Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. RESULTS: OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. CONCLUSIONS: We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.

Advancement and prospects of production, transport, functional activity and structure-activity relationship of food-derived angiotensin converting enzyme (ACE) inhibitory peptides.

Food-derived antihypertensive peptides have attracted increasing attention in functional foods for health promotion, due to their high biological activity, low toxicity and easy metabolism in the human body. Angiotensin converting enzyme (ACE) is a key enzyme that causes the increase in blood pressure in mammals. However, few reviews have summarized the current understanding of ACE inhibitory peptides and their knowledge gaps. This paper focuses on the food origins and production methods of ACE inhibitory peptides. Compared with conventional methods, the advanced technologies and emerging bioinformatics approaches have recently been applied for efficient and targeted release of ACE inhibitory peptides from food proteins. Furthermore, the transport and underlying mechanisms of ACE inhibitory peptides are emphatically described. Molecular modeling and the Michaelis-Menten equation can provide information on how ACE inhibitors function. Finally, we discuss the structure-activity relationships and other bio-functional properties of ACE inhibitory peptides. Molecular weight, hydrophobic amino acid residues, charge, amino acid composition and sequence (especially at the C-terminal and N-terminal) have a significant influence on ACE inhibitory activity. Some studies are required to increase productivity, improve bioavailability of peptides, evaluate their bio-accessibility and efficiency on reducing blood pressure to provide a reference for the development and application of health products and auxiliary treatment drugs.

The characteristics of dome-shaped macula in Chinese children aged 4-6 years using optical coherence tomography angiography.

PURPOSE: To evaluate the characteristics of dome-shaped macula (DSM) in children aged 4-6 years with normal visual acuity using optical coherence tomography angiography. METHOD: This is a cross-sectional study. A total of 19 children aged 4-6 years were included. The results of optical coherence tomography angiography images were analysed to identify and quantify retinal structural and vascular parameters in DSM children. The dome height, dome base, and sub-dome choroidal thickness were manually measured. Participants with DSM and those without DSM from our previous study were compared on these parameters. RESULTS: Nineteen eyes of the preschool subjects with normal visual acuity showed horizontal DSM on optical coherence tomography (OCT). The DSM was significantly smooth and low in the children, and we did not observe differences between sex and age. Compared to the children without DSM, the average axial length was longer, and the average macular vessel density was lower in the DSM group, especially in the deep retinal vascular density. Additionally, the dome height was positively correlated with the sub-dome choroidal thickness. When the dome base/height was increased, the fovea avascular zone (FAZ) area was larger. CONCLUSION: Dome-shaped macula was detected in the preschool children in the process of the emmetropization with normal visual acuity. The changes in macular structure and vasculature provide new ideas for further investigation into the characteristics of DSM formation.

Discovery of triterpenoids as potent dual inhibitors of pancreatic lipase and human carboxylesterase 1.

Pancreatic lipase (PL) is a well-known key target for the prevention and treatment of obesity. Human carboxylesterase 1A (hCES1A) has become an important target for the treatment of hyperlipidaemia. Thus, the discovery of potent dual-target inhibitors based on PL and hCES1A hold great potential for the development of remedies for treating related metabolic diseases. In this study, a series of natural triterpenoids were collected and the inhibitory effects of these triterpenoids on PL and hCES1A were determined using fluorescence-based biochemical assays. It was found that oleanolic acid (OA) and ursolic acid (UA) have the excellent inhibitory effects against PL and hCES1A, and highly selectivity over hCES2A. Subsequently, a number of compounds based on the OA and UA skeletons were synthesised and evaluated. Structure-activity relationship (SAR) analysis of these compounds revealed that the acetyl group at the C-3 site of UA (compound 41) was very essential for both PL and hCES1A inhibition, with IC50 of 0.75 µM and 0.014 µM, respectively. In addition, compound 39 with 2-enol and 3-ketal moiety of OA also has strong inhibitory effects against both PL and hCES1A, with IC50 of 2.13 µM and 0.055 µM, respectively. Furthermore, compound 39 and 41 exhibited good selectivity over other human serine hydrolases including hCES2A, butyrylcholinesterase (BChE) and dipeptidyl peptidase IV (DPP-IV). Inhibitory kinetics and molecular docking studies demonstrated that both compounds 39 and 41 were effective mixed inhibitors of PL, while competitive inhibitors of hCES1A. Further investigations demonstrated that both compounds 39 and 41 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. Collectively, we found two triterpenoid derivatives with strong inhibitory ability on both PL and hCES1A, which can be served as promising lead compounds for the development of more potent dual-target inhibitors targeting on PL and hCES1A.

