Multi-omics analysis of kidney, bone and bone marrow explored potential mechanisms of Erzhi Wan against osteoporosis with kidney-Yin deficiency.

Osteoporosis (OP) is a metabolic bone disease that can lead to major health challenges. The theory of Traditional Chinese medicine believes that kidney-Yin deficiency (KYD) is the main cause of postmenopausal osteoporosis. This study was aimed to investigate the effect of EZW on anti-osteoporosis with KYD, and explore potential mechanisms from the perspective of the kidney, bone and bone marrow through analysis of metabolomics and proteomics. The model of OP with KYD was established by rats treated with bilateral ovariectomy (OVX), and then given intragastric administration of thyroid and reserpine to induce. Micro-CT was applied to determine the microstructures of bone. Serum levels associated with bone turnover markers and kidney-Yin deficiency were detected by enzyme-linked immunosorbent (ELISA) assay. The differential metabolites in the kidney, bone and bone marrow were analyzed by metabolomics. The differentially expressed proteins in these three tissues were detected via proteomics. The findings suggested that EZW could alleviate a variety of metabolites and proteins among the kidney, bone and bone marrow, primarily in amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and lipid metabolism, thus leading to improvements of OP with KYD, which provided theoretical basis for clinical treatment of EZW on OP with KYD.

Arbuscular mycorrhizal fungi improve the competitive advantage of a native plant relative to a congeneric invasive plant in growth and nutrition.

Plant invasions severely threaten natural ecosystems, and invasive plants often outcompete native plants across various ecosystems. Arbuscular mycorrhizal (AM) fungi, serving as beneficial microorganisms for host plants, can greatly influence the competitive outcomes of invasive plants against native plants. However, it remains unclear how AM fungi alter the competitive balance between native and invasive species. A competitive experiment was conducted using an invasive Eupatorium adenophorum paired with a native congener Eupatorium lindleyanum. Specifically, both species were inoculated with (M+) or without (M-) the fungus Glomus etunicatum under intraspecific (Intra-) and interspecific (Inter-) competition. Plant traits were measured and analyzed regarding the growth and nutrition of both species. The results exhibited that the AM fungus significantly increased the height, diameter, biomass, C, N, and P acquisition of both the invasive E. adenophorum and the native E. lindleyanum. The root mycorrhizal colonization and the mycorrhizal dependency of native E. lindleyanum were greater than those of invasive E. adenophorum. Under M+, the Inter-competition inhibited the growth and nutrition of invasive E. adenophorum compared to the Intra- competition. Further, native E. lindleyanum exhibited higher competitiveness than invasive E. adenophorum in growth and nutrition. Meanwhile, the AM fungus significantly improved the competitiveness of native E. lindleyanum over invasive E. adenophorum. In conclusion, AM fungus improved the competitive advantage of native E. lindleyanum over invasive E. adenophorum in growth and nutrition, potentially contributing to native species competitively resisting the invasion of exotic species. These findings emphasize the importance of AM fungi in helping native plants resist the invasion of exotic plants and further contribute to understanding plant invasion prevention mechanisms.

Reaction Center Shifting in Partially Fluorinated Electrolytes for Robust Lithium Metal Battery.

The strategic formulation of a compatible electrolyte plays a pivotal role in extending the longevity of lithium-metal batteries (LMBs). Here, we present findings on a partially fluorinated electrolyte distinguished by a subdued solvation affinity towards Li+ ions and a concentrated anion presence within the primary solvation layer. This distinctive solvation arrangement redirects the focal points of reactions from solvent molecules to anions, facilitating the predominant involvement of anions in the creation of a LiF-enriched solid-electrolyte interphase (SEI). Electrochemical assessments showcase effective Li+ transport kinetics, diminished overpotential polarization for Li nucleation, and prolonged cycling durability in Li||Li cells employing the partially fluorinated electrolyte. When tested in Li||NCM811 cells, the designed electrolyte delivers a capacity retention of 89.30% and exhibits a high average Coulombic efficiency of 99.80% over 100 cycles with a charge-potential cut-off of 4.6 V vs. Li/Li+ under the current density of 0.4 C. Furthermore, even at a current density of 1C, the cells maintain 81.90% capacity retention and a high average Coulombic efficiency of 99.40% after 180 cycles. This work underscores the significance of weak-solvation interaction in partially fluorinated electrolytes and highlights the crucial role of solvent structure in enabling the long-term stability and high-energy density of LMBs.

