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Amino acid metabolic remodeling is a hallmark of cancer, driving an increased nutritional demand for amino acids. Amino acids are pivotal for energetic regulation, biosynthetic support, and homeostatic maintenance to stimulate cancer progression. However, the role of phenylalanine in multiple myeloma (MM) remains unknown. Here, we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow (BM) cells. After the treatment, phenylalanine levels increase in plasma and decrease in BM. This suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM progression. The requirement for phenylalanine by MM cells exhibits a similar pattern. Inhibiting phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib (BTZ) treatment in vitro and murine models. Mechanistically, phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3–CHOP–DR5 pathway. Interference with ATF3 significantly affects phenylalanine deprivation therapy. In conclusion, we have identified phenylalanine metabolism as a characteristic feature of MM metabolic remodeling. Phenylalanine is necessary for MM proliferation, and its aberrant demand highlights the importance of low-phenylalanine diets as an adjuvant treatment for MM.

Temporal interference electrical neurostimulation (TI) is a relatively new method of non-invasive neurostimulation that may be able to stimulate deep brain regions without stimulating the overlying superficial regions. Although some recent studies have demonstrated the success of TI in modulating task-induced BOLD activity in humans, there is limited information on intended and off-target effects of TI during resting-state. We simultaneously performed TI stimulation with the set-up optimized for maximum focality in the left caudate and collected resting-state fMRI data to investigate the effects of TI on human BOLD signals. We found increased BOLD activation in a part of the mid-orbitofrontal cortex (OFC) and parahippocampal gyrus. Results indicate that TI can induce increased BOLD activation in the region that receives the highest magnitude of TI amplitude modulation in humans, with good safety and tolerability profiles. We also show the limits of spatial precision and explore the nature and causes of additional off-target effects. TI may be a promising approach for addressing questions about the causal role of deep brain structures in human cognition and may also afford new clinical treatments.

This research investigates the ecological impacts of heavy metals in downstream river sediments with a focus on carbon emission efficiency in agriculture under the environmental regulation context. In this study, thirty sediment samples have been taken from the downstream region of the Shichuanhe River located in Xi'an, Shaanxi province, China, to analyze the availability of heavy metals. The results show that there are high ecological impacts in relation to the heavy metals and that impacts the carbon emission efficiency in agriculture directly. The analysis has also found the importance of significant environmental regulations in the management of such risks. This research has offered a unique angle on the relationship between heavy metal pollution and agricultural carbon release and has given important information on the improvement of environmental control measures. The implications highlight the need for the implementation of measures to enhance the policies that will help to prevent the ecological threats that are connected with heavy metals in the agricultural areas and, thus, improve the management of the environment.

Abstract Here, based on thin film integrated passive device (TF‐IPD) technology, compact ultra‐wideband (UWB) bandpass filter (BPF) and dual‐band bandpass filter (DBBPF) with equal inductance configuration are proposed. The configuration of equal inductance in a circuit contributes to reducing variables, simplifying the physical structure, and shortening the debugging time in the TF‐IPD design process. Despite all the inductors being equal in value, a wide passband can still be achieved. The measured results show that the centre frequency of UBW BPF is 11.43 GHz, and the 3‐dB fractional bandwidth (FBW) is 133% (3.87–18.99 GHz). And the 3‐dB FBWs of DBBPF centred at 6.5 GHz and 16.2 GHz are 92% (3.51–9.49 GHz) and 35% (13.33–18.98 GHz), respectively. The stopband of UBW BPF and DBBPF can be extended to 47.7 GHz and 44.8 GHz in sizes of 321 µm × 856 µm and 235 µm × 846 µm, respectively (excluding measuring pads).

Abstract A flexible smart coating with electroluminescence effect was designed and fabricated on the surface of gas insulated switch gear (GIS)/gas insulated transmission line (GIL) epoxy insulators based on two‐step curing process. As the AC voltage increases, the luminous area on the insulator surface expands from the centre to the periphery, and the light intensity shows a linear relationship with the applied voltage. Besides, the flexible smart coating can effectively identify the location of metal particle defects and the degree of electric field distortion. The flexible smart coating enhances the surface flashover voltage due to its higher dielectric constant. Simultaneously, metal particle contamination can substantially reduce the insulation performance of epoxy insulators, particularly when they are located near the high‐voltage side. It is hoped that this study can provide a reference for the smart detection of surface defects GIS/GIL basin insulators.

