PDLIM3 knockdown promotes ferroptosis in endometriosis progression via inducing Gli1 degradation and blocking Hedgehog signaling pathway.

AIMS: Current evidence suggests that there is no completely effective method for endometriosis (EMS) without trauma due to diverse adverse effects. Reliable evidence illustrates that inhibiting ferroptosis is a potential strategy for EMS. We sufficiently verified that the expression of endogenous protein PDZ and LIM domain 3 (PDLIM3) was significantly increased in EMS. METHODS: PDLIM3 knockdown reduced primary ectopic endometrial stromal cells' (EESCs) viability and migration, and elevated ferroptosis signaling indicators including Fe2+, malondialdehyde (MDA), and reactive oxygen species (ROS) in EESCs. RESULTS: Mechanistic studies revealed that inhibition of PDLIM3 accelerated glioma-associated oncogene-1 (Gli1) degradation and further deactivated Hedgehog signaling. Gli1 inhibitor, GANT61, abrogated the impact of PDLIM3 deletion on EESC growth, migration, and ferroptosis. In vivo experiments suggested that PDLIM3 reduction repressed the growth of endometrial lesions. Likewise, repression of PDLIM3 promoted ferroptosis and attenuated Hedgehog signaling in endometrial lesions. CONCLUSIONS: Collectively, silencing of PDLIM3 facilitates ferroptosis in EMS by inducing Gli1 degradation and blocking Hedgehog signaling. It may provide an alternative strategy for developing therapeutic agents of EMS in the future.

Quantitative Prediction of Surface Hardness in Cr12MoV Steel and S136 Steel with Two Magnetic Barkhausen Noise Feature Extraction Methods.

The correlation between magnetic Barkhausen noise (MBN) features and the surface hardness of two types of die steels (Cr12MoV steel and S136 steel in Chinese standards) was investigated in this study. Back-propagation neural network (BP-NN) models were established with MBN magnetic features extracted by different methods as the input nodes to realize the quantitative prediction of surface hardness. The accuracy of the BP-NN model largely depended on the quality of the input features. In the extraction process of magnetic features, simplifying parameter settings and reducing manual intervention could significantly improve the stability of magnetic features. In this study, we proposed a method similar to the magnetic Barkhausen noise hysteresis loop (MBNHL) and extracted features. Compared with traditional MBN feature extraction methods, this method simplifies the steps of parameter setting in the feature extraction process and improves the stability of the features. Finally, a BP-NN model of surface hardness was established and compared with the traditional MBN feature extraction methods. The proposed MBNHL method achieved the advantages of simple parameter setting, less manual intervention, and stability of the extracted parameters at the cost of small accuracy reduction.

Stable Isotope Tracer Technique and Network Pharmacology to Reveal Antidepressant Targets and Active Components of Xiaoyao San.

In recent years, the research of mitochondrial dysfunction in depression has drawn the focus of researchers. Our research group previously found that Xiaoyao San (XYS) has improved the mitochondrial structure and the blocked tricarboxylic acid cycle (TCA cycle) in the hippocampal tissue of chronic unpredictable mild stress (CUMS) rats. However, the specific targets and active components of XYS remain unclear, and the potential to improve hippocampal mitochondrial TCA cycle disorder was also unexplored. In this research, a strategy to combine stable isotope-resolved metabolomics (SIRM), network pharmacology and transmission electron microscopy (TEM) was used to explore the potential, targets of action, and active components of XYS to improve hippocampal mitochondrial TCA cycle disorder of CUMS rats. The results of TEM showed that the ultrastructure of hippocampal mitochondria could be improved by XYS. A combination of SIRM and molecular docking showed that pyruvate carboxylase (PC), ATP citrate lyase (ACLK), glutamate dehydrogenase (GLDH), glutamate oxaloacetate transaminase (GOT) and pyruvate dehydrogenase (PDH) were targets of XYS to improve TCA cycle disorder. In addition, troxerutin was found to be the most potential active component of XYS to improve TCA cycle disorder. The above research results can provide new insights for the development of antidepressant drugs.

Precipitation Dominates the Allocation Strategy of Above- and Belowground Biomass in Plants on Macro Scales.