Leucine regulates porcine muscle fiber type transformation via adiponectin signaling pathway.

Leucine can promote slow-twitch muscle fibers formation, and this effect may be mediated by AMPK signaling pathway. In addition, adiponectin (AdipoQ) plays an important role in regulation of muscle fiber type transformation. AdipoQ is located in the upstream of AMPK and its secretion can be regulated by leucine. Therefore, the aim of this study was to explore whether leucine affects muscle fiber type transformation through AdipoQ signaling pathway. Our data showed that 4 mM leucine significantly increased protein expression levels of slow MyHC, Myoglobin, Troponin I-SS, AdipoQ, AdipoR1, phospho-AMPK (p-AMPK) and PGC-1α and mRNA expression levels of AMPKα2, PGC-1α, AdipoQ and AdipoR1, and significantly decreased fast MyHC protein expression. In addition, 4 mM leucine significantly increased the SDH activity while significantly decreased the LDH activity. However, knockdown of AdipoR1 expression by AdipoR1-siRNA abolished leucine-induced upregulation of protein expressions of slow MyHC, AdipoR1, p-AMPK, PGC-1α and NRF1, mRNA expressions of MyHC I, MyHC IIa, AdipoR1, AMPKα2 and PGC-1α, ATP5G, TFAM and NRF1, and mtDNA level, as well as downregulation of protein expression of fast MyHC and mRNA expression of MyHC IIb. Together, our data revealed that leucine promotes muscle fiber type transformation from fast-twitch to slow-twitch through AdipoQ signaling pathway.

Effect of dietary leucine supplementation on skeletal muscle fiber type transformation in weaning piglets.

To investigate the effects of dietary leucine supplementation on muscle fiber type transformation in weaning piglets, 54 21-day-old male DLY (Duroc × Landrace × Yorkshire) weaned piglets were randomly divided into control, 0.25% and 0.5% leucine groups. The experiment lasted for 42 d. The results showed that dietary supplementation of 0.25% leucine significantly increased the protein expressions of slow MyHC, myoglobin and Troponin I-SS and the mRNA expressions of MyHC I, MyHC IIa, Tnni1, Tnnc1, Tnnt1 and myoglobin, while decreased the protein level of fast MyHC and the mRNA level of MyHC IIb in longissimus dorsi (LD) muscle. Furthermore, 0.25% leucine significantly increased succinic dehydrogenase (SDH) activity and decreased lactate dehydrogenase (LDH) activity. In addition, our data found that 0.25% leucine significantly increased serum adiponectin (AdipoQ) concentration, and the protein levels of AdipoQ, adiponectin receptor 1 (AdipoR1), phosphorylated AMP-activated protein kinase (p-AMPK) and PPAR-γ coactivator-1α (PGC-1α) and the mRNA levels of AdipoQ, AdipoR1 and AMPKα2. Together, our findings indicate that leucine promotes porcine skeletal muscle fiber type transformation from fast-twitch to slow-twitch, and the effect may be mediated by AdipoQ-AMPK-PGC-1α signaling pathway.

Study on the antipruritic mechanism of Zanthoxylum bungeanum and Zanthoxylum schinifolium volatile oil on chronic eczema based on H1R and PAR-2 mediated GRPR pathway.

