The role of aryl hydrocarbon receptors in nutrient metabolism and immune regulation at the maternal-fetal interface.

The maternal-fetal interface is composed of the placenta, which is affiliated with the fetus, and the maternal decidua. During pregnancy, the placenta is mainly responsible for nutrient transport and immune tolerance maintenance, which plays a key role in fetal growth and development and pregnancy maintenance. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exists in various cell types at the maternal-fetal interface and is involved in multiple cellular processes. Recent studies have highlighted the role of AhR in regulating various physiological processes, including glucose and lipid metabolism, as well as tryptophan metabolism and immune responses, within non-pregnant tissues. This review shifts focus towards understanding how AhR modulation impacts metabolism and immune regulation at the maternal-fetal interface. This may implicate the development of pregnancy-related complications and the potential target of the AhR pathway for therapeutic strategies against poor pregnancy outcomes.

Impact of paprika and dextrose addition on dry cured loins microbiota and its effect on aroma development.

The impact of paprika and dextrose addition on the surface of dry cured loins was analysed attending to differences in microbiota composition and aroma profile. Three different types of loins containing either dextrose (D), paprika (P) or a mixture of dextrose and paprika (DP) were manufactured. The loins were characterized using physic-chemical parameters, free amino acids, volatile compounds and aroma sensorial analysis, as well as applying microbiological counts and metagenomics of the 16S rRNA gene and its rDNA region. The analysis of volatile compounds clearly distinguished all loins, whereas the total content of free amino acids only separated P from D and DP loins. The main sensory differences were linked to paprika addition, which increased the perception of paprika and smoky odors as well as cured, savoury and cheesy notes. Microbial counts analysis could not differentiate between the three loin types; however, metagenomics analysis revealed clear differences in key bacterial and fungal genera among the three loins. Paprika addition favoured dominance of Latilactobacillus in the microbiota of P loins. On the contrary, dextrose addition caused the dominance of Staphylococcus in the microbiota of D loins. In DP loins, both genera were similarly represented in the bacterial community. Regarding fungi, large differences could be observed within the P and D loins, whereas the proportion of Debaryomyces in DP loins increased. The microbiota composition of DP loins controlled the lipid oxidation phenomenon, reducing the generation of derived volatiles producing rancid notes and increase the volatile compounds derived from amino acids such as branched aldehydes, pyrazines and pyrroles, providing particular aroma notes to the loins.

MISD-IR: material-image subspace decomposition-based iterative reconstruction with spectrum estimation for dual-energy computed tomography.

Background: Dual-energy computed tomography (DECT) is a promising technique, which can provide unique capability for material quantification. The iterative reconstruction of material maps requires spectral information and its accuracy is affected by spectral mismatch. Simultaneously estimating the spectra and reconstructing material maps avoids extra workload on spectrum estimation and the negative impact of spectral mismatch. However, existing methods are not satisfactory in image detail preservation, edge retention, and convergence rate. The purpose of this paper was to mine the similarity between the reconstructed images and the material images to improve the imaging quality, and to design an effective iteration strategy to improve the convergence efficiency. Methods: The material-image subspace decomposition-based iterative reconstruction (MISD-IR) with spectrum estimation was proposed for DECT. MISD-IR is an optimized model combining spectral estimation and material reconstruction with fast convergence speed and promising noise suppression capability. We proposed to reconstruct the material maps based on extended simultaneous algebraic reconstruction techniques and estimation of the spectrum with model spectral. To stabilize the iteration and alleviate the influence of errors, we introduced a weighted proximal operator based on the block coordinate descending algorithm (WP-BCD). Furthermore, the reconstructed computed tomography (CT) images were introduced to suppress the noise based on subspace decomposition, which relies on non-local regularization to prevent noise accumulation. Results: In numerical experiments, the results of MISD-IR were closer to the ground truth compared with other methods. In real scanning data experiments, the results of MISD-IR showed sharper edges and details. Compared with other one-step iterative methods in the experiment, the running time of MISD-IR was reduced by 75%. Conclusions: The proposed MISD-IR can achieve accurate material decomposition (MD) without known energy spectrum in advance, and has good retention of image edges and details. Compared with other one-step iterative methods, it has high convergence efficiency.

Vapor Deposition of Bilayer 3R MoS2 with Room-Temperature Ferroelectricity.

