Triamcinolone acetonide induces the autophagy of Ag85B-treated WI-38 cells via SIRT1/FOXO3 pathway.

BACKGROUND: Tracheobronchial stenosis due to tuberculosis (TSTB) seriously threatens the health of tuberculosis patients. The inflammation and autophagy of fibroblasts affect the development of TSTB. Triamcinolone acetonide (TA) can regulate the autophagy of fibroblasts. Nevertheless, the impact of TA on TSTB and underlying mechanism has remained unclear. OBJECTIVE: To study the impact of TA on TSTB and underlying mechanism. MATERIAL AND METHODS: In order to simulate the TSTB-like model in vitro, WI-38 cells were exposed to Ag85B protein. In addition, the cell counting kit (CCK)-8 assay was applied to assess the function of TA in Ag85B-treated WI-38 cells. Quantitative real-time polymerase chain reaction was applied to detect the mRNA level of sirtuin 1 (SIRT1) and forkhead box O3 (FOXO3a), and autophagy-related proteins were evaluated by Western blot analysis. Vascular endothelial growth factor (VEGF) level was investigated by immunohistochemical staining. Enzyme-linked immunosorbent serologic assay was applied to detect the secretion of inflammatory cytokines. Furthermore, hematoxylin and eosin staining was applied to observe tissue injuries. RESULTS: Ag85B affected WI-38 cell viability in a limited manner, while TA notably suppressed Ag85B-treated WI-38 cell viability. TA induced the apoptosis of Ag85B-treated WI-38 cells in a dose-dependent manner. In addition, Ag85B-treated WI-38 cells demonstrated the upregulation of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), interferon gamma (IFN-γ), and fibrotic proteins (transforming growth factor-beta [TGF-ß] and vascular endothelial growth factor [VEGF]), which can be significantly destroyed by the TA. Meanwhile, TA reversed Ag85-induced inhibition of cell autophagy by mediation of p62, LC3, and Beclin1. Furthermore, silencing of SIRT1/FOXO3a pathway could reverse the effect of TA on the autophagy of Ag85B-treated cells. CONCLUSION: TA significantly induced the autophagy of fibroblasts in Ag85B-treated cells by mediation of SIRT1/FOXO3 pathway. This study established a new theoretical basis for exploring strategies against TSTB.

Investigation on the Mechanism of PAL (100) Surface Modified by APTES.

The interfacial mechanism has always been a concern for 3-aminopropyltriethoxysilane (APTES)-grafted palygorskite (PAL). In this research, the mechanism of graft modification for grafting of APTES to the surface of PAL (100) was studied using density functional theory (DFT) calculation. The results illustrated that different grafting states of the APTES influence the inter- and intramolecular interactions between APTES/PAL (100), which are reflected in the electronic structures. For single-, double-, and three-toothed state APTES-PAL (100), the charge transfer rates from the PAL (100) surface to APTES were 0.68, 1.02, and 0.77 e, respectively. The binding energy results show that PAL (100) modification performance in the double-tooth state is the best compared to the other states, with the lowest value of -181.91 kJ/mol. The double-toothed state has lower barrier energy (94.69, 63.11, and 153.67 kJ/mol) during the modification process. This study offers theoretical insights into the chemical modification of the PAL (100) surface using APTES coupling agents, and can provide a guide for practical applications.

A risk score model based on TGF-ß pathway-related genes predicts survival, tumor microenvironment and immunotherapy for liver hepatocellular carcinoma.

