Ferromagnetic ordering correlated strong metal-oxygen hybridization for superior oxygen reduction reaction activity.

The efficiency of transition-metal oxide materials toward oxygen-related electrochemical reactions is classically controlled by metal-oxygen hybridization. Recently, the unique magnetic exchange interactions in transition-metal oxides are proposed to facilitate charge transfer and reduce activation barrier in electrochemical reactions. Such spin/magnetism-related effects offer a new and rich playground to engineer oxide electrocatalysts, but their connection with the classical metal-oxygen hybridization theory remains an open question. Here, using the MnxVyOz family as a platform, we show that ferromagnetic (FM) ordering is intrinsically correlated with the strong manganese (Mn)-oxygen (O) hybridization of Mn oxides, thus significantly increasing the oxygen reduction reaction (ORR) activity. We demonstrate that this enhanced Mn-O hybridization in FM Mn oxides is closely associated with the generation of active Mn sites on the oxide surface and obtaining favorable reaction thermodynamics under operating conditions. As a result, FM-Mn2V2O7 with a high degree of Mn-O hybridization achieves a record high ORR activity. Our work highlights the potential applications of magnetic oxide materials with strong metal-oxygen hybridization in energy devices.

Electronic structures and quantum capacitance of twisted bilayer graphene with defects based on three-band tight-binding model.

Twisted bilayer graphene (tBLG) with C vacancies would greatly improve the density of states (DOS) around the Fermi level (EF) and quantum capacitance; however, the single-band tight-binding model only considering pz orbitals cannot accurately capture the low-energy physics of tBLG with C vacancies. In this work, a three-band tight-binding model containing three p orbitals of C atoms is proposed to explore the modulation mechanism of C vacancies on the DOS and quantum capacitance of tBLG. We first obtain the hopping integral parameters of the three-band tight-binding model, and then explore the electronic structures and the quantum capacitance of tBLG at a twisting angle of θ = 1.47° under different C vacancy concentrations. The impurity states contributed by C atoms with dangling bonds located around the EF and the interlayer hopping interaction could induce band splitting of the impurity states. Therefore, compared with the quantum capacitance of pristine tBLG (∼18.82 µF cm-2) at zero bias, the quantum capacitance is improved to ∼172.76 µF cm-2 at zero bias, and the working window with relatively large quantum capacitance in the low-voltage range is broadened in tBLG with C vacancies due to the enhanced DOS around the EF. Moreover, the quantum capacitance of tBLG is further increased at zero bias with an increase of the C vacancy concentration induced by more impurity states. These findings not only provide a suitable multi-band tight-binding model to describe tBLG with C vacancies but also offer theoretical insight for designing electrode candidates for low-power consumption devices with improved quantum capacitance.

Application of the cell-based RT-qPCR assay (C-QPA) for potency detection of the novel trivalent rotavirus vaccine in China.

BACKGROUND: Because of the deficiencies of traditional methods in multivalent rotavirus vaccine potency detection, a cell-based quantitative RT-qPCR assay (C-QPA) was established and validated for specificity, precision, and accuracy. METHODS: In order to further validate the robustness of this method in actual titer detection, the linear range and the practical application under different conditions were tested using monovalent and trivalent rotavirus samples and standards. RESULTS: Results showed that the linear range was 2.0-6.5, 3.9-8.3, and 3.5-8.1 UI (unit of infectivity) for G2, G3, and G4, respectively. Besides, unknown sample with high titer exceeding the linear range can be calculated by dilution. The UIs of serotypes G2, G3, and G4 in monovalent and trivalent rotavirus samples showed a relative deviation ≤4.10%, and the monovalent samples of the same serotype with or without protective agents showed a relative deviation ≤4.28%; the coefficient of variation (CV) of at least 176 tests (548 individual runs) of 3 in vitro-transcribed RNA standards with certain concentrations was not higher than 6.50%; the results of the trivalent samples tested by more than 149 times in 5 years (467 individual runs) showed the CVs lower than 12.66%; 15 samples detected by one laboratory showed a CV lower than 9.83%, while other three samples tested by two independent laboratories showed a CV lower than 6.90%. CONCLUSION: In summary, the C-QPA has good linearity, durability, repeatability, and reproducibility in practical application and has been proved by the authority to be widely used in the production, quality control and release of the recently licensed trivalent vaccine in China.

