Cd Clusters Research Articles

Combined plasma protein and memory T cell profiling discern IBD-patient-immunotypes related to intestinal disease and treatment outcomes

Inflammatory bowel disease (IBD) chronicity results from memory T helper cell (Tmem) reactivation. Identifying patient-specific immunotypes is crucial for tailored treatment. We conducted a comprehensive study integrating circulating immune proteins and circulating Tmem, with intestinal tissue histology and mRNA analysis, in therapy-naïve pediatric IBD (Crohn’s disease, CD: n = 62; ulcerative colitis, UC: n = 20; age-matched controls n = 43), and after 10–12 weeks’ induction therapy. At diagnosis, plasma protein profiles unveiled two UC and three CD clusters with distinct disease courses. UC patients displayed unchanged circulating Tmem, while CD exhibited increased frequencies of gut-homing ex-Th17, known for high IFN-γ production. UC#2 had elevated Th17/neutrophil-pathway-related proteins and severe disease, with higher endoscopic and histological damage and Th17/neutrophil infiltration. Although both UC#1 and UC#2 responded to therapy, UC#2 required earlier immunomodulation. CD#3 had lower plasma protein concentrations, especially IFN-γ pathway proteins, fewer gut-homing ex-Th17 and clinically milder disease, confirmed by intestinal gene expression. CD#1 and CD#2 had comparably high Th1-related immune profiles, but CD#1 exhibited higher concentrations of proteins previously associated with poorer prognosis. Both CD clusters responded to induction therapy, with similar one-year outcomes. This study highlights feasibility of discriminating patient-specific immunotypes in IBD, advancing our understanding of immune pathogenesis, needed for tailored treatment strategies.

ценка риска формирования у детей вторичного иммунодефицита в условиях контаминации биосред алюминием и полиморфизма гена клеточной гибели FAS rs1159120 и антигенраспознающего гена толл-подобного рецептора TLR4 rs1927911

Secondary immunodeficiency remains an incompletely understood medical problem, and despite a significant number of international and scientific studies, there is no complete picture of the causes and consequences of this pathology. Metal cations have been proven to participate in the formation of acquired immunodeficiency. In particular, aluminum properties as an immune suppressor have been established and its targets in the body have been identified in case aluminum was present in biological media. However, no evaluations have been accomplished so far as regards the role of specific point genetic changes, that is, polymorphisms in the genes of immune system compartments that determine the risk of negative effects caused by contamination with metal cations, including aluminum. It is quite relevant to search and substantiate immunogenetic markers to create an indicator system for diagnostics and prevention of secondary immunodeficiency states in children associated with aluminum contamination in biological media. We examined 97 preschool children exposed to elevated levels of airborne aluminum (in an area influenced by a metallurgic production). The study groups were divided depending on either presence or absence of secondary immunodeficiency as immune system pathology (common variable immunodeficiency D83). Several markers of the immune system were evaluated: aluminum-specific IgG, CD3+, CD4+, CD8+, CD127-, CD95+, CD284+, and phagocytic activity; we also evaluated polymorphism of TLR4 A8595G (rs1927911) and FAS C14405T (rs1159120) genes of innate and acquired immunity. According to the results obtained by examining biological media composition, children with secondary immunodeficiency had 1.8 times higher aluminum levels in urine (0.0095 ± 0.0014 vs. 0.0054 ± 0.0009 mg/dm3, reference range < 0.0075 mg/dm3) as opposed to their conditionally healthy peers. We established an authentic inverse dependence between the expression level of the main CD clusters (CD3+: r = -0.38; CD4+: r = -0.39; CD8+: r = -0.26) as well as indicators of phagocytic activity (r = -0.22–0.23) and the level of aluminum contamination in biological media (urine). Expression of T-mature lymphocyte clusters was found to be inhibited by 1.3–3.1 times (including T-helper, effector T-lymphocytes, NK-killers, regulatory lymphocytes) and we also detected some changes in expression of specific immunoglobulin of IgG class to aluminum. All this results in an unacceptable level of relative risk (RR = 1.23–1.63) of developing secondary immunodeficiency against increased frequency of allele C and genotype CC of FAS gene (rs1159120) by 1.2 and 1.5 times respectively, as well as minor allele G of TLR4 gene (rs1927911) by 1.8 times relative to the comparison group (OR = 4.05; CI: 1.41–11.59; p = 0.006; RR = 1.23; CI: 1.02–1.48) and (OR = 2.01; CI: 1.04–3.91; p = 0.037; RR = 1.64; CI:1.46–1.94). Toll-dependent and FAS-dependent mechanism of this risk is associated with aluminum contamination. It is recommended to use a combination of immune and genetic markers as indicator ones when evaluating the immune system state, in order to prevent the risk (RR = 1.23–1.63) of secondary immunodeficiency associated with aluminum contamination in biological media.