BACKGROUND: Transforming growth factor-beta (TGF-ß) signal is an important pathway involved in all stages of liver hepatocellular carcinoma (LIHC) initiation and progression. Therefore, targeting TGF- ß pathway may be a potential therapeutic strategy for LIHC. Prediction of patients' tumor cells response requires effective biomarkers. METHODS: From 54 TGF-ß-related genes, this research determined the genes showing the greatest relation to LIHC prognosis, and developed a risk score model with 8 TGF-ß-related genes. The model divided LIHC patients from different datasets and platforms into low- and high-risk groups. Multivariate Cox regression analysis confirmed that the model was an independent prognostic factor for LIHC. The differences in genetic mutation, immune cell infiltration, biological pathway, response to immunotherapy or chemotherapy, and tumor microenvironment in LIHC samples showing different risks were analyzed. RESULTS: Compared with low-risk group, in the training set and test set, high-risk group showed shorter survival, lower stromal score and higher M0 macrophages scores, regulatory T cells (Tregs), helper follicular T cells. Moreover, high-risk samples showed higher sensitivity to cisplatin, imatinib, sorafenib and salubrinal and pyrimethamine. High-risk group demonstrated a significantly higher Tumor Immune Dysfunction and Exclusion (TIDE) score, but would significantly benefit less from taking immunotherapy and was less likely to respond to immune checkpoint inhibitors. CONCLUSIONS: In general, this work provided a risk scoring model based on 8 TGF-ß pathway-related genes, which might be a new potential tool for predicting LIHC.

Transcriptome analysis of hepatopancreas in penaeus monodon under acute low pH stress.

The decrease of seawater pH can affect the metabolism, acid-base balance, immune response and immunoprotease activity of aquatic animals, leading to aquatic animal stress, impairing the immune system of aquatic animals and weakening disease resistance, etc. In this study, we performed high-throughput sequencing analysis of the hepatopancreas transcriptome library of low pH stress penaeus monodon, and after sequencing quality control, a total of 43488612-56271828 Clean Reads were obtained, and GO annotation and KEGG pathway enrichment analysis were performed on the obtained Clean Reads, and a total of 395 DEGs were identified. we mined 10 differentially expressed and found that they were significantly enriched in the Metabolic pathways (ko01100), Biosynthesis of secondary metabolites (ko01110), Nitrogen metabolism (ko00910) pathways, such as PIGA, DGAT1, DGAT2, UBE2E on Metabolic pathways; UGT, GLT1, TIM genes on Biosynthesis of secondary metabolites; CA, CA2, CA4 genes on Nitrogen metabolism, are involved in lipid metabolism, induction of oxidative stress and inflammation in the muscular body of spot prawns. These genes play an important role in lipid metabolism, induction of oxidative stress and inflammatory response in the muscle of the shrimp. In summary, these genes provide valuable reference information for future breeding of low pH-tolerant shrimp.

Blue laser imaging combined with JNET (Japan NBI Expert Team) classification for pathological prediction of colorectal laterally spreading tumors.

BACKGROUND: Blue laser imaging (BLI) can provide useful information on colorectal laterally spreading tumors (LSTs) by visualizing the surface and vessel patterns in detail. The present research aimed to evaluate the diagnostic performance of BLI-combined JNET (Japan NBI Expert Team) classification for identifying LSTs. METHODS: This retrospective, multicenter study included 172 LSTs consisted of 6 hyperplastic polyps/sessile serrated polyps, 94 low-grade dysplasias (LGD), 60 high-grade dysplasias (HGD), 6 superficial submucosal invasive (m-SMs) carcinomas, and 4 deep submucosal invasive carcinomas. The relationship between the JNET classification and the histologic findings of these lesions were then analyzed. RESULTS: For all LSTs, non-experts and experts had a 79.7% and 90.7% accuracy for Type 2A (P = 0.004), a sensitivity of 94.7% and 96.8% (P = 0.718), and a specificity of 61.5% and 83.3% (P = 0.002) for prediction of LGD, respectively. The results also demonstrated 80.8% and 91.3% accuracy for Type 2B (P = 0.005), a sensitivity of 65.2% and 83.3% (P = 0.017), and a specificity of 90.6% and 96.2% (P = 0.097) for predicting HGD or m-SMs. For LST-granular (LST-G) lesions, Type 2A in experts had higher specificity (65.6% vs. 83.6%, P = 0.022) and accuracy (81.8% vs. 91.2%, P = 0.022). Type 2B in experts only had higher accuracy (82.5% vs. 92.0%, P = 0.019). However, no significant differences were noted for any comparisons between non-experts and experts for LST-non-granular (LST-NG) lesions. CONCLUSIONS: BLI combined with JNET classification was an effective method for the precise prediction of pathological diagnosis in patients with LSTs. Diagnostic performance of JNET classification by experts was better than that by non-experts for all examined LST or LST-G lesions when delineating between Type 2A and 2B, but there was no difference for the identification of LST-NG lesions by these two groups.

