A case report of multicentric reticulohistiocytosis with atypical cutaneous presentation.

Multicentric reticulohistiocytosis (MRH) is a rare systemic disorder characterized by histiocytic hyperplasia that mainly involves the skin, mucous membranes, and joints. The typical clinical features include papules, nodules, and arthritis. MRH lesions are relatively extensive but small and scattered. Joint inflammation is characterized by diffuse symmetric polyarthritis as the first symptom, which can be severe and disabling due to destructive joint changes. MRH is easily misdiagnosed in clinical practice. Here, we report the case of an elderly male patient who presented with polyarticular pain in the hip and interphalangeal joints as the first manifestation, followed by the development of large, isolated, bulging skin nodules, which are atypical MRH lesions. This is rare in all MRH case reports, and we made the correct diagnosis by combining skin histopathology, immunohistochemistry, and other clinical examinations. We performed surgical treatment on the local skin lesions of this patient. This case suggests that clinicians should actively correlate the condition and accurately diagnose MRH when encountering atypical skin changes or other diseases as the first symptom and explore the mechanisms of MRH and other clinical manifestations.

High efficiency stimulated rotational Raman scattering of hydrogen pumped by 1064 nm.

Laser-induced breakdown (LIB) and the competition of other Raman processes are major reasons restricting photon conversion efficiency (PCE) of Raman lasers. In this work, 1064 nm was used as the pump source, and stimulated rotational Raman scattering of hydrogen was investigated. The configuration of zooming out and focusing pump beam was applied, and the dimension of the pump beam at the focus spot increased significantly; consequently, LIB was suppressed, and Raman PCE was improved dramatically. With the help of the Raman gas pressure optimization, vibrational Raman could be fully suppressed, and other competition Raman processes could be well controlled. The optimal PCEs of different rotational Raman lasers could be achieved under different conditions. The maximum PCE of the first rotational Stokes (RS1) was improved to 60.7%, and the maximum energy of RS1 reached 204.5 mJ. With the increment of hydrogen pressure, the maximum PCE of the second rotational Stokes (RS2) was improved to 28.2%, and the maximum energy of RS2 reached 123.9 mJ. Furthermore, a 2.1 µm Raman laser was also generated, the maximum PCE of 2.1 µm reached 44.8%, and its pulse energy reached 106.1 mJ.

Two-Color Amplified Spontaneous Emission from Auger-Suppressed Quantum Dots in Liquids.

Colloidal quantum-dot (QD) lasing is normally achieved in close-packed solid-state films, as a high QD volume fraction is required for stimulated emission to outcompete fast Auger decay of optical-gain-active multiexciton states. Here a new type of liquid optical-gain medium is demonstrated, in which compact compositionally-graded QDs (ccg-QDs) that feature strong suppression of Auger decay are liquefied using a small amount of solvent. Transient absorption measurements of ccg-QD liquid suspensions reveal broad-band optical gain spanning a wide spectral range from 560 (green) to 675 nm (red). The gain magnitude is sufficient to realize a two-color amplified spontaneous emission (ASE) at 637 and 594 nm due to the band-edge (1S) and the excited-state (1P) transition, respectively. Importantly, the ASE regime is achieved using quasicontinuous excitation with nanosecond pulses. Furthermore, the ASE is highly stable under prolonged excitation, which stands in contrast to traditional dyes that exhibit strong degradation under identical excitation conditions. These observations point toward a considerable potential of high-density ccg-QD suspensions as liquid, dye-like optical gain media that feature readily achievable spectral tunability and stable operation under intense photoexcitation.

Serum exosomal m6A demethylase FTO promotes gefitinib resistance in non-small cell lung cancer by up-regulating FLRT3, PTGIS and SIRPα expression.