Organic Photocathode Supported by Copper Nanosheets Array for Overall Water Splitting.

The Z-scheme overall solar water splitting is a mimic of natural photosynthesis to convert solar energy into chemical energy. Since the energy levels of most organic semiconductors match well with the hydrogen evolution potential, they have great application prospects as photocathodes in Z-scheme photoelectrochemical systems. However, due to the weak light absorption and difficult carrier separation, the photocurrent density and onset potential of organic photocathodes are still low. To solve these problems, we introduced a copper nanosheets array (Cu NSA) framework under organic layers to increase the surface reaction sites, improve the light absorption and enhance the distribution range of built-in electric field simultaneously. As a result, the photocurrent density and onset potential of poly(3-hexylthiophene) : [6,6]-phenyl-C61 -butyric acid (P3HT : PCBM) photocathode were enhanced significantly. The onset potential increased by 50 mV to 0.65 V vs. RHE, and the photocurrent density reached -1 mA cm-2 at 0 V vs. RHE, which was 18 times that of the sample without Cu NSA. The optimized photocathode was connected with titanium dioxide nanorods array photoanode in a tandem manner to realize the spontaneous overall water splitting. Without bias and co-catalyst, the photocurrent density was maintained at 110 µA cm-2 and the solar-to-fuel conversion efficiency was 0.14 % in neutral solution. These results provide a feasible method for optimizing the performance of organic photocathodes.

A Classification Method for Electronic Components Based on Siamese Network.

In the field of electronics manufacturing, electronic component classification facilitates the management and recycling of the functional and valuable electronic components in electronic waste. Current electronic component classification methods are mainly based on deep learning, which requires a large number of samples to train the model. Owing to the wide variety of electronic components, collecting datasets is a time-consuming and laborious process. This study proposed a Siamese network-based classification method to solve the electronic component classification problem for a few samples. First, an improved visual geometry group 16 (VGG-16) model was proposed as the feature extraction part of the Siamese neural network to improve the recognition performance of the model under small samples. Then, a novel channel correlation loss function that allows the model to learn the correlation between different channels in the feature map was designed to further improve the generalization performance of the model. Finally, the nearest neighbor algorithm was used to complete the classification work. The experimental results show that the proposed method can achieve high classification accuracy under small sample conditions and is robust for electronic components with similar appearances. This improves the classification quality of electronic components and reduces the training sample collection cost.

Characterization of Novel Bacteriophage AhyVDH1 and Its Lytic Activity Against Aeromonas hydrophila.

Phage therapy is an alternative approach to overcome the problem of multidrug-resistant bacteria. Here, a novel bacteriophage AhyVDH1, which infects Aeromonas hydrophila 4572, was isolated and its morphology, one-step growth curve, lytic activity, stability under various conditions, and genome were investigated. Transmission electron microscopy revealed that AhyVDH1 has an icosahedral head 49 nm in diameter and a contractile tail 127 nm in length, suggesting that it belongs to the family Myoviridae. AhyVDH1 showed strong adsorption to the surface of A. hydrophila 4572 (90% in 10 min). The latent period of AhyVDH1 was shown to be 50 min, and the burst size was 274 plaque-forming unit/infected cell. AhyVDH1 was stable at 30 °C for 1 h and lost infectivity after20 min of heating at 60 °C. Infectivity remained unaffected at pH 6-7 for 1 h, while the bacteriophage was inactivated at pH < 4 or > 11. AhyVDH1 has a 39,175-bp genome, with a 58% G + C content and 59 open reading frames. BLAST analysis indicated that the genome sequence of phage AhyVDH1 was related to that of Aeromonas phage Ahp2. Both time and MOI-dependent in vitro A. hydrophila growth inhibition were observed with AhyVDH1.Re-growth of the host bacteria appeared about 12 h after treatment, suggesting its potential therapeutic value in treating A. hydrophila infections, but phage cocktails should be developed.