Exosome-mediated transfer of miR-1260b promotes cell invasion through Wnt/ß-catenin signaling pathway in lung adenocarcinoma.

Increasing evidence confirms that exosome-mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell-cell communication. However, the potential role of exosomal-miR-1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal-miR-1260b on cell invasion. Exosomal-miR-1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real-time polymerase chain reaction assay. The sensitivity and specificity of exosomal-miR-1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772-0.922). Elevated expression of miR-1260b in LAC tissues was positively correlated with exosomal-miR-1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal-miR-1260b secretion. Exosome-mediated transfer of miR-1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal-miR-1260b regulated Wnt/ß-catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome-mediated tumor-cell-to-tumor-cell communication. Targeting exosome-microRNAs may provide new insights into the diagnosis and treatment of LAC.

First-principles theory of atomic-scale friction explored by an intuitive charge density fluctuation surface.

Atomic-scale friction theory, and even superlubricity, is inseparable from charge redistribution, but lacks a bridge to establish the potential link between them. Here, we first report a quantized charge density fluctuation surface (CDFS) by assembling silicene/graphene and germanene/graphene heterostructures and their corresponding homogeneous bilayers for DFT calculations. By observing the PES morphology, we see that it exhibits a decrease in friction by more than two orders of magnitude. A crucial physical quantity controlling the friction was found to be the charge density fluctuation during the friction process via analyzing the CDFSs. Such CDFS holds a universal applicability in van der Waals materials, and is recommended to explore the friction cooperating with PES. This will be a new idea for exploring whether friction is related to electrical properties by defining the conversion factor K for a wide series of interactions, including metallic, covalent, and van der Waals bonding. In particular, the same conversion factor K exists for van der Waals bonding, and a mutual identification between the CDFS and PES can be achieved.

Next-Generation Sequencing Analysis of mRNA Profile in Cisplatin-Resistant Gastric Cancer Cell Line SGC7901.

BACKGROUND Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. MATERIAL AND METHODS To understand the initiation and developmental mechanism underlying cisplatin-resistant GC, we developed cisplatin-resistant SGC7901 cells (SGC7901/DDP) from the parental cells (SGC7901/S) by continuous exposure to increasing concentrations of cisplatin and subjected these 2 cell lines to RNA sequencing analysis. The data were verified by quantitative polymerase chain reaction and their functional role was evaluated by cell counting kit 8 assay and cell apoptosis and cell cycle flow cytometric analysis. Bioinformatics analysis was performed to classify the differentially-expressed genes (DEGs) involved in the development of cisplatin resistance. RESULTS In comparison with SGC7901/S cells, SGC7901/DDP cells showed a total of 3165 DEGs (2014 upregulated and 1151 downregulated, fold change ≥2, and adjusted P value <0.001). qRT-PCR confirmed the reliability of the RNA sequencing results. Depletion of the top 5 upregulated mRNAs reversed the resistant index, increased apoptotic SGC7901/DDP cells, and arrested the cells at G2/M phase. Gene ontology analysis revealed that the DEGs mainly regulate metabolic process, immune system, locomotion, cell adhesion, cell growth, cell death, cytoskeleton organization, cell binding, signal transducing activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway, Rap1 signaling pathway, proteoglycans in cancer, regulation of actin cytoskeleton, and pathways in cancer. CONCLUSIONS The present study is the first to interrogate mRNAs profiles in human GC cells with cisplatin resistance using RNA sequencing, which may assist in discovering potential therapeutic targets for cisplatin-resistant GC patients.

Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1.

