Construction of PARI public health education programs for Chinese undergraduates: a Delphi study.

Objectives: The objective of this study is to develop a consensus among experts on a comprehensive and scientifically sound physical activity-related injuries (PARI) public health education program specifically tailored for undergraduates. Methods: This study designed three rounds of expert consultation by using a Delphi method. A panel of 30 experts from the fields of public health education, sports medicine, anesthesia pain, emergency medicine, and emergency nursing participated in the study. Results: This study successfully established a consensus among experts on the goals, content, teaching methods, and time allocation for the PARI Public Health Education Program for undergraduates. The program encompasses 10 objectives divided into 2 main categories: professional knowledge and skill goals. In terms of content, it includes 5 primary indicators, 22 secondary indicators, and 56 detailed tertiary indicators. Six teaching methods were identified as suitable. Additionally, a typical 60-min educational session was segmented into eight parts, with a proposed time arrangement for each, ensuring comprehensive coverage of all topics. Conclusion: The consensus achieved in this study on the PARI Public Health Education Program for undergraduates lays a crucial foundation for the advancement of health literacy and proactive health management within this demographic. We presented a comprehensive framework for PARI public health education, integrating diverse learning methods and content areas. This systematic approach not only enriched the resources available for undergraduate health education, especially of PARI but also had the potential to significantly impact the implementation and effectiveness of health promotion strategies.

Knowledge, attitudes, practice, and public health education demand regarding PARI prevention: a cross-sectional study among Chinese undergraduates.

Objectives: The purpose of this study was to assess the level of knowledge, attitudes, and practices (KAP) of university students in China regarding the need for PARI and public health education. Methods: A cross-sectional online and offline survey was conducted in China website through Wenjuanxing and in different cities such as Changsha Hunan Province, Shanghai, Chongqing and in different public scenarios, such as hospitals, universities, and commercial venues between September 1 and September 7, 2023, using a 28-question questionnaire designed and reviewed by multidisciplinary experts. Results: A total of 4,096 respondents were recruited for this study, with 3,957 valid questionnaires. The mean knowledge score was 1.84 ± 0.52, the mean attitude score was 2.12 ± 0.51, and the mean practice score was 3.18 ± 0.55. Regression analyses found that: region, grade, school, and weekly anaerobic exercise time were influences on the knowledge score; region, grade, school, and weekly anaerobic exercise time were influences on the attitude score; region, grade, school attended, weekly anaerobic exercise time and weekly anaerobic exercise time as influences on the practice score. Subgroup analyses revealed that undergraduates from southern regions and 985 schools had higher knowledge attitude scores and lower practice scores. As the grade level increased, the knowledge and attitude scores showed a V-shaped trend and the behavior scores showed an inverted V-shaped trend. Correlation analysis found a positive correlation between knowledge and attitude scores, and a negative correlation between both and behavior, respectively. The public health education needs survey found that undergraduate students generally preferred guided instruction methods and content centered on the RICE principles, they preferred learning through books and pamphlets, and they were happy to see relevant content promoted in the campus environment. Conclusion: This study shows that Chinese undergraduate students have less knowledge, neutral attitudes, and good behaviors regarding PARI prevention. Special attention should be paid to meeting the needs of undergraduate students for public health education to equip them with relevant knowledge so that they can better behave in PARI prevention.

A genome-wide association study suggests new susceptibility loci for primary antiphospholipid syndrome.

OBJECTIVES: Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS. METHODS: We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta-analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune-mediated diseases. RESULTS: We revealed genetic associations with PAPS in a regulatory locus within the HLA class II region near HLA-DRA and in STAT1-STAT4 with a genome-wide level of significance. 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele near HLA-DRA is associated with overexpression of HLA-DRB6, HLA-DRB9, HLA-DQA2 and HLA-DQB2 in immune cells, vascular tissue, and nervous tissue. This association is independent of the association between PAPS and HLA-DRB1*1302. Functional analyses highlighted immune-related pathways in PAPS-associated loci. The comparison with other immune-mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren's syndrome, suggesting colocalized causal variations close to STAT1-STAT4, TNPO3, and BLK. CONCLUSIONS: This study represents a comprehensive large-scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.