Comparison of Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in Evaluating Anxiety and Depression in Patients with Psoriatic Arthritis.

BACKGROUND: This study aimed to compare the Hospital Anxiety and Depression Scale (HADS) and the Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) in evaluating anxiety and depression in psoriatic arthritis (PsA) patients. METHODS: A total of 70 PsA patients were enrolled. Demographic and clinical characteristics were collected after enrollment. HADS-A and SAS were used to evaluate the anxiety of PsA patients, while HADS-D and SDS were used to evaluate the depression of PsA patients. RESULTS: Similar results were observed in detecting the rate of anxiety by HADS-A and SAS (27.1 vs. 21.4%, p = 0.424), and there was no difference in classifying the severity of anxiety by HADS-A and SAS (p = 0.347). The Spearman test also disclosed that HADS-A score was positively associated with SAS score (p <0.001). The rates of depression were similar by HADS-D and SDS (27.1 vs. 40.0%; p = 0.108). However, different results were observed in grading the severity of anxiety by HADS-D and SDS (p = 0.009), and no correlation was observed between HADS-D and SDS scores (p = 0.138). The consumption of time for HADS assessment was shorter than that for SAS/SDS assessment (p < 0.001). In addition, a positive correlation of HADS-A score with patients' global assessment (PGA) (p = 0.022) and fatigue scores (p = 0.028) was discovered, and HADS-D score was positively associated with PGA score (p = 0.019). SAS or SDS score presented less correlation with clinical features of PsA patients, which illuminated that only SAS score was positively associated with duration of psoriasis (p = 0.030). CONCLUSION: HADS seems to be a better option for anxiety and depression assessment than SAS/SDS in PsA patients.

Mining the proliferative diabetic retinopathy-associated genes and pathways by integrated bioinformatic analysis.

PURPOSE: Diabetic retinopathy (DR) especially proliferative diabetic retinopathy (PDR) is a serious eye disease. We aimed to identify key pathway and hub genes associated with PDR by analyzing the expression of retinal fibrovascular tissue in PDR patients. METHODS: First raw data were downloaded from the Gene Expression Omnibus database. Median normalization was subsequently applied to preprocess. Differentially expressed genes (DEGs) analyzed with the Limma package. Weighted correlation network analysis (WGCNA) was utilized to build the co-expression network for all genes. Then, we compared the DEGs and modules filtered out by WGCNA. A protein-protein interaction network based on the STRING web site and the Cytoscape software was constructed by the overlapping DEGs. Next, the Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Finally, we used the Comparative Toxicogenomics Database to identify some important pathways and hub genes tightly related to PDR. RESULTS: Functional enrichment analysis showed that the pathway of cytokine-cytokine receptor interaction was significantly related to PDR eight hub genes which were associated with pathway including tumor necrosis factor (TNF), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A), C-C chemokine 20 (CCL20), chemokine (C-X-C motif) ligand 2 (CXCL2), oncostatin M (OSM) interleukin 10 (IL10), interleukin 15 (IL 15), and interleukin 1B (IL1B). CONCLUSIONS: We identified one pathway and eight hub genes, which were associated with PDR. The pathway provided references that will advance the understanding of mechanisms of PDR. Moreover, the hub genes may serve as therapeutic targets for precise diagnosis and treatment of PDR in the future.

The role of PTEN in regulation of hepatic macrophages activation and function in progression and reversal of liver fibrosis.

Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl4-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl4-induced mice but increased to a near-normal level in reversed mice. Moreover, PTEN was significantly decreased in IL4-induced RAW 264.7 cells in vitro and lower expression of PTEN was observed in M2 macrophages in vivo. In addition, loss- and gain-of-function studies suggested that PTEN regulates M2 macrophages polarization via activation of PI3K/Akt/STAT6 signaling, but had a limited effect on M1 macrophages polarization in vitro. Additionally, Ly294002, a chemical inhibitor of PI3K/Akt, could dramatically down-regulate the hallmarks of M2 macrophages. In conclusion, PTEN mediates macrophages activation by PI3K/Akt/STAT6 signaling pathway, which provides novel compelling evidences on the potential of PTEN in liver injury and opens new cellular target for the pharmacological therapy of liver fibrosis.

Enhanced linear absorption coefficient of in-plane monolayer graphene on a silicon microring resonator.

We demonstrate that enhanced linear absorption coefficient (LAC) of in-plane monolayer graphene is determined by the optical transmission spectra of a graphene layer coated symmetrically coupled add-drop silicon microring resonator (SC-ADSMR), of which the value is around 0.23 dB/µm. In contrast to the traditional cut-back method, the measured results aren't dependent on the coupling efficiency between the fiber tip and the waveguide. Moreover, precisely evaluation of graphene layer coated silicon microring resonator (SMR) is crucial for future optoelectronic devices with compact footprint and low power consumption.

Cancer patient autonomy and quality of dying-a prospective nationwide survey in Taiwan.

BACKGROUND: Patient autonomy is an essential factor in the measurement of quality of dying. We aimed to conduct a study to investigate the factors affecting the autonomy of advanced cancer patients in Taiwan. METHODS: We conducted a prospective, multicenter study and recruited 574 advanced cancer patients from four inpatient hospice wards in Taiwan; their quality of dying was measured using the validated good death scale and the audit scale. Physician-assessed autonomy and the other scales were measured in a team conference by the primary care physician and the team 1 week after the patient had passed away. The good death scale was measured twice, once at admission and then after the patient had passed away for comparison. We measured factors affecting the improvement in quality of dying of these patients initially by applying multiple linear regression analysis. Then, taking physician-assessed autonomy as a dependent variable, we identified the factors that affected this variable. RESULTS: The good death score at admission, clear consciousness, number of admission days beyond 7, better physical care, higher physician-assessed autonomy, better emotional support, better communication, better continuity of life, and physician-reported rate of closure were factors affecting the quality of dying. Further analysis identified age (p = 0.031), consciousness (p = 0.01), and total good death scale score at death (p < 0.001) as determinants of physician-assessed autonomy. CONCLUSIONS: We concluded that physician-assessed autonomy would affect a good death and was highly correlated with age, consciousness level, and quality of dying at the end for advanced cancer patients in Taiwan.

Do-not-resuscitate orders and related factors among family surrogates of patients in the emergency department.

PURPOSE: The purpose of this study was to investigate the prevalence of do-not-resuscitate (DNR) orders and to identify relevant factors influencing the DNR decision-making process by patients' surrogates in the emergency department (ED). METHODS: A prospective, descriptive, and correlational research design was adopted. A total of 200 surrogates of cancer or non-cancer terminal patients, regardless of whether they signed a DNR order, were recruited as subjects after physicians of the emergency department explained the patient's conditions, advised on withholding medical treatment, and provided information on palliative care to all surrogates. RESULTS: Of the 200 surrogates, 23 % signed a DNR order for the patients. The demographic characteristics of patients and surrogates, the level of understanding of DNR orders, and factors of the DNR decision had no significant influence on the DNR decision. However, greater severity of disease (odds ratio (OR) = 1.38; 95 % confidence interval (CI) = 0.95-1.74), physician's initiative in discussing with the families (OR = 1.42; 95 % CI = 1.21-1.84), and longer length of hospital stay (OR = 1.06; 95 % CI = 1.03-1.08) were contributing factors affecting patient surrogates' DNR decisions. CONCLUSIONS: The findings of this study indicated that surrogates of patients who were more severe in disease condition, whose physicians initiated the discussion of palliative care, and who stayed longer in hospital were important factors affecting the surrogates' DNR decision-making. Therefore, early initiation of DNR discussions is suggested to improve end-of-life care.

