Oral microbial profiles of extrinsic black tooth stain in primary dentition: A literature review.

The extrinsic black tooth stain (EBS) is commonly found in primary dentition. Patients cannot clean the EBS; this can only be done by professional scaling and debridement. It also has a tendency to reform, which significantly compromises children's aesthetics and even affects their quality of life. However, there is no conclusive evidence on the etiology of the EBS. The associations between the EBS and related oral microbial features is one of the research hot topics. No literature review summarized these research progresses in this area. Therefore, we reviewed the literature on the microbiology of the EBS since 1931 and reported as the following 5 aspects: molecular biotechnology, morphological structure and physiochemical characteristics, microbial etiology hypothesis and core microbial characteristics. The EBS is a special dental plaque mainly composed of Gram-positive bacilli and cocci with scattered calcium deposits that acquired salivary pellicle activates. Early studies showed that the Actinomyces was the main pathogenic bacteria. With advances in biological research techniques, the 'core microbiome' was proposed. The potential pathogenic genera were Actinomyces, Prevotella nigrescens, Pseudotropinibacterium, Leptotrichia, Neisseria and Rothia. However, the pathogenic species of the above genera were still unclear. Currently, it is believed that the EBS consists of iron compounds or black substances that oral bacterial metabolism produces or that the bacterial metabolites formed after chemical reactions in the micro-ecological environment.

Scutellarein Suppresses the Production of ROS and Inflammatory Mediators of LPS-Activated Bronchial Epithelial Cells and Attenuates Acute Lung Injury in Mice.

Scutellarein is a key active constituent present in many plants, especially in Scutellaria baicalensis Georgi and Erigeron breviscapus (vant.) Hand-Mazz which possesses both anti-inflammatory and anti-oxidative activities. It also is the metabolite of scutellarin, with the ability to relieve LPS-induced acute lung injury (ALI), strongly suggesting that scutellarein could suppress respiratory inflammation. The present study aimed to investigate the effects of scutellarein on lung inflammation by using LPS-activated BEAS-2B cells (a human bronchial epithelial cell line) and LPS-induced ALI mice. The results showed that scutellarein could reduce intracellular reactive oxygen species (ROS) accumulation through inhibiting the activation of NADPH oxidases, markedly downregulating the transcription and translation of pro-inflammatory cytokines, including interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand (CXCL) 8 in LPS-activated BEAS-2B cells. The mechanism study revealed that it suppressed the phosphorylation and degradation of IκBα, consequently hindering the translocation of p65 from the cytoplasm to the nucleus and its subsequent binding to DNA, thereby decreasing NF-κB-regulated gene transcription. Notably, scutellarein had no impact on the activation of AP-1 signaling. In LPS-induced ALI mice, scutellarein significantly decreased IL-6, CCL2, and tumor necrosis factor-α (TNF-α) levels in the bronchoalveolar lavage fluid, attenuated lung injury, and inhibited neutrophil infiltration. Our findings suggest that scutellarein may be a beneficial agent for the treatment of infectious pneumonia by virtue of its anti-oxidative and anti-inflammatory activities.

Mechanism of action of Sambucus williamsii Hance var. miquelii in the treatment of osteoporosis analyzed by UHPLC-HRMS/MS combined network pharmacology and experimental validation.

Sambucus williamsii Hance var. miquelii(SWH) is a precious wild Chinese herb whose fruit, rhizome, leaves and root bark can be used as medicine. Sambucus Linn has pharmacological effects such as anti-osteoporosis, promoting fracture healing, anti-viral and anti-inflammatory. In this study, the main chemical components of the alcoholic extracts from SWH were rapidly identified by ultra-high performance liquid chromatography-quadrupole orbit trap high-resolution mass spectrometry (UHPLC- HRMS MS), and a total of 42 compounds were characterized from the alcoholic extracts of SWH. The results of network pharmacological validation showed that kaempferol, quercetin, luteolin, isorhamnetin and morroniside were the main active components, and KEGG enrichment demonstrated that SWH mainly affected the signaling pathways such as PI3K-Akt, TNF and FoxO by modulating the related targets such as AKT1, PIK3R1, EGFR, RELA SRC and PTGS2. The molecular docking results showed binding solid activity between the main active components of SWH and the targets. The network pharmacology was validated by establishing an animal model of osteoporosis (OP) in rats by gavage administration of vitamin A acid. The results of the pharmacological experiments showed that SWH could improve the degree of bone loss in the femur of osteoporotic rats, increase the number of trabeculae and decrease trabeculae porosity, up-regulate the Ca and P content in the serum of OP rats, down-regulate the scope of ALP and BGP in the serum, and promote the calcification of the bone matrix, and then exert the anti-OP efficacy. In this study, network pharmacology and pharmacological experiments verified the pharmacological mechanism of SWH in anti-OP rats. This provides a theoretical basis for the research and development of anti-OP drugs and a reference for the application of other traditional Chinese medicines in treating OP diseases.

