Relationship between phthalates exposures and metabolic dysfunction-associated fatty liver disease in United States adults.

As a new definition for the evidence of hepatic steatosis and metabolic dysfunctions, the relationship between phthalates (PAEs) and metabolic dysfunction-associated fatty liver disease (MAFLD) remains virtually unexplored. This study included 3,137 adults from the National Health and Nutrition Examination Survey spanning 2007-2018. The diagnosis of MAFLD depended on the US Fatty Liver Index (US FLI) and evidence of metabolic dysregulation. Eleven metabolites of PAEs were included in the study. Poisson regression, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were used to assess the associations between phthalate metabolites and MAFLD. After adjusting for potential confounders, Poisson regression analysis showed that mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate were generally significant positively associated with MAFLD (P<0.05). Furthermore, the WQS index constructed for the eleven phthalates was significantly related to MAFLD (OR:1.43; 95%CI: 1.20, 1.70), MEHHP (33.30%), MEP (20.84%), MECPP (15.43%), and mono-isobutyl phthalate (11.78%) contributing the most. This study suggests that exposure to phthalates, individually or in combination, may be associated with an increased risk of MAFLD.

Elevated ADH5 expression suggested better prognosis in kidney renal clear cell carcinoma (KIRC) and related to immunity through single-cell and bulk RNA-sequencing.

BACKGROUND: Despite the rapid advances in modern medical technology, kidney renal clear cell carcinoma (KIRC) remains a challenging clinical problem in urology. Researchers urgently search for useful markers to break through the therapeutic conundrum due to its high lethality. Therefore, the study explores the value of ADH5 on overall survival (OS) and the immunology of KIRC. METHODS: The gene expression matrix and clinical information on ADH5 in the TCGA database were validated using external databases and qRT-PCR. To confirm the correlation between ADH5 and KIRC prognosis, univariate/multivariate Cox regression analysis was used. We also explored the signaling pathways associated with ADH5 in KIRC and investigated its association with immunity. RESULTS: The mRNA and protein levels showed an apparent downregulation of ADH5 in KIRC. Correlation analysis revealed that ADH5 was directly related to histological grade, clinical stage, and TMN stage (p < 0.05). Univariate and multivariate Cox regression analysis identified ADH5 as an independent factor affecting the prognosis of KIRC. Enrichment analysis looked into five ADH5-related signaling pathways. The results showed no correlation between ADH5 and TMB, TNB, and MSI. From an immunological perspective, ADH5 was found to be associated with the tumor microenvironment, immune cell infiltration, and immune checkpoints. Lower ADH5 expression was associated with greater responsiveness to immunotherapy. Single-cell sequencing revealed that ADH5 is highly expressed in immune cells. CONCLUSION: ADH5 could be a promising prognostic biomarker and a potential therapeutic target for KIRC. Besides, it was found that KIRC patients with low ADH5 expression were more sensitive to immunotherapy.

Mechanistic exploration of polytetrafluoroethylene thermal plasma gasification through multiscale simulation coupled with experimental validation.

The ever-growing quantities of persistent Polytetrafluoroethylene (PTFE) wastes, along with consequential ecological and human health concerns, stimulate the need for alternative PTFE disposal method. The central research challenge lies in elucidating the decomposition mechanism of PTFE during high-temperature waste treatment. Here, we propose the PTFE microscopic thermal decomposition pathways by integrating plasma gasification experiments with multi-scale simulations strategies. Molecular dynamic simulations reveal a pyrolysis-oxidation & chain-shortening-deep defluorination (POCD) degradation pathway in an oxygen atmosphere, and an F abstraction-hydrolysis-deep defluorination (FHD) pathway in a steam atmosphere. Density functional theory computations demonstrate the vital roles of 1O2 and ·H radicals in the scission of PTFE carbon skeleton, validating the proposed pathways. Experimental results confirm the simulation results and show that up to 80.12% of gaseous fluorine can be recovered through plasma gasification within 5 min, under the optimized operating conditions determined through response surface methodology.

Association of exposure to polycyclic aromatic hydrocarbons with thyroid hormones in adolescents and adults, and the influence of the iodine status.

