The epithelial tight junctions of intestine were impaired in murine model of type 2 diabetes mellitus (T2DM). The aim of this work was to investigate the alteration of intestinal barrier in T2DM ...patients.
90 patients with T2DM and 28 healthy controls were recruited. Serum lipopolysaccharide (LPS), Zonulin, and intestinal fatty acid binding protein (IFABP) were measured by ELISA, based on which a derived permeability risk score (PRS) was calculated. Subgroup analyses were conducted based on the glycemic control (HbA1c < 7%, or HbA1c ≥ 7%), the amount of chronic diabetic complications, and the use of aspirin at the time.
Serum LPS, Zonulin, and IFABP, and PRS of T2DM group were significantly higher than those of the control group (p < 0.05 for all). Serum LPS and PRS was higher in T2DM patients with poor glycemic control (both p < 0.05). Patients with more chronic complications of diabetes had higher serum LPS and IFABP, and PRS (all p < 0.05). No differences were found in these serum markers between T2DM patients being treated with aspirin or not.
Intestinal barrier function was impaired in T2DM patients. Poor glycemic control and more chronic complications of diabetes were associated with worse intestinal barrier function. Treatment with aspirin did not aggravate the impairment of intestinal barrier in T2DM patients.
•Intestinal barrier function was impaired in patients with type 2 diabetes.•Poor glycemic control was associated with worse intestinal barrier function.•Aspirin did not aggravate the impairment of intestinal barrier in type 2 diabetes.
Observations from the Michelson Interferometer for Global High‐Resolution Thermospheric Imaging onboard the Ionospheric Connection Explorer spacecraft are used to study the response of OI630.0 and ...OI557.7 nm dayglow to a moderate geomagnetic storm on 27 August 2021. The storm reaches a minimum Dst index of −82 nT, significantly impacting the dayglow within the latitudinal range of approximately 20°N–42°N, where the dayglow observations are of good quality. During the geomagnetic storm, the OI630.0 dayglow intensity slightly increases, while the peak volume emission rate (VER) decreases, and the peak height rises noticeably. The F‐layer intensity, peak VER, and the entire‐layer intensity of OI557.7 dayglow decrease significantly. The rise in peak height is not noticeable for the OI557.7 dayglow. The VERs of the both dayglow emissions respond differently to the geomagnetic storm at different altitudes. The OI630.0 dayglow layer as a whole extends upward and rises in altitude. For dayglow averaged above 35°N, the OI630.0 dayglow VER increases above approximately 225 km but decreases below this altitude. The largest increase occurs near 300 km, reaching approximately 82.8%, while the largest decrease occurs around 160 km, reaching about −22.0%. The OI630.0 dayglow intensity increases by approximately 6.3%, the peak VER decreases by about −8.0%, and the peak height rises by approximately 16.3 km, corresponding to a 7.8% increase. The F‐layer intensity, peak VER, and the entire‐layer intensity of OI557.7 dayglow decrease by approximately −27.5%, −32.4% and −17.4%, respectively. The response of the dayglow also depends on longitude and is accompanied by a southward meridional wind.
Plain Language Summary
The atomic oxygen dayglow emissions at 630.0 and 557.7 nm are the brightest airglows in the upper atmosphere and important subjects of research. They indicate the connection between the thermosphere and ionosphere as they are influenced by both plasma and neutral species. Understanding this connection is crucial for studying the effects of space weather. During geomagnetic storms, increased Joule heating and particle heating in the polar regions cause the expansion of the upper atmosphere. This interaction disrupts the ionosphere, affecting the 630.0 and 557.7 nm airglows. The Michelson Interferometer for Global High‐Resolution Thermospheric Imaging onboard the Ionospheric Connection Explorer simultaneously gathers data from both dayglow emissions without the need for duty cycling or scanning. This study examined the response of both dayglow to a moderate geomagnetic storm on 27 August 2021. The results enhance our understanding of thermosphere‐ionosphere coupling and space weather impacts.