Assessing risks of secondary immunodeficiency in children with aluminum contamination in biological media and polymorphism of the cell death gene FAS rs1159120 and the antigen-recognizing gene of the toll-like receptor TLR4 rs1927911

Secondary immunodeficiency remains an incompletely understood medical problem, and despite a significant number of international and scientific studies, there is no complete picture of the causes and consequences of this pathology. Metal cations have been proven to participate in the formation of acquired immunodeficiency. In particular, aluminum properties as an immune suppressor have been established and its targets in the body have been identified in case aluminum was present in biological media. However, no evaluations have been accomplished so far as regards the role of specific point genetic changes, that is, polymorphisms in the genes of immune system compartments that determine the risk of negative effects caused by contamination with metal cations, including aluminum. It is quite relevant to search and substantiate immunogenetic markers to create an indicator system for diagnostics and prevention of secondary immunodeficiency states in children associated with aluminum contamination in biological media. We examined 97 preschool children exposed to elevated levels of airborne aluminum (in an area influenced by a metallurgic production). The study groups were divided depending on either presence or absence of secondary immunodeficiency as immune system pathology (common variable immunodeficiency D83). Several markers of the immune system were evaluated: aluminum-specific IgG, CD3+, CD4+, CD8+, CD127-, CD95+, CD284+, and phagocytic activity; we also evaluated polymorphism of TLR4 A8595G (rs1927911) and FAS C14405T (rs1159120) genes of innate and acquired immunity. According to the results obtained by examining biological media composition, children with secondary immunodeficiency had 1.8 times higher aluminum levels in urine (0.0095 ± 0.0014 vs. 0.0054 ± 0.0009 mg/dm3, reference range < 0.0075 mg/dm3) as opposed to their conditionally healthy peers. We established an authentic inverse dependence between the expression level of the main CD clusters (CD3+: r = -0.38; CD4+: r = -0.39; CD8+: r = -0.26) as well as indicators of phagocytic activity (r = -0.22–0.23) and the level of aluminum contamination in biological media (urine). Expression of T-mature lymphocyte clusters was found to be inhibited by 1.3–3.1 times (including T-helper, effector T-lymphocytes, NK-killers, regulatory lymphocytes) and we also detected some changes in expression of specific immunoglobulin of IgG class to aluminum. All this results in an unacceptable level of relative risk (RR = 1.23–1.63) of developing secondary immunodeficiency against increased frequency of allele C and genotype CC of FAS gene (rs1159120) by 1.2 and 1.5 times respectively, as well as minor allele G of TLR4 gene (rs1927911) by 1.8 times relative to the comparison group (OR = 4.05; CI: 1.41–11.59; p = 0.006; RR = 1.23; CI: 1.02–1.48) and (OR = 2.01; CI: 1.04–3.91; p = 0.037; RR = 1.64; CI:1.46–1.94). Toll-dependent and FAS-dependent mechanism of this risk is associated with aluminum contamination. It is recommended to use a combination of immune and genetic markers as indicator ones when evaluating the immune system state, in order to prevent the risk (RR = 1.23–1.63) of secondary immunodeficiency associated with aluminum contamination in biological media.

