Environmentally persistent free radicals on photoaging microplastics shortens longevity via inducing oxidative stress in Caenorhabditis elegans.

Microplastics (MPs) are ubiquitous environmental contaminants that exert multiple toxicological effects. Current studies have mainly focused on modeled or unaged MPs, which lack environmental relevance. The generation and toxicity of environmentally persistent free radicals (EPFRs) on photoaging polystyrene (PS) have not been well studied, and the role of EPFRs on the toxic effects of photoaged PS is easily ignored. Photoaging primarily produces EPFRs, followed by an increase in reactive oxygen species (ROS) content and oxidative potential, which alter the physicochemical properties of photoaged PS. The mean lifespan and lipofuscin content were significantly altered after acute exposure to photoaged PS for 45 d (PS-45) and 60 d (PS-60) in Caenorhabditis elegans. Intestinal ROS and gst-4::GFP expression were enhanced, concomitant with the upregulation of associated genes. Treatment with N-acetyl-l-cysteine by radical quenching test significantly decreased EPFRs levels on the aged PS and inhibited the acceleration of the aging and oxidative stress response in nematodes. Pearson's correlation analysis also indicated that the EPFRs levels were significantly associated with these factors. Thus, the EPFRs generated on photoaged PS contribute to the acceleration of aging by oxidative stress. This study provides new insights into the potential toxicity and highlights the need to consider the role of EPFRs in the toxicity assessment of photoaged PS.

Neurotoxicity of tetrabromobisphenol-A-bis(2,3-dibromopropyl ether) through the GABAergic and serotonergic neurotransmission in Caenorhabditis elegans.

Tetrabromobisphenol-A-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), a novel additive brominated flame retardant, is being developed for use in polyolefin and copolymers. Despite its emerging application, the neurotoxicity and mechanisms of action of TBBPA-BDBPE remain unexplored. Caenorhabditis elegans was utilized as the model organism to study the neurotoxic effects of TBBPA-BDBPE across environmental concentrations ranging from 0 to 100 µg/L. This investigation focused on various toxicological endpoints such as locomotive behavior, neuronal injury, neurotransmitter transmission, and the regulation of nervous system-related gene expression. Acute exposure to TBBPA-BDBPE at concentrations of 10-100 µg/L significantly impaired nematode movement, indicating potential neurotoxicity. In transgenic nematodes, this exposure also caused damage to γ-aminobutyric acid (GABAergic) and serotonergic neurons, along with notable changes in the levels of GABAergic and serotonergic neurotransmitters. Further molecular studies indicated alterations in neurotransmission-related genes (cat-4, mod-1, unc-25, and unc-47). Molecular docking analysis confirmed the binding affinity of TBBPA-BDBPE to key neurotransmission proteins-CAT-4, MOD-1, UNC-25, and UNC-47. These findings demonstrate that TBBPA-BDBPE exerts neurotoxic effects by impacting GABAergic and serotonergic neurotransmission in nematodes. This study provides new insights into the potential environmental risks of TBBPA-BDBPE.

SUMO-specific peptidase 3 mediates the SUMO3 modification of BECN1 to repress cell autophagy in gliomas.

OBJECTIVE: SUMO Specific Peptidase 3 (SENP3) is involved in the occurrence and development of various cancers. However, its effects on gliomas have been barely reported. Herein, this research was designed to probe the potential mechanisms of SENP3 mediating beclin-1(BECN1) SUMO3 modification in autophagy in gliomas. METHODS: SENP3 expression in gliomas was analyzed through bioinformatic information. Clinical samples of glioma tissues were collected and frozen. SENP3 expression was evaluated with western blot. In glioma cells, autophagy- and apoptosis-related proteins, viability, and apoptosis were assessed with western blot and immunofluorescence, the cell counting kit-8, and flow cytometry, respectively. The SUMO modification of BECN1 and interactions between BECN1 and PIK3C3 were identified with Ni-NTA pull-down and co-immunoprecipitation assays, respectively. The tumor formation assay was carried out in nude mice for in vivo validation. RESULTS: Bioinformatics analysis predicted the overexpression of SENP3 in gliomas, which was confirmed in clinical samples and glioma cells. SENP3 silencing promoted autophagy and apoptosis and inhibited viability in glioma cells, which was counteracted by further autophagy inhibition. Mechanistically, SENP3 facilitated BECN1 deSUMOylation to mediate the SUMO3 modification of BECN1, thus impeding the formation of BECN1-PIK3C3 complexes. The loss of the SUMO part in BECN1 lowered the protein expression of LC3 and the value of LC3BII/LC3BI in glioma cells. Additionally, SENP3 silencing boosted autophagy and repressed tumor growth in mice, which was neutralized by further autophagy repression. CONCLUSION: SENP3 fosters the deSUMOylation of BECN1 to block the formation of BECN1-PIK3C3 complexes, thus restraining glioma cell autophagy.