The allocation of biomass reflects a plant's resource utilization strategy and is significantly influenced by climatic factors. However, it remains unclear how climate factors affect the aboveground and belowground biomass allocation patterns on macro scales. To address this, a study was conducted using aboveground and belowground biomass data for 486 species across 294 sites in China, investigating the effects of climate change on biomass allocation patterns. The results show that the proportion of belowground biomass in the total biomass (BGBP) or root-to-shoot ratio (R/S) in the northwest region of China is significantly higher than that in the southeast region. Significant differences (p < 0.05) were found in BGBP or R/S among different types of plants (trees, shrubs, and herbs plants), with values for herb plants being significantly higher than shrubs and tree species. On macro scales, precipitation and soil nutrient factors (i.e., soil nitrogen and phosphorus content) are positively correlated with BGBP or R/S, while temperature and functional traits are negatively correlated. Climate factors contribute more to driving plant biomass allocation strategies than soil and functional trait factors. Climate factors determine BGBP by changing other functional traits of plants. However, climate factors influence R/S mainly by affecting the availability of soil nutrients. The results quantify the productivity and carbon sequestration capacity of terrestrial ecosystems and provide important theoretical guidance for the management of forests, shrubs, and herbaceous plants.

Climate factors affect forest biomass allocation by altering soil nutrient availability and leaf traits.

Biomass in forests sequesters substantial amounts of carbon; although the contribution of aboveground biomass has been extensively studied, the contribution of belowground biomass remains understudied. Investigating the forest biomass allocation is crucial for understanding the impacts of global change on carbon allocation and cycling. Moreover, the question of how climate factors affect biomass allocation in natural and planted forests remains unresolved. Here, we addressed this question by collecting data from 384 planted forests and 541 natural forests in China. We evaluated the direct and indirect effects of climate factors on the belowground biomass proportion (BGBP). The average BGBP was 31.09% in natural forests and was significantly higher (38.75%) in planted forests. Furthermore, we observed a significant decrease in BGBP with increasing temperature and precipitation. Climate factors, particularly those affecting soil factors, such as pH, strongly affected the BGBP in natural and planted forests. Based on our results, we propose that future studies should consider the effects of forest type (natural or planted) and soil factors on BGBP.

A novel insight for high-rate and low-efficiency glucose metabolism in depression through stable isotope-resolved metabolomics in CUMS-induced rats.

BACKGROUND: Existing research has suggested that depression results in disorders of glucose metabolism in the organism which causing insufficient energy supply. However, the overall changes in glucose metabolism that arise from depression have not been clarified. METHODS: In this study, the depression-like behavior in chronically unpredictable mild stressed rats was investigated, and the fate of glucose was tracked through isotope tracing and mass spectrometry, with a focus on metabolite changes in cecal contents. RESULTS: As indicated by the results, the isotopic results of cecal contents can indicate the metabolic end of the organism. Moreover, the TCA cycle activity was notably reduced, and the gluconeogenesis pathway was abnormally up-regulated in the CUMS-induced rats. The organism expedited other glucose metabolism pathways to make up for the insufficiency of energy. As a result, the activity of the inefficient glycolysis pathway was increased. LIMITATIONS: Existing research has only investigated the metabolism of 13C-glucose, and lipids and proteins have been rarely explored. CONCLUSIONS: The chronic unpredictable mild stress can inhibit the entry of pyruvate into mitochondria in SD rats, such that the activity of TCA is reduced, and insufficient energy supply is caused. The organism is capable of expediting other glucose metabolism rate pathways to make up for the insufficiency of energy, whereas it still cannot compensate for the loss of energy. As a result, CUMS-induced rats exhibited high-rate and low-efficiency glucose metabolism.

N-Glycosylation of LRP6 by B3GnT2 Promotes Wnt/ß-Catenin Signalling.