Use of MRI-based deep learning radiomics to diagnose sacroiliitis related to axial spondyloarthritis.

OBJECTIVES: This study aimed to evaluate the performance of a deep learning radiomics (DLR) model, which integrates multimodal MRI features and clinical information, in diagnosing sacroiliitis related to axial spondyloarthritis (axSpA). MATERIAL & METHODS: A total of 485 patients diagnosed with sacroiliitis related to axSpA (n = 288) or non-sacroiliitis (n = 197) by sacroiliac joint (SIJ) MRI between May 2018 and October 2022 were retrospectively included in this study. The patients were randomly divided into training (n = 388) and testing (n = 97) cohorts. Data were collected using three MRI scanners. We applied a convolutional neural network (CNN) called 3D U-Net for automated SIJ segmentation. Additionally, three CNNs (ResNet50, ResNet101, and DenseNet121) were used to diagnose axSpA-related sacroiliitis using a single modality. The prediction results of all the CNN models across different modalities were integrated using a stacking method based on different algorithms to construct ensemble models, and the optimal ensemble model was used as DLR signature. A combined model incorporating DLR signature with clinical factors was developed using multivariable logistic regression. The performance of the models was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Automated deep learning-based segmentation and manual delineation showed good correlation. ResNet50, as the optimal basic model, achieved an area under the curve (AUC) and accuracy of 0.839 and 0.804, respectively. The combined model yielded the highest performance in diagnosing axSpA-related sacroiliitis (AUC: 0.910; accuracy: 0.856) and outperformed the best ensemble model (AUC: 0.868; accuracy: 0.825) (all P < 0.05). Moreover, the DCA showed good clinical utility in the combined model. CONCLUSION: We developed a diagnostic model for axSpA-related sacroiliitis by combining the DLR signature with clinical factors, which resulted in excellent diagnostic performance.

Enhanced growth resistance but no decline in growth resilience under long-term extreme droughts.

The frequency, intensity, and duration of extreme droughts, with devastating impacts on tree growth and survival, have increased with climate change over the past decades. Assessing growth resistance and resilience to drought is a crucial prerequisite for understanding the responses of forest functioning to drought events. However, the responses of growth resistance and resilience to extreme droughts with different durations across different climatic zones remain unclear. Here, we investigated the spatiotemporal patterns in growth resistance and resilience in response to extreme droughts with different durations during 1901-2015, relying on tree-ring chronologies from 2389 forest stands over the mid- and high-latitudinal Northern Hemisphere, species-specific plant functional traits, and diverse climatic factors. The findings revealed that growth resistance and resilience under 1-year droughts were higher in humid regions than in arid regions. Significant higher growth resistance was observed under 2-year droughts than under 1-year droughts in both arid and humid regions, while growth resilience did not show a significant difference. Temporally, tree growth became less resistant and resilient to 1-year droughts in 1980-2015 than in 1901-1979 in both arid and humid regions. As drought duration lengthened, the predominant impacts of climatic factors on growth resistance and resilience weakened and instead foliar economic traits, plant hydraulic traits, and soil properties became much more important in both climatic regions; in addition, such trends were also observed temporally. Finally, we found that most of the Earth system models (ESMs) used in this study overestimated growth resistance and underestimated growth resilience under both 1-year and 2-year droughts. A comprehensive ecophysiological understanding of tree growth responses to longer and intensified drought events is urgently needed, and a specific emphasis should be placed on improving the performance of ESMs.

Self-Aggregated Nanoscale Metal-Organic Framework for Targeted Pulmonary Decorporation of Uranium.

