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Abstract CSF1R is a receptor tyrosine kinase responsible for the growth/survival/polarization of macrophages and overexpressed in some AML patients. We hypothesized that a novel multi-kinase inhibitor (TKi), narazaciclib (HX301/ON123300), with high potency against CSF1R (IC50 ~ 0.285 nM), would have anti-AML effects. We tested this by confirming HX301’s high potency against CSF1R (IC50 ~ 0.285 nM), as well as other kinases, e.g. FLT3 (IC50 of ~ 19.77 nM) and CDK6 (0.53 nM). An in vitro proliferation assay showed that narazaciclib has a high growth inhibitory effect in cell cultures where CSF1R or mutant FLT3-ITD variants that may be proliferation drivers, including primary macrophages (IC50 of 72.5 nM) and a subset of AML lines (IC50

Study region: The Qinghai Lake basin on the Qinghai-Tibetan Plateau. Study focus: The abrupt rise of the water level of the Qinghai Lake after 2004 has garnered significant attention. Combining remote sensing and observed data, this study estimated the long-term variations in the water area and volume of the lake. In order to explore the factors contributing to the fluctuation in water level, the study developed annual and inter-annual water budgets for two time intervals: 1960 to 2004 and 2004 to 2020. Additionally, a hydrological model was implemented in the Buha River Basin, to gain further insight into the increased runoff and the impact of frozen soil. New hydrological insights for the region: The study found that the rise in lake level since 2004 was primarily driven by increased runoff, followed by increased precipitation, and decreased evaporation. Furthermore, water budgets were established for the freezing period (November to March of the next year) and the thawing period (April to October), respectively. The results revealed that the contribution of surface runoff during the thawing period was significantly larger at 68.20 % compared to 15.64 % during the freezing period, which is consistent to the conclusions of model simulation suggested. These findings suggest that the degradation of frozen soil in the Qinghai Lake Basin was a significant factor positively influencing surface runoff, with its impact intensifying after 2004.

Snow plays a crucial role in the global water and energy cycles, and its melting process can have a series of impacts on hydrological or climatic systems. Accurately capturing the timing of snowmelt runoff is essential for the utilization of snow resources and the early warning of snow-related disasters. A synthetic aperture radar (SAR) offers an effective means for capturing snowmelt runoff onset dates (RODs) over large areas, but its accuracy under different land cover types remains unclear. This study focuses on the Sierra Nevada Mountains and surrounding areas in the western United States. Using a total of 3117 Sentinel-1 images from 2017 to 2023, we extracted the annual ROD based on the Google Earth Engine (GEE) platform. The satellite extraction results were validated using the ROD derived from the snow water equivalent (SWE) data from 125 stations within the study area. The mean absolute errors (MAEs) for the four land cover types—tree cover, shrubland, grassland, and bare land—are 24, 18, 18, and 16 d, respectively. It indicates that vegetation significantly influences the accuracy of the ROD captured from Sentinel-1 data. Furthermore, we analyze the variation trends in the ROD from 2017 to 2023. The average ROD captured by the stations shows an advancing trend under different land cover types, while that derived from Sentinel-1 data only exhibits an advancing trend in bare land areas. It indicates that vegetation leads to a delayed trend in the ROD captured by using Sentinel-1 data, opposite to the results from the stations. Meanwhile, the variation trends of the average ROD captured by both methods are not significant (p > 0.05) due to the impact of the extreme snowfall in 2023. Finally, we analyze the influence of the SWE on RODs under different land cover types. A significant correlation (p < 0.05) is observed between the SWE and ROD captured from both stations and Sentinel-1 data. An increase in the SWE causes a delay in the ROD, with a greater delay rate in vegetated areas. These findings will provide vital reference for the accurate acquisition of the ROD and water resources management in the study area.

Nitrogen oxides (NOx) have long been the focus of air pollution control. Examining the spatial and driving characteristics of NOx emissions at the urban scale and from the supply-chain perspective is critical. Using the inventory method and the environmentally extended input–output analysis, energy-related NOx emissions of 90 cities in eastern China were calculated, and the spatial patterns and driving sectors of urban emissions were analyzed from both production- and consumption-based perspectives. The results show that the production-based emissions of eastern Chinese cities are substantially affected by their industrial structure and are higher in the north and lower in the south. The cities with higher consumption-based emissions are mainly those with large populations and relatively developed economies. Production-based NOx emissions per unit gross domestic product (GDP) are higher in the north and lower in the south, and emissions per unit area are generally higher in coastal areas and lower in inland areas. The emission intensities of 5 selected major urban agglomerations differ, due to the influences of industrial structure and population density. The consumption-based NOx emissions per capita are mainly affected by urban affluence and consumption patterns. The sectors that contribute most to the production-based emissions per unit GDP are mainly “mining and processing”, “petroleum, chemical and non-metallic mineral products”, “metal products”, “production and supply of electricity, natural gas and water” and “transportation, storage, and postal services”, while the sector that contributes most to the consumption-based emissions per capita is the construction industry. Emission reduction strategies are proposed for both consumption-oriented and production-oriented cities.