Reception of Wnt signals by cells is predominantly mediated by Frizzled receptors in conjunction with a co-receptor, the latter being LRP6 or LRP5 for the Wnt/ß-catenin signalling pathway. It is important that cells maintain precise control of receptor activation events in order to properly regulate Wnt/ß-catenin signalling as aberrant signalling can result in disease in humans. Phosphorylation of the intracellular domain (ICD) of LRP6 is well known to regulate Wntß-catenin signalling; however, less is known for regulatory post-translational modification events within the extracellular domain (ECD). Using a cell culture-based expression screen for functional regulators of LRP6, we identified a glycosyltransferase, B3GnT2-like, from a teleost fish (medaka) cDNA library, that modifies LRP6 and regulates Wnt/ß-catenin signalling. We provide both gain-of-function and loss-of-function evidence that the single human homolog, B3GnT2, promotes extension of polylactosamine chains at multiple N-glycans on LRP6, thereby enhancing trafficking of LRP6 to the plasma membrane and promoting Wnt/ß-catenin signalling. Our findings further highlight the importance of LRP6 as a regulatory hub in Wnt signalling and provide one of the few examples of how a specific glycosyltransferase appears to selectively target a signalling pathway component to alter cellular signalling events.

Physiological and transcriptomic responses to cold waves of the most cold-tolerant mangrove, Kandelia obovata.

Mangrove forests inhabit tropical or subtropical intertidal zones and have remarkable abilities in coastline protection. Kandelia obovata is considered the most cold-tolerant mangrove species and has been widely transplanted to the north subtropical zone of China for ecological restoration. However, the physiological and molecular mechanisms of K. obovata under colder climate was still unclear. Here, we manipulated the typical climate of cold waves in the north subtropical zone with cycles of cold/recovery and analyzed the physiological and transcriptomic responses of seedlings. We found that both physiological traits and gene expression profiles differed between the first and later cold waves, indicating K. obovata seedlings were acclimated by the first cold experience and prepared for latter cold waves. 1,135 cold acclimation-related genes (CARGs) were revealed, related to calcium signaling, cell wall modification, and post-translational modifications of ubiquitination pathways. We identified the roles of CBFs and CBF-independent transcription factors (ZATs and CZF1s) in regulating the expression of CARGs, suggesting both CBF-dependent and CBF- independent pathways functioned in the cold acclimation of K. obovata. Finally, we proposed a molecular mechanism of K. obovata cold acclimation with several key CARGs and transcriptional factors involved. Our experiments reveal strategies of K. obovata coping with cold environments and provide prospects for mangrove rehabilitation and management.

Micromagnetic and Robust Evaluation of Surface Hardness in Cr12MoV Steel Considering Repeatability of the Instrument.

The combination of multifunctional micromagnetic testing and neural network-based prediction models is a promising way of nondestructive and quantitative measurement of steel surface hardness. Current studies mainly focused on improving the prediction accuracy of intelligent models, but the unavoidable and random uncertainties related to instruments were seldom explored. The robustness of the prediction model considering the repeatability of instruments was seldom discussed. In this work, a self-developed multifunctional micromagnetic instrument was employed to perform the repeatability test with Cr12MoV steel. The repeatability of the instrument in measuring multiple magnetic features under both static and dynamic conditions was evaluated. The magnetic features for establishing the prediction model were selected based on the consideration of both the repeatability of the instrument and the ability of magnetic features in surface hardness evaluation. To improve the robustness of the model in surface hardness prediction, a modelling strategy considering the repeatability of the instrument was proposed. Through removing partial magnetic features with higher mean impact values from input nodes, robust evaluation of surface hardness in Cr12MoV steel was realized with the multifunctional micromagnetic instrument.

Surface Decarburization Depth Detection in Rods of 60Si2Mn Steel with Magnetic Barkhausen Noise Technique.

Magnetic Barkhausen noise (MBN), sensitive to the microstructure of materials, can be applied in the surface decarburization depth detection of ferromagnetic specimens. However, the effects of core microstructures on the determination results of decarburization depth have not been explored. In this study, MBN was employed to evaluate the magnetic properties of the decarburized 60Si2Mn spring steels with martensitic and pearlitic core microstructures. Spring steel samples were austenitized at different times to generate different decarburization depths. Seven magnetic features were extracted from the MBN butterfly profiles. We used the variation coefficient, linear correlation coefficient, and normalized sensitivity to discuss the influence of the core microstructures on these seven features. The different core microstructures led to a large difference in the ability of MBN features to characterize the decarburization layer depth. However, three features of MBN butterfly profiles demonstrated an approximately linear dependency (linear correlation coefficient > 94%) on surface decarburization depth and monotonically increased with the increase in depth in both core microstructures of spring steels.

