Curcumin-Piperlongumine Hybrid Molecule Increases Cell Cycle Arrest and Apoptosis in Lung Cancer through JNK/c-Jun Signaling Pathway.

The instability of curcumin's structure and the toxic side effects of piperlongumine have limited their potential applications in cancer treatment. To overcome these challenges, we designed and synthesized a novel curcumin-piperlongumine hybrid molecule, 3-[(E)-4-hydroxy-3-methoxybenzylidene]-1-[(E)-3-(3,4,5-trimethoxyphenyl)acryloyl]piperidin-2-one (CP), using a molecular hybridization strategy. CP exhibited enhanced structural stability and safety compared with its parent compounds. Through in vitro and in vivo biological activity screenings, CP effectively inhibited cell proliferation, caused cell cycle arrest in the G2/M phase, and induced apoptosis. Mechanistically, CP-induced apoptosis was partially mediated by cell cycle arrest. Furthermore, we discovered that CP induces cell cycle arrest and apoptosis through the regulation of JNK signaling. These findings highlight the potential of CP as a promising therapeutic agent for lung cancer treatment.

Cyy-287, a novel pyrimidine-2,4-diamine derivative, efficiently mitigates inflammatory responses, fibrosis, and lipid synthesis in obesity-induced cardiac and hepatic dysfunction.

Background: Inflammation and metabolic disorders are important factors in the occurrence and development of obesity complications. In this study, we investigated the protective effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, Cyy-287, on mice fed a high-fat diet (HFD). Methods: The mice were randomly separated into four groups (n ≥ 7): control (regular diet), HFD, HFD with Cyy-287 (5 mg/kg), and HFD with Cyy-287 (20 mg/kg) following HFD feeding for 10 weeks. After a 10-week administration, ALT and AST enzymes, echocardiography, immunohistochemical (IHC), Western blot (WB), Masson and Sirius Red staining were used to evaluate functional and morphological changes to the heart and liver. Microsomes from the mouse liver were extracted to quantify the total amount of CYP450 enzymes after drug treatment. Results: Cyy-287 decreased the levels of serum glucose, LDL, TC, ALT, and AST activities in HFD-treated mice. However, Cyy-287 administration increased ejection fraction (EF) and fractional shortening (FS) index of the heart. Cyy-287 inhibited histopathological changes in the heart and liver; decreased inflammatory activity; significantly diminished p38 mitogen-activated protein kinase (MAPK), the nuclear factor-kappa B (NF-κB) axis, and sterol regulatory element-binding protein-1c (SREBP-1c); and upregulated the AMP-activated protein kinase (AMPK) pathway in HFD-treated mice. Cyy-287 restored the content of hepatic CYP450 enzymes. Conclusion: These findings demonstrated that Cyy-287 protected heart and liver cells from obesity-induced damage by inhibiting inflammation, fibrosis, and lipid synthesis.

Effects of high-intensity interval training, moderate-intensity continuous training, and guideline-based physical activity on cardiovascular metabolic markers, cognitive and motor function in elderly sedentary patients with type 2 diabetes (HIIT-DM): a protocol for a randomized controlled trial.

Background and objective: Sedentary behavior is of increasing concern in older patients with type 2 diabetes mellitus (T2DM) due to its potential adverse effects on cardiovascular health, cognitive function, and motor function. While regular exercise has been shown to improve the health of individuals with T2DM, the most effective exercise program for elderly sedentary patients with T2DM remains unclear. Therefore, the objective of this study was to assess the impact of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and guideline-based physical activity programs on the cardiovascular health, cognitive function, and motor function of this specific population. Methods: This study will be a randomized, assessor-blind, three-arm controlled trial. A total of 330 (1:1:1) elderly sedentary patients diagnosed with T2DM will be randomly assigned the HIIT group (10 × 1-min at 85-95% peak HR, intersperse with 1-min active recovery at 60-70% peak HR), MICT (35 min at 65-75% peak HR), and guideline-based group (guideline group) for 12 weeks training. Participants in the guideline group will receive 1-time advice and weekly remote supervision through smartphones. The primary outcomes will be the change in glycosylated hemoglobin (HbA1c) and brain-derived neurotrophic factor (BDNF) after 12-weeks. Secondary outcomes will includes physical activity levels, anthropometric parameters (weight, waist circumference, hip circumference, and body mass index), physical measurements (fat percentage, muscle percentage, and fitness rate), cardiorespiratory fitness indicators (blood pressure, heart rate, vital capacity, and maximum oxygen), biochemical markers (high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and HbA1c), inflammation level (C-reactive protein), cognitive function (reaction time and dual-task gait test performance), and motor function (static balance, dynamic balance, single-task gait test performance, and grip strength) after 12 weeks. Discussion: The objective of this study is to evaluate the effect of 12 weeks of HIIT, MICT, and a guideline-based physical activity program on elderly sedentary patients diagnosed with T2DM. Our hypothesis is that both HIIT and MICT will yield improvements in glucose control, cognitive function, cardiopulmonary function, metabolite levels, motor function, and physical fitness compared to the guideline group. Additionally, we anticipate that HIIT will lead to greater benefits in these areas. The findings from this study will provide valuable insights into the selection of appropriate exercise regimens for elderly sedentary individuals with T2DM. Ethics and dissemination: This study has been approved by the Ethics Review Committee of the Reproductive Hospital Affiliated with China Medical University (approval number: 202203). Informed consent will be obtained from all participants or their guardians. Upon completion, the authors will submit their findings to a peer-reviewed journal or academic conference for publication. Clinical trial registration: Chinese Clinical Trial Registry, identifier ChiCTR2200061573.