Some studies of endocrine-disrupting polycyclic aromatic hydrocarbon (PAH) exposure and thyroid hormones (THs) are inconclusive. To assess the associations between PAHs and THs, and the influence of the iodine status on PAHs-THs, we employed 648 adolescents (12-19 years old) and 2691 adults from the National Health and Nutrition Examination Survey 2007-2008 and 2011-2012. PAH metabolites [1-hydroxynaphthalene (1-NAP), 2-NAP, 1-hydroxyphenanthrene (1-PHE), 2-PHE, 3-PHE, 2-hydroxyfluorene (2-FLU), 3-FLU, 9-FLU, and 1-hydroxypyrene (1-PYR)], THs [total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3), thyroid stimulating hormone (TSH), and thyroglobulin (Tg)], peripheral deiodinase activity (GD) and thyroid's secretory capacity (GT) were involved. Multiple linear regression and weighted quantile sum (WQS) regression models were used to assess PAH-TH associations and the interaction between PAHs and the iodine status. Stratification analyses were conducted based on sex, smoking and iodine status. For adolescents, in a multivariable-adjusted regression model (ß; 95% CI), 1-PHE (4.08%; 1.01%, and 7.25%), 2-PHE (3.98%; 0.70%, and 7.25%) and 9-FLU (3.77%; 1.10%, 7.47%) were positively correlated with TT3; 3-PHE and 1-PYR interacted with the iodine status (P-int < 0.05); 9-FLU was positively correlated with GD in both sexes. Combined exposure to PAHs was positively associated with Tg (0.137; 0.030, and 0.243), and negatively correlated with TSH (-0.087; -0.166, and -0.008). For adults, 2-NAP was positively correlated with FT3 (0.90%; 0.20%, and 1.61%), FT4 (1.82%; 0.70%, and 2.94%), TT3 (1.31%; 0.10%, and 2.63%), TT4 (2.12%; 0.90%, and 3.36%) and GT (2.22%; 1.01%, and 3.46%), but negatively correlated with TSH (-4.97%; -8.33%, and -1.49%); 1-NAP interacted with the iodine status (P-int < 0.05); 1-PHE was inversely correlated with TT3 in males; 2-PHE was positively correlated with TT3 in females. Combined exposure to PAHs was positively associated with FT3 (0.008; 0.001, and 0.014). Combined exposure to PAHs was positively associated with FT3, TT3 and GD, and negatively correlated with FT4, TT4 and GT in non-smoking adults; but positively associated with Tg (ß = 0.140; 95% CI: 0.042, 0.237) in smoking adults. Our results indicated that combined and individual PAH exposure might be related to THs, and the iodine status had an influence on PAH-TH associations. These associations were not identical between adolescents and adults, and there were sex and smoking status differences.

Detoxification of Fumonisins by Three Novel Transaminases with Diverse Enzymatic Characteristics Coupled with Carboxylesterase.

Fumonisin (FB) is one of the most common mycotoxins contaminating feed and food, causing severe public health threat to human and animals worldwide. Until now, only several transaminases were found to reduce FB toxicity, thus, more fumonisin detoxification transaminases with excellent catalytic properties required urgent exploration for complex application conditions. Herein, through gene mining and enzymatic characterization, three novel fumonisin detoxification transaminases-FumTSTA, FumUPTA, FumPHTA-were identified, sharing only 61-74% sequence identity with reported fumonisin detoxification transaminases. Moreover, the recombinant proteins shared diverse pH reaction ranges, good pH stability and thermostability, and the recombinant protein yields were also improved by condition optimum. Furthermore, the final products were analyzed by liquid chromatography-mass spectrometry. This study provides ideal candidates for fumonisin detoxification and meets diverse required demands in food and feed industries.

Study on the Densification of Osmium by Experiment and First Principle Calculations.