The limited availability of effective agents for removing actinides from the lungs significantly restricts the effectiveness of medical treatments for nuclear emergencies. Inhalation is the primary route of internal contamination in 44.3% of actinide-related accidents, leading to the accumulation of radionuclides in the lungs and resulting in infections and potential tumor formation (tumorigenesis). This study focuses on the synthesis of a nanometal-organic framework (nMOF) material called ZIF-71-COOH, which is achieved by post-synthetic carboxyl functionalization of ZIF-71. The material demonstrates high and selective adsorption of uranyl, while also exhibiting increased particle size (≈2100 nm) when it aggregates in the blood, enabling passive targeting of the lungs through mechanical filtration. This unique property facilitates the rapid enrichment and selective recognition of uranyl, making nano ZIF-71-COOH highly effective in removing uranyl from the lungs. The findings of this study highlight the potential of self-aggregated nMOFs as a promising drug delivery system for targeted uranium decorporation in the lungs.

Automatic Image Segmentation and Grading Diagnosis of Sacroiliitis Associated with AS Using a Deep Convolutional Neural Network on CT Images.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes inflammatory low back pain and may even limit activity. The grading diagnosis of sacroiliitis on imaging plays a central role in diagnosing AS. However, the grading diagnosis of sacroiliitis on computed tomography (CT) images is viewer-dependent and may vary between radiologists and medical institutions. In this study, we aimed to develop a fully automatic method to segment sacroiliac joint (SIJ) and further grading diagnose sacroiliitis associated with AS on CT. We studied 435 CT examinations from patients with AS and control at two hospitals. No-new-UNet (nnU-Net) was used to segment the SIJ, and a 3D convolutional neural network (CNN) was used to grade sacroiliitis with a three-class method, using the grading results of three veteran musculoskeletal radiologists as the ground truth. We defined grades 0-I as class 0, grade II as class 1, and grades III-IV as class 2 according to modified New York criteria. nnU-Net segmentation of SIJ achieved Dice, Jaccard, and relative volume difference (RVD) coefficients of 0.915, 0.851, and 0.040 with the validation set, respectively, and 0.889, 0.812, and 0.098 with the test set, respectively. The areas under the curves (AUCs) of classes 0, 1, and 2 using the 3D CNN were 0.91, 0.80, and 0.96 with the validation set, respectively, and 0.94, 0.82, and 0.93 with the test set, respectively. 3D CNN was superior to the junior and senior radiologists in the grading of class 1 for the validation set and inferior to expert for the test set (P < 0.05). The fully automatic method constructed in this study based on a convolutional neural network could be used for SIJ segmentation and then accurately grading and diagnosis of sacroiliitis associated with AS on CT images, especially for class 0 and class 2. The method for class 1 was less effective but still more accurate than that of the senior radiologist.

Evaporation-driven internal hydraulic redistribution alleviates root drought stress: Mechanisms and modeling.

Many tree species have developed extensive root systems that allow them to survive in arid environments by obtaining water from a large soil volume. These root systems can transport and redistribute soil water during drought by hydraulic redistribution (HR). A recent study revealed the phenomenon of evaporation-driven hydraulic redistribution (EDHR), which is driven by evaporative demand (transpiration). In this study, we confirmed the occurrence of EDHR in Chinese white poplar (Populus tomentosa) through root sap flow measurements. We utilized microcomputed tomography technology to reconstruct the xylem network of woody lateral roots and proposed conceptual models to verify EDHR from a physical perspective. Our results indicated that EDHR is driven by the internal water potential gradient within the plant xylem network, which requires 3 conditions: high evaporative demand, soil water potential gradient, and special xylem structure of the root junction. The simulations demonstrated that during periods of extreme drought, EDHR could replenish water to dry roots and improve root water potential up to 38.9% to 41.6%. This highlights the crucial eco-physiological importance of EDHR in drought tolerance. Our proposed models provide insights into the complex structure of root junctions and their impact on water movement, thus enhancing our understanding of the relationship between xylem structure and plant hydraulics.

Validation of Self-Regulated Writing Strategies for Advanced EFL Learners in China: A Structural Equation Modeling Analysis.