Melittin induces PTCH1 expression by down-regulating MeCP2 in human hepatocellular carcinoma SMMC-7721 cells.

Hepatocellular carcinoma (HCC) has a high mortality rate worldwide and still remains to be a noticeable public health problem. Therefore, new remedies are urgently needed. Melittin, a major component of bee venom, is known to suppress cell growth in various cancers including HCC. However, the mechanism of the anticancer effect of melittin on HCC has not been fully elucidated. It has been reported that Methyl-CpG binding protein 2 (MeCP2) plays a key role in tumor proliferation, apoptosis, migration and invasion. In the present study, we found the high expression of MeCP2 in human HCC tissues and in the SMMC-7721 cell line. MeCP2 silencing inhibited cell proliferation, while over-expression of MeCP2 promoted cell growth in SMMC-7721 cells. It indicates that MeCP2 may be an attractive target for human HCC. We further found that melittin could inhibit cell proliferation by reducing MeCP2 expression in vitro. Interestingly, the inhibitory effect of melittin on cell proliferation was due to a delay in G0/G1 cell cycle progression, without influencing cell apoptosis. Next, we investigated the potential molecular mechanisms and found that MeCP2 could modulate Shh signaling in SMMC-7721 cells. Further study indicates that melittin may induce the demethylation of PTCH1 promoter, resulting in the increased expression of PTCH1. Furthermore, the expression of Shh and GLI1 was significantly lowered upon treatment of melittin. These results suggest that melittin can block Shh signaling in vitro. In short, these results indicate that melittin inhibits cell proliferation by down-regulating MeCP2 through Shh signaling in SMMC-7721 cells.

Abnormal brain-heart electrophysiology in mild and severe orthostatic hypotension.

INTRODUCTION: This study investigated the changes in cardiocerebral electrophysiology in patients with mild orthostatic hypotension (MOH) and severe orthostatic hypotension (SOH) and their relationship with the severity of orthostatic hypotension, psychiatric symptoms, and cognitive dysfunction. METHODS: This study included 72 nonorthostatic hypotension (NOH), 17 with MOH, and 11 with SOH. Seated resting-state heart rate variability (HRV) and quantitative electroencephalogram parameters were synchronized and recorded. HRV measures in the time and frequency domains were analyzed, along with the peak frequency and power of the brain waves. RESULTS: Abnormal neuronal activity was found in FP1 in patients with MOH, whereas it was more widespread in FP1, FP2, and O2 in patients with SOH (P < 0.05). Cardiac and cerebral electrophysiological abnormalities were significantly associated with orthostatic hypotension severity, psychiatric symptoms, and cognitive dysfunction. CONCLUSION: Abnormal EEG activity in patients are mainly manifested in the prefrontal and occipital lobes, especially in patients with SOH. These results may help patients to better understand the mechanisms underlying orthostatic hypotension severity and psychiatric and cognitive impairment in orthostatic hypotension.

Nutritional status and neurodevelopmental levels in infants at high risk of cerebral palsy.

