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Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IRW−K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients. [ABSTRACT FROM AUTHOR]

Plastics are crucial constituents in electronic waste (e-waste) and part of the issue in e-waste recycling and environmental protection. However, previous studies have mostly focused on plastic recovery or thermal behavior of flame retardants, but not both simultaneously. The present study simulated the process of e-waste thermal treatment to explore tetrabromobisphenol A (TBBPA) pyrolysis at various temperatures using polystyrene (PS), polyvinyl chloride (PVC), and e-waste plastics as polymer matrices. Pyrolysis of TBBPA produced bromophenol, bromoacetophenone, bromobenzaldehyde, and bromobisphenol A. Co-pyrolysis with the polymer matrices increased emission factors by 1 − 2 orders of magnitude. The pyrolytic products of TBBPA, TBBPA+PS, and TBBPA+PVC were mainly low-brominated bisphenol A, while that of TBBPA in e-waste plastics was consistently bromophenol. Increasing temperature drove up the proportions of gaseous and particulate products, but lowered the relative abundances of inner wall adsorbed and residual products in pyrolysis of pure TBBPA. In co-pyrolysis of TBBPA with polymer matrix, the proportions of products in different phases were no longer governed solely by temperature, but also by polymer matrix. Co-pyrolysis of TBBPA with PS generated various bromophenols, while that with PVC produced chlorophenols and chlorobrominated bisphenol A. Transformation pathways, deduced by ab initio calculations, include hydrogenation-debromination, isopropylphenyl bond cleavage, oxidation, and chlorination. [Display omitted] • Co-pyrolysis of TBBPA with PS and PVC produces numerous aldehyde and ketone compounds. • Temperature enhances the emission of particulated products from prolysis of TBBPA. • Hydroxylation, methylation, and addition reaction occur in pyrolysis of TBBPA+PS. • Radical Cl• from PVC plays an important role in the co-pyrolysis of TBBPA. [ABSTRACT FROM AUTHOR]