Dysrhythmic saliva microbiota in mobile phone addicts with sleep disorders and restored by acupuncture.

Background: Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives: To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods: MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results: Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions: This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.

Association between serum copper and blood glucose: a mediation analysis of inflammation indicators in the NHANES (2011-2016).

Background: The rising prevalence of diabetes underscores the need for identifying effective prevention strategies. Recent research suggests environmental factors, particularly heavy metals like copper, significantly influence health outcomes, including diabetes, through mechanisms involving inflammation and oxidative stress. This study aims to explore how serum copper levels affect blood glucose, employing NHANES data from 2011 to 2016, to provide insights into environmental health's role in diabetes prevention and management. Methods: The study analyzed data from 2,318 NHANES participants across three cycles (2011-2016), focusing on those with available data on serum copper, inflammatory markers, and blood glucose levels. We utilized principal component analysis for selecting inflammatory markers, mediation analysis to examine direct and indirect effects, multiple linear regression for assessing relationships between markers and glucose levels, and weighted quantile sum regression for evaluating individual and collective marker effects, adjusting for demographic variables and serum copper. Results: Participants averaged 42.70 years of age, with a near-even split between genders. Average serum copper was 119.50 µg/dL, white blood cell count 6.82 × 109/L, and fasting blood glucose 107.10 mg/dL. Analyses identified significant mediation by inflammatory markers (especially white blood cells: 39.78%) in the copper-blood glucose relationship. Regression analyses highlighted a positive correlation between white blood cells (estimate: 1.077, 95% CI: 0.432 to 2.490, p = 0.013) and copper levels and a negative correlation for monocyte percentage (estimate: -1.573, 95% CI: 0.520 to -3.025, p = 0.003). Neutrophil percentage was notably influential in glucose levels. Sensitive analyses confirmed the study's findings. Conclusion: Serum copper levels significantly impact blood glucose through inflammatory marker mediation, highlighting the importance of considering environmental factors in diabetes management and prevention. These findings advocate for public health interventions and policies targeting environmental monitoring and heavy metal exposure reduction, emphasizing the potential of environmental health measures in combating diabetes incidence.

Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Natural lignin nanoparticles target tumor by saturating the phagocytic capacity of Kupffer cells in the liver.

Ligand-receptor recognition serves as the fundamental driving force for active targeting, yet it is still constrained by off-target effects. Herein, we demonstrate that circumventing or blocking the mononuclear phagocyte system (MPS) are both viable strategies to address off-target effects. Naturally derived lignin nanoparticles (LNPs) show great potential to block MPS due to its good stability, low toxicity, and degradability. We further demonstrate the impact of LNPs dosage on in vivo tumor targeting and antitumor efficacy. Our results show that a high dose of LNPs (300 mg/kg) leads to significant accumulation at the tumor site for a duration of 14 days after intravenous administration. In contrast, the low-dose counterparts (e.g., 50, 150 mg/kg) result in almost all LNPs accumulating in the liver. This discovery indicates that the liver is the primary site of LNP capture, leaving only the surplus LNPs the chance to reach the tumor. In addition, although cell membrane-engineered LNPs can rapidly penetrate tumors, they are still prone to capture by the liver during subsequent circulation in the bloodstream. Excitingly, comparable therapeutic efficacy is obtained for the above two strategies. Our findings may offer valuable insights into the targeted delivery of drugs for disease treatment.

Neutrophil glucose flux as a therapeutic target in antiphospholipid syndrome.

Neutrophil hyperactivity and neutrophil extracellular trap release (NETosis) appear to play important roles in the pathogenesis of the thromboinflammatory autoimmune disease known as antiphospholipid syndrome (APS). The understanding of neutrophil metabolism has advanced tremendously in the past decade, and accumulating evidence suggests that a variety of metabolic pathways guide neutrophil activities in health and disease. Our previous work characterizing the transcriptome of APS neutrophils revealed that genes related to glycolysis, glycogenolysis, and the pentose phosphate pathway (PPP) were significantly upregulated. Here, we found that APS patient neutrophils used glycolysis more avidly than healthy control neutrophils, especially when the neutrophils were from APS patients with a history of microvascular disease. In vitro, inhibiting either glycolysis or the PPP tempered phorbol myristate acetate- and APS IgG-induced NETosis, but not NETosis triggered by a calcium ionophore. In mice, inhibiting either glycolysis or the PPP reduced neutrophil reactive oxygen species production and suppressed APS IgG-induced NETosis ex vivo. When APS-associated thrombosis was evaluated in mice, inhibiting either glycolysis or the PPP markedly suppressed thrombosis and circulating NET remnants. In summary, these data identify a potential role for restraining neutrophil glucose flux in the treatment of APS.

