Antioxidant synergistic anti-inflammatory effect in the MAPK/NF-κB pathway of peptide KGEYNK (KK-6) from giant salamander (Andrias davidianus).

BACKGROUND: Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties. RESULTS: KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1ß (764.81 ng mL-1), interleukin-6 (1.06 ng mL-1) and tumor necrosis factor-α (4440.45 ng mL-1). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 µg mL-1; superoxide dismutase: 0.589 µg mL-1) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 µg mL-1). CONCLUSION: Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.

In vitro analysis of monomer leaching in modern dental materials: CAD milled, printed, traditional heat-processed, and auto-polymerizing denture base resins.

PURPOSE: Denture fabrication has shifted from traditional heat-processed and auto-polymerizing materials to computer-aided design and computer-aided manufacturing (CAD-CAM) milled and printed materials. The monomer in traditional materials can induce an allergic reaction in some patients. With the rise in the edentulous population and increasing demand for the fabrication of dentures, these newer materials should be studied for monomer leaching. The purpose of this study was to evaluate the ratio of residual monomer in materials being used for denture bases: CAD-milled polymethylmethacrylate (PMMA), printed denture base resin, heat-processed PMMA, and auto-polymerizing PMMA comparatively. MATERIALS AND METHODS: Milled, printed, heat-activated, and auto-polymerizing denture base specimens (n = 3 for each group, each test run three times) were fabricated according to manufacturer recommendations. Specimens were first immersed in deuterated chloroform (CDCl3), a deuterated organic solvent, to evaluate monomer leaching and to observe physical properties of the materials. NMR spectroscopy was used to evaluate the dissolution of materials and residual monomer to crosslinked polymer ratios at 1, 4, and 9 days. A second group of specimens was then immersed in deuterium oxide (D2O) to evaluate if the residual monomers would leach out of the system. The solution was then analyzed using nuclear magnetic resonance (NMR) spectroscopy for 1 month. The deuterated forms of chloroform (CDCl3) and water (D2O) were used to enable sample characterization by NMR. RESULTS: While the heat-processed, auto-polymerizing, and milled specimens possessed residual monomers, no significant monomer leaching was noted in the printed specimen, while immersed in CDCl3. Similarly, the printed specimen was most resistant to dissolution, as compared to the rest; dissolution of the specimen is indicative of little to no cross-linking. No detectable dissolution of monomer was seen when all specimens were immersed in D2O for up to 1 month. CONCLUSIONS: Residual monomers were not found in the printed denture material in this study in either CDCl3 or D2O, whereas CAD-milled and traditionally processed denture bases still have residual monomers within their respective systems when immersed in organic solvent. None of the specimens tested leached monomers into D2O.

Bimin Kang ameliorates the minimal persistent inflammation in allergic rhinitis by reducing BCL11B expression and regulating ILC2 plasticity.

ETHNOPHARMACOLOGICAL RELEVANCE: Minimal persistent inflammation (MPI) is a major contributor to the recurrence of allergic rhinitis (AR). The traditional Chinese herbal medicine known as Bimin Kang Mixture (BMK) have been used in clinics for decades to treat AR, which can relieve AR symptoms, reduce inflammatory response and improve immune function. However, its mechanism in controlling MPI is still unclear. AIM OF THE STUDY: This study aims to assess the therapeutic effect of BMK on MPI, and elaborate the mechanism involved in BMK intervention in BCL11B regulation of type 2 innate lymphoid cell (ILC2) plasticity in the treatment of MPI. MATERIAL AND METHODS: The effect of BMK (9.1 ml/kg) and Loratadine (15.15 mg/kg) on MPI was evaluated based on symptoms, pathological staining, and ELISA assays. RT-qPCR and flow cytometry were also employed to assess the expression of BCL11B, IL-12/IL-12Rß2, and IL-18/IL-18Rα signaling pathways associated with ILC2 plasticity in the airway tissues of MPI mice following BMK intervention. RESULTS: BMK restored the airway epithelial barrier, and markedly reduced inflammatory cells (eosinophils, neutrophils) infiltration (P < 0.01) and goblet cells hyperplasia (P < 0.05). BCL11B expression positively correlated with the ILC2 proportion in the lungs and nasal mucosa of AR and MPI mice (P < 0.01). BMK downregulated BCL11B expression (P < 0.05) and reduced the proportion of ILC2, ILC3 and ILC3-like ILC2 subsets (P < 0.05). Moreover, BMK promoted the conversion of ILC2 into an ILC1-like phenotype through IL-12/IL-12Rß2 and IL-18/IL-18Rα signaling pathways in MPI mice. CONCLUSION: By downregulating BCL11B expression, BMK regulates ILC2 plasticity and decreases the proportion of ILC2, ILC3, and ILC3-like ILC2 subsets, promoting the conversion of ILC2 to ILC1, thus restoring balance of ILC subsets in airway tissues and control MPI.