The sintering of osmium is critical for the preparation of raw material targets for film coating, which is the main application area of osmium. In order to get a better understanding of the intrinsic mechanism of densification of osmium, a serial study on the sintering behavior of osmium has been made in this study. By the master sintering curve (MSC) and constant heating rate (CHR) method, the sintering activation energy of nanosized osmium is evaluated to be about 340 kJ/mol, which is higher than most other metals. The density-functional theory calculation indicates the higher energy barrier of the surface atom and vacancy migration and lacking migration tunnel of inner point vacancies. For example, the diffusion of osmium atoms on the surface of particles is mainly limited by Os (1010), which has an energy barrier as high as 1.14 eV, that is higher than the W atom on W (110) of 0.99 eV. The vacancy migration energy barrier inside osmium's grains is higher than 3.0 eV, while that of W is only 1.7 eV. This means that it is more difficult for osmium to achieve a high density compared with W, which is consistent with the experimental results. Accordingly, the proposed strategy provides a new opportunity to design a sintering process for target fabrication with excellent properties for various applications.

Crucial Residues of C-Terminal Oligopeptide C60 to Improve the Yield of Prebiotic Xylooligosaccharides by Truncated Mutation.

Increasing the yields of short xylooligosaccharides by enzymatic production is efficient to improve prebiotic effects. Previously, C-terminal oligopeptide C60 was found to accelerate short xylooligosaccharides. Herein, in order to further understand the molecular mechanism of C60, the sequence analysis firstly showed that C60 displays typical properties of a linker (rich in proline/alanine/glycine/glutamine/arginine, 8.33-20.00%). C60 shared the highest identity with the N-terminal region of esterase (98.33%) and high identity with the linker between xylanase and esterase from Prevotella sp. (56.50%), it is speculated to originate from an early linker between XynA and another domain. Besides, structure simulation showed that C60 enhances the molecular interactions between substrate and active residues to improve catalytic efficiency. Moreover, three truncated variants with different lengths of C-terminal regions were successfully generated in Escherichia coli. The specific activities of variants were 6.44-10.24 fold of that of XynA-Tr, and their optimal temperature and pH were the same as XynA-Tr. Three truncated variants released more xylooligosaccharides, especially xylobiose (46.33, 43.41, and 49.60%), than XynA-Tr (32.43%). These results are helpful to understand the molecular mechanism of C60, and also provide new insight to improve the yields of short xylooligosaccharides by molecular modification at the terminal of xylanases.

Cloning, expression, and characterization of a glycosaminoglycan lyase from Vibrio sp. H240.

Glycosaminoglycan lyase is an effective tool for the functional studies of glycosaminoglycans and for the preparation of oligosaccharides. In this study, a new glycosaminoglycan lyase HCLaseV with a molecular weight of 90 kDa was cloned, expressed, and characterized from Vibrio sp. H240. The lyase belonged to the polysaccharide lyase (PL)- 8 family. HCLaseV showed enzyme activities toward chondroitin sulfate A, chondroitin sulfate B, chondroitin sulfate C, and hyaluronic acid. HCLaseV exhibited the highest activity against HA at pH 7.0 and 40 °C. HCLaseV was an endo-type enzyme whose degradation end-product was unsaturated disaccharides. Ca2+ inhibited the activity of HCLaseV to a certain extent, which was different from most of the enzymes in the PL-8 family. Mutagenesis studies showed that the Ca2+ inhibition might be related to the Asn244 residue. The sequence homology was evaluated by mutagenesis studies, and the catalytic residues in HCLaseV were presumed to be His278, Trp485, and Tyr287. These characteristics are helpful for further basic research and application.

First-Principles Study of Mechanical and Thermodynamic Properties of Binary and Ternary CoX (X = W and Mo) Intermetallic Compounds.

In this study, the structural, elastic, and thermodynamic properties of DO19 and L12 structured Co3X (X = W, Mo or both W and Mo) and µ structured Co7X6 were investigated using the density functional theory implemented in the pseudo-potential plane wave. The obtained lattice constants were observed to be in good agreement with the available experimental data. With respect to the calculated mechanical properties and Poisson's ratio, the DO19-Co3X, L12-Co3X, and µ-Co7X6 compounds were noted to be mechanically stable and possessed an optimal ductile behavior; however, L12-Co3X exhibited higher strength and brittleness than DO19-Co3X. Moreover, the quasi-harmonic Debye-Grüneisen approach was confirmed to be valid in describing the temperature-dependent thermodynamic properties of the Co3X and Co7X6 compounds, including heat capacity, vibrational entropy, and Gibbs free energy. Based on the calculated Gibbs free energy of DO19-Co3X and L12-Co7X6, the phase transformation temperatures for DO19-Co3X to L12-Co7X6 were determined and obtained values were noted to match well with the experiment results.

