Human induced pluripotent stem cell based hepatic-modeling of lipid metabolism associated TM6SF2 E167K variant.

BACKGROUND AND AIMS: TM6SF2 rs58542926 (E167K) is related to increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Conflicting mouse study results highlight the need for a human model to understand this mutation's impact. This study aims to create and characterize a reliable human in vitro model to mimic the effects of the TM6SF2-E167K mutation for future studies. APPROACH AND RESULTS: We used gene editing on human human-induced pluripotent stem cells (iPSC) from a healthy individual to create cells with the TM6SF2-E167K mutation. After hepatocyte directed differentiation, we observed decreased TM6SF2 protein expression, increased intracellular lipid droplets and total cholesterol in addition to reduced VLDL secretion. Transcriptomics revealed upregulation of genes involved in lipid, fatty acid, and cholesterol transport, flux, and oxidation. Global lipidomics showed increased lipid classes associated with ER stress, mitochondrial dysfunction, apoptosis, and lipid metabolism. Additionally, the TM6SF2-E167K mutation conferred a pro-inflammatory phenotype with signs of mitochondria and ER stress. Importantly, by facilitating protein folding within the ER of hepatocytes carrying TM6SF2-E167K mutation, VLDL secretion and ER stress markers improved. CONCLUSIONS: Our findings indicate that induced hepatocytes generated from iPSCs carrying the TM6SF2-E167K recapitulate the effects observed in human hepatocytes from individuals with the TM6SF2 mutation. This study characterizes an in vitro model that can be used as a platform to identify potential clinical targets and highlights the therapeutic potential of targeting protein misfolding to alleviate ER stress and mitigate the detrimental effects of the TM6SF2-E167K mutation on hepatic lipid metabolism.

Broadband tunable laser and infrared camouflage by wavelength-selective scattering metamaterial with radiative thermal management.

Metamaterial-based multispectral (including infrared and multiple lasers) camouflage compatible with non-atmospheric window radiative cooling is effective for low observability against multiple detection means. However, simultaneously achieving low reflectance in a non-atmospheric window band and broadband laser scattering, especially for a broadband tunable long-wave infrared laser, remains challenging. This Letter proposes a wavelength-selective scattering metamaterial (WSSM) that realizes effective camouflage for mid-wave infrared (MWIR), long-wave infrared (LWIR), broadband tunable LWIR and near-infrared (NIR) lasers. Moreover, the WSSM achieves radiative cooling in a non-atmospheric window (5-8 µm). The simulated emissivity is 0.19/0.20 in MWIR and LWIR bands, while it is 0.54 in a non-atmospheric window band that ensures radiative cooling. The WSSM also achieves low specular reflectance (4.35%) in 8-12 µm for broadband tunable laser camouflage, together with low reflectance at 1.06 µm and 1.55 µm. The thermal simulation is also conducted, demonstrating that the WSSM has a surface temperature decrement of 12.6°C compared to the conventional low-emissivity reference at the heated temperature of 400°C due to selective emission. The radiation temperatures have a reduction of 37%/64% than the real surface temperature in MWIR and LWIR bands. This work achieves the multispectral compatible camouflage by regulating specular reflection and scattering, providing a novel, to the best of our knowledge, approach for manipulating electromagnetic waves.

Synthesis of AuX (X = Ni, Ga, Mo, Zn, and Cr) Alloy Aerogels as High-Performance Electrocatalytic CO2 Reduction Reaction Catalysts.

Electrocatalytic CO2 reduction reaction (eCO2RR) into value-added chemicals is highly desirable to mitigate the global warming effect and energy crisis. Metal aerogels, as featured by a self-supporting structure, large specific surface area, outstanding conductivity, and a hierarchical porous structure, are ideal electrocatalysts in eCO2RR. Herein, we report a simple and general strategy for constructing a series of Au-based alloy aerogels which contain Au with another metal including Ga, Ni, Mo, Zn, and Cr, respectively. For the first time, the electrocatalytic activities of AuGa aerogels, AuNi aerogels, and AuMo aerogels for CO2RR were studied in detail. The resultant Au81Ga19 aerogel achieves a 95.2% Faradaic efficiency (FE) at -1.16 V versus reversible hydrogen (vs RHE) in H-cells. Impressively, a total 99.4% FE for C1 products (CO + HCOOH) with a current density of 100 mA cm-2 at -0.6 V vs RHE and a large current density of 228 mA cm-2 can be achieved at -0.9 V with a 72.3% FE for the C1 product in a flow cell. Electrochemical characterization and theoretical calculations further revealed that the outstanding performance of the Au-based aerogels was derived from the large specific surface area, abundant grain boundaries, low interfacial charge transfer resistance, and synergetic effect. Overall, this study provides a promising alternative to engineer alloy aerogel electrocatalysts for highly efficient CO2 electroreduction.

