Exposure Assessment of Benzotriazole Ultraviolet Absorbers in Plastic Sports Field Dust and Indoor Dust: Are Plastic Sports Fields High Exposure Scenarios?

Benzotriazole ultraviolet absorbers (BUVs), as emerging contaminants of extensive use, especially in plastic sports fields, have aroused increasing concern due to their potential human and environmental impacts. However, BUV exposure from plastic sports field dust is still unknown. This study compared BUVs in plastic sports field dust and indoor dust for the first time. The order of the geometric mean concentrations of the total BUVs (ΣBUVs) in plastic sports field dust was indoor badminton courts (11023 ng g-1) > basketball courts (4777 ng g-1) > plastic tracks (3779 ng g-1) > synthetic turf (1920 ng g-1) > tennis courts (689 ng g-1). The geometric mean concentrations of ΣBUVs in indoor dust (1150 ng g-1) were lower than those in most plastic sports field dust. The dominant BUV was 2-hydroxy-4-(octyloxy)benzophenone (UV-531) in plastic sports field dust, while 2,2'-methylenebis[4-(1,1,3,3-tetramethylbutyl)-6-2H-benzotriazole-2-yl)phenol] (UV-360) was the dominant BUV in indoor dust. Releases from plastic track materials, sneaker soles, and friction between them might be important BUV sources in plastic track dust. The average estimated daily intakes of ΣBUVs from plastic sports field dust for general exercisers were lower than those from indoor dust, but those for exercisers with long time or professional athletes might be higher, potentially posing health risks.

Prevalence and associated phenotypes of DUSP6, IL17RD and SPRY4 variants in a large Chinese cohort with isolated hypogonadotropic hypogonadism.

BACKGROUND: FGF8-FGFR1 signalling is involved in multiple biological processes, while impairment of this signalling is one of the main reasons for isolated hypogonadotropic hypogonadism (IHH). Recently, several negative modulators of FGF8-FGFR1 signalling were also found to be involved in IHH, including DUSP6, IL17RD, SPRY2 and SPRY4. The aim of this study was to investigate the genotypic and phenotypic spectra of these genes in a large cohort of Chinese patients with IHH. METHODS: A total of 196 patients with IHH were enrolled in this study. Whole-exome sequencing was performed to identify variants, which was verified by PCR and Sanger sequencing. RESULTS: Four heterozygous DUSP6 variants (p.S157I, p.R83Q, p.P188L and p.N355I) were found in six patients. Cryptorchidism, dental agenesis, syndactyly and blue colour blindness were commonly observed in patients with DUSP6 mutations. Six heterozygous IL17RD variants (p.P191L, p.G35V, p.S671L, p.A221T, p.I329M and p.I329V) were found in seven patients. Segregation analysis indicated that 100% (5/5) of probands inherited the IL17RD variants from their unaffected parents, and oligogenicity was found in 4/7 patients. One rare SPRY4 variant (p.T68S) was found in a female patient with Kallmann syndrome who also carried a PLXNA1 mutation. CONCLUSION: Our study greatly enriched the genotypic and phenotypic spectra of DUSP6, IL17RD and SPRY4 in IHH. Mutations in DUSP6 alone seem sufficient to cause IHH in an autosomal dominant manner, whereas IL17RD or SPRY4 mutations may cause IHH phenotypes in synergy with variants in other IHH-associated genes.

ANOS1 variants in a large cohort of Chinese patients with congenital hypogonadotropic hypogonadism. / ä¸­å›½å ˆå¤©æ€§ä½Žä¿ƒæ€§è ºæ¿€ç´ æ€§æ€§è ºåŠŸèƒ½å‡é€€ç—‡æ‚£è€ ANOS1的突变.

