CD Activity Research Articles

Synthesis of Cd (II), Fe (III), Cu (II), and Cr (VI) complexes of Schiff bases and their antibacterial activities

Schiff base and the metal derivatives have been utilized in numerous areas of the economy. Synthesis and antibacterial activities of Cd (II), Cr (VI), Cu (II), and Fe (III) complexes of Schiff bases were evaluated in this work. Complexes synthesized were Bis(1-phenyl-3-methyl-4-Phenyl acetyl 5-pyrazolone)Cadmium (II) (Cd(HPMPP)2), Tris(1-phenyl-3-methyl-4-benzoyl-5-pyrazolone)Iron(III)(Fe(HPMBP)3), Bis(1-phenyl-3-methyl-4-phenylacetyl-5-pyrazolone)Copper (II) (Cu(HPMPP)2), Hexakis(1-phenyl-3-methyl-4-palmitoyl-5-pyrazolone)Chromium (VI) (Cr(HPMPP)6), and Tris(1-phenyl-3-methyl-4- palmitoyl-5-pyrazolone)Iron (III) (Fe(HPMPP)3). The physical state, colour, and melting point of these complexes were determined using appropriate analytical techniques. Results showed that all the complexes were crystalline in nature; their colours were variable, while their melting points were sharp. The solubility of these complexes in deionized water, acetone, methanol, and ethanol was also carried out. The outcome revealed that all the metal complexes were insoluble in deionized water, Cr(HPMPP)6 was soluble in acetone, methanol, and ethanol. However, the solubility of other metal complexes in the organic solvents used was variable. The antibacterial activities of these metal complexes at different concentrations were also tested against distilled water, E. coli, S. aureus, B. subtillus, and S. typhi. The results showed that, antimicrobial activity of these complexes against distilled water was negative whereas, the bacterial growth of all the bacteria was inhibited by the complexes though at different rates. The inhibition rate of microorganisms was inversely proportional to the concentration of the complexes. The antibacterial activities of Cd(HPMPP)2 and Cr(HPMPP)6 were outstanding against the growth of all the bacteria. Thus, a proper processing of these complexes might result in excellent antibacterial drugs. However, more studies on the mode of action of these complexes against microorganisms and their toxicity should be done in order to establish their potentials for pharmaceutical applications.

Effects of polyurethane microplastics combined with cadmium on maize growth and cadmium accumulation under different long-term fertilisation histories

Agricultural production uses different types of fertilisation treatments, typically employing the combined application of organic fertiliser (OF) or organic–inorganic fertiliser (OIF) to improve soil quality. When coupled with cadmium (Cd), microplastics (MPs) affect plant growth and Cd accumulation in soils treated with different fertilisers. This study systematically examined the effects of polyurethane (PU) MPs coupled with Cd on the growth characteristics, root metabolite characteristics, rhizosphere bacterial community structure, and Cd bioavailability of maize under different long-term fertilisation treatments and soil types (red/cinnamon soil). The combined effects of PU MPs and Cd on maize growth differed across fertilisation treatments. Under OF, maize plants accumulated more Cd than under OIF. The accumulation of Cd in maize plants in red soil was twice that in cinnamon soil. Under OF, PU MPs promoted Cd activation by decreasing the soil pH, while root metabolites promoted Cd adsorption sites by synthesising specific amino acids, degrading aromatic compounds, and synthesising pantothenic acid and coenzyme A. Under OF, PU MPs can lower the soil pH to promote the activation of cadmium, while root metabolites promote root growth and increase cadmium adsorption sites by synthesizing specific amino acids, degrading aromatic compounds, and synthesizing pantothenic acid and coenzyme A, hereby promoting root Cd absorption. Under OIF, PU MPs act by influencing the biosynthesis of amino acids in root metabolites, enriching energy metabolism pathways, promoting the transport and translocation of mineral nutrients, thereby amplifying the "toxic effects" of Cd. This study provides new insights into the risk assessment of PU MPs and Cd coupling under different fertilisation treatments, and suggests that the prevention and control of combined PU MPs and Cd pollution in red soil under OF treatment should receive more attention in the future.

