The silent information regulator sirtuin 1 (SIRT1) protein, a highly conserved NAD
-dependent deacetylase belonging to the sirtuin family, is a post-translational regulator that plays a role in ...modulating inflammation. SIRT1 affects multiple biological processes by deacetylating a variety of proteins including histones and non-histone proteins. Recent studies have revealed intimate links between SIRT1 and inflammation, while alterations to SIRT1 expression and activity have been linked to inflammatory diseases. In this review, we summarize the mechanisms that regulate SIRT1 expression, including upstream activators and suppressors that operate on the transcriptional and post-transcriptional levels. We also summarize factors that influence SIRT1 activity including the NAD
/NADH ratio, SIRT1 binding partners, and post-translational modifications. Furthermore, we underscore the role of SIRT1 in the development of inflammation by commenting on the proteins that are targeted for deacetylation by SIRT1. Finally, we highlight the potential for SIRT1-based therapeutics for inflammatory diseases.
A dynamic group key is required for secure communication in the Unmanned Aerial Vehicles Ad-Hoc Network (UAANET). However, due to the unreliable wireless channel and high-dynamic topology of UAANET, ...the situation that a node is missing certain group key broadcast messages occurs frequently. Existing group key distribution schemes cannot be directly applied to the UAANET, because of their poor security or real-time. Therefore, we present a mutual-healing group key distribution scheme based on the blockchain. Firstly, the Ground Control Station (GCS) builds a private blockchain where the group keys distributed by GCS are recorded. Meanwhile, through the blockchain, a dynamic list of UAANET membership certificates is also managed. According to different attack models, a basic mutual-healing protocol and an enhanced one are designed based on the Longest-Lost-Chain mechanism to recover the node's lost group keys with the aid of its neighbors. Security analysis and extensive experiments show that, compared with the existing mutual-healing schemes, our proposed solution can effectively resist various attacks with small overhead on time and storage.
The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we ...show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia. This was associated with a pro-inflammatory T helper type 1 (T(H)1) immune response and increased incidence of colitis in genetically susceptible Il10(−/−), but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10(−/−) mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.
•Photo-assisted sol–gel route was developed to prepare nanostructured Li4Ti5O12 anode.•UV irradiation process is effective to reduce grain size and modulate morphology.•Li4Ti5O12 electrode treated ...with UV irradiation presents superb rate performance.
Photo-assisted sol–gel route was developed to prepare nanostructured Li4Ti5O12 anode materials. Resulting Li4Ti5O12 powders were characterized by phase analysis, microscopic morphology observation, and cyclic charge/discharge tests. As lithium-ion battery electrode, synthesized Li4Ti5O12 material by using the photo-assisted sol–gel route shows specific capacity of 120 mAh g−1 at 10C discharge rate. Furthermore, this material retains 98% of its initial specific capacity at 0.2C after 50 charge/discharge measurements. Outstanding rate capability and cycling stability of this Li4Ti5O12 material are mainly derived from grain refinement induced by ultraviolet photo-irradiation. Therefore, this photo-assisted sol–gel route is attractive alternative method for preparing electrode materials for high-power lithium-ion battery applications.