As a newly emerging organ transplantation technique, islet transplantation has shown the advantages of minimal trauma and high safety since it was first carried out. The proposal of the Edmonton protocol, which has been widely applied, was a breakthrough in this method. However, direct contact between islets and portal vein blood will cause a robust innate immune response leading to massive apoptosis of the graft, and macrophages play an essential role in the innate immune response. Therefore, therapeutic strategies targeting macrophages in the innate immune response have become a popular research topic in recent years. This paper will summarize and analyze recent research on strategies for regulating innate immunity, primarily focusing on macrophages, in the field of islet transplantation, including drug therapy, optimization of islet preparation process, islet engineering and Mesenchymal stem cells cotransplantation. We also expounded the heterogeneity, plasticity and activation mechanism of macrophages in islet transplantation, providing a theoretical basis for further research.

Vegetable production in Subtropical China is distinguished by excessive nitrogen (N) fertilization, frequent irrigation, and multiple crop rotations in a single year. The aforementioned variables are closely related to soil nitrous oxide (N2O) and methane (CH4) emissions. Hence, we conducted a field trial to measure N2O and CH4 emissions using static chamber–gas chromatograph. Four treatments were used: control (CK) with no fertilizer, 100% chemical N fertilization (CN), the conventional 30% chicken manure N plus 70%CN (CMN + CN), and 30% chicken manure biochar N plus 70%CN (CMBN + CN). The annual cumulative N2O emissions reached 12.4, 63.5, 111.8, and 44.1 kg N2O-N ha−1 for the CK, CN, CMN + CN, and CMBN + CN treatments, respectively. Compared to the CN and CMN + CN treatments, the CMBN + CN treatment reduced N2O emissions by 35.9%–65.7%, while it simultaneously increased the total vegetable yield by 16.1% compared to the CN treatment. Seven seasons mean N2O emission factors are 1.3% for CN, 3.8% for CMN + CN, and 0.9% for CMBN + CN. The CH4 emission was negligible, ranging from 0.07 kg CH4-C ha−1 for the CK treatment to 0.8 kg CH4-C ha−1 for the CN treatment. N2O emissions peaked under the conditions of an interior chamber temperature of around 31.9 °C and the water-filled pore space (WFPS) of the soil being approximately 60%. Future climate change will intensify, triggering higher N2O emissions from subtropical vegetable fields. CMB can be one of the best substitutes for direct chicken manure application as a soil supplement because it has a beneficial effect on improving vegetable yield and reducing N2O emissions in Subtropical China.

Physiologically, FoxA1 plays a key role in liver differentiation and development, and pathologically exhibits an oncogenic role in prostate and breast cancers. However, its role and upstream regulation in liver tumorigenesis remain unclear. Here, we demonstrate that FoxA1 acts as a tumor suppressor in liver cancer. Using a CRISPR-based kinome screening approach, noncanonical inflammatory kinase IKBKE has been identified to inhibit FoxA1 transcriptional activity. Notably, IKBKE directly binds to and phosphorylates FoxA1 to reduce its complex formation and DNA interaction, leading to elevated hepatocellular malignancies. Nonphosphorylated mimic Foxa1 knock-in mice markedly delay liver tumorigenesis in hydrodynamic transfection murine models, while phospho-mimic Foxa1 knock-in phenocopy Foxa1 knockout mice to exhibit developmental defects and liver inflammation. Notably, Ikbke knockout delays diethylnitrosamine (DEN)-induced mouse liver tumor development. Together, our findings not only reveal FoxA1 as a bona fide substrate and negative nuclear effector of IKBKE in hepatocellular carcinioma (HCC) but also provide a promising strategy to target IKBEK for HCC therapy. [ABSTRACT FROM AUTHOR]

In this paper, an open‐circuit fault‐tolerant topology of LC‐coupling hybrid active power filter (LC‐HAPF) and its control strategy are proposed at the switch level, which can greatly improve the reliability of the system. The proposed structure has a contactor between the midpoint of each bridge arm and the negative bus of the dc‐link capacitor. When a single‐phase fault occurs, the proposed LC‐HAPF can be reconstructed into a three‐phase four‐switch system to compensate for the harmonic and reactive power, while the power quality compensation effect is hardly affected. When a two‐phase fault occurs, the operation of the normal bridge arm is not affected, and the two faulty bridge arms can suppress harmonic current and compensate for a fixed reactive power through the passive filters. When the bridge arms all fail, the whole device acts as a passive filter to suppress the harmonic current of the load and to compensate for reactive power as well. Finally, the effectiveness of the proposed topology and its control strategy is verified by simulation and experiment results. In this paper, an open‐circuit fault‐tolerant topology of LC‐coupling hybrid active power filter (LC‐HAPF) and its control strategy are proposed at the switch level, which can greatly improve the reliability of the system. The proposed structure has a contactor between the midpoint of each bridge arm and the negative bus of the dc‐link capacitor. [ABSTRACT FROM AUTHOR]