Comparison of fidaxomicin, thuricin CD, vancomycin and nisin highlights the narrow spectrum nature of thuricin CD

ABSTRACT Vancomycin and metronidazole are commonly used treatments for Clostridioides difficile infection (CDI). However, these antibiotics have been associated with high levels of relapse in patients. Fidaxomicin is a new treatment for CDI that is described as a narrow spectrum antibiotic that is minimally active on the commensal bacteria of the gut microbiome. The aim of this study was to compare the effect of fidaxomicin on the human gut microbiome with a number of narrow (thuricin CD) and broad spectrum (vancomycin and nisin) antimicrobials. The spectrum of activity of each antimicrobial was tested against 47 bacterial strains by well-diffusion assay. Minimum inhibitory concentrations (MICs) were calculated against a select number of these strains. Further, a pooled fecal slurry of 6 donors was prepared and incubated for 24 h with 100 µM of each antimicrobial in a mini-fermentation system together with a no-treatment control. Fidaxomicin, vancomycin, and nisin were active against most gram positive bacteria tested in vitro, although fidaxomicin and vancomycin produced larger zones of inhibition compared to nisin. In contrast, the antimicrobial activity of thuricin CD was specific to C. difficile and some Bacillus spp. The MICs showed similar results. Thuricin CD exhibited low MICs (<3.1 µg/mL) for C. difficile and Bacillus firmus, whereas fidaxomicin, vancomycin, and nisin demonstrated lower MICs for all other strains tested when compared to thuricin CD. The narrow spectrum of thuricin CD was also observed in the gut model system. We conclude that the spectrum of activity of fidaxomicin is comparable to that of the broad-spectrum antibiotic vancomycin in vitro and the broad spectrum bacteriocin nisin in a complex community.

Development and application of machine learning models for prediction of soil available cadmium based on soil properties and climate features

Identifying the key influencing factors in soil available cadmium (Cd) is crucial for preventing the Cd accumulation in the food chain. However, current experimental methods and traditional prediction models for assessing available Cd are time-consuming and ineffective. In this study, machine learning (ML) models were developed to investigate the intricate interactions among soil properties, climate features, and available Cd, aiming to identify the key influencing factors. The optimal model was obtained through a combination of stratified sampling, Bayesian optimization, and 10-fold cross-validation. It was further explained through the utilization of permutation feature importance, 2D partial dependence plot, and 3D interaction plot. The findings revealed that pH, surface pressure, sensible heat net flux and organic matter content significantly influenced the Cd accumulation in the soil. By utilizing historical soil surveys and climate change data from China, this study predicted the spatial distribution trend of available Cd in the Chinese region, highlighting the primary areas with heightened Cd activity. These areas were primarily located in the eastern, southern, central, and northeastern China. This study introduces a novel methodology for comprehending the process of available Cd accumulation in soil. Furthermore, it provides recommendations and directions for the remediation and control of soil Cd pollution.

Comprehensive insight into the transformation mechanism of Cd fractionation in the components of paddy soils under cysteine leaching

Cadmium (Cd) contamination in paddy soils poses a serious threat to agricultural production and human health. In this study, cysteine was selected as the leaching agent for remediating Cd-contaminated paddy soils because of its effective, low cost and ecofriendly characteristics. Microcosmic simulation experiment was using to investigate the fate of Cd and elucidate the transformation mechanism of Cd in the key components of paddy soil under cysteine leaching. Results showed that the total Cd removal rate of paddy soils reached 46.8–87.4% under the optimal conditions. This was mainly attributed to the decrease of exchangeable fraction (F1), carbonate bound fraction (F2), iron/manganese-bound fraction (F3) and organic matter bound fraction (F4) of Cd. After cysteine leaching, soil fertility was promoted due to the increase in nitrate nitrogen (NN), ammonia nitrogen (AN), available phosphorus (AP) and organic matter (OM). pH, CaCO3, available potassium (AK), NN, AP, amorphous iron oxides (Feo) were the main contributors to Cd fractionation transformation. The desorption of Cd from ferrihydrite (Fh) and goethite (Gt) surfaces is hypothesized to stem from dual mechanisms: the dissolution due to the low solution pH and the reducibility of cysteine, which facilitated the conversion of Fh and Gt to hematite (Hm). And the -SH complexation also ascribed to the activation of Cd bound by Fe-OH in Fh and Gt and oxygen-containing functional groups in humic acid (Ha). For chlorite (Ch), the primary driver for Cd desorption was identified as an ion-exchange process, whereby electrostatically adsorbed Cd2+ were replaced by H+ produced by cysteine protonation.

Evaluation of cadmium phytoextraction potential of peanut and the rhizospheric properties of specific cultivars