This study aims to validate self-regulated writing strategies for advanced EFL learners through a structural equation modeling analysis. Two sets of advanced, university-level EFL learners in China were recruited on the basis of results from a nationwide standardized English test. Sample 1 consisted of 214 advanced learners and served mainly as a data source for exploratory factor analysis. Sample 2 consisted of 303 advanced learners; data from this group were used to conduct confirmatory factor analyses. The results confirmed the goodness of fit of the hierarchical, multidimensional structure of self-regulated writing strategies. This hierarchic model has the higher order of self-regulation and the second order of nine self-regulated writing strategies that belong to four dimensions. In terms of model comparisons, the indices of Model 1 (nine-factor correlated model of EFL writing strategies for SRL) and Model 2 (four-factor second-order model of EFL writing strategies for SRL) mark significant improvements in terms of fit over the indices of Model 3 (one-factor second-order model of EFL writing strategies for SRL). This means the four-factor model (cognition, metacognition, social behavior, and motivational regulation) offered a better explanation for advanced EFL learners than the model treating self-regulated writing strategies as a single convergent factor. These findings, in some ways, differ from the results of earlier research on EFL learners' self-regulated writing strategies, and the findings of this study have certain implications for L2 writing teaching and learning.

Bupleurum chinense exerts a mild antipyretic effect on LPS-induced pyrexia rats involving inhibition of peripheral TNF-α production.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix, the dried roots of Bupleurum chinense DC. (BC) or Bupleurum scorzonerifolium Willd., is one of the most frequently used traditional Chinese medicines. As the species in Xiao-Chai-Hu decoction, BC has been used as an antipyretic medicine with a long history. However, its antipyretic characteristics and underlying mechanism(s) remain unclear. AIM OF THE STUDY: To elucidate the antipyretic characteristics and mechanism(s) of BC used in its traditional way. METHODS: The water extract of BC (BCE) was prepared according to the traditional decocting mode. Murine fever and endotoxemia models were induced by intravenous injection of lipopolysaccharide (LPS). In vitro complement activation assay and the levels of TNF-α, IL-6, IL-1ß, and C5a were determined by ELISA. RESULTS: BCE exerted a confirmed but mild antipyretic effect on LPS-induced fever of rat. In vitro, it significantly lowered LPS-elevated TNF-α in the supernatant of rat complete blood cells and THP-1 cells, but failed to decrease IL-6 and IL-1ß. In murine endotoxemia models, BCE markedly decreased serum TNF-α, but had no impact on IL-6 and IL-1ß. BCE also restricted complement activation in vitro and in vivo. Nevertheless, the mixture of saikosaponin A and D could not suppress supernatant TNF-α of monocytes and serum TNF-α of endotoxemia mice. CONCLUSIONS: The present study dissects the peripheral mechanism for the antipyretic effect of BC used in the traditional way. Our findings indicate that BCE directly suppresses monocyte-produced TNF-α, thus decreasing circulating TNF-α, which may be responsible for its mild but confirmed antipyretic action.

Anti-oxidative and anti-inflammatory activities of the ethanol extract of edible flower from Chimonanthus praecox.

Chimonanthi Praecocis Flos, namely wintersweet flower, is the edible flower or flower bud of Chimonanthus praecox (L.) Link which is a deciduous shrub plant originated from China and is widely cultivated as a garden or ornamental plant all over the world. However, few studies focused on its anti-inflammatory property. In the present study, we explored the anti-inflammatory and anti-oxidative activities of ethanol extract of Chimonanthi Praecocis Flos (CPE) which contained 7.980% ± 0.176% total flavonoids and 1.461% ± 0.041% total alkaloids. In LPS-stimulated RAW264.7 macrophages, CPE significantly decreased the production of NO and prostaglandin E2 (PGE2) through reducing the expressions of their synthases-inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). It also suppressed the transcription and translation of pro-inflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Further research revealed that CPE impeded the phosphorylation and degradation of IκBα, thus restraining the nuclear translocation of p65, and consequently dampening NF-κB signaling. In endotoxemia mice, several pro-inflammatory cytokines in serum were also decreased after CPE treatment. Besides anti-inflammatory activity, anti-oxidative activity is another important capacity of wintersweet flower. Indeed, CPE reduced LPS-elevated intracellular total reactive oxygen species (ROS) level by weakening NADPH oxidase activity in cell system. Moreover, it directly scavenged DPPH radical and superoxide anion, and exerted ferric reducing ability in cell-free system. Our findings demonstrate that wintersweet flower can be used as a beneficial natural product or an additive by virtue of its anti-oxidative and anti-inflammatory properties.

