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Objectives: Age-bilirubin-international normalized ratio -creatinine (ABIC) score was originally proposed as a tool to assess alcoholic hepatitis survival and to identify patients who respond to corticosteroid treatment. Since the components of this score are associated with prognosis in patients with heart failure, the purpose of this study was to determine the relationship between ABIC score and long-term prognosis of elderly patients with acute exacerbation of chronic heart failure. Methods: This is a retrospective cohort study of elderly patients with acute exacerbation of chronic heart failure who were hospitalized for the first time in the Second Affiliated Hospital of Chongqing Medical University from February 2017 to December 2017. The main clinical outcome was all-cause mortality within three years. Cox regression and Lasso regression were used to screen variables and build a prognostic model. Combined with the ABIC score, the final model was adjusted, and the predictive ability of the model was evaluated. The screened variables with ABIC score were incorporated into the multivariate Cox regression analysis and a nomogram prediction model was built. The receiver operating characteristic curve and calibration curve were used to evaluate the predictive ability and accuracy of the model, respectively. Results: A total of 365 patients with acute exacerbation of chronic heart failure were included (median age 78 years, 50.7% female). During the 3-year follow-up period, 87 patients experienced all-cause death, including 53 cardiac deaths. A total of 4 variables (NT-proBNP, BUN, RDW-CV and prealbumin) were screened by univariate Cox regression analysis and Lasso regression analysis. The multivariate COX regression results showed that the risk of death increased by 33% with the increase of ABIC score by 1 point (after correcting NT-proBNP, BUN, RDW-CV and prealbumin). The results of ROC curve analysis show that the area under the curve (AUC) of the ABIC score is 0.685, while the AUC of the Nomograph including the ABIC score is 0.840. Conclusions: The ABIC score is associated with long-term adverse outcomes in elderly hospitalized patients with chronic heart failure exacerbations. But its predictive ability for adverse events needs further exploration.

DNA ligase (LIG) plays a key role in connecting the 3′-OH end of a DNA strand to the 5′-P end of another DNA strand, resulting in the formation of a phosphodiester bond. It has been reported that LIGs (including LIG1, LIG3 and LIG4) play important roles in the occurrence and progression of many cancers. However, the role of LIGs in breast cancer (BC) is still unclear. In this study, we aim to reveal the expression level, function, and prognostic value of LIGs in BC. Bioinformatic tools were used to study the expression level, potential function and prognostic value of LIG1 and LIG3 in BC patients. ENCORI was used to predict microRNAs (miRNAs) that regulate LIG1 and LIG3 and established a valuable miRNA–mRNA regulation network for BC. We found that the expression of LIG1 and LIG3 was upregulated in BC and predicted high relapse-free survival (RFS) in BC patients. Functional annotation analysis was performed to reveal the role of LIG1 and LIG3 in BC. In addition, hsa-miR-22-3p was identified to be potentially involved in the regulation of LIG3. We suggest that LIG1 and LIG3 are novel valuable prognostic biomarkers for BC and has-miRNA-22-3p may be a potential therapeutic target for BC.

Hydrolysis plays an imperative role in the abiotic transformation process of antibiotics in aqueous solutions. However, little information is available on the hydrolysis process of spectinomycin (an aminocyclitol antibiotic). This study systematically investigated the spectinomycin hydrolysis kinetics and mechanisms under different pH via experiments and density functional theory (DFT) computation. Hydrolysis was first conducted in a pure water system under pH of 4.0-9.0 and temperature of 25 °C, 50 °C and 70 °C, respectively. Results showed that hydrolysis was highly dependent on pH and temperature. When pH 6.0, spectinomycin hydrolysis was accelerated by the catalysis of OH

The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database. Kaplan-Meier plotter was used to analyze prognostic value of MCMs in human BC patients. Furthermore, we constructed a MCM coexpression gene network and performed functional annotation analysis through DAVID to reveal the functions of MCMs and coexpressed genes. The data showed that the expression of MCM2–8 and MCM10 but not MCM1 and MCM9 was upregulated in BC. Kaplan-Meier plotter analysis revealed that high transcriptional levels of MCM2, MCM4–7, and MCM10 were significantly related to low relapse-free survival (RFS) in BC patients. In contrast, high levels of MCM1 and MCM9 predicted high RFS for BC patients. This study suggests that MCM2, MCM4–7, and MCM10 possess great potential to be valuable prognostic biomarkers for BC and that MCM1 and MCM9 may serve as potential treatment targets for BC patients.