Phytoextraction is an effective technique for removing cadmium (Cd) from contaminated farmland, thus achieving real ecological restoration. To clarify the potential of peanut phytoextraction, we designed a pot experiment to assess the Cd accumulation in peanut. In addition, the contribution of rhizosphere microorganisms in Cd accumulation was explored. The results demonstrate that the Cd content in peanut tissue ranked as follows: stem > leaf > root > needle > husk > kernel, with Cd mainly accumulated in the stems (41.92%) and leaves (40.27%). The bioconcentration factor for all cultivars was greater than 1, in agreement with the concept of phytoextraction. Cd extraction from peanut plants grown per season was appreciable, estimated as being from 28.5 g Cd ha−1 to 121.5 g Cd ha−1. Subsequently, based on the Cd accumulation characteristics, cultivars BS1016 and HY20 were identified as the high Cd-accumulating cultivars (HACs), and LH11 and LH14 were identified as the low Cd-accumulating cultivars (LACs), for further study as specific cultivars. For Cd-contaminated soil, high accumulation in HACs was associated with increased Cd bioavailability. The peanut rhizosphere attracted different microorganisms to cope with Cd stress. Compared with LACs, the rhizosphere of HACs tended to be enriched with high Cd-resistant microorganisms, which directly or indirectly participate in Cd activation (for example, Acidimicrobiia class of bacteria, Rhizophlyctis genus of fungi). Correlation analysis confirmed that Rhizophlyctis was a good choice to enhance the potential for Cd phytoextraction using peanut. This study demonstrates the advantages and rhizosphere mechanisms of using peanut for bioremediating Cd-contaminated soil, providing a new approach for remediation and targeted regulation of Cd-contaminated farmland.

Correlation Between Serum and Fecal Biomarkers and Patient-Reported Outcomes in Patients with Crohn's Disease and Ulcerative Colitis.

Patient-reported outcomes (PROs), such as the short CD activity index (sCDAI) and partial Mayo Score (PMS), are used to define clinical remission in IBD, but may not represent the true degree of inflammation and endoscopy is invasive. Non-invasive testing options include c-reactive protein (CRP) and fecal calprotectin (FCP). The aim of this study was to assess the degree of correlation of non-invasive biomarkers with PROs and the impact other clinical variables can have on their levels. We reviewed data collected from the prospective cohort, Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD), comprised of over 3000 patients from 17 tertiary referral centers. Demographic and clinical variables were analyzed by disease type, disease severity was based on PROs, and baseline CRP and FCP were measured. For comparative analysis, we performed Fisher's exact test and Welch's t test, where p < 0.05 was significant. 1547 patients were included; 63% had CD, 56% were female, with an average disease duration of 13.6years. CRP and FCP were associated with symptom severity in inflammatory CD. CRP was useful to differentiate symptoms across different disease locations in CD, whereas FCP was associated with symptom severity in Crohn's colitis only. For UC, FCP was able to distinguish symptom severity better in distal UC, whereas in extensive or pancolitis, it was useful only to distinguish severe symptoms from other categories of symptom severity. PROs correlate with CRP and FCP; however, disease location and phenotype impact their ability to distinguish symptom severity.

The effect of quorum sensing on cadmium- and lead-containing wastewater treatment using activated sludge: Removal efficiency, enzyme activity, and microbial community

Quorum sensing (QS) is prevalent in activated sludge processes; however, its essential role in the treatment of heavy metal wastewater has rarely been studied. Therefore, in this study, acyl homoserine lactone (AHL)-mediated QS was used to regulate the removal performance, enzyme activity, and microbial community of Cd- and Pb-containing wastewater in a sequencing batch reactor (SBR) over 30 cycles. The results showed that exogenous AHL strengthened the removal of Cd(II) and Pb(II) in their coexistence wastewater during the entire period. The removal of NH4+-N, total phosphorus, and chemical oxygen demand (COD) was also enhanced by the addition of AHL despite the coexistence of Cd(II) and Pb(II). Meanwhile, the protein content of extracellular polymeric substances was elevated and the microbial metabolism and antioxidative response were stimulated by the addition of AHL, which was beneficial for resistance to heavy metal stress and promoted pollutant removal by activated sludge. Microbial sequencing indicated that AHL optimized the microbial community structure, with the abundance of dominant taxa Proteobacteria and Unclassified_f_Enterobacteriaceae increasing by 73.9% and 59.2% maximally, respectively. This study offers valuable insights into the mechanisms underlying Cd(II) and Pb(II) removal as well as microbial community succession under AHL availability in industrial wastewater.

Cd Activation Mechanisms of High-Enriched Rapeseed (Brassica Napus L.) in Rhizosphere Soil

Cd Activation Mechanisms of High-Enriched Rapeseed (Brassica Napus L.) in Rhizosphere Soil