OBJECTIVE: To observe the antipruritic effect and mechanism of the volatile oil of Zanthoxylum bungeanum and Zanthoxylum schinifolium on chronic eczema to provide data support for clinical application and new drug development of Zanthoxylum bungeanum and Zanthoxylum schinifolium. METHODS: The model of chronic eczema was established by using 2-dinitrochlorobenzene (DNCB), and the composition and content of volatile oil in Zanthoxylum schinifolium and Zanthoxylum bungeanum was determined by gas chromatography-mass spectrometry (GC-MS). The antipruritic effect by (EASI) score of eczema area and severity index and scratching times was then evaluated. Then, the contents of histamine, gastrin-releasing peptide (GRP), interleukin-4 (IL-4), and immunoglobulin E (IgE) in serum of rats was determined by enzyme-linked immunosorbent assay (ELISA). The tissue morphology was observed by HE staining. The expressions of H1R, PAR-2, TRPV1, TRPA1, and GRPR was then detected by immunohistochemistry, Western blot, and QRT-PCR. RESULTS: The results revealed that there were differences in the composition of volatile oil between Zanthoxylum bungeanum and Zanthoxylum schinifolium. Compared to the model group, the medium-dose group of Zanthoxylum bungeanum and Zanthoxylum schinifolium group significantly increased the difference of EASI score and scratching times, significantly decreased the concentrations of IL-4, IgE, GRP, and histamine, and significantly decreased the expression levels of H1R, PAR-2, TRPV1, and GRPR. The degree of inhibition on the pathological manifestations of chronic eczema was evident. There was no significant difference in antipruritic effect between the two groups. The expression of TRPA1 was inconsistent at the protein and gene level, which needs to be further researched. CONCLUSION: The volatile oil of Zanthoxylum bungeanum and Zanthoxylum schinifolium can reduce the expression of H1R, PAR-2, TRPV1, and GRPR. The mechanism may be through the H1R and PAR-2-mediated GRPR pathway intervention to achieve the effect, both of which have the same antipruritic effect.

Iron Restriction Alleviates Atherosclerosis in ApoE KO Mice: An iTRAQ Proteomic Analysis.

The "iron hypothesis" of atherosclerosis has long been controversial. Several studies have shown that dietary iron restriction or low-iron diets can effectively alleviate atherosclerosis in rabbits and mice. However, the underlying molecular mechanisms of these phenomena remain to be elucidated. In this study, we further evaluated possible correlations between a low-iron diet and atherosclerosis alleviation by using a quantitative proteomic approach. For this purpose, apolipoprotein E knockout (ApoE KO) mice were divided into three groups and fed a normal diet (ND), a high-fat diet (HFD), or a high-fat +low-iron diet (HFD + LI). Our results showed that the HFD-LI improved atherosclerosis by decreasing en face lesions of the aorta and reducing the accumulation of macrophages and disordered smooth muscle cells. HFD-LI also decreased iron levels, serum hepcidin levels and the serum concentration of low-density lipoprotein cholesterol (LDL-C). The use of the isobaric tag for absolute quantification (iTRAQ) proteomic method and subsequent multi-technique molecular validation indicated that many of the proteins involved in atherosclerotic inflammation, vascular remodeling, and focal adhesion had significant changes in their expression among the diet groups. Importantly, the proteins Gal-3 and VCAM1, which are key participants of atherosclerosis pathogenesis, revealed lower expression after a low-iron diet. The present findings widely support the "iron hypothesis" of atherosclerosis. Further studies are suggested to fully understand the implications of these results.

Acetyl-CoA Deficiency Is Involved in the Regulation of Iron Overload on Lipid Metabolism in Apolipoprotein E Knockout Mice.

The role of dietary iron supplementation in the development of nonalcoholic fatty liver disease (NAFLD) remains controversial. This study aimed to investigate the effect of excess dietary iron on NAFLD development and the underlying mechanism. Apolipoprotein E knockout mice were fed a chow diet, a high-fat diet (HFD), or an HFD containing 2% carbonyl iron (HFD + Fe) for 16 weeks. The serum and liver samples were acquired for biochemical and histopathological examinations. Isobaric tags for relative and absolute quantitation were performed to identify differentially expressed proteins in different groups. Excess dietary iron alleviated HFD-induced NAFLD, as evidenced by significant decreases in serum/the hepatic accumulation of lipids and the NAFLD scores in HFD + Fe-fed mice compared with those in HFD-fed mice. The hepatic acetyl-CoA level was markedly decreased in the HFD + Fe group compared with that in the HFD group. Important enzymes involved in the source and destination of acetyl-CoA were differentially expressed between the HFD and HFD + Fe groups, including the enzymes associated with cholesterol metabolism, glycolysis, and the tricarboxylic acid cycle. Furthermore, iron overload-induced mitochondrial dysfunction and oxidative stress occurred in mouse liver, as evidenced by decreases in the mitochondrial membrane potential and antioxidant expression. Therefore, iron overload regulates lipid metabolism by leading to an acetyl-CoA shortage that reduces cholesterol biosynthesis and might play a role in NAFLD pathogenesis. Iron overload-induced oxidative stress and mitochondrial dysfunction may impair acetyl-CoA formation from pyruvate and ß-oxidation. Our study provides acetyl-CoA as a novel perspective for investigating the pathogenesis of NAFLD.