Colorimetric discrimination and spectroscopic detection of tyrosine enantiomers based on melamine induced aggregation of l-cysteine/Au nanoparticles.

Au nanoparticles (AuNPs) are decorated by l-cysteine (L-Cys), and the resultant chiral L-Cys/AuNPs can be used for colorimetric discrimination and spectroscopic detection of the tyrosine (Tyr) enantiomers. Melamine (Mel) can induce the aggregation of the L-Cys/AuNPs through ligand exchange, leading to a distinct color change from wine red to purple. Owing to the same rotatory direction of L-Cys/AuNPs and L-Tyr, the L-Cys/AuNPs exhibit a significantly higher binding affinity toward L-Tyr than D-Tyr, and thus the Mel induced aggregation of the L-Cys/AuNPs is greatly alleviated by the protection from the L-Tyr protective layer. Therefore, the Tyr enantiomers can be simply discriminated by naked eyes. In addition, the absorbance of the aggregated L-Cys/AuNPs at ∼630 nm increases linearly with decreasing concentrations of L-Tyr ranging from 10 nM to 1 mM due to the weakened protection effect from L-Tyr, and thus spectroscopic detection of L-Tyr can also be accomplished by the developed L-Cys/AuNPs with a limit of detection (LOD) of 5.3 nM.

3D-printed scaffold harboring copper ions combined with near-infrared irradiation for local therapy of cancer.

Cancer is a major health threat and a leading cause of human death worldwide. Surgical resection is the primary treatment for most cancers; however, some patients develop locoregional recurrence. Here, we developed an in situ cancer therapeutic system aimed to locally treat cancer and prevent postoperative recurrence. A functional scaffold, based on alginate/gelatin and crosslinked with copper ions, was fabricated by 3D printing and showed an excellent photothermal effect under near-infrared (NIR) irradiation. The combination of copper ions and NIR effectively killed thyroid cancer cells and patient-derived organoids, indicating a synergetic and broad-spectrum antitumor effect on thyroid cancer through the chemo-photothermal therapy. This implantable stent is designed to provide effective treatment in the vicinity of the tumor site and can be degraded without secondary surgery. The copper-loaded hydrogel scaffold may be a potential candidate for local cancer treatment and pave the way for precise and effective cancer therapy.

Erratum to "Research trends in cholangiocarcinoma treatments during the last 3 decades" [Heliyon 9(7) (July 2023) e17100].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17100.].

Thermal-controlled cellular uptake of "hot" nanoparticles.

Nanoparticles (NPs) have shown immense potential in the field of biomedical applications, particularly in NP-based photothermal therapy, which offers a remote-controlled approach to achieve precise temperature control for site-specific heating and sub-cellular tumor treatment. However, the molecular mechanisms underlying related cellular activities, such as the cellular uptake behavior of irradiated NPs in photothermal effects, remain elusive. In this study, we conducted a thorough investigation of the interaction between an irradiated NP with elevated temperature (ranging from 270 to 360 K) and a model bilayer membrane composed of DPPC or DOPC using nonequilibrium coarse-grained molecular dynamics simulations with the implicit-solvent Dry Martini force field. We observe that the interaction between a "hot" NP and a membrane is thermally regulated. In addition, the wrapping of membranes around NPs exhibits a strong dependence on the temperature of the irradiated NP, demonstrating a step-like change in behavior. This membrane wrapping effect is attributed to the heat conduction between NPs and membrane lipids, which occurs almost simultaneously with the membrane deformation and wrapping of NPs during the NP-membrane interaction process. Especially, during the process of heat conduction, a gel-to-fluid phase transition of the membrane may occur, which plays a crucial role in determining the deformation behavior of the membrane. Moreover, it is found that the membrane lipids in the two leaflets exhibit obvious and asymmetric molecular-level responses to heat flux, characterized by significant changes in packing states (e.g., the order parameter of lipid tails and area per lipid) and possible interdigitation between lipids. Furthermore, the thermal-controlled wrapping effect is tightly linked to the properties of NPs (e.g., size, NP-lipid affinity) and lipid species. Our findings are valuable for comprehending the thermal-regulated cellular internalization of NPs and offer insights into devising strategies to precisely modulate NP endocytosis by exploiting the interplay between heating and NP properties.

