Sodium Octahydridotriborate as a Solid Electrolyte with Excellent Stability Against Sodium-Metal Anode.

Solid-state sodium metal batteries have been extensively investigated because of their potential to improve safety, cost-effectiveness, and energy density. The development of such batteries urgently required a solid-state electrolyte with fast Na-ion conduction and favorable interfacial compatibility. Herein, the progress on developing the NaB3H8 solid-state electrolytes is reported, which show a liquid-like ionic conductivity of 0.05 S cm-1 at 56 °C with an activation energy of 0.35 eV after an order-disorder phase transformation, matching or surpassing the best single-anion hydridoborate conductors investigated up to now. The steady polarization voltage and significantly decreased resistance are achieved in the symmetric Na/NaB3H8/Na cell, indicating the great electrochemical stability and favorable interfacial contact with the Na metal of NaB3H8. Furthermore, a Na/NaB3H8/TiS2 battery, the first high-rate (up to 1 C) solid-state sodium metal battery using the single-anion hydridoborate electrolyte, is demonstrated, which exhibits superior rate capability (168.2 mAh g-1 at 0.1 C and 141.2 mAh g-1 at 1 C) and long-term cycling stability (70.9% capacity retention at 1 C after 300 cycles) at 30 °C. This work may present a new possibility to solve the interfacial limitations and find a new group of solid-state electrolytes for high-performance sodium metal batteries.

Lipid Nanoparticle-Mediated Delivery of CRISPR-Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism.

Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, is reported to exacerbate hepatic steatosis in NAFLD mice and patients, indicating its probability of being a therapeutic target for NAFLD treatment. In this study, the therapeutic potential of Rubicon blockage is investigated. Lipid nanoparticles carrying Rubicon-specific CRISPR-Cas9 components exhibited liver accumulation, cell internalization, and Rubicon knockdown. A single administration of the nanoparticles results in attenuated lipid deposition and hepatic steatosis, with lower circulating lipid levels and decreased adipocyte size in NAFLD mice. Furthermore, the increase of phosphatidylcholine and phosphatidylethanolamine levels can be observed in the NAFLD mice livers after Rubicon silencing, along with regulatory effects on metabolism-related genes such as CD36, Gpcpd1, Chka, and Lpin2. The results indicate that knockdown of Rubicon improves glycerophospholipid metabolism and thereby ameliorates the NAFLD progression, which provides a potential strategy for NAFLD therapy via the restoration of Rubicon.

A Unified Synthetic Approach to the Pleurotin Natural Products.

The asymmetric total syntheses of four pleurotin natural products, namely, (-)-pleurotin, (+)-leucopleurotin, (+)-leucopleurotinic acid, and (+)-dihydropleurotinic acid, were described in a concise manner. Key transformations feature a Johnson-Claisen rearrangement, a diastereo-controlled sequential hydroboration-oxidation, a SOMO/photoredox activated aldehyde α-alkylation, and oxidative cyclizations.

Multi-gene phylogenetic and taxonomic contributions to Xylaria (Ascomycota) associated with fallen fruits from China.

Morphological and phylogenetic analyses on samples of Xylaria species associated with fallen fruits from China were carried out, and two new species were described, namely X.aleuriticola and X.microcarpa. Xylariaaleuriticola is found on fallen fruits of Aleuritesmoluccana, and characterized by stromata dichotomously branched several times with long acute sterile apices, fertile parts roughened with perithecia and tomentose, and ellipsoid to fusiform ascospores. Xylariamicrocarpa differs in its very small stromata with dark brown tomentum, light brown ascospores with an inconspicuous straight germ slit, and grows on leguminous pods. The differences between the new species and morphologically similar species are discussed. Phylogenetic analyses on ITS-RPB2-TUB sequences confirmed that the two species are clearly separated from other species of the genus Xylaria. Xylarialiquidambaris is reported as a new record from China. A key to the Xylaria species associated with fallen fruits and seeds reported from China is provided to facilitate future studies of the genus.

Efficacy comparison between Mathieu combined urethral plate incision and onlay island flap urethroplasty for distal hypospadias in patients with urethral plate stenosis.