Bioaccessibility of Metals in Soils at Typical Legacy Industrial Sites: In Vitro Evaluation Using Physiologically-Based Extraction.

Risk assessment of soil metal pollution based on total metal contents might give overestimates by neglecting the bioaccessibility of the pollutants to soil biota. Physiologically-based extraction tests (PBET) are in vitro methods for evaluation of bioaccessibility of soil pollutants. A total of 27 soil samples collected from four types of legacy industrial site representing metal smelting, lead-acid battery factories, chemical plants and steel plants were analyzed for the bioaccessibility of six potentially toxic metals using a PBET method. The metal pollutants at the industrial sites depended on the former industrial processes and emissions. The highest proportions of gastric phase and intestinal phase in these soil samples were 43.9% for Cd and 27% for Cu, respectively. Factors affecting metal bioaccessibility included type of industry and soil properties. The soils at a lead-acid battery factory showed relatively high bioaccessibility of Pb, Zn and Cd and those at the steel plant showed relatively low metal bioaccessibility. Soil organic matter and clay contents were positively related to metal bioaccessibility but soil pH and CEC showed negative relationships. Further studies are recommended to determine the speciation of the bioaccessible metals in these soils.

Assessment of the retinal vasculature in healthy Chinese preschool children aged 4-6 years old using optical coherence tomography angiography.

PURPOSE: To establish normal parameters of macular and optic disc vasculature by optical coherence tomography angiography (OCTA) in healthy preschool children aged 4-6 years old in China. OCTA reflects retinal metabolism and development in children at these ages and could be used clinically and in future studies to aid diagnosis and prediction of retinal abnormalities and developmental stagnation. METHODS: In this cross-sectional study, we measured foveal, parafoveal, and perifoveal vessel density in the superficial capillary plexus (SCP); the deep capillary plexus (DCP), the foveal avascular zone (FAZ), and the radial capillary peripapillary (RPC) in the optic disc using investigational spectral-domain OCTA. The magnification effect of the FAZ area and microvasculature measurements was corrected by Littman and the modified Bennett formula. RESULTS: A total of 242 eyes (116 males and 126 females, 5.31 ± 0.73 years) were recruited for the analysis. The mean macular vessel density was 48.10 ± 2.92% and 48.74 ± 6.51% in the SCP and the DCP, respectively. The RPC vessel density was 47.17 ± 2.52%, 47.99 ± 4.48%, and 48.41 ± 3.07% in the whole image, inside disc, and peripapillary, respectively; and the mean FAZ area was 0.28 ± 0.11 mm2. A significant difference between male and female participants was found in the retinal vasculature (DCP, SCP, and RPC). None of these parameters were significantly different in age (P > 0.05), except that DCP slightly increased with aging. The right and left eyes had good consistency in the parameters of the macula and optic disc. CONCLUSIONS: Our study establishes the macular and optic disc OCTA reference values in 4- to 6-year-old healthy preschool children. They may be used in longitudinal OCTA studies and clinical applications.

Knockdown of TBRG4 suppresses proliferation, invasion and promotes apoptosis of osteosarcoma cells by downregulating TGF-ß1 expression and PI3K/AKT signaling pathway.