Cloning and characterization of two chondroitin sulfate ABC lyases from Edwardsiella tarda LMG2793.

Chondroitinase ABC can be used to prepare chondroitin sulfate (CS) oligosaccharides efficiently and environmentally. It also promotes nerve recovery through enzymatic degradation of glycosaminoglycan chains in damaged nerve tissue. In this study, two new chondroitin sulfate ABC lyases were expressed and characterized from Edwardsiella tarda LMG2793, with molecular weight of 116.8 kDa and 115.9 kDa, respectively. Two lyases ChABC I and ChABC II belonged to the polysaccharide lyase (PL) family 8. ChABC I and ChABC II showed enzyme activity towards chondroitin sulfate A (CS-A), CS-B, CS-C and CS-D, but had no activity towards hyaluronan (HA). The optimal temperature for ChABC I to exhibit the highest activity against CS-A was 40 °C and the optimal pH was 7.0. ChABC II showed the highest activity to CS-A at optimal temperature of 40 °C and pH of 9.0. ChABC I and ChABC II were stable at 37 °C and remained about 90 % of activity after incubation at 37 °C for 3 h. Many metal ions had no effect on the activity of ChABC I and ChABC II. These properties were beneficial to their further basic research and application. ChABC I was an endo-type enzyme while ChABC II was an exo-type enzyme. A group of amino acids were selected for further study by evaluating the sequence homology with other CS degradation lyases. Mutagenesis studies speculated that the catalytic residues in ChABC I were His522, Tyr529 and Arg581. The catalytic residues of ChABC II were His498, Tyr505 and Arg558. This work will contribute to the structural and functional characterization of biomedically relevant CS and promote the application of CS lyase in further basic research and therapeutics.

What factors affect the methodological and reporting quality of clinical practice guidelines for osteoporosis? Protocol for a systematic review.

BACKGROUND: Osteoporosis is a disease with a high prevalence and low treatment rate, which poses a serious threat to the lives of patients and brings a heavy economic burden. Clinical practice guidelines (CPGs) provide vital guidance for disease management. Up to now, different countries, regions, and organizations have issued a certain number of CPGs for osteoporosis, but the recommendations in different guidelines are inconsistent. This protocol plans to evaluate the quality of the CPGs for osteoporosis and then make a comparative analysis of the recommendations in the CPGs. METHODS: Several databases including PubMed, Web of Science, Embase, and Cochrane Library, as well as the official website of relevant organizations will be searched. Screen and data extraction will be performed by two reviewers independently, and the third reviewer help to resolve the divergence between them. Using the AGREE II instrument and RIGHT checklist to assess the methodological and reporting quality of the CPGs. The extracted recommendations, including but not limited to screening, diagnosis, evaluation and treatment, will be summarized and analyzed, and the results will be presented in tabular form. Bubble charts will be used to show quality differences between CPGs and to describe the correlation between methodological and reporting quality through regression analysis. Excel, EndnoteX9 and SPSS 25.0 will be used. RESULT: To evaluate the advantages and disadvantages of the existing CPGs of osteoporosis and analyze the similarities and differences between the recommendations, the results will be published in a peer-reviewed journal. CONCLUSION: This study will provide systematic evidence for existing CPGs of osteoporosis and to provide a reference for CPGs users. PROTOCOL REGISTRATION: INPLASY 202070031.

Transcriptomics Study to Determine the Molecular Mechanism by which sIL-13Rα2-Fc Inhibits Caudal Intervertebral Disc Degeneration in Rats.