OBJECTIVES: Congenital hypogonadotropic hypogonadism (CHH) is a rare congenital gonadal dysplasia caused by defects in the synthesis, secretion or signal transduction of hypothalamic gonadotropin releasing hormone. The main manifestations of CHH are delayed or lack puberty, low levels of sex hormones and gonadotropins, and may be accompanied with other clinical phenotypes. Some patients with CHH are also accompanied with anosmia or hyposmia, which is called Kalman syndrome (KS). ANOS1, located on X chromosome, is the first gene associated with CHH in an X-linked recessive manner. This study aims to provide a basis for the genetic diagnosis of CHH by analyzing the gene variant spectrum of ANOS1 in CHH and the relationship between clinical phenotype and genotype. METHODS: In this study, whole exome sequencing (WES) was used to screen rare sequencing variants (RSVs) of ANOS1 in a Chinese cohort of 165 male CHH patients. Four commonly used in silico tools were used to predict the function of the identified RSVs in coding region, including Polyphen2, Mutation Taster, SIFT, and Combined Annotation Dependent Depletion (CADD). Splice Site Prediction by Neural Network (NNSPLICE) was employed to predict possibilities of intronic RSVs to disrupt splicing. American College of Medical Genetics and Genomics (ACMG) guidelines was used to assess the pathogenicity of the detected RSVs. The ANOS1 genetic variant spectrum of CHH patients in Chinese population was established. The relationship between clinical phenotype and genotype was analyzed by collecting detailed clinical data. RESULTS: Through WES analysis for 165 CHH patients, ANOS1 RSVs were detected in 17 of them, with the frequency of 10.3%. A total of 13 RSVs were detected in the 17 probands, including 5 nonsense variants (p.T76X, p.R191X, p.W257X, p.R262X, and p.W589X), 2 splicing site variants (c.318+3A>C, c.1063-1G>C), and 6 missense variants (p.N402S, p.N155D, p.P504L, p.C157R, p.Q635P, and p.V560I). In these 17 CHH probands with ANOS1 RSVs, many were accompanied with other clinical phenotypes. The most common associated phenotype was cryptorchidism (10/17), followed by unilateral renal agenesis (3/17), dental agenesis (3/17), and synkinesia (3/17). Eight RSVs, including p.T76X, p.R191X, p.W257X, p.R262X, p.W589X, c.318+3A>C, c.1063-1G>C, and p.C157R, were predicted to be pathogenic or likely pathogenic ANOS1 RSVs by ACMG. Eight CHH patients with pathogenic or likely pathogenic ANOS1 variants had additional features. In contrast, only one out of nine CHH patients with non-pathogenic (likely benign or uncertain of significance) ANOS1 variants according to ACMG exhibited additional features. And function of the non-pathogenic ANOS1 variants accompanied with other CHH-associated RSVs. CONCLUSIONS: The ANOS1 genetic spectrum of CHH patients in Chinese population is established. Some of the correlations between clinical phenotype and genotype are also established. Our study indicates that CHH patients with pathogenic or likely pathogenic ANOS1 RSVs tend to exhibit additional phenotypes. Although non-pathogenic ANOS1 variants only may not be sufficient to cause CHH, they may function together with other CHH-associated RSVs to cause the disease.

GHK-Cu-liposomes accelerate scald wound healing in mice by promoting cell proliferation and angiogenesis.

Glycyl-l-histidyl-l-lysine (GHK)-Cu is considered to be an activator of tissue remodeling, and has been used in cosmetic products. In this study, we prepared liposomes encapsulating GHK-Cu and analyzed their effect on human umbilical vein endothelial cells (HUVECs) proliferation and scald wound healing in mice. The nanoscaled GHK-Cu-liposomes promoted HUVECs proliferation, with a 33.1% increased rate. Flow cytometry analysis showed increased cell number at G1 stage and decreased cell number at G2 stage after GHK-Cu-liposomes treatment. Western blotting indicated that the expression of vascular endothelial growth factor and fibroblast grow factors-2 were both enhanced, as well as cell cycle-related proteins CDK4 and CyclinD1. In a mice scald model, angiogenesis in burned skin treated with GHK-Cu-liposomes was better compared with free GHK-Cu, and immunofluorescence analysis showed enhanced signal of CD31 and Ki67 in GHK-Cu-liposomes treated mice. Moreover, the wound healing time was shortened to 14 days post injury. Our results provide the evidence that GHK-Cu-liposomes could be utilized as a treatment for skin wounds.

Inverse colloidal crystal membranes for hydrophobic interaction membrane chromatography.

Hydrophobic interaction membrane chromatography has gained interest due to its excellent performance in the purification of humanized monoclonal antibodies. The membrane material used in hydrophobic interaction membrane chromatography has typically been commercially available polyvinylidene fluoride. In this contribution, newly developed inverse colloidal crystal membranes that have uniform pores, high porosity and, therefore, high surface area for protein binding are used as hydrophobic interaction membrane chromatography membranes for humanized monoclonal antibody immunoglobulin G purification. The capacity of the inverse colloidal crystal membranes developed here is up to ten times greater than commercially available polyvinylidene fluoride membranes with a similar pore size. This work highlights the importance of developing uniform pore size high porosity membranes in order to maximize the capacity of hydrophobic interaction membrane chromatography.