This study investigates the molecular mechanism of FTO m6A demethylase in non-small cell lung cancer (NSCLC) and gefitinib resistance using GEO and TCGA databases. Differentially expressed genes (DEGs) were screened from RNA-seq data sets of serum exosomes of gefitinib-resistant NSCLC patients in the GEO database and the NSCLC data set in the GEPIA2 database. From this analysis, FTO m6A demethylase was found to be significantly upregulated in the serum exosomes of gefitinib-resistant NSCLC patients. To identify downstream genes affected by FTO m6A demethylase, weighted correlation network analysis and differential expression analysis were performed, resulting in the identification of three key downstream genes (FLRT3, PTGIS, and SIRPA). Using these genes, the authors constructed a prognostic risk assessment model. Patients with high-risk scores exhibited a significantly worse prognosis. The model could predict the prognosis of NSCLC with high accuracy measured by AUC values of 0.588, 0.608, and 0.603 at 1, 3, and 5 years respectively. Furthermore, m6A sites were found in FLRT3, PTGIS, and SIRPA genes, and FTO was significantly positively correlated with the expression of these downstream genes. Overall, FTO m6A demethylase promotes gefitinib resistance in NSCLC patients by upregulating downstream FLRT3, PTGIS, and SIRPA expression, with these three downstream genes serving as strong prognostic indicators.

Sediment-water distribution and potential sources of polyhalogenated carbazoles in a coastal river locating at a north metropolis, China.

The fate and transformation of PHCZs in the coastal river environment are not yet comprehensively understood. Paired river water and surface sediment were collected, and 12 PHCZs were analyzed to find out their potential sources and investigate the distribution of PHCZs between river water and sediment. The concentration of ∑PHCZs varied from 8.66 to 42.97 ng/g (mean 22.46 ng/g) in sediment and 17.91 to 81.82 ng/L (mean 39.07 ng/L) in river water. 18-B-36-CCZ was the dominant PHCZ congener in sediment, while 36-CCZ was in water. Meanwhile, the logKoc values for CZ and PHCZs were among the first calculated in the estuary and the mean logKoc varied from 4.12 for 1-B-36-CCZ to 5.63 for 3-CCZ. The logKoc values of CCZs were higher than those of BCZs, this may suggest that sediments have a higher capacity for accumulation and storage of CCZs than highly mobile environmental media.

Stimulated vibrational-rotational Raman scattering of hydrogen pumped at a 1064-nm laser.

A ∼2.1-µm laser is within an atmospheric transmission window and can be used in remote sensing. In this work, a 1064-nm laser was used as the pump source, pressurized hydrogen was used as the Raman active medium, and a dual-wavelength ∼2.1-µm Raman laser was generated. The 2147-nm laser was generated by a combination processes of stimulated vibrational Raman scattering and stimulated rotational Raman scattering, while a 2132-nm laser was generated by stimulated S-branch vibrational Raman scattering. Optimizing experimental conditions yielded a maximum pulse energy of 76.1 mJ, a peak power of ∼9.2M W, and a photon conversion efficiency of 29.8%.

Reduction-responsive dextran-based Pt(IV) nano-prodrug showed a synergistic effect with doxorubicin for effective melanoma treatment.

Melanoma, the deadliest skin cancer with high metastasis potential, has posed a great threat to human health. Accordingly, early efficient blocking of melanoma progression is vital in antitumor treatment. Herein, a reduction-responsive dextran-based Pt(IV) nano-prodrug (PDPN) was synthesized and used for doxorubicin (DOX) delivery to combat melanoma synergistically. First, PDPN was prepared by one-pot chemical coupling of carboxylated methoxy poly(ethylene glycol) (mPEG), dextran (Dex), and the crosslinking agent cisPt (IV)-COOH. PDPN had a spherical structure (Rh = 34 ± 11.3 nm). Then, DOX was encapsulated into the PDPN core to form DOX-loaded PDPN (PDPN-DOX). The obtained PDPN-DOX displayed reduction-responsive release of DOX and Pt, thus showing a synergistic anticancer effect in B16F10 cells (combination index, 0.46). Furthermore, in vivo experiments demonstrated that PDPN-DOX was effective for the synergistic treatment of subcutaneous melanoma. Collectively, the as-prepared PDPN could serve as a promising and versatile nano-prodrug carrier for the co-delivery of chemotherapeutics in tumor combination therapy.

