The anti-hyperglycemic effect of metformin is believed to be caused by its direct action on signaling processes in hepatocytes, leading to lower hepatic gluconeogenesis. Recently, metformin was ...reported to alter the gut microbiota community in humans, suggesting that the hyperglycemia-lowering action of the drug could be the result of modulating the population of gut microbiota. However, the critical microbial signaling metabolites and the host targets associated with the metabolic benefits of metformin remained elusive. Here, we performed metagenomic and metabolomic analysis of samples from individuals with newly diagnosed type 2 diabetes (T2D) naively treated with metformin for 3 d, which revealed that Bacteroides fragilis was decreased and the bile acid glycoursodeoxycholic acid (GUDCA) was increased in the gut. These changes were accompanied by inhibition of intestinal farnesoid X receptor (FXR) signaling. We further found that high-fat-diet (HFD)-fed mice colonized with B. fragilis were predisposed to more severe glucose intolerance, and the metabolic benefits of metformin treatment on glucose intolerance were abrogated. GUDCA was further identified as an intestinal FXR antagonist that improved various metabolic endpoints in mice with established obesity. Thus, we conclude that metformin acts in part through a B. fragilis-GUDCA-intestinal FXR axis to improve metabolic dysfunction, including hyperglycemia.
Hypoxia-inducible factor (HIF) 1α is a metabolic regulator that plays an important role in immunologic responses. Previous studies have demonstrated that HIF1α participates in the M1 polarization of ...macrophages. To clarify the mechanism of HIF1α-induced polarization of M1 macrophage, myeloid-specific HIF1α overexpression (Lysm HIF1α lsl) mice were employed and the bone marrow-derived and peritoneal macrophages were isolated. RT-PCR results revealed that HIF1α overexpression macrophage had a hyperinflammatory state characterized by the upregulation of M1 markers. Cellular bioenergetics analysis showed lower cellular oxygen consumption rates in the Lysm HIF1α lsl mice. Metabolomics studies showed that HIF1α overexpression led to increased glycolysis and pentose phosphate pathway intermediates. Further results revealed that macrophage M1 polarization, induced by HIF1α overexpression, was via upregulating the mRNA expression of the genes related to the glycolysis metabolism. Our results indicate that HIF1α promoted macrophage glycolysis metabolism, which induced M1 polarization in mice.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Postoperative delirium (POD) is a common postoperative complication that is relevant to poor outcomes. Therefore, it is critical to find effective methods to identify patients with high ...risk of POD rapidly. Creating a fully automated score based on an automated machine‐learning algorithm may be a method to predict the incidence of POD quickly.
Materials and methods
This is the secondary analysis of an observational study, including 531 surgical patients who underwent general anesthesia. The least absolute shrinkage and selection operator (LASSO) was used to screen essential features associated with POD. Finally, eight features (age, intraoperative blood loss, anesthesia duration, extubation time, intensive care unit ICU admission, mini‐mental state examination score MMSE, Charlson comorbidity index CCI, postoperative neutrophil‐to‐lymphocyte ratio NLR) were used to established models. Four models, logistic regression, random forest, extreme gradient boosted trees, and support vector machines, were built in a training set (70% of participants) and evaluated in the remaining testing sample (30% of participants). Multivariate logistic regression analysis was used to explore independent risk factors for POD further.
Results
Model 1 (logistic regression model) was found to outperform other classifier models in testing data (area under the curve AUC of 80.44%, 95% confidence interval CI 72.24%–88.64%) and achieve the lowest Brier Score as well. These variables including age (OR = 1.054, 95%CI: 1.017~1.093), extubation time (OR = 1.027, 95%CI: 1.012~1.044), ICU admission (OR = 2.238, 95%CI: 1.313~3.793), MMSE (OR = 0.929, 95%CI: 0.876~0.984), CCI (OR = 1.197, 95%CI: 1.038~1.384), and postoperative NLR (OR = 1.029, 95%CI: 1.002~1.057) were independent risk factors for POD in this study.
