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Diabetes is a common metabolic disorder that has become a major health problem worldwide. In this study, we investigated the role of rutin in attenuating diabetes and preventing diabetes-related colon lesions in mice potentially through regulation of gut microbiota. The rutin from tartary buckwheat as analyzed by HPLC was administered intragastrically to diabetic mice, and then the biochemical parameters, overall community structure and composition of gut microbiota in diabetic mice were assayed. The results showed that rutin lowered serum glucose and improved serum total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride concentrations, tumor necrosis factor-α, interleukin-6, and serum insulin in diabetic mice. Notably, rutin obviously alleviated colon lesions in diabetic mice. Moreover, rutin also significantly regulated gut microbiota dysbiosis and enriched beneficial microbiota, such as Akkermansia (p < 0.05). Rutin selectively increased short-chain fatty acid producing bacteria, such as Alistipes (p < 0.05) and Roseburia (p < 0.05), and decreased the abundance of diabetes-related gut microbiota, such as Escherichia (p < 0.05) and Mucispirillum (p < 0.05). Our data suggested that rutin exerted an antidiabetic effect and alleviated colon lesions in diabetic mice possibly by regulating gut microbiota dysbiosis, which might be a potential mechanism through which rutin alleviates diabetes-related symptoms.

(1) Background: pancreatic cancer is one of the most serious cancers due to its rapid and inevitable fatality, which has been proved very difficult to treat, compared with many other common cancers. Thus, developing an effective therapeutic strategy, especially searching for potential drugs, is the focus of current research. The exact mechanism of rutin in pancreatic cancer remains unknown. (2) Method: three pancreatic cancer cell lines were used to study the anti-pancreatic cancer effect of rutin. The potent anti-proliferative, anti-migration and pro-apoptotic properties of rutin were uncovered by cell viability, a wound-healing migration assay, and a cell apoptosis assay. High-throughput sequencing technology was used to detect the change of miRNAs expression. Immunoblotting analysis was used to detect the expression of apoptotic proteins. (3) Results: CCK-8 and EDU assays revealed that rutin significantly inhibited pancreatic cancer cells’ proliferation (p < 0.05). A wound-healing assay showed that rutin significantly suppressed pancreatic cancer cells’ migration (p < 0.05). A flow cytometric assay showed that rutin could promote pancreatic cancer cells’ apoptosis. Intriguingly, rutin significantly upregulated miR-877-3p expression to repress the transcription of Bcl-2 and to induce pancreatic cancer cell apoptosis. Accordingly, rutin and miR-877-3p mimics could promote apoptotic protein expression. (4) Conclusions: our findings indicate that rutin plays an important role in anti-pancreatic cancer effects through a rutin-miR-877-3p-Bcl-2 axis and suggests a potential therapeutic strategy for pancreatic cancer.

Macau, the world’s largest casino hub with the largest gambling revenues, has received increasing attention as a research focus. Macau attracts more and more Chinese outbound tourists each year due to its gambling industry monopoly in Greater China. Macau is positioning itself as a ‘world center of tourism and leisure’ and has set out plans to become a broader-based tourist destination with economic diversification. Thus, an understanding of people’s varied motivations plays an important role in the current status of an environment with a moderate diversification of economic development. The objective of this study is to classify the outbound mainland Chinese tourists in Macau into more homogeneous subgroups on the basis of their travel motivations. Thirteen motivation items are extracted into four factors (namely knowledge and culture, relaxation, entertainment and gambling, and prestige) through exploratory factor analysis. Three distinct market segments are identified—freedom seekers, multi-purpose seekers, and fun and special interest in gambling seekers—based on a cluster analysis using k-means methodology. This study also presents the socio-demographic and trip characteristic differences among these three segments.

