An increasing amount of evidence reveals that the gut microbiota is involved in the pathogenesis and progression of various cardiovascular diseases. In patients with heart failure (HF), splanchnic ...hypoperfusion causes ischemia and intestinal edema, allowing bacterial translocation and bacterial metabolites to enter the blood circulation via an impaired intestinal barrier. This results in local and systemic inflammatory responses. Gut microbe-derived metabolites are implicated in the pathology of multiple diseases, including HF. These landmark findings suggest that gut microbiota influences the host's metabolic health, either directly or indirectly by producing several metabolites. In this review, we mainly discuss a newly identified gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), which appears to participate in the pathologic processes of HF and can serve as an early warning marker to identify individuals who are at the risk of disease progression. We also discuss the potential of the gut–TMAO–HF axis as a new target for HF treatment and highlight the current controversies and potentially new and exciting directions for future research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
During the past decade, the electronic healthcare (e-health) system has been evolved into a more patient-oriented service with smaller and smarter wireless devices. However, these convenient smart ...devices have limited computing capacity and memory size, which makes it harder to protect the user's massive private data in the e-health system. Although some works have established a secure session key between the user and the medical server, the weaknesses still exist in preserving the anonymity with low energy consumption. Moreover, the misuse of biometric information in key agreement process may lead to privacy disclosure, which is irreparable. In this study, we design a dynamic privacy protection mechanism offering the biometric authentication at the server side whereas the exact value of the biometric template remains unknown to the server. And the user anonymity can be fully preserved during the authentication and key negotiation process because the messages transmitted with the proposed scheme are untraceable. Furthermore, the proposed scheme is proved to be semantic secure under the real-or-random model. The performance analysis shows that the proposed scheme suits the e-health environment at the aspect of security and resource occupation.
Since ancient times, the Southern Silk Road and the Maritime Silk Road have carried economic, cultural and political functions, promoted regional economic and trade cooperation, and promoted regional ...cultural integration. Yunnan is the intersection of the Maritime Silk Road and the Land Silk Road, and its geographical and strategic location is of great significance. In recent years, the central government has put forward the “the Belt and Road (B&R) “ initiative. As one of the 13 provinces (municipalities directly under the Central Government) defined by the Silk Road Economic Belt, Yunnan has rich resource advantages, cultural advantages and regional advantages. Relying on its unique geographical advantages, rich natural resources and diverse folk culture, Yunnan has become one of the important tourist destinations in China. Especially with the deepening of the “B&R” initiative, Yunnan’s international status has become increasingly prominent. The “B&R” strategy is of great significance to the development of Yunnan’s tourism industry. On the one hand, it opens up markets for tourism, and on the other hand, it promotes the development of Yunnan’s tourism industry to face the world. Based on the current situation of the development of Yunnan’s tourism industry in the context of the “B&R” initiative, this paper analyzes the opportunities and challenges faced by the development of Yunnan’s tourism industry in the context of the “B&R” initiative, and finally puts forward effective development strategies for Yunnan’s tourism industry.
Applying the angular spectrum theory, we derive the expression of a new Hermite-Gaussian (HG) vortex beam. Based on the new Hermite-Gaussian (HG) vortex beam, we establish the model of the received ...probability density of orbital angular momentum (OAM) modes of this beam propagating through a turbulent ocean of anisotropy. By numerical simulation, we investigate the influence of oceanic turbulence and beam parameters on the received probability density of signal OAM modes and crosstalk OAM modes of the HG vortex beam. The results show that the influence of oceanic turbulence of anisotropy on the received probability of signal OAM modes is smaller than isotropic oceanic turbulence under the same condition, and the effect of salinity fluctuation on the received probability of the signal OAM modes is larger than the effect of temperature fluctuation. In the strong dissipation of kinetic energy per unit mass of fluid and the weak dissipation rate of temperature variance, we can decrease the effects of turbulence on the received probability of signal OAM modes by selecting a long wavelength and a larger transverse size of the HG vortex beam in the source's plane. In long distance propagation, the HG vortex beam is superior to the Laguerre-Gaussian beam for resisting the destruction of oceanic turbulence.
