The role of nonhistone lactylation in disease.

In 2019, a novel post-translational modification termed lactylation was identified, which established a connection among lactate, transcriptional regulation and epigenetics. Lactate, which is traditionally viewed as a metabolic byproduct, is now recognized for its significant functional role, including modulating the tumor microenvironment, engaging in signaling and interfering in immune regulation. While research on lactylation (KLA) is advancing, the focus has primarily been on histone lactylation. This paper aims to explore the less-studied area of nonhistone lactylation, highlighting its involvement in certain diseases and physiological processes. Additionally, the clinical relevance and potential implications of nonhistone lactylation will be discussed.

Prefrontal cortex astrocytes in major depressive disorder: exploring pathogenic mechanisms and potential therapeutic targets.

Major depressive disorder (MDD) is a prevalent mental health condition characterized by persistent feelings of sadness and hopelessness, affecting millions globally. The precise molecular mechanisms underlying MDD remain elusive, necessitating comprehensive investigations. Our study integrates transcriptomic analysis, functional assays, and computational modeling to explore the molecular landscape of MDD, focusing on the DLPFC. We identify key genomic alterations and co-expression modules associated with MDD, highlighting potential therapeutic targets. Functional enrichment and protein-protein interaction analyses emphasize the role of astrocytes in MDD progression. Machine learning is employed to develop a predictive model for MDD risk assessment. Single-cell and spatial transcriptomic analyses provide insights into cell type-specific expression patterns, particularly regarding astrocytes. We have identified significant genomic alterations and co-expression modules associated with MDD in the DLPFC. Key genes involved in neuroactive ligand-receptor interaction pathways, notably in astrocytes, have been highlighted. Additionally, we developed a predictive model for MDD risk assessment based on selected key genes. Single-cell and spatial transcriptomic analyses underscored the role of astrocytes in MDD. Virtual screening of compounds targeting GPR37L1, KCNJ10, and PPP1R3C proteins has identified potential therapeutic candidates. In summary, our comprehensive approach enhances the understanding of MDD's molecular underpinnings and offers promising opportunities for advancing therapeutic interventions, ultimately aiming to alleviate the burden of this debilitating mental health condition. KEY MESSAGES: Our investigation furnishes insightful revelations concerning the dysregulation of astrocyte-associated processes in MDD. We have pinpointed specific genes, namely KCNJ10, PPP1R3C, and GPR37L1, as potential candidates warranting further exploration and therapeutic intervention. We incorporate a virtual screening of small molecule compounds targeting KCNJ10, PPP1R3C, and GPR37L1, presenting a promising trajectory for drug discovery in MDD.

Sirt1 mitigates hepatic lipotoxic injury induced by high-fat-diet in fish through Ire1α deacetylation.

BACKGROUND: Silent information regulator protein 1 (Sirt1) is crucial in regulating lipid metabolism, but its specific role and mechanism in fish hepatic lipotoxic injury remain undefined. OBJECTIVES: This study aimed to elucidate the regulatory role of Sirt1 and the underlying mechanisms in dietary lipid-induced hepatic lipotoxic injury in a marine teleost black seabream. METHODS: Black seabream were fed a control diet (12% lipid level), HFD (18% lipid level, oleic acid [OA]-rich), or HFD supplemented with 0.25%, 0.50%, or 1.00% resveratrol (RSV) for 8 weeks. The cultured hepatocytes were stimulated by OA (OA, 200µM), OA supplemented with RSV (20µM), or transfection with sirt1-small interfering RNA (sisirt1). Biochemical indices, gene expression (qPCR), and histology, transmission electron microscope (TEM), immunofluorescence, Western blot (WB), flow cytometry (FCM), and immunoprecipitation assays were conducted to evaluate hepatic lipid deposition, lipid metabolism, endoplasmic reticulum stress (ERS), inflammation and apoptosis, and determine protein interactions between Sirt1 and Ire1α. RESULTS: In vivo, RSV supplementation increased mRNA and protein expression levels of sirt1 (236.2%±16.1%, and 53.1%±14.3%) and down-regulated the mRNA and phosphorylated protein expression levels of ire1α/ Ire1α (46.0%±7.6% and 38.6%± 7.0%,), jnk/Jnk (57.6±7.3% and 122.1%) and nf-κb/Nf-κb p65 (41.7%±7.1% and 24.6%±0.8%) compared to the HFD group. Similar patterns were found in the in vitro experiments, however, after knockdown of sirt1, although the cells were incubated with RSV, the expression levels of ire1α/ Ire1α, jnk/Jnk and nf-κb/Nf-κb p65 showed no significant differences compared to the OA treatment. Moreover, we found that mutation of K61 to arginine to mimic Ire1α deacetylation confers protection against Ire1α mediated OA-rich HFD-induced inflammation and apoptosis. CONCLUSION: The findings revealed that Sirt1 protects against OA-rich HFD-induced hepatic lipotoxic injury via deacetylation of Ire1α on K61, hence, reducing Ire1α autophosphorylation level, and suppressing Jnk and Nf-κb p65 activation. This mechanism is elucidated for the first time in fish.