Research trends in cholangiocarcinoma treatments during the last 3 decades.

Background: Over the past 30 years, numerous studies have focused on the treatment of cholangiocarcinoma (CCA), and these treatments have greatly evolved. Objectives: To better understand the research trends, we evaluated the most influential publications and attempted to identify their characteristics using bibliometric methods. Methods: The most influential publications were identified from the Clarivate Analytics Web of Science Core Collection database. The general characteristics of included papers were identified, and the research trends were explored via the bibliometric method. Results: The average total number of citations for of the listed publications were 312 (range from 165 to 1922). The highest number of papers were published during period II (2001-2010, n = 50), followed by period III (2011-2020, n = 28), and period I (1991-2000, n = 22). The United States and Germany have made remarkable achievements in this field. Institutionally, Mayo Clinic and Memorial Sloan-Kettering Cancer Center were the leading institutions, with Blumgart and Zhu from the United States being the most influential authors. Close collaboration was established between the leading countries, institutions, and authors. The Annals of Surgery contributed the most to the papers with the highest total number of citations. Surgery predominated during period I (n = 14, 63.6%), with a gradual decline occurring during periods II (n = 19, 41.3%, P = 0.085) and period III (n = 3, 9.4%, P = 0.002). Contrastingly, the number of publications related to systemic therapy has increased significantly since period II and peaked in period III. Conclusions: Surgery remains the most important treatment for CCA. However systemic therapy has become a research and clinical application hotspot. These findings will contribute to the translation of treatments for CCA and provide researchers with relevant research directions.

Microbial colonization of microplastics in wastewater accelerates the aging process associated with oxidative stress and the insulin/IGF1 signaling pathway.

Although polystyrene (PS)-induced toxicity in organisms has been documented, adverse effects on lifespan and molecular mechanisms underlying microbial colonization of PS remain elusive. Herein, physicochemical properties of biofilm-developed PS (B-PS) incubated in wastewater were altered compared with virgin PS (V-PS). Bacterial community adherence to the B-PS surface were also impacted. Acute exposure to V-PS (100 µg/L) and B-PS (10 µg/L) significantly altered the mean lifespan and lipofuscin accumulation of Caenorhabditis elegans, suggesting that B-PS exposure at environmentally relevant concentrations could more severely accelerate the aging process than V-PS. Generation of ROS, gst-4::GFP expression, and oxidative stress-related gene expression were significantly altered following B-PS exposure. Moreover, B-PS exposure increased the nucleus-cytoplasm translocation of DAF-16 and altered the expression of genes encoding the insulin/IGF1 signaling (IIS) pathway. Compared with wild-type nematodes, the daf-16 mutation markedly enhanced lipofuscin accumulation and reduced mean lifespan, whereas daf-2, age-1, pdk-1, and akt-1 mutants could recover lipofuscin accumulation and mean lifespan. Accordingly, B-PS exposure accelerated the aging process associated with oxidative stress and the IIS pathway, and the DAF-2-AGE-1-PDK-1-AKT-1-DAF-16 signaling cascade may play a critical role in regulating the lifespan of C. elegans. This study provides new insights into the potential risks associated with microbial colonization of microplastics.

Insight into the effect of catalytic reactions on correlations of soot oxidation activity and microspatial structures.

