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Chronic hepatitis B (CHB) virus infection, causing immune dysfunction and chronic hepatitis, is one of the leading risk factors for hepatocellular cancer. We investigated how Arthrospira affected hepatitis B surface antigen (HBsAg) reduction in CHB patients under continued nucleos(t)ide analogues (NA). Sixty CHB patients who had been receiving NA for at least one year with undetectable HBV DNA were randomized into three groups: control and oral Arthrospira at 3 or 6 g daily add-on therapy groups. Patients were followed up for 6 months. Oral Arthrospira-diet mice were established to investigate the possible immunological mechanism of Arthrospira against HBV. Within 6 months, mean quantitative HBsAg (qHBsAg) decreased in the oral Arthrospira add-on therapy group. Interestingly, interferon gamma (IFN-γ) increased but TNF-α, interleukin 6 (IL-6), hepatic fibrosis, and steatosis decreased in the add-on groups. In mice, Arthrospira enhanced both innate and adaptive immune system, especially natural killer (NK) cell cytotoxicity, B cell activation, and the interleukin 2 (IL-2), IFN-γ immune response. Arthrospira may modulate IL-2- and TNF-α/IFN-γ-mediated B and T cell activation to reduce HBsAg. Also, Arthrospira has the potential to restore immune tolerance and enhance HBsAg seroclearance in CHB patients through promoting T, B, and NK cell activation.

Renal leptospirosis caused by leptospiral infection is characterised by tubulointerstitial nephritis and tubular dysfunction, resulting in acute and chronic kidney injury. Metabolomic and transcriptomic data from a murine model of Leptospira infection were analysed to determine whether metabolomic data from urine were associated with transcriptome changes relevant to kidney injury caused by Leptospira infection. Our findings revealed that 37 metabolites from the urine of L. interrogans-infected mice had significantly different concentrations than L. biflexa-infected and non-infected control mice. Of these, urinary L-carnitine and acetyl-L-carnitine levels were remarkably elevated in L. interrogans-infected mice. Using an integrated pathway analysis, we found that L-carnitine and acetyl-L-carnitine were involved in metabolic pathways such as fatty acid activation, the mitochondrial L-carnitine shuttle pathway, and triacylglycerol biosynthesis that were enriched in the renal tissues of the L. interrogans-infected mice. This study highlights that L-carnitine and acetyl-L-carnitine are implicated in leptospiral infection-induced kidney injury, suggesting their potential as metabolic modulators.

Derangements in cardiac energy metabolism have been shown to contribute to the development of heart failure (HF). This study combined transcriptomics and metabolomics analyses to characterize the changes and reversibility of cardiac energetics in a rat model of cardiac volume overload (VO) with the creation and subsequent closure of aortocaval fistula. Male Sprague–Dawley rats subjected to an aortocaval fistula surgery for 8 and 16 weeks exhibited characteristics of compensated hypertrophy (CH) and HF, respectively, in echocardiographic and hemodynamic studies. Glycolysis was downregulated and directed to the hexosamine biosynthetic pathway (HBP) and O-linked-N-acetylglucosaminylation in the CH phase and was further suppressed during progression to HF. Derangements in fatty acid oxidation were not prominent until the development of HF, as indicated by the accumulation of acylcarnitines. The gene expression and intermediates of the tricarboxylic acid cycle were not significantly altered in this model. Correction of VO largely reversed the differential expression of genes involved in glycolysis, HBP, and fatty acid oxidation in CH but not in HF. Delayed correction of VO in HF resulted in incomplete recovery of defective glycolysis and fatty acid oxidation. These findings may provide insight into the development of innovative strategies to prevent or reverse metabolic derangements in VO-induced HF.

Accurately evaluating particle surface micro-texture levels and distribution at different wavelength scales of granular material is critical to optimise service stability of granular material under long-term dynamic loads. Firstly, generalised regression neural network (GRNN) and empirical mode decomposition (EMD) were adopted to impute missing data points and remove the arc-shaped tendency of granular materials' particle wear raw surface profile. Then, granular materials' particle surface micro-texture levels and their distribution within constant bandwidth narrow band spectrum and octave/fractional octave band spectrum were obtained with spectral analysis method, which could characterise granular materials' particle surface properties at different wavelength scales. Fourteen types of parent rocks of granular materials were tested with a modified micro tribological experiment simulating tribological behaviour among particle contact interfaces under dynamic loads. A contrastive analysis with traditionally used surface mean roughness was performed. The results indicate that the micro-texture levels and their distribution obtained in this study can detect the level of the exact texture scales (i.e. 32 and 2 μm wavelengths) significantly influencing the kinetic friction coefficient of granular materials, while surface mean roughness can only represent the global surface property. A high correlation was found between normalised micro-texture level (i.e. 32 μm) and Moh's hardness and coefficient of friction. [ABSTRACT FROM AUTHOR]

