypes. Furthermore, boosted Hsp110-STAT3 interaction resulted in abnormal proliferation and migration via elevating p-STAT3 and c-Myc in HPAECs. Notably, we successfully identified compound 6 as potent Hsp110-STAT3 interaction inhibitor, which effectively inhibited HPAECs proliferation and migration, and significantly ameliorated right heart hypertrophy and vascular remodeling of rats with PAH. Conclusions Our studies suggest that elevated Hsp110 plays a vital role in HPAECs and inhibition of the Hsp110-STAT3 interaction is a novel strategy for improving vascular remodeling. In addition, compound 6 could serve as a promising lead compound for developing first-in-class drugs against PAH.