Coupling Reliable Interfacial Carrier Migration Channels with Visible-Light Response Antennas in ZnO-Based Heterostructure for Ameliorated Photocatalytic Hydrogen Generation.

Engineering targeted and reliable charge transfer pathways in multiphase photocatalysts remains a challenge. Herein, we conceptualize the Cd@CdS-ZnO/reduced graphene oxide (rGO)/ZnS heterostructures coupled with reliable carrier migration channels and visible-light response antennas by building rGO-integrated electrochemical nanoreactors and an ion-exchange process. In this ternary catalyst, the Cd clusters and rGO perform as charge relays to boost carrier transport via the Z-scheme route and accelerate photogenerated carriers to react with surface-adsorbed substances. Meanwhile, thanks to CdS, the heterostructures have photocatalytic properties under visible light illumination and can also inhibit self-corrosion by shielding Cd clusters to avoid disrupting charge transfer channels. Therefore, the special heterostructure demonstrates fascinating photocatalytic hydrogen production activity without the intervention of cocatalysts. This work provides a feasible protocol for improving the interfaces between metals and semiconductors to achieve efficient photocatalytic hydrogen generation.

Synthesis of novel coordination polymer Cd-MOF and fluorescent probe detection of Fe3+, Cr2O72−, and ceftriaxone sodium (CRO)

In this contribution, Cd-MOF (1) complex with stable fluorescence properties was constructed by using 3dpu (N, N' -bis(3-pyridyl) urea) and H2IPA (isophtalic acid) as the organic ligands and Cd(NO3)2·4H2O as the metal nodes. The structure of the complex 1 was characterized by infrared spectroscopy, single crystal X-ray diffraction, powder X-ray diffraction (XRD), thermal gravimetric analysis (TGA), ultraviolet-visible spectroscopy, SEM and ICP-MS. The Cd-MOF with Cd cluster as the node, and 3dpu and IPA2− as linkers, exhibited excellent thermal and chemical stabilities. It was extended to the three-dimensional supramolecular framework by π - π stacking interaction and hydrogen bonding interaction. Importantly, complex 1 can be used as excellent fluorescent sensors toward Fe3+, Cr2O72−, and CRO (ceftriaxone sodium) with a low limit of detection and a high quenching constant, and have good anti-interference and recyclable characteristics. In addition, complex 1 has the advantages of high sensitivity and selectivity for detecting CRO in simulated human urine.

Structures and luminescence properties of one co‐edge bi‐rhomboid [Zn6] based 1D stair‐stepping polymer and one quasi‐linear tetra‐nuclear [Cd4] cluster with orotic acid

AbstractWith orotic acid (H3OA) as building ligand, one one‐dimensional (1D) Zn(II) coordination polymer, [Zn2(HOA)(μ2‐OH)(μ3‐OH)(H2O)]n (1), and one tetra‐nuclear Cd(II) cluster, [Cd4(HOA)4(μ2‐OH2)2(H2O)10] (2), have been synthesized at 90 °C and room temperature, respectively. Single‐crystal X‐ray diffraction analyses reveal that complex 1 has an 1D stair‐stepping structure consisting of co‐edge bi‐rhomboid [Zn6] structural motif and μ3‐HOA2− linker, and 2 owns a quasi‐linear tetra‐nuclear [Cd4] cluster structure fastened by μ2‐OH2 and HOA2− fixators. The solid‐state photophysical properties were investigated and 1 and 2 display a distinct emission centered at 374 and 393 nm, respectively.

DOP04 Single cell RNA sequencing reveals a potential role for IFNγ in priming circulating monocytes for intestinal inflammatory function in Crohn’s Disease.