The urban heat island (UHI) effect caused by urbanization is a major environmental concern. Utilizing cooling effects of water bodies as one type of ecosystem service is an important way to mitigate ...UHI in urban areas during the daytime. This study aims to examine the influence of water bodies’ cooling effects on the urban land surface temperature (LST). The potential influence on the relationship between urban land cover and the LST are also discussed. The daytime LST in April was retrieved from Landsat-8 thermal infrared band and the grid-based method was adopted to analyze the potential influence. The results indicated that Suzhou Bay is broadly capable of lowering daytime temperatures. The cooling distance can reach 800 m in horizontal space, and the maximum cooling effect was 3.02 °C. Furthermore, the distance to the Suzhou Bay is a great factor for the relationship between land cover and the LST. We found that the cooling effects have weakened the correct quantitative correlation between land cover (e.g., green space and impervious surface) and the LST, particularly green space in the range of 200 m. In addition, the cooling effects have strengthened the “cool edge” phenomenon when analyzing the relationship between the normal difference vegetation index (NDVI) and the LST. We suggest that the distance to the water bodies should be effectively utilized in the microclimate regulation provided by ecosystem services of water bodies. When investigating the thermal effects of urban land, urban planners and designers should consider water bodies’ effects on surrounding areas. These findings have implications for understanding the role of water bodies with ecosystem services of temperature mitigation, which must be fully appreciated for sustainable urban and landscape planning.
Long-read de novo genome assembly continues to advance rapidly. However, there is a lack of effective tools to accurately evaluate the assembly results, especially for structural errors. We present ...Inspector, a reference-free long-read de novo assembly evaluator which faithfully reports types of errors and their precise locations. Notably, Inspector can correct the assembly errors based on consensus sequences derived from raw reads covering erroneous regions. Based on in silico and long-read assembly results from multiple long-read data and assemblers, we demonstrate that in addition to providing generic metrics, Inspector can accurately identify both large-scale and small-scale assembly errors.
It is often believed that for open source software (OSS) projects the faster the release, the better for attracting user interest in the software. Whether this is true, however, is still open to ...question. There is considerable information asymmetry between OSS projects and potential users as project quality is unobservable to users. We suggest that innovation speed of OSS project can signal the unobservable project quality and attract users’ interest in downloading and using the software. We contextualize innovation speed of OSS projects as initial release speed and update speed and examine their impacts on user interest. Drawing on the signaling theory, we propose a signaling effect through which a higher initial release speed or update speed increases user interest, while the effect diminishes as initial release or update speed increases. Using a large-scale panel data set from 7442 OSS projects on SourceForge between 2007 and 2010, our results corroborate the inverted U-shaped relationships between initial release speed and user downloads and between update speed and user downloads.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Central sensitization is an important mechanism of chronic migraine (CM) and is related to the inflammatory response of microglia. The NOD-like receptor protein 3 (NLRP3) inflammasome may regulate ...the inflammatory process of microglia in several neurological diseases, but its role in CM is largely unknown. Therefore, the aim of this study was to identify the precise role of microglial NLRP3 in CM.
An experimental CM mouse model was established by repeated intraperitoneal (i.p) injection with nitroglycerin (NTG). We evaluated the expression levels of NLRP3 and its downstream interleukin (IL)-1β protein in the trigeminal nucleus caudalis (TNC; which is a central area relevant to migraine pain) at different time points. To further examine the effects of the NLRP3 inflammasome pathway on central sensitization of CM, we examined MCC950, an NLRP3 inflammasome-specific inhibitor, and IL-1ra, an IL-1β antagonist, whether altered NTG-induced mechanical hyperalgesia of the periorbital area and hind paw. The effect of MCC950 and IL-1ra on c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK) and calcitonin gene-related peptide (CGRP) expression in the TNC were also analyzed. The cell localization of NLRP3 and IL-1β in the TNC was evaluated by immunofluorescence staining.