Ganoderma lucidum spore extract improves sleep disturbances in a rat model of sporadic Alzheimer's disease.

Introduction: Ganoderma lucidum (G. lucidum, Lingzhi) has long been listed as a premium tonic that can be used to improve restlessness, insomnia, and forgetfulness. We previously reported that a rat model of sporadic Alzheimer's disease (sAD) that was induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) showed significant learning and cognitive deficits and sleep disturbances. Treatment with a G. lucidum spore extract with the sporoderm removed (RGLS) prevented learning and memory impairments in sAD model rats. Method: The present study was conducted to further elucidate the preventive action of RGLS on sleep disturbances in sAD rats by EEG analysis, immunofluorescence staining, HPLC-MS/MS and Western blot. Results: Treatment with 720 mg/kg RGLS for 14 days significantly improved the reduction of total sleep time, rapid eye movement (REM) sleep time, and non-REM sleep time in sAD rats. The novelty recognition experiment further confirmed that RGLS prevented cognitive impairments in sAD rats. We also found that RGLS inhibited the nuclear factor-κB (NF-κB)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammatory pathway in the medial prefrontal cortex (mPFC) in sAD rats and ameliorated the lower activity of γ-aminobutyric acid (GABA)-ergic neurons in the parabrachial nucleus (PBN). Discussion: These results suggest that inhibiting the neuroinflammatory response in the mPFC may be a mechanism by which RGLS improves cognitive impairment. Additionally, improvements in PBN-GABAergic activity and the suppression of neuroinflammation in the mPFC in sAD rats might be a critical pathway to explain the preventive effects of RGLS on sleep disturbances in sAD.

Sporoderm-removed Ganoderma lucidum spores ameliorated early depression-like behavior in a rat model of sporadic Alzheimer's disease.

Introduction: Ganoderma lucidum: (G. lucidum, Lingzhi) is a medicinal and edible homologous traditional Chinese medicine that is used to treat various diseases, including Alzheimer's disease and mood disorders. We previously reported that the sporoderm-removed G. lucidum spore extract (RGLS) prevented learning and memory impairments in a rat model of sporadic Alzheimer's disease (sAD), but the effect of RGLS on depression-like behaviors in this model and its underlying molecular mechanisms of action remain unclear. Method: The present study investigated protective effects of RGLS against intracerebroventricular streptozotocin (ICV-STZ)-induced depression in a rat model of sAD and its underlying mechanism. Effects of RGLS on depression- and anxiety-like behaviors in ICV-STZ rats were assessed in the forced swim test, sucrose preference test, novelty-suppressed feeding test, and open field test. Results: Behavioral tests demonstrated that RGLS (360 and 720 mg/kg) significantly ameliorated ICV-STZ-induced depression- and anxiety-like behaviors. Immunofluorescence, Western blot and enzyme-linked immunosorbent assay results further demonstrated that ICV-STZ rats exhibited microglia activation and neuroinflammatory response in the medial prefrontal cortex (mPFC), and RGLS treatment reversed these changes, reflected by the normalization of morphological changes in microglia and the expression of NF-κB, NLRP3, ASC, caspase-1 and proinflammatory cytokines. Golgi staining revealed that treatment with RGLS increased the density of mushroom spines in neurons. This increase was associated with elevated expression of brain-derived neurotrophic protein in the mPFC. Discussion: In a rat model of ICV-STZ-induced sAD, RGLS exhibits antidepressant-like effects, the mechanism of which may be related to suppression of the inflammatory response modulated by the NF-κB/NLRP3 pathway and enhancement of synaptic plasticity in the mPFC.

Reactive Force Field Molecular Dynamics Investigation of NH3 Generation Mechanism during Protein Pyrolysis Process.

The mechanism of ammonia formation during the pyrolysis of proteins in biomass is currently unclear. To further investigate this issue, this study employed the AMS 2023.104 software to select proteins (actual proteins) as the model compounds and the amino acids contained within them (assembled amino acids) as the comparative models. ReaxFF molecular dynamics simulations were conducted to explore the nitrogen transformation and NH3 generation mechanisms in three-phase products (char, tar, and gas) during protein pyrolysis. The research results revealed several key findings. Regardless of whether the model compounds are actual proteins or assembled amino acids, NH3 is the primary nitrogen-containing product during pyrolysis. However, as the temperature rises to higher levels, such as 2000 K and 2500 K, the amount of NH3 decreases significantly in the later stages of pyrolysis, indicating that it is being converted into other nitrogen-bearing species, such as HCN and N2. Simultaneously, we also observed significant differences between the pyrolysis processes of actual proteins and assembled amino acids. Notably, at 2000 K, the amount of NH3 generated from the pyrolysis of assembled amino acids was twice that of actual proteins. This discrepancy mainly stems from the inherent structural differences between proteins and amino acids. In proteins, nitrogen is predominantly present in a network-like structure (NH-N), which shields it from direct external exposure, thus requiring more energy for nitrogen to participate in pyrolysis reactions, making it more difficult for NH3 to form. Conversely, assembled amino acids can release NH3 through a simpler deamination process, leading to a significant increase in NH3 production during their pyrolysis.

