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Background: Urine-derived stem cells (USCs) were considered to be an ideal source of stem cells for repairing urological diseases. However, the proliferative ability of USCs significantly decreased when cultured on plastic dishes, which limited their clinical application. It was found that collagen gels could promote the proliferation of USCs, but the underlying molecular mechanisms were unclear. background: Urine-derived stem cells (USCs) were considered to be an ideal source of stem cells for repairing urological diseases. However, the proliferation ability of USCs would be significantly decreased when cultured in a conventional medium, which limited its clinical application. We found that the proliferation ability of USCs would be promoted when cultured on collagen gels, which is the main component of extracellular matrix (ECM), making the cells receive more stimulation of growth signals, but the underlying mechanism remains unclear. It was reported that a non-selective cation channel, Piezo1, and the Hippo pathway key effector, transcriptional co-activator, YAP, may be responsible for the mechano-growth signal transduction. Objective: This study aims to discuss the mechanically activated cation channel Piezo1 and the transcriptional coactivator YAP to mediate the mechano-growth signal transduction and, to investigate the roles of Piezo1 and YAP in regulating the proliferation of USCs. objective: To investigate the proliferation of urine-derived stem cells and the possible mechanism of USCs proliferation regulation. Methods: USCs were cultured on collagen gels (group COL), or plastic dishes (group NON). MTT assay, Scratch assay, EDU staining, and immunofluorescence (IF) of Ki67 were performed to evaluate the proliferation of USCs; IF of YAP was conducted to observe its nuclear localization; calcium imaging experiment was executed to evaluate the function of Piezo1; western blot was used to compare changes in protein expression of YAP, LATS1, ERK1/2, and p-ERK1/2. In addition, the regulatory effect of YAP on the proliferative capacity of USCs was confirmed by intervening YAP with its inhibitor verteporfin (VP); and the inhibitor or activator of Piezo1, GsMTx4 or Yoda1 was used to explore the effect of Piezo1 on the nuclear localization of YAP, the proliferation of USCs and the regeneration of injured bladder. method: In the present study, USCs were cultured on collagen gels (group COL) or in a conventional medium (group NON), we firstly confirmed the regulatory effect of YAP on the proliferative capacity of USCs by intervening YAP with its inhibitor verteporfin (VP), then, using the inhibitor and activator of Piezo1, GsMTx4Yoda1, the effects of Piezo1 on YAP and USCs on the damaged bladder were verified. At last, the expression changes of ERK1/2 or LAST1 were identified by WB to distinguish which Hippo pathway was involved. Results: The results showed that cell proliferation was significantly enhanced in USCs in the COL group with the nuclear accumulation of YAP compared with the NON group and VP attenuated these effects. The expression and function of Piezo1 were higher in the COL group compared with the NON group. Blockage of Piezo1 by GsMTx4 decreased nuclear localization of YAP, the proliferation of USCs, and caused the failure of bladder reconstruction. Activation of Piezo1 by Yoda1 increased the nuclear expression of YAP, and the proliferation of USCs, which further improved the regeneration of the injured bladder. Finally, the ERK1/2 rather than LATS1 was revealed to participate in the Piezo1/YAP signal cascades of USCs proliferation. Conclusion: Taken together, Piezo1-ERK1/2-YAP signal cascades are involved in regulating the proliferation ability of USCs in collagen gels which would be beneficial for the regeneration of the bladder. conclusion: we considered that the Piezo1-ERK1/2-YAP signal cascade may be involved in regulating the proliferation ability of USCs on collagen gels. other: No

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.

This study investigates households’ car ownership decisions in response to changes in vehicle quota control and transport infrastructure in Singapore. Unlike previous cross-sectional studies, we calibrate a dynamic car ownership model with a pseudo panel constructed from repeated cross-sectional travel surveys, controlling for the persistence of car ownership and unobserved heterogeneity. We find that the tightening of vehicle quota control and improved rail transit accessibility have reduced households’ desire to purchase cars. The long-run effect of these two policies is larger than their short-run effect due to the existence of true state dependence. The impact of expressway-network expansion is insignificant.