Tyrosine kinase inhibitors (TKIs) directed against BCR-ABL1, the product of the Philadelphia (Ph) chromosome, have revolutionized treatment of patients with chronic myeloid leukemia (CML). However, acquired resistance to TKIs is a significant clinical problem in CML, and TKI therapy is much less effective against Ph(+)B-cell acute lymphoblastic leukemia (B-ALL). BCR-ABL1, via phosphorylated Tyr177, recruits the adapter GRB2-associated binding protein 2 (GAB2) as part of a GRB2/GAB2 complex. We showed previously that GAB2 is essential for BCR-ABL1-evoked myeloid transformation in vitro. Using a genetic strategy and mouse models of CML and B-ALL, we show here that GAB2 is essential for myeloid and lymphoid leukemogenesis by BCR-ABL1. In the mouse model, recipients of BCR-ABL1-transducedGab2(-/-)bone marrow failed to develop CML-like myeloproliferative neoplasia. Leukemogenesis was restored by expression of GAB2 but not by GAB2 mutants lacking binding sites for its effectors phosphatidylinositol 3-kinase (PI3K) or SRC homology 2-containing phosphotyrosine phosphatase 2 (SHP2). GAB2 deficiency also attenuated BCR-ABL1-induced B-ALL, but only the SHP2 binding site was required. The SHP2 and PI3K binding sites were differentially required for signaling downstream of GAB2. Hence, GAB2 transmits critical transforming signals from Tyr177 to PI3K and SHP2 for CML pathogenesis, whereas only the GAB2-SHP2 pathway is essential for lymphoid leukemogenesis. Given that GAB2 is dispensable for normal hematopoiesis, GAB2 and its effectors PI3K and SHP2 represent promising targets for therapy in Ph(+)hematologic neoplasms.

Quantifying Macroscopic Friction of Diamond-like Carbon Films by Microscopic Adsorption and Removal of Water Molecules.

The adsorption and desorption of water molecules, which affect the physical and chemical properties of the sliding interface, are critical for the friction behaviors of two solid contacts in atmosphere environment. The amount of water adsorbed on the open surface is a function of gas pressure according to an adsorption equation. However, for a confined sliding interface, the variation of surface fraction covered by gas molecules with water vapor pressure and its induced effects on friction have not been figured out. In this work, the macroscopic friction of diamond-like carbon (DLC) films in a water vapor atmosphere is quantified on the basis of microscopic adsorption and removal of water molecules. The studies correlate the fraction of water molecules adsorbed on the interface of self-mated DLC films with water vapor pressure to illustrate the direct relationship between friction coefficient and gas pressure by first-principles calculations and model fitting. The calculated results revealed that chemisorption and physisorption of water molecules occur on the surfaces of hydrogen-free DLC films (ta-C) and hydrogenated DLC films (HCF). Then, the relation between friction and gas pressure was built by employing a fractional coverage model based on the linear adsorption equation and gas removal. The obtained model agrees well with the typical experimental results about the steady-state friction coefficient of both highly hydrogenated DLC film (HCF) and tetrahedral amorphous carbon (ta-C) film during sliding at various water vapor pressures. In addition, it gave the curves of fractional surface coverage as a function of water vapor pressure. These results show that the frictional coefficient of DLC films could be predicted on the basis of fractional surface coverage as well as the intrinsic characters on surface chemistry. We suggest that the model may be thus extended to understand and predict the friction of DLC films under a specific gas pressure at a low load and speed.

Synthesis and evaluation of new 5-aminolevulinic acid derivatives as prodrugs of protoporphyrin for photodynamic therapy.

Protoporphyrin IX (PpIX) is used as a photosensitizer in the photodynamic diagnosis (PDD) and photodynamic therapy (PDT) of cancer and is synthesized intracellularly from 5-aminolevulinic acid (5-ALA) precursors. Thirteen novel 5-ALA derivatives were designed and synthesized appropriately with tailored hydrophilicity and lipophilicity. The generation of PpIX was detected and their antitumor activity in vitro and in vivo was also investigated. It was shown that compounds 9b-c, 11b-c and 13a displayed a characteristic long wavelength absorption peak at 593 nm after 5 h incubation in mice fibrosarcoma S180 cells. After being exposed to 600 nm laser light irradiation, these compounds can inhibit cell proliferation in S180 cells in vitro. The growth of S180 cell tumors in Kunming mice was significantly inhibited by these compounds in vivo. Among these compounds, 13a has low dark toxicity and high phototoxicity, which makes it an effective and promising prodrug for PDT.

