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Water-based drilling fluids can cause hydration of the wellbore rocks, thereby leading to instability. This study aimed to synthesize a hydrophobic small-molecule polymer (HLMP) as an inhibitor to suppress mud shale hydration. An infrared spectral method and a thermogravimetric technique were used to characterize the chemical composition of the HLMP and evaluate its heat stability. Experiments were conducted to measure the linear swelling, rolling recovery rate, and bentonite inhibition rate and evaluate accordingly the inhibition performance of the HLMP. Moreover, the HLMP was characterized through measurements of the zeta potential, particle size distribution, contact angles, and interlayer space testing. As confirmed by the results, the HLMP could successfully be synthesized with a favorable heat stability. Furthermore, favorable results were found for the inhibitory processes of the HLMP on swelling and dispersed hydration during mud shale hydration. The positively charged HLMP could be electrically neutralized with clay particles, thereby inhibiting diffusion in the double electron clay layers. The hydrophobic group in the HLMP molecular structure resulted in the formation of a hydrophobic membrane on the rock surface, enhancing the hydrophobicity of the rock. In addition, the small molecules of the HLMP could plug the spaces between the layers of bentonite crystals, thereby reducing the entry of water molecules and inhibiting shale hydration. [ABSTRACT FROM AUTHOR]

Mutton has recently been identified to be a consumer favorite, and intermuscular fat is the key factor in determining meat tenderness. Long- chain acyl-CoA synthetase 1 (ACSL1) is a vital subtype of the ACSL family that is involved in the synthesis of lipids from acyl-CoA and the oxidation of fatty acids. The amplification of the ACSL1 gene using rapid amplification of cDNA ends revealed that the alternative polyadenylation (APA) results in two transcripts of the ACSL1 gene. Exon 18 had premature termination, resulting in a shorter CDS region. In this study, the existence of two transcripts of varying lengths translated normally and designated ACSL1-a and ACSL1-b was confirmed. Overexpression of ACSL1-a can promote the synthesis of an intracellular diglyceride, while ACSL1-b can promote triglyceride synthesis. The transfection of ACSL1 shRNA knocks down both the transcripts, the triglyceride content was significantly reduced after differentiation and induction; and lipidome sequencing results exhibited a significant decrease in 14-22 carbon triglyceride metabolites. The results of the present study indicated that the ACSL1 gene played a crucial role in the synthesis of triglycerides. Furthermore, the two transcripts involved in various interactions in the triglyceride synthesis process may be the topic of interest for future research and provide a more theoretical basis for sheep breeding. [ABSTRACT FROM AUTHOR]

Valproic acid/sodium valproate (VPA) is a widely used anticonvulsant drug for maintenance treatment of bipolar disorders. In order to balance the efficacy and adverse events of VPA treatment, an individualized dose regimen is necessary. This study aimed to establish an individualized medication model of VPA for patients with bipolar disorder based on machine learning and deep learning techniques. The sequential forward selection (SFS) algorithm was applied for selecting a feature subset, and random forest was used for interpolating missing values. Then, we compared nine models using XGBoost, LightGBM, CatBoost, random forest, GBDT, SVM, logistic regression, ANN, and TabNet, and CatBoost was chosen to establish the individualized medication model with the best performance (accuracy = 0.85, AUC = 0.91, sensitivity = 0.85, and specificity = 0.83). Three important variables that correlated with VPA daily dose included VPA TDM value, antipsychotics, and indirect bilirubin. SHapley Additive exPlanations was applied to visually interpret their impacts on VPA daily dose. Last, the confusion matrix presented that predicting a daily dose of 0.5 g VPA had a precision of 55.56% and recall rate of 83.33%, and predicting a daily dose of 1 g VPA had a precision of 95.83% and a recall rate of 85.19%. In conclusion, the individualized medication model of VPA for patients with bipolar disorder based on CatBoost had a good prediction ability, which provides guidance for clinicians to propose the optimal medication regimen. [ABSTRACT FROM AUTHOR]