Gene profiling reveals the role of inflammation, abnormal uterine muscle contraction and vascularity in recurrent implantation failure.

Objective: Recurrent implantation failure (RIF) is now disturbing numerous infertile couples accepting assisted reproductive technology (ART). And the endometrial factors are crucial causes of recurrent implantation failure. However, its mechanism is still unclear. Thus, the aim of this study is to identify altered biologic processes in endometrium that may contribute to recurrent implantation failure. Methods: We recruited two microarray datasets (GSE103465, GSE111974) from Gene Expression Omnibus database (GEO), which contain endometrium from RIF and normal women during implantation period. Using the online tools GEO2R and Venny, we identified Differentially Expressed Genes (DEGs) of selected datasets, and obtained common DEGs. Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCatar pathway enrichment were conducted with Enrichr platform, "ssgsea" and "ggplot2" package of RStudio. PPI networks and hub gene related TF-gene interaction and TF-miRNA co-regulation networks were built via online tools STRING and NetworkAnalyst. Immune infiltration analysis was performed by CIBERSORT platform. Recurrent implantation failure subgroup identification was achieved through "ConsensusClusterPlus," "tsne," "ssgsea", and "ggpubr" package in RStudio. Diagnostic characteristic ROC curves were constructed via "pROC" and "ggplot2" package of RStudio. Enrichr platform was utilized to find drugs targeting hub genes. Results: 26 common DEGs were confirmed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes/BioCarta analysis determined common DEGs were mainly enriched in inflammation associated pathways including TNF, NF-κB, IL-4, IL-10, IL-6, and TGF-ß signaling pathways. Five hub genes (PTGS2, VCAM1, EDNRB, ACTA2, and LIF) and related TF-gene and TF-miRNA interactions were identified. Immune infiltration analysis indicated the importance of macrophage M2 in recurrent implantation failure patients. Importantly, subgroup identification analysis highlighted that recurrent implantation failure patients can be divided into two subgroups with different phenotypes. Moreover, the ROC curves and drugs may provide new diagnostic and therapeutic thought for recurrent implantation failure.

Prognostic markers of ferroptosis-related long non-coding RNA in lung adenocarcinomas.

Ferroptosis is a recently established type of iron-dependent programmed cell death. Growing studies have focused on the function of ferroptosis in cancers, including lung adenocarcinoma (LUAD). However, the factors involved in the regulation of ferroptosis-related genes are not fully understood. In this study, we collected data from lung adenocarcinoma datasets of the Cancer Genome Atlas (TCGA-LUAD). The expression profiles of 60 ferroptosis-related genes were screened, and two differentially expressed ferroptosis subtypes were identified. We found the two ferroptosis subtypes can predict clinical outcomes and therapeutic responses in LUAD patients. Furthermore, key long non-coding RNAs (lncRNAs) were screened by single factor Cox and least absolute shrinkage and selection operator (LASSO) based on which co-expressed with the 60 ferroptosis-related genes. We then established a risk score model which included 13 LUAD ferroptosis-related lncRNAs with a multi-factor Cox regression. The risk score model showed a good performance in evaluating the outcome of LUAD. What's more, we divided TCGA-LUAD tumor samples into two groups with high- and low-risk scores and further explored the differences in clinical characteristics, tumor mutation burden, and tumor immune cell infiltration among different LUAD tumor risk score groups and evaluate the predictive ability of risk score for immunotherapy benefit. Our findings provide good support for immunotherapy in LUAD in the future.