Plexin D1 negatively regulates macrophage-derived foam cell migration via the focal adhesion kinase/Paxillin pathway.

BACKGROUND: Macrophage-derived foam cell formation is a hallmark of atherosclerosis and is retained during plaque formation. Strategies to inhibit the accumulation of these cells hold promise as viable options for treating atherosclerosis. Plexin D1 (PLXND1), a member of the Plexin family, has elevated expression in atherosclerotic plaques and correlates with cell migration; however, its role in macrophages remains unclear. We hypothesize that the guidance receptor PLXND1 negatively regulating macrophage mobility to promote the progression of atherosclerosis. METHODS: We utilized a mouse model of atherosclerosis based on a high-fat diet and an ox-LDL- induced foam cell model to assess PLXND1 levels and their impact on cell migration. Through western blotting, Transwell assays, and immunofluorescence staining, we explored the potential mechanism by which PLXND1 mediates foam cell motility in atherosclerosis. RESULTS: Our study identifies a critical role for PLXND1 in atherosclerosis plaques and in a low-migration capacity foam cell model induced by ox-LDL. In the aortic sinus plaques of ApoE-/- mice, immunofluorescence staining revealed significant upregulation of PLXND1 and Sema3E, with colocalization in macrophages. In macrophages treated with ox-LDL, increased expression of PLXND1 led to reduced pseudopodia formation and decreased migratory capacity. PLXND1 is involved in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK. Additionally, FAK inhibitors counteract the ox-LDL-induced migration suppression by modulating the phosphorylation states of FAK, Paxillin and their downstream effectors CDC42 and PAK. CONCLUSION: Our findings indicate that PLXND1 plays a role in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK to promoting atherosclerosis.

The therapeutic role of γδT cells in TNBC.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that presents significant therapeutic challenges due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. As a result, conventional hormonal and targeted therapies are largely ineffective, underscoring the urgent need for novel treatment strategies. γδT cells, known for their robust anti-tumor properties, show considerable potential in TNBC treatment as they can identify and eliminate tumor cells without reliance on MHC restrictions. These cells demonstrate extensive proliferation both in vitro and in vivo, and can directly target tumors through cytotoxic effects or indirectly by promoting other immune responses. Studies suggest that expansion and adoptive transfer strategies targeting Vδ2 and Vδ1 γδT cell subtypes have shown promise in preclinical TNBC models. This review compiles and discusses the existing literature on the primary subgroups of γδT cells, their roles in cancer therapy, their contributions to tumor cell cytotoxicity and immune modulation, and proposes potential strategies for future γδT cell-based immunotherapies in TNBC.

Quantitative turbidimetric characterization of stabilized complex coacervate dispersions.

Stabilizing complex coacervate microdroplets is desirable due to their various applications, such as bioreactors, drug delivery vehicles, and encapsulants. Here, we present quantitative characterization of complex coacervate dispersion stability inferred by turbidimetry measurements. The stability of the dispersions is shown to be modulated by the concentrations of comb polyelectrolyte (cPE) stabilizers and salt. We demonstrate cPEs as effective stabilizers for complex coacervate dispersions independent of the chemistry or length of the constituent polyelectrolytes, salts, or preparation routes. By monitoring the temporal evolution of dispersion turbidity, we show that cPEs suppress microdroplet coalescence with minimal change in microdroplet sizes over 48 hours, even at salt concentrations up to 300 mM. The number density and average microdroplet size are shown to be controlled by varying the cPE and salt concentrations. Lastly, turbidity maps, akin to binodal phase maps, depict an expansion of the turbid two-phase region and an increase in the salt resistance of the coacervates upon the introduction of cPEs. The coacervate salt resistance is shown to increase by >3×, and this increase is maintained for up to 15 days, demonstrating that cPEs impart higher salt resistance over extended durations.

Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu's arteritis.

OBJECTIVES: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK. METHODS: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments. RESULTS: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients. CONCLUSIONS: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.

Neonicotinoid insecticides in paddy fields: Dissipation dynamics, migration, and dietary risk.

