Post-crotonylation oxidation by a monooxygenase promotes acetyl-CoA synthetase degradation in Streptomyces roseosporus.

Protein post-translational modifications (PTMs) with various acyl groups play central roles in Streptomyces. But whether these acyl groups can be further modified, and the influences of these potential modifications on bacterial physiology have not been addressed. Here in Streptomyces roseosporus with rich crotonylation, a luciferase monooxygenase LimB is identified to elaborately regulate the crotonylation level, morphological development and antibiotic production by oxidation on the crotonyl groups of an acetyl-CoA synthetase Acs. This chemical modification on crotonylation leads to Acs degradation via the protease ClpP1/2 pathway and lowered intracellular crotonyl-CoA pool. Thus, we show that acyl groups after PTMs can be further modified, herein named post-PTM modification (PPM), and LimB is a PTM modifier to control the substrate protein turnover for cell development of Streptomyces. These findings expand our understanding of the complexity of chemical modifications on proteins for physiological regulation, and also suggest that PPM would be widespread.

TINAVI robot-assisted one-stage anteroposterior surgery in lateral position for severe thoracolumbar fracture dislocation: A case report.

BACKGROUND: The combined anterior/posterior approach appears to be capable of reconstructing spinal stability, correcting thoracolumbar deformity, and promoting neural recovery in severe thoracolumbar fracture dislocation. However, this type of operation requires changing the body position during the procedure, resulting in a lengthy operation time. As a universal surgical robot, TINAVI robot has achieved good surgical results in clinical surgery. But to our knowledge, no reports describing TINAVI robot-assisted single lateral position anteroposterior surgery for thoracolumbar fracture dislocation. CASE SUMMARY: We describe a case of a 16-year-old female patient with severe thoracolumbar fracture and dislocation underwent surgery assisted by the TINAVI robot. A one-stage combined anterior and posterior operation was performed on a severe thoracolumbar fracture dislocation using the TINAVI robot, and the operation was completed in right lateral position. CONCLUSION: The TINAVI robot-assisted one-stage anterior and posterior surgery in right lateral position for severe thoracolumbar fracture and dislocation is both safe and effective.

Phosphorylation of C(sp3)-H Bonds via 1,4-Palladium Migration.

1,4-Palladium migration has emerged as a reliable method for directed C-H functionalization. In contrast to coupling with carbon nucleophiles, limited examples with heteroatom nucleophiles have been reported. Herein we report a palladium-catalyzed intermolecular C(sp3)-H phosphorylation reaction via 1,4-palladium migration, which is often difficult because of the strong coordination of phosphorus reagents to palladium catalysts. Phosphorylation of C(sp3)-H bonds is accomplished in good reaction yields with excellent regioselectivity. The judicious selection of the phosphine ligand proved to be the key to the success of this cascade process.

Palladium-catalyzed cross-coupling of unreactive C(sp3)-H bonds with azole C(sp2)-H bonds by using bromide as a traceless directing group.

A palladium-catalyzed intermolecular cross-coupling of unreactive C(sp3)-H bonds and azole C(sp2)-H bonds with bromide as a traceless directing group is described. The judicious selection of the bulky and electron-rich phosphine ligand is the key for the success of this cascade process. The protocol features a broad substrate scope, excellent regioselectivity, and good functional group tolerance.

Multiplexed Analysis of Endogenous Guanidino Compounds via Isotope-Coded Doubly Charged Labeling: Application to Lung Cancer Tissues as a Case.