Enhancing immunogenicity and antiviral protection of inactivated porcine reproductive and respiratory syndrome virus vaccine in piglets.

OBJECTIVE: Porcine interferon-γ (poIFN-γ) and porcine granulocyte-macrophage colony-stimulating factor (poGM-CSF) are multifunctional cytokines that exhibit robust antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV). In this study, the immunoadjuvant effects of recombinant poIFN-γ-poGM-CSF fusion protein in inactivated PRRSV vaccine administered to piglets were assessed. ANIMALS: Twenty-eight 4-week-old specific pathogen-free piglets. METHODS: The experimental piglets were divided into control, highly pathologic PRRSV, PRRSV killed virus vaccine (KV), poIFN-γ-poGM-CSF, KV + 1.0 mg poIFN-γ-poGM-CSF, KV + 2.0 mg poIFN-γ-poGM-CSF, and KV + 4.0 mg poIFN-γ-poGM-CSF groups. A recombinant poIFN-γ-linker-poGM-CSF fusion gene was constructed via splicing by overlap extension PCR and prepared using an Escherichia coli expression system, after which its adjuvant activity in the context of PRRSV KV administration was assessed. RESULTS: This analysis revealed the successful construction of the poIFN-γ-linker-poGM-CSF fusion gene via splicing by overlap extension PCR, with recombinant poIFN-γ-linker-poGM-CSF successfully being prepared in E coli with a plasmid vector for expressing thioredoxin fusion proteins with an enterokinase site. Importantly, the coadministration of poIFN-γ-linker-poGM-CSF and PRRSV KV significantly increased neutralizing antibody titers, accelerated viral clearance, reduced clinical symptoms, and prevented highly pathogenic PRRSV infection. CLINICAL RELEVANCE: The recombinant poIFN-γ-poGM-CSF fusion protein is a promising candidate adjuvant for use in the context of swine immunization and viral challenge.

Rainfall-runoff partitioning in small watersheds of different vegetation types in the loess area based on hydrogen and oxygen isotope tracing.

Recognizing watershed runoff process and its component sources is a prerequisite for the rational use of water resources. To elucidate the effects and quantitative contributions of various vegetation types on the components of watershed runoff, we centered on the Caijiachuan main channel watershed in Jixian, Shanxi and five sub-watersheds with distinct vegetation types. By tracking the hydrological responses to two representative rainfall events and assessing the spatiotemporal variations in hydrogen and oxygen isotope signatures, we aimed to discern disparities in the runoff processes across these sub-watersheds and pinpoint their constituent origins. The results showed that under medium rainfall condition, the contribution rates of event water to the river flow of each watershed were in an order of protected forest (94.3%) > Caijiachuan main channel (83.1%) > agro-pastoral composite (64.3%) > plantation-secondary forest (52.4%) > cropland (0.3%) > secondary forest (0.0%); under light rainfall condition, plantation-secondary forest (52.4%) > protected forest (58.5%) > cropland (40.6%) > secondary forest (15.8%) > agro-pastoral composite (12.5%) > Caijiachuan main channel (9.3%). The event water contribution rate of secondary forest and protected forest watersheds to runoff was higher than that of plantation watersheds. The secondary forests watersheds had a stronger runoff storage capacity. The event water contribution rate of protected forest and agro-pastoral composite watersheds under medium rainfall intensity condition was greater than that under light rainfall intensity condition, while the event water contribution rate of cropland, plantation-secondary forest, and secondary forest watersheds was in adverse. The event water contribution to the runoff of forested watersheds was greater than that of cropland watersheds, which may be related to the presence of silt dams at the mouth of agricultural watershed channels. This study can provide a scientific basis for the analysis of water conservation and runoff change attribution in the loess area of west Shanxi.