Extraction of honokiol from Artemisia argyi and in vitro and in vivo investigation of its antifungal activity.

Extracts from plants used in Chinese medicine can be good sources of fungicides for agricultural applications. In this study, we separated and identified antifungal compounds from four traditional Chinese medicine extracts and evaluated their antifungal activities in vitro and in vivo. In vitro, honokiol extracted from Artemisia argyi showed broad-spectrum antimicrobial and mycelial inhibitory activity with EC50 in the range 3.56 - 33.85 µg/mL against eight plant pathogens. q-PCR indicated that honokiol might induce cell cancerisation and inhibit cellular respiration, which provided significant insights into honokiol function in tobacco resistance to molecular mechanisms of the phytopathogenic fungus Phytophthora nicotianae. In vivo, honokiol significantly decreased the rate of fungal infection in eggplants, potatoes, grapes, cherry tomatoes, and cucumbers, and enhanced disease resistance in tobacco. Overall, our results indicate that honokiol has the potential to control a variety of fungal and oomycete diseases, and A. argyi could be a source of honokiol.

Metabolites from Bacillus subtilis J-15 Affect Seedling Growth of Arabidopsis thaliana and Cotton Plants.

Bacillus subtilis J-15 is a plant growth-promoting rhizobacteria isolated from the soil rhizosphere of cotton and is resistant to cotton verticillium wilt. This study evaluated the effects of metabolites of J-15 (J-15-Ms), including mycosubtilin, on plant growth using Arabidopsis and cotton plants. The results showed that J-15-Ms promoted Arabidopsis seeding growth at lower concentrations of 0.2 µg/mL but inhibited the growth at higher concentrations, such as 20 µg/mL. Similar results were obtained in cotton. Thus, J-15-Ms-treated plants showed low-concentration-induced growth promotion and high-concentration-induced growth inhibition. The J-15-Ms components were analyzed by liquid chromatography-mass spectrometry. Correlation analysis using the J-15 genomic databases suggested that J-15 may synthesize indoleacetic acid via the indole-3-pymvate pathway and indole-3-acetamide pathway. Treatment with mycosubtilin, a purified peptide from J-15-Ms, showed that the peptide promoted Arabidopsis growth at a low concentration (0.1 µg/mL) and inhibited plant growth at high concentrations (higher than 1 µg/mL), which also significantly increased plant lateral root number. Transcriptomic analysis showed that mycosubtilin might promote lateral root development and inhibit plant primary root growth by regulating the expression of the plant hormone signaling pathway. This study reveals the mechanism of Bacillus subtilis J-15 in affecting plant growth.

Precipitation and soil nutrients determine the spatial variability of grassland productivity at large scales in China.

Changes in net primary productivity (NPP) to global change have been studied, yet the relative impacts of global change on grassland productivity at large scales remain poorly understood. Using 182 grassland samples established in 17 alpine meadows (AM) and 21 desert steppes (DS) in China, we show that NPP of AM was significantly higher than that of DS. NPP increased significantly with increasing leaf nitrogen content (LN) and leaf phosphorus content (LP) but decreased significantly with increasing leaf dry matter content (LDMC). Among all abiotic factors, soil nutrient factor was the dominant factor affecting the variation of NPP of AM, while the NPP of DS was mainly influenced by the changing of precipitation. All abiotic factors accounted for 62.4% of the spatial variation in the NPP of AM, which was higher than the ability to explain the spatial variation in the NPP of DS (43.5%). Leaf traits together with soil nutrients and climatic factors determined the changes of the grassland productivity, but the relative contributions varied somewhat among different grassland types. We quantified the effects of biotic and abiotic factors on grassland NPP, and provided theoretical guidance for predicting the impacts of global change on the NPP of grasslands.

Climatic Factors Determine the Distribution Patterns of Leaf Nutrient Traits at Large Scales.