Abstract Background Hyper-inflammatory monocyte-derived cells accumulate in the intestine and contribute to pathology in inflammatory bowel disease (IBD). Our previous work has shown that intestinal monocyte-derived cells from Crohn’s Disease patients have a reduced response to the immunoregulatory cytokine IL-10 and that this property is already established in circulating monocytes prior to their arrival in the intestine. Here, we have used scRNAseq and functional experiments to define the scope of IBD-associated changes in blood monocytes and explore the role of inflammatory cytokines in shaping these. Methods Total monocytes were isolated from the peripheral blood of 12 newly diagnosed, treatment naive IBD patients with active endoscopic disease (6 Crohn’s Disease [CD] and 6 Ulcerative Colitis [UC]) and 10 healthy controls (HC) by negative magnetic selection. scRNAseq was performed using the 10x Genomics Chromium 3’ assay at a target capture rate of 1000 cells/sample and sequencing at ~50,000 reads/cell. Data were analysed using Cell Ranger, Seurat, Metascape and Gene Set Enrichment Analysis. Blood CD14+ monocytes from healthy donors were pre-incubated in medium alone or with IFNγ (100U/ml) for 24 hours. Inhibition of LPS-induced TNFα production by IL-10 was measured by intracellular cytokine staining and flow cytometry. Results UMAP clustering identified six transcriptionally distinct monocyte clusters: clusters 0, 1 and 2 mapped to classical monocytes; cluster 3 to non-classical monocytes; cluster 4 to intermediate monocytes; and cluster 5 contained platelet signals. The proportion of cluster 4 was increased in CD patients compared to HC. Differential gene expression analysis of CD and UC monocyte clusters compared to healthy controls identified a total of 246 differentially expressed genes (DEGs) in CD and 149 in UC. Only 39 of these DEGs were significantly affected in both diseases. Both CD and UC DEGs were significantly enriched for pathways related to cytokine signalling and inflammation (Figure 1). IFNγ and TNFα -response gene sets were positively enriched in CD, but negatively enriched in UC (Figure 2). Pre-treatment of healthy monocytes with IFNγ in vitro reduced their response to IL-10 as measured by inhibition of LPS-induced TNFα (Figure 3). Conclusion Expression of genes associated with inflammation and cytokine signaling are altered in blood monocytes from IBD patients implying their modification by systemic signals prior to arrival in the intestinal mucosa. Cytokine- (IFNγ and TNFα) stimulated genes are differentially affected in CD and UC monocytes. In CD, systemic IFNγ may reduce the responsiveness of monocytes to IL-10 to prime them for inflammatory function.

5G/5G+ network management employing AI-based continuous deployment

Purpose:The paper proposes a novel concept of deployment process dedicated to continuous development, integration, testing, and upgrading the software-defined AI/ML-based functionalities in 5G/5G+ cellular networks, reliable and minimally invasive for network infrastructure, users, and service quality, automating DevOps and performance management towards the zero-touch networks. The idea is demonstrated by the continuous deployment framework, where a virtual cluster of representative cellular network resources coexists synchronously with the operator network serving the thousands-to-millions of end-users. Performance KPIs measured in this twinning subnetwork is the time series exhibiting the complex interrelations governing a temporal state of the whole system. Methods:One of the crucial problems is the detection when the changes of configuration of individual base station impacted its performance, which was realized by change points identification using an enhanced-PELT (e-PELT) algorithm. This yielded a sequence of complex data patterns (between successive change points) into sections of unique waveforms corresponding to stable network conditions. The e-PELT scheme includes a peak removal and an ACPO module for automatic penalty search. Results:e-PELT algorithm, validated against experimental data in comparative studies, outperforms the AMOC, Binary Segmentation, and BOCPD schemes, increasing the F1-score by more than 12% and the Accuracy by 10% over the PELT baseline. Conclusion:The results obtained in a CD cluster with fixed and automated penalty search show that e-PELT provides outstanding results, proving that the proposed approach can be successfully applied to analyze data sequences from different 5G network configurations. The concept of AI/ML-featured Continuous Deployment Framework dedicated to cellular networks can impact the development and integration of new telecommunication features, including possible extension for the role of standardized NWDAF module in customer networks, enhanced with the application of methodology outlined in the paper.

Photocatalytic reductive C-O bond scission promoted by low-work-function Cd single atoms and clusters.