The atomic clocks, whether operating at optical or microwave region, can be divided into two categories according to their working mode, namely the passive clocks and active clocks. The passive clocks, whose standard frequency is locked to an ultra-narrow atomic spectral line, such as laser cooled Cs beam or lattice trapped Sr atoms, depend on the spontaneous emission line. On the contrary, the active clocks, in which the atoms are used as the gain medium, are based on the stimulated emission radiation, their spectrum can be directly used as the frequency standard. Up to now, the active hydrogen maser has been the most stable microwave atomic clocks. Also, the Sr superradiant active atomic clock is prospects for a millihertz-linewidth laser. Moreover, the optical clocks are expected to surpass the performance of microwave clocks both in stability and uncertainty, since their higher working frequency. The active optical clock has the potential to improve the stability of the best clocks by 2 orders of magnitude. In this work, we introduce the development of active optical clocks, and their types is classified according to the energy-level structure of atoms for stimulated radiation.

Background: Oral administration remains the most common route for drug absorption. Emerging evidence highlights the important role of gut microbiome in the pharmacokinetics of oral medications. Glycyrrhizic acid (GL), a widely used hepatoprotective drug, is orally administrated and subsequently biotransformed by the gut microbiota into its active metabolite, glycyrrhetinic acid (GA), which exerts a therapeutic effect. However, it remains unclear whether the disturbance of the gut microbiome directly impacts the metabolism of GL. Methods: Antibiotic cocktail and probiotic Lacticaseibacillus rhamnosus R0011 were applied as two interventions targeting the gut microbiome. Pharmacokinetic parameters were evaluated by LC-MS, and 16S rRNA sequencing was applied to analyze the gut microbiome composition. The transcriptome analysis of Caco-2 cells was used to elucidate the regulation mechanism of polar metabolites resulting from gut microbiome perturbation. Results: R0011 supplementation could significantly increase the Area Under Curve (AUC) value of GA, which was positively correlated with the change in gut microbiome composition. In contrast, the plasma levels of GA were nearly undetectable following antibiotic intervention. Furthermore, the relative expressions of transporter multidrug resistance gene 1 (MDR1) in the ileum were site specifically downregulated under the probiotic intervention. The polar gut microbial metabolites may play a crucial role in differentiated regulating MDR1 expression, likely through the modulation of transcription factors FoxO1 and TP53. Conclusions: Our research provides new insights into the regulatory mechanism by which the gut microbiome affects the bioabsorption of orally administrated drugs, potentially offering strategies to optimize drug bioavailability and improve clinical efficacy.

Little is known about the diversity, community composition, or distribution of benthic microbial eukaryotes in organic carbon (OC)-rich mangrove sediments. We hypothesized that the distribution of microeukaryotes was related to the spatial heterogeneity of mangrove sediment geochemistry due to tidal zonation and the rhizosphere effect. A range of geochemical properties of surface sediments were characterized, and alpha and beta diversities of microeukaryotes in a mangrove ecosystem were investigated using MiSeq sequencing of 18S rRNA genes. We found that the sequence proportions of Chlorophyta and Bacillariophyta were notably high in the datasets. Both operational taxonomic unit (OTU) richness and microeukaryotic community structure (MCS) were significantly different between the OC-rich upper tidal zone and the sulfate- and ammonium-rich lower tidal zone, indicating a strong response of microeukaryotic diversity to tidal zonation. The zonewise community differences were characterized by distinct shifts in the proportions and OTUs of chlorophytes, diatoms, and fungi. However, neither OTU richness nor MCS was significantly different between near-root and bulk sediments, though several geochemical parameters varied. Similarly, the assemblages of fungi showed a pattern of tidal zonation. Overall, variations in MCS in mangrove sediments were mainly driven by the quantity and quality of organic matter, grain size, and concentration of sulfate.

Lasing in the bad-cavity regime has promising applications in quantum precision measurement and frequency metrology due to the reduced sensitivity of the laser frequency to cavity-length fluctuations. Thus far, relevant studies have been mainly focused on conventional cavities whose finesse is high enough that the resonance linewidth is sufficiently narrow compared to the cavity’s free spectral range, though still in the bad-cavity regime. However, lasing output from the cavity whose finesse is close to the limit of 2 has never been experimentally accessed. Here, we demonstrate an extremely bad-cavity laser, analyze the physical mechanisms limiting cavity finesse, and report on the worst-ever laser cavity with finesse reaching 2.01. The optical cavity has a reflectance close to zero and only provides weak optical feedback. The laser power can be as high as tens of μ W and the spectral linewidth reaches a few kHz, over one thousand times narrower than the gain bandwidth. In addition, the measurement of cavity pulling reveals a pulling coefficient of 0.0148, the lowest value ever achieved for a continuous-wave laser. Our findings open up an unprecedentedly innovative perspective for future new ultra-stable lasers, which could possibly trigger future discoveries in optical clocks, cavity QED, continuous-wave superradiant laser, and explorations of quantum many-body physics.