The aim of the study was to compare the efficacy of Mathieu combined urethral plate incision (Mathieu-IP) versus onlay island flap urethroplasty in patients with distal hypospadias complicated by urethral stenosis. The clinical data of 70 patients with distal hypospadias complicated by urethral plate stenosis treated in the Department of Urology, Anhui Provincial Children's Hospital (Hefei, China), from May 2019 to May 2022, were retrospectively analyzed. Thirty-eight patients underwent Mathieu-IP (Mathieu-IP group) and 32 underwent onlay island flap urethroplasty (Onlay group). Follow-ups at 1 month, 6 months, and 12 months postoperatively assessed operative time, complications, urethral meatus morphology, and family satisfaction. The Mathieu-IP group had significantly shorter operative time (mean ± standard deviation [s.d.]: 81.58 ± 5.18 min) versus the Onlay group (mean ± s.d.: 110.75 ± 6.05 min; P < 0.05). Surgical success rates were 78.9% (Mathieu-IP group) and 75.0% (Onlay group), with no significant difference ( P > 0.05). Complications were comparable between the groups. The Mathieu-IP group resulted in a vertical slit-shaped urethral meatus in 89.5% versus 13.8% in the Onlay group ( P < 0.05). Family satisfaction with general penile appearance and skin shape showed no significant differences, but the Mathieu-IP group had higher satisfaction with meatal position ( P < 0.05). Mathieu-IP offers simplicity, safety, and shorter operative time compared to Onlay. Both the techniques effectively treat urethral plate stenosis in distal hypospadias, with reduced postoperative complications compared to tubularized incised plate urethroplasty. Mathieu-IP results in a vertical slit-shaped urethral meatus which enhances urinary stream, indicating its potential for broader adoption.

Involvement of autophagy in mesaconitine-induced neurotoxicity in HT22 cells revealed through integrated transcriptomic, proteomic, and m6A epitranscriptomic profiling.

Background: Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb Aconitum carmichaelii, is commonly used to treat various diseases. Previous studies have indicated the potent toxicity of aconitum despite its pharmacological activities, with limited understanding of its effects on the nervous system and the underlying mechanisms. Methods: HT22 cells and zebrafish were used to investigate the neurotoxic effects of MA both in vitro and in vivo, employing multi-omics techniques to explore the potential mechanisms of toxicity. Results: Our results demonstrated that treatment with MA induces neurotoxicity in zebrafish and HT22 cells. Subsequent analysis revealed that MA induced oxidative stress, as well as structural and functional damage to mitochondria in HT22 cells, accompanied by an upregulation of mRNA and protein expression related to autophagic and lysosomal pathways. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed a correlation between the expression of autophagy-related genes and N6-methyladenosine (m6A) modification following MA treatment. In addition, we identified METTL14 as a potential regulator of m6A methylation in HT22 cells after exposure to MA. Conclusion: Our study has contributed to a thorough mechanistic elucidation of the neurotoxic effects caused by MA, and has provided valuable insights for optimizing the rational utilization of traditional Chinese medicine formulations containing aconitum in clinical practice.

Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans.

Gelsemium elegans Benth. (G. elegans) is a traditional medicinal herb that has anti-inflammatory, analgesic, sedative, and detumescence effects. However, it can also cause intestinal side effects such as abdominal pain and diarrhea. The toxicological mechanisms of gelsenicine are still unclear. The objective of this study was to assess enterotoxicity induced by gelsenicine in the nematodes Caenorhabditis elegans (C. elegans). The nematodes were treated with gelsenicine, and subsequently their growth, development, and locomotion behavior were evaluated. The targets of gelsenicine were predicted using PharmMapper. mRNA-seq was performed to verify the predicted targets. Intestinal permeability, ROS generation, and lipofuscin accumulation were measured. Additionally, the fluorescence intensities of GFP-labeled proteins involved in oxidative stress and unfolded protein response in endoplasmic reticulum (UPRER) were quantified. As a result, the treatment of gelsenicine resulted in the inhibition of nematode lifespan, as well as reductions in body length, width, and locomotion behavior. A total of 221 targets were predicted by PharmMapper, and 731 differentially expressed genes were screened out by mRNA-seq. GO and KEGG enrichment analysis revealed involvement in redox process and transmembrane transport. The permeability assay showed leakage of blue dye from the intestinal lumen into the body cavity. Abnormal mRNAs expression of gem-4, hmp-1, fil-2, and pho-1, which regulated intestinal development, absorption and catabolism, transmembrane transport, and apical junctions, was observed. Intestinal lipofuscin and ROS were increased, while sod-2 and isp-1 expressions were decreased. Multiple proteins in SKN-1/DAF-16 pathway were found to bind stably with gelsenicine in a predictive model. There was an up-regulation in the expression of SKN-1:GFP, while the nuclear translocation of DAF-16:GFP exhibited abnormality. The UPRER biomarker HSP-4:GFP was down-regulated. In conclusion, the treatment of gelsenicine resulted in the increase of nematode intestinal permeability. The toxicological mechanisms underlying this effect involved the disruption of intestinal barrier integrity, an imbalance between oxidative and antioxidant processes mediated by the SKN-1/DAF-16 pathway, and abnormal unfolded protein reaction.