Interaction of poly dimethyl diallyl ammonium chloride with sludge components: Anaerobic digestion performance and adaptive changes of anaerobic microbes.

The wide utilization of poly dimethyl diallyl ammonium chloride (polyDADMAC) in industrial conditions leads to its accumulation in waste activated sludge (WAS), thereby affecting subsequent WAS treatment processes. This work investigated the interaction between polyDADMAC and WAS components from the perspective of anaerobic digestion (AD) performance and anaerobes adaptability variation. The results showed that polyDADMAC decreased the content of biodegradable organic substrates (i.e., soluble protein and carbohydrate) by binding with the functional groups and then settling to the solid phase, thus impeding the subsequent utilization. Higher concentrations of polyDADMAC prompted an initial protective response of excreting organic substrates into extracellular environment, but its toxicity to archaea was irreversible. Consequently, polyDADMAC inhibited the processes of AD and induced a 30 % reduction in methane production with 0.05 g polyDADMAC/g total suspended solid (TSS) addition. Changes in microbial community structure indicated that archaea involved in methane production (e.g., Anaerolineaceae sp. and Methanosaeta sp.) were inhibited when exposed to polyDADMAC. However, several adaptive bacteria with the ability of utilizing complex organics and participating in nitrogen cycle (e.g., Aminicenantales sp. and Ellin6067 sp.) were enriched with the above dosage. Specifically, the decreased abundance of genes relevant to methane metabolism pathway (i.e., mer and cdh) and increased abundance of genes involved in metabolism of cofactors and vitamins (e.g., nad and thi) indicated the toxicity of polyDADMAC and the irritant response of microflora. Moreover, polyDADMAC underwent degradation in AD system, resulting in a 12 % reduction in 15 days, accompanied by an increase in the -NO2 functional group. In general, this study provided a thorough understanding of the interaction between polyDADMAC and WAS components, raising concerns regarding the elimination of endogenous pollutants during AD.

Hydrocyclone combines with alkali-thermal pretreatment to enhance short-chain fatty acids production from anaerobic fermentation of waste activated sludge.

The production of short-chain fatty acids (SCFAs) through anaerobic fermentation of waste activated sludge (WAS) is commonly constrained by limited substrate availability, particularly for WAS with low organic content. Combining the hydrocyclone (HC) selection with alkali-thermal (AT) pretreatment is a promising solution to address this limitation. The results indicated that HC selection modified the sludge properties by enhancing the ratio of mixed liquid volatile suspended solids (MLVSS)/mixed liquid suspended solids (MLSS) by 19.0% and decreasing the mean particle size by 17.4%, which were beneficial for the subsequent anaerobic fermentation process. Under the optimal HC + AT condition, the peak value of SCFAs production reached 4951.9 mg COD/L, representing a 23.2% increase compared to the raw sludge with only AT pretreatment. Mechanism investigations revealed such enhancement beyond mechanical separation. It involved an increase in bound extracellular polymeric substances (EPS) through HC selection and the disruption of sludge spatial structure by AT pretreatment. Consequently, this combination pretreatment accelerated the transfer of particulate organics (i.e., bound EPS and intracellular components) to the supernatant, thus increasing the accessibility of WAS substrate to hydrolytic and acidifying bacteria. Furthermore, the microbial structure was altered with the enrichment of key functional microorganisms, probably due to the facilitation of substrate biotransformation and product output. Meanwhile, the activity of hydrolases and SCFAs-forming enzymes increased, while that of methanogenic enzymes decreased. Overall, this strategy successfully enhanced SCFAs production from WAS while reducing the environmental risks of WAS disposal.