Two-dimensional ultrathin ferroelectrics have attracted much interest due to their potential application in high-density integration of non-volatile memory devices. Recently, 2D van der Waals ferroelectric based on interlayer translation has been reported in twisted bilayer h-BN and transition metal dichalcogenides (TMDs). However, sliding ferroelectricity is not well studied in non-twisted homo-bilayer TMD grown directly by chemical vapor deposition (CVD). In this paper, for the first time, experimental observation of a room-temperature out-of-plane ferroelectric switch in semiconducting bilayer 3R MoS2 synthesized by reverse-flow CVD is reported. Piezoelectric force microscopy (PFM) hysteretic loops and first principle calculations demonstrate that the ferroelectric nature and polarization switching processes are based on interlayer sliding. The vertical Au/3R MoS2/Pt device exhibits a switchable diode effect. Polarization modulated Schottky barrier height and polarization coupling of interfacial deep states trapping/detrapping may serve in coordination to determine switchable diode effect. The room-temperature ferroelectricity of CVD-grown MoS2 will proceed with the potential wafer-scale integration of 2D TMDs in the logic circuit.

Sea Urchin-Like NiCo-LDH Hollow Spheres Anchored on 3D Graphene Aerogel for High-Performance Supercapacitors.

To enhance the inherent poor conductivity and low cycling stability of dimetallic layered double hydroxides (LDHs) materials, designing a synergistic effect between EDLC capacitors and pseudocapacitors is an efficient strategy. In this paper, we utilized a solvothermal technique employing Co-glycerate as a precursor to prepare sea urchin-like NiCo-LDH hollow spheres anchored on a 3D graphene aerogel. The unique morphology of these hollow microspheres significantly expand the specific surface area and exposes more active sites, while reducing the volume changes of materials during long-term charging and discharging processes. The 3D graphene aerogel serves as a conductive skeleton, improving the material's electrical conductivity and buffering high current. The sea urchin-like NiCo-LDH hollow spheres anchored on 3D graphene aerogel (H-NiCo-LDH@GA) has a specific surface area of 51 m2 g-1 and the ID/IG value is 1.02. The H-NiCo-LDH@GA demonstrate a significant specific capacitance of 236.8 mAh g-1 at 1 A g-1, with a remarkable capacity retention rate of 63.1 % even at 20 A g-1. Even after 8000 cycles at 10 A g-1, the capacity retention still remains at 96.3 %, presenting excellent cycling stability.

Microplastic exposure disturbs sleep structure, reduces lifespan, and decreases ovary size in Drosophila melanogaster.

The organ-specific toxicity resulting from microplastic (MP) exposure has been extensively explored, particularly concerning the gut, liver, testis, and lung. However, under natural conditions, these effects are not restricted to specific organs or tissues. Investigating whether MP exposure presents a systemic threat to an entire organism, impacting factors such as lifespan, sleep, and fecundity, is essential. In this study, we investigated the effects of dietary exposure to two different doses of MPs (1-5 µm) using the terrestrial model organism Drosophila melanogaster. Results indicated that the particles caused gut damage and remained within the digestive system. Continuous MP exposure significantly shortened the lifespan of adult flies. Even short-term exposure disrupted sleep patterns, increasing the length of daytime sleep episodes. Additionally, one week of MP exposure reduced ovary size, with a trend towards decreased egg-laying in mated females. Although MPs did not penetrate the brain or ovaries, transcriptome analysis revealed altered gene expression in these tissues. In the ovary, Gene Ontology (GO) analysis indicated genotoxic effects impacting inflammation, circadian regulation, and metabolic processes, with significant impacts on extracellular structure-related pathways. In the brain, GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism. Overall, this study provides compelling evidence of the systemic negative effects of MP exposure, highlighting the urgent need to address and mitigate environmental MP pollution.

MKK3 depletion attenuates intestinal injury after traumatic hemorrhagic shock by restoring mitochondrial function.