Leaf nutrient content and its stoichiometric relationships (N/P ratio) are essential for photosynthesis and plant growth and development. Previous studies on leaf nutrient-related functional traits have mainly focused on the species level and regional scale, but fewer studies have investigated the distribution patterns of the leaf N and P contents (LN, LP) and N/P ratios (N/P) in communities and their controlling factors at a large scale; therefore, we used LN, LP, and N/P data at 69 sites from 818 forests in China. The results showed significant differences (p < 0.05) in the LN, LP, and N/P at different life forms (tree, shrub, and herb). Neither LN, LP, nor N/P ratios showed significant patterns of latitudinal variation. With the increase in temperature and rainfall, the LN, LP, and leaf nutrient contents increased significantly (p < 0.001). Across life forms, LN at different life forms varied significantly and was positively correlated with soil P content (p < 0.001). The explanatory degree of climatic factors in shaping the spatial variation patterns of LN and N/P was higher than that of the soil nutrient factors, and the spatial variation patterns of the leaf nutrient traits of different life forms were shaped by the synergistic effects of climatic factors and soil nutrient factors.

Climate factors determine the utilization strategy of forest plant resources at large scales.

Plant functional traits are a representation of plant resource utilization strategies. Plants with higher specific leaf area (SLA) and lower leaf dry matter content (LDMC) exhibit faster investment-return resource utilization strategies. However, the distribution patterns and driving factors of plant resource utilization strategies at the macroscale are rarely studied. We investigated the relative importance of climatic and soil factors in shaping plant resource utilization strategies at different life forms in forests using data collected from 926 plots across 163 forests in China. SLA and LDMC of plants at different life forms (i.e., trees, shrubs, and herbs) differ significantly. Resource utilization strategies show significant geographical differences, with vegetation in the western arid regions adopting a slower investment-return survival strategy and vegetation in warmer and wetter areas adopting a faster investment-return survival strategy. SLA decreases significantly with increased temperature and reduced rainfall, and vegetation growing in these conditions exhibits conservative resource utilization. Mean annual precipitation (MAP) is a key climatic factor that controls the resource utilization strategies of plants at the macroscale. Plants use resources more conservatively as soil pH increases. The influence of climate and soil factors is coupled to determine the resource utilization strategies of plants occupying different life forms at the macroscale, but the relative contribution of each varies across life forms. Our findings provide a theoretical framework for understanding the potential impact of increasing global temperatures on plant resource utilization.

Quantitative Proteomics of Chromochloris zofingiensis Reveals the Key Proteins Involved in Cell Growth and Bioactive Compound Biosynthesis.

Glucose metabolism regulates cell growth and affects astaxanthin accumulation in the green algae Chromochloris zofingiensis. Hub gene functioning in this bioactive compound has been illustrated at the genome, transcriptome and metabolome level, but is rather limited from a proteome aspect. Microalgal cell produce an enhanced biomass (8-fold higher) but decreased lipid and astaxanthin content (~20% less) in the glucose condition compared to the control. Here, we investigate the proteomic response of C. zofingiensis grown with and without glucose using an LC-MS/MS-based Tandem Mass Tag (TMT) approach. The proteomic analysis demonstrated that glucose supplementation triggers the upregulation of 105 proteins and downregulation of 151 proteins. Thus, the carbon and energy flux might flow to cell growth, which increased the associated protein abundance, including DNA polymerase, translation initiation factor, 26S proteasome regulatory subunits, and the marker enzyme of the TCA cycle ribosomal protein. Moreover, the glucose supplement triggered the downregulation of proteins mainly involved in photosynthesis, chloroplasts, valine, leucine and isoleucine biosynthesis, 2-oxocarboxylic acid metabolism, and pantothenate and CoA biosynthesis pathways. This proteomic analysis is likely to provide new insights into algal growth and lipid or astaxanthin accumulation upon glucose supplementation, providing a foundation for further development of C. zofingiensis as oleaginous microalga for bioengineering applications.

Recent Advancements and Future Perspectives of Microalgae-Derived Pharmaceuticals.