Importance: Nutrition is associated with neurodevelopment. Infants at high risk of cerebral palsy (CP) usually suffer from undernutrition, yet the relationship between nutritional status and neurodevelopmental levels is unclear. Objective: To describe the nutritional status characteristics of infants at high risk of CP, and to explore the relationship between neurodevelopmental levels and nutritional status. Methods: This single-center cross-sectional study enrolled infants at high risk of CP, with corrected age from 0 days to 12 months. Weight and height were measured and calculated into z-scores, which were used to classify the nutritional status based on the World Health Organization growth charts and American Society for Parenteral and Enteral Nutrition standards. The Bayley Scales of Infant and Toddler Development were used to evaluate the developmental levels of gross motor, fine motor, cognition, receptive communication, and expressive communication. Results: A total of 479 infants at high risk of CP were recruited, with 43.4% classified as undernutrition. Compared to those with normal neurodevelopment, the odds of moderate and severe undernutrition were about 1.8 and 3.9 times higher in gross motor delay, 2.2 and 3.1 times higher in fine motor delay, 2.5 and 9.4 times higher in cognition delay, 2.2 and 3.9 times higher in receptive communication delay, and 3.0 and 5.6 times higher in expressive communication delay. There were significant positive correlations between nutritional status and neurodevelopmental levels (P < 0.001). Interpretation: Undernutrition and neurodevelopmental delays are prevalent among infants at high risk of CP. Worse nutritional status was correlated with lower neurodevelopmental levels.

Nomogram-based risk assessment model for left ventricular hypertrophy in patients with essential hypertension: Incorporating clinical characteristics and biomarkers.

Left ventricular hypertrophy (LVH) is a hypertensive heart disease that significantly escalates the risk of clinical cardiovascular events. Its etiology potentially incorporates various clinical attributes such as gender, age, and renal function. From mechanistic perspective, the remodeling process of LVH can trigger increment in certain biomarkers, notably sST2 and NT-proBNP. This multicenter, retrospective study aimed to construct an LVH risk assessment model and identify the risk factors. A total of 417 patients with essential hypertension (EH), including 214 males and 203 females aged 31-80 years, were enrolled in this study; of these, 161 (38.6%) were diagnosed with LVH. Based on variables demonstrating significant disparities between the LVH and Non-LVH groups, three multivariate stepwise logistic regression models were constructed for risk assessment: the "Clinical characteristics" model, the "Biomarkers" model (each based on their respective variables), and the "Clinical characteristics + Biomarkers" model, which amalgamated both sets of variables. The results revealed that the "Clinical characteristics + Biomarkers" model surpassed the baseline models in performance (AUC values of the "Clinical characteristics + Biomarkers" model, the "Biomarkers" model, and the "Clinical characteristics" model were .83, .75, and .74, respectively; P < .0001 for both comparisons). The optimized model suggested that being female (OR: 4.26, P <.001), being overweight (OR: 1.88, p = .02) or obese (OR: 2.36, p = .02), duration of hypertension (OR: 1.04, P = .04), grade III hypertension (OR: 2.12, P < .001), and sST2 (log-transformed, OR: 1.14, P < .001) were risk factors, while eGFR acted as a protective factor (OR: .98, P = .01). These findings suggest that the integration of clinical characteristics and biomarkers can enhance the performance of LVH risk assessment.

Humoral and cellular immune responses induced by serogroup W135 meningococcal conjugate and polysaccharide vaccines.

Investigating the mechanisms by which W135 meningococcal conjugate (PSW135-TT) activates adaptive immune responses in mice can provide a comprehensive understanding of the immune mechanisms of bacterial polysaccharide conjugate vaccines. We compared B-cell and T-cell immune responses immunized with W135 meningococcal capsular polysaccharides (PSW135), tetanus toxoid (TT) and PSW135-TT in mice. The results showed that PSW135-TT could induce higher PSW135-specific and TT-specific IgG antibodies with a significant enhancement after two doses. All serum antibodies immunized with PSW135- TT had strong bactericidal activity, whereas none of the serum antibodies immunized with PSW135 had bactericidal activity. Besides, IgM and IgG antibodies immunized with PSW135-TT after two doses were positively correlated with the titer of bactericidal antibodies. We also found Th cells favored Th2 humoral immune responses in PSW135-TT, PSW135, and TT-immunized mice, especially peripheral blood lymphocytes. Furthermore, PSW135-TT and TT could effectively activate bone marrow derived dendritic cells (BMDCs) and promote BMDCs to highly express major histocompatibility complex Ⅱ (MHCⅡ), CD86 and CD40 molecules in mice, whereas PSW135 couldn't. These data verified the typical characteristics of PSW135-TT and TT as T cell dependent antigen (TD-Ag) and PSW135 as T cell independent antigen (TI-Ag), which will be very helpful for further exploration of the immune mechanism of polysaccharide-protein conjugate vaccines and improvement of the quality of bacterial polysaccharide conjugate vaccines in future.