BACKGROUND: Traumatic hemorrhagic shock (THS) is a complex pathophysiological process resulting in multiple organ failure. Intestinal barrier dysfunction is one of the mechanisms implicated in multiple organ failure. The present study aimed to explore the regulatory role of mitogen-activated protein kinase kinase 3 (MKK3) in THS-induced intestinal injury and to elucidate its potential mechanism. METHODS: Rats were subjected to trauma and hemorrhage to establish a THS animal model. MKK3-targeted lentiviral vectors were injected via the tail vein 72 h before modeling. Twelve hours post-modeling, the mean arterial pressure (MAP) and heart rate (HR) were monitored, and histological injury to the intestine was assessed via H&E staining and transmission electron microscopy. Mitochondrial function and mitochondrial reactive oxygen species (ROS) were evaluated. IEC-6 cells were exposed to hypoxia to mimic intestinal injury following THS in vitro. RESULTS: MKK3 deficiency alleviated intestinal injury and restored mitochondrial function in intestinal tissues from THS-induced rats and hypoxia-treated IEC-6 cells. In addition, MKK3 deficiency promoted Sirt1/PGC-1α-mediated mitochondrial biogenesis and restricted Pink1/Parkin-mediated mitophagy in the injured intestine and IEC-6 cells. Furthermore, the protective effect of MKK3 knockdown against hypoxia-induced mitochondrial damage was strengthened upon simultaneous LC3B/Pink1/Parkin knockdown or weakened upon simultaneous Sirt1 knockdown. CONCLUSION: MKK3 deficiency protected against intestinal injury induced by THS by promoting mitochondrial biogenesis and restricting excessive mitophagy.

Altered bile acid and correlations with gut microbiome in transition dairy cows with different glucose and lipid metabolism status.

The transition from pregnancy to lactation is critical in dairy cows. Among others, dairy cows experience a metabolic stress due to a large change in glucose and lipid metabolism. Recent studies revealed that bile acids (BA), besides being involved in both the emulsification and solubilization of fats during intestinal absorption, can also affect the metabolism of glucose and lipids, both directly or indirectly by affecting the gut microbiota. Thus, we used untargeted and targeted metabolomics and 16S rRNA sequencing approaches to investigate the concentration of plasma metabolites and BA, the composition of the rectum microbial community, and assess their interaction in transition dairy cows. In Experiment 1, we investigated BA and other blood parameters and gut microbiota in dairy cows without clinical diseases during the transition period, which can be seen as well adapted to the challenge of changed glucose and lipid metabolism. As expected, we detected an increased plasma concentration of ß-hydroxybutyrate (BHBA) and nonesterified fatty acids (NEFA) but decreased concentration of glucose, cholesterol, and triglycerides (TG). Untargeted metabolomic analysis of the plasma revealed primary BA biosynthesis was one of the affected pathways, and was consistent with the increased concentration of BA in the plasma. A correlation approach revealed a complex association between BA and microbiota with the host plasma concentration of glucose and lipid metabolites. Among BA, chenodeoxycholic acid derivates such as glycolithocholic acid, taurolithocholic acid, lithocholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites (such as glucose, TG, and NEFA). In Experiment 2, we investigated early postpartum dairy cows with or without hyperketonemia (HPK). As expected, HPK cows had increased concentration of NEFA and decreased concentrations of glucose and triglycerides. The untargeted metabolomic analysis of the plasma revealed that primary BA biosynthesis was also one of the affected pathways. Even though the BA concentration was similar among the 2 groups, the profiles of taurine conjugated BA changed significantly. A correlation analysis also revealed an association between BA and microbiota with the concentration in plasma of glucose and lipid metabolites (such as BHBA). Among BA, cholic acid and its derivates such as taurocholic acid, tauro α-muricholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites. Our results indicated an association between BA, intestinal microbe, and glucose and lipid metabolism in transition dairy cows. These findings provide new insight into the adaptation mechanisms of dairy cows during the transition period.

Melatonin improves mouse oocyte quality from 2-ethylhexyl diphenyl phosphate-induced toxicity by enhancing mitochondrial function.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.

Identifying gut microbiota with high specificity for ischemic stroke with large vessel occlusion.

Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.

U-shaped relationship between non-high-density lipoprotein cholesterol and cognitive impairment in Chinese middle-aged and elderly: a cross-sectional study.