Objective: To determine whether polymorphisms in IL-6 and IL-12 contribute to the etiology of coal workers' pneumoconiosis (CWP) in a Chinese Hui population, and to evaluate the efficacy and safety of high frequency oscillatory ventilation (HFOV) in the treatment of CWP. Introduction: Genes and the environments interplay in the development of CWP, and the association between the potential functional polymorphisms in many genes and CWP have been reported. Methods: We genotyped the IL-6-634C/G (rs1800796) and IL-12B-1188A/C (rs3212227) polymorphisms in a casecontrol study including 160 CWP patients and 150 dust-exposed control subjects of Chinese Hui population, and analyzed the associations between these genetic variants and CWP risk. We also evaluated the efficacy and safety of HFOV for whole lung lavage (WLL) in the treatment of CWP. Results: Carrying the C allele of IL-6-634C/G (rs1800796) was associated with decreased risk of CWP (p < 0.05). No significant differences in allele or genotype frequencies of IL-12B-1188A/C was found between the CWP cases and control subjects (p > 0.05). Compared with CWP patients with routine WLL, CWP patients received HFOV showed better pulmonary functions. HFOV treatment also yield a significant higher efficient rate (97.50%) than WLL treatment (81.25%, p = 0.001). CWP patients receiving HFOV and WLL treatment both showed significantly increased serum contents of Clara cell protein 16 (CC16) and superoxide dismutase (SOD), and decreased serum contents of serum malonaldehyde (MDA). While the increasing of CC16 and SOD, and decreasing of MDA in patients receiving HFOV was more noticeable than patients receiving WLL. Conclusions: Taking together, the -634C/G polymorphisms in IL-6 play a role in the etiology of CWP. HFOV, when applied in CWP patients, significant improves their pulmonary functions. [ABSTRACT FROM AUTHOR]

Objective: Puerarin has the potential of regulating the differentiation of preadipocytes, but its mechanism of action has not yet been elucidated. Adipocytes found in adipose tissue, the main endocrine organ, are the main sites of lipid deposition, and are widely used as a cell model in the study of in vitro fat deposition. This study aimed to investigate the effects of puerarin on adipogenesis in vitro. Methods: Puerarin was added to the culture medium during the process of adipogenesis. The proliferation and differentiation of bovine preadipocytes was measured through cell viability and staining with oil red O. The content of triacylglycerol was measured using a triglyceride assay kit. The mRNA and protein expression levels of adipogenic genes, peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer-binding protein-α, were measured using quantitative real-time polymerase chain reaction and western blotting, respectively. Results: The addition of puerarin significantly increased adipogenesis of bovine preadipocytes and enhanced the mRNA and protein level expression of PPARγ (p<0.01). The expression of P-Akt increased after adipogenic hormonal induction, whereas puerarin significantly increased PPARγ expression by promoting the Akt signaling component, P-Akt. The mechanism of adipogenesis was found to be related to the phosphorylation level of Ser473, which may activate the downstream signaling of the Akt pathway. Conclusion: Puerarin was able to promote the differentiation of preadipocytes and improve fat deposition in cattle. The mechanism of adipogenesis was found to be related to the phosphorylation level of Ser473. [ABSTRACT FROM AUTHOR]

The amount of municipal solid waste in China is increasing at an unprecedented pace. This is due to continued urbanization and improved standards of living. Waste-to-energy (WTE) incineration technologies offer viable and potentially profitable solutions. Many innovative WTE technologies have emerged in the past decade. This study uses network theory and social network analysis to investigate the evolution of social network structures for WTE technologies considering global network properties, major actors' centrality and collaboration relationships. Using a dataset of patents pertaining to waste heat during the period 2006-2015, this study finds that the overall WTE innovation network exhibits qualities of a Barabasi-Albert (BA) scale-free network with minority organizations linking to abundant organizations. Many of the major participants are involved in WTE research and have developed collaborative relationships. Their innovation network has social network characteristics and is similar to industrial supply chains. Recommendations are proposed that shed light on the development of WTE innovation networks and efficient diffusion of information. [ABSTRACT FROM PUBLISHER]