Endogenous guanidino compounds (GCs), nitrogen-containing metabolites, have very important physiological activities and participate in biochemical processes. Therefore, accurately characterizing the distribution of endogenous GCs and monitoring their concentration variations are of great significance. In this work, a new derivatization reagent, 4,4'-bis[3-(dimethylamino)propyl]benzyl (BDMAPB), with isotope-coded reagents was designed and synthesized for doubly charged labeling of GCs. BDMAPB-derivatized GCs not only promote the MS signal but also form multicharged quasimolecular ions and abundant fragment ions. With this reagent, an isotope-coded doubly charged labeling (ICDCL) strategy was developed for endogenous GCs with high-resolution liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF MS). The core of this methodology is a 4-fold multiplexed set of [d0]-/[d4]-/[d8]-/[d12]-BDMAPB that yields isotope-coded derivatized GCs. Following a methodological assessment, good linear responses in the range of 25 nM to 1 µM with correlation coefficients over 0.99 were achieved. The limit of detection and the limit of quantitation were below 5 and 25 nM, respectively. The intra- and interday precisions were less than 18%, and the accuracy was in the range of 77.3-122.0%. The percentage recovery in tissues was in the range of 85.1-113.7%. The results indicate that the developed method facilitates long-term testing and ensures accuracy and reliability. Finally, the method was applied for the simultaneous analysis of endogenous GCs in four types of lung tissues (solid adenocarcinoma, solid squamous-cell carcinoma, ground-glass carcinoma, and paracancerous tissues) for absolute quantification, nontargeted screening, and metabolic difference analysis. It is strongly believed that ICDCL combined with isotope-coded BDMAPB will benefit the analysis and study of endogenous GCs.

The Gut Microbiota and Traditional Chinese Medicine: A New Clinical Frontier on Cancer.

Gut microbiota is a complex microecosystem, which is called the second genome of the human body. Herbal medicine can balance tumor-suppressing bacteria and tumor-promoting bacteria and exert its anti-cancer effect by regulating gut microbiota. Traditional Chinese medicine (TCM) has a history of thousands of years in prevention and treatment of diseases in China. In recent decades, TCM has been shown to have an obvious advantage in prolonging the survival time and improving the living quality of patients with cancer. Notably, gut microbiota has become a new pathway to understanding TCM. In this review, we will focus on gut microbiota and tumor progression, especially the diversity, functionality and metabolites of gut microbiota affected by TCM in various cancer. We will also discuss the potential mechanism of gut microbiota for exploring TCM in anti-cancer effect. This article aims to comprehensively review the anti-cancer research of TCM by regulating gut microbiota, and address future perspectives and challenges of gut microbiota in TCM intervention for cancer.

Intelligent Brushing Monitoring Using a Smart Toothbrush with Recurrent Probabilistic Neural Network.

Smart toothbrushes equipped with inertial sensors are emerging as high-tech oral health products in personalized health care. The real-time signal processing of nine-axis inertial sensing and toothbrush posture recognition requires high computational resources. This paper proposes a recurrent probabilistic neural network (RPNN) for toothbrush posture recognition that demonstrates the advantages of low computational resources as a requirement, along with high recognition accuracy and efficiency. The RPNN model is trained for toothbrush posture recognition and brushing position and then monitors the correctness and integrity of the Bass Brushing Technique. Compared to conventional deep learning models, the recognition accuracy of RPNN is 99.08% in our experiments, which is 16.2% higher than that of the Convolutional Neural Network (CNN) and 21.21% higher than the Long Short-Term Memory (LSTM) model. The model we used can greatly reduce the computing power of hardware devices, and thus, our system can be used directly on smartphones.

Urine metabolic profiles in paediatric asthma.

BACKGROUND AND OBJECTIVE: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology. METHODS: Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes. RESULTS: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma. CONCLUSION: Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.

[Clinical and pathological features and the misdiagnosis of childhood Alport syndrome: a retrospective analysis of 91 cases].