A hyaluronic acid-based dissolving microneedle patch loaded with 5-aminolevulinic acid for improved oral leukoplakia treatment.

INTRODUCTION: A local microneedle patch loaded with 5-aminolevulinic acid (ALA) was constructed to improve the efficiency of ALA photodynamic treatment of oral leukoplakia, reduce local photosensitivity reactions, and promote the healing of lesions. METHODS: The microneedle patch loaded with ALA was constructed with the hyaluronic acid (HA) solution (ALA-HAMN), and its morphology, strength, mucosal penetration, and biocompatibility were tested. RESULTS: In vivo safety and permeability tests confirmed that ALA-HAMN had good biocompatibility and could penetrate the mucosal barrier and quickly dissolve and release ALA for in situ transdermal administration. The 4-nitroquinoline oxide (NQO) rat model experiment showed that ALA-HAMN can significantly improve photodynamic therapy (PDT) efficiency and has no damage to mucosal tissue compared with the commonly used ALA cotton ball dressing. CONCLUSIONS: The ALA-loaded microneedle patch was successfully constructed for the photodynamic treatment of oral leukoplakia, and the photodynamic efficiency and comfort of oral leukoplakia were improved, which provided an effective delivery mode to improve clinical ALA-PDT treatment of oral leukoplakia (OLK).

Electrochemical production of HO2- and O2 for sulfide removal from sewage.

In this study, a comparative analysis of two electrochemical methods for sulfide control in sewer networks was performed for the first time. In addition, the mechanism of sulfide control by HO2- was elucidated, and an analysis of the device operation and electrolyte selection was performed. The two-electron oxygen reduction reaction (2e--ORR) using untreated gas diffusion electrode (GDE) was superior to the hydrogen evolution reaction (HER) using stainless-steel mesh in terms of cell voltage, product formation, and sulfide suppression. The GDE maintained a stable HO2⁻ production capacity, achieving a concentration of 4566.6 ± 173.3 mg L⁻¹ with a current efficiency (CE) of 84.13 ± 3.5 %. During the electrolysis period, a stable dissolved oxygen (DO) level in sewage was consistently observed due to continuous in-situ oxygen production in anode. HO2- exhibited a notable increase in sewage pH (10.20 ± 0.01), effectively inhibiting the release of 99.93 % of sulfides. Moreover, the combined treatment of HO2- and DO significantly surpassed that of individual treatments. Seawater treated with cation exchange resin (CER) emerged as the most promising alternative to freshwater as the electrolyte. Overall, this study demonstrates that in-situ generation of HO2⁻ and oxygen is a more effective strategy for sulfide control in sewer systems.

Transcriptomic and Metabolomic Analysis Reveal the Effects of Light Quality on the Growth and Lipid Biosynthesis in Chlorella pyrenoidosa.

Light quality has significant effects on the growth and metabolite accumulation of algal cells. However, the related mechanism has not been fully elucidated. This study reveals that both red and blue light can promote the growth and biomass accumulation of Chlorella pyrenoidosa, with the enhancing effect of blue light being more pronounced. Cultivation under blue light reduced the content of total carbohydrate in Chlorella pyrenoidosa, while increasing the content of protein and lipid. Conversely, red light decreased the content of protein and increased the content of carbohydrate and lipid. Blue light induces a shift in carbon flux from carbohydrate to protein, while red light transfers carbon flux from protein to lipid. Transcriptomic and metabolomic analysis indicated that both red and blue light positively regulate lipid synthesis in Chlorella pyrenoidosa, but they exhibited distinct impacts on the fatty acid compositions. These findings suggest that manipulating light qualities can modulate carbon metabolic pathways, potentially converting protein into lipid in Chlorella pyrenoidosa.

Catalytic divergence of O-methyltransferases shapes the chemo-diversity of polymethoxylated bibenzyls in Dendrobium catenatum.