Study on the Evolution of Physical Parameters and Dynamic Compression Mechanical Properties of Granite after Different Heating and Cooling Cycles.

The study of the evolution law of basic physical parameters and dynamic compression performance of deep granite under the environment of the heating-cooling cycle is of great significance for the stability evaluation of deep underground engineering and the development of deep resources. In this study, heating-cooling cycle tests and dynamic compression tests were conducted on a large number of fine-grained granite specimens with heating temperatures from 200 to 600 °C and times from one to twenty times using a box-type high-temperature muffle furnace and Hopkinson pressure bar (SHPB) test system, and the evolution law of basic physical parameters and dynamic compression mechanical properties of fine-grained granite were studied using theoretical and fitting analysis. The test results showed that: the changes of the basic physical parameters of granite have obvious temperature effect; 600 °C is a threshold value for the changes of each physical parameter of granite; the sensitivity of each physical parameter to the number of heating and cooling cycles is small before 600 °C; and the sensitivity of each physical parameter to the number of heating and cooling cycles significantly increases at 600 °C. The dynamic compressive strength and elastic modulus of granite decreased with the increase in heating and cooling cycles, and the maximum decrease rate was 89.1% and 85.9%, respectively, and the strain rate linearly increased with the increase in heating and cooling cycles, and the maximum strain rate was 123 s-1. The temperature, the number of heating and cooling cycles, and the impact air pressure, all had significant effects on the damage mode and crushing degree of granite.

Wave Dissipation and Energy-Absorption Characteristics of Wave-Absorbing Metal Plates with Different Aperture Sizes and Thicknesses under True-Triaxial Static-Dynamic-Coupling Loading.

Deep rock masses exist in a complex environment with multi-field coupling; therefore, it is necessary to develop a true-triaxial static-dynamic-coupling loading test machine to explore their characteristics and mechanical response mechanism. To meet the test requirements of true-triaxial loading and strong disturbance, a wave-absorbing metal plate was selected as the boundary material between the granite and transmission end, and the modified SHPB was used to perform static-dynamic-coupling loading tests. In this study, two series of experiments on wave- absorbing metal plates were conducted, which were fixed aperture sizes with different thicknesses and fixed thicknesses with different aperture sizes. The static-dynamic-coupling loading tests on each aperture size and plate thickness were carried out under the condition of equal energy impact. The effects of the aperture size and plate thickness on the incident- and reflection-stress curves, reflectivity, energy consumption law, energy evolution, and other mechanical properties of the wave-absorbing metal plate materials were studied. The results show that the peak stress and reflectivity decrease with increasing aperture size and plate thickness, and the influence of the thickness is greater than that of the aperture size. The energy-absorption rate of the wave-absorbing metal plate increased with increasing thickness and aperture size and was maximized when the aperture size and thickness were 6-7 mm and 3-4 mm, respectively. The variation trend of the energy reflectance is opposite to that of the energy absorption and reaches a minimum when the aperture size is 6-7 mm and plate thickness is 3-4 mm. The energy transmittance of the wave-absorbing metal plate fluctuated in a stable range, but the variation range was less obvious compared to that of the energy-absorption rate.

The potential of endophytic fungi isolated from cucurbit plants for biocontrol of soilborne fungal diseases of cucumber.

The ability of endophytic fungi isolated from cucurbit plants to suppress soilborne diseases and the relationship between antagonism and disease suppression were studied. In dual culture tests of 1044 strains of 90 genera and three pathogenic fungi, 47.1 % of the endophytic fungal strains showed antagonistic effects on at least one pathogen; 186 strains against Rhizoctonia solani, 371 strains against Sclerotinia sclerotiorum, and 403 strains against Fusarium oxysporum f. sp. cucumerinum. The main antagonistic type of the strains of one genus generally was identical to one pathogen. In the pot experiment of cucumber inoculated with R. solani and endophytic fungi, 74.3 % and 33.3 % of 288 strains showed control efficacy of more than 50 % and more than 80 % on cucumber Rhizoctonia root rot respectively. These strains were mostly distributed in Fusarium, Chaetomium, Colletotrichum and Acrocalymma. There were some differences in the proportion of strains with better disease suppressive effects between strain sources. No significant correlation existed between the disease suppression of a strain in vivo and its antagonism against the pathogen in vitro. Most growth-promoting strains had good suppressive effects on cucumber Rhizoctonia root rot. In this study, 82 endophytic fungal strains had good disease suppressive effects and no obvious adverse effects on cucumber growth, and 35 of them showed obvious growth-promoting effects, which suggested that endophytic fungi from cucurbit plants have excellent potential for plant disease control.