Toxicity and oxidative stress of HepG2 and HL-7702 cells induced by PAH4 using oil as a carrier.

Polycyclic aromatic hydrocarbons (PAHs), a widespread class of food pollutants, are commonly exposed to humans along with edible oil. The dietary exposure pattern of PAH4 was simulated to study the toxicity and oxidative stress of oil-based PAH4 on hepatocytes. The findings demonstrated that oil-based PAH4 induced cell viability and mitochondrial membrane potential decreased and promoted apoptosis and oxidative stress in a concentration-dependent manner. Benzo[a]pyrene had the strongest toxicity and HL-7702 cells were more sensitive to toxicity than HepG2 cells, due to differences in induced CYP1A enzyme activity. Oil-based PAH4 had greater cytotoxicity than PAH4, attributed to the synergistic effect of oil and PAH4. Furthermore, oil-based PAH4 induced oxidative stress in HepG2 and HL-7702 cells through the same AHR-Nrf2-KEAP1 pathway, which was elucidated by detecting genes and proteins expression. This study lays the foundation for elucidating the harm of dietary exposure to PAHs and reminds us that food composition may increase the harm of PAHs.

Combined toxicity of oil-based PAH4 mixtures on HL-7702 cells.

Polycyclic aromatic hydrocarbons (PAHs) as a group of prevalent persistent organic pollutants in the environment are always found as mixtures. The combined toxicity of oil-based PAH4 seems seldom to be mentioned. To evaluate the combined toxicity of oil-based PAH4 mixtures on HL-7702 cells, the effects of single, binary, ternary, and quaternary mixtures on cell viability were examined, and the concentration addition model and combination index (CI)-isobologram model were selected to predict the toxicological interactions of the mixtures. The results showed that the PAH4 mixtures had a concentration-dependent effect on cell viability. The CI model was more suitable for elucidating the toxicity interactions of mixtures. In addition, the combined toxicity of BaA + BaP and BaA + Chr + BbF + BaP was antagonistic, BaA + Chr, BaA + BbF, Chr + BbF, and BaA + Chr + BbF was synergistic, and the remaining mixtures shifted from antagonistic to synergistic. Antagonistic effects were observed in all mixtures containing BaP, indicating that oil-based PAH4 mixtures containing BaP had a mitigating effect on cytotoxicity. Furthermore, BbF was identified as playing a key role in the synergistic effects in binary and ternary mixtures. This study provided a new acknowledgment to assess the interactions of PAH4 mixtures which is helpful for further study of the toxicity risks in the environment.

Health effects and externalities of the popularization of sanitary toilets: evidence from Rural China.

BACKGROUND: This study aimed to assess the impact of the increased prevalence of sanitary toilets in rural areas on the health of rural residents, and whether the popularity thereof has a positive externality. This study investigates whether the broader use of sanitary toilets has had a positive effect on the health of people who do not have access to them. METHODS: Data from the China Family Panel Studies from 2012 to 2014 and a two-way fixed effect model were used to investigate the relationship between the prevalence of village sanitary toilets and the health of rural residents of all ages. RESULTS: The results showed that: (1) the increase in the prevalence of sanitary toilets in villages is conducive to improving the health level of rural residents; (2) the widespread adoption of sanitary toilets in rural areas has improved the health of not only residents with access to these toilets but also residents without access; (3) the health of children is more sensitive to improvements in sanitary conditions of toilets; and (4) there are significant regional differences in the impact of the popularity of sanitary toilets on the health of rural residents. CONCLUSIONS: This study found that the popularity of sanitary toilets has externalities, improving not only the health of residents who use them but also the health of other residents. This study enriches the literature in the field of health effects of sanitation improvement, while providing a reference for developing countries to further enhance the living environment in rural areas. In the future, the popularization of sanitary toilets should be vigorously promoted to reduce the incidence of diseases.

Calcium-binding motif-mediated binding of redundant calcium offers a chimeolysin enhanced bactericidal activity and extended host range under physiological conditions.