Metastatic crohn’s disease in a child: rare extraintestinal manifestation

Extraintestinal manifestations occur in every second child with Crohn’s disease, can affect any organ system, and determine the type of therapy and prognosis of the disease. The skin is the most frequent “target organ” of all extraintestinal manifestations, the spectrum of skin lesions is extremely clinically and pathogenically heterogeneous. Metastatic Crohn’s disease (MBC) is a rare extraintestinal manifestation of the disease, approaches to the diagnosis and management of which are not standardized in either adults or children. The most frequent description of MBC in the literature is skin damage, although interstitial lung damage, bone and muscle damage, and ENT organs, could be destructive. MCD lesions vary in morphology and can arise anywhere on the skin, rarely undergo reverse development, require special approaches to therapy. The primary diagnosis of such elements is extremely difficult, often delated, biopsy is required for a definitive diagnosis - the detection of epithelioid granuloma and its elements outside the gastrointestinal tract. Therapeutic approaches to MCD are not standardized now, they are carried out according to the protocols of CD management, and the effect of the use of oral steroids, a-TNFa drugs is shown. A case of metastatic Crohn’s disease in a 16-year-old teenager with an unusual localization - the nasal septum is described. The destructive nature of the lesion with the formation of perforation of the nasal septum determined the difficult path of differential diagnosis with Wegener’s granulomatosis. Morphological examination of the biopsy of the nasal mucosa revealed epithelioid cells of sarcoid-like granuloma. Systemic glucocorticosteroids use (GCS) led to epithelialization of the nasal septum defect and a decrease in the activity of CD in the intestine mucosa.

Rice straw returning enhances cadmium activation by accelerating iron cycling thus hydroxyl radical production in paddy soils during drainage

Straw returning is widely found elevating the bioavailability of cadmium (Cd) in paddy soils with unclear biogeochemical mechanisms. Here, a series of microcosm incubation experiments were conducted and spectroscopic and microscopic analyses were employed. The results showed that returning rice straw (RS) efficiently increased amorphous Fe and low crystalline Fe (II) to promote the production of hydroxyl radicals (OH) thus Cd availability in paddy soils during drainage. On the whole, RS increased OH and extractable Cd by 0.2–1.4 and 0.1–3.3 times, respectively. While the addition of RS effectively improved the oxidation rate of structural Fe (II) mineral (i.e., FeS) to enhance soil Cd activation (up to 38.5 %) induced by the increased OH (up to 69.2 %). Additionally, the existence of CO32− significantly increased the efficiency level on OH production and Cd activation, which was attributed to the improved reactivity of Fe (II) by CO32− in paddy soils. Conclusively, this study emphasizes risks of activating soil Cd induced by RS returning-derived OH, providing a new insight into evaluating the safety of straw recycling.

A226 NEUTROPHIL-TO-LYMPHOCYTE RATIO AT DIAGNOSIS PREDICTS COLONOSCOPIC ACTIVITY IN PEDIATRIC INFLAMMATORY BOWEL DISEASES (PIBD)

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has been recently identified as a potential biomarker for several autoimmune conditions. NLR predicts disease activity in adults with inflammatory bowel diseases (IBD) but had not been studied in pediatric IBD. Aims Investigate the link between NLR and baseline colonoscopic disease activity in UC and CD, the need for surgery or admission, and one-year therapy response in children. Methods Pediatric IBD patients were prospectively enrolled into the CIDsCaNN database [Canada-wide inception cohort for pediatric patients with IBD]. The cohort included patients diagnosed between 2003–2022 based on ileocolonoscopy, histopathology, and established diagnostic criteria. Patients were excluded if they had other conditions affecting NLR, such as neoplasms and autoimmune diseases. Endoscopic disease activity was assessed using the Mayo endoscopic score (MES; dichotomized as low (0, 1) or high activity (2, 3)) in UC and SES-CD score (as continuous variable) in CD. Logistic regression was used to test the link between predictors and binary outcomes. Simple linear regression was used to analyze the relationship between continuous variables. Results 576 UC and 1076 CD patients ampersand:003C18 years old were included. In UC, baseline NLR was significantly associated with baseline MES in univariate and multivariable logistic regression (multivariable OR= 1.5, 95% CI= 1.1–1.99, p= 0.019; Table). Patients with high-activity MES have significantly higher neutrophils (p= 0.0003), but lymphocytes wasn't different between the two groups. In CD, NLR was significantly correlated with SES-CD score in univariate and multivariable simple linear regression (multivariable coefficient= 1.4, 95% CI= 0.7–2.2, pampersand:003C0.0001; Fig1). Additionally, NLR predicted biologic-free remission in the CD cohort only in univariate analysis. NLR did not predict other the need for admission or surgery either in UC or CD. Conclusions Pediatric IBD patients with higher baseline NLR had a higher endoscopic disease activity. This establishes the significance of NLR as a non-invasive biomarker to help direct clinical decision making. This association suggests a role for neutrophils, as innate immunity cells in the acute stage of inflammation. Multivariable logistic regression of the relation between baseline labs in pediatric UC and Mayo endoscopic score Scatter plot demonstrating the relationship between baseline NLR and baseline SES-CD score Funding Agencies C.H.I.L.D.