BACKGROUND: The relationship between blood lipids and cognitive function has long been a subject of interest, and the association between serum non-high-density lipoprotein cholesterol (non-HDL-C) levels and cognitive impairment remains contentious. METHODS: We utilized data from the 2011 CHARLS national baseline survey, which after screening, included a final sample of 10,982 participants. Cognitive function was assessed using tests of episodic memory and cognitive intactness. We used multiple logistic regression models to estimate the relationship between non-HDL-C and cognitive impairment. Subsequently, utilizing regression analysis results from fully adjusted models, we explored the nonlinear relationship between non-HDL-C as well as cognitive impairment using smooth curve fitting and sought potential inflection points through saturation threshold effect analysis. RESULTS: The results showed that each unit increase in non-HDL-C levels was associated with a 5.5% reduction in the odds of cognitive impairment (OR = 0.945, 95% CI: 0.897-0.996; p < 0.05). When non-HDL-C was used as a categorical variable, the results showed that or each unit increase in non-HDL-C levels, the odds of cognitive impairment were reduced by 14.2%, 20.9%, and 24% in the Q2, Q3, and Q4 groups, respectively, compared with Q1. In addition, in the fully adjusted model, analysis of the potential nonlinear relationship by smoothed curve fitting and saturation threshold effects revealed a U-shaped relationship between non-HDL-C and the risk of cognitive impairment, with an inflection point of 4.83. Before the inflection point, each unit increase in non-HDL-C levels was associated with a 12.3% decrease in the odds of cognitive impairment. After the tipping point, each unit increase in non-HDL-C levels was associated with an 18.8% increase in the odds of cognitive impairment (All p < 0.05). CONCLUSION: There exists a U-shaped relationship between non-HDL-C and the risk of cognitive impairment in Chinese middle-aged and elderly individuals, with statistical significance on both sides of the turning points. This suggests that both lower and higher levels of serum non-high-density lipoprotein cholesterol increase the risk of cognitive impairment in middle-aged and elderly individuals.

Traceability of gushing water in the MiddleRoute of the South-to-North Water Diversion (Beijing section) through the river area.

To trace the origin of the gushing water in the riverine area of the Beijing section of The Middle Route of South-to-North Water Diversion Project, a dataset was established comprising water chemistry, three-dimensional fluorescence spectra, and stable isotopes for different water bodies. Results indicated significant differences in Electrical Conductivity (EC), Total Dissolved Solids (TDS), and Ca2+ concentration among the gushing water, river water, and the water from the Middle Route of South-to-North Water Diversion Project (MRSD). Analysis using parallel factor analysis (PARAFAC) and fluorescence index revealed that dissolved organic matter (DOM) in the MRSD mainly originated from endogenous sources, while the river water and gushing water showed influences from both endogenous and exogenous sources. Nitrate sources varied among the water bodies, with distinct contributions from domestic sewage and fertilizer sources. The evaporation lines of river water and gushing water exhibited similar intercepts and slopes, but their intercepts and slopes are much smaller than those of the MRSD, suggesting stronger kinetic evaporative fractionation. In conclusion, the gushing water in the riverine area of the MRSD was determined to originate from the river, providing a fast and efficient method for gushing water source identification.

Prediction of myofascial pelvic pain syndrome based on random forest model.

Objective: The objective is to construct a random forest model for predicting the occurrence of Myofascial pelvic pain syndrome (MPPS) and compare its performance with a logistic regression model to demonstrate the superiority of the random forest model. Methods: We retrospectively analyze the clinical data of female patients who underwent pelvic floor screening due to chronic pelvic pain at the Pelvic Floor Rehabilitation Center of the Third Affiliated Hospital of Zhengzhou University from January 2021 to December 2023. A total of 543 female patients meeting the study's inclusion and exclusion criteria are randomly selected from this dataset and allocated to the MPPS group. Furthermore, 702 healthy female patients who underwent pelvic floor screening during routine physical examinations within the same timeframe are randomly selected and assigned to the non-MPPS group. Chi-square test and rank-sum test are used to select demographic variables, pelvic floor pressure assessment data variables, and modified Oxford muscle strength grading data for logistic univariate analysis. The selected variables are further subjected to multivariate logistic regression analysis, and a random forest model is also established. The predictive performance of the two models is evaluated by comparing their accuracy, sensitivity, specificity, precision, receiver operating characteristic (ROC) curve, and area under the curve (AUC) area. Results: Based on a dataset of 1245 cases, we implement the random forest algorithm for the first time in the screening of MPPS. In this investigation, the Logistic regression model forecasts the accuracy, sensitivity, specificity, and precision of MPPS at 69.96 %, 57.46 %, 79.63 %, and 68.57 % respectively, with an AUC of the ROC curve at 0.755. Conversely, the random forest prediction model exhibits accuracy, sensitivity, specificity, and precision rates of 87.11 %, 90.66 %, 90.91 %, and 83.51 % respectively, with an AUC of the ROC curve at 0.942. The random forest model showcases exceptional predictive performance during the initial screening of MPPS. Conclusion: The random forest model has exhibited exceptional predictive performance in the initial screening evaluation of MPPS disease. The development of this predictive framework holds significant importance in refining the precision of MPPS prediction within clinical environments and elevating treatment outcomes. This research carries profound global implications, given the potentially elevated misdiagnosis rates and delayed diagnosis proportions of MPPS on a worldwide scale, coupled with a potential scarcity of seasoned healthcare providers. Moving forward, continual refinement and validation of the model will be imperative to further augment the precision of MPPS risk assessment, thereby furnishing clinicians with more dependable decision-making support in clinical practice.