Identification of key candidate genes and pathways in rheumatoid arthritis and osteoarthritis by integrated bioinformatical analysis.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common joint disorders. Although they have shown analogous clinical manifestations, the pathogenesis of RA and OA are different. In this study, we used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE153015 to identify gene signatures between RA and OA joints. The relevant data on 8 subjects obtained from large joints of RA patients (RA-LJ), 8 subjects obtained from small joints of RA patients (RA-SJ), and 4 subjects with OA were investigated. Differentially expressed genes (DEGs) were screened. Functional enrichment analysis of DEGs including the Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, which were mainly associated with T cell activation or chemokine activity. Besides, protein-protein interaction (PPI) network analysis was performed, and key modules were identified. Hub genes of RA-LJ and OA groups were screened, they were CD8A, GZMB, CCL5, CD2, and CXCL9, whereas CD8A, CD2, IL7R, CD27, and GZMB were hub genes of RA-SJ and OA group. The novel DEGs and functional pathways between RA and OA identified in this study may provide new insight into the underlying molecular mechanisms and therapeutic strategies of RA and OA.

COVID-19 infection characteristics, risk factors and its potential impacts on Takayasu arteritis: a web-based survey in a large cohort.

Objectives: To investigate the characteristics of COVID-19 and its impact on patients with Takayasu's arteritis (TAK). Methods: A web-based survey was administered to a TAK cohort and their co-residents in China during January 2023. Infection symptoms, post-acute sequelae of COVID-19 (PASC), potential impacts of COVID-19 on patients' disease condition, treatment and immune-related parameters were analyzed. In addition, risk factors for COVID-19 and disease relapse after infection were explored. Results: The infection rate was significantly lower in patients with TAK than in co-residents (79.13% vs 90.67%, p=0.025). TAK patients were more prone to gastrointestinal symptoms (17.78% vs 5.88%, p=0.024), sleep problems (25.15% vs 10.29%, p=0.011), and symptoms involving more than 2 organs (58.90% vs 35.29%, p=0.001) after infection. Although only 2.45% of TAK patients were hospitalized and none progressed to life-threatening conditions, they were more likely to suffer from PASC (26.38% vs 13.24%, p=0.029), especially active patients. Active disease after the pandemic was significantly lower in infected patients than uninfected patients (21/163, 12.88% vs. 11/43, 25.58%, p=0.041). The presence of multiple system symptoms was a risk factor for active TAK after infection [OR: 3.62 (95% CI 1.06-12.31), p=0.040]. Moreover, csDMARDs treatment was a risk factor for COVID-19 infection [OR: 3.68 (95% CI 1.56-8.66), p=0.002]. Conclusion: Although TAK patients with COVID-19 have more acute and post-acute symptoms, there is no adverse outcome and the risk of disease relapse does not increase. Patients treated with csDMARDs may be at higher risk of infection and deserve more clinical attention.

cyy-287, a novel pyrimidine-2,4-diamine derivative, inhibits tumor growth of EGFR-driven non-small cell lung cancer via the ERK pathway.

In recent decades, EGFR-targeted tyrosine kinase inhibitors (TKIs) have been proven to be an effective therapy for EGFR-mutant non-small cell lung cancer (NSCLC). However, resistance to EGFR-TKIs limits their clinical application. In the present study, we investigate the antitumor effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, cyy-287, in NSCLC. We find that cyy-287 has a high affinity for lung tissue and inhibits the proliferation of NSCLC cells. Interestingly, the significant suppression of migration and induction of apoptosis by cyy-287 are only observed in EGFR-driven but not in EGFR-wild-type (wt) cells. According to the RNA sequencing and KEGG enrichment analysis results, cyy-287 markedly inhibits the MAPK pathway in EGFR-driven PC9 cells, and western blot analysis results further indicate that cyy-287 selectively blocks the ERK pathway in EGFR-driven cells. Meanwhile, apoptosis induced by cyy-287 could be partially reversed by ERK pathway inhibition. Further experiment indicates that cyy-287 inhibits the EGFR pathway in both EGFR-driven and EGFR-overexpressing cells. Interestingly, it only induces apoptosis in EGFR-driven cells, not in EGFR-overexpressing cells. The growth of EGFR-driven cells is suppressed by cyy-287 in vivo, with fewer side effects. Our results suggest that cyy-287 may be a potential therapeutic drug with promising antitumor effects against NSCLC.