Catechol chitosan coated dual-loaded liposomes based on oxidation and saccharification mechanisms for enhancing skin anti-aging effects.

Skin aging has become a major urgent problem to be solved. Evidence reveals that oxidation and glycosylation are two dominant inducements of aging. Resveratrol (RES) with outstanding anti-oxidant effect and carnosine (CAR) with superb anti-glycation property were selected as two model drugs to evaluate the feasibility of their synergistic anti-aging effect. RES and CAR at the most desired mass ratio, supplying the most superior synergistic anti-aging effects were further encapsulated in liposomes (LP), which were separately coated with chitosan (CS) and catechol chitosan (Cat-CS) to increase the transdermal penetration. Their anti-aging efficacy was explored in human skin fibroblast (HSF) and human immortalized keratinocytes (HaCaT) cells, as well as the back skin of guinea pigs. Herein, RES and CAR at the mass ratio of 2:1 exhibited the most ideal synergistic anti-aging effect. The constructed liposomes have been shown to possess excellent fundamental properties and sustained-release properties. The aging-related indicator levels in the two cells and guinea pigs were obviously improved for the RES + CAR@Cat-CS-LP group. Additionally, skin appearance, tissue morphology, and collagen content were visibly improved, indicating its perfect anti-aging effect. In conclusion, RES + CAR@Cat-CS-LP is expected to be exploited as a potential anti-aging drug delivery system.

Enzyme-Mineralized PVASA Hydrogels with Combined Toughness and Strength for Bone Tissue Engineering.

Enzymatic mineralization is an advanced mineralization method that is often used to enhance the stiffness and strength of hydrogels, but often accompanied by brittle behavior. Moreover, the hydrogel systems with dense networks currently used for enzymatic mineralization are not ideal materials for bone repair applications. To address these issues, two usual bone repair hydrogels, poly(vinyl alcohol) (PVA) and sodium alginate (SA), were selected to form a double-network structure through repeated freeze-thawing and ionic cross-linking, followed by enzyme mineralization. The results demonstrated that both enzymatic mineralization and double-network structure improved the mechanical and biological properties and even exhibited synergistic effects. The mineralized PVASA hydrogels exhibited superior comprehensive mechanical properties, with a Young's modulus of 1.03 MPa, a storage modulus of 103 kPa, and an equilibrium swelling ratio of 132%. In particular, the PVASA hydrogel did not suffer toughness loss after mineralization, with a high toughness value of 1.86 MJ/m3. The prepared hydrogels also exhibited superior biocompatibility with a cell spreading area about 13 times that of mineralized PVA. It also effectively promoted cellular osteogenic differentiation in vitro and further promoted the formation of new bone in the femur defect region in vivo. Overall, the enzyme-mineralized PVASA hydrogel demonstrated combined strength and toughness and great potential for bone tissue engineering applications.

Multifunctional nanofibrous scaffolds for enhancing full-thickness wound healing loaded with Bletilla striata polysaccharides.

The considerable challenge of wound healing remains. In this study, we fabricated a novel multifunctional core-shell nanofibrous scaffold named EGF@BSP-CeO2/PLGA (EBCP), which is composed of Bletilla striata polysaccharide (BSP), Ceria nanozyme (CeO2) and epidermal growth factor (EGF) as the core and poly(lactic-co-glycolic acid) (PLGA) as the shell via an emulsion electrospinning technique. An increase in the BSP content within the scaffolds corresponded to improved wound healing performance. These scaffolds exhibited increased hydrophilicity and porosity and improved mechanical properties and anti-UV properties. EBCP exhibited sustained release, and the degradation rate was <4 % in PBS for 30 days. The superior biocompatibility was confirmed by the MTT assay, hemolysis, and H&E staining. In addition, the in vitro results revealed that, compared with the other groups, the EBCP group presented excellent antioxidant and antibacterial effects. More importantly, the in vivo results indicated that the wound closure rate of the EBCP group reached 94.0 % on day 10 in the presence of H2O2. The results demonstrated that EBCP could comprehensively regulate the wound microenvironment, possess hemostatic abilities, and significantly promote wound healing. In conclusion, the EBCP is promising for facilitating the treatment of infected wounds and represents a potential material for clinical applications.

Borneol-modified PEGylated graphene oxide as a nanocarrier for brain-targeted delivery of ginsenoside Rg1 against depression.