Key Points
The OI630.0 dayglow emission layer moves and extends upward during the geomagnetic storm
The OI630.0 dayglow emission response varies with altitude, increasing above ∼225 km and decreasing below it
Both OI630.0 and OI557.7 dayglow responses depend on longitude, maximizing in the longitude sector around 70°W during this storm
Compared to bulk metal–organic framework (MOF), 2D MOF nanosheets have gained intensive research attention due to their ultrathin thickness and large surface area with highly accessible active sites. ...However, structural deterioration and morphological damage have impeded producing high‐quality MOF nanosheets during exfoliation. Here, first a new layered bulk MOF ZSB‐1 is synthesized and several solvents such as isopropanol, methanol, n‐hexyl alcohol, and N,N‐dimethylformamide are surveyed to examine their performance for the exfoliation of layered ZSB‐1. As a result, a highly solvent‐stable metal–organic framework rectangular nanosheet retaining undamaged morphology is obtained by the soft‐physical method in n‐hexyl alcohol. Theoretical simulations reveal that the strong interaction energy between n‐hexyl alcohol and MOF layers is responsible for the best exfoliation performance of making the bulk MOF into nanosheets. In addition, ZSB‐1 shows a tunable fluorescence peak position, fluorescent lifetime, and quantum yield by simply changing the solvent and morphology. Besides, the ZSB‐1 was selected as a fluorescence sensor to detect metal ions, and ZSB‐1 nanosheet exhibits excellent sensing ability for Fe3+. It is worth noting that the ZSB‐1 nanosheet has better detection limit performance of 0.054 × 10−6
m than that of its bulk counterpart.
A highly solvent‐stable metal–organic framework (MOF) nanosheet retaining undamaged morphology and structural integrity is obtained. Theoretical simulations reveal that the strong interaction energy between solvent and MOF layers is responsible to the best exfoliation performance of making bulk MOF into nanosheets. This work provides a 2D MOF fluorescence sensor with tunable luminescent property by simply changing the solvent and morphology.
Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily ...Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved.
Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations.
The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose:
Statistical model based iterative reconstruction (MBIR) methods have been introduced to clinical CT systems and are being used in some clinical diagnostic applications. The purpose of this ...paper is to experimentally assess the unique spatial resolution characteristics of this nonlinear reconstruction method and identify its potential impact on the detectabilities and the associated radiation dose levels for specific imaging tasks.
Methods:
The thoracic section of a pediatric phantom was repeatedly scanned 50 or 100 times using a 64‐slice clinical CT scanner at four different dose levels CTDIvol =4, 8, 12, 16 (mGy). Both filtered backprojection (FBP) and MBIR (Veo®, GE Healthcare, Waukesha, WI) were used for image reconstruction and results were compared with one another. Eight test objects in the phantom with contrast levels ranging from 13 to 1710 HU were used to assess spatial resolution. The axial spatial resolution was quantified with the point spread function (PSF), while the z resolution was quantified with the slice sensitivity profile. Both were measured locally on the test objects and in the image domain. The dependence of spatial resolution on contrast and dose levels was studied. The study also features a systematic investigation of the potential trade‐off between spatial resolution and locally defined noise and their joint impact on the overall image quality, which was quantified by the image domain‐based channelized Hotelling observer (CHO) detectability index d′.
Results:
(1) The axial spatial resolution of MBIR depends on both radiation dose level and image contrast level, whereas it is supposedly independent of these two factors in FBP. The axial spatial resolution of MBIR always improved with an increasing radiation dose level and/or contrast level. (2) The axial spatial resolution of MBIR became equivalent to that of FBP at some transitional contrast level, above which MBIR demonstrated superior spatial resolution than FBP (and vice versa); the value of this transitional contrast highly depended on the dose level. (3) The PSFs of MBIR could be approximated as Gaussian functions with reasonably good accuracy. (4) Thez resolution of MBIR showed similar contrast and dose dependence. (5) Noise standard deviation assessed on the edges of objects demonstrated a trade‐off with spatial resolution in MBIR. (5) When both spatial resolution and image noise were considered using the CHO analysis, MBIR led to significant improvement in the overall CT image quality for both high and low contrast detection tasks at both standard and low dose levels.