The Effects of Preslaughter Electrical Stunning on Serum Cortisol and Meat Quality Parameters of a Slow-Growing Chinese Chicken Breed.

Electrical stunning is widely utilized prior to a neck cut to induce unconsciousness in order to improve animal welfare and slaughter efficiency in the broiler production industry. However, slaughter without stunning is still very commonly used in China, in part because there is a belief that stunning reduces meat quality. The purpose of this study was to determine whether the physical (hemorrhages, pH, drip loss, and shear force) and chemical (inosinic monophosphate concentration and reducing sugar content) properties of broiler meat differed between chickens in preslaughter stunning and nonstunned slaughter groups, and whether the groups differed in their levels of cortisol as an indicator of stress. Serum cortisol levels of the nonstunned group were nearly twice as high as those in the stunned group (p < 0.05). Several meat quality indicators were better in the stunned group than in the nonstunned group. We concluded that electrical stunning prior to slaughter significantly decreases the stress caused by slaughter, resulting in both improved animal welfare and meat quality traits.

Discovery of Potent and Orally Bioavailable Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for the Treatment of Osteosarcoma.

Platelet-derived growth factor receptors (PDGFRs) are now considered promising targets for the treatment of osteosarcoma. Herein, the design, synthesis, and structure-activity relationships (SAR) of novel pyrimidine-2,4-diamine derivatives that selectively inhibit PDGFRα/ß kinases have been studied. The screening cascades revealed that 7m was the preferred compound among these derivatives, with IC50 values of 2.4 and 0.9 nM for PDGFRα and PDGFRß, respectively. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) experiment revealed that 7m has a substantial cytotoxic effect against all osteosarcoma cancer cell lines; 7m also displayed robust antitumor effects and low toxicity in a xenograft model. Additionally, 7m showed excellent bioavailability (F = 62.9%), suitable half-life (T1/2 = 2.12 h), satisfactory metabolic stability, and weak CYP isoform inhibitory activity, suggesting that 7m is a potential drug candidate for PDGFR-driven osteosarcoma.

Investigation of Apnea Testing During Brain Death Determination in China.

Apnea testing (AT) is one of the key steps for brain death (BD) diagnosis and confirmation. However, the completion rate of AT is not well in China. The aim of this study was to investigate the completion rates of the AT during BD determination in China and analyze the determinant factors. We reviewed and analyzed potential BD patients registered in our database from 2013 to 2019. The patients were divided into those with completed and aborted AT. Preconditions and organ function status were compared between the two groups. A total of 1,531 (1,301 adults and 230 pediatrics) cases of potential BD were extracted, and BD determination was performed 2,185 and 377 times in adults and pediatrics respectively. The nonperformance and aborted rates of AT were 12.2% and 34.5% in adults, and 11.7% and 44.4% in pediatrics respectively. Compared with the completed group, the aborted group had a lower PaO2, systolic blood pressure, PaO2/FiO2 ratios, and higher alveolar-arterial (A-a) gradient both in adults and pediatrics, and higher PaCO2 and higher heart rates in adults. PaO2 and A-a gradient had higher predictive efficacy for AT completion in both adults and pediatrics. The implementation and completion rates of AT are not ideal in China. PaO2 and A-a gradient are important factors for the successful completion of AT and should be optimized before AT.

Evaluation of PAHs in edible parts of vegetables and their human health risks in Jinzhong City, Shanxi Province, China: A multimedia modeling approach.

Knowledge of the origins of polycyclic aromatic hydrocarbon (PAH) in vegetables is essential to reduce human health risks induced by dietary exposure. The current study developed a vegetation-advanced multimedia model, SESAMe-Veg, to identify the major uptake pathway of 15 priority PAHs in vegetables and assess the PAHs in edible parts of cabbages and carrots in Jinzhong City, Shanxi Province, China. The model was well evaluated against site- and plant-specific measurements. Edible parts exhibited lower PAH concentrations than the other parts for both vegetables. The estimated concentrations of ΣPAH15 were 79 ng/g in cabbage shoots and 83 ng/g in carrot roots. Higher concentrations were estimated in shoots of the leafy vegetable than in roots of the root vegetable for most PAHs. Although air-shoot is the major transport pathway, 98% was deposition of particles, which was attached outside and could be removed relatively easily by washing. Soils might be the origin of PAHs inside vegetables, especially for lighter PAHs. PYR was more likely to be stored in roots than other congeners. The translocation of PAHs inside vegetables was negligible. Adulthood dietary exposure to local vegetables probably caused a high health risk; however, contributions from consuming cabbages and especially carrots were low. Females generally exhibited slightly higher risks than males of exposure to PAHs in local vegetables. Considering the dominant role of particle deposition, carefully vegetable washing before ingestion could reduce this risk. This study has provided a functional tool to evaluate vegetable contamination by PAHs. CAPSULE: A vegetation-advanced multimedia model of PAHs in different parts of vegetables and other environmental media was developed to evaluate the potential health risk to local populations of different sexes and ages via vegetable ingestion.