The active components of turmeric oil (TO) were analyzed using gas chromatography-mass spectrometry (GC-MS), gas chromatography-ion mobility spectrometry (GC-IMS), and electronic nose. The major components of TO were found to be ar-curcumone (23.09%), curcumone (21.36%), and β-curcumone (14.93%). In order to maximize the stability of TO and to mask its irritating substances, a microemulsion encapsulating it (TO-ME) was constructed by the water titration method. Based on the pseudo ternary phase diagram constructed, the optimal process parameters were determined as follows: TO as the oil phase, Tween-80 as the surfactant, propylene glycol as the co-surfactant, deionized water as the aqueous phase, a mass ratio of surfactant to co-surfactant of 4:1, a mass ratio of mixed surfactant to oil phase of 8:2, and a water content of 70% in the microemulsion. The largest area of the microemulsion region was formed under these conditions. The resultant microemulsion had a pH of 6.81 ± 0.02, a density of (1.053 ± 0.001) g/mL, a polydispersity index (PDI) of 0.27 ± 0.11, and an average particle size of (32.81 ± 14.54) nm. The microemulsion was characterized as an oil-in-water (O/W) type microemulsion, with spherical or ellipsoidal droplets. The prepared TO-ME exhibited good centrifugal stability, storage stability, and resistance to oral and gastric digestion, and could be released and utilized in the intestine. The microemulsion system significantly improved the scavenging capacity of TO against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radical. In conclusion, microemulsion encapsulation significantly improved the stability and antioxidant activity of TO while effectively facilitating its release and digestion in the intestine. Our research results provide a theoretical basis for the high-value development and utilization of TO.

ABSTRACT: The decline in eggshell quality resulting from aging hens poses a threat to the financial benefits of the egg industry. The deterioration of eggshell quality with age can be attributed to changes in its ultrastructure and chemical composition. Specific matrix proteins in eggshells have a role in controlling crystal growth and regulating structural organization. However, the variations in ultrastructure and organic matrix of eggshells in aging hens remain poorly understood. This study assessed the physical traits, mechanical quality, chemical content, as well as the microstructural and nanostructural properties of eggs from Jing Tint 6 hens at 38, 58, 78, and 108 wk of age. Subsequently, a quantitative proteomic analysis was conducted to identify differences in protein abundance in eggshells between the ages of 38 and 108 wk. The results indicated a notable decline in shell thickness, breaking strength, index, fracture toughness, and stiffness in the 108-wk-age group compared to the other groups (P < 0.05). The ultrastructure variations primarily involved an increased ratio of the mammillary layer and a reduced thickness of the effective layer of eggshell in the 108-wk-age group (P < 0.05). However, no significant differences in eggshell compositions were observed among the various age groups (P > 0.05). Proteomic analysis revealed the identification of 76 differentially expressed proteins (DEPs) in the eggshells of the 38-wk-age group and 108-wk-age group, which comprised proteins associated with biomineralization, calcium ion binding, immunity, as well as protein synthesis and folding. The downregulation of ovocleidin-116, osteopontin, and calcium-ion-related proteins, together with the upregulation of ovalbumin, lysozyme C, and antimicrobial proteins, has the potential to influence the structural organization of the eggshell. Therefore, the deterioration of eggshell quality with age may be attributed to the alterations in ultrastructure and the abundance of matrix proteins.

Cold stress is an important limiting factor affecting spring tea quality. This study analyzed the effects of foliar spraying of brassinolide (BR) at concentrations of 0.05, 0.1, 0.5, and 1 mg/L on the chlorophyll index, nitrogen balance index, quality, antioxidant defense system, and secondary metabolite profiles in leaves of Camellia sinensis cv. Fuding-dabaicha grown at 4 °C for 48 h. All exogenous BR treatments significantly increased leaf nitrogen balance index, with the highest effect at 0.1 mg/L, which also significantly increased leaf chlorophyll index. BR treatments distinctly increased tea polyphenol, catechin, amino acid, and caffeine levels at cold stress, with the greatest effect at 0.1 mg BR/L. Foliar spraying of BR showed no effect on the expression of CsGOGAT at cold stress, but it differentially regulated the expression of CsHMGR, CsGDH, and CsGs, accompanied by their expression being up-regulated under 0.1 mg BR/L treatment. BR-treated plants exhibited a low level of oxidative damage at cold stress based on malondialdehyde levels, which was associated with higher glutathione levels and CsCAT and CsSOD gene expression levels under BR concentrations of 0.05 mg/L and 0.1 mg/L. Non-targeted metabolomics found a total of 26,175 metabolites, the majority of which were lipids and lipid-like molecules (8.97%) and organic heterocyclic compounds (8.97%). BR treatments with 0.05, 0.1, 0.5, and 1 mg/L triggered 1181, 1997, 2414, and 1455 differential metabolites, respectively, accompanied by more differential metabolites being up-regulated. Among them, 18 differential metabolites were associated with tea quality. The enriched pathways of differential metabolites were mainly caffeine metabolism, amino acid synthesis and metabolism, alkaloid synthesis and metabolism, and flavonoid synthesis, depending on the BR concentrations used. Caffeine metabolism was an BR-inducible differential metabolite pathway. Taken together, foliar spraying of BR (0.1 mg/L) improved leaf antioxidant capacity and quality as well as modulated secondary metabolites and their pathways in cold-stressed tea.