OBJECTIVES: Calcium-binding motifs are shared by multiple bacteriophage lysins; however, the influence of calcium on the enzymatic activity and host range of these enzymes is still not understood. To address this, ClyF, a chimeric lysin with a putative calcium-binding motif, was used as a model for in vitro and in vivo investigations. METHODS: The concentration of calcium bound to ClyF was determined by atomic absorption spectrometry. The influence of calcium on the structure, activity and host range of ClyF was assessed by circular dichroism and time-kill assays. The bactericidal activity of ClyF was evaluated in various sera and a mouse model of Streptococcus agalactiae bacteraemia. RESULTS: ClyF has a highly negatively charged surface around the calcium-binding motif that can bind extra calcium, thereby increasing the avidity of ClyF for the negatively charged bacterial cell wall. In line with this, ClyF exhibited significantly enhanced staphylolytic and streptolytic activity in various sera containing physiological calcium, including human serum, heat-inactivated human serum, mouse serum and rabbit serum. In a mouse model of S. agalactiae bacteraemia, intraperitoneal administration of a single dose of 25 µg/mouse ClyF fully protected the mice from lethal infection. CONCLUSIONS: The present data collectively showed that physiological calcium improves the bactericidal activity and host range of ClyF, making it a promising candidate for the treatment of infections caused by multiple staphylococci and streptococci.

Architecture of Nanoantioxidant Based on Mesoporous Organosilica Trp-Met-PMO with Dipeptide Skeleton.

A nanoantioxidant of mesoporous organosilica (Trp-Met-PMO) based on the framework of tryptophan-methionine dipeptide was first designed and constructed by condensation between self-created dipeptide organosilica precursor (Trp-Met-Si) and tetraethyl orthosilicate (TEOS) in alkaline conditions under the template hexadecyl trimethyl ammonium bromide (CTAB). Trp-Met-Si was prepared by the reaction between dipeptide Trp-Met and conventional organosilicon coupling agent isocyanatopropyltriethoxysilane (IPTES) via a multiple-step reaction method. The material Trp-Met-PMO was confirmed by XRD, FT-IR and N2 adsorption-desorption analysis. The material Trp-Met-5-PMO with low amounts of organosilica precursor remained a mesoporous material with well-ordered 2D hexagonal (P6mm) structure. With increasing amounts of organosilica precursor, a mesoporous structure was still formed, as shown in the material Trp-Met-100-PMO with the highest amounts of organosilica precursor. Moreover, pore size distribution, surface area and porosity of Trp-Met-PMO are regulated with different amounts of organosilica precursor Trp-Met-Si. The antioxidant activity of Trp-Met-PMO was evaluated by ABTS free radical-scavenging assay. The results showed that antioxidant activity was largely enhanced with increasing contents of organosilica precusor Trp-Met-Si in the skeleton. The material Trp-Met-40-PMO exhibited maximum scavenging capacity of ABTS free radicals, the inhibition percent was 5.88%. This study provides a design strategy for nanoantioxidant by immobilizing short peptides within the porous framework of mesoporous material.

Deep Neural Network for 3D Shape Classification Based on Mesh Feature.

Virtual reality, driverless cars, and robotics all make extensive use of 3D shape classification. One of the most popular ways to represent 3D data is with polygonal meshes. In particular, triangular mesh is frequently employed. A triangular mesh has more features than 3D data formats such as voxels, multi-views, and point clouds. The current challenge is to fully utilize and extract useful information from mesh data. In this paper, a 3D shape classification network based on triangular mesh and graph convolutional neural networks was suggested. The triangular face of this model was viewed as a unit. By obtaining an adjacency matrix from mesh data, graph convolutional neural networks can be utilized to process mesh data. The studies were performed on the ModelNet40 dataset with an accuracy of 91.0%, demonstrating that the classification network in this research may produce effective results.

Impact of fertility on the longevity of older rural Chinese women: an analysis of a longitudinal survey.