CdS-based Schottky junctions for efficient visible light photocatalytic hydrogen evolution.

Heterojunctions photocatalysts play a crucial role in achieving high solar-hydrogen conversion efficiency. In this work, we mainly focus on the charge transfer dynamics and pathways for sulfides-based Schottky junctions in the photocatalytic water splitting process to clarify the mechanism of heterostructures photocatalysis. Sulfides-based Schottky junctions (CdS/CoP and CdS/1T-MoS2) were successfully constructed for photocatalytic water splitting. Because of the higher work function of CdS than that of CoP and 1T-MoS2, the direction of the built-in electric field is from CoP or 1T-MoS2 to semiconductor. Therefore, CoP and 1T-MoS2 can act as electrons acceptors to accelerate the transfer of photo-generated electron on the surface of CdS, thus improving the charge utilization efficiency. Meanwhile, CoP and 1T-MoS2 as active sites can also promote the water dissociation and lower the H+ reduction overpotential, thus contributing to the excellent photocatalytic hydrogen production activity (23.59 mmol·h-1·g-1 and 1195.8 mol·h-1·g-1 for CdS/CoP and CdS/1T-MoS2).

Relationship between the longitudinal trajectory of the triglyceride-glucose index and the development of CKD: an 8-year retrospective longitudinal cohort study.

Background: The triglyceride-glucose (TyG) index, a simple surrogate marker of insulin resistance, is significantly associated with chronic kidney disease (CKD). However, there is limited research on the longitudinal trajectory of TyG index over time and its relationship with CKD. Objective: To analyse the characteristics of the longitudinal trajectory of the TyG index over time and its association with the development of CKD in a health check-up population. Methods: Participants who underwent at least three annual health check-ups at the Health Management Center of Sichuan Provincial People's Hospital from 2015 to 2022 were included in this retrospective cohort study. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The latent class mixed model (LCMM) was used to identify the TyG index trajectory of the study population. A Cox proportional hazard model was used to estimate the CKD incidence risk in different quartile groups and the association of changes in the TyG index trajectory with the development of CKD. Results: A total of 4,921 participants were included in this study, and they were divided into four groups according to the quartiles of the baseline TyG index: Q1 (5.43-6.66), Q2 (6.67-7.04), Q3 (7.05-7.43), and Q4 (7.43-9.97). There was no difference in the risk of CKD occurrence among the TyG groups. Three different TyG index trajectories were identified in this study: a high-level group, middle-level stable group and low-level stable group, respectively. The incidence rate of CKD in the high-level TyG index trajectory group was 2.399 times greater than that in the low-level stable trajectory group (HR=2.399, 95% CI 1.167-4.935). Conclusion: Individuals with long-term exposure to high TyG index levels had a significantly greater risk of CKD. Routine monitoring of the TyG index and its longitudinal trend will aid in the risk stratification of CKD in the general population and will be helpful for CKD prevention and targeted management.

Propofol regulates the progression of hepatocellular carcinoma via the POLR2L/TGF-ß signaling pathway.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Propofol has been reported to modulate tumorigenesis in HCC; the aim of this study was to investigate the effect of the interaction of propofol with POLR2L on HCC tumor progression in HCC. Methods: The propofol-related GSE101724 dataset was analyzed using weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) to identify overlapping genes. Key genes were selected from The Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC)-DEGs for prognostic analysis. The impact of POLR2L on LIHC patient survival was assessed, followed by in vitro experiments to validated its effects on HCC cell behavior and signaling pathways. Results: Fourteen overlapping genes were identified in the turquoise module (highest correlation) of up-regulated DEGs and GSE101724. Further analysis obtained 11 key overlapping genes from 14 overlapping genes and TCGA-LIHC-DEGs, among which HSPE1 and POLR2L showed significant prognostic correlation. Patients with LIHC have a worse chance of surviving when their POLR2L expression is elevated. Knockdown POLR2L significantly inhibited the proliferation, invasion, and migration of HCC cell lines. Downregulation of POLR2L was accompanied by induced apoptosis, cell cycle arrest, and modulation of the expression of apoptosis-related genes. Propofol was found to downregulate POLR2L expression, inhibiting cell proliferation and growth. Further, it was shown that propofol controlled the development of HCC by influencing the POLR2L/TGF-ß signaling loop. Conclusions: The results validated the predictive relevance of POLR2L in HCC and emphasized that propofol can regulate HCC progression through the POLR2L/TGF-ß signaling pathway.