BACKGROUND: Intervertebral disc degeneration is related to tissue fibrosis. ADAMTS can degrade the important components of the ECM during the process of intervertebral disc degeneration, ultimately resulting in the loss of intervertebral disc function. sIL-13Rα2-Fc can inhibit fibrosis and slow down the degeneration process, but the mechanism involved remains unclear. OBJECTIVE: To determine the mechanism by which sIL-13Rα2-Fc inhibits ECM degradation and reduces intervertebral disc tissue fibrosis using a transcriptomics analysis. METHODS: A rat model of caudal intervertebral disc degeneration was established, and Sirius red staining was used to observe the pathological changes in the caudal intervertebral disc. Transcriptome sequencing was employed to assess the gene expression profiles of the intervertebral disc tissues in the model group and the sIL-13Rα2-Fc-treated group. Differentially expressed genes were identified and analyzed using GO annotation and KEGG pathway analyses. Real-time fluorescence quantitative PCR was used to verify the expression levels of candidate genes. The levels of GAG and HA were quantitatively assessed by ELISA, and the levels of collagen I and collagen II were analyzed by western blotting. RESULTS: Sirius red staining showed that in the model group, the annulus fibrosus was disordered, the number of breaks increased, and the type I collagen protein levels increased, whereas in the sIL-13Rα2-Fc group, the annulus fibrosus was ordered, the number of breaks decreased, and the type II collagen protein levels increased. In comparison with the model group, we identified 58 differentially expressed genes in the sIL-13Rα2-Fc group, and these were involved in 35 signaling pathways. Compared with those in the model group, the mRNA expression levels of Rnux1, Sod2, and Tnfaip6 in the IL-13Rα2-Fc group were upregulated, and the mRNA expression levels of Aldh3a1, Galnt3, Fgf1, Celsr1, and Adamts8 were downregulated; these results were verified by real-time fluorescence quantitative PCR. TIMP-1 (an ADAMTS inhibitor) and TIMP-1 combined with the sIL-13Rα2-Fc intervention increased the levels of GAG and HA, inhibited the expression of type I collagen, and promoted the expression of type II collagen. CONCLUSION: Adamts8 may participate in the degradation of ECM components such as GAG and HA and lead to an imbalance in the ECM of the intervertebral disc, resulting in intervertebral disc degeneration. sIL-13Rα2-Fc promoted anabolism of the ECM and increased the levels of ECM components by inhibiting the expression of Adamts8, thus maintaining the dynamic equilibrium of the ECM and ultimately delaying intervertebral disc degeneration.

Enhancing the performance of blue quantum-dot light-emitting diodes through the incorporation of polyethylene glycol to passivate ZnO as an electron transport layer.

The balance between charge transport and charge injection is always a key factor in enhancing the performance of quantum-dot light-emitting diodes (QD-LEDs), particularly for the blue QDs due to their large optical band gap and relatively low valence band level compared with their green and red counterparts. High performance blue QD-LEDs have been demonstrated by blending polyethylene glycol (PEG) into solution-processed ZnO nanocrystals as the electron transport layer. PEG can effectively tune the electron mobility of ZnO and simultaneously passivate its surface defect states. As a result, the maximum current efficiency (CE) and external quantum efficiency (EQE) of the blue QD-LEDs increased from 4.33 cd A-1 and 9.98% for pure ZnO to 8.03 cd A-1 and 14.84% for 4% PEG blended into ZnO, respectively. Furthermore, operational lifetime of the device is also significantly improved from 8.95 h to 25.06 h. This result indicates that PEG is a promising material for regulating the charge balance of the blue QD-LEDs.

Cloning, Expression, and Characterization of a New Glycosaminoglycan Lyase from Microbacterium sp. H14.

Glycosaminoglycan (GAG) lyase is an effective tool for the structural and functional studies of glycosaminoglycans and preparation of functional oligosaccharides. A new GAG lyase from Microbacterium sp. H14 was cloned, expressed, purified, and characterized, with a molecular weight of approximately 85.9 kDa. The deduced lyase HCLaseM belonged to the polysaccharide lyase (PL) family 8. Based on the phylogenetic tree, HCLaseM could not be classified into the existing three subfamilies of this family. HCLaseM showed almost the same enzyme activity towards hyaluronan (HA), chondroitin sulfate A (CS-A), CS-B, CS-C, and CS-D, which was different from reported GAG lyases. HCLaseM exhibited the highest activities to both HA and CS-A at its optimal temperature (35 °C) and pH (pH 7.0). HCLaseM was stable in the range of pH 5.0-8.0 and temperature below 30 °C. The enzyme activity was independent of divalent metal ions and was not obviously affected by most metal ions. HCLaseM is an endo-type enzyme yielding unsaturated disaccharides as the end products. The facilitated diffusion effect of HCLaseM is dose-dependent in animal experiments. These properties make it a candidate for further basic research and application.