BACKGROUND: This study evaluates the impact of fertility during the childbearing period on the longevity of older rural Chinese women and verifies whether any trade-off exists between women's longevity and their number of children to provide empirical evidence for improving health intervention policies and formulating active fertility policies in low-fertility countries. METHODS: Based on the data of the deaths of 1623 older adults aged 65 and above during 2014-2018 in the Chinese Longitudinal Healthy Longevity Survey, this study explores the relationship between the number of children born and older rural women's longevity using the ordinary least squares method. Furthermore, the impact of fertility on the longevity of men and women in rural and urban areas, along with other reproductive behaviours on older rural women's longevity, were analysed. RESULTS: There was a significant negative correlation between the number of children born and women's longevity (ß = - 0.555, p < 0.05). Additionally, their longevity exhibited a decreasing trend with having birthed more sons and an increasing trend with more daughters. Age at first and last births had a significant positive relationship with rural women's longevity; however, the effect of fertility on the longevity of older rural and urban men and older urban women was not significant. CONCLUSIONS: It is confirmed that there is a trade-off between fertility and longevity for rural women in China. Future research should focus on compensating for the decline in female longevity caused by the number of children born and promote the concept of a healthy pregnancy, scientific nurture, and gender equality in fertility.

[The physiology of plant seed aging: a review].

Seed quality plays an important role in the agricultural and animal husbandry production, the effective utilization of genetic resources, the conservation of biodiversity and the restoration and reconstruction of plant communities. Seed aging is a common physiological phenomenon during storage. It is a natural irreversible process that occurs and develops along with the extension of seed storage time. It is not only related to the growth, yield and quality of seed and seedling establishment, but also has an important effect on the conservation, utilization and development of plant germplasm resources. The physiological mechanisms of seed aging are complex and diverse. Most studies focus on conventional physiological characterization, while systematic and comprehensive in-depth studies are lacking. Here we review the recent advances in understanding the physiology of seed aging process, including the methods of seed aging, the effect of aging on seed germination, and the physiological and molecular mechanisms of seed aging. The change of multiple physiological parameters, including seed vigor, electrical conductivity, malondialdehyde content and storage material in the seed, antioxidant enzyme activity and mitochondrial structure, were summarized. Moreover, insights into the mechanism of seed aging from the aspects of transcriptome, proteome and aging related gene function were summarized. This study may facilitate the research of seed biology and the conservation and utilization of germplasm resources.

Antioxidant capacity and interaction of endogenous phenolic compounds from tea seed oil.

Endogenous phenols play a significant role in delaying oil rancidity. In this study, the profile of 22 endogenous phenols was determined from tea seed oil by UPLC-MS/MS, of which 15 phenols were identified for the first time. Then seven phenols with high content and strong antioxidant capacity were selected to investigate interaction using the DPPH· and Rancimat. It was found that the interaction of combinations was inconsistent in different media. Combined quercetin + esculetin, caffeoyl tartaric acid + esculetin, caffeoyl tartaric acid + gentisic acid and esculetin + gentisic acid showed synergistic antioxidant effects in oil and ethanol systems. Moreover, through the evaluation of the lipid oxidation process, combined esculetin + gentisic acid exhibited the greatest synergistic antioxidant effect. Notably, combined quercetin + esculetin had an inhibitory effect on the formation of volatile compounds. These findings may provide a basis for explaining the oxidation stability of tea seed oil.

Access to sanitary toilets and health outcomes: A panel data analysis using two-way fixed effects model.