This paper investigates Søren Kierkegaard's concept of the self in his subjective thought, along with its implications for spiritual education. First of all, I argue that spirituality plays an essential role in life education. Apart from the meaning of spirit and spirituality, the development of spiritual education reveals that spiritual thought is unique and sacred. Second, by interpreting Kierkegaard's ideas on the self and subjectivity, this paper points out his vision of spirtuality and the meaning of a human being as a subjective existence. Third, this paper explores Kierkegaard's reflections on subjectivity in relation to the self, others and transcendence. Hence, the aim of this paper is to utilize Kierkegaard's existential thought of selfhood to spiritual education in Taiwan, providing a richer and more comprehensive perspective on spirituality. It concludes by expecting students to become spiritual subjects and lifelong learners. [ABSTRACT FROM AUTHOR]

Abstract Background Significant genetic association has been found in patients with severe carotid artery stenosis (CAS). The present study wished to investigate if metabolites may also act as biomarkers for CAS. Methods Consecutive patients with at least one carotid artery stenosis > = 60% on cerebral angiography were prospectively recruited from May 2007 to January 2016. Normal controls were recruited from outpatient clinic who had no stroke and coronary artery disease (CAD) history, and the brain magnetic resonance or computed tomographic angiography showed bilateral CAS

Abstract Background Rice planthoppers (main brown planthopper, Nilaparvata lugens Stål; BPH) was one of substantial threats to Asia rice production as its serious destruction and difficulties in control under field conditions. Notably, host-plant resistance was proved to be one of the effective ways to manage the pest. And stronger virulence will probably emergence when continuous use of insecticides. Therefore, more resistance genes with different resistance mechanisms were needed to be detected and then applied in the rice breeding practice. Results Resistance genes in the rice variety IR64 were evaluated considering the seedling bulk test and seedling survival rate. As a result, a locus with a large LOD score of 7.23 was found between markers RM302 and YM35 on chromosome 1. The locus explained 36.9% of phenotypic variation and was tentatively denominated Bph37. Moreover, Bph1 was detected to be harbored by the markers RM28366 and RM463, and had the largest LOD score of 2.08, explaining 7.7% of phenotypic variance in the same mapping population. Finally, the preliminary-near-isogenic-lines (pre-NILs) carrying Bph37 exhibited significant tolerance to the insects. But no antibiotic or antixenotic effects were observed in the resistant plants when infested with the insects. Conclusions We mapped one major BPH resistance gene Bph37 in consideration of seedling survival rate and the resistance lines showed tolerance to BPH. The detected gene should be beneficial for understanding the resistance mechanism of rice to BPH and for insect-resistance rice breeding programs.

Abstract Highly branched metallic nanostructures, which possess a large amount of catalyst active sites and surface-enhanced Raman scattering (SERS) hot spots owing to their large surface areas, multi-level branches, corners, and edges, have shown potential in various applications including catalysis and SERS. In this study, well-defined dendritic silver (Ag) nanostructures were prepared by a facile and controllable electrochemical deposition strategy. The morphology of Ag nanostructures is controlled by regulating electrodeposition time and concentration of AgNO3 in the electrolyte solution. Compared to conventional Ag nanoparticle films, dendritic Ag nanostructures exhibited larger SERS enhancement ascribed to the numerous hot spots exist in the nanogaps of parallel and vertically stacked multilayer Ag dendrites. In addition, the prepared dendritic Ag nanostructures show 3.2-fold higher catalytic activity towards the reduction of 4-nitrophenol (4-NP) by NaBH4 than the Ag nanoparticle films. The results indicate that the dendritic Ag nanostructures represent a unique bifunctional nanostructure that serves as both efficient catalysts and excellent SERS substrates, which may be further employed as a nanoreactor for in situ investigation and real-time monitoring of catalytic reactions by SERS technique.