External tagging methods can aid in the research of leopard coral grouper (Plectropomus leopardus) in terms of its spatio-temporal behavior at population and individual scales. However, due to the strong exclusion ability and the damage to the body wall of P. leopardus, the retention rate of traditional invasive tagging methods is low. To develop a non-invasive identification method for P. leopardus, we adopted a multiscale image processing method based on matched filters with Gaussian kernels and partial differential equation (PDE) multiscale hierarchical decomposition with the deep convolutional neural network (CNN) models VGG19 and ResNet50 to extract shape and texture image features of individuals. Then based on image features, we used three classifiers Random forest (RF), support vector machine (SVM), and multilayer perceptron (MLP)) for individual recognition on sequential images of P. leopardus captured for 50 days. The PDE, ResNet50 and MLP combination obtained a maximum accuracy of 0.985 ± 0.045 on the test set. For individual temporal tracking recognition, feature extraction and model training were performed using images taken in 1-20 days. The classifier could achieve an accuracy of 0.960 ± 0.049 on the test set consisting of images collected in the periods of 20-50 days. The results show that CNNs with the PDE decomposition can effectively and accurately identify P. leopardus.

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.

Anaerobic digestion (AD) has been widely employed for converting various biowastes into renewable energy. However, AD of gentamicin mycelial residues (GMRs, a byproduct of gentamicin production) is limited by ammonia inhibition and antimicrobial resistance risk. Compared to mesophilic AD (MMAD) of GMRs, this study looked into three semicontinuous AD processes, i.e., codigestion with wheat straw, thermophilic digestion (TAcoD), and AD at shortened retention time (RT). Results showed that a stable and safe AD could be achieved under suitable operating conditions. Co-digestion could effectively mitigate the adverse effect of ammonia inhibition. The methane production increased by 35.86% in TAcoD compared to that in MMAD and 43.99% of hazardous waste was reduced in TAcoD. Concerning the antimicrobial resistance of AD system, gentamicin was degraded efficiently and the degradation process was not involved in the expression of antibiotic resistance genes (ARGs) related to modifying enzyme. Effective removal of ARGs under three operating strategies was associated with a higher reduction in bacterial abundance of potential hosts. In addition, the changes in the relevant proteins for transformation and conjugation as predicted by PICRUSt suggested that thermophilic condition and shorter RT were conducive to the reduction of the dissemination risks of ARGs.

The increasing preference for ageing-in-place highlights the pivotal role of the neighbourhood environment in meeting the mobility needs of older adults. This paper examines the combined associations of objective and subjective measures of built environment features with older adults' travel pattern in Singapore. A multivariate ordered probit (OP) modelling framework is applied to examine older adults' daily trip frequency by four transport modes: walking, public bus, Mass Rapid Transit/Light Rapid Transit (MRT/LRT), and private motorized modes, while controlling for the correlations among the use of different modes. The results show that while perceived access to recreational facilities exert independent positive effects on older adults' daily walking trip frequency and enhance the effects of comparable objective measures, other subjective measures do not significantly moderate the effects of objective features on walking trip-making, including those of actual access to utilitarian destinations, the availability of sheltered walkways and unsafe pedestrian crossings near residence. The results also find independent positive effects of perceptions of transit proximity and comfortable and safe pedestrian connections on older adults’ daily transit trip-making.

Summary Background & aims Previous studies on the association between skipping breakfast and risk of cardiovascular disease and all cause mortality have drawn controversial conclusions. Therefore, we carried out a meta-analysis to illuminate this association. Methods Studies about the association between skipping breakfast and risk of cardiovascular disease and all cause mortality were identified by searching Pubmed, Embase, Cochrane, and Web of Science databases until June 2019. Then we screened articles for eligibility, extracted data, and pooled the results using a random-effects model. Results Seven cohort studies concerning a total of 221,732 participants were included in this meta-analysis. Skipping breakfast was associated with elevated risk of cardiovascular disease (relative risk 1.22 95% confidence interval 1.10–1.35) and all cause mortality (relative risk 1.25 95% confidence interval 1.11–1.40) compared with eating breakfast regularly. Conclusion Skipping breakfast increases the risk of cardiovascular disease and all cause mortality. Eating breakfast regularly may promote cardiovascular health and decrease all cause mortality.

Anaerobic digestion (AD) is an effective technology to dispose antibiotic mycelial residues, but biogas production is influenced by hydrolysis rates and antibiotic residue. Herein, the effects of thermal hydrolysis pretreatment for AD of spectinomycin mycelial residues (SMRs) were investigated. The results showed that the removal ratio of spectinomycin was increased while the temperature of pretreatment was escalating. Meanwhile, thermal hydrolysis facilitated the dissolution of organic matters. However, non-biodegradable substances measured by fluorescence excitation–emission matrix accumulated and thus had an adverse influence on biogas production. Based on batch assays, the optimal pretreatment temperature for SMRs was 120 °C. The removal of spectinomycin was benefit for biogas production (increasing by 7.6%), and the overall biogas production increased by 27.6% compared with 289.90 mL gVS−1 of untreated SMRs. The microbial community analysis revealed that spectinomycin (265 mg L−1) might influence bacteria in the early stage of AD (first 5 days), while redundancy analysis showed that spectinomycin had a non-significant influence on community succession over the 32 days of fermentation.