Based on the data regarding the renovation of the toilets of 30 provinces (municipalities) in rural China from 2005 to 2017, this study utilized a two-way fixed effect model to empirically test the impact of access to sanitary toilets on health, which include intestinal infectious diseases (consisting of hepatitis A, dysentery, and typhoid) and child mortality (consisting of perinatal mortality, infant mortality, and the mortality rate of children under 5). This study attempted to assess the health outcomes of the "toilet revolution" in rural China. The results showed that: (1) Access to sanitary toilets effectively reduced the incidence of hepatitis A and dysentery. For every 1% increase in the rate of access to sanitary toilets, the incidence of hepatitis A was reduced by 5.6%, and the incidence of dysentery was reduced by 36.5%. (2) Access to sanitary toilets does not significantly reduce child mortality. (3) There are obviously regional differences in the impact of access to sanitary toilets on the health outcomes. The renovation of sanitary toilets has shown the most significant effect on reducing the incidence of intestinal infectious diseases in the central region as well as the effect on reducing child mortality in the western region. It is implied that the health outcomes of China's "toilet revolution" may provide supporting evidence and experience for other developing countries and regions in implementing toilet renovation projects.

Intrinsic Antimicrobial Peptide Facilitates a New Broad-Spectrum Lysin LysP53 to Kill Acinetobacter baumannii In Vitro and in a Mouse Burn Infection Model.

Antimicrobial resistance-related infections of Gram-negative pathogens pose a huge threat to global public health. Lysins, peptidoglycan hydrolases from bacteriophages, are expected as an alternative weapon against drug-resistant bacteria. In the present study, we report a new lysin LysP53 from Acinetobacter baumannii phage 53. Bioinformatic analysis revealed that LysP53 contains a positively charged N-terminal region and a putative peptidase catalytic domain. In vitro biochemical experiments showed that LysP53 is active against multiple antibiotic-resistant Gram-negative bacteria, including A. baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, with a reduction of 5 logs in viable A. baumannii number after exposure to 100 µg/mL LysP53 for 1 h. Further studies showed that LysP53 contains a functional antimicrobial peptide, i.e., N-terminal 33 aa, with a comparable spectrum of activity to LysP53. In an A. baumannii-associated mouse model of burn infection, a single dose of 14 µg/mouse LysP53 (57.6 µM) showed higher decolonization efficacy than 4 µg/mouse minocycline- (874 µM; p < 0.05) and buffer-treated groups (p <0.001), leading to a bacterial reduction of 3 logs. Our findings collectively establish that LysP53 could be a promising candidate in the treatment of topical infections caused by multiple Gram-negative pathogens.

Does the Internet Use Improve the Mental Health of Chinese Older Adults?

Purpose: The Internet has become an important part of daily life. However, older adults in China remain digital refugees amid the rapid development of digital information technology. This study attempts to scientifically answer how Internet use affects the subjective welfare of older adults. Method: Using data from the 2014 and 2016 China Longitudinal Aging Social Survey (CLASS), a combination of ordinary least squares, ordered logit regression models, and propensity score matching (PSM) models were used to analyze the effects of Internet use on the mental health of Chinese older adults. Results: Our findings suggest that Internet use affects the mental health of older adults and increases the incidence of their depressive symptoms. These findings are robust to changing the key indicators, research method, and sample. Further heterogeneity analysis reveals that the negative effects on mental health are more evident for specific groups of older adults, such as those who are women, younger and middle-aged, high-income, non-rural Hukou, less educated, and living with others. Conclusions: Cultivating the ability of older adults to use the Internet and maintain a rational attitude while doing so can prevent its negative impact on their life satisfaction. Moreover, it can improve their attitudes toward using the technology and reduce their anxiety.

Three Polyoxovanadates-Based Organic-Inorganic Hybrids: Structural Variation, Bifunctional Electrocatalytic Activities, and Computational Studies.