Neonicotinoid insecticides (NNIs) have caused widespread contamination of multiple environmental media and posed a serious threat to ecosystem health by accidently injuring non-target species. This study collected samples of water, soil, and rice plant tissues in a water-soil-plant system of paddy fields after spaying imidacloprid (IMI), thiamethoxam (THM), and clothianidin (CLO) to analyze their distribution characteristics and migration procedures and to assess related dietary risks of rice consumption. In the paddy water, the concentrations of NNIs showed a dynamic change of increasing and then decreasing during about a month period, and the initial deposition of NNIs showed a trend of CLO (3.08 µg/L) > THM (2.74 µg/L) > IMI (0.97 µg/L). In paddy soil, the concentrations of the three NNIs ranged from 0.57 to 68.3 ng/g, with the highest residual concentration at 2 h after application, and the concentration trend was opposite to that in paddy water. The initial deposition amounts of IMI, THM, and CLO in the root system were 5.19, 3.02, and 5.24 µg/g, respectively, showing a gradual decrease over time. In the plant, the initial deposition amounts were 19.3, 9.36, and 52.6 µg/g for IMI, THM, and CLO, respectively, exhibiting concentration trends similar to those in the roots. Except for IMI in soil, the dissipation of the NNIs conformed to the first-order kinetic equation in paddy water, soil, and plant. The results of bioconcentration factors (BCFs) and translocation factor (TF) indicated that NNIs can be bi-directionally transported in plants through leaf absorption and root uptake. The risk of NNIs intake through rice consumption was low for all age groups, with a slightly higher risk of exposure in males than in females.

Mitogenomic phylogeny, biogeography, and cryptic divergence of the genus Silurus (Siluriformes: Siluridae).

The genus Silurus, an important group of catfish, exhibits heterogeneous distribution in Eurasian freshwater systems. This group includes economically important and endangered species, thereby attracting considerable scientific interest. Despite this interest, the lack of a comprehensive phylogenetic framework impedes our understanding of the mechanisms underlying the extensive diversity found within this genus. Herein, we analyzed 89 newly sequenced and 20 previously published mitochondrial genomes (mitogenomes) from 13 morphological species to reconstruct the phylogenetic relationships, biogeographic history, and species diversity of Silurus. Our phylogenetic reconstructions identified eight clades, supported by both maximum-likelihood and Bayesian inference. Sequence-based species delimitation analyses yielded multiple molecular operational taxonomic units (MOTUs) in several taxa, including the Silurus asotus complex (four MOTUs) and Silurus microdorsalis (two MOTUs), suggesting that species diversity is underestimated in the genus. A reconstructed time-calibrated tree of Silurus species provided an age estimate of the most recent common ancestor of approximately 37.61 million years ago (Ma), with divergences among clades within the genus occurring between 11.56 Ma and 29.44 Ma, and divergences among MOTUs within species occurring between 3.71 Ma and 11.56 Ma. Biogeographic reconstructions suggested that the ancestral area for the genus likely encompassed China and the Korean Peninsula, with multiple inferred dispersal events to Europe and Central and Western Asia between 21.78 Ma and 26.67 Ma and to Japan between 2.51 Ma and 18.42 Ma. Key factors such as the Eocene-Oligocene extinction event, onset and intensification of the monsoon system, and glacial cycles associated with sea-level fluctuations have likely played significant roles in shaping the evolutionary history of the genus Silurus.

Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke.

Background: Hemorrhagic stroke (HS), a leading cause of death and disability worldwide, has not been clarified in terms of the underlying biomolecular mechanisms of its development. Circulating metabolites have been closely associated with HS in recent years. Therefore, we explored the causal association between circulating metabolomes and HS using Mendelian randomization (MR) analysis and identified the molecular mechanisms of effects. Methods: We assessed the causal relationship between circulating serum metabolites (CSMs) and HS using a bidirectional two-sample MR method supplemented with five ways: weighted median, MR Egger, simple mode, weighted mode, and MR-PRESSO. The Cochran Q-test, MR-Egger intercept test, and MR-PRESSO served for the sensitivity analyses. The Steiger test and reverse MR were used to estimate reverse causality. Metabolic pathway analyses were performed using MetaboAnalyst 5.0, and genetic effects were assessed by linkage disequilibrium score regression. Significant metabolites were further synthesized using meta-analysis, and we used multivariate MR to correct for common confounders. Results: We finally recognized four metabolites, biliverdin (OR 0.62, 95% CI 0.40-0.96, PMVMR = 0.030), linoleate (18. 2n6) (OR 0.20, 95% CI 0.08-0.54, PMVMR = 0.001),1-eicosadienoylglycerophosphocholine* (OR 2.21, 95% CI 1.02-4.76, PMVMR = 0.044),7-alpha-hydroxy-3 -oxo-4-cholestenoate (7-Hoca) (OR 0.27, 95% CI 0.09-0.77, PMVMR = 0.015) with significant causal relation to HS. Conclusion: We demonstrated significant causal associations between circulating serum metabolites and hemorrhagic stroke. Monitoring, diagnosis, and treatment of hemorrhagic stroke by serum metabolites might be a valuable approach.