Suspended sediment concentration (SSC) is an important indicator for coastal morphodynamics and health, exhibiting significant periodic variations at multiple timescales in response to various cyclic ...forcing factors. Identification of key periods and the extraction of corresponding amplitudes and phases can greatly aid effort to characterize the representative portrayal of SSC, which contributes to further physical interpretation. Remote sensing missions are intended to satisfy the retrieval of long-term SSC variations. However, the unevenly spaced characteristic and low effective sampling rates of the retrieved time series would hamper the extraction and interpretation of the feature changes. Here, we retrieved a 9-year SSC time series in a coastal tidal basin of Jiangsu coast, China, based on hourly GOCI satellite images from 2011 to 2019, and applied the Lomb-Scargle periodogram with the phase-folded method to extract their periodic information. On the basis of the unevenly spaced data with effective rate of 6.9%, the semidiurnal, diurnal, fortnightly, and seasonal cycles were successfully identified as the main periods, with amplitudes of 33.1, 23.4, 54.1, and 71.4 mg/L, respectively. In accordance with investigations into phase lags between SSC and forcing factors, we found that the unimodal SSC pattern at the semidiurnal timescale was induced by flood dominance, while the diurnal inequality of water level and wave intensity accounts for the SSC variation at the diurnal timescale. Tidal ranges vary consistently with the SSC in the fortnightly scale while background wave dominates the SSC variation in the seasonal timescale, the latter resulting in the seasonal difference in semidiurnal and fortnightly SSC cycles. The annual semidiurnal SSC variations experience a regime shift from 2014 to 2016, which is in consistency with the sequential reclamation. The research presents a typical application of long-term unevenly spaced observations into coastal SSC, and the proposed methodology can be extended to similar studies aiming at uncovering the mechanism of SSC variations at multiple timescales.
•Unevenly spaced satellite time series with low effective rates can be analyzed with new methods.•4 main cycles of sediment concentration were recognized, with amplitudes and phases extracted.•Various periodic patterns suggest the varied effects of waves and tides at different timescales.
Interleukin (IL)-10 is elevated in cancer and is thought to contribute to immune tolerance and tumor growth. Defying these expectations, the adoptive transfer of IL-10-expressing T cells to mice with ...polyposis attenuates microbial-induced inflammation and suppresses polyposis. To gain better insights into how IL-10 impacts polyposis, we genetically ablated IL-10 in T cells in APC(Δ468) mice and compared the effects of treatment with broad-spectrum antibiotics. We found that T cells and regulatory T cells (Treg) were a major cellular source of IL-10 in both the healthy and polyp-bearing colon. Notably, T cell-specific ablation of IL-10 produced pathologies that were identical to mice with a systemic deficiency in IL-10, in both cases increasing the numbers and growth of colon polyps. Eosinophils were found to densely infiltrate colon polyps, which were enriched similarly for microbiota associated previously with colon cancer. In mice receiving broad-spectrum antibiotics, we observed reductions in microbiota, inflammation, and polyposis. Together, our findings establish that colon polyposis is driven by high densities of microbes that accumulate within polyps and trigger local inflammatory responses. Inflammation, local microbe densities, and polyp growth are suppressed by IL-10 derived specifically from T cells and Tregs.
Sepsis is a fatal disease with a high rate of morbidity and mortality, during which acute lung injury is the earliest and most serious complication. Injury of pulmonary microvascular endothelial ...cells (PMVECs) induced by excessive inflammation plays an important role in sepsis acute lung injury. This study is meant to explore the protective effect and mechanism of ADSCs exosomes on excessive inflammation PMVECs injury.
We successfully isolated ADSCs exosomes, the characteristic of which were confirmed. ADSCs exosomes reduced excessive inflammatory response induced ROS accumulation and cell injury in PMVECs. Besides, ADSCs exosomes inhibited excessive inflammatory response induced ferroptosis while upregulated expression of GPX4 in PMVECs. And further GPX4 inhibition experiments revealed that ADSCs exosomes alleviated inflammatory response induced ferroptosis via upregulating GPX4. Meanwhile, ADSCs exosomes could increase the expression and nucleus translocation of Nrf2, while decrease the expression of Keap1. miRNA analysis and further inhibition experiments verified that specific delivery of miR-125b-5p by ADSCs exosomes inhibited Keap1 and alleviated ferroptosis. In CLP induced sepsis model, ADSCs exosomes could relieve the lung tissue injury and reduced the death rate. Besides, ADSCs exosomes alleviated oxidative stress injury and ferroptosis of lung tissue, while remarkably increase expression of Nrf2 and GPX4.