Molecularly imprinted nanoparticles reveal regulatory scaffolding features in Pyk2 tyrosine kinase.

Pyk2 is a multi-domain non-receptor tyrosine kinase that serves dual roles as a signaling enzyme and scaffold. Pyk2 activation involves a multi-stage cascade of conformational rearrangements and protein interactions initiated by autophosphorylation of a linker site. Linker phosphorylation recruits Src kinase, and Src-mediated phosphorylation of the Pyk2 activation loop confers full activation. The regulation and accessibility of the initial Pyk2 autophosphorylation site remains unclear. We employed peptide-binding molecularly imprinted nanoparticles (MINPs) to probe the regulatory conformations controlling Pyk2 activation. MINPs differentiating local structure and phosphorylation state revealed that the Pyk2 autophosphorylation site is protected in the autoinhibited state. Activity profiling of Pyk2 variants implicated FERM and linker residues responsible for constraining the autophosphorylation site. MINPs targeting each Src docking site disrupt the higher-order kinase interactions critical for activation complex maturation. Ultimately, MINPs targeting key regulatory motifs establish a useful toolkit for probing successive activational stages in the higher-order Pyk2 signaling complex.

Modeling and optimization of triclosan biodegradation by the newly isolated Bacillus sp. DL4: kinetics and pathway speculation.

Triclosan is a widely used antibacterial agent and disinfectant, and its overuse endangered ecological safety and human health. Therefore, reducing residual TCS concentrations in the environment is an urgent issue. Bacillus sp. DL4, an aerobic bacterium with TCS biodegradability, was isolated from pharmaceutical wastewater samples. Response surface methodology (RSM) and artificial neural network (ANN) were carried out to optimize and verify the different condition variables, and the optimal growth conditions of strain DL4 were obtained (35 °C, initial pH 7.31, and 5% v/v). After 48 h of cultivation under the optimal conditions, the removal efficiency of strain DL4 on TCS was 95.89 ± 0.68%, which was consistent with the predicted values from RSM and ANN models. In addition, higher R2 value and lower MSE and ADD values indicated that the ANN model had a stronger predictive capability than the RSM model. Whole genome sequencing results showed that many functional genes were annotated in metabolic pathways related to TCS degradation (e.g., amino acid metabolism, xenobiotics biodegradation and metabolism, carbohydrate metabolism). Main intermediate metabolites were identified during the biodegradation process by liquid chromatography-mass spectrometry (LC-MS), and a possible pathway was hypothesized based on the metabolites. Overall, this study provides a theoretical foundation for the characterization and mechanism of TCS biodegradation in the environment by Bacillus sp. DL4.

Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.

Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.

Magnetic solid-phase extraction of tetracyclines from milk using metal-organic framework MIL-101(Cr)-NH2 functionalised hydrophilic magnetic nanoparticles.

Novel metal-organic framework MIL-101(Cr)-NH2 functionalised hydrophilic polydopamine-modified Fe3O4 magnetic nanoparticles (Fe3O4@PDA@MIL-101(Cr)-NH2) were synthesised and used as magnetic solid-phase extraction (MSPE) adsorbents for extracting tetracyclines (TCs) from milk samples. The integrated Fe3O4@PDA@MIL-101(Cr)-NH2 exhibited convenient magnetic separation and exceptional multi-target binding capabilities. Furthermore, the PDA coating significantly enhanced the hydrophilicity and extraction efficiency of the material, thereby facilitating the extraction of trace TCs. Various factors affecting MSPE, such as adsorbent dosage, extraction time, pH value, and desorption conditions, were optimised. The developed MSPE method coupled with high-performance liquid chromatography demonstrated good linearity (R2 ≥ 0.9989), acceptable accuracy (82.2%-106.1%), good repeatability (intra-day precision of 0.8%-4.7% and inter-day precision of 1.1%-4.5%), low limits of detection (2.18-6.25 µg L-1), and low limits of quantification (6.54-18.75 µg L-1) in TCs detection. The approach was successfully used for the quantification of trace TCs in real milk samples.