Occurrence and characteristics of microplastics in the Haihe River: An investigation of a seagoing river flowing through a megacity in northern China.

Freshwater systems serve as important sources and transportation routes for marine microplastic pollution, and inadequate attention has been paid to this situation. Data on microplastic pollution of typical seagoing rivers in northern China are lacking. In the current study, we investigated the distribution and characteristics of microplastics in the main stream of the Haihe River, which flows through a metropolis with a high population density and level of industrialization and then flows into the Bohai Sea. The microplastic samples were collected by manta trawls with pore sizes of 333 µm, and the microplastic concentrations ranged from 0.69 to 74.95 items/m3. Fibers dominated in the surface water of the Haihe River; their shapes that were categorized as fibers, film, foam, fragments, and spheres, and contributed 17.4-86.7% of the total microplastics studied. The size distribution of the microplastics was concentrated in a range of 100-1000 µm, with 54.7% of the total sizes corresponding to the 333-µm trawl. Micro-Fourier transform infrared (µ-FT-IR) spectra showed that the main components were polyethylene, poly(ethylene-propylene) copolymer, and polypropylene. Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) measurements revealed scratches, micropores, and cracks on the surfaces of the microplastics due to mechanical friction, chemical oxidation and degradation processes. The results of this study confirmed the high abundance and high diversity of microplastics in an urban river and indicated appreciable impacts from point-source inputs on the microplastic pollution, such as effluents from wastewater treatment plants (WWTPs).

Melatonin prevents endothelial dysfunction in SLE by activating the nuclear receptor retinoic acid-related orphan receptor-α.

Atherosclerotic cardiovascular disease confers significant morbidity and mortality in patients with systemic lupus erythematosus (SLE). A substantial proportion of patients with SLE display accelerated endothelial dysfunction, which precedes cardiovascular disease. Melatonin and its nuclear receptor retinoid-related orphan receptor alpha (RORα) have been reported to have some protective effects on the development of atherosclerosis. However, the function of melatonin in SLE-induced endothelial dysfunction and the role that RORα plays are still unknown. In this study, we found that RORα protein expression was decreased in aortas of lupus-prone mice and in human umbilical vein endothelial cells (HUVECs) cultured with medium containing sera of patients with SLE. Melatonin-treated HUVECs showed a decrease of pro-inflammatory mRNAs [interleukin-1beta (IL-1ß), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)] under the stimulation of SLE medium. Melatonin increased nitric oxide and antioxidant mRNAs (SOD1, GPX1, and CAT) and downregulated reactive oxygen species (ROS) level in HUVECs, which may subsequently delay endothelial senescence and promote HUVEC proliferation and repair after injury. Melatonin inhibited SLE medium-induced RAW264.7 macrophage migration. HUVECs pretreated with melatonin expressed less adhesion-related proteins (ICAM-1 and VCAM-1); as a result, these cells adhered to fewer peripheral blood monocytes. In addition, we also showed that the protective effects of melatonin on endothelial cells were largely diminished when RORα was knockdown in HUVECs. In conclusion, by targeting the nuclear receptor RORα, melatonin preserves normal functions of endothelium in SLE by its anti-inflammatory, antioxidant, and anti-senescence effects. RORα may have the potential to become a prophylactic or therapeutic target in preventing endothelial dysfunction and atherosclerotic cardiovascular disease in patients with SLE.

Structural equation modeling of PAHs in surrounding environmental media and field yellow carrot in vegetable bases from Northern China: In comparison with field cabbage.