C-O bond scission via photocatalysis is an important step in biomass depolymerization. Here, we demonstrate the scission of strong ether C-O bonds promoted by low-work-function Cd single atoms and clusters. Their loading on ZnS benefits C-H bond scission, thus weakening the C-O bond for chemical bond breaking.

New definitions of human lymphoid and follicular cell entities in lymphatic tissue by machine learning

Histological sections of the lymphatic system are usually the basis of static (2D) morphological investigations. Here, we performed a dynamic (4D) analysis of human reactive lymphoid tissue using confocal fluorescent laser microscopy in combination with machine learning. Based on tracks for T-cells (CD3), B-cells (CD20), follicular T-helper cells (PD1) and optical flow of follicular dendritic cells (CD35), we put forward the first quantitative analysis of movement-related and morphological parameters within human lymphoid tissue. We identified correlations of follicular dendritic cell movement and the behavior of lymphocytes in the microenvironment. In addition, we investigated the value of movement and/or morphological parameters for a precise definition of cell types (CD clusters). CD-clusters could be determined based on movement and/or morphology. Differentiating between CD3- and CD20 positive cells is most challenging and long term-movement characteristics are indispensable. We propose morphological and movement-related prototypes of cell entities applying machine learning models. Finally, we define beyond CD clusters new subgroups within lymphocyte entities based on long term movement characteristics. In conclusion, we showed that the combination of 4D imaging and machine learning is able to define characteristics of lymphocytes not visible in 2D histology.

Metabolome-wide association study suggests antagonistic responses to cadmium and selenium in diseased human lungs

Background and Aim: Cadmium (Cd) is a toxic environmental metal that binds selenium (Se) and contributes to many lung diseases. Humans have widespread exposures to Cd through diet and cigarette smoking, and studies in rodent models show that Se can protect against Cd toxicities. We performed metabolome-wide association study (MWAS) of Cd and Se in diseased and non-diseased human lungs to test for possible Cd-Se interactions. Methods: We analyzed tissue from 31 human lung explants, including 25 from patients with end-stage lung diseases, including idiopathic pulmonary fibrosis, cystic fibrosis, and chronic obstructive lung disease (COPD)/emphysema. We used ICP-MS (Inductively Coupled Plasma Mass Spectrometry) to measure Cd and Se, and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to conduct metabolomics analysis. Results: Metabolic pathway associations with Cd were similar to those previously observed in experimental models, including amino acid, lipid and energy-related pathways, many of which were also associated with Se. Two-way hierarchical cluster analysis (HCA) of metabolites associated with Cd revealed separation of individuals according to disease, with COPD/emphysema in the highest Cd cluster, and non-diseased individuals in the lowest Cd cluster. HCA of Se-associated metabolites revealed that COPD/emphysema also clustered by lower Se compared to others. More pathway associations occurred for the ratio of Cd:Se than either Cd or Se alone, suggesting an antagonistic relationship, and network analysis showed that most metabolites were associated with either Cd or Se. A relatively small number of polyunsaturated fatty acids and metabolites associated with inflammatory signaling had high Eigenvector centrality scores, suggesting a central mechanism of antagonistic interaction. Conclusions: Overall, the data show that metabolic pathway responses in human lung vary with Cd:Se ratio in a pattern suggesting that Se is antagonistic to Cd toxicity. Keyword: Human lung disease, environmental metals, metabolic disruption, high-resolution metabolomics.