The effects of dietary leucine on the growth performances, body composition, metabolic abilities and innate immune responses in black carp Mylopharyngodon piceus.

The present study was focused on the growth, body composition, metabolic abilities and innate immune responses in juvenile black carp Mylopharyngodon piceus fed with six levels of dietary leucine (7.3, 12.4, 16.2, 21.9, 28.3 and 34.5 g kg-1) for 9 weeks. Results showed that the highest weight gain (WG) and the lowest feed conversion ratio (FCR) was obtained at 23.5 and 23.9 g kg-1 dietary leucine using second-order polynomial model, respectively. Adequate dietary leucine content (21.9 and 28.3 g kg-1) could significantly up-regulate the expression levels of neuropeptide Y (NPY) and ghrelin (GRL) in the brain of black carp juveniles. The protein efficiency ratio (PER), feed efficiency ratio (FER) and protein deposition ratio (PDR) were also significantly increased by adequate dietary leucine content (21.9 and 28.3 g kg-1) (p < 0.05). Adequate dietary leucine content (21.9 and 28.3 g kg-1) could significantly up-regulate the activities of metabolic enzymes, such as α amylase, trypsin, chymotrypsin and elastase in the liver of Black carp (p < 0.05). However, the activities of alanine transaminase (ALT), aspartate aminotransferase (AST) and leucine aminopeptidase (LAP) were significantly reduced in the fish serum by adequate dietary leucine content (21.9 and 28.3 g kg-1) compared with leucine-deficient diet (7.3 and 12.4 g kg-1). In addition, 21.9 and 28.3 g kg-1 dietary leucine could significantly increase complement component 3 (C3) and C4 contents, lysozyme (LYZ) activities in the serum compared with the leucine-deficient diet (7.3 and 12.4 g kg-1) (p < 0.05). Furthermore, optimal dietary leucine could also significantly up-regulate the mRNA expression levels of LYZ, interferon α (IFN-α), hepcidin (HEPC), natural resistance-associated macrophage protein (NRAMP), C3 and C9 in the blood of juvenile black carp compared with the leucine-deficient diets (7.3 and 12.4 g kg-1) (p < 0.05). In conclusion, these results suggest that adequate dietary leucine (21.9 and 28.3 g kg-1) could increase growth performances, improve metabolic abilities and then enhance non-specific immunities in black carp juveniles.

Attraction induced frictionless sliding of rare gas monolayer on metallic surfaces: an efficient strategy for superlubricity.

Friction on a nanoscale revealed rich load-dependent behavior, which departs strongly from the long-standing Amonton's law. Whilst electrostatic repulsion-induced friction collapse for rare gas sliding over metallic surfaces in a high-load regime was reported by Righi et al. (Phys. Rev. Lett., 2007, 99, 176101), the significant role of attraction on frictional properties has not been reported to date. In this study, the frictional motion of Xe/Cu(111), Xe/Pd(111) and Ar/Cu(111) was studied using van der Waals corrected density functional calculations. An attraction-induced zero friction, which is a signal of superlubricity, was found for the sliding systems. The superlubric state results from the disappearance of the potential corrugation along the favored sliding path as a consequence of the potential crossing in the attractive regime when the interfacial pressure approaches a critical-value. The finding of an attraction-driven friction drop, together with the repulsion-induced collapse in the high-load regime, which breaks down the classic Amonton's law, provides a distinct approach for the realization of inherent superlubricity in some adsorbate/substrate interfaces.

Molecular cloning, characterization and mRNA expression of six peroxiredoxins from Black carp Mylopharyngodon piceus in response to lipopolysaccharide challenge or dietary carbohydrate.