In order to study the Brazilian splitting characteristics of the frozen stone mixture under the coupling effect of freezing temperature and size effect, Brazilian splitting experiments were conducted on 5-10, 10-15, 15-20, and 5-20 mm particle size frozen soil-rock mixture samples after freezing at −10, −15, −20, −25, −30, −35, and −40 ℃ to investigate the effects of freezing temperature and different particle sizes on the splitting tensile strength of the samples. The effects of freezing temperature and different particle sizes on the splitting tensile strength of the samples were investigated, and the strain field evolution of the frozen soil-rock mixture during the Brazilian splitting experiments was further reproduced by digital imagine correlation (DIC). The experimental results show that the tensile strain is concentrated in the sample center with initial crack produced and the splitting damage pattern of the samples is curved and folded, and the larger the particle size is, the more curved the crack is; frozen soil-rock mixture goes through the linear elastic deformation stage when it breaks, and goes through the plastic-brittle damage stage with the increase of tensile stress and the decrease of freezing temperature; the splitting tensile strength has strong temperature sensitivity and increases approximately linearly with the decrease of freezing temperature; the size effect leads to the variability of sample strength, and the splitting tensile strengths are in the order of 5-10, 5-20, 10-15, and 15-20 mm particle size samples.

Strong impact does serious harm to the military industries so it is necessary to choose reasonable cushioning material and design effective buffers to prevent the impact of equipment. Based on the capillary property entangled porous metallic wire materials (EPMWM), this paper designed a composite buffer which uses EPMWM and viscous fluid as cushioning materials under the low-speed impact of the recoil force device of weapon equipment (such as artillery, mortar, etc.). Combined with the capillary model, porosity, hydraulic diameter, maximum pore diameter and pore distribution were used to characterize the pore structure characteristics of EPMWM. The calculation model of the damping force of the composite buffer was established. The low-speed impact test of the composite buffer was conducted. The parameters of the buffer under low-speed impact were identified according to the model, and the nonlinear model of damping force was obtained. The test results show that the composite buffer with EPMWM and viscous fluid can absorb the impact energy from the recoil movement effectively, and provide a new method for the buffer design of weapon equipment (such as artillery, mortar, etc.).

The PD-1/PD-L1 pathway is considered as one of the most promising immune checkpoints in tumour immunotherapy. However, researchers are faced with the inherent limitations of antibodies, driving them to pursue PD-L1 small molecule inhibitors. Virtual screening followed by experimental validation is a proven approach to discover active compounds. In this study, we employed multistage virtual screening methods to screen multiple compound databases to predict new PD-1/PD-L1 ligands. 35 compounds were proposed by combined analysis of fitness scores, interaction pattern and MM-GBSA binding affinities. Enzymatic assay confirmed that 10 out of 35 ligands were potential PD-L1 inhibitors, with inhibitory rate higher than 50% at the concentration of 30 µM. Among them, ZDS20 was identified as the most effective inhibitor with low micromolar activity (IC50 = 3.27 μM). Altogether, ZDS20 carrying novel scaffold was identified and could serve as a lead for the development of new classes of PD-L1 inhibitors.

According to Milankovitch’s theory, periodic climate change in Earth’s history is controlled by the periodic changes in the Earth’s orbit and axis of rotation. Milankovitch cycle include eccentricity, obliquity, and precession cycles. In addition to them, there are also some amplitude modulation (AM) cycles that affect the climate system through a series of “nonlinear” feedback processes, such as the 173 kyr obliquity AM cycle. Previous studies have demonstrated that the ∼170 kyr cycle modulate the paleoclimate and carbon cycle at mid-high latitude regions in the Meso-Cenozoic. However, due to the limitation of astronomical solutions and the lack of high-resolution geological records, the ∼170 kyr cycle has been less reported in the Paleozoic Era. In this study, cyclostratigraphic analysis of natural gamma ray (GR) logging data from four wells (Ji30, Ji31, Ji32, and Ji174) and total organic carbon (TOC) data from well Ji174 penetrating the Early Permian Lucaogou Formation in Jimusar Sag, Junggar Basin suggests preservation of eccentricity, obliquity, and precession cycles, and the ∼170 kyr AM cycle. Through the astronomical tuning of GR logging data obtained from four wells to eccentricity target cycles, we established the floating astronomical time scale (ATS). The results indicate an average sedimentation rate ranging from 7.4 to 9.5 cm/kyr and a duration from 2.8 to 3.2 million years (Myr) for the Lucaogou Formation. The differences in sedimentation rate and duration among these four wells may result from different well locations. Moreover, the ∼170 kyr cycle signal has been identified in the detrended GR logging and TOC data series, and its obliquity AM series. This signal might be attributed to the obliquity AM cycles originated from the interaction between s3 and s6 (s3 and s6 represent the precession of nodes of Earth and Saturn), which was recorded in the GR logging and TOC data time series due to nonlinear responses within the depositional system.