Three bimetallic organic-inorganic hybrids based on the [V2O6]2- building unit, [Cu(pty)(V2O6)]·H2O (1), [Cu(pty)(V2O6)] (2), [Cu(tpy)(V2O6)] (3), (pty = 4'-(4″-pyridyl)-2,2':6',2″-terpyridine, tpy = 2,2':6',2″-terpyridine), were synthesized via a one-pot method. Hybrid 1 has a 1D straight chain architecture with [V2O6]2- clusters and Cu-pty complexes; hybrids 2 and 3 possess a 2D sheet structure including 10-membered rings assembled from four [Cu(pty)]2+ motifs and six [V2O6]2- clusters in 2, and two [Cu(tpy)]2+ units and eight [V2O6]2- clusters in 3. Noteworthy, hybrids 1-3 can be employed as bifunctional electrocatalysts for electroreduction of nitrite and electrooxidation of ascorbic acid. Additionally, theoretical calculations including the molecular electrostatic potential and the frontier molecular orbital were performed to estimate the electronic structure of hybrids 1-3. The natural bond orbital analysis was also calculated to interpret the electron charge distribution.

Untargeted LC-MS-based metabolomics revealed specific metabolic changes in cotyledons and roots of Ricinus communis during early seedling establishment under salt stress.

Early seedling development is one of the most crucial period of the plant's life cycle, which is highly susceptible to adverse environmental conditions, especially those impose by salt stress. Castor plant (Ricinus communis) is a famous non-edible oilseed and salt-resistant crop worldwide. However, the specific metabolic responses in the cotyledons and roots of this species during seedling establishment under salt stress are still not clearly understood. In the present study, 16 d castor seedlings were treated with 150 mM NaCl for 6 d, and the metabolite profiling of cotyledons and roots was conducted using liquid chromatography (LC) combined with electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS). The Principal Component Analysis (PCA) results showed that the metabolites were great differed in cotyledons and roots under salt stress. There were 38 differential metabolites, mainly including fatty acid, nucleic acid and organic acids in the cotyledons, but only 19 differential metabolites, mainly including fatty acid and organic acids in the roots under such condition. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that flavone and flavonol biosynthesis, pantothenate and CoA biosynthesis, citrate cycle and carotenoid biosynthesis were the common metabolic pathways in response to salt stress in the two organs. Salt stress caused metabolite process alteration mainly on carbon and nitrogen metabolisms, and the carbon allocation from root to cotyledon was increased. Additionally, changes of amino acids and nucleic acids profiles were only found in the cotyledons, and the roots could enhance the activity of antioxidant enzyme systems to scavenge ROS under salinity. In conclusion, the present research provides an improved understanding on specific physiological changes in the cotyledons in castor early seedlings, and explores their interaction under salt stress.

A Choline-Recognizing Monomeric Lysin, ClyJ-3m, Shows Elevated Activity against Streptococcus pneumoniae.

Streptococcus pneumoniae is a leading pathogen for bacterial pneumonia, which can be treated with bacteriophage lysins harboring a conserved choline binding module (CBM). Such lysins regularly function as choline-recognizing dimers. Previously, we reported a pneumococcus-specific lysin ClyJ comprising the binding domain from the putative endolysin gp20 from the Streptococcus phage SPSL1 and the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain from the PlyC lysin. A variant of ClyJ with a shortened linker, i.e., ClyJ-3, shows improved activity and reduced cytotoxicity. Resembling typical CBM-containing lysins, ClyJ-3 dimerized upon binding with choline. Herein, we further report a choline-recognizing variant of ClyJ-3, i.e., ClyJ-3m, constructed by deleting its C-terminal tail. Biochemical characterization showed that ClyJ-3m remains a monomer after it binds to choline yet exhibits improved bactericidal activity against multiple pneumococcal strains with different serotypes. In an S. pneumoniae-infected bacteremia model, a single intraperitoneal administration of 2.32 µg/mouse of ClyJ-3m showed 70% protection, while only 20% of mice survived in the group receiving an equal dose of ClyJ-3 (P < 0.05). A pharmacokinetic analysis following single intravenously doses of 0.29 and 1.16 mg/kg of ClyJ-3 or ClyJ-3m in BALB/c mice revealed that ClyJ-3m shows a similar half-life but less clearance and a greater area under curve than ClyJ-3. Taken together, the choline-recognizing monomer ClyJ-3m exhibited enhanced bactericidal activity and improved pharmacokinetic proprieties compared to those of its parental ClyJ-3 lysin. Our study also provides a new way for rational design and programmed engineering of lysins targeting S. pneumoniae.