Peroxiredoxin (Prx) belongs to a cellular antioxidant protein family that plays important roles in innate immune function and anti-oxidative capability. In the present study, six Prxs were cloned from Black carp Mylopharyngodon piceus (MpPrx) by homology cloning and rapid amplification of cDNA ends (RACE) techniques. There were 199, 197, 250, 260, 189 and 222 amino acids in six MpPrxs, respectively. BLAST analysis reveals that MpPrxs shares high identities and similar characteristics with other known Prxs from animals. The phylogenetic analysis evidenced three major subclasses corresponding to one-Cys-Prx (MpPrx6), typical two-Cys-Prx (MpPrx1-4) and atypical 2-Cys-Prx (MpPrx5) that reflected the present hierarchy of vertebrates and invertebrates. Although six MpPrxs are constitutively expressed in all tissues, relatively higher-level mRNA expression levels of six MpPrxs can be detected in liver, eyes, heart and adipose tissues by real-time PCR assays. The transcriptional patterns of six MpPrxs mRNA in liver were detected by real-time PCR in Black carp after lipopolysaccharide (LPS) challenge and treated with graded levels of dietary carbohydrate (CHO) (106.5, 194.3, 288.4 and 379.1 g kg(-1)), respectively. These results showed that stimulation with LPS could induce up-expression of six MpPrxs mRNA, and the variations of MpPrx4 were more sensitive than these of other MpPrxs in the liver of Black carp. Compared with those in group with 106.5 g kg(-1) dietary CHO, the expression levels of MpPrx2, MpPrx3 and MpPrx6 were significantly down-regulated while MpPrx5 were significantly induced in liver of Black carp fed with adequate dietary CHO (194.3 g kg(-1)). In addition, significant up-regulations of MpPrx2, MpPrx3 and MpPrx6 were observed in Black carp fed with excessive dietary CHO (379.1 g kg(-1)). And MpPrx4 could be constantly induced with increasing dietary CHO contents in this study. These results indicated that MpPrxs were constitutive and inducible proteins and might play important roles in innate immune function after LPS challenge and regulating redox homeostasis in the metabolism of dietary CHO.

The effects of dietary carbohydrate on the growth, antioxidant capacities, innate immune responses and pathogen resistance of juvenile Black carp Mylopharyngodon piceus.

The present study was focused on the growth, antioxidant capacities, innate immune responses and pathogen resistance in juvenile Black carp Mylopharyngodon piceus fed with graded levels of dietary carbohydrate (CHO) (0.6, 106.5, 194.3, 288.4, 379.1 and 473.8 g kg(-1)) for 9 weeks. Results showed that highest weight gain and special growth ratio was obtained at 288.4 g kg(-1) dietary CHO. And adequate dietary CHO content (288.4 g kg(-1)) could significantly increase the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (Gpx), promote reduced glutathione (GSH) content and then increase the total antioxidant capacities (TAOC) in the liver of M. piceus. However, the malondialdehyde (MDA) levels in the fish liver could be significantly aggravated by excessive dietary CHO. Serum cortisol (COL) levels could be significantly increased in juvenile Black carp M. piceus fed with 379.1 g kg(-1) dietary CHO compared with CHO-deficient diets. Activities of alanine transaminase (GPT) and aspartate transaminase (GOT) were both decreased in the serum of juvenile Black carp M. piceus fed with 194.3 g kg(-1) dietary CHO compared with CHO-deficient diets (0.6 and 106.5 g kg(-1)) or CHO-excess diets (379.1 and 473.8 g kg(-1)). In addition, 288.4 g kg(-1) dietary CHO could significantly up-regulate the mRNA expression levels of hepcidin (HEPC), natural resistance-associated macrophage protein (NRAMP), tumor necrosis factor-α (TNF-α) and interferon (IFN), lysozyme (LYZ) and complement component 3 (C3) in the blood and liver samples of juvenile Black carp M. piceus compared with the CHO-deficient diets (0.6 and 106.5 g kg(-1)). Moreover, 288.4 g kg(-1) dietary CHO could also enhance the contents of C3 and plasma nitrogen monoxide (NO), and increase the activities of LYZ and total nitric oxide synthase (t-NOS) in the serum compared with the CHO-deficient or CHO-excess diets. Furthermore, the survival rates were also increased by adequate dietary CHO (194.3 and 288.4 g kg(-1)) fed to juvenile Black carp M. piceus after infection with Aeromonas hydrophila. In conclusion, these results suggest that adequate dietary CHO (288.4 g kg(-1)) could increase growth, reduce oxidative stress, enhance innate immune responses, improve the health states and then promote disease resistance in juvenile Black carp M. piceus.

Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome.

The RASopathies constitute a family of autosomal-dominant disorders whose major features include facial dysmorphism, cardiac defects, reduced postnatal growth, variable cognitive deficits, ectodermal and skeletal anomalies, and susceptibility to certain malignancies. Noonan syndrome (NS), the commonest RASopathy, is genetically heterogeneous and caused by functional dysregulation of signal transducers and regulatory proteins with roles in the RAS/extracellular signal-regulated kinase (ERK) signal transduction pathway. Mutations in known disease genes account for approximately 80% of affected individuals. Here, we report that missense mutations altering Son of Sevenless, Drosophila, homolog 2 (SOS2), which encodes a RAS guanine nucleotide exchange factor, occur in a small percentage of subjects with NS. Four missense mutations were identified in five unrelated sporadic cases and families transmitting NS. Disease-causing mutations affected three conserved residues located in the Dbl homology (DH) domain, of which two are directly involved in the intramolecular binding network maintaining SOS2 in its autoinhibited conformation. All mutations were found to promote enhanced signaling from RAS to ERK. Similar to NS-causing SOS1 mutations, the phenotype associated with SOS2 defects is characterized by normal development and growth, as well as marked ectodermal involvement. Unlike SOS1 mutations, however, those in SOS2 are restricted to the DH domain.

Effect of Th17 and Treg axis disorder on outcomes of pulmonary arterial hypertension in connective tissue diseases.

This prospective cohort study is to verify the hypothesis that the balance of Th17 and Treg cells frequencies in the peripheral circulation is disturbed in patients with varying degrees of connective tissue diseases-associated pulmonary arterial hypertension (CTD-aPAH) and to prove the influence of Th17/Treg imbalance on prognosis. We detected the frequencies and absolute counts of Th17 and Treg cells and related serum cytokines secretion and expressions of key transcription factors in 117 patients with connective tissue diseases (CTD), 53 patients with CTD-aPAH, and 48 healthy volunteers. Moreover, the median value according to levels of Th17/Treg ratios in patients with CTD-aPAH was chosen as basis of group division for survival analysis. CTD-aPAH patients revealed significant increase in peripheral Th17 cells, Th17-related cytokines, and ROR γt mRNA levels. They also presented a significant decrease in Treg cells, Treg-related cytokines, and Foxp3 mRNA levels as compared with CTD patients and healthy controls. More importantly, the Th17/Treg ratio was significantly related to the severity and prognosis of CTD-aPAH. This study indicated that the Th17/Treg axis disorder plays a critical role in CTD-aPAH. Furthermore, the dynamic balance between Th17 and Treg cells was likely to influence prognosis of patients with CTD-aPAH.

Recirculating aquaculture system as microbial community and water quality management strategy in the larviculture of Scylla paramamosain.