Non-criteria antiphospholipid antibodies and calprotectin as potential biomarkers in pediatric antiphospholipid syndrome.

Our study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in pediatric APS patients. We found that 79% of pediatric APS patients had at least one non-criteria aPL at moderate-to-high titer. Univariate logistic regression demonstrated that positive anti-beta-2 glycoprotein I domain 1 (anti-D1) IgG (p = 0.008), anti-phosphatidylserine/prothrombin (aPS/PT) IgG (p < 0.001), and aPS/PT IgM (p < 0.001) were significantly associated with venous thrombosis. Positive anti-D1 IgG (p < 0.001), aPS/PT IgG (p < 0.001), and aPS/PT IgM (p = 0.001) were also associated with non-thrombotic manifestations of APS, such as thrombocytopenia. Increased levels of calprotectin were detected in children with APS. Calprotectin correlated positively with absolute neutrophil count (r = 0.63, p = 0.008) and negatively with platelet count (r = -0.59, p = 0.015). Mechanistically, plasma from pediatric APS patients with high calprotectin levels impaired platelet viability in a dose-dependent manner.

Maresin 1 Activates LGR6 to Alleviate Neuroinflammation via the CREB/JMJD3/IRF4 Pathway in a Rat Model of Subarachnoid Hemorrhage.

Neuroinflammation is an early event of brain injury after subarachnoid hemorrhage (SAH). Whether the macrophage mediators in resolving inflammation 1 (MaR1) is involved in SAH pathogenesis is unknown. In this study, 205 male Sprague-Dawley rats were subjected to SAH via endovascular perforation in the experimental and control groups. MaR1 was dosed intranasally at 1 h after SAH, with LGR6 siRNA and KG-501, GSK-J4 administered to determine the signaling pathway. Neurobehavioral, histological and biochemical data were obtained from the animal groups with designated treatments. The results showed: (i) The leucine-rich repeat containing G protein-coupled receptor 6 (LGR6) was decreased after SAH and reached to the lowest level at 24 h after SAH. Jumonji d3 (JMJD3) protein levels tended to increase and peaked at 24 h after SAH. LGR6 and JMJD3 expression were co-localized with microglia. (ii) MaR1 administration mitigated short-term neurological deficits, brain edema and long-term neurobehavioral performance after SAH, and attenuated microglial activation and neutrophil infiltration. (iii) Knockdown of LGR6, inhibition of CREB phosphorylation or JMJD3 activity abolished the anti-neuroinflammatory effect of MaR1 on the expression of CREB, CBP, JMJD3, IRF4, IRF5, IL-1ß, IL-6 and IL-10, thus prevented microglial activation and neutrophil infiltration. Together, the results show that MaR1 can activate LGR6 and affect CREB/JMJD3/IRF4 signaling to attenuate neuroinflammation after SAH, pointing to a potential pharmacological utility in this disorder.

Low ectonucleotidase activity and increased neutrophil-platelet aggregates in patients with antiphospholipid syndrome.

ABSTRACT: Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. This phenotype was replicated by treating healthy neutrophils and platelets with patient-derived antiphospholipid antibodies or ectonucleotidase inhibitors.

Cancer-Thylakoid Hybrid Membrane Camouflaged Thulium Oxide Nanoparticles with Oxygen Self-Supply Capability for Tumor-Homing Phototherapy.

Nanomaterials that generate reactive oxygen species (ROS) upon light irradiation have significant applications in various fields, including photodynamic therapy (PDT) that is widely recognized as a highly momentous strategy for the eradication of cancer cells. However, the ROS production rate of photosensitizers, as well as the tumor hypoxia environment, are two major challenges that restrict the widespread application of PDT. In this study, a cancer-thylakoid hybrid membrane-camouflaged thulium oxide nanoparticles (Tm2O3) for tumor-homing phototherapy through dual-stage-light-guided ROS generation and oxygen self-supply is developed. Tm2O3 as a type II photosensitizer are viable for NIR-stimulated ROS generation due to the unique energy levels, large absorption cross section, and long lifetime of the 3H4 state of Tm ions. The thylakoid membrane (TK) plays a catalase-like role in converting hydrogen peroxide into oxygen and also acts as a natural photosensitizer that can generate lethal ROS through electron transfer when exposed to light. In addition, fluorescence dye DiR is embedded in the hybrid membrane for in vivo tracing as well as photothermal therapy. Results show that tumors in Tm2O3@TK-M/DiR group are effectively ablated following dual-stage-light irradiation, highlighting the promising potential of rare-earth element-based type II photosensitizers in various applications.