Abstract Background A reduction in bond strength of bleached enamel has been confirmed in the literature. Although limited information is available, it is conceivable that the veneer preparation process may remove the impacted enamel and further eliminate the compromised bond strength between the composite resin and bleached enamel. This study aimed to evaluate the effect of surface removal following bleaching on the micro-shear bond strength (μSBS) of bleached enamel. Methods Forty-eight specimens were prepared from bovine incisors and were randomly divided into 2 groups (n = 24): group B (bleaching with 40% hydrogen peroxide for 2 × 45 min with a 1-week interval) and group C (control group without bleaching treatment). Immediately after receiving the treatments, 0.5 mm of the enamel was removed from the specimen surface, followed by bonding of composite resin to the enamel surface. Each group was further divided into 2 subgroups of 12 specimens each: subgroup T (with 5000 thermocycles in water baths at 5 °C and 55 °C), and subgroup N (without thermocycling). The μSBS values were measured using a universal testing machine and subjected to two-way analysis of variance (α = 0.05). The fracture modes of the specimens were observed using a stereomicroscope. Results The μSBS values of the different groups ranged from 21.42 to 25.21 MPa. Following a surface reduction of 0.5 mm, bleaching treatment and thermocycling did not significantly affect the μSBS values (P = 0.348 and P = 0.507, respectively). No significant interaction was found between the bleaching treatment and thermocycling (P = 0.514). All the groups exhibited a high percentage of mixed failures. Compared with group C, group B exhibited higher percentage of adhesive failure. Conclusion The results suggested that the bonding procedure could be performed on the bleached enamel following a surface reduction of 0.5 mm immediately after the bleaching treatment.

Abstract Background The transfer of whole mitochondria that occurs during cell contact has been found to support cancer progression. However, the regulatory role of mitochondria alone is difficult to elucidate due to the complex microenvironment. Currently, mitochondrial transplantation is an available approach for restoring mitochondrial function in mitochondrial diseases but remains unclear in breast cancer. Herein, effects of mitochondrial transplantation via different approaches in breast cancer were investigated. Methods Whole mitochondria (approximately 10.5 μg/ml) were transported into MCF-7 breast cancer cells via passive uptake or Pep-1-mediated delivery. Fresh mitochondria isolated from homeoplasmic 143B osteosarcoma cybrids containing mitochondrial DNA (mtDNA) derived from health individuals (Mito) or mtDNA with the A8344G mutation (Mito8344) were conjugated with cell-penetrating peptide Pep-1 (P-Mito) or not conjugated prior to cell co-culture. Before isolation, mitochondria were stained with MitoTracker dye as the tracking label. After 3 days of treatment, cell viability, proliferation, oxidative stress, drug sensitivity to Doxorubicin/Paclitaxel and mitochondrial function were assessed. Results Compared with P-Mito, a small portion of Mito adhered to the cell membrane, and this was accompanied by a slightly lower fluorescent signal by foreign mitochondria in MCF-7 cells. Both transplantations induced cell apoptosis by increasing the nuclear translocation of apoptosis-inducing factor; inhibited cell growth and decreased oxidative stress in MCF-7 cells; and increased the cellular susceptibility of both the MCF-7 and MDA-MB-231 cell lines to Doxorubicin and Paclitaxel. Mitochondrial transplantation also consistently decreased Drp-1, which resulted in an enhancement of the tubular mitochondrial network, but a distinct machinery through the increase of parkin and mitochondrial fusion proteins was observed in the Mito and P-Mito groups, respectively. Furthermore, although there were no differences in energy metabolism after transplantation of normal mitochondria, metabolism was switched to the energetic and glycolytic phenotypes when the mitochondria were replaced with dysfunctional mitochondria, namely, Mito8344 and P-Mito8344, due to dramatically induced glycolysis and reduced mitochondrial respiration, respectively. Consequently, transplant-induced growth inhibition was abolished, and cell growth in the Mito8344 group was even higher than that in the control group. Conclusion This study reveals the antitumour potential of mitochondrial transplantation in breast cancer via distinct regulation of mitochondrial function.

PLA2G6-associated neurodegeneration (PLAN) is a rare autosomal recessive disorder caused by PLA2G6 mutations. This study aimed to investigate the clinical characteristics and mutation spectrum of PLAN and to investigate the founder effects in Chinese PLAN patients. Six Chinese PLAN families were clinically examined in detail and whole-exome sequencing was performed in the probands. Haplotype analysis was performed in five families with the PLA2G6 c.991G > T mutation using 23 single nucleotide polymorphism markers. Furthermore, all previously reported PLA2G6 mutations and patients in China were reviewed to summarize the genetic and clinical features of PLAN. Interestingly, we found that one patient had hereditary spastic paraplegia and showed various atypical clinical characteristics of PLAN, and five patients had a phenotype of parkinsonism. All probands were compound heterozygotes for PLA2G6 variants, including four novel pathogenic/likely pathogenic mutations (c.967G > A, c.1450G > T, c.1631T > C, and c.1915delG) and five known pathogenic mutations. Haplotype analyses revealed that patients carrying PLA2G6 c.991G > T mutations shared a haplotype of 717 kb. The frequencies of psychiatric features, cognitive decline, and myoclonus in Chinese patients with PLA2G6-related parkinsonism were significantly different from those in European patients. Thus, our study expands the clinical and genetic spectrum of PLAN and provides an insightful view of the founder effect to better diagnose and understand the disease.