An integrative non-invasive malignant brain tumors classification and Ki-67 labeling index prediction pipeline with radiomics approach.

BACKGROUND: The histological sub-classes of brain tumors and the Ki-67 labeling index (LI) of tumor cells are major factors in the diagnosis, prognosis, and treatment management of patients. Many existing studies primarily focused on the classification of two classes of brain tumors and the Ki-67LI of gliomas. This study aimed to develop a preoperative non-invasive radiomics pipeline based on multiparametric-MRI to classify-three types of brain tumors, glioblastoma (GBM), metastasis (MET) and primary central nervous system lymphoma (PCNSL), and to predict their corresponding Ki-67LI. METHODS: In this retrospective study, 153 patients with malignant brain tumors were involved. The radiomics features were extracted from three types of MRI (T1-weighted imaging (T1WI), fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted imaging (CE-T1WI)) with three masks (tumor core, edema, and whole tumor masks) and selected by a combination of Pearson correlation coefficient (CORR), LASSO, and Max-Relevance and Min-Redundancy (mRMR) filters. The performance of six classifiers was compared and the top three performing classifiers were used to construct the ensemble learning model (ELM). The proposed ELM was evaluated in the training dataset (108 patients) by 5-fold cross-validation and in the test dataset (45 patients) by hold-out. The accuracy (ACC), sensitivity (SEN), specificity (SPE), F1-Score, and the area under the receiver operating characteristic curve (AUC) indicators evaluated the performance of the models. RESULTS: The best feature sets and ELM with the optimal performance were selected to construct the tri-categorized brain tumor aided diagnosis model (training dataset AUC: 0.96 (95% CI: 0.93, 0.99); test dataset AUC: 0.93) and Ki-67LI prediction model (training dataset AUC: 0.96 (95% CI: 0.94, 0.98); test dataset AUC: 0.91). The CE-T1WI was the best single modality for all classifiers. Meanwhile, the whole tumor was the most vital mask for the tumor classification and the tumor core was the most vital mask for the Ki-67LI prediction. CONCLUSION: The developed radiomics models led to the precise preoperative classification of GBM, MET, and PCNSL and the prediction of Ki-67LI, which could be utilized in clinical practice for the treatment planning for brain tumors.

Myotonic dystrophy type 1 presenting with dyspnea: A case report.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a genetic neuromuscular disease involving multiple systems, especially the cardiopulmonary system. The clinical phenotype of DM1 patients is highly variable, which limits early diagnosis and treatment. In the present study, we reported a 35-year-old female DM1 patient with dyspnea as the primary onset clinical manifestation, analyzed her family's medical history, and reviewed related literature. CASE SUMMARY: A 35-year-old woman was admitted to the hospital with dyspnea of 1 mo duration, and sleep apnea for 3 d. Her respiratory pattern and effort were normal, but limb muscle tension was low. Investigation into the patient's medical history revealed that she might have hereditary neuromuscular disease. Electromyography showed that her myotonia potentials were visible in the resting state of the examined muscles, with decreased motor unit potential time limit and amplitude. Genetic testing for DM1 revealed that the cytosine-thymine-guanine (CTG) repeat number of the DMPK gene exceeded 50, while cytosine-CTG expansion in intron 1 of ZNF9 gene was < 30 repeats. The patient was diagnosed with DM1. CONCLUSION: DM1 is a genetic neuromuscular disease involving multiple systems, and the clinical phenotype in DM1 is extremely variable. Some patients with DM1 may be presented at the respiratory department because of dyspnea, which should be cautioned by the pulmonologists. There may be no obvious or specific symptoms in the early stage of disease, and clinicians should improve their understanding of DM1 and make an early diagnosis, which will improve patients' quality of life.

Low-Loss, High-Transparency Luminescent Solar Concentrators with a Bioinspired Self-Cleaning Surface.