Considering the bioavailability and bioaccessibility of metal(loid)s for risk assessment of soils affected by different non-ferrous metal activities in Southwest China.

Toxic metal(loid)s released into the soil by non-ferrous metal mining and smelting activities pose a serious threat to residents and the surrounding ecosystem. Considering only total metal(loid) concentrations likely overestimates routine (eco)toxicological risk assessment of soil. We hypothesize that considering metal(loid) bioavailability/accessibility will improve the accuracy of risk assessment. To test this hypothesis, four mining areas in Southwest China, including mining and surrounding sites, were studied. Bioavailability was determined considering metal(loid)s leached by a simulated strong acid rain (SSAR) treatment. In the four areas, the mining site showed higher cumulative releases of metal(loid)s under SSAR treatment than the agricultural field located in the surrounding sites. Thus, the bioavailable metal(loid)s contents were continuously being released during SSAR treatment and likely increased the environmental risk. Ecological and health risk assessment of soil, calculated using total metal(loid)s content, was corrected considering bioavailable/accessible metal(loid)s, which was determined by the heavy metal(loid)s forms and in vitro simulated intestinal stages. Although the corrected indices indicated that the risk of metal(loid)s-contaminated soil was reduced, unfavorable ecological and health risks remained in the four areas. Our study provides new perspectives to better predict the risk of bioavailable/accessible metal(loid)s in non-ferrous metal contaminated and surrounding soils.

EGC enhances tumor antigen presentation and CD8+ T cell-mediated antitumor immunity via targeting oncoprotein SND1.

The Staphylococcal nuclease and Tudor domain containing 1 (SND1) has been identified as an oncoprotein. Our previous study demonstrated that SND1 impedes the major histocompatibility complex class I (MHC-I) assembly by hijacking the nascent heavy chain of MHC-I to endoplasmic reticulum-associated degradation. Herein, we aimed to identify inhibitors to block SND1-MHC-I binding, to facilitate the MHC-I presentation and tumor immunotherapy. Our findings validated the importance of the K490-containing sites in SND1-MHC-I complex. Through structure-based virtual screening and docking analysis, (-)-Epigallocatechin (EGC) exhibited the highest docking score to prevent the binding of MHC-I to SND1 by altering the spatial conformation of SND1. Additionally, EGC treatment resulted in increased expression levels of membrane-presented MHC-I in tumor cells. The C57BL/6J murine orthotopic melanoma model validated that EGC increases infiltration and activity of CD8+ T cells in both the tumor and spleen. Furthermore, the combination of EGC with programmed death-1 (PD-1) antibody demonstrated a superior antitumor effect. In summary, we identified EGC as a novel inhibitor of SND1-MHC-I interaction, prompting MHC-I presentation to improve CD8+ T cell response within the tumor microenvironment. This discovery presents a promising immunotherapeutic candidate for tumors.

Cell-penetrating protein-recognizing polymeric nanoparticles through dynamic covalent chemistry and double imprinting.

Molecular recognition of proteins is key to their biological functions and processes such as protein-protein interactions (PPIs). The large binding interface involved and an often relatively flat binding surface make the development of selective protein-binding materials extremely challenging. A general method is reported in this work to construct protein-binding polymeric nanoparticles from cross-linked surfactant micelles. Preparation involves first dynamic covalent chemistry that encodes signature surface lysines on a protein template. A double molecular imprinting procedure fixes the binding groups on the nanoparticle for these lysine groups, meanwhile creating a binding interface complementary to the protein in size, shape, and distribution of acidic groups on the surface. These water-soluble nanoparticles possess excellent specificities for target proteins and sufficient affinities to inhibit natural PPIs such as those between cytochrome c (Cytc) and cytochrome c oxidase (CcO). With the ability to enter cells through a combination of energy-dependent and -independent pathways, they intervene apoptosis by inhibiting the PPI between Cytc and the apoptotic protease activating factor-1 (APAF1). Generality of the preparation and the excellent molecular recognition of the materials have the potential to make them powerful tools to probe protein functions in vitro and in cellulo.

Association between vitamin B2 intake and prostate-specific antigen in American men: 2003-2010 National Health and Nutrition Examination Survey.

BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.

Size-dependent reactivity of VnO+ (n = 1-9) clusters with ethane.