Depression is a chronic mental disorder which threatens human health and lives. However, the treatment of depression remains challenging largely due to blood brain barrier (BBB), which restricts drugs from entering the brain, resulting in a poor distribution of antidepressants in the brain. In this work, a novel brain-targeted drug delivery system was developed based on borneol-modified PEGylated graphene oxide (GO-PEG-BO). GO-PEG-BO was characterized and proved to possess excellent biocompatibility. By incorporating borneol, GO-PEG-BO could penetrate BBB efficiently by opening tight junctions and inhibiting the efflux system of BBB. The targeted distribution of GO-PEG-BO in the brain was observed by an in vivo biodistribution study. Moreover, GO-PEG-BO exhibited a neuroprotective effect, which is beneficial to the treatment of depression. Ginsenoside Rg1 (GRg1), which can relieve depressive symptoms but difficult to cross BBB, was loaded to GO-PEG-BO for the therapy of depression. In depressive rats, GRg1/GO-PEG-BO improved stress-induced anhedonia, despair and anxiety, and comprehensively relieved the depressive symptoms. In conclusion, GO-PEG-BO could serve as a promising nanocarrier for brain-targeted drug delivery, and provide a new strategy for the therapy of depression.

Inhibition of aged microplastics and leachates on methane production from anaerobic digestion of sludge and identification of key components.

Large amounts of microplastics (MPs) accumulate in the sludge anaerobic digestion system after being treated by the wastewater treatment plants, inevitably leading to aging and chemicals leaching. However, no information is available about the effects of aged MPs and leachates on the anaerobic digestion of sludge. In this study, the effects of different aged MPs ((polyethylene (PE), polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polylactic acid (PLA)) and leachates on anaerobic methanogenesis of sludge were investigated. PLA-related treatments caused no adverse effects on anaerobic digestion. While PE-, PET-, and PVC-related treatments significantly inhibited methane production with an order of leachates (26.4-42.4 %) > MPs (16.1-22.9 %) > aged MPs (2.4-11.8 %). For different leachates, PET leachate caused the strongest inhibitory effects. The same order was found for the methane potential and hydrolysis coefficient. These results suggest that the inhibition of MPs on methanogenesis is mainly caused by the leachates. Based on biochemical and microbial community analysis, the primary mechanism is that the leachates induce oxidative stress, damaging microbial cells and reducing microbial activity, consequently inhibiting methanogenesis. Furthermore, via effect-directed analysis, methyl benzoate (MB), dimethyl phthalate (DMP), and 2,4-Di-tert-butylphenol (DTBP) were identified as key components in the PET-leachate inhibiting anaerobic methanogenesis.

Rapid and sensitive identification of RNA from the emerging pathogen, coxsackievirus A6.

BACKGROUND: Hand, foot and mouth disease (HFMD) is caused by members of the family Picornaviridae in the genus Enterovirus. It has been reported that coxsackievirus A6 (CVA6) infections are emerging as a new and major cause of epidemic HFMD. Sporadic HFMD cases positive for CVA6 were detected in the mainland of China in recent years. To strengthen the surveillance of CVA6 infections and outbreak control, the clinical diagnosis is urgently needed to distinguish the CVA6 infection disease from other infections. METHODS: In order to develop a sensitive quantitative real-time RT-PCR assay for rapid detection of CVA6 RNA, primers and probe were designed to target the VP1 gene segment of CVA6. The conservation of the target segment was firstly analyzed by bioinformatic technology. The specificity of the real-time RT-PCR was further confirmed by detecting other related viruses and standard curves were established for the sensitivity evaluation. The pharyngeal swab samples from the EV71 and CVA16 unrelated HFMD patients were applied for CVA6 detection through the established method. RESULTS: Based on the primer-probe set to detect the target VP1 gene segment of CVA6, the quantitative real-time RT-PCR assay could discriminate CVA6 infection from other resemble viral diseases with a potential detection limit of 10 viral copies/ml. The specificity of the assay was determined by sequence alignment and experimentally tested on various related viruses. The standard curve showed that the amplification efficiency of templates with different concentrations of templates was almost the same (R2 >0.99). Evaluation of the established method with pharyngeal swabs samples showed good accordance with the results from serology diagnosis. CONCLUSION: This study is the first report developing a VP1 gene-based quantitative real-time RT-PCR for rapid, stable and specific detection of CVA6 virus. The real-time RT-PCR established in this study can be used as a reliable method for early diagnosis of CVA6 infection.

Effects of chronic exposure to different sizes and polymers of microplastics on the characteristics of activated sludge.

