Pre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the ...pathogenesis of PE remains unknown.
We performed a case-control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation.
Patients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly
and
, were enriched, whereas beneficial bacteria, including
and
, were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria,
, and inflammatory cytokine levels were significantly increased.
This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.
Dysbiosis, departure of the gut microbiome from a healthy state, has been suggested to be a powerful biomarker of disease incidence and progression
. Diagnostic applications have been proposed for ...inflammatory bowel disease diagnosis and prognosis
, colorectal cancer prescreening
and therapeutic choices in melanoma
. Noninvasive sampling could facilitate large-scale public health applications, including early diagnosis and risk assessment in metabolic
and cardiovascular diseases
. To understand the generalizability of microbiota-based diagnostic models of metabolic disease, we characterized the gut microbiota of 7,009 individuals from 14 districts within 1 province in China. Among phenotypes, host location showed the strongest associations with microbiota variations. Microbiota-based metabolic disease models developed in one location failed when used elsewhere, suggesting that such models cannot be extrapolated. Interpolated models performed much better, especially in diseases with obvious microbiota-related characteristics. Interpolation efficiency decreased as geographic scale increased, indicating a need to build localized baseline and disease models to predict metabolic risks.
Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide ...concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions. CKD patients had higher percentages of opportunistic pathogens from gamma-Proteobacteria and reduced percentages of beneficial microbes, such as Roseburia, Coprococcus, and Ruminococcaceae. The PICRUSt analysis demonstrated that eight genes involved in choline, betaine, L-carnitine and trimethylamine (TMA) metabolism were changed in the CKD patients. Moreover, we transferred faecal samples from CKD patients and healthy controls into antibiotic-treated C57BL/6 mice and found that the mice that received gut microbes from the CKD patients had significantly higher plasma TMAO levels and different composition of gut microbiota than did the comparative mouse group. Our present study demonstrated that CKD patients had increased plasma TMAO levels due to contributions from both impaired renal functions and dysbiosis of the gut microbiota.
In the electronics industry, the efficient recovery and capture of sulfur hexafluoride (SF6) from SF6/N2 mixtures is of great importance. Herein, three metal–organic frameworks with fine‐tuning pore ...structures, Cu(peba)2, Ni(pba)2, and Ni(ina)2, were designed for SF6 capture. Among them, Ni(ina)2 has perfect pore sizes (6 Å) that are comparable to the kinetic diameter of sulfur hexafluoride (5.2 Å), affording the benchmark binding affinity for SF6 gas. Ni(ina)2 exhibits the highest SF6/N2 selectivity (375.1 at 298 K and 1 bar) and ultra‐high SF6 uptake capacity (53.5 cm3 g−1 at 298 K and 0.1 bar) at ambient conditions. The remarkable separation performance of Ni(ina)2 was verified by dynamic breakthrough experiments. Theoretical calculations and the SF6‐loaded single‐crystal structure provided critical insight into the adsorption/separation mechanism. This porous coordination network has the potential to be used in industrial applications.
The metal–organic framework (MOF) Ni(ina)2 has pore sizes (6 Å) that are perfectly compatible with the kinetic diameter of sulfur hexafluoride (5.2 Å), affording the benchmark binding affinity for this potent greenhouse gas that is used in the electronics industry.
Current automated structural topology design methods can only deal with limited design spaces or simplified architectural layouts for lack of data or a proper representation of structure topology. To ...address this, the abundant information of manually designed architectural and structural layouts should be exploited to guide the topology design. To achieve automatic generation of structural topologies according to real‐world architectural layouts, this research introduces StrucTopo‐generative adversarial network (GAN), an end‐to‐end generative model with node and edge generation stages based on proper graph representation. Nodes are generated using an image‐to‐image translation model, and edges are generated with a GAN‐based approach. The model is trained and tested on a dataset of 300 complex architectural and structural layouts. Measured against the manually designed topologies, the results indicate that the proposed model can generate reasonable structural topologies, with a recall of 97% and an intersection‐over‐union of 80% in node generation, with a precision of 92% and a recall of 91% in edge generation. Additionally, the joint generation shows a graph similarity of 72%. The proposed model is the first of its kind to consider complex architectural layout constraints in the generation of structural topology, marking a step forward in applying artificial intelligence to practical structural design.
•A test on a large-scale composite frame with wide floor slabs is conducted.•The effect of floor loads on the seismic behaviour of the frame is considered.•The weld fracture near exterior joints ...impacts the global performance greatly.•The effective slab width is 0.75 times column width with obvious shear lag effect.•Deformation characteristics and force mechanism under cyclic loading are discussed.
The steel–concrete composite frame systems are widely used in multistory and high-rise buildings owing to good mechanical performance and high construction efficiency. In previous research on the composite frame systems, many lateral cyclic tests were conducted on specimens with small-width floor slabs without floor loads, which could not precisely reflect the actual behaviour of composite frames in spatial multistory buildings. Therefore, this paper presents an experimental study on the seismic behaviour of composite frames with wide floor slabs considering the effect of floor loads. The specimen was a two-story two-span composite frame with the scale ratio of 0.5, and three load cases, including the vertical floor loading test, the lateral cyclic loading test and the pushover test, were respectively applied to investigate the mechanical performance of the composite frame. The slab crack development, mid-span deflection and strain distribution of slab reinforcements in the vertical floor loading test were discussed. The overall responses of the specimen in the lateral cyclic loading test and pushover test were analysed, including failure phenomena, load–displacement curves, strength and stiffness degradation, energy dissipation capacity and deformation characteristics. Moreover, the seismic performance of columns, beams, slabs and joints in the specimen was discussed in detail and the force mechanism of the composite frame was revealed based on the structural analysis of components. The results indicated that the specimen exhibited sufficient load-bearing capacity, good ductility, stable strength and stiffness degradation and excellent energy dissipation capacity under the combination of vertical floor loads and lateral loads. The welds at the bottom flange near the exterior joint fractured under cyclic loading, which was found to have significant influence on the deformation pattern and force mechanism of the composite frame. The shear lag effect was obvious in the wide floor slabs and the effective width of the slabs was estimated to be nearly 0.75 times the column width.