A catalyst is usually coated on Diesel particulate filter (DPF) for assisted regeneration. In this paper, the oxidation activity and pore structure evolutions of soot under the effect of CeO2 are explored. CeO2 effectively increases the oxidation activity of soot and reduces the initial activation energy; in the meantime, the addition of CeO2 changes the soot oxidation mode. Pure soot particles tend to produce the porous structure in the oxidation process. Mesopores promote the diffusion of oxygen, and macropores contribute to reduce the agglomeration of soot particles. Additionally, CeO2 provides the active oxygen for soot oxidation and promotes the multi-point oxidation at the beginning of soot oxidation. With the oxidation proceeding, catalysis causes the collapsion of soot microspatial structures, in the meantime, the macropores caused by the catalytic oxidation are filled by CeO2. It results in the tight contact between soot and catalyst, further promoting the formation of the available active oxygen for soot oxidation. This paper is meaningful to analyze the oxidation mechanism of soot under catalysis, which lays a foundation for improving the regeneration efficiency of DPF and reducing the particle emission.

The generation of environmentally persistent free radicals on photoaged microbeads from cosmetics enhances the toxicity via oxidative stress.

Microbeads used in personal care products have been one of the important sources of microplastics (MPs), and little has been reported on their environmental behaviors and health risks. The characteristics of environmentally persistent free radicals (EPFRs) and the toxicity assessment of MPs (environmentally relevant concentrations) from cosmetics during photoaging remains largely unknown. In this study, the formation of EPFRs on polyethylene (PE) microbeads from facial scrubs under light irradiation and their toxicity were investigated using C. elegans as a model organism. The results suggested that light irradiation induced the generation of EPFRs, which accelerates the aging process and alters the physicochemical properties of PE microbeads. Acute exposure to PE (1 mg/L) at photoaged times of 45-60 d significantly decreased the physiological indicators (e.g., head thrashes, body bends, and brood size). The oxidative stress response and stress-related gene expression were also enhanced in nematodes. The addition of N-acetyl-l-cysteine induced significant inhibition of toxicity and oxidative stress in nematodes exposed to 45-60 d of photoaged PE. The Pearson correlation results showed that the concentration of EPFRs was significantly correlated with physiological indicators, oxidative stress, and related-genes expression in nematodes. The data confirmed that the generation of EPFRs combined with heavy metals and organics contributed to toxicity induced by photoaged PE, and oxidative stress might be involved in regulating adverse effects in C. elegans. The study provides new insight into the potential risks of microbeads released into the environment during photoaging. The findings also highlight the necessity for considering the role of EPFRs formation in evaluating the impacts of microbeads.

Establishment of papillary thyroid cancer organoid lines from clinical specimens.

Papillary thyroid cancer (PTC) is a common malignancy of the endocrine system, and its morbidity and mortality are increasing year by year. Traditional two-dimensional culture of cell lines lacks tissue structure and is difficult to reflect the heterogeneity of tumors. The construction of mouse models is inefficient and time-consuming, which is difficult to be applied to individualized treatment on a large scale. Clinically relevant models that recapitulate the biology of their corresponding parental tumors are urgently needed. Based on clinical specimens of PTC, we have successfully established patient-derived organoids by exploring and optimizing the organoid culture system. These organoids have been cultured stably for more than 5 passages and successfully cryopreserved and retried. Histopathological and genome analysis revealed a high consistency of the histological architectures as well as mutational landscapes between the matched tumors and organoids. Here, we present a fully detailed method to derive PTC organoids from clinical specimens. Using this approach, we have developed PTC organoid lines from thyroid cancer samples with a success rate of 77.6% (38/49) until now.

Risk Stratification and Overall Survival Prediction in Advanced Gastric Cancer Patients Based on Whole-Volume MRI Radiomics.