Luminescent solar concentrators (LSCs) have emerged as a disruptive technology that can potentially enable carbon-neutral buildings. The issues with current LSCs, however, are low optical efficiencies and limited long-term outdoor stability. Here we simultaneously address them by developing an LSC with aggregation-induced-emission (AIE) molecules embedded in a polydimethylsiloxane (PDMS) matrix. The AIE-emitter displayed a near unity emission quantum yield when embedded in the PDMS and the apparent absorption-emission Stokes shift reached 0.59 eV, effectively suppressing the reabsorption loss of waveguided photons inside an LSC. Moreover, the surface texture of the PDMS matrix was engineered using a bioinspired nanolithography method with a natural lotus leaf as the template. This allowed the fabricated AIE-PDMS LSC to inherit the superhydrophobic, self-cleaning properties of the leaf and meanwhile to possess a light-trapping capability. Our 100 cm2 LSC, when coupled with commercial Si PVs, delivered efficient solar power conversion, high visible transmittance, and high working stability.

Oxypeucedanin relieves LPS-induced acute lung injury by inhibiting the inflammation and maintaining the integrity of the lung air-blood barrier.

INTRODUCTION: Acute lung injury (ALI) is commonly accompanied by a severe inflammatory reaction process, and effectively managing inflammatory reactions is an important therapeutic approach for alleviating ALI. Macrophages play an important role in the inflammatory response, and this role is proinflammatory in the early stages of inflammation and anti-inflammatory in the late stages. Oxypeucedanin is a natural product with a wide range of pharmacological functions. This study aimed to determine the effect of oxypeucedanin on lipopolysaccharide (LPS)-induced ALI. METHODS AND RESULTS: In this study, the following experiments were performed based on LPS-induced models in vivo and in vitro. Using myeloperoxidase activity measurement, ELISA, qRT-PCR, and Western blotting, we found that oxypeucedanin modulated the activity of myeloperoxidase and decreased the expression levels of inflammatory mediators such as TNF-α, IL-6, IL-1ß, MPO, COX-2 and iNOS in LPS-induced inflammation models. Meanwhile, oxypeucedanin inhibited the activation of PI3K/AKT and its downstream NF-κB and MAPK signaling pathways. In addition, oxypeucedanin significantly decreased the pulmonary vascular permeability, which was induced by LPSs, and the enhanced expression of tight junction proteins (Occludin and Claudin 3). CONCLUSIONS: In conclusion, this study demonstrated that the anti-inflammatory mechanism of oxypeucedanin is associated with the inhibition of the activation of PI3K/AKT/NF-κB and MAPK signaling pathways and the maintenance of the integrity of the lung air-blood barrier.

Integrated head and neck imaging of symptomatic patients with stroke using simultaneous non-contrast cardiovascular magnetic resonance angiography and intraplaque hemorrhage imaging as compared with digital subtraction angiography.

BACKGROUND: Both stenosis rate and intraplaque hemorrhage (IPH) are important predictors of stroke risk. Simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) cardiovascular magnetic resonance (CMR) imaging can detect both stenosis rate and IPH. We aimed to evaluate consistency between SNAP and digital subtraction angiography (DSA) to assess symptomatic patients with stroke and explore the performance of SNAP to identify IPH and the clinical factors associated with IPH. METHODS: Eighty-one symptomatic patients with stroke, admitted to Wuhan Union Hospital who underwent CMR high-resolution vessel wall imaging (HR-VWI) and SNAP, were retrospectively identified. For patients who received interventional therapy, the imaging functions of SNAP and HR-VWI were compared with DSA. The diameters of the intracranial and carotid vessels were measured, and stenotic vessels were identified. The consistency of SNAP and HR-VWI in identifying IPH was also examined, and the correlations between IPH and clinical factors were analyzed. RESULTS: SNAP was more consistent with DSA than HR-VWI in measuring vascular stenosis (intraclass correlation coefficient [ICC]SNAP-DSA = 0.917, ICC HR-VWI-DSA = 0.878). Regarding the diameter measurements of each intracranial and carotid vessel segment, SNAP was superior or similar to HR-VWI, and both were consistent with DSA in the measurement of major intracranial vascular segments. HR-VWI and SNAP exhibited acceptable agreement in identifying IPH (Kappa = 0.839, 95% confidence interval [CI]: 0.704-0.974). Patients who underwent interventional therapy had a higher plaque burden (P < 0.001). Patients with IPH had lower levels of high-density lipoprotein cholesterol (HDL) (P = 0.038) and higher levels of blood glucose (P = 0.007) and cystatin C (P = 0.040). CONCLUSIONS: CMR SNAP is consistent with DSA in measuring vessel diameters and identifying atherosclerosis stenosis in each intracranial and carotid vessel segment. SNAP is also a potential alternative to HR-VWI in identifying stenosis and IPH.