Renal ischemia-reperfusion (I/R) injury is one of the major causes of acute kidney injury. However, there is still no effective treatment for this disease. Basic fibroblast growth factor (bFGF) has been reported to be beneficial for recovery from ischemic diseases. It is vital to increase the local concentration and reduce the diffusion of bFGF in vivo for renal I/R injury therapy. A targeted growth factor delivery system that responds to specific biological signals in the regenerative environment to guide release has been highlighted in tissue repair. In the present study, a specific peptide was fused with bFGF and called bFGF-kidney injury targeting (KIT-bFGF), and this compound specifically targeted kidney injury molecule-1 both in hypoxic renal HK-2 cells in vitro and ischemic kidneys in vivo after intravenous injection. When administered to rat models of renal I/R injury, KIT-bFGF attenuated renal tubule damage and fibrosis, and promoted functional recovery compared to the effects of native bFGF and the control. We also investigated the mechanism by which KIT-bFGF activated the ERK1/2 and Akt signaling pathways to significantly reduce apoptosis and protect against ischemic injury in the kidney. These results demonstrated that targeted delivery of KIT-bFGF could be an effective strategy for the treatment of renal I/R injury.

To tackle the high latency and slow encoding speed of 8B/10B encoder circuits in high-speed serial interfaces, a parallel structure for polarity pre-processing based on logic operations is proposed to optimize encoder performance in this article. Firstly, the encoding process is divided into polarity pre-processing and coding two pipeline stages. This method equals each stage’s delay and decreases the coding waiting period. Additionally, the structure employs polarity pre-processing to optimize the critical delay paths into multi-stage heterodyne gates in series. Therefore, the effect of the number of input bytes on the critical delay path can be significantly reduced. The effectiveness of our proposed encoder is demonstrated to encode 4-byte loads by VCS simulation and synthesized using Synopsys’ Design Compiler tool upon the SMIC 65nm process. Results show that a high operating frequency of 909MHz with a 2245.68µm2 footprint area can be achieved. Compared with the cascaded and polarity-selective structures, the proposed framework has advantages in terms of speed and resource usage. These advantages greatly help to meet the high-speed transmission requirement.

Background: Immunologic graft rejection is the main complication of corneal transplants. This study aimed to investigate the effect of melatonin (MT) on the rejection of corneal transplantation.Methods: Corneal allografts were performed by grafting corneas from BALB/C mice to C57BL/6 hosts. MT (50 mg/kg) was intraperitoneally injected into the hosts every day from the day of transplantation. The survival of grafts was observed by slit lamp biomicroscopy, and inflammatory cell infiltration was detected by hematoxylin and eosin staining and immunohistochemistry. The balance of Teff and Treg immune cells in draining lymph nodes (DLNs) was detected by flow cytometry. The levels of cytokines related to the grafts and DLNs were detected using real-time fluorescence quantitative PCR. Additionally, we used the mouse macrophage line RAW264.7 to study the effect of MT on the activation of NLRP3 inflammatory body.Results: MT treatment improved the graft survival rate, reduced inflammatory cell infiltration in the graft, decreased the percentage of Th1/Th17 cells in the DLNs, and increased the percentage of Treg cells. Melatonin inhibited the activation of the NLRP3 inflammasome, thereby reducing the expression of IL-1β and other related proinflammatory cytokines such as MCP-1, MIP-1, NLRP3, ASC, TNF-a and VEGF-A (all p < 0.05).Conclusion: Our study demonstrates that MT promotes the survival of mouse corneal grafts by inhibiting NLRP3-mediated immune regulation, reducing immune cell activation and cell migration, and inhibiting the production of inflammatory-related cytokines. Treatment with MT might provide a potential clinical therapeutic target for corneal transplantation.

BACKGROUND Epithelial splicing regulatory proteins (ESRPs), including ESRP1 and ESRP2, are important proteins for alternative splicing of mRNAs and are reported to promote or inhibit the progression of some tumors. However, the effects of ESRPs in breast cancer are still unknown. MATERIAL AND METHODS In this study, we detected the transcriptional level and alterations of ESRP1 in patients with breast cancer based on the Oncomine, Gene Expression Profiling Interactive Analysis, Gene Expression-Based Outcome for Breast Cancer Online, and cBioPortal databases. Using immunohistochemistry and quantitative polymerase chain reaction, the expression pattern of ESRP1 in breast cancer was analyzed. Analysis of the clinicopathological characteristics and function of ESRP1 in breast cancer were actualized through the University of Alabama Cancer database and Database for Annotation, Visualization and Integrated Discovery. Using the Kaplan-Meier plotter, the prognostic values of ESRP1 in patients with breast cancer were analyzed. The Encyclopedia of RNA Interactomes database was used to predict miRNAs that regulated ESRP1. RESULTS We found that ESRP1 was significantly overexpressed in patients with breast cancer, compared with patients without breast cancer, and had statistically significant clinicopathological characteristics. Kaplan-Meier plotter analysis indicated that the elevated expression of ESRP1 was associated with poor prognosis in patients with breast cancer. Furthermore, hsa-miR-181c-5p was identified to be potentially involved in the regulation of ESRP1. CONCLUSIONS These results suggest that ESRP1 is a valuable target for the precise treatment of breast cancer and a potential biomarker for the prognosis of patients with breast cancer.