Antimony isotopic fractionation induced by Sb(V) adsorption on ß-MnO2.

Antimony (Sb) isotopes hold immense promise for unraveling Sb biogeochemical cycling in environmental systems. Mn oxides help control the fate of Sb via adsorption reactions, yet the behavior and mechanisms of Sb isotopic fractionation on Mn oxides are poorly understood. In this study, we examine the Sb isotopic fractionation induced by adsorption on ß-MnO2 in different experiments (kinetic, isothermal, effect of pH). We observe that adsorption on ß-MnO2 surfaces preferentially enriches lighter Sb isotopes through equilibrium fractionation, with Δ123Sbaqueous-adsorbed of 0.55-0.79 ‰. Neither the pH or surface coverage affects the fractionation magnitude. The analysis of extended X-ray absorption fine structure (EXAFS) demonstrates that the enrichment of light isotope results from the adsorption of inner-sphere complexation on solids. Our finding of this study enhances our comprehension of the impact of ß-MnO2 on Sb isotopic fractionation behavior and mechanism and facilitate the applicability of Sb isotopes as effective tracers to elucidate the origins and pathways of Sb contamination in environmental systems, as well as provide a new insight into forecasting the isotopic fractionation of other similar metals adsorbed by manganese oxides.

Deep Boosting Learning: A Brand-New Cooperative Approach for Image-Text Matching.

Image-text matching remains a challenging task due to heterogeneous semantic diversity across modalities and insufficient distance separability within triplets. Different from previous approaches focusing on enhancing multi-modal representations or exploiting cross-modal correspondence for more accurate retrieval, in this paper we aim to leverage the knowledge transfer between peer branches in a boosting manner to seek a more powerful matching model. Specifically, we propose a brand-new Deep Boosting Learning (DBL) algorithm, where an anchor branch is first trained to provide insights into the data properties, with a target branch gaining more advanced knowledge to develop optimal features and distance metrics. Concretely, an anchor branch initially learns the absolute or relative distance between positive and negative pairs, providing a foundational understanding of the particular network and data distribution. Building upon this knowledge, a target branch is concurrently tasked with more adaptive margin constraints to further enlarge the relative distance between matched and unmatched samples. Extensive experiments validate that our DBL can achieve impressive and consistent improvements based on various recent state-of-the-art models in the image-text matching field, and outperform related popular cooperative strategies, e.g., Conventional Distillation, Mutual Learning, and Contrastive Learning. Beyond the above, we confirm that DBL can be seamlessly integrated into their training scenarios and achieve superior performance under the same computational costs, demonstrating the flexibility and broad applicability of our proposed method.

Exploring salt tolerance mechanisms using machine learning for transcriptomic insights: case study in Spartina alterniflora.

Salt stress poses a significant threat to global cereal crop production, emphasizing the need for a comprehensive understanding of salt tolerance mechanisms. Accurate functional annotations of differentially expressed genes are crucial for gaining insights into the salt tolerance mechanism. The challenge of predicting gene functions in under-studied species, especially when excluding infrequent GO terms, persists. Therefore, we proposed the use of NetGO 3.0, a machine learning-based annotation method that does not rely on homology information between species, to predict the functions of differentially expressed genes under salt stress. Spartina alterniflora, a halophyte with salt glands, exhibits remarkable salt tolerance, making it an excellent candidate for in-depth transcriptomic analysis. However, current research on the S. alterniflora transcriptome under salt stress is limited. In this study we used S. alterniflora as an example to investigate its transcriptional responses to various salt concentrations, with a focus on understanding its salt tolerance mechanisms. Transcriptomic analysis revealed substantial changes impacting key pathways, such as gene transcription, ion transport, and ROS metabolism. Notably, we identified a member of the SWEET gene family in S. alterniflora, SA_12G129900.m1, showing convergent selection with the rice ortholog SWEET15. Additionally, our genome-wide analyses explored alternative splicing responses to salt stress, providing insights into the parallel functions of alternative splicing and transcriptional regulation in enhancing salt tolerance in S. alterniflora. Surprisingly, there was minimal overlap between differentially expressed and differentially spliced genes following salt exposure. This innovative approach, combining transcriptomic analysis with machine learning-based annotation, avoids the reliance on homology information and facilitates the discovery of unknown gene functions, and is applicable across all sequenced species.