An ultrawide field-of-view pinhole compound eye using hemispherical nanowire array for robot vision.

Garnering inspiration from biological compound eyes, artificial vision systems boasting a vivid range of diverse visual functional traits have come to the fore recently. However, most of these artificial systems rely on transformable electronics, which suffer from the complexity and constrained geometry of global deformation, as well as potential mismatches between optical and detector units. Here, we present a unique pinhole compound eye that combines a three-dimensionally printed honeycomb optical structure with a hemispherical, all-solid-state, high-density perovskite nanowire photodetector array. The lens-free pinhole structure can be designed and fabricated with an arbitrary layout to match the underlying image sensor. Optical simulations and imaging results matched well with each other and substantiated the key characteristics and capabilities of our system, which include an ultrawide field of view, accurate target positioning, and motion tracking function. We further demonstrate the potential of our unique compound eye for advanced robotic vision by successfully completing a moving target tracking mission.

Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/ß-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity.

Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, ß-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt/ß-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells.

A Novel Bifunctional Fusion Protein (Anti-IL-17A-sST2) Protects against Acute Liver Failure, Modulating the TLR4/MyD88 Pathway and NLRP3 Inflammasome Activation.

Acute liver failure (ALF) is a serious inflammatory disorder with high mortality rates, which poses a significant threat to human health. The IL-33/ST2 signal is a crucial regulator in inflammation responses associated with lipopolysaccharide (LPS)-induced macrophages. The IL-17A signaling pathway promotes the release of chemokines and inflammatory cytokines, recruiting neutrophils and T cells under LPS stimulation, thus facilitating inflammatory responses. Here, the potential therapeutic benefits of neutralizing the IL-17A signal and modulating the IL-33/ST2 signal in ALF were investigated. A novel dual-functional fusion protein, anti-IL-17A-sST2, was constructed, which displayed high purity and biological activities. The administration of anti-IL-17A-sST2 resulted in significant anti-inflammatory benefits in ALF mice, amelioration of hepatocyte necrosis and interstitial congestion, and reduction in TNF-α and IL-6. Furthermore, anti-IL-17A-sST2 injection downregulated the expression of TLR4 and NLRP3 as well as important molecules such as MyD88, caspase-1, and IL-1ß. The results suggest that anti-IL-17A-sST2 reduced the secretion of inflammatory factors, attenuated the inflammatory response, and protected hepatic function by regulating the TLR4/MyD88 pathway and inhibiting the NLRP3 inflammasome, providing a new therapeutic approach for ALF.

Harnessing Renewable Lignocellulosic Potential for Sustainable Wastewater Purification.

Utilizing renewable lignocellulosic resources for wastewater remediation is crucial to achieving sustainable social development. However, the resulting by-products and the synthetic process characterized by complexity, high cost, and environmental pollution limit the further development of lignocellulose-based materials. Here, we developed a sustainable strategy that involved a new functional deep eutectic solvent (DES) to deconstruct industrial xylose residue into cellulose-rich residue with carboxyl groups, lignin with carboxyl and quaternary ammonium salt groups, and DES effluent rich in lignin fragments. Subsequently, these fractions equipped with customized functionality were used to produce efficient wastewater remediation materials in cost-effective and environmentally sound manners, namely, photocatalyst prepared by carboxyl-modified cellulose residue, biochar-based adsorbent originated from modified lignin, and flocculant synthesized by self-catalytic in situ copolymerization of residual DES effluent at room temperature. Under the no-waste principle, this strategy upgraded the whole components of waste lignocellulose into high-value-added wastewater remediation materials with excellent universality. These materials in coordination with each other can stepwise purify high-hazardous mineral processing wastewater into drinkable water, including the removal of 99.81% of suspended solids, almost all various heavy metal ions, and 97.09% chemical oxygen demand, respectively. This work provided promising solutions and blueprints for lignocellulosic resources to alleviate water shortages while also advancing the global goal of carbon neutrality.