A264 IDENTIFYING CLINICAL PREDICTORS FOR SUCCESS OF EXCLUSIVE ENTERAL NUTRITION INDUCTION THERAPY IN PEDIATRIC CROHN DISEASE

Abstract Background Current treatments for IBD focus on reducing inflammation, mostly through suppression of the immune system. Exclusive enteral nutrition (EEN) is recognized as the first line therapy for mild-to-moderate luminal pediatric Crohn disease patients pCD. Although EEN is safe, as it does not suppress the immune system, it poses considerable challenges to patients, mostly due to palatability and monotony of the formula and treatment costs. Moreover, the efficacy of EEN varies greatly from patient to patient. Therefore, there is a need to distinguish between responders and non-responder patients. Aims Identify clinical features associated with efficacy of EEN induction therapy and apply machine learning to build a classifier to identify EEN non-responders. Methods The Canadian Children Inflammatory Bowel Disease Network prospectively enrolled and followed new onset pediatric IBD cases. Prospective data for 308 pCD with EEN as their first treatment for CD are available. Patients with weighted Pediatric CD Activity Indexes (wPCDAI) collected after at least 4 weeks on EEN were compiled into a dataset (n=108). For this analysis, treatment response was defined as a wPCDAI reduction of at least 12.5 points of a patient’s wPCDAI baseline score. The dataset includes 26 features for each of the 108 pCD patients at time of diagnosis. This included blood test results (Hgb, ESR, CRP, Alb, Htc, Plt), Paris Classifications, height, and weight Z-scores, as well as wPCDAI, SES-CD (simple endoscopic score, CD), PGA (physician global assessment), and Mayo scores. Odds ratios were calculated to determine whether any features were associated with response to EEN induction therapy. Then, the most relevant features were identified with regularization techniques and a machine learning classifier for predicting response to EEN was built. Results Results showed that the appropriate subset of features to include for optimal accuracy over model simplicity are n=4 (PUCAI, PGA, SES-CD scores, and hematocrit). Also, an increase in PGA score (e.g., moving from “mild disease” to “moderate disease”) was associated with an increase in the chance of EEN failure (OR 3.1, 95% CI [1.7,5.8], p=0.0001). The best classifier for predicting EEN response was a random forest consisting of 20 decision trees. The classifier achieved an area under the ROC curve of 0.75 ± 0.07 Conclusions Our results suggest that it is possible to produce a classifier capable of predicting EEN clinical remission with an accuracy over 60%. Higher PGA, PUCAI, and SES-CD scores show potential for predicting patients less likely to respond to EEN induction. This research has the potential to provide better quality of life for children who live with IBD. Funding Agencies CIHRIMAGINE SPOR Network , Women and Children's Health Research Institute

Mobilization of Cadmium and Arsenic During Anoxic-Oxic Alteration in Paddy Soils: A Vital Role of Manganese

ABSTRACT Flooding and drainage of paddy fields can induce the activation of soil cadmium (Cd)/arsenic (As), which will accumulate in rice grains and threaten human health. Mn oxides influence soil Cd and As availability, but few detailed studies have been reported on how Mn redox simultaneously affects Cd and As mobility during flooding and drainage. Two paddy soils with various Mn contents were incubated under three redox conditions, namely 30-d reduction, 30-d oxidation and 20-d reduction subsequent with 10-d oxidation, to investigate Cd and As migration. During reduction, the soil abundant in native Mn oxides possessed more high-valence Mn oxides, which promoted As oxidation and retarded the reductive dissolution of Fe (oxyhydro)oxides, thereby decreasing As mobility. Cd mobility mainly depended on the conversion between Fe-Mn oxides-bound Cd and exchangeable Cd. The high Mn content was conducive to decreasing Cd mobilization. Furthermore, the oxidation of As in soils was linked with a Fenton-like effect. The generated hydroxyl radicals (•OH) decreased with oxidation and the oxidation of Mn(II) by •OH inhibited As migration but promoted Cd activation. In summary, the mobility of Cd and As was lower in Mn rich soils, which may involve the immobilization, oxidation and catalytic effects of Mn oxides.