Case Report: Patient With Lung Adenocarcinoma With ALK-HLA-DRB1 Rearrangement Shows Impressive Progression-Free Survival After Sequential Crizotinib and Ceritinib Treatment.

The anaplastic lymphoma kinase (ALK) gene rearrangement is a driving mutation that underlies about 5-6% of non-small cell lung cancer (NSCLC) cases. Lung cancers that are ALK gene rearrangement-positive can be effectively treated with ALK inhibitors. However, the response of patients with rarer ALK gene rearrangements to ALK inhibitors remains unknown. Herein, we described a case of lung adenocarcinoma carrying ALK-HLA-DRB1 fusion in a 48-year-old nonsmoking woman. A similar case of ALK-HLA-DRB1 rearrangement in NSCLC has not been described previously neither in NSCLC nor in other disease. The patient achieved a progression-free survival of 18 months after sequential therapy consisting of crizotinib and then ceritinib during the follow-up. These findings provide basis for the application of ALK inhibitors in patients carrying the rare ALK-HLA-DRB1 fusion.

A Novel Subtraction Method to Reduce Metal Artifacts of Cerebral Aneurysm Embolism Coils.

OBJECTIVE: To investigate a novel subtraction method (S-MAR), combing metal artifact reduction (MAR), virtual monochromatic imaging (VMI), and subtraction CT angiography (CTA) to remove the metal artifacts of coils after endovascular embolotherapy of intracranial aneurysms. METHOD: In this retrospective study, 29 patients with 38 coils after endovascular embolotherapy of intracranial aneurysms who underwent cerebral CTA using a dual-layer detector spectral CT were included. Conventional CT images (CI), virtual non-enhanced (VNC) images and VMI ranging from 40 to 120 KeV in steps of 10 were reconstructed. These images were then postprocessed to CIMAR, VMIMAR and VNCMAR with MAR software (O-MAR; Philips Healthcare, Cleveland, OH, USA). The novel subtraction method (S-MAR) was derived from subtraction imaging between VNCMAR and the optimal VMIMAR. Contrast-to-noise (CNR) and Noise(Background) of CI, CIMAR, VMI, and VMIMAR were calculated quantitatively. Two Independent radiologists qualitatively assessed artifacts in all images using coil artifact score (CA score), a 5-point Likert scale. Besides, all coils were divided into two groups (group 1: diameter < 5.0 mm, group 2: diameter ≥ 5.0 mm). Differences between two groups were statistically analyzed. RESULTS: The optimal KeV was 40 KeV. Strong correlations between diameter of coils and the CA score of CI were found (rs = 0.652, P < 0.05). CNR, Noise and CA score were significantly improved by CIMAR and VMIMAR compared with CI (P < 0.05). The S­MAR showed significantly better performance compared with CI, CIMAR, VMI, and VMIMAR in reducing metal coil artifacts according to the CA score (P < 0.05), especially in group 2. CONCLUSION: The novel S­MAR proved to be a promising method to reduce coil metal artifacts and elevate the vessel visualization adjacent to coils. It could develop to be widely used in cerebral CTA after coiled aneurysms.

Altered brain network in first-episode, drug-naive patients with major depressive disorder.