Transforming growth factor beta regulator 4 (TBRG4) is a novel regulator in tumorigenic progression of several tumors. However, so far, the expression and functions of TBRG4 in osteosarcoma are unknown. The aim of this study was to investigate the potential biological functions of TBRG4 in osteosarcoma. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of TBRG4 in osteosarcoma tissues and cell lines. The levels of TBRG4 protein in osteosarcoma tissues were assessed by immunohistochemistry. Lentivirus-mediated short hairpin (sh) RNA was employed to knock down TBRG4 in osteosarcoma cells, and the expressions of TBRG4 mRNA and protein were determined by qRT-PCR and Western blot assay, respectively. Subsequently, the proliferation, clonogenic ability, apoptosis and invasion of osteosarcoma cells were measured using high content screening analysis and CCK8 assay, tumor sphere formation assay, flow cytometry and Transwell invasion assays, respectively. Furthermore, the osteosarcoma cells growth and metastasis in vivo were detected, and the effect of TBRG4 on the transforming growth factor ß1 (TGF-ß1) and PI3K/AKT signaling pathway was explored by qRT-PCR and Western blot assay, respectively. The results showed the levels of TBRG4 were overexpressed in osteosarcoma tissues and cell lines, confirming that the high TBRG4 expression was related to advanced tumor stages, large tumor size, and lymph node metastasis. Functional assays showed knockdown of TBRG4 could inhibit proliferation, invasion and induce apoptosis of osteosarcoma cells in vitro, and could also suppress osteosarcoma growth and metastasis in vivo. By examining the expression levels of TGF-ß1, p-PI3K, PI3K, p-AKT and AKT, it showed that the suppression of TBRG4 would reduce TGF-ß1 expression and inactivate the PI3K/AKT signaling pathway. These results showed for the first time that TBRG4 knockdown could suppress osteosarcoma progression, suggesting TBRG4 might be a promising therapeutic target for osteosarcoma treatment.

Effects of electrode thickness and crystal water on pseudocapacitive performance of layered birnessite MnO2.

Manganese dioxide (MnO2) nanomaterials with two-dimensional (2D) layered birnessite structures are promising pseudocapacitive electrode materials. However, the effects of structural factors on their electrochemical performance is not fully understood. We synthesize alkali-free crystal water containing 2D layered birnessite MnO2 electrodes with controllable mass loading from 0.1 to 19.3 mg cm-2 to investigate the effects of electrode thickness and crystal water functions on crystal structure and pseudocapacitive behavior, to promote its industrialization. We find that the crystal water enlarges the interlayer space of birnessite MnO2 with electrolyte ions transported much more easily, resulting in higher specific capacitance of 702 F g-1 (70.2 mF cm-2) and excellent cycling stability of 20 000 charge-discharge cycles even at a mass loading of up to 10.8 mg cm-2. Such gains in specific capacitance are weakened significantly with raised mass loading. Thus, compared to a carbon cloth substrate, a carbon nanotube film with enhanced electron space transport capability presents better performance, indicating an effective strategy for higher mass loading cases. The present work sheds light on an efficient method for achieving high capacitance and mass loading together, for practical applications.

HIF-1α induces immune escape of prostate cancer by regulating NCR1/NKp46 signaling through miR-224.

BACKGROUND: Metastasis of prostate cancer (PCa) is largely affected by natural killer (NK) cells. This study aimed to clarify the mechanisms underlying tumor cells escaping from NK cells mediated by HIF-1α. METHODS: MiR-224 expression in lymphocytes and HIF-1α protein level in NK cells were determined by qRT-PCR and western blot, respectively. The amount of NKp46+ NK cells was detected with flow cytometry. The IFN-γ level was examined by enzyme linked immunosorbent assay (ELISA). NK cells were tested for cytolytic activity with a Non-Radioactive Cytotoxicity Assay, and treated with oxygenglucose deprivation (OGD) for hypoxia simulation. Interaction between miR-224 and NCR1 was evaluated with dual luciferase reporter assay. RESULTS: MiR-224 was down-regulated in lymphocytes isolated from prostate cancer tissues (n = 10). Overexpression of miR-224 protected prostate cancer from NK cells. HIF-1α increased miR-224 to inhibit the killing capability of NK cells on prostate cancer. MiR-224 controlled the expression of NCR1. Overexpression of miR-224 protected prostate cancer from NK cells through NCR1/NKp46 signaling. Suppression of HIF-1α enhanced the cytotoxicity of NK cells on prostate cancer via miR-224/NCR1 pathway. CONCLUSION: HIF-1α inhibits NCR1/NKp46 pathway through up-regulating miR-224, which affects the killing capability of NK cells on prostate cancer, thus inducing immune escape of tumor cells.