NON-INVASIVE DETERMINATION OF DISEASE ACTIVITY IN CROHN’S DISEASE BY SERUM LUMINEX PROFILING

Abstract BACKGROUND &amp; AIMS Crohn’s disease (CD) is a chronic inflammatory disease with a complex pathogenesis; treatment and management largely depend on disease activity assessment, which can be challenging and invasive. The aim of this study was to assess the ability of multiplex Luminex technology to identify serum cytokine and/or chemokine markers of disease activity. METHODS Serum samples were prospectively obtained from 103 CD and 40 healthy controls undergoing colonoscopy. CD activity was determined by histologic assessment of colonoscopic biopsies. The Simple Endoscopic Score for Crohn’s Disease (SES) was available for 94 CD patients. We determined if the SES score was predictive of histologic activity (normal, quiescent, mild, moderate, or severe). Patient demographics and clinical history were obtained by chart review. Serum cytokines and chemokines were measured by a 47-plex Luminex assay. Analytes that had more than 70% of values below the lower limit of detection were excluded (GMCSF, IL3, IL17A, IL22, and TNFβ). Analyte profiles in controls v. CD patients were compared using the Mann-Whitney U test with Benjamini-Hochberg (BH) adjustment given multiple comparisons, and by disease activity (control v. inactive v. active) using the Kruskal-Wallis test, with post-hoc Dunn’s test with BH adjustment. RESULTS 34 CD patients were inactive (normal, quiescent) and 69 CD patients had active disease (mild, moderate, severe) on histology. Use of steroids, immunomodulators, and biologics did not differ significantly between the active and inactive CD groups. There was a strong positive correlation between SES score and histologic disease severity (Spearman’s r = 0.58, p&amp;lt;0.001). After BH adjustment, 16 analytes were significantly increased in CD v. controls: Fractalkine, GROα, IFNα2, IL1β, IL4, IL6, IL10, IL13, IL25, IL17F, IL18, MCP3, MCSF, PDGFAA, PDGFABBB, and TGFα. As shown in Table 1, when categorized by disease activity, 4 analytes were significantly increased and one analyte was significantly decreased in inactive disease v. control; 18 analytes were significantly increased in active v. control; and one analyte, CXCL9, which attracts effector T cells to sites of inflammation, was significantly increased in active v. inactive disease. CONCLUSIONS In CD patients, 16 of 42 serum cytokines and chemokines detectable by Luminex assay were increased v. healthy controls. When stratified by histologic disease activity, multiple analytes were found to be increased in inactive or active CD v. controls. Thus, CD is associated with alterations in serum cytokines and chemokines, which was much more frequent in CD patients with histologically active disease. Serum cytokine/chemokine profiling may be a non-invasive strategy to reduce the need for frequent colonoscopy in CD to assess disease activity. Table 1 Serum analyte profiles compared by disease activity (control v. inactive v. active). Data are shown in pg/mL as mean ± SD. p-values are calculated using Kruskal-Wallis test with post-hoc Dunn’s test with BH adjustment for multiple comparisons where 0.05 was considered significant. *p

P454 Systemic free thiols associate with clinical and biochemical disease activity in Inflammatory Bowel Disease: a prospective diagnostic validation study

Abstract Background In the pathophysiology of inflammatory bowel diseases (IBD), oxidative stress plays an important role. Lower levels of plasma free thiols (FT) reflect a higher oxidative stress burden and correlate with IBD disease activity. However, their clinical significance as biomarker for disease activity remains unclear. This study aimed to prospectively validate the utility of plasma FT levels as biomarker for clinical, biochemical, and endoscopic disease activity in patients with IBD. Methods In an ongoing prospective diagnostic trial aiming to include 100 IBD patients, we conducted an interim analysis of plasma FT levels in 52 patients with IBD (24 Crohn's disease [CD], 21 ulcerative colitis [UC], and 7 patients with undetermined IBD). Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and faecal calprotectin [fCal]). Endoscopic disease activity was quantified with the Mayo endoscopic subscore for UC and the Simple Endoscopic Score (SES-CD) for CD. Plasma FT levels were assessed for correlations with disease activity parameters using linear and logistic regressions models. Discriminative capacity of biomarkers was evaluated through calculating receiver operating characteristics (ROC) statistics. Results Plasma FT levels were significantly negatively correlated in clinical parameters, like HBI (r = -0.53, p &amp;lt; 0.05) (Fig. 1A). Other inflammatory biomarkers, like CRP, were also negatively correlated with plasma FT levels and were reduced in patients with active IBD (r = -0.43, p &amp;lt; 0.05) (Fig. 1B). Plasma FT levels accurately discriminated between CD patients with clinically quiescent (HBI &amp;lt; 5) and active disease (HBI ≥ 5) (AUC = 0.80, p = 0.02, Fig. 1C), better than fCal (AUC = 0.55, p = 0.83). Plasma FT were not significantly different for biochemically quiescent (CRP &amp;lt; 5 mg/l) and active (CRP ≥ 5mg/l) disease (AUC = 0.69, p = 0.20, Fig. 1D). Both Mayo and SES-CD scores, after adjusting for confounders, also exhibited a trend towards negative association with plasma FT levels (Fig. 1E). Figure 1 Conclusion Further completion of the trial will reveal whether systemic FT levels will reflect endoscopically observed disease activity, and this interim analysis shows strong correlations FT levels and parameters of clinically and biochemically active disease. Measuring systemic FTs in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity. Funding None

P207 It’s time to include capsule endoscopy to assess mucosal activity as part of the ‘treat-to-target’ strategy in Crohn’s disease: a real-life experience from a reference center in Argentina