Cost-effective and readily accessible 3d transition metals (TMs) have been considered as promising candidates for alkane activation while 3d TMs especially the early TMs are usually not very reactive with light alkanes. In this study, the reactivity of Vn+ and VnO+ (n = 1-9) cluster cations towards ethane under thermal collision conditions has been investigated using mass spectrometry and density functional theory calculations. Among Vn+ (n = 1-9) clusters, only V3-5+ can react with C2H6 to generate dehydrogenation products and the reaction rate constants are below 10-13 cm3 molecule-1 s-1. In contrast, the reaction rate constants for all VnO+ (n = 1-9) with C2H6 significantly increase by about 2-4 orders of magnitude. Theoretical analysis evidences that the addition of ligand O affects the charge distribution of the metal centers, resulting in a significant increase in the cluster reactivity. The analysis of frontier orbitals indicates that the agostic interaction determines the size-dependent reactivity of VnO+ cluster cations. This study provides a novel approach for improving the reactivity of early 3d TMs.

Traditional Chinese medicine improved diabetic kidney disease through targeting gut microbiota.

CONTEXT: Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal disease that requires renal replacement therapies, such as dialysis and transplantation. The gut microbiota, an integral aspect of human evolution, plays a crucial role in this condition. Traditional Chinese medicine (TCM) has shown promising outcomes in ameliorating DKD by addressing the gut microbiota. OBJECTIVE: This review elucidates the modifications in gut microbiota observed in DKD and explores the impact of TCM interventions on correcting microbial dysregulation. METHODS: We searched relevant articles from databases including Web of Science, PubMed, ScienceDirect, Wiley, and Springer Nature. The following keywords were used: diabetic kidney disease, diabetic nephropathy, gut microbiota, natural product, TCM, Chinese herbal medicine, and Chinese medicinal herbs. Rigorous criteria were applied to identify high-quality studies on TCM interventions against DKD. RESULTS: Dysregulation of the gut microbiota, including Lactobacillus, Streptococcus, and Clostridium, has been observed in individuals with DKD. Key indicators of microbial dysregulation include increased uremic solutes and decreased short-chain fatty acids. Various TCM therapies, such as formulas, tablets, granules, capsules, and decoctions, exhibit unique advantages in regulating the disordered microbiota to treat DKD. CONCLUSION: This review highlights the importance of targeting the gut-kidney axis to regulate microbial disorders, their metabolites, and associated signaling pathways in DKD. The Qing-Re-Xiao-Zheng formula, the Shenyan Kangfu tablet, the Huangkui capsule, and the Bekhogainsam decoction are potential candidates to address the gut-kidney axis. TCM interventions offer a significant therapeutic approach by targeting microbial dysregulation in patients with DKD.

Efficacy of ultrasound-guided stellate ganglion block in relieving acute postoperative pain: a systematic review and meta-analysis.

OBJECTIVE: The efficacy of ultrasound-guided stellate ganglion block (SGB) in alleviating postoperative pain remains unclear. This meta-analysis was performed to determine the efficacy of ultrasound-guided SGB in relieving acute postoperative pain in patients undergoing surgery with general anesthesia. METHODS: This systematic review and meta-analysis focused on randomized controlled trials comparing SGB with control or placebo. The primary outcome was the pain score at 24 hours after surgery. A random-effects model was used to calculate the mean difference (MD) or risk ratio with a confidence interval (CI) of 95%. RESULTS: Eight studies involving 470 patients were included in the meta-analysis. The results revealed that ultrasound-guided SGB was significantly associated with a lower pain score at 24 hours after surgery (MD = -0.74; 95% CI = -1.39, -0.08; I2 = 86%; low evidence) and at 8 hours after surgery (MD = -0.65; 95% CI = -1.03, -0.28; I2 = 29%; moderate evidence). CONCLUSION: Ultrasound-guided SGB is effective in alleviating acute postoperative pain. However, considering the limited number of trials performed to date, more large-scale and high-quality randomized controlled trials are required to confirm these findings.

GR/P300 Regulates MKP1 Signaling Pathway and Mediates Depression-like Behavior in Prenatally Stressed Offspring.