Erianin, crepidatin, and chrysotobibenzyl are typical medicinal polymethoxylated bibenzyls (PMBs) that are commercially produced in Dendrobium species. PMBs' chemo-diversity is mediated by the manifold combinations of O-methylation and hydroxylation in a definite order, which remains unsolved. To unequivocally elucidate the methylation mechanism of PMBs, 15 possible intermediates in the biosynthetic pathway of PMBs were chemically synthesized. DcOMT1-5 were highly expressed in tissues where PMBs were biosynthesized, and their expression patterns were well-correlated with the accumulation profiles of PMBs. Moreover, cell-free orthogonal tests based on the synthesized intermediates further confirmed that DcOMT1-5 exhibited distinct substrate preferences and displayed hydroxyl-group regiospecificity during the sequential methylation process. The stepwise methylation of PMBs was discovered from SAM to dihydro-piceatannol (P) in the following order: P → 3-MeP → 4-OH-3-MeP → 4-OH-3,5-diMeP → 3,3'(4'),5-triMeP → 3,4,4',5-tetraMeP (erianin) or 3,3',4,5-tetraMeP (crepidatin) → 3,3',4,4',5-pentaMeP (chrysotobibenzyl). Furthermore, the regioselectivities of DcOMTs were investigated by ligand docking analyses which corresponded precisely with the catalytic activities. In summary, the findings shed light on the sequential catalytic mechanisms of PMB biosynthesis and provide a comprehensive PMB biosynthetic network in D. catenatum. The knowledge gained from this study may also contribute to the development of plant-based medicinal applications and the production of high-value PMBs.

A clinical-radiomics nomogram for the prediction of the risk of upper gastrointestinal bleeding in patients with decompensated cirrhosis.

Objective: To develop a model that integrates radiomics features and clinical factors to predict upper gastrointestinal bleeding (UGIB) in patients with decompensated cirrhosis. Methods: 104 decompensated cirrhosis patients with UGIB and 104 decompensated cirrhosis patients without UGIB were randomized according to a 7:3 ratio into a training cohort (n = 145) and a validation cohort (n = 63). Radiomics features of the abdominal skeletal muscle area (SMA) were extracted from the cross-sectional image at the largest level of the third lumbar vertebrae (L3) on the abdominal unenhanced multi-detector computer tomography (MDCT) images. Clinical-radiomics nomogram were constructed by combining a radiomics signature (Rad score) with clinical independent risk factors associated with UGIB. Nomogram performance was evaluated in calibration, discrimination, and clinical utility. Results: The radiomics signature was built using 11 features. Plasma prothrombin time (PT), sarcopenia, and Rad score were independent predictors of the risk of UGIB in patients with decompensated cirrhosis. The clinical-radiomics nomogram performed well in both the training cohort (AUC, 0.902; 95% CI, 0.850-0.954) and the validation cohort (AUC, 0.858; 95% CI, 0.762-0.953) compared with the clinical factor model and the radiomics model and displayed excellent calibration in the training cohort. Decision curve analysis (DCA) demonstrated that the predictive efficacy of the clinical-radiomics nomogram model was superior to that of the clinical and radiomics model. Conclusion: Clinical-radiomics nomogram that combines clinical factors and radiomics features has demonstrated favorable predictive effects in predicting the occurrence of UGIB in patients with decompensated cirrhosis. This helps in early diagnosis and treatment of the disease, warranting further exploration and research.

Building High-Density Polar Hybrid Perovskites via Intercalation of Cs+ and Aromatic Diamine for Passive X-ray Detection.

2D organic-inorganic hybrid perovskites (OIHPs) have shown great promise in direct X-ray detection. The development of high-performance passive X-ray detectors in 2D OIHPs calls for an increase in material density while maintaining structural polarity, which is becoming quite challenging. Here, a high-density, polar 2D alternating-cation-intercalated (ACI) perovskite, (4-AP)Cs2Pb2I8 (B, 4-AP = 4-amidinopyridinium), capable of addressing this problem is successfully constructed by introducing heavy Cs+ into the interlayer space of an aromatic Dion-Jacobson (DJ) perovskite (4-AP)PbI4 (A). Through such a DJ-to-ACI design, the newly developed 2D OIHP B not only significantly increases its density to 4.23 g cm-3 (even higher than that of 3D MAPbI3) but also crystallizes in a polar space group (Ama2), which further leads to enhanced X-ray attenuation and an obvious polar photovoltage (1.1 V) under X-ray irradiation. As a result, X-ray detectors fabricated by high-quality single crystals of B exhibit excellent and stable detection performance under self-powered mode with a high sensitivity of 107 µC Gy-1 cm-2 and a low detection limit of 289 nGy s-1. This work provides implications for the future exploration and regulation of novel ACI OIHPs for high-performance photoelectronic devices.