OBJECTIVE: To explore the clinical and pathological features and the diagnosis of childhood Alport syndrome (AS). METHODS: A retrospective analysis was performed on clinical data of 91 children with AS. RESULTS: Hematuria was observed in all 91 patients, of whom 86 were accompanied with proteinuria. Sixty-one children with X-Linked AS (XL-AS) had positive family history. Renal biopsy was performed on 82 children. Mild to moderate mesangial proliferation was observed in 74 cases. Small amounts of immune complexes deposits in the glomerular mesangial area were observed in 48 cases. Glomerular basement membrane (GBM) attenuation, thickening and layering were observed in 53 cases by electron microscopy (EM). In 63 cases receiving renal tissue type IV collagen α3 and α5 chain immunofluorescence detection, 58 were diagnosed with AS, including 53 cases of XL-AS and 5 cases of autosomal recessive AS. In 91 cases of AS, 58 were diagnosed as AS by renal tissue type IV collagen α3 and α5 chain immunofluorescence, 21 were diagnosed by EM, one was diagnosed by skin biopsy, and 12 were diagnosed by gene detection. Six novel mutations of COL4A5 gene were found. Forty-five cases were misdiagnosed before the diagnosis of AS. Forty-one of the 45 cases received steroids and/or immunosuppressant therapy. CONCLUSIONS: The clinical manifestations and pathological changes are not specific in children with AS, resulting in a higher rate of misdiagnosis. Typical lesions of GBM under EM are only observed in a part of patients. There is a high novel mutation rate of COL4A5 in the detected AS children.

Tyrosine-protein phosphatase non-receptor type 12 expression is a good prognostic factor in resectable non-small cell lung cancer.

Tyrosine-protein phosphatase non-receptor type 12 (PTPN12) has been considered to be a tumor suppressor in human cancer, but its clinical and prognostic significance in non-small cell lung cancer (NSCLC) has not been well elucidated.A retrospective analysis of 215 patients with surgically resected NSCLCs from Sun Yat-Sen University Cancer Center between April 2002 and March 2005 was performed using immunohistochemistry and Western Blot to analyze PTPN12 expression. The association between PTPN12 expression and patient survival was investigated.Western Blots showed that the expression level of PTPN12 were higher in normal paracancerous lung tissues than in NSCLC tissues. High PTPN12 expression was less common in the presence than in the absence of visceral pleural invasion (p=0.038). Patients with PTPN12-high tumors had a longer disease-free survival (DFS) (P<0.001) and overall survival (OS) (p<0.001), especially for those with non-squamous cell carcinoma (non-SCC) (DFS, p<0.001; OS, p<0.001). Multivariate analysis confirmed that PTPN12 positivity was associated with increased survival duration (DFS, p<0.001; OS, p<0.001), independent of prognostic indicator.High PTPN12 expressive levels are associated with favorable survival duration in patients with NSCLC, especially those with non-SCC. Our study suggests that PTPN12 expression is a valuable prognostic biomarker for NSCLC patients.

Cadmium-induced membrane lipid peroxidation and changes in antioxidant enzyme activities and peroxidase isoforms in Jerusalem artichoke seedlings.

Jerusalem artichoke (Helianthus tuberosus L.) seedlings cultured in sandy media were treated with Hoagland nutrition solution with different concentrations of Cd(NO(3))(2) from 0 to 400 micromol/L. After 50 days' treatment, Cd accumulation, activities of peroxidase (POD, EC 1.11.1.7), superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6) were measured and electrophoretograms of POD isoenzymes were analyzed. The accumulation of Cd in seedlings increased from Cd 50-100 micromol/L, after which further increases in Cd concentration resulted in only small increases in accumulation of Cd in seedlings. MDA content was markedly higher than control values indicating the enhanced membrane lipid peroxidation in roots and leaves. POD activities in leaf and root extracts increased with an increase of Cd concentration from 0 to 50 and 100 micromol/L and then decreased with further increases to 200 and 400 micromol/L. Under moderate Cd level of 50-200 micromol/L, SOD activities in leaf and root extracts increased whereas with a higher Cd level of 400 micromol/L marked inhibitions in enzyme activities were observed. With increase in Cd concentration marked elevations in CAT activities in leaves and roots were observed. Results of electrophoresis show that the alteration of POD isoenzyme was noticeable to Cd and an additional POD isoenzyme LP10 appeared. It is suggested that POD isoenzyme of Jerusalem artichoke seedlings could be used as bioindicator for soil contamination by Cd.