Abstract Background The evaluation of the small bowel (SB) in known Crohn’s disease (kCD) has a significant impact on prognosis with potential therapeutic implications. The treat-to-target strategy is widely accepted, emphasizing that endoscopic healing is associated with improved long-term outcomes. Although capsule endoscopy (CE) shows promise in monitoring the small bowel in kCD, there is limited evidence supporting routine use. The aim of this study was to investigate clinical utility of CE to assess activity and extension of kCD and to evaluate whether the results of CE modify the therapeutic decisions. Methods We conducted a single center retrospective cohort study. Adult patients submitted to CE for kCD from Nov-2012 to Nov-2023 were included. Data on demography, previous research, medications for IBD and follow-up were analyzed. Univariate analysis was carried out to identify CE features associated with changes in therapeutic management. A p value &amp;lt;0.05 was considered statistically significant. Results A total of 572 CE protocols were performed, of which 76 were in kCD adult patients. The mean age was 36 years (range 16–76), 59% were males and median disease duration was 5.4 years. The CE reached the cecum in 97% and retention was observed in only two patients (2.6%) without necessity of surgical removal. Thirty two of 76 CE protocols (42%) had findings consistent with mucosal activity of CD. The lesions identified by CE included ulcers 30 (39%), erythema and villous edema 21 (28%), stenosis 2 (3%) and were distributed mainly in the distal part of the SB (3rd tertile) in 27 (35%), but in 15 (20%) the proximal SB (1st and 2nd tertile) was also affected. The mean Lewis Score (LS) was 576 (135-5392). Normal or clinically insignificant inflammatory changes (LS &amp;lt;135) ruled out SB mucosal activity in 44 (58%) patients. The results of the CE modified therapeutic decisions in 29 (38%) patients as follows: 17 were started new biological therapy and 7 were optimized. CEs consistent with mucosal inflammatory activity (LS ≥135) were more frequently associated with changes in therapeutic management (OR: 11, 95% CI 4-35, p: 0.04). When both magnetic resonance enterography (MRE) and CE were utilized to assess SB mucosal activity, diagnostic yields of MRE and CE were 45% and 42% respectively. But of the 8 patients with proximal SB affected in CE, only 1 showed inflammatory activity in the MRE. Conclusion In our cohort, CE in patients with kCD added valuable clinical information and had a great impact on therapeutic decisions. These results suggest that CE could be incorporated into the treat-to-target strategy for patients with CD. However, randomized controlled trials are required to confirm this recommendation.

P864 The Effect of Ustekinumab on Mucosal Inflammation in Paediatric Crohn’s Disease: The REALITI Real-World Evidence Effectiveness Study

Abstract Background Crohn's disease (CD) research using real world evidence (RWE) has been hampered by lack of validated endoscopic outcome measures. The recently validated Simplified Endoscopic Mucosal Assessment of CD (SEMA-CD) provides a reliable way to evaluate mucosal inflammation in paediatric CD patients (pts), making it suitable for use in clinical practice and relevant to real world data. REALITI is a RWE study of the effectiveness and safety of ustekinumab (UST) in paediatric pts. Methods REALITI used data from pts with CD in the ImproveCareNow (ICN) registry. Colonoscopy reports (reports) from 2010-2020 identified by chart review were redacted and uploaded to the registry. Central endoscopy readers underwent SEMA-CD training and were randomly assigned to score reports. No reader reviewed reports from their own institution. Three readers independently scored reports blinded to each other’s scores and to clinical information. Demographic and clinical data, prospectively recorded in ICN, were summarized and compared between pts with and without endoscopy. Clinical remission was defined as Short Paediatric CD Activity Index (sPCDAI) ≤10 and endoscopic remission as SEMA-CD ≤1. Results Analyses of mucosal inflammation by SEMA-CD in 114 pts age 2 to &amp;lt;18 yr with moderate-severe CD (sPCDAI ≥30) and body weight ≥40 kg at UST initiation (baseline) and after 52 weeks (wk) of treatment are reported. Overall, 77/114 pt had ≥1 report during the study and 20 had a report at Wk 52. Baseline median age of all pts was 16 yr (interquartile range [IQR] 15-16). Pts with endoscopic assessments (N=77) vs pts without (N=37) were more often female (56% vs 41%) and had more ileocolonic disease activity (73% vs 54%), perianal disease (39% vs 35%), and stricturing phenotype (B2; 10% vs 5%), respectively. No pts had B2/B3 phenotype. At baseline, median sPCDAI for all pts was 40 (IQR 35-50; N=114) and median SEMA-CD was 8.5 (IQR 5-13; N=38). At Wk 52, 4/20 pts (20% [95% CI, 8.1%, 41.6%]) were in endoscopic remission. Despite small sample sizes, there appears to be lower clinical remission rates at Wk 52 in pts with baseline endoscopic assessments (17/77; 22.1% [95% CI, 14.3%, 32.5%]) vs without (10/37; 27.0% [95% CI, 15.4%, 43,0%). Conclusion Use of SEMA-CD to assess mucosal inflammation in paediatric pts with moderate-severe CD treated with UST demonstrated rates of endoscopic remission similar to clinical remission at Wk 52. Endoscopy was performed more often in sicker pts, with a greater proportion of pts who did not undergo endoscopy achieving clinical remission. Future routine SEMA-CD assessment of mucosal inflammation in clinical practice may improve analyses in observational and retrospective studies.