•The S-C–W-B criterion is inadequate for avoiding the column hinges in RC frames.•A biaxial bending strength model of RC columns under axial load is developed.•A biaxial overstrength factor is ...proposed to improve the S-C–W-B criterion.•The inelastic response of RC frames under biaxial seismic excitation is investigated.•The effect of the biaxial overstrength factor is validated by FEM analysis.
In several earthquakes, numerous reinforced concrete (RC) frames subjected to seismic excitation exhibit a collapse pattern characterised by column hinges, although these frames are designed according to the strong-column–weak-beam (S-C–W-B) criterion. The effect of biaxial seismic excitation on the disparity between the design and the actual performance of RC frames is investigated in this study. First, a modified load contour method was proposed to derive a closed-form equation of the biaxial bending moment strength, which was verified based on numerical and experimental results. Subsequently, a group of time-history analyses of a simple frame modelled using fibre beam-column elements subjected to biaxial seismic excitation were conducted to verify that the current S-C–W-B criterion is inadequate for preventing the occurrence of column hinges. A biaxial overstrength factor was developed based on the proposed equation, and the reinforcement of columns was appropriately amplified using this factor to prevent the occurrence of column hinges under biaxial excitation; this approach was proved to be effective through another group of time-history analyses. Thus, the findings of this study can serve as a basis for improving the seismic design of RC frames, which will enable the construction of safer engineering structures.
Over the last decades, the fabrication of 3D tissues has become commonplace in tissue engineering and regenerative medicine. However, conventional 3D biofabrication techniques such as scaffolding, ...microengineering, and fiber and cell sheet engineering are limited in their capacity to fabricate complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility to fabricate biomimetic, volumetric tissues that are structurally and functionally relevant. It enables precise control of the composition, spatial distribution, and architecture of resulting constructs facilitating the recapitulation of the delicate shapes and structures of targeted organs and tissues. This Review systematically covers the history of bioprinting and the most recent advances in instrumentation and methods. It then focuses on the requirements for bioinks and cells to achieve optimal fabrication of biomimetic constructs. Next, emerging evolutions and future directions of bioprinting are discussed, such as freeform, high‐resolution, multimaterial, and 4D bioprinting. Finally, the translational potential of bioprinting and bioprinted tissues of various categories are presented and the Review is concluded by exemplifying commercially available bioprinting platforms.
Recent advances in translating 3D bioprinting to the clinics are reviewed, including developments in bioprinting strategies, innovations in bioinks for bioprinting, advances in bioprinting of complex architectures, and the translational potential of bioprinted tissue‐like structures. Commercially available bioprinting platforms are briefly discussed toward the end.
Xanthine oxidase (XO) is a key enzyme in the generation and development of hyperuricemia. Thiazolidine-2-thione, a typical heterocyclic compound, have been widely used in the field of drug synthesis. ...In this study, a series of novel thiazolidine-2-thione derivatives were synthesized as XO inhibitors, and the XO inhibitory potencies of obtained compounds were evaluated by in vitro enzyme catalysis. The result shown that compound 6k behaved the strongest XO inhibitory activity with an IC50 value of 3.56 μmol/L, which was approximately 2.5-fold more potent than allopurinol. The structure-activity relationship revealed that the phenyl-sulfonamide group was indispensable for thiazolidine-2-thione derivatives to produce XO inhibitory activity. The enzyme inhibition kinetics analyses confirmed that compound 6k exerted a mixed-type XO inhibition. Additionally, the molecular docking results suggested that the 4-fluorophenyl-sulfonyl moiety could interact with Gly260 and Ile264 in the innermost part of the active pocket through 2 hydrogen bonds, while the thiazolidinethione moiety could form two hydrogen bonds with Glu263 and Ser347 in hydrophobic pockets. In summary, the results described above suggested that compound 6k could be a valuable lead compound for the treatment of hyperuricemia as a novel XO inhibitor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AbstractFour shear-critical RC shear walls were tested under a tension-bending-shear load to replicate seismic behavior of the bottom shear wall in high-rise buildings. The axial tension ratio ranged ...from 0 to 0.5 and the aspect ratio was 1.06. The shear compression failure mode was observed for each specimen, characterized by the formation of an inclined crack at 45° and direct strut action. The shear displacement was a dominant deformation component throughout the loading history. When the axial tension force increased from 0 to 1,293 kN, the ultimate drift ratio increased from 0.90% to 2.38%, while shear capacity linearly decreased from 1,507 to 895 kN. The load–displacement curve showed a significant pinching effect and strength degradation effect. In addition, this paper reports an innovative experimental method to obtain shear resistance of transverse reinforcement (Vs) based on the plasticity theory and strain measuring result. Test results using this method show that not all horizontal distributed rebar yield simultaneously at the ultimate capacity. The US code-specified shear strength contribution of horizontal distributed rebar was found to be unsafe for each test specimen. Finally, a database of RC shear walls subject to combined tension-bending-shear load was established to evaluate shear strength formulas in design codes. The comparison showed the Chinese code predicted spuriously higher tension-shear capacity, while the US code predicted conservative capacity. Based on the developed database, a simplified design formula is proposed with adequate safety concerns and accuracy.
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