Conclusions
We have built and validated a high‐performing algorithm to demonstrate the extent to which patient risk changes of POD during the perioperative period, thus leading to a rational therapeutic choice.
The accumulation of multiple risk factors is critical for the occurrence of POD, and there is currently no single treatment.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Before traffic forecasting, it is usually necessary to aggregate the information by a certain length of time. An aggregation size that is too short will make the data unstable and cause the forecast ...result to be too biased. On the other hand, if the aggregation size is too large, the data information will be lost, resulting in the forecast results tending towards an average or slow response. With the development of intelligent transportation systems, especially the development of urban traffic control systems, high requirements are placed on the real-time accuracy of traffic forecasting. Therefore, it is an essential topic of traffic forecasting research to determine aggregation sizes. In this paper, the mutual information between the forecast input information and the forecast result and the sequence complexity of the forecast result measured by approximate entropy, sample entropy, and fuzzy entropy are considered; then, the optimal data aggregation size is given. To verify the proposed method, the validated data obtained from the simulation is aggregated and calculated with different aggregation sizes, then used for forecasting. By comparing the prediction performance of different aggregate sizes, the optimal aggregate size was found to reduce MSE by 14–30%. The results show that the method proposed in this paper is helpful for selecting the optimal data aggregation size in forecasting and can improve the performance of prediction.
Due to the high degree of weathering, the red clay slope has low anti-disintegration performance, and the clay easily becomes wet and disintegrates after soaking in water. It causes geological ...problems such as slope collapse caused by soil softening. To study the disintegration characteristics of modified red clay, the disintegration test of red clay modified by using lignin fiber, clay particles and lime was carried out, analyzing the disintegration characteristics of improved red clay from physical and chemical perspectives and analyzing the improvement mechanism of three modifiers with the scanning electron microscopy test. The analysis results show that the water-holding capacity and disintegration resistance of soil mixed with lignin fiber decrease; the disintegration time of reshaped red clay increases with the increase in clay content; and the average disintegration rate of the soil decreases with the increase in clay content. With the increase in lime content, the soil cement increases. The integrity of the soil is enhanced, and its anti-disintegration ability is improved; the saturated moisture content of reshaped red clay increases with the increase in lignin fiber and clay content, while the saturated moisture content of soil decreases with the increase in lime content. The damage analysis shows that the larger the damage factor of soil, the worse its anti-disintegration ability, and the easier the soil disintegrates. The purpose of this paper is to explore the essence of the soil disintegration phenomenon, and on this basis, using high-quality improved materials, to improve the soil, which easily disintegrates. This move aims to significantly enhance the anti-disintegration ability of the soil, thereby improving its resistance to softening and disintegration, thereby effectively improving and maintaining the ecological environment. At the same time, the improved soil will help to improve the utilization rate of the slope and foundation soil, thereby reducing the economic cost of maintenance engineering. Against the current background of sustainable economic, social, and ecological development, it is of great strategic significance to ensure the sustainable availability of land resources in specific areas and maintain their productivity and ecological stability for a long time. The research into this subject not only helps to deepen the understanding of soil disintegration, but also provides strong technical support for the rational utilization of land resources and the protection of the ecological environment.
In response to the current situation where general methods cannot effectively compensate for the phase delay of ordinary optical mixers, a multi-layer spatial beam-splitting optical mixer is designed ...using total reflection triangular prisms and polarization beam splittings (PBS). The phase delay is generated by the wave plate, and the mixer can use the existing parallel plates in the structure to individually compensate for the phase of the four output beams. A mixer model is established based on the structure, and the influence of the position and orientation of the optical components on the phase delay is analyzed. The feasibility of the phase compensation method is simulated and analyzed. The results show that the mixer can effectively compensate for the four outputs of the optical mixer over a wide range.