P660 Serum Leucine-rich Alpha-2 Glycoprotein Can be a Biomarker for Selecting Anti-Cytokine Biologics in Patients with Inflammatory Bowel Disease: A Multicentre Prospective Cohort Study

Abstract Background Serum leucine-rich alpha-2 glycoprotein (LRG) is a biomarker reflecting endoscopic activity in patients with inflammatory bowel disease (IBD). However, it remains unclear whether serum LRG can predict the effectiveness of anti-cytokine biologics (biologics) in patients with IBD. This study aimed to evaluate whether serum LRG could predict the effectiveness and serum trough concentrations of biologics in patients with IBD. Methods This was a multicentre prospective cohort study including patients with IBD (including ulcerative colitis [UC] or Crohn’s disease [CD]) who received the biologics [ustekinumab (UST), anti-tumor necrosis factor (anti-TNF)] from January 2019 to March 2023 at 15 hospitals participating in the Osaka Gut Forum. The effectiveness of biologics was evaluated by clinical remission (CR) at week 8. We defined CR as a partial Mayo score of 2 or lower, with each subscore of 0 or 1 for UC and a CD activity index of &amp;lt; 150 for CD. Factors associated with CR at week 8 such as backgrounds, disease activities and concomitant medications at week 0 were analyzed by Cox proportional hazards model. For each biologic, we compared the effectiveness of biologics in the high LRG group with that in the low LRG group divided by the median serum LRG levels at week 0 (cut-off = 18.2 μg/mL). Results A total of 184 patients with IBD (UC, 80; CD, 104) were enrolled (UST/ anti-TNF, 119/ 65; biologic exposure, 31.5%; median disease duration, 6 years [Interquartile range (IQR) 1-14]). Median serum LRG levels at week 0 and serum C-reactive protein levels at week 0 were 18.2 μg/mL [IQR 12.5-28.1] and 0.19 mg/dL [IQR 0.03-0.77], respectively. At week 0, 63 (34.2%) and 64 (34.8%) patients concomitantly received corticosteroids and immunomodulators, respectively. In 184 patients with IBD, multivariate analysis revealed that serum LRG level at week 0 &amp;lt; 18.2 μg/mL was extracted as a significant factor for CR at week 8 (Odds ratio: OR 2.70, 95% confidence interval: CI 1.22-5.96). In patients who received UST, the proportion of CR at week 8 in the low-LRG group (76.9%) was significantly higher than that in the high-LRG group (59.3%, P = 0.038). In patients who received anti-TNF, however, the proportion of CR in the low-LRG group (84.6%) was not differ from that in the high-LRG group (82.1%, P = 0.781). Median serum trough concentrations of UST at week 8 in the low-LRG group (10.9 μg/mL, IQR 6.7-13.4) was significantly higher than that in the high-LRG group (5.3 μg/mL, IQR 2.4-8.3, P &amp;lt; 0.001). Conclusion Serum LRG could predict the effectiveness and serum trough concentrations of UST and be a biomarker for selecting biologics in patients with IBD.

Effect and mechanisms of soil functional groups in bacterial-enhanced cadmium contaminated soil phytoremediation

Considering the detrimental impact of heavy metals on agricultural soils, in situ remediation technology has gained considerable attention worldwide. Green materials have emerged as a promising option for enhancing plant-mediated remediation of contaminated soils. In this study, bacteria capable of mobilising cadmium (Cd) and promoting plant growth were screened and isolated. A synergistic system was established by combining bone meal and chitosan as soil amendments with the Cd-mobilising bacteria to improve the extraction of available Cd from soils by plants. The highest Cd accumulation was observed in the bone meal + bacteria, which increased by 131.81% when compared to the control group (CK). The highest available Cd content was observed in the chitosan + bacteria, which increased by 52.31% when compared to CK. Fourier-transform infra-red spectroscopy and X-ray photoelectron spectroscopy results revealed that organic compounds, such as hydroxyl and carboxyl groups, and aliphatic compounds in the soil were crucial in mobilising Cd. Cd activation occurred through substitution of protons in the functional groups and chelation, leading to the formation of chelates with Cd2+ and in turn, facilitating Cd mobilisation in the soil. The incorporation of bone meal and chitosan into phytoremediation strategies can enhance the ability of bacteria to mobilise Cd, thereby increasing the effectiveness of phytoremediation.