Wastewater treatment plants (WWTPs) have become an important source of microplastics (MPs) contamination and most MPs remain in the sludge inducing potential impacts on sludge disposal. However, little is known about the influence of MPs on the characteristics of sludge, which is essential for sludge disposal. In this study, the dewaterability of activated sludge in response to chronic exposure (60 days) to MPs of different sizes (213.7 nm ~ 4.2 mm) and polymers (polystyrene, polyethylene, and polyvinyl chloride) were investigated. Overall, different particle sizes caused more evident effects on sludge dewatering than different polymer types did. Millimeter MPs (~4 mm) dramatically reduced the dewaterability of sludge by 29.6% ~ 47.7%. These effects were mainly caused by the physical crushing of MPs on sludge flocs, except polyvinyl chloride (PVC)-MPs, possibly containing additives, induced toxicity on sludge. Moreover, 100 mg/L nano-size MPs (213 nm) also reduced the dewatering performance of sludge. The potential mechanism is that nano-size MPs inhibited sludge activity and decreased the abundance of key microorganisms, which subsequently altered the composition and spatial distribution of extracellular polymeric substances (EPS), and finally impeded sludge dewatering. Our results highlight the impacts of different sizes of MPs on the characteristics of sludge, affecting the final disposal of sludge.

[Comparison of the differences in pain and the effect of ibuprofen in reducing endodontic flare-up after single-visit root canal therapy between Uyghur and Han patients with chronic apical periodontitis].

PURPOSE: To compare the incidence of postoperative pain of chronic periapical periodontitis patients with root canal therapy between Han and Uygur, and the effect of ibuprofen in reducing endodontic flare-up after single-visit root canal therapy between Uyghur and Han patients with chronic apical periodontitis, in order to provide a basis for clinical administration. METHODS: Two hundred and fifty Uyghur and 250 Han patients with chronic apical periodontitis in their incisor, canine and premolar were collected, and randomly divided into 2 groups: experimental group and control group. After single-visit root canal therapy, Uyghur patients in the experimental group (UEG) and Han patients in the experimental group (HEG) took ibuprofen capsules according to the drug instructions; while Uyghur patients in the control group (UCG) and Han patients in the control group(HCG) took placebo capsules. Both doctors and patient kept blind from the drug capsules and group of the patients. The incidence, degree of endodontic Flare-up at 6, 12, 24, 48, 72 hours and 1 week after root canal therapy were recorded and analyzed by χ2 test using SPSS11.0 software package. RESULTS: During the experiment, the incidence of E flare-up in Uygur patients was higher than in Han patients; the incidence of E flare-up in different groups in orders from high to low was: UCG>HCG>UEG>HEG. Chi-square test showed that there were significant differences between the two groups. In view of time distribution, most of flare-up happened between 24~48 hours after root canal therapy with the highest degree in all 4 groups. Regardless of the incidence or degree of flare-up, HEG and HCG were significantly greater than UEG and UCG. CONCLUSIONS: Ibuprofen can reduce and prevent flare-up for both Uyghur and Han patients, but it has better effect on Han patients.

Interleukin-6 first plays pro- then anti-inflammatory role in early versus late acute renal allograft rejection.

This study aimed to investigate the potential role of IL-6 in acute T-cell-mediated renal rejection (ACR) during different periods post-transplantation. Fifty-three patients with ACR (32 of whom developed ACR within the first month; 12, between 2 and 6 months; and 9, between 7 and 12 months post-transplantation), 31 patients with delayed graft function (DGF), and 38 recipients with stable renal allograft function were recruited. Luminex analysis was used to monitor levels of IL-6, sIL-6R, IL-1α, IL-1ß, and IL-1 receptor antagonist (IL-1Ra) in 228 serum samples from 122 patients, including ACR patients before and during rejection, and after rejection reversal, DGF patients, and stable controls. The associations between IL-6 levels and sIL-6R, IL-1α, IL-1ß, and IL-1Ra levels were analyzed using Spearman correlation analysis. In patients who developed ACR within the first month post-transplantation, serum IL-6 concentrations increased significantly compared to the stable control group, but decreased in patients who developed ACR between 2 and 12 months post-transplantation. Concomitantly, levels of sIL-6R gradually increased when ACR occurred between 2 and 12 months post-transplantation. IL-6 levels correlated with IL-1ß levels in early stage ACR and with levels of IL-1Ra in late stage ACR. Our results suggest that IL-6 acts as a pro-inflammatory cytokine during early-stage ACR, and plays an anti-inflammatory role during later stages post-transplantation.