Restoring blood supply is an effective way for the therapy of myocardial infarction (MI). It was reported a specific angiogenic peptide (VMP) derived from vascular endothelial growth factor (VEGF) could activate its receptor to mimic the biological activity of VEGF. In this study, in order to improve the local concentration in infarction region, a collagen-binding domain was synthesized with VMP to construct collagen binding domain (CBD)-VMP peptides. The fused CBD-VMP could bind specifically to collagen which was rich in cardiac extracellular matrix (c-ECM), without impacting the biological activity of VMP peptides. When the CBD-VMP peptides loaded on collagen scaffold and implanted into the rats subcutaneously, significant vascularization was observed. Then, CBD-VMP peptides binding with injectable c-ECM injected into the MI rat by intramuscular administration, significant blood vessels regeneration, and decrease of cell apoptosis were observed, that corelated with the recovery of cardiac function. It might be an alternative promising strategy for the clinical application of MI.

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.

The primary functions of the bladder are storing urine under low and stable pressure and micturition. Various forms of trauma, tumors, and iatrogenic injuries can cause the loss of or reduce bladder function or capacity. If such damage is not treated in time, it will eventually lead to kidney damage and can even be life-threatening in severe cases. The emergence of tissue engineering technology has led to the development of more possibilities for bladder repair and reconstruction, in which the selection of scaffolds is crucial. In recent years, a growing number of tissue-engineered bladder scaffolds have been constructed. Therefore, this paper will discuss the development of tissue-engineered bladder scaffolds and will further analyze the limitations of and challenges encountered in bladder reconstruction.

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.

Mechanotransduction is associated with organ development and homoeostasis. Piezo1 and Piezo2 are novel mechanosensitive ion channels (MSCs) in mammals. MSCs are membrane proteins that are critical for the mechanotransduction of living cells. Current studies have demonstrated that the Piezo protein family not only functions in volume regulation, cellular migration, proliferation, and apoptosis but is also important for human diseases of various systems. The complete loss of Piezo1 and Piezo2 function is fatal in the embryonic period. This review summarizes the role of Piezo1 in diseases of different systems and perspectives potential treatments related to Piezo1 for these diseases.

Transport pricing and infrastructure investment are widely seen as essential elements in policy packages aiming to address transport challenges. However, their respective and collective causal influences on travel behaviour have not been sufficiently examined. In this study, we investigate the effects of vehicle quota control and transport infrastructure investment on vehicle travel in Singapore, with a pseudo panel created from three repeated cross-sectional household surveys. We find that vehicle quota control has a substantial influence on vehicle usage by constraining car ownership. However, this mitigation effect might be partially offset by the higher car usage among car owners who want to make more out of their investment in private cars, confirming the existence of sunk cost effect in transport pricing. Careful design of vehicle quota control policies is thus necessary to avoid the overuse issue. We also find that rail transit network expansion reduces vehicle usage, while expressway network expansion increases it. An integrated approach that combines pricing measures to discourage vehicle usage and public transport investment to provide alternatives to driving may be more effective in achieving transport sustainability.

Objective: To examine how neighborhood-based cognitive and structural social capital are associated with individual quality of life among a sample of community-dwelling older adults in Singapore. Method: Using survey data from 981 older adults (aged 55 years and above) in nine residential neighborhoods, multilevel models simultaneously estimated the effects of independent variables at the individual and neighborhood levels on quality of life (CASP-12). Results: Social cohesion (β = 1.39, p < .01) and associational membership (β = 19.16, p < .01) were associated with higher quality of life in models adjusted for neighborhood facilities and individual sociodemographics, social networks, functional limitations, global cognitive status, and medical conditions. Discussion: The results suggest that place-based or neighborhood social capital may be important for older person’s well-being. It identifies the contribution of structural (associational membership) and cognitive (social cohesion) social capital to the well-being of community-dwelling older adults in Singapore.