Although the effects of growth hormone (GH) therapy on spinocerebellar ataxia type 3 (SCA3) have been examined in transgenic SCA3 mice, it still poses a nonnegligible risk of cancer when used for a long term. This study investigated the efficacy of IGF-1, a downstream mediator of GH, in vivo for SCA3 treatment. IGF-1 (50 mg/kg) or saline, once a week, was intraperitoneally injected to SCA3 84Q transgenic mice harboring a human ATXN3 gene with a pathogenic expanded 84 cytosine–adenine–guanine (CAG) repeat motif at 9 months of age. Compared with the control mice harboring a 15 CAG repeat motif, the SCA3 84Q mice treated with IGF-1 for 9 months exhibited the improvement only in locomotor function and minimized degeneration of the cerebellar cortex as indicated by the survival of more Purkinje cells with a more favorable mitochondrial function along with a decrease in oxidative stress caused by DNA damage. These findings could be attributable to the inhibition of mitochondrial fission, resulting in mitochondrial fusion, and decreased immunofluorescence staining in aggresome formation and ataxin-3 mutant protein levels, possibly through the enhancement of autophagy. The findings of this study show the therapeutic potential effect of IGF-1 injection for SCA3 to prevent the exacerbation of disease progress.

Hexavalent chromium, namely, Cr(VI), is a significant threat to ecological and food safety. Current detection methods are not sensitive to Cr(VI). A photoelectrochemical (PEC) sensor based on bismuth vanadate (BiVO4) was developed for sensitive detection of Cr(VI). First, BiVO4-X (X: the pH of the reaction precursor solution) was synthesized using a facile surfactant-free hydrothermal method. The BiVO4-X morphology was well controlled according to pH values, showing rock-like (X = 1), wrinkled bark-like (X = 4), carnation-like (X = 7), and the collapsed sheet-like morphologies (X = 9, 12). BiVO4-7 exhibited excellent photoelectric performance due to a proper band structure under visible light and a large specific surface area. Then, BiVO4-7 was used to construct a PEC sensor to detect Cr(VI), which was demonstrated to have a low detection limit (10 nM) and wide detection range (2–210 μM). The BiVO4-7 PEC sensor had a stable output signal, as well as excellent reproducibility, repeatability, and selectivity. We used the BiVO4-7 PEC sensor to detect Cr(VI) in real environmental and food samples, resulting in a satisfactory recovery of 90.3–103.0%, as determined by comparison with results obtained using a spectrophotometric method. The BiVO4-7 PEC sensor is promising for practical application to heavy metal detection in the food and environment.

Increasing renewable energy penetration into integrated community energy systems (ICESs) requires more efficient methods to prevent power fluctuations of the tie-line (connection of the ICESs to the main grid). In this paper, centrally-controlled air conditioners are considered as a virtual energy storage system (VESS). The optimal thermostat regulation is used to manage the charging/discharging power of the VESS within the customer comfort level range and the virtual state of charge (VSOC) is used to describe the charging/discharging power of the VESS. On this basis, the model of the hybrid energy storage system is built with a VESS and a battery storage system (BSS). Then, an optimal coordination control strategy (OCCS) for a hybrid energy storage system is developed considering the state-space equation to describe the OCCS, the constraints of the OCCS, and the objective function to express the optimal coordination control performance. Finally, the influence of the outdoor temperature and the deadband of air conditioners on the results of the OCCS is analyzed. Results show that the OCCS can realize optimal allocation of the storage response amount to trace the reference target accurately and guarantee both the state of charge (SOC) of the batteries in a reasonable range to prolong the battery life and ensure the level of comfort experienced by users.