Conclusions:
Due to the intrinsic nonlinearity of the MBIR method, many well‐known CT spatial resolution and noise properties have been modified. In particular, dose dependence and contrast dependence have been introduced to the spatial resolution of CT images by MBIR. The method has also introduced some novel noise‐resolution trade‐off not seen in traditional CT images. While the benefits of MBIR regarding the overall image quality, as demonstrated in this work, are significant, the optimal use of this method in clinical practice demands a thorough understanding of its unique physical characteristics.
Objective
Induction of secondary necrosis/pyroptosis contributes to the toxicity of chemotherapeutic drugs, in which gasdermin E (GSDME) plays critical roles. This study aimed to explore whether ...GSDME is involved in mediating the cytotoxic effects of cisplatin and doxorubicin on mouse macrophages.
Methods
RAW 264.7 cells and bone marrow‐derived macrophages (BMDMs) were treated with cisplatin or doxorubicin. Propidium iodide staining was used to assay necrosis, and immunoblotting was performed to detect protein expression. GSDME was knocked down by using small interfering RNA. Mice were injected intraperitoneally to evaluate toxicity to macrophages in vivo. Flow cytometry and immunofluorescence microscopy were adopted to analyse phenotypes of peritoneal cells. Cytokine levels were assayed by cytometric bead array.
Results
Both cisplatin and doxorubicin dose‐dependently induced necrosis in mouse RAW 264.7 macrophages and BMDMs. Accompanying this, multiple caspases were activated, concomitant with the cleavage of poly (ADP‐ribose) polymerase. Consistent with caspase‐3 activation, GSDME was cleaved to generate its N‐terminal fragment (GSDME‐NT), thus leading to secondary necrosis/pyroptosis. Inhibition of caspase‐3 significantly attenuated the generation of GSDME‐NT concurrently with decreased necrosis in macrophages. GSDME knockdown also evidently decreased the necrosis in RAW 264.7 and BMDMs. Besides, cisplatin administration depleted peritoneal macrophages in mice, which was associated with caspase‐3 activation and GSDME‐NT generation. Consistent with the macrophage depletion, cisplatin administration significantly decreased survival of mice with bacterial infection.
Conclusion
Chemotherapeutic cisplatin and doxorubicin exerted their cytotoxicity on macrophages partly by inducing caspase‐3/GSDME‐mediated secondary necrosis.
•Tree peony cultivars can be also used as new edible oil resources.•The dominant compounds in tree peony oil were ALA, LA, OA, PA and SA.•Sixty cultivars were classified into six clusters by ...hierarchical cluster analysis.•Seeds from different cultivars could be mixed in practical production.
Seeds from Paeonia ostii and Paeoniarockii have been recently identified as novel resources of α-linolenic acid (ALA) in China. To assess whether tree peony cultivars can be used as oil resource, fatty acids (FAs) in 60 cultivars were monitored and evaluated in this study. The results indicated that the composition and content of FAs varied dramatically among different cultivars, in which ALA, linoleic acid, oleic acid, palmitic acid, and stearic acid were the dominant. The 60 cultivars were classified into six clusters by hierarchical cluster analysis, and they were quite distinct from each other. Finally, six cultivars with high yield and high quality were screened out, comprising of ‘Liuliguanzhu’, ‘Hongguanyupei’, ‘LSS-2’, ‘LSS-1’, ‘Jingshenhuanfa’ and ‘LSS-11’. These cultivars were appropriately applied in practical oil production. Overall, tree peony oil with abundant unsaturated fatty acids especially ALA was proved to be a top-grade source for edible oil and nutritional supplements.