Recent studies have demonstrated that chronic hepatitis B virus (HBV) infection is associated with reduced antigen-presenting capacity and insufficient cytotoxic T lymphocyte (CTL) production. The molecular chaperone tapasin mediates binding of the transporter associated with antigen processing (TAP), and has an important role in endogenous antigen processing and presentation, and the induction of specific CTL responses. The present study aimed to determine whether tapasin is associated with chronic HBV (CHB) infection. The mRNA expression levels of tapasin were detected in peripheral blood mononuclear cells from 27 patients with CHB, 20 patients with acute HBV (AHB) and 26 healthy controls by reverse transcription-quantitative polymerase chain reaction. In addition, CD8+ T immune responses were evaluated in all groups, and the correlation between tapasin expression and CD8+ responses was analyzed. The results demonstrated that the mRNA expression levels of tapasin were significantly downregulated in patients with CHB compared with in healthy controls and patients with AHB. Furthermore, the apoptotic rate of CD8+ T cells was increased in patients with CHB compared with in the other two groups. The percentage of interferon (IFN)-γ+CD8+ T cells was reduced in patients with CHB compared with in patients with AHB and healthy controls, and serum cytokine levels (IFN-γ, interleukin-2 and tumor necrosis factor-α) were generally low in patients with CHB. Furthermore, the mRNA expression levels of tapasin were positively correlated with IFN-γ production by CD8+ T cells, and were inversely correlated with the apoptotic ratio of CD8+ T cells. These results indicate that decreased expression of tapasin may be closely associated with CHB, and suggest an important role for tapasin in the pathogenesis of CHB. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is characterized by functionally impaired type 1 T-helper cell (Thl) immunity and poor HBV-specific T-cell responses. Ubiquitin (Ub), a highly conserved small regulatory protein, commonly serves as a signal for target proteins that are recognized and degraded in proteasomes. The rapid degradation of Ub-mediated antigens results in efficient stimulation of cell-mediated immune responses. Thus, the Ub-HBV core antigen (HBcAg)-cytoplasmic transduction peptide (CTP) fusion protein was designed for specific delivery of a foreign modified antigen to the cytoplasm of antigen-presenting cells. HBV transgenic mice were used to determine whether Ub-HBcAg-CTP would restore HBV-specific immune responses and anti-viral immunity in these animals. The results demonstrated that synthesized Ub-HBcAg-CTP not only significantly increased the levels of interleukin-2 and interferon (IFN)-compared with those in the HBcAg-CTP, IFN-a, Ub-HBcAg, HBcAg and phosphate-buffered saline groups, but additionally induced the highest IFN-+ CD8+ T-cell numbers and HBV-specific cytotoxic T lymphocyte (CTL) responses, indicating a strong immune response. In addition, enhancement of specific CTL activity provoked by the fusion protein reduced hepatitis B surface antigen (HBsAg) and HBV DNA serum levels and diminished the expression of HBsAg and HBcAg in liver tissue of HBV transgenic mice, suggesting that there was a therapeutic effect. In conclusion, the present study provided evidence that Ub-HBcAg-CTP activated the Th1-dependent immunity, triggered functional T cell responses and subsequently inhibited viral replication in HBV transgenic mice. These observations suggested that the fusion protein may represent an innovative and promising candidate for active immunotherapy during chronic and persistent HBV. [ABSTRACT FROM AUTHOR]

Cluster of differentiation (CD)8+ cytotoxic T lymphocytes (CTLs) have a key role in the elimination of hepatitis B virus (HBV)-infected cells. Ubiquitin (Ub) functions as a marker for protein degradation, which may promote the generation of peptides appropriate for major histocompatibility complex class I presentation, while the HBV core antigen (HBcAg) possesses marked immunogenic properties. However, it remains to be elucidated whether Ub-modified HBcAg is able to effectively elicit significant CD8+ CTL activity. In order to address this issue, a prokaryotic vector was constructed to express the Ub-HBcAg-cytoplasmic transduction peptide (CTP). The fusion protein was successfully expressed and subsequently pulsed into bone-marrow-derived dendritic cells (DCs). It was confirmed that with assistance from the cell-penetrating properties of CTP, the fusion protein was able to directly penetrate into the cytoplasm of DCs. The results revealed that the Ub-HBcAg-CTP fusion protein not only increased the expression of surface molecules in DCs and cytokine secretion from proliferating T cells, but also induced T cells to differentiate into specific CTLs and enhanced their antiviral ability. In conclusion, the Ub-HBcAg-CTP fusion protein promoted DC maturation, enhanced the presentation of targeting antigens and efficiently induced HBcAg-specific CTL immune responses in vitro. [ABSTRACT FROM AUTHOR]

Persistent hepatitis B virus (HBV) infection is characterized by a weak adaptive immune response, which is considered to be due to an imbalance of T helper cell types 1 and 2 (Thl/Th2). Suppressors of cytokine signaling (SOCS) family members, particularly SOCS1 and SOCS3, have been demonstrated to be important in the regulation of T cell differentiation. Previous studies by our group showed that the expressed and purified fusion protein of cytoplasmic transduction peptide (CTP) and HBV core antigen 18-27 (HBcAgl8-27)-tapasin was able to enter the cytoplasm of bone marrow-derived dendritic cells (BMDCs), promoting the maturation of BMDCs and efficiently enhancing T cell immune responses in vitro. In the present study, HBcAg-specific immune responses induced by CTP-HBcAgl8-27-tapasin in HBV were assessed in transgenic mice, and SOCS 1 and SOCS3 were identified as negative regulators of this response. The Thl/Th2 cytokine ratio was analyzed by ELISA. The expression of T cell-specific T-box transcription factor (T-bet) and GATA-binding protein 3 (GATA-3), SOCS1 and SOCS3 were detected by real-time quantitative polymerase chain reaction and western blot analysis. The results demonstrated that CTP-HBcAgl8-27-tapasin significantly increased the Thl/Th2 cytokine ratio in HBV transgenic mice. CTP-HBcAgl8-27-tapasin immunization more efficiently suppressed the expression of serum hepatitis B surface antigen (HBsAg), HBV DNA as well as liver HBsAg and HBcAg in HBV transgenic mice. Furthermore, CTP-HBcAgl8-27-tapasin promotes T-bet but reduces GATA-3 expression. In addition, the expression of SOCS1 and SOCS3 was significantly downregulated in the CTP-HBcAgl8-27-tapasin group compared with the control groups. In conclusion, the present study demonstrated that CTP-HBcAgl8-27-tapasin enhanced the Thl/Th2 cytokine ratio and antiviral immunity by suppressing SOCS1/3 in HBV transgenic mice. [ABSTRACT FROM AUTHOR]