Biodegradable microplastics aggravate greenhouse gas emissions from urban lake sediments more severely than conventional microplastics.

Freshwater ecosystems, such as urban lake sediments, have been identified as important sources of greenhouse gases (GHGs) to the atmosphere, as well as persistent sinks for ubiquitous microplastics due to the high population density and frequent anthropogenic activity. The potential impacts of microplastics on GHG production, however, remain underexplored. In this study, four types of common biodegradable microplastics (BMPs) versus four conventional non-biodegradable microplastics (NBMPs) were artificially exposed to urban lake sediments to investigate the responses of nitrous oxide (N2O) and methane (CH4) production, and make a comparison regarding how the biodegradability of microplastics affected GHG emissions. Importantly, results suggested that BMPs aggravated N2O and CH4 production in urban lake sediments more severely than conventional NBMPs. The production rates of N2O and CH4 increased by 48.78-71.88 % and 30.87-69.12 %, respectively, in BMPs groups, while those increased by only 0-25.69 % and 6.46-10.46 % with NBMPs exposure. Moreover, BMPs insignificantly affected nitrification but facilitated denitrification, while NBMPs inhibited both processes. BMPs not only created more oxygen-limited microenvironment, greatly promoting N2O production via nitrifier denitrification pathway, but also provided dissolved organic carbon favoring heterotrophic denitrification, which was primarily supported by the enriched denitrifiers and functional genes. In contrast, NBMPs slightly upregulated nitrifier denitrification pathway to generate N2O, and showed a toxic inhibition on both nitrifiers and denitrifiers. In addition, both BMPs and NBMPs promoted hydrogen-dependent methanogenic pathway but suppressed acetate-dependent pathway. The greater enhancement of CH4 production with BMPs exposure was attributed to the additional organic carbon substrates derived from BMPs and the stimulated microbial methane metabolism activities.

CliqueFluxNet: Unveiling EHR Insights with Stochastic Edge Fluxing and Maximal Clique Utilisation Using Graph Neural Networks.

Electronic Health Records (EHRs) play a crucial role in shaping predictive are models, yet they encounter challenges such as significant data gaps and class imbalances. Traditional Graph Neural Network (GNN) approaches have limitations in fully leveraging neighbourhood data or demanding intensive computational requirements for regularisation. To address this challenge, we introduce CliqueFluxNet, a novel framework that innovatively constructs a patient similarity graph to maximise cliques, thereby highlighting strong inter-patient connections. At the heart of CliqueFluxNet lies its stochastic edge fluxing strategy - a dynamic process involving random edge addition and removal during training. This strategy aims to enhance the model's generalisability and mitigate overfitting. Our empirical analysis, conducted on MIMIC-III and eICU datasets, focuses on the tasks of mortality and readmission prediction. It demonstrates significant progress in representation learning, particularly in scenarios with limited data availability. Qualitative assessments further underscore CliqueFluxNet's effectiveness in extracting meaningful EHR representations, solidifying its potential for advancing GNN applications in healthcare analytics.

Autocrine IL-8 Contributes to Propionibacterium Acnes-induced Proliferation and Differentiation of HaCaT Cells via AKT/FOXO1/ Autophagy.

OBJECTIVE: Proprionibacterium acnes (P. acnes)-induced inflammatory responses, proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris (AV). P. acnes was found to enhance the production of interleukin-8 (IL-8) by keratinocytes. This study aimed to investigate the role of IL-8 in P. acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism. METHODS: The P. acnes-stimulated HaCaT cell (a human keratinocyte cell line) model was established. Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1 (CXCR1) and C-X-C motif chemokine receptor 2 (CXCR2) on HaCaT cells. Cell counting kit-8 (CCK-8) assay, 5-ethynyl-20-deoxyuridine (EdU) assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P. acnes, the IL-8 neutralizing antibody, the CXCR2 antagonist (SB225002), or the CXCR1/CXCR2 antagonist (G31P). Western blotting, nuclear and cytoplasmic separation, CCK-8 assay, and EdU assay were employed to determine the downstream pathway of CXCR2 after P. acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist, the protein kinase B (AKT) antagonist (AZD5363), or the constitutively active forkhead box O1 (FOXO1) mutant. Finally, autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine (3-MA). RESULTS: The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P. acnes stimulation. The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P. acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling. In brief, IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis. Subsequently, phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P. acnes-induced keratinocytes. CONCLUSION: This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P. acnes-induced keratinocytes, suggesting a potential therapeutic target for AV.