CCR2 antagonist represses fibroblast-like synoviocyte-mediated inflammation in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease with a global incidence of approximately 1%. Its complex pathogenesis makes the development of RA-related therapeutics very difficult. Existing drugs for RA have many side effects and are prone to drug resistance. One potential target for RA drugs includes C-Cchemokinereceptortype2 (CCR2), which belongs to the G protein-coupled receptor family. A series of RA drugs targeting CCR2 have been developed; however, the pre-clinical and clinical research results for CCR2 antagonists are inconsistent. We found that CCR2 was also expressed in primary Fibroblast-like synoviocyte (FLS) from patients with RA. CCR2 antagonists can inhibit inflammatory cytokines and matrix metalloproteinases released by RA-FLS but do not affect the proliferation and migration ability of RA-FLS. In addition, CCR2 antagonist-treated RA-FLS indirectly repressed macrophage-mediated inflammation and rescued the viability of chondrocytes. Finally, a CCR2 antagonist ameliorated the collagen-induced arthritic (CIA). CCR2 antagonists may exert anti-inflammatory effects on RA-FLS by inhibiting the JAK-STAT pathway. In summary, a CCR2 antagonist can exert anti-inflammatory effects by acting on RA-FLS. This study provides a new experimental basis for the use of CCR2 antagonists in the development of RA drugs.

Advanced glycation end products promote osteoporosis by inducing ferroptosis in osteoblasts.

Advanced glycation end products (AGEs) have been widely reported to play an important role in osteoporosis (OP), particularly in diabetes­related OP. The aim of the present study was to investigate the effect of AGEs on osteoblast function and the underlying mechanisms. The level of bone mineral density (BMD), serum AGEs and fasting blood glucose (FBG) was measured in patients with OP and healthy individuals, and the correlation between AGE levels and BMD or FBG was then analyzed. For the in vitro experiments, the hFOB1.19 osteoblast cell line was cultured in medium containing AGEs and serum from healthy individuals or patients with OP, and with or without type­2 diabetes mellitus (T2DM). Cell proliferation, differentiation, mineralization, apoptosis and ferroptosis were evaluated using Cell Counting Kit­8 and alkaline phosphatase (ALP) assays, Alizarin red and TUNEL staining, iron indicator, lipid peroxidation tests and western blot analysis, respectively. In a separate set of experiments, the ferroptosis inhibitor, deferoxamine (DFO), was also added to the culture medium of cells treated with AGEs and serum from patients with OP and T2DM. The results demonstrated that patients with OP had a higher level of serum AGEs and FBG compared with that in healthy individuals. The level of serum AGEs in patients with OP was negatively correlated with BMD, but was positively correlated with FBG. In addition, AGEs and serum from patients with OP markedly inhibited hFOB1.19 cell proliferation, ALP production and mineralized nodule formation. Apoptosis and ferroptosis were significantly promoted by AGEs and serum from patients with OP. Moreover, serum from OP patients with T2DM caused stronger effect than that from OP patients with normal FBG. However, DFO reversed the effects induced by AGEs and serum from patients with OP and T2DM on hFOB1.19 cells. Collectively, AGEs could disrupt the functions of osteoblasts by inducing cell ferroptosis, thus contributing to OP.