Mulberry and Hippophae-based solid beverage promotes weight loss in rats by antagonizing white adipose tissue PPARγ and FGFR1 signaling.

Obesity, a multifactorial disease with many complications, has become a global epidemic. Weight management, including dietary supplementation, has been confirmed to provide relevant health benefits. However, experimental evidence and mechanistic elucidation of dietary supplements in this regard are limited. Here, the weight loss efficacy of MHP, a commercial solid beverage consisting of mulberry leaf aqueous extract and Hippophae protein peptides, was evaluated in a high-fat high-fructose (HFF) diet-induced rat model of obesity. Body component analysis and histopathologic examination confirmed that MHP was effective to facilitate weight loss and adiposity decrease. Pathway enrichment analysis with differential metabolites generated by serum metabolomic profiling suggests that PPAR signal pathway was significantly altered when the rats were challenged by HFF diet but it was rectified after MHP intervention. RNA-Seq based transcriptome data also indicates that MHP intervention rectified the alterations of white adipose tissue mRNA expressions in HFF-induced obese rats. Integrated omics reveals that the efficacy of MHP against obesogenic adipogenesis was potentially associated with its regulation of PPARγ and FGFR1 signaling pathway. Collectively, our findings suggest that MHP could improve obesity, providing an insight into the use of MHP in body weight management.

Unveiling the Impact of ApoF Deficiency on Liver and Lipid Metabolism: Insights from Transcriptome-Wide m6A Methylome Analysis in Mice.

Lipid metabolism participates in various physiological processes and has been shown to be connected to the development and progression of multiple diseases, especially metabolic hepatopathy. Apolipoproteins (Apos) act as vectors that combine with lipids, such as cholesterol and triglycerides (TGs). Despite being involved in lipid transportation and metabolism, the critical role of Apos in the maintenance of lipid metabolism has still not been fully revealed. This study sought to clarify variations related to m6A methylome in ApoF gene knockout mice with disordered lipid metabolism based on the bioinformatics method of transcriptome-wide m6A methylome epitranscriptomics. High-throughput methylated RNA immunoprecipitation sequencing (MeRIP-seq) was conducted in both wild-type (WT) and ApoF knockout (KO) mice. As a result, the liver histopathology presented vacuolization and steatosis, and the serum biochemical assays reported abnormal lipid content in KO mice. The m6A-modified mRNAs were conformed consensus sequenced in eukaryotes, and the distribution was enriched within the coding sequences and 3' non-coding regions. In KO mice, the functional annotation terms of the differentially expressed genes (DEGs) included cholesterol, steroid and lipid metabolism, and lipid storage. In the differentially m6A-methylated mRNAs, the functional annotation terms included cholesterol, TG, and long-chain fatty acid metabolic processes; lipid transport; and liver development. The overlapping DEGs and differential m6A-modified mRNAs were also enriched in terms of lipid metabolism disorder. In conclusion, transcriptome-wide MeRIP sequencing in ApoF KO mice demonstrated the role of this crucial apolipoprotein in liver health and lipid metabolism.

Transcriptomic insights into the lipotoxicity of high-fat high-fructose diet in rat and mouse.