Four new dual-functional electro-catalysts formed from small molybdenum clusters and Cu-pyridyl complexes.

By changing N-heterocyclic ligands in the same Mo7/Cu/N-ligand reaction systems, four new organic-inorganic hybrids based on isopolymolybdates, [Cu2(tpy)2(ß-Mo8O26)0.5(γ-Mo8O26)0.5]·0.25H2O (1), [Cu2(tpy)2(H2O)2(ß-Mo8O26)] (2), [Cu(bpy)(Mo3O10)]·H2O (3), and [Cu(bpy)(H2O)(ß-Mo8O26)0.5]0.5 (4) (tpy = 2,2':6',2''-terpyridine and bpy = 2,6-bis(pyrazol-1-yl) pyridine), were prepared using hydrothermal methods at different pH values. X-ray structural analysis shows that compound 1 has a 1D {-ß-[Mo8O26]-Cu2-γ-[Mo8O26]}n straight chain structure with mixed ß-[Mo8O26] and γ-[Mo8O26] polyoxoanions; compound 2 possesses a 3D supramolecular structure based on [Cu(tpy)]2+ motifs and ß-[Mo8O26] clusters; and compound 3 has a 1D chain structure built from [Cu(bpy)]2+ and [Mo3O10]2- units. In compound 4, [ß-Mo8O26] clusters are linked by [Cu(bpy)]2+ motifs to give rise to a 2D sheet structure including {(ß-Mo8O26)4Cu4} 8-membered rings. Cyclic voltammograms of compounds 1-4 display discrepant dual-functional electro-catalytic activities toward the reduction of nitrite and the oxidation of ascorbic acid in acidic solution. Electrocatalytic tests indicate that the [Mo3O10]2--based organic-inorganic hybrid exhibits better electro-catalytic performances than [Mo8O26]4--type hybrids towards oxidation and reduction.

Three polyoxometalates-based organic-inorganic hybrids decorated with Cu-terpyridine complexes exhibiting dual functional electro-catalytic behaviors.

By adjusting polyoxometalates in the same POM/Cu/terpyridine reaction systems, three new organic-inorganic hybrid solid materials based on Cu-terpyridine complexes, [Cu3(tpy)3(H2O)2(HPMoVI8VIV4O40(VIVO)2)]·2H2O (1), Cu5(tpy)5(H2O)2(α-PW12O40)2 (2), and [Cu3(tpy)3(H2O)4(α-P2W18O62)]·4H2O (3) (tpy = 2,2':6',2''-terpyridine), were prepared by using one-pot methods. X-ray structural analyses show that compounds 1-3 with a 1D chain structure constructed from Cu/tpy complexes were modified using bi-capped Keggin, Keggin and Wells-Dawson POMs. Compounds 1-3 have been fabricated to a bulk-modified carbon paste electrode to explore the electrochemical properties. Cyclic voltammetry demonstrates discrepant dual functional electro-catalytic activities toward the reduction of nitrite and the oxidation of ascorbic acid because of variant POMs. The results show that the PW12-Keggin-type hybrid exhibits a better dual functional electro-catalytic performance than bi-capped Keggin and Wells-Dawson hybrids for the reduction of nitrite and the oxidation of ascorbic acid.

The association between occupational-related mechanical stress and radiographic damage in psoriatic arthritis.