Objectives: Enterovirus 71 (EV71) may cause neurological and fatal cases. EV71 3C plays an important role on viral replication and possess proteolysis activity. To delineate pathogenesis of EV71 virulence, we studied EV71 3C genetics, protease activity and correlated the results with clinical severity. Methods: EV71 cases were collected; 3C of EV71 was sequenced and linked with clinical severity. 3C protease activity, viral replication rates of EV71 infectious clones with different 3C and 3C interaction with host proteins were analyzed. Results: The polymorphisms of EV71 3C at the 79th amino acid were associated with clinical severity. About 26% (62/234) patients infected by EV71 with wild-type 3C (T79) had neurological involvement but 78% (25/32) patients infected by EV71 with mutant 3C (T79V) did (p

The coronavirus disease 2019 (COVID-19) pandemic has become a global threat. Increases in cardiac biomarkers are common and are associated with adverse outcomes in patients with COVID-19. Although these increases are more likely to occur in cases with concomitant cardiac disease, the differences in cardiac biomarker levels between patients with and without cardiac disease and their associations with in-hospital mortality are largely unknown. A consecutive serial of laboratory-confirmed COVID-19 cases was retrospectively enrolled. Clinical characteristics, laboratory results, and outcome data were collected. The levels of cardiac biomarkers were evaluated and compared by stratifying patients according to concomitant cardiac conditions and clinical classifications. The prognostic efficacy of cardiac biomarker levels on admission was also assessed. Among the overall study population and survived patients, the cardiac biomarker levels at both the early and late stages in cardiac patients were significantly higher than those in non-cardiac patients. However, their concentrations in cardiac patients were comparable to non-cardiac ones among non-survivors. The cardiac biomarker levels at the late stage of the disease were significantly decreased compared to those at the early stage among patients who were alive. Whereas, the late-stage biomarker levels were significantly increased in patients who ultimately died. Subgroup analysis illustrated that increases in cardiac biomarkers were closely related to the severity of the disease, and were prognostic for high risks of in-hospital mortality in non-cardiac, rather than in cardiac patients. Myo and NT-proBNP, rather than Hs-TnI and CK-MB, were independently associated with in-hospital mortality in the overall population and non-cardiac patients. However, these associations were not significant among cardiac patients. In conclusion, our results helped better understand the release pattern and prognostic performance of cardiac biomarkers in patients with COVID-19. Increased levels of Myo and NT-proBNP on admission could be useful markers for early identifying high-risk patients. However, special attention must be paid when implementing the prognostic function for cardiac patients.

Background: This study aimed to deconvolve the levels of infiltrating immune cells in non-small cell lung cancer (NSCLC) and to identify specific gene co-expression modules associated with prognosis of NSCLC. Materials and Methods: CIBERSORT algorithm was employed to infer the relative abundance of 22 immune cell subtypes in 1751 NSCLC subjects. The patterns of immune infiltration were identified for NSCLC with different clinical and genomic features and were used to construct an immunoscore by LASSO regression associated with NSCLC survival. Weighted gene co-expression network analysis (WGCNA) was employed to identify specific modules related to immunoscore and NSCLC survival. An integrated prognostic model was constructed with immunoscore combined with the available clinical variables and the selected gene modules to predict the prognosis of NSCLC. Results: We found distinct immune infiltration patterns for NSCLC with different genotype. EGFR-mutant NSCLC was characterized by enriched resting memory CD4+ T cell. An immunoscore was established based on the infiltration abundance of 17 selected immune cell subtypes. Patients with a low immunoscore had a prolonged survival and higher abundance of CD4+ T cell, resting dendritic cells and resting mast cells. The WGCNA analysis identified the gene modules significantly associated with immunoscore and the prognosis of NSCLC. The immunoscore was further incorporated with clinical parameters and selected gene modules to fit a predictive model which stratified patients into subgroups with significantly different survival. Conclusion: The distinct immune profiles are associated with differential overall survival of NSCLC and the integrated model can robustly predict the prognosis of NSCLC.

Dynamic loads such as the train vibration load usually act on the shield tunnel lining in the long term, which could make the initial flaws in shield segment propagate and gradually weaken the robustness of the tunnel structure. In this paper, a three-dimensional numerical model of shield tunnel lining structure with the initial defect is built to study its dynamic reaction and fatigue crack propagation under the train vibration load. Furthermore, the damage to intact shield segment caused by train vibration load is studied by employing the rain-flow counting method and the Miner damage theory, and a rational fatigue life estimation for the concrete shield tunnel lining is finally made. Results show that crack propagation is influenced by both the train speed and train axle, the higher the train speed, the longer the final crack, and train axle has a larger influence than train speed on the crack propagation in shield tunnel segment. The shield tunnel lining structure of Nanjing Metro Line 5 can meet the demand of working for a hundred years under the current working conditions.