Along with the increasing prevalence of obesity worldwide, the deleterious effects of high-calorie diet are gradually recognized through more and more epidemiological studies. However, the concealed and chronic causality whitewashes its unhealthy character. Given an ingenious mechanism orchestrates the metabolic adaptation to high-fat high-fructose (HFF) diet and connive its lipotoxicity, in this study, an experimental rat/mouse model of obesity was induced and a comparative transcriptomic analysis was performed to probe the mystery. Our results demonstrated that HFF diet consumption altered the transcriptomic pattern as well as different high-calorie diet fed rat/mouse manifested distinct hepatic transcriptome. Validation with RT-qPCR and Western blotting confirmed that SREBP1-FASN involved in de novo lipogenesis partly mediated metabolic self-adaption. Moreover, hepatic ACSL1-CPT1A-CPT2 pathway involved in fatty acids ß-oxidation, played a key role in the metabolic adaption to HFF. Collectively, our findings enrich the knowledge of the chronic adaptation mechanisms and also shed light on future investigations. Meanwhile, our results also suggest that efforts to restore the fatty acids metabolic fate could be a promising avenue to fight against obesity and associated steatosis and insulin resistance challenged by HFF diet.

Personalized Driver Gene Prediction Using Graph Convolutional Networks with Conditional Random Fields.

Cancer is a complex and evolutionary disease mainly driven by the accumulation of genetic variations in genes. Identifying cancer driver genes is important. However, most related studies have focused on the population level. Cancer is a disease with high heterogeneity. Thus, the discovery of driver genes at the individual level is becoming more valuable but is a great challenge. Although there have been some computational methods proposed to tackle this challenge, few can cover all patient samples well, and there is still room for performance improvement. In this study, to identify individual-level driver genes more efficiently, we propose the PDGCN method. PDGCN integrates multiple types of data features, including mutation, expression, methylation, copy number data, and system-level gene features, along with network structural features extracted using Node2vec in order to construct a sample-gene interaction network. Prediction is performed using a graphical convolutional neural network model with a conditional random field layer, which is able to better combine the network structural features with biological attribute features. Experiments on the ACC (Adrenocortical Cancer) and KICH (Kidney Chromophobe) datasets from TCGA (The Cancer Genome Atlas) demonstrated that the method performs better compared to other similar methods. It can identify not only frequently mutated driver genes, but also rare candidate driver genes and novel biomarker genes. The results of the survival and enrichment analyses of these detected genes demonstrate that the method can identify important driver genes at the individual level.

Molecular and morphological data reveal two new species of Tropicoporus (Hymenochaetaceae, Basidiomycota) from Australia and tropical Asia.

Phylogenetic analyses and morphological examination confirmed two new species in the tropical polypore genus Tropicoporus, T.oceanianus and T.zuzaneae, from Australia and tropical Asia, respectively. A phylogenetic analysis based on the two DNA markers including the nuclear ribosomal internal transcribed spacer (ITS) region and the large subunit (nLSU) gene shows that these two new species form two independent lineages nested in the genus Tropicoporus. T.oceanianus is characterized by perennial and ungulate basidiomata, the occasional presence of hymenial setae, a trimitic hyphal structure in the context and a dimitic hyphal system in the trama, and broadly ellipsoid to subglobose basidiospores measuring 5.2-6 × 4-5 µm. T.zuzaneae is characterized by perennial and resupinate basidiomata with distinct receding margin, glancing pores, very thin to almost lacking subiculum, a dimitic hyphal structure, the absence of any setal elements, broadly ellipsoid to subglobose basidiospores measuring 3.8-4.9 × 3-4.2 µm. The differences among the new species and their phylogenetically related and morphologically similar species are discussed.

Ultra-Sensitive and Stable Multiplexed Biosensors Array in Fully Printed and Integrated Platforms for Reliable Perspiration Analysis.

Electrochemical biosensors have emerged as one of the promising tools for tracking human body physiological dynamics via non-invasive perspiration analysis. However, it remains a key challenge to integrate multiplexed sensors in a highly controllable and reproducible manner to achieve long-term reliable biosensing, especially on flexible platforms. Herein, a fully inkjet printed and integrated multiplexed biosensing patch with remarkably high stability and sensitivity is reported for the first time. These desirable characteristics are enabled by the unique interpenetrating interface design and precise control over active materials mass loading, owing to the optimized ink formulations and droplet-assisted printing processes. The sensors deliver sensitivities of 313.28 µA mm-1 cm-2 for glucose and 0.87 µA mm-1 cm-2 for alcohol sensing with minimal drift over 30 h, which are among the best in the literature. The integrated patch can be used for reliable and wireless diet monitoring or medical intervention via epidermal analysis and would inspire the advances of wearable devices for intelligent healthcare applications.

