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While Candida albicans alcohol dehydrogenase I (Adh1) conventionally functions as an alcohol dehydrogenase, this study builds upon previous work to redefine its novel role in regulating hyphal morphogenesis and elucidates the underlying mechanisms. Adh1 knockout strains exhibited hyperfilamentation, suggesting that Adh1 directly regulates true hyphal development, independent of its canonical metabolic activity. Leveraging this phenotype, a ‘reverse screening strategy’ identified 2‐hydroxyanthraquinone (HAQ) through high‐throughput screening as a potent inhibitor of biofilm formation and hyphal growth by targeting Adh1. Biochemical and structural analyses confirmed HAQ's direct binding to Adh1's F224/A254/Q257 interface. Mechanistically, affinity purification‐mass spectrometry revealed Adh1 modulates the SNF1 signalling axis by accelerating SNF1 dephosphorylation via interactions with Bmh1/Ssb1 regulators, thereby inhibiting hyphal conversion. HAQ disrupted these interactions, reducing SNF1 phosphorylation levels in an Adh1‐dependent manner. This work establishes Adh1 as both an endogenous SNF1 pathway suppressor and an exogenous drug target, while demonstrating the efficacy of phenotype‐driven discovery pipelines. The findings provide a novel antifungal strategy targeting virulence‐regulating metabolic enzymes and validate HAQ as a lead compound for therapeutic development against C. albicans pathogenicity. Based on the ADH1 knockout strain, HAQ was identified through forward/reverse genetic screening of 114 natural products and analysis of protein ligand and protein–protein interactions. With the help of HAQ, a new mechanism for regulating the phosphorylation level of Adh1–SNF1 has been revealed, in which HAQ binds to Adh1 to release dephosphorylation factors Bmh1 and Ssb1, thereby reducing the phosphorylation level of SNF1 and inhibiting hyphal growth.

Targeted cancer drug therapy has emerged as a critical treatment modality for advanced hepatocellular carcinoma (HCC). The discovery and development of novel anti-HCC drug therapeutics with improved pharmacological properties remains an urgent priority in oncology drug discovery. In this study, we designed and synthesised a new series of 1,2,3-triazole-cored structures incorporating aryl urea. Fifteen analogs were prepared nucleophilic addition and copper-catalyzed azide-alkyne cycloaddition (CuAAC) with excellent yields. These synthesised compounds were evaluated for their potential antitumor activities. Notably, compounds and exhibited the lowest IC values (10.80 ± 0.14 and 11.62 ± 3.72 μM) against HuH-7 cells. Further investigations suggested compound and induced cell apoptosis, stimulated DNA damage, and autophagy against HuH-7 cells. Acute toxicity measurement also demonstrated the safety of the compounds. These findings suggested the triazole-cored analogs and are suggested to be promising candidates for the treatment of HCC and their potential for further pharmaceutical development.

The development of novel targeted therapies for hepatocellular carcinoma remains a critical need in oncology. This study aimed to design and evaluate a new series of triazole-urea hybrid compounds for their anti-cancer potential. A series of urea compounds bearing terminal alkynyl groups were synthesized an assembly and post-modification strategy. Subsequent Click chemistry yielded the novel triazole-urea hybrids ( - , - , - ). Their anti-proliferative effects were assessed against multiple human cancer cell lines (lung: H460, H1299, A549, PC-9; liver: Huh-7; breast: MCF-7) and normal liver cells (L02) using the CCK-8 assay. Mechanisms were investigated through apoptosis, autophagy, and DNA damage assays. An acute oral toxicity study was conducted in female KM mice at a dose of 500 mg/kg, with thorough monitoring of body weight, organ coefficients, and histopathology of major organs. Most compounds exhibited potent, concentration- and time-dependent anti-proliferative activity against Huh-7 liver cancer cells, with only marginal effects on other tested cancer lines. Crucially, no cytotoxicity was observed in normal L02 cells. Mechanistic studies revealed that the lead compound induced apoptosis, autophagy, and DNA damage in Huh-7 cells. The in vivo assay demonstrated no drug-related mortality or significant adverse effects on body weight, organ coefficients, or histology at 500 mg/kg over 14 days, indicating a high maximum tolerated dose and an excellent preliminary safety profile. These findings demonstrate the selective anti-liver cancer efficacy and favorable in vivo safety of these triazole-urea hybrids, particularly compound , underscoring their strong potential as promising therapeutic candidates for hepatocellular carcinoma.