Turning foes to friends: Advanced "in situ nanovaccine" with dual immunoregulation for enhanced immunotherapy of metastatic triple-negative breast cancer.

As a "cold tumor", triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an "in situ nanovaccine" Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an "in situ nanovaccine" to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid-derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, "cold tumor" was transformed into a "hot tumor", not only implementing a "turning foes to friends" therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.

Dynamic mRNA network profiles in macrophages challenged with lipopolysaccharide.

OBJECTIVES: To elucidate the transcriptome of macrophages in an inflammation model induced by lipopolysaccharide (LPS), providing insight into the molecular basis of inflammation. METHODS: We utilized RNA sequencing (RNA-seq) to analyze dynamic changes in gene expression in RAW264.7 macrophages treated with LPS at multiple time points. Differentially expressed genes (DEGs) were identified using the edgeR package. Short Time-series Expression Miner (STEM) and KEGG pathway enrichment analyses were conducted to determine temporal expression patterns during inflammation. RESULTS: We identified 2,512 DEGs, with initial inflammatory responses occurring in two distinct phases at 1 h and 3 h. Venn diagram analysis revealed 78 consistently dysregulated genes throughout the inflammatory process. A key module of 18 dysregulated genes was identified, including Irg1, which may exert an inhibitory effect on inflammation. Further, a second metabolic shift in activated macrophages was observed at the late middle stage (12 h). Multi-omics analysis highlighted the ribosome's potential regulatory role in the inflammatory response. CONCLUSIONS: This study provides a detailed view of the molecular mechanisms underlying inflammation in macrophages and reveals a dynamic genetic landscape crucial for further research. Our findings underscore the complex interaction between gene expression, metabolic shifts, and ribosomal functions in response to LPS-induced inflammation.

Antibiotics and polycyclic aromatic hydrocarbons in marine food webs of the Yellow River Estuary: Occurrence, trophic transfer, and human health risks.

Antibiotics and polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants in the aquatic region encompassing the estuary of the Yellow River and Laizhou Bay. But little information is available about the trophic transfer of antibiotics and PAHs in the marine food web of this area. This study investigated the occurrence and trophic transfer of 19 antibiotics and 16 PAHs in marine organisms from a food web of Laizhou Bay of the Yellow River estuary. Sulfonamides, fluoroquinolones, and 2 to 4-ring PAHs were the dominant contaminants in organisms. There was a significant positive correlation between the log total concentration of sulfonamides and trophic level (TL). Sulfadiazine, sulfamethazine, and erythromycin had biomagnification effects, while ciprofloxacin and ofloxacin had biological dilution effects. The log total concentration of PAHs had a significant negative correlation with TL. Naphthalene, fluorene, anthracene, pyrene, and benzo[g,h,i]perylene had biological dilution effects. The distinct correlations of trophic magnification factors Dow of antibiotics and Kow of 2 to 5-ring PAHs, indicating that the potential of these two coefficients for predicting their transfer. Risk assessment indicated that the consumption of seafood containing antibiotics and PAHs in Laizhou Bay of the Yellow River estuary posed health and carcinogenic risks to human, respectively.

Nano-enzyme hydrogels for cartilage repair effectiveness based on ternary strategy therapy.

Designing artificial nano-enzymes for scavenging reactive oxygen species (ROS) in chondrocytes (CHOs) is considered the most feasible pathway for the treatment of osteoarthritis (OA). However, the accumulation of ROS due to the amount of nano-enzymatic catalytic site exposure and insufficient oxygen supply seriously threatens the clinical application of this therapy. Although metal-organic framework (MOF) immobilization of artificial nano-enzymes to enhance active site exposure has been extensively studied, artificial nano-enzymes/MOFs for ROS scavenging in OA treatment are still lacking. In this study, a biocompatible lubricating hydrogel-loaded iron-doped zeolitic imidazolate framework-8 (Fe/ZIF-8/Gel) centrase was engineered to scavenge endogenous overexpressed ROS synergistically generating dissolved oxygen and enhancing sustained lubrication for CHOs as a ternary artificial nano-enzyme. This property enabled the nano-enzymatic hydrogels to mitigate OA hypoxia and inhibit oxidative stress damage successfully. Ternary strategy-based therapies show excellent cartilage repair in vivo. The experimental results suggest that nano-enzyme-enhanced lubricating hydrogels are a potentially effective OA treatment and a novel strategy.