Comparative proteomic analysis reveals insights into the response of Cryptolaemus montrouzieri to bottom-up transfer of cadmium and lead across a multi-trophic food chain

Contamination of agro-ecosystems with heavy metals can affect the development and reproduction of insect natural enemies. This study reports a detailed Tandem Mass Tag based quantitative proteomic analysis of underlying mechanisms responsible for stress response of Cryptolaemus montrouzieri against heavy metals (cadmium (Cd) and lead (Pb)) transported across a multi-trophic food chain. A total of 6639 proteins were detected under Cd as well as Pb stress. In Pb versus the control cluster, 69 proteins (28 up-regulated and 41 down-regulated) were differentially expressed whereas 268 proteins were differentially expressed under Cd versus the control cluster, having 198 proteins up-regulated and 70 down-regulated proteins. The analysis of differentially expressed proteins showed that 27 proteins overlapped in both clusters representing the core proteome to Pb and Cd stress. The bioinformatics analysis demonstrated that these proteins were mapped to 57 and 99 pathways in Pb versus control and Cd versus control clusters, respectively. The functional classification by COG, GO and KEGG databases showed significant changes in protein expression by C. montrouzieri under Pb and Cd stress. The heavy metal stress (Pb and Cd) induced significant changes in expression of proteins like hexokinase (HK), succinyl-CoA, trypsin like proteins, cysteine proteases, cell division cycle proteins, and yellow gene proteins. The results provide detailed information on the protein expression levels of C. montrouzieri and will serve as basic information for future proteomic studies on heavy metal responses of insect predators within a multi-trophic food chain.

Highly dispersed Cd cluster supported on TiO2 as an efficient catalyst for CO2 hydrogenation to methanol

The conversion of CO2 to methanol with high activity and high selectivity remains challenging owing to the kinetic and thermodynamic limitations associated with the low chemical reactivity exhibited by CO2. Herein, we report a novel Cd/TiO2 catalyst exhibiting a methanol selectivity of 81%, a CO2 conversion of 15.8%, and a CH4 selectivity below 0.7%. A combination of experimental and computational studies revealed that the unique electronic properties exhibited by the Cd clusters supported by the TiO2 matrix were responsible for the high selectivity of CO2 hydrogenation to methanol via the HCOO* pathway at the interfacial catalytic sites.

P061 Circulating inflammatory protein and cellular profiles at time of diagnosis classify inflammatory bowel disease patients according to their underlying immune response and clinical disease course

Abstract Background Chronicity of inflammatory bowel disease (IBD) is driven by reactivation of inflammatory memory CD4+ T helper (Th) cells which activate an inflammatory cascade involving innate immune cells and structural intestinal tissue cells. Because of disease heterogeneity, novel treatment strategies tailored to more precisely target the patient’s individual immune defect are required to prevent disease reactivation. We hypothesize that analysis of changes in circulating inflammatory protein abundance combined with phenotyping of circulating Th cells allow to dissect underlying immune pathogenesis and aim to stratify pediatric IBD patients accordingly. Methods We performed plasma analysis of 92 inflammatory proteins in a cohort of pediatric IBD patients (CD: n=62; UC/IBD-U: n=20), patients with suspicion of IBD but negative diagnosis (n=13) and age-matched healthy controls (HC: n=30). Peripheral blood was obtained at diagnosis and after induction treatment (t=10–14 weeks). Plasma protein concentrations were assessed with Olink Proximity Extension Assay technology® and Th cells were analyzed with flow cytometry. Results Thirty-six plasma proteins discriminated pediatric IBD patients from HC. CD and UC/IBD-U patients shared increased abundance of 17 proteins amongst which interleukin-6 and oncostatin-M. Increased abundance of the Th1 cytokine interferon-γ was strictly associated with CD while Th17-associated interleukin-17A was significantly more abundant in UC/IBD-U. Hierarchical clustering of plasma protein profiles discriminated 2 clusters of UC patients with different clinical disease activity and disease extent. In CD, three patient clusters were identified. CD#3 patients had lower clinical disease activity, lower C-reactive protein and higher blood albumin concentrations, while clusters CD#1 and CD#2 had comparable clinical parameters. CD#1 patients had higher abundance of 14 proteins associated with neutrophil function and interferon-γ signaling while CD#2 patients had a marked increase in frequencies of activated (HLA-DR+) memory Th cells. The three CD clusters responded differently to therapy with CD#1 patients exhibiting more modulated proteins and greater fold changes, CD#2 patients showing intermediate modulation and CD#3 patients exhibiting only a few changes. Conclusion Combined plasma immune protein and circulating Th cell profiling combined with in depth clinical monitoring discriminates subgroups of pediatric IBD patients during active disease which differ in their response to induction therapy. Abbreviations: CD: Crohn’s disease; UC: ulcerative colitis; IBD-U: IBD-unclassified.