OBJECTIVE: To assess the association between occupational-related mechanical factors and the severity of radiographic peripheral and axial joint damage in patients with longstanding Psoriatic Arthritis (PsA). METHODS: Patients with longstanding PsA (disease duration≥10 years) were identified from a prospective longitudinal cohort. Using an occupation history questionnaire, patients were asked to report all paid employments since the age of 18. The key predictor variables included various occupational-related mechanical exposures. A job classification database was used to rate the level of exposure to various occupational physical activities. The outcomes were the extent of radiographic damage in the peripheral and axial joints, as measured by the modified Steinbrocker score (mSS), and the modified Stokes Ankylosing Spondylitis Spine Score (mSASSS). The association between the predictors and outcome variables was assessed by negative binomial regression models after adjusting for potential confounding variables. RESULTS: A total of 307 eligible patients were analyzed. In the multivariable analysis, exposure to prolonged repetitive hand movements (exp(ß) 1.17 (95% 1.07, 1.28)) and occupations that required higher level of finger dexterity (exp(ß) 1.27 (95% 1.09, 1.47)) were associated with a higher mSS. With regards to axial damage, none of the occupational exposures or workers abilities was associated with mSASSS. CONCLUSION: High level of occupation-related mechanical stress is associated with increased radiographic peripheral joint damage among patients with longstanding PsA. This finding supports the potential role of micro-trauma in the pathogenesis of PsA.

Effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric kidney transplantation: a systematic review and meta-analysis of observational studies.

BACKGROUND: CYP3A5 genetic polymorphisms have been reported to be strongly associated with the tacrolimus pharmacokinetics in adult kidney transplantation. However, there is no published meta-analysis in the influence of CYP3A5 variants on the requirements of the tacrolimus dose in pediatric renal-transplant recipients (RTRs). We wished to determine the effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric RTRs. METHODS: A literature search was conducted to include relevant articles by searching PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. Pharmacokinetic-associated parameters such as dose administration, as well as concentrations and dose-adjusted concentrations of tacrolimus were extracted and the meta-analysis undertaken. RESULTS: The meta-analysis involved four studies and one study series involving 268 pediatric RTRs. A significant difference was observed in the mean trough concentration/dose of tacrolimus between recipients carrying CYP3A5* 3/*3 variants (referred to as "non-expressers") and those carrying CYP3A5*1 (referred to as "expressers") [standard mean difference (SMD)=-1.09, 95% confidence interval (CI): -1.92 to -0.25, P=0.011]. Moreover, significance was observed in the mean daily dose of tacrolimus between non-expressers and expressers in pediatric RTRs (SMD=0.44, 95% CI: 0.20 to 0.68, P<0.001). CONCLUSION: Our meta-analysis identified a positive correlation between CYP3A5 genotypes and tacrolimus pharmacokinetics in pediatric RTRs.

Role of endothelial-to-mesenchymal transition induced by TGF-ß1 in transplant kidney interstitial fibrosis.

Chronic allograft dysfunction (CAD) induced by kidney interstitial fibrosis is the main cause of allograft failure in kidney transplantation. Endothelial-to-mesenchymal transition (EndMT) may play an important role in kidney fibrosis. We, therefore, undertook this study to characterize the functions and potential mechanism of EndMT in transplant kidney interstitial fibrosis. Proteins and mRNAs associated with EndMT were examined in human umbilical vein endothelial cells (HUVECs) treated with transforming growth factor-beta1 (TGF-ß1) at different doses or at different intervals with western blotting, qRT-PCR and ELISA assays. Cell motility and migration were evaluated with motility and migration assays. The mechanism of EndMT induced by TGF-ß1 was determined by western blotting analysis of factors involved in various canonical and non-canonical pathways. In addition, human kidney tissues from control and CAD group were also examined for these proteins by HE, Masson's trichrome, immunohistochemical, indirect immunofluorescence double staining and western blotting assays. TGF-ß1 significantly promoted the development of EndMT in a time-dependent and dose-dependent manner and promoted the motility and migration ability of HUVECs. The TGF-ß/Smad and Akt/mTOR/p70S6K signalling pathways were found to be associated with the pathogenesis of EndMT induced by TGF-ß1, which was also proven in vivo by the analysis of specimens from the control and CAD groups. EndMT may promote transplant kidney interstitial fibrosis by targetting the TGF-ß/Smad and Akt/mTOR/p70S6K signalling pathways, and hence, result in the development of CAD in kidney transplant recipients.