Alpine plants in nitrogen-deficient environments can acquire nitrogen by associating with endophytic nitrogen-fixing microorganisms that inhabit their roots and leaves to form symbiotic relationships. However, research is limited on nitrogen-fixing bacterial communities in the roots and leaves of alpine grassland plants, especially regarding the differences between various plant parts. In this study, we compared the root and leaf bacterial communities of four alpine plant families (Asteraceae, Leguminosae, Poaceae, and Rosaceae) in the alpine meadow ecosystem of Naqu, Tibet, using culture-based methods, 16S rRNA, and nifH gene pyrosequencing. The results showed greater bacterial diversity in the root compared to the leaf, and Fabaceae plants harbored a higher abundance of nitrogen-fixing bacteria. Interestingly, the roots and leaves of non-Fabaceae plants (Kobresia, Festuca ovina, and Leontopodium) also harbored abundant nitrogen-fixing communities such as Microbacterium, Curtobacterium, and Rhodococcus. Compared with subtropical environments, Cyanobacteria are important symbiotic nitrogen-fixing bacteria in plants of alpine ecosystems. These findings indicate that plant species and plant parts strongly influence the selection of bacterial populations. Understanding these microbial ecological functions in alpine grasslands provides scientific insights for optimizing agricultural practices and ecosystem management.

Alpine plants in nitrogen-deficient environments can acquire nitrogen by associating with endophytic nitrogen-fixing microorganisms that inhabit their roots and leaves to form symbiotic relationships. However, research is limited on nitrogen-fixing bacterial communities in the roots and leaves of alpine grassland plants, especially regarding the differences between various plant parts. In this study, we compared the root and leaf bacterial communities of four alpine plant families ( Asteraceae , Leguminosae , Poaceae , and Rosaceae ) in the alpine meadow ecosystem of Naqu, Tibet, using culture-based methods, 16S rRNA, and nifH gene pyrosequencing. The results showed greater bacterial diversity in the root compared to the leaf, and Fabaceae plants harbored a higher abundance of nitrogen-fixing bacteria. Interestingly, the roots and leaves of non- Fabaceae plants ( Kobresia , Festuca ovina , and Leontopodium ) also harbored abundant nitrogen-fixing communities such as Microbacterium , Curtobacterium , and Rhodococcus . Compared with subtropical environments, Cyanobacteria are important symbiotic nitrogen-fixing bacteria in plants of alpine ecosystems. These findings indicate that plant species and plant parts strongly influence the selection of bacterial populations. Understanding these microbial ecological functions in alpine grasslands provides scientific insights for optimizing agricultural practices and ecosystem management. Highlights 1 Compared to subtropical plants, the relative abundance of Cyanobacteria in the endophytic microbial communities of alpine plants increases significantly. 2 Roots of alpine plants have higher bacterial diversity, Proteobacteria phylum, and lower Cyanobacteria (based on 16S rRNA and nifH genes) than leaves. 3 The Fabaceae root has significantly lower diversity of nitrogen-fixing bacteria compared to other alpine plants.

Entangled two-qubit states are the core building blocks for constructing quantum communication networks. Their accurate verification is crucial to the functioning of the networks, especially for untrusted networks. In this work we study the self-testing of two-qubit entangled states via steering inequalities, with robustness analysis against noise. More precisely, steering inequalities are constructed from the tilted Clauser-Horne-Shimony-Holt inequality and its general form, to verify the general two-qubit entangled states. The study provides a good robustness bound, using both local extraction map and numerical semidefinite-programming methods. In particular, optimal local extraction maps are constructed in the analytical method, which yields the theoretical optimal robustness bound. To further improve the robustness of one-sided self-testing, we propose a family of three measurement settings steering inequalities. The result shows that three-setting steering inequality demonstrates an advantage over two-setting steering inequality on robust self-testing with noise. Moreover, to construct a practical verification protocol, we clarify the sample efficiency of our protocols in the one-sided device-independent scenario.