Anaerobic co-digestion (AcoD) of gentamicin mycelial residues (GMRs), a kind of nitrogen-rich biowaste, and wheat straw (WS) is an attractive technology for the recycling of GMRs. However, the effects of the co-substrate ratio on methane production, system stability and antimicrobial resistance during co-digestion remain unclear. Thus, this study aimed to fill in the blanks through AcoD of GMRs and WS with different mixing ratios (1:0, 2:1, 1:1, 1:2, 0:1, VS basis) via batch tests. Results showed that AcoD facilitated methane production than mono anaerobic digestion and reduced the accumulation of the toxic substances, such as ammonia nitrogen and humic-like substances. The maximum methane production was obtained at the reactors with the mixing ratio of 1:1 and 1:2 (R-1:1 and R-1:2), which matched with the relative abundance of key enzymes related to methanogenesis predicted by PICRUSt. Microbial community analysis indicated that Methanosaeta was the most dominant methanogen in the AcoD reactors. The highest relative abundance of Methanosaeta (45.1%) was obtained at R-1:1 due to the appropriate AcoD conditions, thus, providing greater possibilities for high stability of AcoD system. Additionally, AcoD of the GMRs and WS under the mixing ratio of 1:1 and 1:2 did not prompt the increase of antibiotic resistance genes (ARGs). Not only that, the likelihood of horizontal gene transfer declined in R-1:1 due to the weaker connection and transport between host and recipient bacteria. Findings of this study suggested that the suitable mixing ratio of GMRs and WS contributes to methane production and system stability, and reduces the dissemination risks of ARGs.

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.

Acyl-coenzyme A binding domain containing 3 (ACBD3) is a multifunctional protein residing in the Golgi apparatus and is involved in several signaling pathways. The current knowledge on ACBD3 has been extended to virology. ACBD3 has recently emerged as a key factor subverted by viruses, including kobuvirus, enterovirus, and hepatitis C virus. The ACBD3-PI4KB complex is critical for the role of ACBD3 in viral replication. In most cases, ACBD3 plays a positive role in viral infection. ACBD3 associates with viral 3A proteins from a variety of Picornaviridae family members at membrane contact sites (MCSs), which are used by diverse viruses to ensure lipid transfer to replication organelles (ROs). In this review, we discuss the mechanisms underlying the involvement of ACBD3 in viral infection at MCSs. Our review will highlight the current research and reveal potential avenues for future research.

Diabetic cardiac autonomic neuropathy (DCAN) is a common and serious complication of diabetes mellitus (DM), is manifested by nerve fiber injury in the sympathetic and parasympathetic nerve of the autonomic nervous system, and causes hypertension, cardiac arrhythmias, silent myocardial infarction, and sudden death. Our previous study observed that P2X3 receptor in superior cervical ganglia in rat was associated with sympathetic neuropathy caused by myocardial ischemia. However, whether the P2X3 receptor is involved in the diabetic cardiac autonomic neuropathy and the underlying mechanisms remain unclear. The aim of this research was explored the effect of P2X3 short hairpin RNA (shRNA) on information transmission of sympathetic nerve induced by DCAN. Sprague-Dawley (SD) male rats were randomly divided into four groups: Control, DM, DM treated with P2X3 shRNA and DM treated with scramble shRNA. Blood pressure, heart rate and heart rate variability were measured in each group. The expression of P2X3 in stellate ganglion (SG) was detected by immunohistochemistry, western blotting and QPCR. Results showed that P2X3 shRNA alleviated blood pressure and heart rate, improved heart rate variability, decreased the up-regulated expression levels of P2X3, interleukin-1beta and tumor necrosis factor alpha in stellate ganglion (SG) of diabetic rats. P2X3 shRNA also reduced the incremental concentration of serum epinephrine and the phosphorylation level of extracellular regulated protein kinases1/2 in diabetic rats. These results indicated that P2X3 shRNA could decrease sympathetic activity via inhibiting P2X3 receptor in the SG to alleviate DCAN.

Utilising time-stamped lifelogging images collected from a sample of 30 older adults in three neighbourhoods of Singapore, this study explores older adults’ daily walking travel patterns and their associations with neighbourhood-level built environment features. The visual lifelogging method uses a wearable camera to automatically record individual activities from a “first-person” perspective and capture novel information of environmental features encountered by individuals in real time. The findings reveal that older participants in the study areas, on average, take about 4 walking trips per day with an average trip length of about 15 minutes. Neighbourhood facilities including public open spaces, senior activity centres, and food courts are the most visited destinations while urban design features such as covered walkways, tree shades and street furniture are frequently encountered during walking trips.