A new two-dimensional homochiral cadmium(II) coordination polymer: synthesis, structure determination, optical properties, and fluorescent sensing

A new two-dimensional (2D) homochiral cadmium(II) coordination polymer, {[Cd4(OH)2(L)2(pea)4]·CH3OH} n (1) (pea = (S)-1-phenylethanamine), was solvothermally synthesized based on an enantiomerically pure chiral ligand (S)-5-(((1-carboxy-2-phenylethyl)amino) methyl)isophthalic acid (H3L). Crystal structure analysis shows that 1 is a 2D homochiral framework consisting of coaxial double-helical chains where a pair of left- and right-handed 21 helixes shares tetranuclear Cd cluster subunits [Cd4(μ 3-OH)2]. Topologically, 1 is an interesting 3,6-connected network with the point symbol of (43)2(46·66·83). The thermal stability and solid-state optical properties, including circular dichroism, and nonlinear optical and luminescent properties of 1 were systematically investigated. Furthermore, the fluorescence response of 1 to various common solvents and metal ions was preliminarily studied. Interesting enough, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), acetone and Fe3+ ion have strong quenching effect on the fluorescence of 1, indicating that 1 has certain potential application in the visual detection of these species.

P021 Circulating inflammatory protein and cellular profiles at time of diagnosis classify inflammatory bowel disease patients according to their underlying immune response and clinical disease course

Abstract Background Chronicity of inflammatory bowel disease (IBD) is driven by reactivation of inflammatory memory CD4+ T helper (Th) cells which activate an inflammatory cascade involving innate immune cells and structural intestinal tissue cells. Because of disease heterogeneity, novel treatment strategies tailored to more precisely target the patient’s individual immune defect are required to prevent disease reactivation. We hypothesize that analysis of changes in circulating inflammatory protein abundance combined with phenotyping of circulating Th cells allow to dissect underlying immune pathogenesis and we aim to stratify pediatric IBD patients accordingly. Methods We performed plasma analysis of 92 inflammatory proteins in a cohort of pediatric IBD patients (CD: n=62; UC/IBD-U: n=20), patients with suspicion of IBD but negative diagnosis (n=13) and age-matched healthy controls (HC: n=30). Peripheral blood was obtained at diagnosis and after induction treatment (t=10–14 weeks). Plasma protein concentrations were assessed with Olink Proximity Extension Assay technology® and Th cells were analyzed with flow cytometry. Samples were clustered using hierarchical clustering with Ward linkage. Differential protein abundance was assessed with t-tests at t=0 and a mixed effect model after treatment. Results Thirty-six plasma proteins discriminated pediatric IBD patients from HC. CD and UC/IBD-U patients shared increased abundance of 17 proteins amongst which interleukin-6 and oncostatin-M. Increased abundance of the Th1 cytokine interferon-γ was strictly associated with CD while Th17-associated interleukin-17A was significantly more abundant in UC/IBD-U. Hierarchical clustering of plasma protein profiles discriminated 2 clusters of UC patients with different clinical disease activity and disease extent. In CD, three patient clusters were identified. CD#1 patients had lower clinical disease activity, lower C-reactive protein and higher blood albumin concentrations. Clusters CD#2 and CD#3 had comparable clinical parameters. CD#3 patients had higher abundance of 14 proteins associated with neutrophil function and interferon-γ signaling while CD#2 patients had a marked increase in frequencies of activated (HLA-DR+) memory Th cells. The three CD clusters responded differently to therapy with CD#1 patients exhibiting only a few changes, CD#2 patients showing intermediate modulation and CD#3 patients exhibiting more modulated proteins and greater fold changes. Conclusion Combined plasma immune protein and circulating Th cell profiling discriminates subgroups of pediatric IBD patients during active disease which differ in their response to therapy. Abbreviations: CD: Crohn’s disease; UC: ulcerative colitis; IBD-U: IBD-unclassified.