Synthetic MRI in the detection and quantitative evaluation of sacroiliac joint lesions in axial spondyloarthritis.

Objective: Our primary objective was to verify the hypothesis that synthetic magnetic resonance imaging (MRI) is similar to conventional MRI in detecting sacroiliac joint lesions in patients with axial spondyloarthritis (axSpA). A secondary objective was to assess the quantitative value of synthetic mapping in bone marrow edema (BME) and fat metaplasia. Methods: A total of 132 axSpA patients who underwent synthetic and conventional MRI from October 2019 to March 2021 were included in this prospective study. Two independent readers visually evaluated active inflammatory (BME, capsulitis, enthesitis, and inflammation at site of erosion) and structural lesions (erosion, sclerosis, ankylosis, and fat metaplasia) of the sacroiliac joints on conventional and synthetic magnetic resonance (MR) images. In addition, T1, T2, and proton density (PD) values, which were generated by synthetic mapping, were used to further quantitatively evaluate BME and fat metaplasia. A McNemar test was used to compare the differences between the two methods in the detection of sacroiliac joint lesions. Intraclass correlation coefficients (ICCs) were used to assess the inter-reader consistency of quantitative values. Mann-Whitney tests were performed, and receiver operating characteristic (ROC) curves were created for all quantitative analyses. Results: There were no statistical difference between synthetic and conventional MRI in the detection of sacroiliac joint lesions (all p-values > 0.05). A total of 103 images of BME and 111 images of fat metaplasia were quantitatively evaluated using T1, T2, and PD values. The consistency of quantitative values among readers was good (ICC 0.903-0.970). T1 and T2 values were consistently higher in BME than in normal marrow (p < 0.001), but PD values were not significantly different (p = 0.830). T2 and PD values were higher in fat metaplasia than in normal marrow, but T1 values were lower (p < 0.001). In the case of BME, T1 values had greater diagnostic efficiency [area under the curve (AUC) 0.99] than T2 values (AUC 0.78). There were no significant differences in the diagnostic efficiency of T1 (AUC 0.88), T2 (AUC 0.88), and PD (AUC 0.88) values in the case of fat metaplasia. Conclusion: Synthetic MRI is as effective as conventional MRI in detecting sacroiliac joint lesions in patients with axSpA. Furthermore, synthetic mapping can accurately quantify BME and fat metaplasia.

Resibufogenin, one of bufadienolides in toad venom, suppresses LPS-induced inflammation via inhibiting NF-κB and AP-1 pathways.

Toad venom is a traditional Chinese medicine that has a long history in treating infectious and inflammatory diseases, such as carbuncle, pharyngitis. As one of the major active components in toad venom, resibufogenin (RBG) possesses a variety of pharmacological activities, including lowering blood pressure, reducing proteinuria and preventing oxidative stress. But only its antitumor activity attracts widespread attention in these years. This study aimed to explore the nonnegligible anti-inflammatory activity of RBG in vivo and in vitro. In endotoxemia mice, a single intraperitoneal administration of RBG significantly lowered serum TNF-α, IL-6 and MCP-1 levels. In LPS-stimulated macrophages, RBG decreased LPS-induced pro-inflammatory mediators' productions (e.g., iNOS, IL-6, TNF-α and MCP-1) through suppressing their transcriptions. Mechanism study showed that RBG hindered IκBα phosphorylation and prevented nuclear translocation of p65, thus inactivating nuclear factor-κB (NF-κB) signaling. Concurrently, RBG also dampened activator protein-1 (AP-1) signaling through inhibiting the phosphorylation levels of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Besides LPS (TLR4 ligand) model, RBG also inhibited Pam3CSK4 (TLR2 ligand)- or poly I:C (TLR3 ligand)-induced inflammatory reactions, suggesting that its target(s) site is(are) not on the cytomembrane. These findings not only support the pharmacological basis for the traditional use of toad venom in inflammatory diseases, but also provide a promising anti-inflammatory candidate.

A comparative study of spike protein of SARS-CoV-2 and its variant Omicron (B.1.1.529) on some immune characteristics.