The mixer has a compact structure, good performance, and significant advantages in phase error control, production, and tuning, making it suitable for free-space coherent optical communication systems. KCI Citation Count: 0
A novel methodology toward the diversity-oriented asymmetric construction of densely functionalized isoxazole-dispirobisoxindoles was developed. This approach is distinguished by an organocatalytic ...stereo- and appealing β-regioselective 3 + 2 cycloaddition reaction of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles and 3-isothiocyanato oxindoles. Complex polycyclic oxindoles
3
featuring two different oxindole moieties and three contiguous stereocenters were smoothly afforded in up to 96% yield, 96% ee, and >20 : 1 dr. The described method, which is different from our previous work of α-regioselective asymmetric annulation of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles, is the first β-regioselective asymmetric annulation.
A novel methodology toward the diversity-oriented asymmetric construction of densely functionalized isoxazole-dispirobisoxindoles was developed.
In this paper, radiation patterns of a single‐layer microstrip antenna, which can be switched to operate under dual TM11 modes of a circular patch and a TM21 mode of a concentric annular shorted ring ...patch, is investigated and presented. Broadside and monopole‐like patterns under multi modes are combined to broaden the antenna main‐beam coverage. Besides, based on the current distributions of these modes, several slots are etched to realize antenna miniaturization. The miniaturized pattern reconfigurable antenna with a joint wide beam is applied to a dual‐polarized 5 × 5 planar array, which can scan its main beam from −60° to 60° in both orthogonal planes with a gain fluctuation less than 3 dB. In addition, the array is synthesized with the convex optimization approach to obtain low sidelobe level in its wide‐angle scanning range, validated by a full‐wave simulation study followed by the experimental verification.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Phosphatidylinostitol-3-kinase (PI3K) is the potential anticancer target in the PI3K/Akt/ mTOR pathway. Here we reviewed the ATP-competitive small molecule PI3K inhibitors in the past few years, ...including the pan Class I PI3K inhibitors, the isoform-specific PI3K inhibitors and/or the PI3K/mTOR dual inhibitors.
Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is involved in tumor cell growth process. However, its role and molecular mechanism in liver cancer is still not fully understood. In ...this study, we found that MALAT1 was significantly expressed in liver cancer cell lines. And knockdown of MALAT1 suppressed proliferation, migration and invasion of HepG2 cells, accompanied with decrease of Rho-associated coiled-coil-forming protein kinase 1 (ROCK1), α-smooth muscle actin (α-SMA), N-cadherin, Vimentin and TWIST. Significantly, MALAT1 deletion sensitized HepG2 cells to 5-FU-induced cell cycle arrest in G1 phase, as evidenced by the significant reduction in Cyclin D1 and CDK4 and increase in p53, p21 and p27 protein levels. In addition, MALAT1 knockdown triggered 5-FU induced apoptosis in HepG2 cells by inducing intrinsic apoptosis-related signals, including Cyto-c, Apaf-1, cleaved Caspase-9/-7/-3 and poly (ADP-ribose) polymerase (PARP). Furthermore, phosphorylated nuclear factor-κB (p-NF-κB) was also down-regulated by MALAT1 silence. Importantly, suppression of IKKα/NF-κB significantly elevated apoptosis and reduced liver cancer cell viability in MALAT1-knockdown cells with 5-FU incubation. The nude mice transplantation model also confirmed the promoted sensitivity of MALAT1-silenced HepG2 cells to 5-FU by blocking tumor cell proliferation and inducing apoptosis. Therefore, our data supplied a potential mechanism by which knockdown of MALAT1 might play an important role in augmenting sensitivity of HepG2 cells to 5-FU in therapeutic approaches, demonstrating suppressing of MALAT1 may serve as a combination with chemotherapeutic agents in liver cancer treatment.
•MALAT1 knockdown inhibits liver cancer cell proliferation.•MALAT1 silence enhances apoptosis and liver cancer cells sensibility to 5-FU incubation.•MALAT1 deficiency related increase in sensitivity of liver cancer cells was associated with regulation of NF-κB.•MALAT1 knockdown reduces tumor growth in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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