The Solvent Induced Inter-Dimensional Phase Transformations of Cobalt Zeolitic-Imidazolate Frameworks.

Studying inter-dimensional phase transitions of zeolitic-imidazolate frameworks (ZIFs) is essential for developing strategies in controlling morphology and properties. Herein, the inter-dimensional topotactic phase transformations of 3D ZIF-67 to 2D ZIF-L are investigated in detail by employing a simple and efficient solvent-induced growth method. In addition to ZIF-67 and ZIF-L, a series of novel core-shell composites of ZIF-67@ZIF-L, with unprecedented morphologies, are also obtained and well-defined. The different behaviors of the amine hydrogen of 2-MIM in the solvents play a pivotal role for inter-dimensional phase transformations, and in combination with the concentration of 2-MIM, the 2D to 3D phase transformations are also revealed. The findings are very beneficial for morphological design of the ZIFs, along with exploration of the corresponding properties. Impressively, Co-ZIFs exhibit interesting tunable CO2 adsorption behaviors with the phase evolution, which might bring broader understanding for designing CO2 detection and adsorption devices.

[Protection of Fufang Zhenzhu Tiaozhi Formula on NAFLD in Mice by Regulating ERS].

Objective: To investigate the effect of Fufang Zhenzhu Tiaozhi formula( FZT) in a long-term high-fat diet-induced nonalcoholic fatty liver disease( NAFLD) mouse model and to study the regulation of hepatic endoplasmic reticulum stress( ERS). Methods: Mice model with NAFLD was established by feeding purified high-fat diet,and treated with FZT at the same time. After treatment with FZT for 20 weeks, the plasma total cholesterol( TC),hepatic TG, triglyceride( TG) level,liver tissue pathology morphology and expression of lipid metabolism, ERS related genes were observed,and measured the effect of FZT on NAFLD in mice. Results: Compared with normal control group,plasma and hepatic TC,TG level were significantly increased in model group( P < 0. 05); compared with model group,the plasma and hepatic TC,TG level were significantly lower in FZT high and low-dose group( P < 0. 05); XBP-1,PERK and SREBP-1c mRNA expression of liver tissue were significantly lower( P < 0. 05). Conclusion: FZT can significantly alleviate NAFLD in mice which induced by a long-term high-fat diet, reduction of the hepatic ERS activity may be one of its mechanisms alleviate NAFLD.

A Luminescent Hypercrosslinked Conjugated Microporous Polymer for Efficient Removal and Detection of Mercury Ions.

A hypercrosslinked conjugated microporous polymer (HCMP-1) with a robustly efficient absorption and highly specific sensitivity to mercury ions (Hg(2+)) is synthesized in a one-step Friedel-Crafts alkylation of cost-effective 2,4,6-trichloro-1,3,5-triazine and dibenzofuran in 1,2-dichloroethane. HCMP-1 has a moderate Brunauer-Emmett-Teller specific surface (432 m(2) g(-1)), but it displays a high adsorption affinity (604 mg g(-1)) and excellent trace efficiency for Hg(2+). The π-π* electronic transition among the aromatic heterocyclic rings endows HCMP-1 a strong fluorescent property and the fluorescence is obviously weakened after Hg(2+) uptake, which makes the hypercrosslinked conjugated microporous polymer a promising fluorescent probe for Hg(2+) detection, owning a super-high sensitivity (detection limit 5 × 10(-8) mol L(-1)).

CXCL13 promotes the effect of bone marrow mesenchymal stem cells (MSCs) on tendon-bone healing in rats and in C3HIOT1/2 cells.