A deep learning fusion network trained with clinical and high-frequency ultrasound images in the multi-classification of skin diseases in comparison with dermatologists: a prospective and multicenter study.

Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases. Methods: Between Jan 10, 2017, and Dec 31, 2020, the DMFN model was trained and validated using 1269 close-ups and 11,852 HFUS images from 1351 skin lesions. The monomodal convolutional neural network (CNN) model was trained and validated with the same close-up images for comparison. Subsequently, we did a prospective and multicenter study in China. Both CNN models were tested prospectively on 422 cases from 4 hospitals and compared with the results from human raters (general practitioners, general dermatologists, and dermatologists specialized in HFUS). The performance of binary classification (benign vs. malignant) and multiclass classification (the specific diagnoses of 17 types of skin diseases) measured by the area under the receiver operating characteristic curve (AUC) were evaluated. This study is registered with www.chictr.org.cn (ChiCTR2300074765). Findings: The performance of the DMFN model (AUC, 0.876) was superior to that of the monomodal CNN model (AUC, 0.697) in the binary classification (P = 0.0063), which was also better than that of the general practitioner (AUC, 0.651, P = 0.0025) and general dermatologists (AUC, 0.838; P = 0.0038). By integrating close-up and HFUS images, the DMFN model attained an almost identical performance in comparison to dermatologists (AUC, 0.876 vs. AUC, 0.891; P = 0.0080). For the multiclass classification, the DMFN model (AUC, 0.707) exhibited superior prediction performance compared with general dermatologists (AUC, 0.514; P = 0.0043) and dermatologists specialized in HFUS (AUC, 0.640; P = 0.0083), respectively. Compared to dermatologists specialized in HFUS, the DMFN model showed better or comparable performance in diagnosing 9 of the 17 skin diseases. Interpretation: The DMFN model combining analysis of clinical close-up and HFUS images exhibited satisfactory performance in the binary and multiclass classification compared with the dermatologists. It may be a valuable tool for general dermatologists and primary care providers. Funding: This work was supported in part by the National Natural Science Foundation of China and the Clinical research project of Shanghai Skin Disease Hospital.

A Novel Ultrafiltrate Extract of Propolis Exerts Anti-inflammatory Activity through Metabolic Rewiring.

Thousands of years ago, humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti-inflammatory properties, both in vitro and in vivo. Total flavonoids and total phenolic acids content in P30K were 244.6 mg/g and 275.8 mg/g respectively, while the IC50 value of inhibition of cyclooxygenase-2 (COX-2) was 8.30 µg/mL. The anti-inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)-induced acute liver and lung injury. Mechanistically, integrated GC-MS and LC-MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro-inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol-O-methyltransferases (COMT), 11ß-hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.

Dynamic simulation of land use change and habitat quality assessment under climate change scenarios in Nanchang, China.

Investigating habitat quality under different climate scenarios holds significant importance for sustainable land resource management and ecological conservation. In this study, considering Nanchang as a case study, a coupled patch-generating land use simulation (PLUS) and system dynamics (SD) model was employed in the simulation and prediction of land usage under shared socioeconomic pathway (SSP) and representative concentration pathway (RCP) scenarios. To assess the habitat quality in Nanchang from 2000 to 2020 and in 2030 under three diverse climate scenarios, we used the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model to analyze spatial and temporal changes. The findings indicate that the regions of forest land, cultivated land, and grassland in Nanchang City will dramatically decrease by 2030, the construction land will rapidly expand, and the fluctuations in the unutilized land and water area will be minimal. Additionally, the habitat quality declined from 2000 to 2020, and its spatial distributions changed. Zones having a high overall habitat quality were distributed in the mountains, hills, and lake areas, whereas those with relatively low quality were found in cultivated and urban areas. Under three climate scenarios, in 2030, the habitat quality index for Nanchang City will show a decreasing trend, mainly owing to areas with an index of 0.3-0.5 transitioning to <0.3. Considering each scenario, the degree of habitat degradation increased in the order SSP585>SSP245>SSP119. The findings of this study will inform high-quality development and biodiversity conservation in Nanchang City.