The main control goal in batch process is to get a high yield of products. In this paper, to maximize the yield of 1,3-propanediol (1,3-PD) in bioconversion of glycerol to 1,3-PD, we consider an optimal control problem involving a nonlinear time-delay system. The control variables in this problem include the initial concentrations of biomass and glycerol and the terminal time of the batch process. By a time-scaling transformation, we transcribe the optimal control problem into a new one with fixed terminal time, which yields a new nonlinear system with variable time-delay. The gradients of the cost and constraint functionals with respect to the control variables are derived using the costate method. Then, a gradient-based optimization method is developed to solve the optimal control problem. Numerical results show that the yield of 1,3-PD at the terminal time is increased considerably compared with the experimental data. [ABSTRACT FROM AUTHOR]

Mathematical modeling and parameter estimation are critical steps in the optimization of biotechnological processes. In the 1,3-propanediol (1,3-PD) production by glycerol fermentation process under anaerobic conditions, 3-hydroxypropionaldehyde (3-HPA) accumulation would arouse an irreversible cessation of the fermentation process. Considering 3-HPA inhibitions to cells growth and to activities of enzymes, we propose a novel mathematical model to describe glycerol continuous cultures. Some properties of the above model are discussed. On the basis of the concentrations of extracellular substances, a parameter identification model is established to determine the kinetic parameters in the presented system. Through the penalty function technique combined with an extension of the state space method, an improved genetic algorithm is then constructed to solve the parameter identification model. An illustrative numerical example shows the appropriateness of the proposed model and the validity of optimization algorithm. Since it is difficult to measure the concentrations of intracellular substances, a quantitative robustness analysis method is given to infer whether the model is plausible for the intracellular substances. Numerical results show that the proposed model is of good robustness. [ABSTRACT FROM AUTHOR]

Aim: Chronic hepatitis B virus (HBV) infection is thought to involve the imbalance of T-helper (Th)1/Th2 cells. Many procedures found Notch signaling involved the proliferation and differentiation of T lymphocytes during development and peripheral functions. The aim of this study was to discover the effect of blockage of Notch1 signaling to Th cells and the mechanisms involved in chronic hepatitis B patients. Methods: CD4+ T cells from hepatitis B patients and healthy volunteers were isolated, and Notch1 expression of CD4+ T cells was determined by reverse transcription polymerase chain reaction (RT–PCR). Blockage of Notch1 signaling of peripheral blood mononuclear cells (PBMC) from chronic hepatitis B patients, Th1- and Th2-type cytokines were assayed by enzyme-linked immunosorbent assay and levels of T-bet, GATA-3 mRNA were measured by RT–PCR. Results: Notch1 expression of CD4+ T cells from chronic hepatitis B patients was upregulated, on the contrary to that from acute hepatitis B patients and healthy volunteers. Blockage of Notch1 signaling can strongly inhibit the production of Th2-type cytokines and the expression of GATA-3; the production of Th1-type cytokines and the expression of T-bet, however, were enhanced. Conclusion: Blockage of Notch1 signaling could regulate the immune balance of Th1/Th2 in chronic hepatitis B patients, which may be mediated partly by regulating transcription factors T-bet and GATA-3. [ABSTRACT FROM AUTHOR]

We fabricated exchange-coupled composite films with perpendicular anisotropy using nanograins of L10 FePt as a magnetically hard base layer and FePt : SiO2 as a relatively soft phase. The degree of anisotropy and nanostructure in the soft layer was controlled by varying the deposition temperature. Growth of the low-anisotropy layer followed the particulate structure of the base layer at deposition temperatures of 390°C or greater. Perpendicular coercivities were strongly dependent on both the anisotropy and thickness of the softer layer. [ABSTRACT FROM AUTHOR]