OBJECTIVES: Mesenchymal stem cells (MSCs) are potential effective therapy for tissue repair and bone regeneration. In present study, the effects of CXC chemokine ligand-13 (CXCL13) were evaluated on tendon-bone healing of rats. METHODS: Tendon bone healing of the rat model was established and biomechanical testing was performed at 2, 4, 8 weeks after surgery. Murine mesenchymal cell line (C3HIOT1/2 cells) was cultured. The expression of miRNA-23a was detected by real-time PCR. The protein expression of ERK1/2, JNK and p38 was detected by western blotting. MiR-23a mimic and inhibitor were used to overexpress or silence the expression of miR-23a. RESULTS: MSCs significantly elevated the levels of ultimate load to failure, stiffness and stress in specimens of rats, the effects of which were enhanced by CXCL13. The expression of miR-23a was down-regulated and the protein of ERK1/2 level was up-regulated by CXCL13 treatment in both in vivo and in vitro experiments. ERK1/2 expression was elevated by overexpression of miR-23a and reduced by miR-23a inhibitor. CONCLUSIONS: These findings revealed that CXCL13 promoted the tendon-bone healing in rats with MSCs treatment, and implied that the activation of ERK1/2 via miR-23a was involved in the process of MSCs treated bone regeneration.

Orthodontic decompensation and correction of skeletal Class III malocclusion with gradual dentoalveolar remodeling in a growing patient.

An 8-year-old girl with a skeletal Class III malocclusion was treated in 2 phases. Maxillary expansion and protraction were carried out as the early intervention. However, her maxillary hypoplasia and mandibular hyperplasia deteriorated with age. The phase 2 comprehensive treatment began with proper mechanics when she was 12 years old with growth potential. In the maxillary arch, an auxiliary rectangular wire was used with a round main wire and an opening spring to create space for the impacted teeth and to bodily move the anterior teeth forward. Decompensation of mandibular incisors and correction of the Class III malocclusion were achieved by short Class III elastics with light forces and a gentle interaction between the rectangular wires and the lingual root-torque slots. The phase 2 active treatment period was 4 years 8 months. The 2-year follow-up indicated that our treatment results were quite stable.

Association of Dietary Retinol Intake and Serum Neurofilament Light Chain Levels: Results from NHANES 2013-2014.

BACKGROUND: There is increasing evidence suggesting that serum neurofilament light chain (sNfL) levels can be used as biomarkers for axonal injury. Retinol is recognized for its significant involvement in nervous system function, but the precise connection between dietary retinol and sNfL levels remains uncertain. OBJECTIVE: Our objective was to investigate the relationship between dietary retinol intake and sNfL, and to find an optimal retinol intake level for neurological health. METHODS: In the National Health and Nutrition Examination Survey (NHANES), conducted from 2013 to 2014, a cohort of 1684 participants who met the criteria were selected for the study. sNfL levels were measured from stored serum samples using a novel high-throughput immunoassay platform from Siemens Healthineers. Assessment of dietary retinol intake was performed by a uniformly trained interviewer through a 24 h dietary recall method. A generalized linear model was evaluated to assess the correlation between dietary retinol intake and sNfL concentrations. Furthermore, the nonlinear association between the two is further explored using restricted cubic spline (RCS) analysis. RESULTS: Upon adjusting for potential confounders, a 10% increase in dietary retinol intake was associated with a 3.47% increase in sNfL levels (95% CI: 0.54%, 6.49%) across all participants. This relationship was more pronounced in specific subgroups, including those under 60 years of age, non-obese, impaired estimated glomerular filtration rate (eGFR), and non-diabetic. In subgroup analysis, among those younger than 60 years of age (percent change: 3.80%; 95% CI: 0.43%, 7.28%), changes were found in non-obese participants (percent change: 6.28%; 95% CI: 2.66%, 10.02%), those with impaired eGFR (percent change: 6.90%; 95% CI: 1.44%, 12.65%), and non-diabetic patients (percentage change: 4.17%; 95% CI: 1.08%, 7.36%). RCS analysis showed a linear relationship between dietary retinol intake and sNfL levels. Furthermore, the positive correlation between the two was more significant after the inflection point, according to piecewise linear analysis. CONCLUSION: This current investigation uncovered a J-shaped relationship between dietary retinol and sNfL levels, suggesting that axonal damage can occur when dietary retinol intake increases more than a specific threshold. These findings need to be further confirmed in future prospective studies to determine the precise intake level that may trigger axonal injury.