Supra-Carbon Dots Formed by Fe3+-Driven Assembly for Enhanced Tumor-Specific Photo-Mediated and Chemodynamic Synergistic Therapy

We herein report a facile method to fabricate a multifunctional cancer theranostic nanoplatform via Fe3+-driven assembly of photosensitizer (chlorine e6, Ce6)-decorated red emissive carbon dots (Ce6-RCDs). The as-prepared Supra-CDs (i.e., CD clusters; also termed as Fe-Ce6-RCDs) are found to not only retain the intrinsic photosensitization, fluorescence (FL), and photothermal properties of the Ce6-RCDs component but also be endowed with the chemodynamic therapy (CDT) function by the introduced Fe3+ via the Fenton reaction that can specifically occur in tumor sites. The suitable size (∼36 nm) of the Supra-CDs enables enhanced tumor accumulation, thus achieving significantly improved FL imaging-guided anticancer performance by combining photodynamic, photothermal, and chemodynamic therapeutic modalities. More interestingly, the multi-subcellular structure (including nucleolus and cytoplasm)-targeting capacity of the Supra-CDs further enhances their therapeutic outcomes. This work not only develops a Fe3+-mediated self-assembly approach to construct a multifunctional cancer theranostic nanoplatform but also emphasizes the ion-interference role of the Fe3+-mediated CDT in anticancer nanomedicines.

Blood group systems

Blood group systems

X-RAY PROPERTIES OF THE NON-COOL-CORE CLUSTER OF GALAXIES ABELL 2147

XMM-Newton data of the medium-richness non-cD cluster of galaxies Abell 2147, at a redshift of z= 0.035, were analyzed for radial distributions of its X-ray surface brightness, temperature, and metal abundances. The measured X-ray temperature is constant at 5.2 ± 0.8 keV up to ~3’ (~ 130 kpc) from the center, while it decreases to ≤ 3.5 keV at ~13’ (~ 600 kpc). The obtained abundance profile is consistent with being constant at 0.26 ± 0.08 times the Solar value, although a slight outward decrease is suggested. The X-ray surface brightness can be described by a single -model, with = 0.50 ± 0.14 and a core radius of 145” ± 45” = 105 ± 33 kpc. These properties of Abell 2147 agree with those of the best-studies non-cD cluster, Abell 1060. When compared with typical cD clusters, Abell 2147 agrees in its X-ray properties in outer regions, including in particular the outward temperature decrease. However, in the central regions (within ~ 100 kpc), Abell 2147, as well as Abell 1060, lacks major characteristics seen in many cD clusters; the temperature decrease, the abundance enhancements, and evidence for nested two scale lengths in the gravitational potential.

Enhanced nucleation and precipitation hardening in Al–Mg–Si(–Cu) alloys with minor Cd additions

This work reports a novel effect of impurity element Cd on enhancing the precipitation kinetics and increasing the peak hardness of Al–Mg–Si(–Cu) alloys during artificial ageing. It is found that the number density of age hardening Mg–Si(–Cu) precipitates is greatly increased by Cd addition (~0.06 at.%) at both the under-aged and peak-aged stages. A systematic study on the precipitation behaviour by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) shows that most Mg–Si(–Cu) precipitates in the Cd-containing Al–Mg–Si alloys are associated with Cd-rich precipitates and have highly disordered structures. It is also found that the formation of Q'/C-like sub-units in Mg–Si(–Cu) precipitates is significantly promoted by Cd additions. To explore the nucleation mechanism under the influence of Cd addition, atom probe tomography (APT) is applied to study the solute clustering behaviour in the early stages of artificial ageing, and density functional theory (DFT) calculations are used to evaluate the binding energies of different solute-vacancy complexes and therefore the formation kinetics of Mg–Si–Cd clusters.