Thrombosis recurrence and major bleeding in non-anticoagulated thrombotic antiphospholipid syndrome patients: Prospective study from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) clinical database and repository ("Registry").

BACKGROUND: Long-term anticoagulant therapy is generally recommended for thrombotic antiphospholipid syndrome (TAPS) patients, however it may be withdrawn or not introduced in routine practice. OBJECTIVES: To prospectively evaluate the risk of thrombosis recurrence and major bleeding in non-anticoagulated TAPS patients, compared to anticoagulated TAPS, and secondly, to identify different features between those two groups. PATIENTS/METHODS: Using an international registry, we identified non-anticoagulated TAPS patients at baseline, and matched them with anticoagulated TAPS patients based on gender, age, type of previous thrombosis, and associated autoimmune disease. Thrombosis recurrence and major bleeding were prospectively analyzed using Kaplan-Meier method and compared using a marginal Cox's regression model. RESULTS: As of June 2022, 94 (14 %) of the 662 TAPS patients were not anticoagulated; and 93 of them were matched with 181 anticoagulated TAPS patients (median follow-up 5 years [interquartile range 3 to 8]). The 5-year thrombosis recurrence and major bleeding rates were 12 % versus 10 %, and 6 % versus 7 %, respectively (hazard ratio [HR] 1.38, 95 % confidence interval [CI] 0.53 to 3.56, p = 0.50 and HR 0.53; 95 % CI 0.15 to 1.86; p = 0.32, respectively). Non-anticoagulated patients were more likely to receive antiplatelet therapy (p < 0.001), and less likely to have more than one previous thrombosis (p < 0.001) and lupus anticoagulant positivity (p = 0.01). CONCLUSION: Fourteen percent of the TAPS patients were not anticoagulated at recruitment. Their recurrent thrombosis risk did not differ compared to matched anticoagulated TAPS patients, supporting the pressing need for risk-stratified secondary thrombosis prevention trials in APS investigating strategies other than anticoagulation.

Calprotectin Impairs Platelet Survival in Patients With Primary Antiphospholipid Syndrome.

OBJECTIVE: While thrombosis and pregnancy loss are the best-known clinical features of antiphospholipid syndrome (APS), many patients also exhibit "extra-criteria" manifestations, such as thrombocytopenia. The mechanisms that drive APS thrombocytopenia are not completely understood, and no clinical biomarkers are available for predicting antiphospholipid antibody (aPL)-mediated thrombocytopenia. Calprotectin is a heterodimer of S100A8 and S100A9 that is abundant in the neutrophil cytoplasm and released upon proinflammatory neutrophil activation. Here, we sought to evaluate the presence, clinical associations, and potential mechanistic roles of circulating calprotectin in a cohort of primary APS and aPL-positive patients. METHODS: Levels of circulating calprotectin were determined in plasma by the QUANTA Flash chemiluminescent assay. A viability dye-based platelet assay was used to assess the potential impact of calprotectin on aPL-mediated thrombocytopenia. RESULTS: Circulating calprotectin was measured in 112 patients with primary APS and 30 aPL-positive (without APS criteria manifestations or lupus) patients as compared to patients with lupus (without APS), patients with unprovoked venous thrombosis (without aPL), and healthy controls. Levels of calprotectin were higher in patients with primary APS and aPL-positive patients compared to healthy controls. After adjustment for age and sex, calprotectin level correlated positively with absolute neutrophil count (r = 0.41, P < 0.001), positively with C-reactive protein level (r = 0.34, P = 0.002), and negatively with platelet count (r = -0.24, P = 0.004). Mechanistically, we found that calprotectin provoked aPL-mediated thrombocytopenia by engaging platelet surface toll-like receptor 4 and activating the NLRP3-inflammasome, thereby reducing platelet viability in a caspase-1-dependent manner. CONCLUSION: These data suggest that calprotectin has the potential to be a functional biomarker and a new therapeutic target for APS thrombocytopenia.