Effect of sIL-13Rα2-Fc on the progression of rat tail intervertebral disc degeneration.

BACKGROUND: The incidence of degenerative disc disease caused by intervertebral disc injury is increasing annually, seriously affecting the quality of life of patients and increasing the disease burden on society. The mechanisms of intervertebral disc degeneration include changes in extracellular matrix (ECM) deposition and tissue fibrosis. sIL-13Rα2-Fc potently inhibits interleukin (IL)-13, as well as blocks related cell signaling pathways and inhibits fibrosis in certain tissues. However, it is unknown whether sIL-13Rα2-Fc inhibits fibrosis in injured intervertebral discs and slows the process of degeneration. We hypothesized that sIL-13Rα2-Fc delays the progression of intervertebral disc degeneration by inhibiting intervertebral disc fibrosis and improving ECM deposition. METHODS: A rat tail intervertebral disc degeneration model was established. Pathological changes in rat intervertebral disc tissue were observed by hematoxylin and eosin staining and Masson staining. Glycosaminoglycan (GAG), chondroitin sulfate (CS), keratan sulfate (KS), and hyaluronic acid (HA) contents were quantitatively analyzed by enzyme-linked immunosorbent assay. Type I and type II collagen expression levels were analyzed by reverse transcription-PCR and western blotting. RESULTS: Hematoxylin and eosin staining and Masson staining revealed annulus fibrosus rupture, disordered arrangement, decreased nucleus pulposus tissue, and decreased collagen fiber in the rat intervertebral disc tissue. Following treatment with sIL-13Rα2-Fc, pathological changes in the rat intervertebral disc were reduced. Rat intervertebral disc tissue showed decreased GAG, CS-KS, and (HA) contents, increased type I collagen levels, and decreased type II collagen levels in degenerated intervertebral discs. sIL-13Rα2-Fc intervention increased the contents of GAG, CS, KS, and HA; inhibited the expression of type I collagen; and promoted the expression of type II collagen. CONCLUSION: These results demonstrate that intervertebral disc degeneration is associated with tissue fibrosis. sIL-13Rα2-Fc can regulate type I and type II collagen expression levels by increasing GAG, CS, KS, and HA contents, thereby slowing the progression of intervertebral disc degeneration.

Removal of Cu2+, Cd2+ and Pb2+ from aqueous solutions by magnetic alginate microsphere based on Fe3O4/MgAl-layered double hydroxide.

In this work, the magnetic alginate microsphere of Fe3O4/MgAl-LDH (Fe3O4/LDH-AM) was prepared by immobilizing the Fe3O4/LDH with calcium alginate (CA) and was used to remove Cd2+, Pb2+, and Cu2+ from aqueous solutions. The obtained Fe3O4/LDH-AM was characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, X-ray photoelectron spectroscopy, and Brunauer-Emmett-Teller surface area determination. The results indicated that the surface groups of the alginate and LDH were retained and so was the crystal structure in the alginate microsphere. The adsorption performance of the Fe3O4/LDH-AM for Cd2+, Pb2+, and Cu2+ in aqueous solutions was evaluated by batch and column adsorption experiments. The effects of adsorption conditions, kinetics, isotherms, mechanisms, and potential applications were investigated. The adsorption kinetic data conformed to the pseudo-second-order kinetic equation, and the isotherm data fit well with the Freundlich and Langmuir isotherm models. The adsorption mechanism of Cd2+, Pb2+, and Cu2+ by the Fe3O4/LDH-AM entailed complexation and precipitation. The experimental breakthrough curves were correlated with the Thomas model. Moreover, the Fe3O4/LDH-AM displayed superior regeneration and reusability. These results suggest that the Fe3O4/LDH-AM is an efficient adsorbent for the removal of heavy metals and can be effectively employed in practical applications.