Composite dietary antioxidant index is associated with renal anemia: a cross-sectional study.

An increasing evidence suggested that chronic kidney disease (CKD) is closely related to oxidative stress, and dietary antioxidant intake can serve as a primary preventive measure for CKD. However, the relationship between composite dietary antioxidant index (CDAI) and renal anemia is not well understood. We postulated that elevated CDAI levels would be inversely related to a higher likelihood of renal anemia. The standardized calculation of CDAI was performed to investigate the relationship between them by a binary regression model. A non-linear relationship was examined through restricted cubic spline curves, and then pinpointed the inflection point. Subgroup analysis was then used to assess the robustness of the model. Finally 5880 participants were included in the study and a notable correlation between CDAI and renal anemia was found (P < 0.0001). In the multivariate linear regression model with adjustment for all confounding variables, the odds ratio (OR) and 95% confidence interval (CI) was 0.96 (0.94, 0.98; P < 0.0001), A non-linear relationship between CDAI and renal anemia was explored through restricted cubic splines, with a inflection at 6.005. Before the inflection point, for each unit rise in CDAI, the prevalence of renal anemia decreased by 5.7%. Subgroup analysis showed no statistically significant differences in interactions between any subgroups (P > 0.05). Our findings indicated a non-linear negative correlation between CDAI and renal anemia. The causal relationship still needs to be further clarified through large-scale prospective studies.

Predicting graft and patient outcomes following kidney transplantation using interpretable machine learning models.

The decision to accept a deceased donor organ offer for transplant, or wait for something potentially better in the future, can be challenging. Clinical decision support tools predicting transplant outcomes are lacking. This project uses interpretable methods to predict both graft failure and patient death using data from previously accepted kidney transplant offers. Using more than 25 years of transplant outcome data, we train and compare several survival analysis models in single risk settings. In addition, we use post hoc interpretability techniques to clinically validate these models. Neural networks show comparable performance to the Cox proportional hazard model, with concordance of 0.63 and 0.79 for prediction of graft failure and patient death, respectively. Donor and recipient ages, the number of mismatches at DR locus, dialysis type, and primary renal disease appear to be important features for transplant outcome prediction. Owing to their good predictive performance and the clinical relevance of their post hoc interpretation, neural networks represent a promising core component in the construction of future decision support systems for transplant offering.

Quercetin Modulates Ferroptosis via the SIRT1/Nrf-2/HO-1 Pathway and Attenuates Cartilage Destruction in an Osteoarthritis Rat Model.

Osteoarthritis (OA) is the most common joint disease, causing symptoms such as joint pain, swelling, and deformity, which severely affect patients' quality of life. Despite advances in medical treatment, OA management remains challenging, necessitating the development of safe and effective drugs. Quercetin (QUE), a natural flavonoid widely found in fruits and vegetables, shows promise due to its broad range of pharmacological effects, particularly in various degenerative diseases. However, its role in preventing OA progression and its underlying mechanisms remain unclear. In this study, we demonstrated that QUE has a protective effect against OA development both in vivo and in vitro, and we elucidated the underlying molecular mechanisms. In vitro, QUE inhibited the expression of IL-1ß-induced chondrocyte matrix metalloproteinases (MMP3 and MMP13) and inflammatory mediators such as INOS and COX-2. It also promoted the expression of collagen II, thereby preventing the extracellular matrix (ECM). Mechanistically, QUE exerts its protective effect on chondrocytes by activating the SIRT1/Nrf-2/HO-1 and inhibiting chondrocyte ferroptosis. Similarly, in an OA rat model induced by anterior cruciate ligament transection (ACLT), QUE treatment improved articular cartilage damage, reduced joint pain, and normalized abnormal subchondral bone remodeling. QUE also reduced serum IL-1ß, TNF-α, MMP3, CTX-II, and COMP, thereby slowing the progression of OA. QUE exerts chondroprotective effects by inhibiting chondrocyte oxidative damage and ferroptosis through the SIRT1/Nrf-2/HO-1 pathway, effectively alleviating OA progression in rats.