Objective. Gout is a chronic disease that causes inflammatory arthritis, which is closely related to urate accumulation induced by a disorder of uric acid metabolism and the consequent deposition of monosodium urate crystals. Dendrobium loddigesii Rolfe is an herbal medicine that has been used in some traditional Chinese medicine formulae in the treatment of gout. This study aimed to explore and verify the antigout activity of Dendrobium loddigesii extract (DLE) on alleviating the hyperuricaemia of mice and the acute gouty arthritis of rats. Methods. An animal model of hyperuricaemia was established using potassium oxonate (PO). We analysed the expression of uric acid transporter mRNA in the kidney in the hyperuricaemic mice after treatment with DLE. Simultaneously, a monosodium urate crystal-induced acute gouty arthritis rat model was used to evaluate the effects of DLE, according to the level of ankle swelling, as well as the protein levels of inflammatory receptors and cytokines, as assayed by WB and ELISA. Results. DLE alleviated hyperuricaemia in mice and inhibited acute gouty arthritis in rats (P < 0.05). Meanwhile, DLE regulated the levels of uric acid transporters mRNA transcripts, including mouse organic anion transporter 1 (mOAT1), organic anion transporter 3 (mOAT3), urate transporter 1 (mURAT1), and glucose transporter 9 (mGLUT9) in the kidney (P < 0.05), suggesting that DLE promoted uric acid metabolism. Furthermore, DLE significantly suppressed the protein levels of TLRs, MyD88, and NF-κB in the ankle joint's synovium (P < 0.05), and the serum levels of IL-1β, IL-6, and TNF-α were also reduced, which demonstrated the anti-inflammatory effects of DLE. Conclusion. DLE alleviates hyperuricaemia by regulating the transcription level of uric acid transporters in the kidney. It also inhibits acute gouty arthritis by inhibiting the pathway of TLRs/MyD88/NF-κB in the ankle joint's synovium. The findings of the present study imply that DLE alleviates gout by promoting uric acid metabolism and inhibiting inflammation related to the TLRs/MyD88/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Objectives: A radiographic study was designed to measure the relationship of the exiting nerve root and its surroundings to the corresponding intervertebral disc for percutaneous transforaminal endoscopic lumbar interbody fusion to better understand the regional anatomy and to improve clinical applications. Methods: A retrospective study from January 2017 to October 2017 was conducted at Tianjin Hospital. CT images were obtained from patients presenting low back pain (110 patients), and analysis was performed bilaterally from L2‐3 to L5S1. In the rotating coronal plane we analyzed: the nerve root–dural sac distance at the superior and inferior margins of the disc (Js, Ji); the nerve root–pedicle distance at the medial, middle, and lateral borders of the pedicle (Pa, Pb, Pc); the pedicle width (W); and the safe working zone, defined as a trapezoid bounded by the inferior pedicle and the exiting nerve root (S). In the transverse plane, the nerve root‐articular process and the shortest distance for the nerve root‐articular process joint surface were analyzed at the superior and inferior margins of the disc (Gs, Gi), respectively. The groups were analyzed using ANOVA, and paired t‐tests were used to compare the left and right sides. Results: From L2‐3 to L5S1, the distance of the nerve root to the dural sac was larger at the inferior margin of the disc. From L2‐3 to L5S1, each segment of the vertebral nerve root‐pedicle distance gradually decreased from medial to lateral. From L2‐3 to L5S1, the distance from the exiting nerve root to the middle and lateral margins of the pedicle gradually decreased, with L5S1 being the minimum. Some significant differences were observed between the left and right sides for L4‐5 and L5S1. The pedicle width of the vertebral body and the mean area for the safe working zone gradually increased from L2‐3 to L5S1. In the axial plane, the shortest distance between the nerve root and articular process joint surface at the inferior margin of the disc was greater than the distance for the nerve root to the articular process at the superior margin of the disc from L2‐3 to L5S1. There were no significant differences between the two sides. Conclusions: It is more difficult to implant a cage with a width of 10 mm above the L3‐4 level. By removing part of the superior articular process, the safe working area can be expanded, and damage to the nerve or other structures can be avoided when implanting a cage. [ABSTRACT FROM AUTHOR]

This paper creatively proposes a cluster boundary sampling method based on density clustering to solve the problem of resampling in IDS classification and verify its effectiveness experimentally. We use the clustering density threshold and the boundary density threshold to determine the cluster boundaries, in order to guide the process of resampling more scientifically and accurately. Then, we adopt the penalty factor to regulate the data imbalance effect on SVM classification algorithm. The achievements and scientific significance of this paper do not propose the best classifier or solution of imbalanced data set and just verify the validity and stability of proposed IDS resampling method. Experiments show that our method acquires obvious promotion effect in various imbalanced data sets. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidium andersoni initiates infection by releasing sporozoites from oocysts through excystation. However, the proteins involved in excystation are unknown. Determining the proteins that participate in the excystation of C. andersoni oocysts will increase our understanding of the excystation process. Methods: Cryptosporidium andersoni oocysts were collected and purified from the feces of naturally infected adult cows. Tandem mass tags (TMT), coupled with liquid chromatography–tandem mass spectrometry (LC–MS/MS) proteomic analysis, were used to investigate the proteomic expression profiles of C. andersoni oocysts before and after excystation. Results: Proteomic analysis identified a total of 1586 proteins, of which 17 were differentially expressed proteins (DEPs) upon excystation. These included 10 upregulated and seven downregulated proteins. The 17 proteins had multiple biological functions associated with control of gene expression at the level of transcription and biosynthetic and metabolic processes. Quantitative real-time RT-PCR of eight selected genes validated the proteomic data. Conclusions: This study provides information on the protein composition of C. andersoni oocysts as well as possible excystation factors. The data may be useful in identifying genes for diagnosis, vaccine development, and immunotherapy for Cryptosporidium. [ABSTRACT FROM AUTHOR]