BACKGROUND: Resting-state functional magnetic resonance imaging has been widely used for the assessment of brain functional network, yet with inconsistent results. The present study aimed to investigate intranetwork and internetwork connectivity differences between patients with major depressive disorder (MDD) and healthy controls at the integrity, network and edge levels of 8 well-defined resting state networks. METHODS: Thirty patients with MDD and sixty-three healthy control subjects were recruited in this study. RESULTS: Compared with healthy controls, patients with MDD showed increased node degree in the right amygdala and putamen, increased connectivity strength in the deep gray matter network (DGN) and increased functional connectivity in intranetwork and internetwork. Meanwhile, MDD showed decreased connectivity strength in visual network-DGN pair. LIMITATIONS: The sample size was small, and all patients in this study were of Asian ethnicity, especially Han individuals. CONCLUSIONS: These findings demonstrate that MDD cases and healthy controls may have divergent intranetwork and internetwork connectivity at an early stage without confounding influence of medication. These differences may underlie cognitive and behavioral alterations in patients with MDD. And these differences may help with the discrimination of patients and healthy people at an early stage of MDD. More studies in the future are warranted to assist in the diagnosis of this burdensome disease.

Association between dietary inflammatory index and cognitive impairment: A meta-analysis.

Aims: Cognitive impairment is an increasingly urgent global public health challenge. Dietary Inflammatory Index (DII) is a literature-derived score that links diet to inflammation. The relationship between DII and cognitive impairment remains controversial. Therefore, our study aimed to analysis the role of DII on the risk of cognitive impairment by meta-analysis. Methods: PubMed, Cochrane Library, MEDLINE, Web of Science and EMBASE databases were searched up to July 2022. Newcastle-Ottawa scale (NOS) and Joanna Briggs Institute (JBI) Checklist were performed to estimate the quality of studies. Results: Nine observational studies with 19,379 subjects were included. Our study found that higher DII could elevate the risk of cognitive impairment (OR = 1.46, 95%CI = 1.26, 1.69). Meanwhile, the OR of cognitive impairment was 1.49 (95%CI = 1.21, 1.83) for cross-sectional studies and 1.42 (95%CI = 1.12, 1.79) for cohort studies, respectively. Conclusion: Our meta-analysis indicated that higher DII (indicating a more pro-inflammatory diet) is related to increased risk of cognitive impairment.

lncRNA TINCR attenuates the proliferation and invasion, and enhances the apoptosis of cutaneous malignant melanoma cells by regulating the miR­424­5p/LATS1 axis.

Cutaneous malignant melanoma (CMM) is responsible for ≥1/2 of skin cancer­related mortalities. The aberrant expression of long non­coding RNAs (lncRNAs) has been associated with the development of CMM. However, to the best of our knowledge, the role of the lncRNA TINCR ubiquitin domain containing (TINCR) in CMM has not been previously investigated, and thus, the current study aimed to evaluate this in vitro and in vivo. Reverse transcription­quantitative PCR (RT­qPCR) was used to analyze microRNA (miR)­424­5p expression, and RT­qPCR and western blotting were used to measure TINCR, large tumor suppressor kinase 1 (LATS1), cellular communication network factor 2 (CTGF), cellular communication network factor 1 (CCN1) and AXL receptor tyrosine kinase (AXL) mRNA and protein expression levels, respectively. Cell Counting Kit­8, flow cytometry and Transwell assays were used to detect the proliferation, apoptosis and invasion of CMM cell lines, respectively. The binding sites between TINCR and miR­424­5p were predicted using the miRDB database. A dual luciferase reporter assay and RT­qPCR were used to identify the relationship between TINCR and miR­424­5p in CMM cell lines. The bioinformatics analysis revealed that TINCR was one of the most significantly downregulated lncRNAs in CMM, and advanced stage CMM tissues showed the greatest decrease in TINCR expression. Moreover, in the collected CMM tissues and tested cell lines of the current study, TINCR expression was found to be downregulated compared with the respective controls. Notably, TINCR overexpression inhibited the expression levels of CTGF, CCN1 and AXL, decreased the proliferation and invasion, and induced the apoptosis of CMM cell lines. In addition, a mutual binding association was identified between miR­424­5p and TINCR in CMM cells. LATS1, a target of miR­424­5p, was found to be positively regulated by TINCR. TINCR activated Hippo signaling and repressed the activity of Yes 1 associated transcriptional regulator by regulating LATS1 expression, while LATS1 knockdown reversed the effect of TINCR overexpression on CMM cells. Collectively, the findings of the present study suggested that TINCR may attenuate the progression of CMM by regulating the miR­424­5p/LATS1 signaling axis. These results indicated that TINCR may play a tumor suppressive role in CMM.

Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells.

BACKGROUND AND PURPOSE: Skin tissue is the natural barrier that protects our body, the damage of which can be repaired by the epidermal stem cells (ESCs). However, external factors abolish the self-repair ability of ESCs by inducing oxidative stress and severe inflammation. Apremilast is a small molecular inhibitor of phosphodiesterase 4 that was approved for the treatment of psoriasis. In the present study, the protective property of Apremilast against IL-1α-induced dysfunction on epidermal stem cells, as well as the preliminary mechanism, will be investigated. METHODS: ESCs were isolated from neonatal mice. The expression levels of TNF-α, IL-8, IL-12, MMP-2, and MMP-9 were detected using real-time PCR and ELISA. MitoSOX Red assay was used to determine the level of mitochondrial reactive oxygen species (ROS). Western blot and real-time PCR were utilized to determine the expression levels of IL-1R1, Myd88, and TRAF6. Activation of NF-κB was assessed by measuring the p-NF-κB p65 and luciferase activity. Capacities of ESCs were evaluated by measuring the gene expressions of integrin ß1 and Krt19 using real-time PCR. RESULTS: Firstly, the expression levels of TNF-α, IL-8, IL-12, MMP-2, MMP-9 and IL-1R1, as well as the ROS level, were significantly elevated by IL-1α but greatly suppressed by treatment with Apremilast. Subsequently, we found that the activated Myd88/TRAF6/NF-κB signaling pathway induced by stimulation with IL-1α was significantly inhibited by the introduction of Apremilast. As a result, Apremilast protected ESCs against IL-1α-induced impairment in capacities of ESCs, this was verified by the elevated expression levels of integrin ß1 and Krt19. CONCLUSIONS: Apremilast might ameliorate IL-1α-induced dysfunction in ESCs by mitigating oxidative stress and inflammation through inhibiting the activation of the Myd88/TRAF6/NF-κB signaling pathway.

Occurrence and potential sources of polyhalogenated carbazoles in farmland soils from the Three Northeast Provinces, China.

Polyhalogenated carbazoles (PHCZs) have been detected in various environments frequently and have attracted increasing attention for their multiple toxicities. However, only a few reports record the occurrence of PHCZs in farmland soils, and the sources of which were not yet been implemented. In this study, 12 PHCZs and carbazole (CZ) were screened in farmland soil samples from the Three Northeast Provinces, and the ∑PHCZs were in the range of 18.16-219.67 ng/g dw. 36-CCZ was the dominant congener (40.67%) in farmland soils, followed by 3-CCZ (14.51%), and average percentages of other congeners were lower than 10%. A concrete analysis of the sources of PHCZs in the soil was conducted, revealing the diversity of PHCZs sources. Potential toxic effects associated with the levels of PHCZs were evaluated via the toxic equivalency (TEQ) approach, and the TEQs of PHCZs (TEQPHCZs) were in the range of 2.24-14.06 pg TEQ/g dw. Notwithstanding the 1368-CCZ with a low concentration level, the mean contribution to TEQPHCZs was up to 24.24%, preceded only by 36-CCZ (39.69%), showing the congeners with low concentration also may pose potential risks to the environment. Partial PHCZs congeners (2-BCZ, 3-BCZ, 36-CCZ, 136-BCZ, and 2367-BCZ) showed significant correlations (r = 0.45-0.63, p < 0.05) with the total organic carbon (TOC). Significant correlations were shown between PHCZ congeners replaced by halogens of the same species and quantity (r = 0.40-0.99, p < 0.01). In view of the fact that the high concentration level of PHCZs in the soil and their source diversity, more environmental monitoring and risk assessments of PHCZs should be of particular concern.