Accumulating evidence suggests that prenatal stress (PNS) increases offspring susceptibility to depression, but the underlying mechanisms remain unclear. We constructed a mouse model of prenatal stress by spatially restraining pregnant mice from 09:00-11:00 daily on Days 5-20 of gestation. In this study, western blot analysis, quantitative real-time PCR (qRT‒PCR), immunofluorescence, immunoprecipitation, chromatin immunoprecipitation (ChIP), and mifepristone rescue assays were used to investigate alterations in the GR/P300-MKP1 and downstream ERK/CREB/TRKB pathways in the brains of prenatally stressed offspring to determine the pathogenesis of the reduced neurogenesis and depression-like behaviors in offspring induced by PNS. We found that prenatal stress leads to reduced hippocampal neurogenesis and depression-like behavior in offspring. Prenatal stress causes high levels of glucocorticoids to enter the fetus and activate the hypothalamic‒pituitary‒adrenal (HPA) axis, resulting in decreased hippocampal glucocorticoid receptor (GR) levels in offspring. Furthermore, the nuclear translocation of GR and P300 (an acetylation modifying enzyme) complex in the hippocampus of PNS offspring increased significantly. This GR/P300 complex upregulates MKP1, which is a negative regulator of the ERK/CREB/TRKB signaling pathway associated with depression. Interestingly, treatment with a GR antagonist (mifepristone, RU486) increased hippocampal GR levels and decreased MKP1 expression, thereby ameliorating abnormal neurogenesis and depression-like behavior in PNS offspring. In conclusion, our study suggested that the regulation of the MKP1 signaling pathway by GR/P300 is involved in depression-like behavior in prenatal stress-exposed offspring and provides new insights and ideas for the fetal hypothesis of mental health.

Biochar-Enhanced Three-Dimensional Conductive Network Thick Electrodes for Efficient Lithium Extraction from Salt Lake Brines with High Magnesia-lithium Ratios.

Enhancing the kinetic performance of thick electrodes is essential for improving the efficiency of lithium extraction processes. Biochar, known for its affordability and unique three-dimensional (3D) structure, is utilized across various applications. In this study, we developed a biochar-based, 3D-conductive network thick electrode (∼20 mg·cm-2) by in-situ deposition of LiFePO4 (LFP) onto watermelon peel biomass (WB). Utilizing Density Functional Theory (DFT) calculations complemented by experimental data, we confirmed that this The thick electrode exhibits outstanding kinetic properties and a high capacity for lithium intercalation in brines, even in environments where the Magnesia-lithium ratios are significantly high. The electrode showed an impressive intercalation capacity of 30.67 mg·g-1 within 10 minutes in a pure lithium solution. It also maintained high intercalation performance (31.17 mg·g-1) in simulated brines with high Magnesia-lithium ratios. Moreover, in actual brine, it demonstrated a significant extraction capacity (23.87 mg·g-1), effectively lowering the Magnesia-lithium ratio from 65 to 0.50. This breakthrough in high-conductivity thick electrode design offers new perspectives for lithium extraction technologies.

Positive Effect of 6-Gingerol on Functional Plasticity of Microglia in a rat Model of LPS-induced Depression.

Neuroinflammation has emerged as a crucial factor in the development of depression. Despite the well-known anti-inflammatory properties of 6-gingerol, its potential impact on depression remains poorly understood. This study aimed to investigate the antidepressant effects of 6-gingerol by suppressing microglial activation. In vivo experiments were conducted to evaluate the effect of 6-gingerol on lipopolysaccharide (LPS)-induced behavioral changes and neuroinflammation in rat models. In vitro studies were performed to examine the neuroprotective properties of 6-gingerol against LPS-induced microglial activation. Furthermore, a co-culture system of microglia and neurons was established to assess the influence of 6-gingerol on the expression of synaptic-related proteins, namely synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), which are influenced by microglial activation. In the in vivo experiments, administration of 6-gingerol effectively alleviated LPS-induced depressive behavior in rats. Moreover, it markedly suppressed the activation of rat prefrontal cortex (PFC) microglia induced by LPS and the activation of the NF-κB/NLRP3 inflammatory pathway, while also reducing the levels of inflammatory cytokines IL-1ß and IL-18. In the in vitro experiments, 6-gingerol mitigated nuclear translocation of NF-κB p65, NLRP3 activation, and maturation of IL-1ß and IL-18, all of which were induced by LPS. Furthermore, in the co-culture system of microglia and neurons, 6-gingerol effectively restored the decreased expression of SYP and PSD95. The findings of this study demonstrate the neuroprotective effects of 6-gingerol in the context of LPS-induced depression-like behavior. These effects are attributed to the inhibition of microglial hyperactivation through the suppression of the NF-κB/NLRP3 inflammatory pathway.