BACKGROUND: The prognosis of advanced gastric cancer (AGC) patients has attracted much attention, but there is a lack of evaluation method. MRI-based radiomics has the potential to evaluate AGC patients' prognosis. PURPOSE: To identify and validate the risk stratification and overall survival (OS) in AGC patients using MRI-based radiomics. STUDY TYPE: Retrospective. SUBJECTS: A total of 233 patients (168 males, 63.6 ± 11.1 years; 65 females, 59.7 ± 11.8 years) confirmed AGC were collected. The data were randomly divided into a training (164) and validation set (69). SEQUENCE: A 3.0 T, axial T2-weighted, diffusion-weighted imaging, and contrast-enhanced T1-weighted (CE-T1WI). ASSESSMENT: Radiologist 1 segmented 233 patients and radiologist 2 segmented randomly 50 patients on CE-T1WI. The risk score (RS) was summed by each sample based on the radiomics features and correlation coefficients. Patients were followed up for 7-67 months (median 41; 138 dead and 95 alive). STATISTICAL TESTS: The intraclass correlation coefficient (ICC) and Kappa value were calculated. Differences in survival analysis were assessed by Kaplan-Meier curves and log-rank test. Cox-regression analysis was performed to identify the radiomics features and clinical indicators associated with OS. The calibration curves were built to assess the model. A two-tailed P value < 0.05 was considered statistically significant. RESULTS: Integrated with age, lymphovascular invasion (LVI) and RS, a survival combined model was built. The area under the curve (AUC) for predicting 3-year and 5-year OS was 0.765 and 0.788 in the training set, 0.757 and 0.729 in the validation set. There was no significant difference between the radiomics model and survival combined model for 3-year (0.690 vs. 0.757, P = 0.425) and 5-year OS (0.687 vs. 729, P = 0.412) in the validation set. The calibration curves showed a high degree of fit for the survival combined model. DATA CONCLUSION: This study established a survival combined model that might help AGC patients in future clinical decision-making. EVIDENCE LEVEL: 33 TECHNICAL EFFICACY: Stage 5.

Papillary thyroid cancer organoids harboring BRAFV600E mutation reveal potentially beneficial effects of BRAF inhibitor-based combination therapies.

BACKGROUNDS: Papillary thyroid cancer (PTC), which is often driven by acquired somatic mutations in BRAF genes, is the most common pathologic type of thyroid cancer. PTC has an excellent prognosis after treatment with conventional therapies such as surgical resection, thyroid hormone therapy and adjuvant radioactive iodine therapy. Unfortunately, about 20% of patients develop regional recurrence or distant metastasis, making targeted therapeutics an important treatment option. Current in vitro PTC models are limited in representing the cellular and mutational characteristics of parental tumors. A clinically relevant tool that predicts the efficacy of therapy for individuals is urgently needed. METHODS: Surgically removed PTC tissue samples were dissociated, plated into Matrigel, and cultured to generate organoids. PTC organoids were subsequently subjected to histological analysis, DNA sequencing, and drug sensitivity assays, respectively. RESULTS: We established 9 patient-derived PTC organoid models, 5 of which harbor BRAFV600E mutation. These organoids have been cultured stably for more than 3 months and closely recapitulated the histological architectures as well as mutational landscapes of the respective primary tumors. Drug sensitivity assays of PTC organoid cultures demonstrated the intra- and inter-patient specific drug responses. BRAFV600E inhibitors, vemurafenib and dabrafenib monotherapy was mildly effective in treating BRAFV600E-mutant PTC organoids. Nevertheless, BRAF inhibitors in combination with MEK inhibitors, RTK inhibitors, or chemotherapeutic agents demonstrated improved efficacy compared to BRAF inhibition alone. CONCLUSIONS: These data indicate that patient-derived PTC organoids may be a powerful research tool to investigate tumor biology and drug responsiveness, thus being useful to validate or discover targeted drug combinations.

Mesenchymal Stem Cell-Originated Exosomal Lnc A2M-AS1 Alleviates Hypoxia/Reperfusion-Induced Apoptosis and Oxidative Stress in Cardiomyocytes.