The emergence of Omicron variant raises great concerns because of its rapid transmissibility and its numerous mutations in spike protein (S-protein). S-protein can act as a pathogen-associated molecular pattern and complement activator as well as antigen. We compared some immune characteristics of trimer S-proteins for wild type (WT-S) and B.1.1.529 Omicron (Omicron-S) to investigate whether the mutations have affected its pathogenicity and antigenic shift. The results indicated that WT-S and Omicron-S directly activated nuclear factor-κB (NF-κB) and induced the release of pro-inflammatory cytokines in macrophages, but the actions of Omicron-S were weaker. These inflammatory reactions could be abrogated by a Toll-like receptor 4 antagonist TAK-242. Two S-proteins failed to induce the production of antiviral molecular interferon-ß. In contrast to pro-inflammatory effects, the ability of two S-proteins to activate complement was comparable. We also compared the binding ability of two S-proteins to a high-titer anti-WT-receptor-binding domain antibody. The data showed that WT-S strongly bound to this antibody, while Omicron-S was completely off-target. Collectively, the mutations of Omicron have a great impact on the pro-inflammatory ability and epitopes of S-protein, but little effect on its ability to activate complement. Addressing these issues can be helpful for more adequate understanding of the pathogenicity of Omicron and the vaccine breakthrough infection.

Music-based casual video game training alleviates symptoms of subthreshold depression.

Objectives: In this preregistered study, we investigated the beneficial effects of music-based casual video game training on the depression, anxiety and stress symptoms in a cohort of young individuals with subthreshold depression and the underlying mechanisms. Methods: The study included 56 young individuals (18-26 years of age) with subthreshold or mild depression based on the Beck Depression Inventory-II (BDI-II) scores between 14 and 19. They were randomly assigned into the experimental group (n = 28) or the control group (n = 28). The experimental group underwent music-based casual video game training for 4 weeks. During the same time, the control group participants conducted daily life activities without any intervention. The study participants in the two groups were analyzed using the Depression Anxiety and Stress Scale (DASS-21) during the baseline before the intervention, as well as DASS-21, Positive and negative Affect Scale (PANAS), General Self-efficacy Scale (GSES), and the Emotional Regulation Questionnaire (ERQ) twice a week during the 4 weeks of intervention. Results: The depression, anxiety, and stress symptoms were significantly reduced in the experimental group participants after 4 weeks of music-based video game training compared with the control group. The DAS scores in the experimental group were alleviated in the third and fourth weeks of training compared with the control group. Moreover, analysis using the general linear model demonstrated that the number of training weeks and self-efficacy were associated with significant reduction in depression, anxiety and stress. Furthermore, our results demonstrated that self-efficacy was correlated with positive emotion and emotional regulation. Conclusion: Our study showed that music-based casual video game training significantly decreased depression, anxiety, and stress in the young individuals with subthreshold depression by enhancing self-efficacy.

MAPKs/AP-1, not NF-κB, is responsible for MCP-1 production in TNF-α-activated adipocytes.

Obesity is associated with the infiltration of monocytes/macrophages into adipose tissue in which MCP-1 plays a crucial role. But the regulatory mechanism of MCP-1 expression in adipocytes is not well defined. Our results demonstrated that TNF-α induced abundant MCP-1 production in adipocytes, including 3T3-L1 pre- (≈ 9 to 18-fold), mature adipocytes (≈ 4 to 6-fold), and primary adipocytes(< 2-fold), among which 3T3-L1 pre-adipocytes showed the best reactiveness. Thus, 3T3-L1 pre-adipocytes were used for the most of following experiments. At the transcriptional level, TNF-α (20 ng/mL) also promoted the mRNA expression of MCP-1. It is well recognized that the engagement of TNF-α with its receptor can trigger both NF-κB and AP-1 signalling, which was also confirmed in our study (5-fold and 2-fold). Unexpectedly and counterintuitively, multiple NF-κB inhibitors with different mechanisms failed to suppress TNF-α-induced MCP-1 production, but rather the inhibitors for any one of MAPKs (JNK, ERK and p38) could do. This study, for the first time, reveals that MAPKs/AP-1 but not NF-κB signalling is responsible for MCP-1 production in TNF-α-activated adipocytes. These findings provide important insight into the role of AP-1 signalling in adipose tissue, and may lead to the development of therapeutical repositioning strategies in metaflammation.Abbreviations: AP-1, activator protein-1; CHX, cycloheximide; IR, insulin resistance; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κB; RT-qPCR, quantitative real-time PCR; T2DM, type 2 diabetes mellitus; TRE, triphorbol acetate-response element.