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.

Hepatitis C virus (HCV) entry is mediated by multiple co-receptors including scavenger receptor class B, type I (SR-BI). To elucidate the interactome of human SR-BI, we performed immunoprecipitation (IP) experiment coupled with mass spectrometry (MS) analysis. UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1), a key component of calnexin cycle involved in protein glycosylation, was identified as a SR-BI-interacting protein. Silencing UGGT1 or N-glycosylation inhibitor treatment reduced SR-BI protein level. Further study demonstrated that human SR-BI was N-glycosylated at nine asparagines. Moreover, HCV entry and infection were reduced by the absence of UGGT1. Interestingly, silencing SR-BI reduced protein stability of UGGT1 and protein quality control function mediated by UGGT1. Our finding not only identified UGGT1 as a HCV host factor, but also identified a UGGT1-mediated protein folding function for SR-BI.

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.

Urban mobility is a key ingredient to fostering social interaction and resilience. At the neighbourhood level, enhanced mobility can be achieved through investment in transport infrastructure, which in turn can promote greater community interaction and exchange, and in the process contribute to social resilience. This study examines the influence of transport infrastructure investment on household work and non-work travel demand in Singapore, with the main purpose of investigating whether improved transport accessibility brought by transport infrastructure investment prompts additional out-home trips; and if so, to what extent and in what way does transport infrastructure investment influence household travel demand. Our study indicates that the travel demand for both work and non-work purposes is mainly determined by households’ socioeconomic and demographic characteristics. Rail transit accessibility and expressway proximity do not influence travel demand significantly. Land use mix and population density have a positive influence, though small in magnitude, on household travel demand, and consequently on mobility, which contributes to greater social resilience.

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%).

Increasing CO2 emissions from the transport sector have raised substantial concerns among researchers and policy makers. This research examines the impact of the built environment on individual transport emissions through two mediate variables, vehicle usage and vehicle type choice, within a structural equation modelling (SEM) framework. We find that new-urbanism-type built environment characteristics, including high density, mixed land use, good connectivity, and easy access to public transport systems help reduce transport CO2 emissions. Such mitigating effect is achieved largely through the reduced vehicle miles travelled (VMT) and is enhanced slightly by the more efficient vehicles owned by individuals living in denser and more diverse neighborhoods, all else being equal. Our research findings provide some new evidence that supports land use policies as an effective strategy to reduce transport CO2 emissions.

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

Introduction An increasing body of evidence suggests that regular physical activity can have important beneficial effects on individuals’ health into later years. This research investigated the inter-relationships between neighbourhood built environment, physical activity and three physical health outcomes among older adults in Singapore. Methods Drawing on 2018 data from 810 community-dwelling older adults in Singapore, a simultaneous equation approach was utilised to disentangle the complex interactions among built environment (both objective and self-reported measurements), physical activity and physical health (i.e., body mass index, functional capability and presence or absence of ‘three high’ chronic diseases) while controlling for other confounding factors, including socio-demographics and health behaviour. Results The accessibility to destinations (e.g., parks, open spaces, playgrounds) and other walkability features (e.g., neighbourhood safety, covered footpath) could promote transportation or recreational outdoor physical activity and therefore, health among older residents in Singapore. Interestingly, built environment characteristics related differently to physical activity undertaken for transportation and recreational purposes. There was a bi-directional relationship between an older adult's functional status and transport-related physical activity. There was also evidence that the connection between number of chronic diseases and recreational physical activity was reciprocal. Conclusion Insights into the built environment-physical activity-physical health relationships highlight the importance of supportive built environment in the process of health enhancement for older people.

Community question answering (CQA) services provide platforms for increasing number of users to seek for help and exchange ideas in recent years. As a professional community, Quora is quite different from other traditional CQA websites, such as Baidu Zhidao and Yahoo! Answers. As users' social statuses play a more important role, besides just raising questions and finding a proper answer which the asker is satisfied with, people are inclined to have more discussions about the question, corresponding answers and related topics. Due to the spirit of wiki, people, especially some leading users work hard together to make the community a knowledge base of high quality, which in turn attracts more people to take part in this job. Thus, in this study, we focus on detecting leading users within a specific topic area of professional CQA services. A leading capacity model is utilized and three major criteria, which are authority, activity and influence, are taken into consideration. Then, an improved Borda count model is proposed to make a collective decision. Experimental results show effectiveness of the proposed method for finding leading users.