Non-coplanar helimagnetism in the layered van-der-Waals metal DyTe3.

Van-der-Waals magnetic materials can be exfoliated to realize ultrathin sheets or interfaces with highly controllable optical or spintronics responses. In majority, these are collinear ferro-, ferri-, or antiferromagnets, with a particular scarcity of lattice-incommensurate helimagnets of defined left- or right-handed rotation sense, or helicity. Here, we report polarized neutron scattering experiments on DyTe3, whose layered structure has highly metallic tellurium layers separated by double-slabs of dysprosium square nets. We reveal cycloidal (conical) magnetic textures, with coupled commensurate and incommensurate order parameters, and probe the evolution of this ground state in a magnetic field. The observations are well explained by a one-dimensional spin model, with an off-diagonal on-site term that is spatially modulated by DyTe3's unconventional charge density wave (CDW) order. The CDW-driven term couples to antiferromagnetism, or to the net magnetization in an applied magnetic field, and creates a complex magnetic phase diagram indicative of competing interactions in this easily cleavable van-der-Waals helimagnet.

Palladium-Catalyzed Atroposelective Suzuki-Miyaura Coupling to Construct Axially Chiral Tetra-Substituted α-Boryl Styrenes.

Palladium-catalyzed Suzuki-Miyaura (SM) coupling is a valuable method for forming C─C bonds, including those between aryl moieties. However, achieving atroposelective synthesis of axially chiral styrenes via SM coupling remains challenging. In this study, a palladium-catalyzed atroposelective Suzuki-Miyaura coupling between gem-diborylalkenes and aryl halides is presented. Using the monophosphine ligand Me-BI-DIME (L2), a range of axially chiral tetra-substituted acyclic styrenes with high yields and excellent enantioselectivities are successfully synthesized. Control experiments reveal that the gem-diboryl group significantly influences the product enantioselectivities and the coupling prefers to occur at sites with lower steric hindrance. Additionally, the alkenyl boronate group in the products proves versatile, allowing for various transformations while maintaining high optical purities.

m6Aexpress-enet: Predicting the regulatory expression m6A sites by an enet-regularization negative binomial regression model.

As the most abundant mRNA modification, m6A controls and influences many aspects of mRNA metabolism including the mRNA stability and degradation. However, the role of specific m6A sites in regulating gene expression still remains unclear. In additional, the multicollinearity problem caused by the correlation of methylation level of multiple m6A sites in each gene could influence the prediction performance. To address the above challenges, we propose an elastic-net regularized negative binomial regression model (called m6Aexpress-enet) to predict which m6A site could potentially regulate its gene expression. Comprehensive evaluations on simulated datasets demonstrate that m6Aexpress-enet could achieve the top prediction performance. Applying m6Aexpress-enet on real MeRIP-seq data from human lymphoblastoid cell lines, we have uncovered the complex regulatory pattern of predicted m6A sites and their unique enrichment pathway of the constructed co-methylation modules. m6Aexpress-enet proves itself as a powerful tool to enable biologists to discover the mechanism of m6A regulatory gene expression. Furthermore, the source code and the step-by-step implementation of m6Aexpress-enet is freely accessed at https://github.com/tengzhangs/m6Aexpress-enet.

Spatiotemporal variation, fluxes and risk evaluation of neonicotinoid insecticides within the midsection of Yangtze River, China: An exploration as ecological protection threshold.

Neonicotinoid insecticides (NNIs) have attracted global concern due to its extensive use in agricultural activities and their potential risks to the animal and human health, however, there is limited knowledge on the regional traits and ecological risks of NNIs in the aquatic environments. We herein investigated the occurrence of NNIs within the midsection of Yangtze River in China, offering the inaugural comprehensive report on NNIs within this region. In this study, eleven NNIs were analyzed in 108 river water and sediment samples from three seasons (normal, dry and wet season). We detected a minimum of seven NNIs in the water and four NNIs in the sediment, with total concentrations ranging from 12.33 to 100.5 ng/L in water and 0.08-5.68 ng/g in sediment. The levels of NNIs in both river water and sediment were primarily influenced by the extent of agricultural activities. The estimated annual load of NNIs within the midsection of Yangtze River totaled 40.27 tons, April was a critical contamination period. Relative potency factor (RPF) analysis of the human exposure risk revealed that infants faced the greatest exposure risk, with an estimated daily intake of 11.27 ng kg-1∙bw∙d-1. We established the acute and chronic thresholds for aquatic organisms by employing the Species Sensitive Distribution (SSD) method (acute: 384.1 ng/L; chronic: 168.9 ng/L). Based on the findings from this study, 33% of the river water samples exceeded the chronic ecological risks thresholds, indicating the urgent need for intervention programs to guarantee the safety of the river for aquatic life in the Yangtze River Basin.