The structure and function of the water microbial community can change dramatically between different rearing modes. Yet investigations into the relationships between microbial community and water quality remain obscure. We provide the first evidence that rearing modes alter bacterial community and water quality in the rearing water of the mud crab (Scylla paramamosain) larvae. The juveniles in the recirculating aquaculture system (RAS) had a higher viability than those in the water exchange system (WES). RAS had the significantly lower levels of total ammonia nitrogen (TAN), NH3, NO2--N, total nitrogen (TN), total dissolved solids (TDS), and chemical oxygen demand than those of WES. The number of significantly different amplicon sequence variants between rearing modes increased as the larvae developed. NH3, TAN, TDS, NO2--N, and TN were closely related to the late alterations in water bacterial community. Both the FAPROTAX tool and quantitative PCR analysis showed enhanced nitrogen cycling functional potential of water bacterial community of RAS. Random forest analysis identified the enriched water bacteria especially heterotrophic bacteria such as Phaeodactylibacter, Tenacibaculum, and Hydrogenophaga, which were vital in removing nitrogenous compounds via simultaneous nitrification and denitrification. Notably, RAS could save 18.5 m3 of seawater relative to WES in larviculture on the scale of 2.5 m3. Together, these data indicate that RAS could function as microbial community and water quality management strategy in the larviculture of crab.

Acquisition of molecular rolling lubrication by self-curling of graphite nanosheet at cryogenic temperature.

Friction as a fundamental physical phenomenon dominates nature and human civilization, among which the achievement of molecular rolling lubrication is desired to bring another breakthrough, like the macroscale design of wheel. Herein, an edge self-curling nanodeformation phenomenon of graphite nanosheets (GNSs) at cryogenic temperature is found, which is then used to promote the formation of graphite nanorollers in friction process towards molecular rolling lubrication. The observation of parallel nanorollers at the friction interface give the experimental evidence for the occurrence of molecular rolling lubrication, and the graphite exhibits abnormal lubrication performance in vacuum with ultra-low friction and wear at macroscale. The molecular rolling lubrication mechanism is elucidated from the electronic interaction perspective. Experiments and theoretical simulations indicate that the driving force of the self-curling is the uneven atomic shrinkage induced stress, and then the shear force promotes the intact nanoroller formation, while the constraint of atomic vibration decreases the dissipation of driving stress and favors the nanoroller formation therein. It will open up a new pathway for controlling friction at microscale and nanostructural manipulation.

RADCURE: An open-source head and neck cancer CT dataset for clinical radiation therapy insights.

PURPOSE: This manuscript presents RADCURE, one of the most extensive head and neck cancer (HNC) imaging datasets accessible to the public. Initially collected for clinical radiation therapy (RT) treatment planning, this dataset has been retrospectively reconstructed for use in imaging research. ACQUISITION AND VALIDATION METHODS: RADCURE encompasses data from 3346 patients, featuring computed tomography (CT) RT simulation images with corresponding target and organ-at-risk contours. These CT scans were collected using systems from three different manufacturers. Standard clinical imaging protocols were followed, and contours were manually generated and reviewed at weekly RT quality assurance rounds. RADCURE imaging and structure set data was extracted from our institution's radiation treatment planning and oncology information systems using a custom-built data mining and processing system. Furthermore, images were linked to our clinical anthology of outcomes data for each patient and includes demographic, clinical and treatment information based on the 7th edition TNM staging system (Tumor-Node-Metastasis Classification System of Malignant Tumors). The median patient age is 63, with the final dataset including 80% males. Half of the cohort is diagnosed with oropharyngeal cancer, while laryngeal, nasopharyngeal, and hypopharyngeal cancers account for 25%, 12%, and 5% of cases, respectively. The median duration of follow-up is five years, with 60% of the cohort surviving until the last follow-up point. DATA FORMAT AND USAGE NOTES: The dataset provides images and contours in DICOM CT and RT-STRUCT formats, respectively. We have standardized the nomenclature for individual contours-such as the gross primary tumor, gross nodal volumes, and 19 organs-at-risk-to enhance the RT-STRUCT files' utility. Accompanying demographic, clinical, and treatment data are supplied in a comma-separated values (CSV) file format. This comprehensive dataset is publicly accessible via The Cancer Imaging Archive. POTENTIAL APPLICATIONS: RADCURE's amalgamation of imaging, clinical, demographic, and treatment data renders it an invaluable resource for a broad spectrum of radiomics image analysis research endeavors. Researchers can utilize this dataset to advance routine clinical procedures using machine learning or artificial intelligence, to identify new non-invasive biomarkers, or to forge prognostic models.