Empirical natural language processing (NLP) systems in application domains (e.g., healthcare, finance, education) involve interoperation among multiple components, ranging from data ingestion, human annotation, to text retrieval, analysis, generation, and visualization. We establish a unified open-source framework to support fast development of such sophisticated NLP workflows in a composable manner. The framework introduces a uniform data representation to encode heterogeneous results by a wide range of NLP tasks. It offers a large repository of processors for NLP tasks, visualization, and annotation, which can be easily assembled with full interoperability under the unified representation. The highly extensible framework allows plugging in custom processors from external off-the-shelf NLP and deep learning libraries. The whole framework is delivered through two modularized yet integratable open-source projects, namely Forte (for workflow infrastructure and NLP function processors) and Stave (for user interaction, visualization, and annotation).

As a new product of rapid urbanization, the sprawl of urban construction land can objectively reflect urban land use efficiency, which is of great significance to China's new urban construction. This study aimed to summarize the expansion patterns and utilization efficiency of urban construction land in China from the perspectives of the status, speed and trends of expansion, and to uncover the key factors that lead to the differential distribution of the expansion of construction land. It can also provide land management experience for other countries with rapid expansion of construction land. The results show the following. (1) The expansion of China's construction land presents a \"point–line–plane\" pattern of evolution, forming changing stages of point-like aggregation, linear series and planar spread. (2) China's construction land shows the characteristics of disorderly spread, a low utilization rate and low output efficiency. The speed of expansion presents clear characteristics of being high in the east and low in the west, mostly concentrated in the Yangtze River Delta, Pearl River Delta and the Beijing–Tianjin–Hebei urban agglomeration. Shanghai, Beijing, Shenzhen and Guangzhou have the highest intensity of construction land use. In Shandong Peninsula and eastern coastal areas, the intensity of the construction land use is generally high. In Xinjiang and Xizang, the intensity of construction land use is relatively low. (3) The urban economic level, population size, industrial structure, foreign investment and land policies have significant effects on the spatial distribution of the expansion of construction land.

It is important to study the temporal and spatial change characteristics and the decreasing trend in cultivated land in China in the past decades, analyze the core influencing factors of the cultivated land decrease, and understand the regularity and trend in the cultivated land change. This study has important guiding significance for ensuring food security in China and optimizing and adjusting the pattern of land spatial development and utilization. Based on the data of China’s urban cultivated land change from 1990 to 2022, this study analyzes the pattern of cultivated land protection and destruction in China from the perspective of the total cultivated land change, the increase and decrease evolution characteristics, and future trends and determines the main driving factors of cultivated land destruction in the process of urbanization. The results show the following: (1) The goal of the dynamic balance policy of cultivated land in China from 1990 to 2022 has been basically achieved, but regional differences still exist, which show a spatial pattern of planar contraction and belt growth. There is a new feature of a “southwest, northwest, and northeast” increase, while there is a “central” decrease. (2) Cultivated land has gradually shown a trend of growth rather than contraction, the cultivated land contraction shows a trend of crossing the “Hu–Huanyong Line” and moving westward, and the center of gravity of the cultivated land contraction has shifted to the periphery of the Chengdu–Chongqing area. The cultivated land growth shows a trend of moving southeast across the “Hu–Huanyong Line”, and developed provinces such as Guangdong, Fujian, and Zhejiang have gradually become the new centers of cultivated land growth. This coincides with the strict implementation of basic cultivated land protection policies in developed areas of China in recent years. (3) Factors such as the urban population size, economic level, agricultural scale, industrial structure, and other types of land scale have different degrees of impact on the destruction and restoration of cultivated land.

Ferroelectric domain wall memories have been proposed as a promising candidate for nonvolatile memories, given their intriguing advantages including low energy consumption and high-density integration. Perovskite oxides possess superior ferroelectric prosperities but perovskite-based domain wall memory integrated on silicon has rarely been reported due to the technical challenges in the sample preparation. Here, we demonstrate a domain wall memory prototype utilizing freestanding BaTiO 3 membranes transferred onto silicon. While as-grown BaTiO 3 films on (001) SrTiO 3 substrate are purely c -axis polarized, we find they exhibit distinct in-plane multidomain structures after released from the substrate and integrated onto silicon due to the collective effects from depolarizing field and strain relaxation. Based on the strong in-plane ferroelectricity, conductive domain walls with reading currents up to nanoampere are observed and can be both created and erased artificially, highlighting the great potential of the integration of perovskite oxides with silicon for ferroelectric domain wall memories. Integrating ferroelectric perovskite oxides on Si is highly desired for electronic applications but challenging. Here, the authors show emergent in-plane ferroelectricity and promising nonvolatile memories based on resistive domain wall in BaTiO 3 /Si.