BACKGROUND: Mesenchymal stem cell (MSC)-derived exosomes play significant roles in ameliorating cardiac damage after myocardial ischemia-reperfusion (I/R) injury. Long non-coding RNA alpha-2-macroglobulin antisense RNA 1 (Lnc A2M-AS1) was found that might protect against myocardial I/R. However, whether Lnc A2M-AS1 delivery via MSC-derived exosomes could also regulate myocardial I/R injury remains unknown. METHODS: Exosomes were isolated by ultracentrifugation, and qualified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Hypoxia/reoxygenation (H/R) treatment in human cardiomyocytes was used to mimic the process of myocardial I/R in vitro. The viability and apoptosis of cardiomyocytes were detected using cell counting kit-8, flow cytometry, and Western blot assays. The contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) were evaluated using corresponding commercial kits. The quantitative real-time polymerase chain reaction and Western blot were used to determine the expression levels of Lnc A2M-AS1, microRNA (miR)-556-5p, and X-linked inhibitor of apoptosis protein (XIAP). The binding interaction between miR-556-5p and Lnc A2M-AS1 or XIAP was confirmed by the dual-luciferase reporter, RIP and pull-down assays. RESULTS: Exosomes isolated from hMSCs (hMSCs-exo) attenuated H/R-induced apoptosis and oxidative stress in cardiomyocytes. Lnc A2M-AS1 was lowly expressed in AMI patients and H/R-induced cardiomyocytes. Besides, Lnc A2M-AS1 was detectable in hMSCs-exo, exosomes derived from Lnc A2M-AS1-transfected hMSCs weakened H/R-induced apoptosis and oxidative stress, and enhanced the protective action of hMSCs-exo on H/R-induced cardiomyocytes. Further mechanism analysis showed that Lnc A2M-AS1 acted as a sponge for miR-556-5p to increase XIAP expression level. Importantly, miR-556-5p overexpression or XIAP knockdown reversed the action of exosomal Lnc A2M-AS1 on H/R-induced cardiomyocytes. CONCLUSION: Lnc A2M-AS1 delivery via MSC-derived exosomes ameliorated H/R-induced cardiomyocyte apoptosis and oxidative stress via regulating miR-556-5p/XIAP, opening a new window into the pathogenesis of myocardial I/R injury.

A cloud-based consultation and collaboration system for radiotherapy: Remote decision support services for community radiotherapy centers.

PURPOSE: This study aimed to establish a cloud-based radiotherapy consultation and collaboration system, then investigated the practicability of remote decision support for community radiotherapy centers using the system. METHODS AND MATERIALS: A cloud-based consultation and collaboration system for radiotherapy, OncoEvidance®, was developed to provide remote services of LINAC modeling, simulation CT data import/export, target volume and organ-at-risk delineation, prescription, and treatment planning. The system was deployed on a hybrid cloud. A federate of public nodes, each corresponding to a medical institution, are managed by a central node where a group of consultants have registered. Users can access the system through network using computing devices. The system has been tested at three community radiotherapy centers. One accelerator was modeled. 12 consultants participated the remote radiotherapy decision support and 77 radiation treatment plans had been evaluated remotely. RESULTS: All the passing rates of per-beam dose verification are > 94% and all the passing rates of composite beam dose verification are > 99%. The average downloading time for one set of simulation CT data for one patient from Internet was within 1 min under the cloud download bandwidth of 8 Mbps and local network bandwidth of 100 Mbps. The average response time for one consultant to contour target volumes and make prescription was about 24 h. And that for one consultant to design and optimize a IMRT treatment plan was about 36 h. 100% of the remote plans passed the dosimetric criteria and could be imported into the local TPS for further verification. CONCLUSION: The cloud-based consultation and collaboration system saved the travel time for consultants and provided high quality radiotherapy to patients in community centers. The under-staffed community radiotherapy centers could benefit from the remote system with lower cost and better treatment quality control.

Pathogenic roles of neutrophil-derived alarmins (S100A8/A9) in heart failure: From molecular mechanisms to therapeutic insights.

An excessive neutrophil count is recognized as a valuable predictor of inflammation and is associated with a higher risk of adverse cardiac events in patients with heart failure. Our understanding of the effectors used by neutrophils to inflict proinflammatory actions needs to be advanced. Recently, emerging evidence has demonstrated a causative role of neutrophil-derived alarmins (i.e. S100A8/A9) in aggravating cardiac injuries by induction of inflammation. In parallel with the neutrophil count, high circulating levels of S100A8/A9 proteins powerfully predict mortality in patients with heart failure. As such, a deeper understanding of the biological functions of neutrophil-derived S100A8/A9 proteins would offer novel therapeutic insights. Here, the basic biology of S100A8/A9 proteins and their pleiotropic roles in cardiovascular diseases are discussed, focusing on heart failure. We also consider the evidence that therapeutic targeting of S100A8/A9 proteins by the humanized vaccine, antibodies or inhibitors is able to town down inflammatory injuries.

Variations in surface functional groups, carbon chemical state and graphitization degree during thermal deactivation of diesel soot particles.