During a harvest period, a set of field samples, including ambient air (gaseous and particulate phases), dust fall, surface soil and peel-surrounding soil, and yellow carrot tissues (leaf, peel, and core), were collected in a vegetable bases near a large coking manufacturer in Shanxi Province, Northern China. Based on the determinations of the concentrations and compositions of 15 USEPA priority polycyclic aromatic hydrocarbons (PAHs), the statistical results determined by a factor analysis (FA), combined with the isomeric ratios of paired species and the local emission inventory, indicated that coal combustion and vehicular exhaust served as the main emission sources of PAHs in the local environment and in yellow carrot tissues and that the coking industry was a secondary source. In terms of the transport pathways of PAHs in the surrounding media and yellow carrot tissues, the simulation results of a structural equation model (SEM) showed that the PAHs in ambient air were closely associated with those in dust fall, and these in turn had a positive correlation with the PAHs in surface soil, due to air-soil exchange. Furthermore, the PAHs in yellow carrot leaf were mainly derived from those in dust fall via leaf surface absorption, while peel uptake played a dominant role in the accumulation of PAHs in the edible core of yellow carrot. This was different from the case of cabbage, which was characterized by the prevailing contribution from leaf surface absorption. The current study supplied additional evidence to explore the transport pathways of PAHs from environmental media to tissues of different vegetables (leafy vegetables and root vegetables). CAPSULE: A combination of structural equation modeling with factor analysis was employed to quantitatively identify the dominant transport pathways of PAHs among multiple surrounding media and the different tissues of yellow carrot.

The small molecule macrophage migration inhibitory factor antagonist MIF098, inhibits pulmonary hypertension associated with murine SLE.

Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE), with unclear etiopathogenesis. We evaluated the role of macrophage migration inhibitory factor (MIF), which has been implicated in idiopathic pulmonary hypertension (PH), in SLE-associated PAH. Circulating MIF was measured in SLE patients, SLE-PAH patients, and healthy donors. In situ pulmonary artery MIF protein expression was determined in spontaneous SLE mice (MRL/lpr) and hypoxia-induced C57BL/6J mice. Daily MIF098 was administered to C57BL/6J mice, and these mice were maintained in a hypoxic chamber for 4 weeks. The right ventricular systolic pressure (RVSP) and pathological characteristics of the pulmonary artery (PA), such as hyperproliferation, muscularization, and fibrosis were then measured in each group of mice. Data were also obtained in vitro using pulmonary smooth muscle cells (PASMC) challenged with platelet-derived growth factor (PDGF)-BB or 1% O2 hypoxia. As a result, circulating MIF was elevated in SLE-PAH patients compared with SLE patients or healthy donors. Higher RVSP SLE mice produced more MIF protein than lower RVSP SLE mice in the pulmonary artery. MIF098 decreased RVSP and inhibited distal pulmonary artery hyperproliferation, muscularization, and collagen deposition in hypoxia challenged mice. In addition, MIF098 inhibited PASMC proliferation and migration by regulating mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK/ERK1/2) signal- and cell-cycle-related proteins. MIF098 also reduced collagen synthesis by inhibiting the TGFß1/Smad2/Smad3 pathway in cell-based experiments. In conclusion, MIF may serve as a biomarker and a therapeutic target of SLE-associated PAH. Pharmacologic MIF antagonism may be an effective means to ameliorate SLE-PAH.

Effects of temperature on the emission of particulate matter, polycyclic aromatic hydrocarbons, and polybrominated diphenyl ethers from the thermal treatment of printed wiring boards.

The effects of temperature on the emission of pollutants during the thermal treatment of electronic waste have rarely been investigated. The emission of particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs) from the thermal treatment of printed wiring boards was investigated over a temperature range of 320-600 °C. The emission factors (EFs) were determined to be within 1.6-7.6 g/kg, 2.23-11.9 µg/g, and 0.9-5.5 µg/g, respectively. High temperatures increased the formation of PAHs and CO, but decreased the emission of PBDEs, PM, and organic carbon. A temperature of 480 °C was determined to be optimal. Low-molecular-weight components were the dominant PAH species. The compositional profiles of PBDEs were clearly observed to vary with the temperature. Small particles (< 2.1 µm) that were more affected by temperature were dominant in PM, particle-bound PAHs, and PBDEs at all temperatures. High temperature increased the EFs of gaseous PAHs but had no remarkable effect on those of particulate PAHs. The freshly emitted PAHs primarily existed in the particulate phase at low temperatures, while the gaseous phase PAHs became prevailing at ≥ 520 °C. The particulate PBDEs were more susceptible to temperature and overwhelmingly dominant over the entire temperature range considered.