Collectively, we illustrated a novel potentially therapeutic mechanism that miR-125b-5p in ADSCs exosomes could alleviate the inflammation induced PMVECs ferroptosis in sepsis induced acute lung injury via regulating Keap1/Nrf2/GPX4 expression, hence improve the acute lung injury in sepsis.
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Wave‐ and current‐supported gravity flows (WCSGFs) represent a primary mechanism responsible for the transport of sediment along gentle coastal and continental slopes. However, due to limited in situ ...measurements, the dynamic processes involved in the downslope movement of WCSGFs along such slopes remain poorly understood. Here, tripods were strategically deployed on a muddy coastal slope in central Jiangsu, China. We found that WCSGFs occurred following a wave event, particularly during tidal slack periods. In instances where WCSGF events coincide with low slack water, the observed time lags between break and toe sites align with expectations based on gravity‐driven velocities and distances, thereby corroborating the gravitationally induced sediment transport across the gently sloping coast. Comparatively, WCSGF events during high slack water were suggested to originate from the upper tidal flat of the cross‐shore profile and were unable to reach the toe site. Waves are crucial in supporting the downslope transport of WCSGFs. In addition to sustaining the cross‐shore movement of WCSGFs, currents suspend sediments from the high‐concentration layer, dispersing them into the overlying water column. This suspension helps extinguishing WCSGFs. The local slope at the toe site lacks the necessary gravitational force to propel high‐concentration layers further offshore, as evidenced by the abnormally low drag coefficient (CD) derived from the theoretical WCSGF model. Despite their short‐lived nature and limited travel distance, the WCSGFs examined in this study make a significant contribution to cross‐shore sediment transport. This study contributes to a better understanding of WCSGF dynamics and their importance in coastal sediment transport.
The time lags observed between the occurrence of WCSGF events at break and toe sites provide evidence of downslope sediment transport along a gently sloping coastal region. The cross‐shore movement of WCSGFs will slow down in response to an increase in current and a decrease in bed slope. WCSGF processes generate heightened cross‐shelf sediment flux, despite their relatively short‐lived duration and limited travel distance.
Diet-induced obesity (DIO) is a significant health concern which has been linked to structural and functional changes in the gut microbiota. Exercise (Ex) is effective in preventing obesity, but ...whether Ex alters the gut microbiota during development with high fat (HF) feeding is unknown.
Determine the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and in HF-DIO.
Male C57BL/6 littermates (5 weeks) were distributed equally into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12 weeks and used for bacterial DNA isolation. DNA was subjected both to quantitative PCR using primers specific to the 16S rRNA encoding genes for Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification using the Illumina MiSeq platform. Data were analyzed using a one or two-way ANOVA or Pearson correlation.
HF diet resulted in significantly greater body weight and adiposity as well as decreased glucose tolerance that were prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with principal coordinates analysis indicated clustering by both diet and Ex at week 12. Sequencing demonstrated Ex-induced changes in the percentage of major bacterial phyla at 12 weeks. A correlation between total Ex distance and the ΔCt Bacteroidetes: ΔCt Firmicutes ratio from qPCR demonstrated a significant inverse correlation (r2 = 0.35, p = 0.043).
Ex induces a unique shift in the gut microbiota that is different from dietary effects. Microbiota changes may play a role in Ex prevention of HF-DIO.
Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an ...additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally raised counterparts. Examination of gut microbiota in conventionally raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary composition. Additionally, specific microbial metabolites induced under low- or high-fat feeding, particularly short-chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet.
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•Diurnal variations in gut microbes and function are driven by dietary and host cues•High-fat diets disturb diurnal patterns of gut microbial structure and function•Microbial metabolite oscillations are linked to host circadian rhythm and metabolism•Disturbances of host-microbe circadian networks may promote diet-induced obesity
Circadian rhythm influences health and metabolism. Leone et al. show that the gut microbiota exhibits diurnal oscillations in composition and metabolite production that are driven by diet and associated with the host circadian rhythm. Diet-induced dysbiosis disturbs the balance between microbe and host circadian networks, affecting metabolism and obesity.
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