Study on the Influence of Metal Substrates on Protective Performance of the Coating by EIS.

The degradation process of a red iron oxide epoxy coating on three kinds of metals under a periodic cycling exposure to 3.5 wt% NaCl solution (45 °C 12 h + 25 °C 12 h) was comparatively studied using electrochemical impedance spectroscopy (EIS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD) methods. The influence of the metal substrates (carbon steel, brass, and Al alloy) on the protection performance of the coating was analyzed using variations in the electrochemical and chemical parameters. The failure criteria of the coating were discussed. The results show that the coating on the three substrates presents different failure times, with the coating on steel presenting the shortest time and the coating on Al alloy the longest time. The characteristics of metal substrates and their corrosion products influence the coating failure behavior. The corrosion products with loose and hygroscopic properties of steel and brass have promoting effects on the diffusion of water through the coating. The passive film of the Al alloy substrate and the formation of salt film containing Cl- have corrosion-inhibiting effects on the substrate. Evaluation of the coating performance by |Z|0.01Hz should consider the characteristics of the metal substrates.

HFD-exacerbated Metabolic Side Effects of Olanzapine Are Suppressed by ER Stress Inhibitor.

OBJECTIVE: Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary habits. This study investigated the progressive deterioration of olanzapine-induced metabolic disorders in the presence of a high-fat diet (HFD) and explored the involvement of endoplasmic reticulum (ER) stress. METHODS: Female Sprague-Dawley rats fed on a standard chow diet or HFD were treated with olanzapine (3 mg/kg/day) and the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 1 and 0.5 g/kg/day) for 8 days. Changes in body weight, food intake, and plasma lipids were assessed. Hepatic fat accumulation was evaluated using oil red O staining. Western blotting and immunofluorescence assays were employed to examine the expression of ER stress markers, NOD-like receptor pyrin domain-containing protein 3 (NLRP3), and proopiomelanocortin (POMC) in the hypothalamus or liver. RESULTS: Compared to olanzapine alone, olanzapine+HFD induced greater weight gain, increased hyperlipidemia, and enhanced hepatic fat accumulation (P<0.05). Co-treatment with 4-PBA exhibited a dose-dependent inhibition of these effects (P<0.05). Further mechanistic investigations revealed that olanzapine alone activated ER stress, upregulated NLRP3 expression in the hypothalamus and liver, and downregulated hypothalamic POMC expression. The HFD exacerbated these effects by 50%-100%. Moreover, co-administration of 4-PBA dose-dependently attenuated the olanzapine+HFD-induced alterations in ER stress, NLRP3, and POMC expression in the hypothalamus and liver (P<0.05). CONCLUSION: HFD worsened olanzapine-induced weight gain and lipid metabolic disorders, possibly through ER stress-POMC and ER stress-NLRP3 signaling. ER stress inhibitors could be effective in preventing olanzapine+HFD-induced metabolic disorders.

Interaction of the antiphospholipid syndrome autoantigen beta-2 glycoprotein I with DNA and neutrophil extracellular traps.

Beta-2 glycoprotein I (ß2GPI) is a phospholipid-binding plasma protein and prominent autoantigen in antiphospholipid syndrome (APS). Here, we tested the hypothesis that ß2GPI might bind to not only phospholipids, but also cell-free DNA and neutrophil extracellular traps (NETs). We report that ß2GPI interacts with cell-free DNA from different species, as well as NETs, in a dose-dependent manner, retarding their migration in an agarose-gel electrophoretic mobility shift assay. We confirm the direct binding interaction of ß2GPI with DNA and NETs by ELISA. We also demonstrate that ß2GPI colocalizes with NET strands by immunofluorescence microscopy. Finally, we provide evidence that ß2GPI-DNA complexes can be detected in the plasma of APS patients, where they positively correlate with an established biomarker of NET remnants. Taken together, our findings indicate that ß2GPI interacts with DNA and NETs, and suggest that this interaction may play a role as a perpetuator and/or instigator of autoimmunity in APS.