We propose a Nitsche method for multiscale partial differential equations, which retrieves the macroscopic information and the local microscopic information at one stroke. We prove the convergence of the method for second order elliptic problem with bounded and measurable coefficients. The rate of convergence may be derived for coefficients with further structures such as periodicity and ergodicity. Extensive numerical results confirm the theoretical predictions.

We present a new numerical method for solving the elliptic homogenization problem. The main idea is that the missing effective matrix is reconstructed by solving the local least-squares in an offline stage, which shall be served as the input data for the online computation. The accuracy of the proposed method are analyzed with the aid of the refined estimates of the reconstruction operator. Two dimensional and three dimensional numerical tests confirm the efficiency of the proposed method, and illustrate that this online-offline strategy may significantly reduce the cost without loss of accuracy.

Chikungunya fever (CHIKF) is an acute infectious disease that is mediated by the mosquito-transmitted chikungunya virus (CHIKV). People infected with CHIKV may experience high fever, severe joint pain, skin rash, and headache. In recent years, this disease has become a global public health problem. However, there is no licensed vaccine available for CHIKV. Accumulating research data have provided novel approaches and new directions for the development of CHIKV vaccines. Our review focuses on recent progress in CHIKV vaccine studies. The potential vaccine candidates are classified into seven types: inactivated vaccine, subunit vaccine, live-attenuated vaccine, recombinant virus-vectored vaccine, virus-like particle vaccine, chimeric vaccine, and nucleic acid vaccine. These studies will provide important insights into the future development of CHIKV vaccines.

Chikungunya virus (CHIKV) is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain. Although the protein-protein interactions (PPIs) between nonstructural proteins of CHIKV have been extensively established, the complete CHIKV intraviral interactome remains to be elucidated. In this study, we examined all possible CHIKV intraviral PPIs by immunoprecipitation and constructed the intraviral interactome of CHIKV. We reported 19 novel PPIs including the homo-oligomerization of TF. Disulfide bonds promoted the oligomerization of CHIKV TF protein. 2-BP, a palmitoylation inhibitor reduced the palmitoylation of TF and increased TF oligomerization. A quadruple mutant of Cys33, Cys35, Cys41, and Cys43 in TF blocked its palmitoylation and reduced oligomerization. Furthermore, we determined the association of TF with nsP1 and nsP3 in a palmitoylation-dependent manner. Construction of intraviral interactome of CHIKV provides the basis for further studying the function of CHIKV proteins., Highlights • An intraviral interactome of CHIKV proteins is constructed. • CHIKV TF is homo-oligomerized. • CHIKV TF is palmitoylated. • TF interacts with nsP1 and nsP3 in a palmitoylation-dependent manner.

Gentamicin mycelial residues (GMRs) are microbial fermentation residues of the pharmaceutical industry. In this study, anaerobic digestion of GMRs in combination with microwave-alkaline pretreatment (MAPT) was first employed to enhance methane production and the efficiency of gentamicin degradation. The anaerobic digestion batch tests were conducted to optimize the MAPT conditions, and semi-continuous tests of three-month duration were carried out to investigate the anaerobic digestion performance and fate of gentamicin. The results indicated that the GMRs flocs were substantially disintegrated after MAPT, and the average particle size was significantly related to methane production (p 12) suggested that the excessive alkali dosage in the pretreatment process adversely affected the anaerobic digestion performance due to the solubilization or generation of the refractory compounds (e.g. melanoidin). An increase of 58.05% in methane production (323.33 ± 11.88 mL gVS−1) was accomplished by MAPT in the sable running stage of the semi-continuous stirring tank reactor. The analysis of gentamicin mass balance in anaerobic digestion process demonstrated that the degradation was a preponderant mechanism for gentamicin removal. Simultaneously, MAPT facilitated the release of gentamicin trapped in flocs, thus, effectively improving the average degradation efficiency of gentamicin in anaerobic digestion process (degradation efficiency: 97.70 ± 0.63%).

Alkaline-thermal (AT) pretreatment is an economical and efficient pretreatment method to improve anaerobic biodegradability of biowaste. This study investigated the effect of AT pretreatment of spectinomycin mycelial residues (SMRs) for promoting anaerobic biodegradability along with the reduction of antibiotic resistance genes (ARGs), and thus obtained the optimal conditions of AT pretreatment. Biomethane potential (BMP) test was conducted to evaluate the anaerobic biodegradability of untreated and pretreated SMRs, and the fate of ARGs was tracked by quantitative polymerase chain reaction. Results showed that the modified Gompertz model fitted the results of BMP tests satisfactorily. Furthermore, AT pretreatment promoted BMP (B0) and reduced lag phase (λ) effectively. These were attributed to the solubilization of SMRs. The analyses of the changes in dissolved organic matter indicated that AT pretreatment could facilitate the solubilization of both biodegradable (e.g. protein) and recalcitrant matter (e.g. humic-like, analyzing by EEMs-PARAFAC), which had a significant corresponding positive (Person correlation, p