The thermal deactivation of diesel soot particles exerts a significant influence on the control strategy for the regeneration of diesel particulate filters (DPFs). This work focused on the changes in the surface functional groups, carbon chemical state, and graphitization degree during thermal treatment in an inert gas environment at intermediate temperatures of 600°C, 800°C, and 1000°C and explore the chemical species that were desorbed from the diesel soot surface during thermal treatment using a thermogravimetric analyser coupled with a gas-chromatograph mass spectrometer (TGA-GC/MS). The surface functional groups and carbon chemical state were characterized using Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The graphitization degree was evaluated by means of Raman spectroscopy (RS). The concentrations of aliphatic C-H, C-OH, C=O, and O-C=O groups are reduced for diesel soot and carbon black when increasing the thermal treatment temperature, while the sp2/sp3 hybridized ratio and graphitization degree enhance. These results provide comprehensive evidence of the decreased reactivity of soot samples. Among oxygenated functional groups, the percentage reduction during thermal treatment is the largest for the O-C=O groups owing to its worst thermodynamic stability. TGA-GC/MS results show that the aliphatic and aromatic chains and oxygenated species would be desorbed from the soot surface during 1000°C thermal treatment of diesel soot.

Assessing the inflammatory severity of the terminal ileum in Crohn disease using radiomics based on MRI.

BACKGROUND: Evaluating inflammatory severity using imaging is essential for Crohn's disease, but it is limited by potential interobserver variation and subjectivity. We compared the efficiency of magnetic resonance index of activity (MaRIA) collected by radiologists and a radiomics model in assessing the inflammatory severity of terminal ileum (TI). METHODS: 121 patients were collected from two centers. Patients were divided into ulcerative group and mucosal remission group based on the TI Crohn's disease Endoscopic Severity Index. The consistency of bowel wall thickness (BWT), relative contrast enhancement (RCE), edema, ulcer, MaRIA and features of the region of interest between radiologists were described by weighted Kappa test and intraclass correlation coefficient (ICC), and developed receiver operating curve of MaRIA. The radiomics model was established using reproducible features of logistic regression based on arterial staging of T1WI sequences. Delong test was used to compare radiomics with MaRIA. RESULTS: The consistency between radiologists were moderate in BWT (ICC = 0.638), fair in edema (κ = 0.541), RCE (ICC = 0.461), MaRIA (ICC = 0.579) and poor in ulcer (κ = 0.271). Radiomics model was developed by 6 reproducible features (ICC = 0.93-0.96) and equivalent to MaRIA which evaluated by the senior radiologist (0.872 vs 0.883 in training group, 0.824 vs 0.783 in validation group, P = 0.847, 0.471), both of which were significantly higher than MaRIA evaluated by junior radiologist (AUC: 0.621 in training group, 0.557 in validation group, all, P < 0.05). CONCLUSION: The evaluation of inflammatory severity could be performed by radiomics objectively and reproducibly, and was comparable to MaRIA evaluated by the senior radiologist. Radiomics may be an important method to assist junior radiologists to assess the severity of inflammation objectively and accurately.

CXCR4 blockade in macrophage promotes angiogenesis in ischemic hindlimb by modulating autophagy.

Chemokine receptor CXCR4 plays a crucial role in leukocyte recruitment and inflammation regulation to influence tissue repair in ischemic diseases. Here we assessed the effect of CXCR4 expression in macrophages on angiogenesis in the ischemic hindlimb of a mouse. Inflammatory cells were increased in the ischemic muscles of hindlimb, and CXCR4 was highly expressed in the infiltrated macrophages but not in neutrophils. Myeloid-specific CXCR4 knockout attenuated macrophage infiltration and subsequent reduced inflammatory response in the ischemic hindlimb, accompanied with better blood reperfusion and higher capillary density as compared with that in LysM Cre+/- (Cre) mice. Similar outcomes were also observed in CRE mice whose bone marrow cells were replaced with those from CXCR4-deficient mice. Gene ontology cluster analysis reviewed that Decorin, a negative regulator of angiogenesis, was reduced in CXCR4-deficient macrophages. CXCR4-deficient macrophages were less inducible into M1 phase by lipopolysaccharide and more favorable for M2 polarization under oxygen/glucose deprivation condition. Enhanced autophagy was detected in CXCR4-deficient macrophages, which was associated with less expression of both Decorin and the inflammatory cytokines. In summary, myeloid-specific CXCR4 deficiency reduced monocyte infiltration and the secretion of inflammatory cytokines and Decorin from macrophages, thus blunting inflammation response and promoting angiogenesis in the ischemic hindlimb.