NiSe@NiOOH core–shell hyacinth-like nanostructures supported on nickel foam (NF) have been successfully synthesized by a facile solvothermal selenization and subsequent in situ electrochemical ...oxidation (ISEO). First, the unique NiSe/NF nanopillar arrays were prepared in N,N-dimethylformamide (DMF) as a precursor template that can provide a large surface area, excellent conductivity, and robust support. Next, amorphous NiOOH covering the surface of NiSe nanopillars was fabricated by ISEO, as confirmed by XPS andEDX spectroscopy. SEM images revealed the hyacinth-like morphology of NiSe@NiOOH/NF with NiOOH as the shell and NiSe as the core. The electrochemical performance of NiSe@NiOOH/NF for the oxygen evolution reaction (OER) was investigated. NiSe@NiOOH/NF demonstrates an obviously enhanced OER activity with much lower overpotential of 332 mV at 50 mA cm–2 compared to other Ni-based electrocatalysts. The low charge-transfer resistance (R ct), large electrochemical double-layer capacitance (C dl) of electrochemically active surface areas (ECSAs), and excellent long-term stability of NiSe@NiOOH/NF confirm the enhancement of its electrochemical performance for the OER, which can be ascribed to the large amount of active sites derived from the amorphous NiOOH shell and the good conductivity and stability derived from the NiSe core. In addition, the synergistic effect between the NiSe core and NiOOH shell could serve for a highly efficient OER electrocatalyst.
Disintegration of aerobic granular sludge (AGS) is a challenging issue in the long-term operation of an AGS system. Chemical oxygen demand (COD)-to-nitrogen (N) ratio (COD/N), often variable in ...industrial wastewaters, could be a destabilizing factor causing granule disintegration. This study investigates the impact of this ratio on AGS disintegration and identifies the key causes, through close monitoring of AGS changes in its physical and chemical characteristics, microbial community and treatment performance. For specific comparison, two lab-scale air-lift type sequencing batch reactors, one for aerobic granular and the other for flocculent sludge, were operated in parallel with three COD/N ratios (4, 2, 1) applied in the influent of each reactor. The decreased COD/N ratios of 2 and 1 strongly influenced the stability of AGS with regard to physical properties and nitrification efficiency, leading to AGS disintegration when the ratio was decreased to 1. Comparatively the flocculent sludge maintained relatively stable structure and nitrification efficiency under all tested COD/N ratios. The lowest COD/N ratio resulted in a large microbial community shift and extracellular polymeric substances (EPS) reduction in both flocculent and granular sludges. The disintegration of AGS was associated with two possible causes: 1) reduction in net tyrosine production in the EPS and 2) a major microbial community shift including reduction in filamentous bacteria leading to the collapse of granule structure.
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•Impact of variable COD/N ratio on granule stability assessed and compared to flocs.•Decreasing COD/N ratio caused granule disintegration and treatment deterioration.•Flocs showed better stability and treatment performance under varying COD/N.•Desirable granule properties were closely associated with tyrosine-like EPS.•Major microbial shift observed with decreasing COD/N, especially from 2 to 1.
Tau, an important pathological protein of Alzheimer's disease (AD), can mediate the toxicity of amyloid β (Aβ). Thus, reduction of Tau with chemical molecules may offer a novel strategy for treating ...AD. Here, we designed and synthesized a series of multifunctional molecules that contained Tau-recognition moieties and E3 ligase-binding moieties to enhance Tau degradation. Among these molecules, TH006 had the highest activity of inducing Tau degradation by increasing its poly-ubiquitination. The decrement in Tau induced by TH006 could decrease the cytotoxicity caused by Aβ. Furthermore, TH006 could regulate the Tau level in the brain of an AD mouse model. Therefore, partial reduction of Tau with such multifunctional peptides may open up a novel therapeutic strategy for AD treatment.
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•Synthesized multifunctional PROTACs peptide TH006 effectively induces Tau degradation•TH006 increases poly-ubiquitination of Tau depending on VHL E3 ligase•Decrement of Tau induced by TH006 reduces the cytotoxicity caused by Aβ•TH006 can promote Tau reduction in primary neuron cells and 3xTg-AD mice
Tau, involved in Alzheimer's disease, is an intrinsically disordered protein which is difficult to be regulated. Chu et al. design and synthesize a multifunctional PROTACs peptide, TH006, to induce intracellular Tau degraded by increasing its poly-ubiquitination. Partial reduction of Tau induced by TH006 prevents cytotoxicity caused by Aβ.
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