An HFD negatively influences both joint and liver health in rabbits with and without an enzymatically-induced model of arthritis.

Osteoarthritis (OA) is a common arthritis types in animals that causes persistent pain and reduces quality of life. Although a high-fat diet (HFD) is widely believed to induce obesity and have adverse effects on the body, the connection between HFD and joint health is not well understood. Therefore, in this study, 32 healthy male New Zealand rabbits were randomly divided into four groups: healthy rabbits fed a standard diet (NDG, n=8) or an HFD (HDG, n=8), rabbits fed a standard diet (OAG, n=8) and an HFD (HOG, n=8), and arthritis was induced by intra-articular enzyme injection. After 12 weeks of HFD feeding, articular cartilage, synovium, and subchondral bone were isolated and collected. Joint tissue damage was evaluated using histopathological and imaging tests. The results showed that there was no significant difference in body weight between rabbits fed a normal diet and those fed an HFD. However, the HFD led to an increase in joint injuries in both induced and non-induced arthritis rabbits. Specifically, the HFD induced lipid metabolism disorders and liver damage in vivo, significantly elevating the levels of serum inflammatory cytokines and bone metabolism markers. Moreover, HFD exacerbated articular cartilage damage in the joints and increased the accumulation of inflammatory cells in synovial tissue, resulting in a notable increase in synovial macrophages and inflammatory cytokines. Additionally, HFD accelerated the bone resorption process in subchondral bone, leading to the destruction of bone mass and subchondral bone microstructure. In summary, the results of this study indicate that an HFD can cause histological damage to the articular cartilage, synovium, and subchondral bone in rabbits, exacerbating arthritis in pre-existing joint damage. Notably, weight is not the primary factor in this effect.

Accuracy of subtraction fractional flow reserve with computed tomography in identifying early revascularization in patients with coronary artery disease.

OBJECTIVES: The diagnostic performance of fractional flow reserve with computed tomography (FFR-CT) is affected by the presence of calcified plaque. Subtraction can remove the influence of calcification in coronary computed tomography angiography (CCTA) to increase confidence in the diagnosis of coronary artery stenosis. Our purpose is to investigate the accuracy of post-subtraction FFR-CT in predicting early revascularization. DESIGN: Based on CCTA data of 237 vessels from 79 patients with coronary artery disease, subtraction CCTA images were obtained at a local post-processing workstation, and the conventional and post-subtraction FFR-CT measurements and the difference in proximal and distal FFR-CT values of the narrowest segment of the vessel (ΔFFR-CT) were analyzed for their accuracy in predicting early coronary artery hemodynamic reconstruction. RESULTS: With FFR-CT ≤ 0.8 as the criterion, the accuracy of conventional and post-subtraction FFR-CT measurements in predicting early revascularization was 73.4% and 77.2% at the patient level, and 64.6% and 72.2% at the vessel level, respectively. The specificity of post-subtraction FFR-CT measurements was significantly higher than that of conventional FFR-CT at both the patient and vessel levels (P of 0.013 and 0.015, respectively). At the vessel level, the area under the curve of receiver operating characteristic was 0.712 and 0.797 for conventional and post-subtraction ΔFFR-CT, respectively, showing a difference (P = 0.047), with optimal cutoff values of 0.07 and 0.11, respectively. CONCLUSION: The post-subtraction FFR-CT measurements enhance the specificity in predicting early revascularization. The post-subtraction ΔFFR-CT value of the stenosis segment > 0.11 may be an important indicator for early revascularization.

Pentavalent Rotavirus Vaccine Coverage and Trends in Rotavirus Detection Before and After This Vaccination in Chengdu, China.

Pentavalent rotavirus vaccine (RV5) coverage and changes in rotavirus detection in the prevaccine and postvaccine era in Chengdu were investigated. The results showed that the coverage of RV5 had been increasing but still relatively low. Nevertheless, the dramatical decline in the rotavirus detection was observed after the introduction of RV5. Efforts to improve the coverage of rotavirus vaccination should continue to maximize the public health benefits.