Traditional lasers function using resonant cavities, in which the round-trip optical path is equal to an integer multiple of the intracavity wavelengths to constructively enhance the spontaneous emission rate. Taking advantage of the cavity enhancement effect, the narrowest sub-10-mHz-linewidth laser and a 10 −16 -fractional-frequency-stability superradiant active optical clock (AOC) have been achieved. However, a laser with atomic spontaneous radiation being destructively inhibited in an anti-resonant cavity, where the atomic resonance is exactly between two adjacent cavity resonances, has not been reported. Herein, we experimentally demonstrate the inhibited laser. Compared with traditional AOCs, which exhibit superiority in terms of the high suppression of cavity noise, the suppression of the cavity-pulling effect of an inhibited laser can be further improved by a factor of 2 F / π 2 , which is improved from 26 to 53 times. This study will guide further development of AOCs with better stability, and thus, it is significant for quantum metrology and may lead to new research in the laser physics and cavity quantum electrodynamics fields. Lasers in general are operated using a cavity resonant with emitters. In this study, the authors demonstrated a laser operating under an anti-resonant condition, where the emitter resonance is equally detuned from two Fabry–Perot fringes. This configuration may pave the way for reducing the laser linewidth and cavity pulling effect.

The demand of high-end electromagnetic wave absorbing materials puts forward higher requirements on comprehensive performances of small thickness, lightweight, broadband, and strong absorption. Herein, a novel multi-layer stepped metamaterial absorber with gradient electromagnetic properties is proposed. The complex permittivity and permeability of each layer are tailored via the proportion of carbonyl-iron and carbon-fiber dispersing into the epoxy resin. The proposed metamaterial is further optimized via adjusting the electromagnetic parameters and geometric sizes of each layer. Comparing with the four-layer composite with gradient electromagnetic properties which could only realize reflection loss (RL) of less than −6 dB in 2.0–40 GHz, the optimized stepped metamaterial with the same thickness and electromagnetic properties realizes less than −10 dB in the relevant frequency range. Additionally, the RL of less than −15 dB is achieved in the frequency range of 11.2–21.4 GHz and 28.5–40 GHz. The multiple electromagnetic wave absorption mechanism is discussed based on the experimental and simulation results, which is believed to be attributed to the synergy effect induced by multi-scale structures of the metamaterial. Therefore, combining multi-layer structures and periodic stepped structures into a novel gradient absorbing metamaterial would give new insights into designing microwave absorption devices for broadband electromagnetic protections.

Chronic hyperglycaemia is a devastating factor that causes diabetes-induced damage to the retina and kidney. However, the precise mechanism by which hyperglycaemia drives apoptotic cell death is incompletely known. Herein, we found that FOXD1, a FOX family transcription factor specifically expressed in the retina and kidney, regulated the transcription of BCL-2, a master regulator of cell survival. Intriguingly, the protein level of FOXD1, which responded negatively to hyperglycaemic conditions, was controlled by the TRIM21-mediated K48-linked polyubiquitination and subsequent proteasomal degradation. The TRIM21-FOXD1-BCL-2 signalling axis was notably active during diabetes-induced damage to murine retinal and renal tissues. Furthermore, we found that tartary buckwheat flavonoids effectively reversed the downregulation of FOXD1 protein expression and thus restored BCL-2 expression and facilitated the survival of retinal and renal tissues. In summary, we identified a transcription factor responsible for BCL-2 expression, a signalling axis (TRM21-FOXD1-BCL-2) underlying hyperglycaemia-triggered apoptosis, and a potential treatment for deleterious diabetic complications.