Selective Phytotoxic Effects of Sesquiterpenoids from Sonchus arvensis as a Preliminary Approach for the Biocontrol of Two Problematic Weeds of Wheat.

The objective of this study is to find new selective allelochemicals for managing two problematic weeds redroot pigweed (Amaranthus retroflexus) and common lambsquarters (Chenopodium album) with minimal negative effects on wheat, thereby facilitating the development of eco-friendly botanical herbicide. Three new sesquiterpenoids, sonarvenolide A-C (1-3), and nine known sesquiterpenoids (4-12) were isolated from Sonchus arvensis. Compound 1 was a rare peroxide-substituted eudesmane-type sesquiterpenoid, and compound 3 was a rare iphionane-type sesquiterpenoid. Notably, compounds 1, 3, 4, 6-8, and 11 showed selectivity phytotoxic activity. In particular, compounds 1, 3, and 4 exhibited excellent germination inhibitory effect on A. retroflexus (IC50 = 32.0-129.0 µM), higher than that of the positive control triasulfuron (IC50 = 141.7 µM), and compound 4 showed excellent inhibition on C. album (IC50 = 82.0 µM), higher than that of triasulfuron (IC50 = 100.9 µM). In addition, compounds 1, 3, and 4 showed allelopathy to the growth of two weeds, which were more potent than or close to that of triasulfuron. Furthermore, these compounds were not toxic to wheat even at a high concentration (1000 µM). Structure-activity relationships (SARs) revealed that the presence of peroxides or the absence of hydroxyl at C-5 in the eudesmane-type sesquiterpenoids could strengthen the inhibitory activities. The discovery of selective allelochemicals provides not only a new choice to control two problematic weeds of wheat but also new natural lead compounds for herbicides.

In Vivo Uranium Decorporation by a Tailor-Made Hexadentate Ligand.

The sequestration of uranium, particularly from the deposited bones, has been an incomplete task in chelation therapy for actinide decorporation. Part of the reason is that all previous decorporation ligands are not delicately designed to meet the coordination requirement of uranyl cations. Herein, guided by DFT calculation, we elaborately design a hexadentate ligand (TAM-2LI-MAM2), whose preorganized planar oxo-donor configuration perfectly matches the typical coordination geometry of the uranyl cation. This leads to an ultrahigh binding affinity to uranyl supported by an in vitro desorption experiment of uranyl phosphate. Administration of this ligand by prompt intraperitoneal injection demonstrates its uranyl removal efficiencies from the kidneys and bones are up to 95.4% and 81.2%, respectively, which notably exceeds all the tested chelating agents as well as the clinical drug ZnNa3-DTPA, setting a new record in uranyl decorporation efficacy.

Unlocking Drought-Induced Tree Mortality: Physiological Mechanisms to Modeling.

Drought-related tree mortality has become a major concern worldwide due to its pronounced negative impacts on the functioning and sustainability of forest ecosystems. However, our ability to identify the species that are most vulnerable to drought, and to pinpoint the spatial and temporal patterns of mortality events, is still limited. Model is useful tools to capture the dynamics of vegetation at spatiotemporal scales, yet contemporary land surface models (LSMs) are often incapable of predicting the response of vegetation to environmental perturbations with sufficient accuracy, especially under stressful conditions such as drought. Significant progress has been made regarding the physiological mechanisms underpinning plant drought response in the past decade, and plant hydraulic dysfunction has emerged as a key determinant for tree death due to water shortage. The identification of pivotal physiological events and relevant plant traits may facilitate forecasting tree mortality through a mechanistic approach, with improved precision. In this review, we (1) summarize current understanding of physiological mechanisms leading to tree death, (2) describe the functionality of key hydraulic traits that are involved in the process of hydraulic dysfunction, and (3) outline their roles in improving the representation of hydraulic function in LSMs. We urge potential future research on detailed hydraulic processes under drought, pinpointing corresponding functional traits, as well as understanding traits variation across and within species, for a better representation of drought-induced tree mortality in models.