Microalgal cells serve as solar-powered factories that produce pharmaceuticals, recombinant proteins (vaccines and drugs), and valuable natural byproducts that possess medicinal properties. The main advantages of microalgae as cell factories can be summarized as follows: they are fueled by photosynthesis, are carbon dioxide-neutral, have rapid growth rates, are robust, have low-cost cultivation, are easily scalable, pose no risk of human pathogenic contamination, and their valuable natural byproducts can be further processed. Despite their potential, there are many technical hurdles that need to be overcome before the commercial production of microalgal pharmaceuticals, and extensive studies regarding their impact on human health must still be conducted and the results evaluated. Clearly, much work remains to be done before microalgae can be used in the large-scale commercial production of pharmaceuticals. This review focuses on recent advancements in microalgal biotechnology and its future perspectives.

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We examined the distribution of melanin during the development of the larvae of Schizothorax o'connori except the eyes with histological method. The results showed that after hatching, the appearance sequence of melanin in different organs were following an order of the outer membrane of neurocranium, the pericardial cavity and the dorsal skin, and the peritoneum and the spinal cord. Specifically, melanin appeared in the outer membrane of neurocranium around 5 DAH (days after hatching), in the pericardial cavity and the back skin at 7 DAH, and in the peritoneum and the spinal cord at 10 DAH. Melanin was found in the skin and internal organs (the outer membrane of neurocranium, the pericardial cavity, the peritoneum, the spinal cord) of S. o'connori at 10 DAH, which was mainly distributed on the back. The appearance and distribution of melanin in the postembryonic development of S. o'connori might be related to the high ultraviolet radiation. Our results could provide reference for further research on the UV protection mechanism of melanin for fish and provide theoretical support for the optimization of rearing conditions for larvae in the plateau.

Comparison of Phenolic and Flavonoid Compound Profiles and Antioxidant and α-Glucosidase Inhibition Properties of Cultivated Soybean (Glycine max) and Wild Soybean (Glycine soja).

Wild soybean (Glycine soja Sieb.et Zucc; WS) has been used as a traditional food in China for many years and contains significantly higher levels of isoflavones than cultivated soybean (Glycine max; CS), but the secondary metabolites, including flavonoids and the phenolic composition differences between them, remain unclear. The results showed that WS possessed significantly higher total phenolic and flavonoid content and exhibited better antioxidant and α-glucosidase inhibition activities as well as excellent protective effects against H2O2-induced oxidative injury in a human endothelial cell line. Through metabolomic analysis, 642 metabolites were identified, and 238 showed differential expression, with 151 upregulated and 87 downregulated. A total of 79 flavonoid compounds were identified, 42 of which were upregulated in WS. 2'-Hydroxygenistein, garbanzol, protocatechuic aldehyde, ligustilide, and resveratrol were the most discriminated compounds in WS. The metabolic pathway analysis of differential metabolites related to the biosynthesis of flavonoids and phenolic acids were the biosynthesis of phenylpropanoids, flavonoids, isoflavonoids, flavones, and flavonols. This study substantially elucidated differences in the content of flavonoids and biological activities between WS and CS, which is useful information for the effective utilization of these two black soybean species in food processing.

Assembly of Multi-Spheroid Cellular Architectures by Programmable Droplet Merging.

Artificial multicellular systems are gaining importance in the field of tissue engineering and regenerative medicine. Reconstruction of complex tissue architectures in vitro is nevertheless challenging, and methods permitting controllable and high-throughput fabrication of complex multicellular architectures are needed. Here, a facile and high-throughput method is developed based on a tunable droplet-fusion technique, allowing programmed assembly of multiple cell spheroids into complex multicellular architectures. The droplet-fusion technique allows for construction of various multicellular architectures (double-spheroids, multi-spheroids, hetero-spheroids) in a miniaturized high-density array format. As an example of application, the propagation of Wnt signaling is investigated within hetero-spheroids formed from two fused Wnt-releasing and Wnt-reporter cell spheroids. The developed method provides an approach for miniaturized, high-throughput construction of complex 3D multicellular architectures and can be applied for studying various biological processes including cell signaling, cancer invasion, embryogenesis, and neural development.