The Spartina alterniflora genome sequence provides insights into the salt-tolerance mechanisms of exo-recretohalophytes.

Spartina alterniflora is an exo-recretohalophyte Poaceae species that is able to grow well in seashore, but the genomic basis underlying its adaptation to salt tolerance remains unknown. Here, we report a high-quality, chromosome-level genome assembly of S. alterniflora constructed through PacBio HiFi sequencing, combined with high-throughput chromosome conformation capture (Hi-C) technology and Illumina-based transcriptomic analyses. The final 1.58 Gb genome assembly has a contig N50 size of 46.74 Mb. Phylogenetic analysis suggests that S. alterniflora diverged from Zoysia japonica approximately 21.72 million years ago (MYA). Moreover, whole-genome duplication (WGD) events in S. alterniflora appear to have expanded gene families and transcription factors relevant to salt tolerance and adaptation to saline environments. Comparative genomics analyses identified numerous species-specific genes, significantly expanded genes and positively selected genes that are enriched for 'ion transport' and 'response to salt stress'. RNA-seq analysis identified several ion transporter genes including the high-affinity K+ transporters (HKTs), SaHKT1;2, SaHKT1;3 and SaHKT1;8, and high copy number of Salt Overly Sensitive (SOS) up-regulated under high salt conditions, and the overexpression of SaHKT2;4 in Arabidopsis thaliana conferred salt tolerance to the plant, suggesting specialized roles for S. alterniflora to adapt to saline environments. Integrated metabolomics and transcriptomics analyses revealed that salt stress activate glutathione metabolism, with differential expressions of several genes such as γ-ECS, GSH-S, GPX, GST and PCS in the glutathione metabolism. This study suggests several adaptive mechanisms that could contribute our understanding of evolutional basis of the halophyte.

SMEK1 ablation promotes glucose uptake and improves obesity-related metabolic dysfunction via AMPK signaling pathway.

Obesity has become a major risk of global public health. SMEK1 is also known as a regulatory subunit of protein phosphatase 4 (PP4). Both PP4 and SMEK1 have been clarified in many metabolic functions, including the regulation of hepatic gluconeogenesis and glucose transporter gene expression in yeast. Whether SMEK1 participates in obesity and the broader metabolic role in mammals is unknown. Thus, we investigated the function of SMEK1 in white adipose tissue and glucose uptake. GWAS/GEPIA/GEO database was used to analyze the correlation between SMEK1 and metabolic phenotypes/lipid metabolism-related genes/obesity. Smek1 KO mice were generated to identify the role of SMEK1 in obesity and glucose homeostasis. Cell culture and differentiation of stromal-vascular fractions (SVFs) and 3T3-L1 were used to determine the mechanism. 2-NBDG was used to measure the glucose uptake. Compound C was used to confirm the role of AMPK. We elucidated that SMEK1 was correlated with obesity and adipogenesis. Smek1 deletion enhanced adipogenesis in both SVFs and 3T3-L1. Smek1 KO protected mice from obesity and had protective effects on metabolic disorders, including insulin resistance and inflammation. Smek1 KO mice had lower levels of fasting serum glucose. We found that SMEK1 ablation promoted glucose uptake by increasing p-AMPKα(T172) and the transcription of Glut4 when the effect on AMPK-regulated glucose uptake was due to the PP4 catalytic subunits (PPP4C). Our findings reveal a novel role of SMEK1 in obesity and glucose homeostasis, providing a potential new therapeutic target for obesity and metabolic dysfunction.NEW & NOTEWORTHY Our study clarified the relationship between SMEK1 and obesity for the first time and validated the conclusion in multiple ways by combining available data from public databases, human samples, and animal models. In addition, we clarified the role of SMEK1 in glucose uptake, providing an in-depth interpretation for the study of its function in glucose metabolism.