Repeated NTG administration induced acute and chronic mechanical hyperalgesia and increased expression of NLRP3 and IL-1β. Blockade of NLRP3 or IL-1β reduced NTG-induced hyperalgesia, and this effect was accompanied by a significant inhibition of the NTG-induced increase in p-ERK, c-Fos and CGRP levels in the TNC. Immunofluorescence staining revealed that NLRP3 and IL-1β were mainly expressed in microglia in the TNC, and the IL-1β receptor, IL-1R, was mainly expressed in neurons in the TNC.
These results indicate that NLRP3 activation in the TNC participates in the microglial-neuronal signal by mediating the inflammatory response. This process contributes to the central sensitization observed in CM.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Periodontal ligament stem cells (PDLSCs) are considered as candidate cells for the regeneration of periodontal and alveolar bone tissues. Antisense to the cerebellar degeneration-related protein 1 ...transcript (CDR1as), which is a newly discovered circular RNA (circRNA), has been reported to act as an miR-7 sponge and to be involved in many biological processes. Here, we investigated the potential roles of CDR1as and miR-7 in the osteogenic differentiation of PDLSCs.
The expression pattern of CDR1as and miR-7 in PDLSCs during osteogenesis was detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Then we overexpressed or knocked down CDR1as or miR-7 to confirm whether they were involved in the regulation of osteoblast differentiation in PDLSCs. Alkaline phosphatase (ALP) and alizarin red S (ARS) staining were used to detect the activity of osteoblasts and mineral deposition. Furthermore, a dual luciferase reporter assay was conducted to analyze the binding of miR-7 to growth differentiation factor (GDF)5. To further verify the role of CDR1as in osteoblast differentiation, we conducted animal experiments in vivo. New bone formation in specimens was analyzed by microcomputed tomography (micro-CT), hematoxylin and eosin staining, and immunofluorescence staining.
We observed that CDR1as was significantly upregulated during the osteogenic differentiation, whereas miR-7 was significantly downregulated. Moreover, knockdown of CDR1as and overexpression of miR-7 inhibited the ALP activity, ARS staining, and expression of osteogenic genes. Overexpression of miR-7 significantly reduced the activity of luciferase reporter vectors containing the wild-type, but not the mutant, 3' untranslated region (UTR) sequence of GDF5. Furthermore, knockdown of GDF5 partially reversed the effects of miR-7 inhibitor on osteoblast differentiation. Downregulation of CDR1as or GDF5 subsequently inhibited phosphorylation of Smad1/5/8 and p38 mitogen-activated protein kinases (MAPK), while upregulation of miR-7 decreased the level of phosphorylated Smad1/5/8 and p38 MAPK. In vivo, CDR1as knockdown lead to less bone formation compared with the control group as revealed by micro-CT and the histological analysis.
Our results demonstrated that CDR1as acts as a miR-7 inhibitor, triggering the upregulation of GDF5 and subsequent Smad1/5/8 and p38 MAPK phosphorylation to promote osteogenic differentiation of PDLSCs. This study provides a novel understanding of the mechanisms of osteogenic differentiation, and suggests a potential method for promoting bone formation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Phase-sensitive optical time-domain reflectometry (Φ-OTDR) has been widely used in various applications for its distributed measurement capability of dynamic disturbance along the entire length of ...sensing fiber. However, traditional Φ-OTDR cannot make high-precision measurement on the external disturbance-induced strain due to the randomly distributed position and reflectivity of scattering points within the optical fiber. In this paper, ultra-weak fiber Bragg grating (UWFBG) array has been proposed to generate strong and controllable reflections while providing acceptable insertion loss. Active laser frequency sweeping and unwrapping algorithms were included to set up a definite relationship between strain value and variation of interference power between neighboring reflection lights. With the assistant of UWFBG array, the capability of Φ-OTDR has been upgraded to be able to take high-precision measurement on strain. In the experiment, multipoint με level dynamic strain variation has been fully captured at the end of a 5-km long sensing fiber with 2 m spatial resolution. The measured strain value was compared to the calibrated one obtained with Mach-Zehnder Interferometer method. These two values fit with each other quite well with a maximum deviation of 6.2 nε, which confirmed the validity and accuracy of the proposed method.
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