Histone deacetylases facilitate Th17-cell differentiation and pathogenicity in autoimmune uveitis via CDK6/ID2 axis.

INTRODUCTION: Autoimmune uveitis (AU) is a prevalent ocular autoimmune disease leading to significant visual impairment. However, underlying pathogenesis of AU required to develop more efficient therapy remain unclear. METHODS: We isolated peripheral blood mononuclear cells (PBMCs) from AU patients and performed single-cell RNA sequencing (scRNA-seq). Besides, experimental autoimmune uveitis (EAU) model was established and treated with histone deacetylase inhibitor (HDACi) Belinostat or vehicle. We extracted immune cells from Blank, EAU, and HDACi-treated EAU mice and used scRNA-seq, flow cytometry, siRNA, specific inhibitors, and adoptive transfer experiments to explore the role of HDACs and its downstream potential molecular mechanisms in the immune response of EAU and AU. RESULTS: We found highly expressed histone deacetylases (HDACs) family in AU patients and identified it as a key factor related to CD4+ effector T cell differentiation in the pathogenesis of AU. Our further studies showed that targeted inhibition of HDACs effectively alleviated EAU, restored its Th17/Treg balance, and reduced inflammatory gene expression, especially in CD4+ T cells. Post-HDACs inhibition, Treg proportions increased with enhanced immunomodulatory effects. Importantly, HDACs exhibited a positive promoting role on Th17 cells. Based on scRNA-seq screening and application of knock-down siRNAs and specific inhibitors in vitro and vivo, we identified CDK6 as a key downstream molecule regulated by HDAC1/3/6 through acetyl-histone H3/p53/p21 axis, which is involved in Th17 pathogenicity and EAU development. Additionally, HDACs-regulated CDK6 formed a positive loop with ID2, inducing PIM1 upregulation, promoting Th17 cell differentiation and pathogenicity, and correlates with AU progression. CONCLUSION: Based on the screening of clinical samples and downstream molecular functional validation experiments, we revealed a driving role for HDACs and the HDACs-regulated CDK6/ID2 axis in Th17 cell differentiation and pathogenicity in AU, proposing a promising therapeutic strategy.

Strong Covalent Coupling in Vertically Layered SnSe2/PTAA Heterojunctions Enabled High Performance Inorganic-Organic Hybrid Photodetectors.

Controllable large-scale integration of two-dimensional (2D) materials with organic semiconductors and the realization of strong coupling between them still remain challenging. Herein, we demonstrate a wafer-scale, vertically layered SnSe2/PTAA heterojunction array with high light-trapping ability via a low-temperature molecular beam epitaxy method and a facile spin-coating process. Conductive probe atomic force microscopy (CP-AFM) measurements reveal strong rectification and photoresponse behavior in the individual SnSe2 nanosheet/PTAA heterojunction. Theoretical analysis demonstrates that vertically layered SnSe2/PTAA heterojunctions exhibit stronger C-Se covalent coupling than that of the conventional tiled type, which could facilitate more efficient charge transfer. Benefiting from these advantages, the SnSe2/PTAA heterojunction photodetectors with an optimized PTAA concentration show high performance, including a responsivity of 41.02 A/W, an external quantum efficiency of 1.31 × 104%, and high uniformity. The proposed approach for constructing large-scale 2D inorganic-organic heterostructures represents an effective route to fabricate high-performance broadband photodetectors for integrated optoelectronic systems.

Recent advances in spoilage mechanisms and preservation technologies in beef quality: A review.

Beef is a popular meat product that can spoil and lose quality during postharvest handling and storage. This review examines different preservation methods for beef, from conventional techniques like low-temperature preservation, irradiation, vacuum packing, and chemical preservatives, to novel approaches like bacteriocin, essential oil, and non-thermal technologies. It also discusses how these methods work and affect beef quality. The review shows that beef spoilage is mainly due to enzymatic and microbial activities that impact beef freshness, texture, and quality. Although traditional preservation methods can extend beef shelf life, they have some drawbacks and limitations. Therefore, innovative preservation methods have been created and tested to improve beef quality and safety. These methods have promising results and potential applications in the beef industry. However, more research is needed to overcome the challenges and barriers for their commercialization. This review gives a comprehensive and critical overview of the current and emerging preservation methods for beef and their implications for the beef supply chain.

High-sensitivity, ultrawide linear range, antibacterial textile pressure sensor based on chitosan/MXene hierarchical architecture.

It is still a great challenge for the flexible piezoresistive pressure sensors to simultaneously achieve wide linearity and high sensitivity. Herein, we propose a high-performance textile pressure sensor based on chitosan (CTS)/MXene fiber. The hierarchical "point to line" architecture enables the pressure sensor with high sensitivity of 1.16 kPa-1 over an ultrawide linear range of 1.5 MPa. Furthermore, the CTS/MXene pressure sensor possesses a low fatigue over 1000 loading/unloading cycles under 1.5 MPa pressure load, attributed to the strong chemical bonding between CTS fiber and MXene and excellent mechanical stability. Besides, the proposed sensor shows good antibacterial effect benefiting from the strong interaction between polycationic structure of CTS/MXene and the predominantly anionic components of bacteria surface. The sensor is also applied to detect real-time human action, an overall classification accuracy of 98.61% based on deep neural network-convolutional neural network (CNN) for six human actions is realized.

Reducing brain Aß burden ameliorates high-fat diet-induced fatty liver disease in APP/PS1 mice.

High-fat diet (HFD)-induced fatty liver disease is a deteriorating risk factor for Alzheimer's disease (AD). Mitigating fatty liver disease has been shown to attenuate AD-like pathology in animal models. However, it remains unclear whether enhancing Aß clearance through immunotherapy would in turn attenuate HFD-induced fatty liver or whether its efficacy would be compromised by long-term exposure to HFD. Here, the therapeutic potentials of an anti-Aß antibody, NP106, was investigated in APP/PS1 mice by HFD feeding for 44 weeks. The data demonstrate that NP106 treatment effectively reduced Aß burden and pro-inflammatory cytokines in HFD-fed APP/PS1 mice and ameliorated HFD-aggravated cognitive impairments during the final 18 weeks of the study. The rejuvenating characteristics of microglia were evident in APP/PS1 mice with NP106 treatment, namely enhanced microglial Aß phagocytosis and attenuated microglial lipid accumulation, which may explain the benefits of NP106. Surprisingly, NP106 also reduced HFD-induced hyperglycemia, fatty liver, liver fibrosis, and hepatic lipids, concomitant with modifications in the expressions of genes involved in hepatic lipogenesis and fatty acid oxidation. The data further reveal that brain Aß burden and behavioral deficits were positively correlated with the severity of fatty liver disease and fasting serum glucose levels. In conclusion, our study shows for the first time that anti-Aß immunotherapy using NP106, which alleviates AD-like disorders in APP/PS1 mice, ameliorates fatty liver disease. Minimizing AD-related pathology and symptoms may reduce the vicious interplay between central AD and peripheral fatty liver disease, thereby highlighting the importance of developing AD therapies from a systemic disease perspective.

Kurarinone regulates Th17/Treg balance and ameliorates autoimmune uveitis via Rac1 inhibition.

INTRODUCTION: Autoimmune uveitis (AU) is a severe intraocular autoimmune disorder with a chronic disease course and a high rate of blindness. Kurarinone (KU), a major component of the traditional Chinese medicine Sophorae Flavescentis Radix, possesses a wide spectrum of activities and has been used to treat several inflammation-related diseases. OBJECTIVE: We aimed to investigate the effects of KU on AU and its modulatory mechanisms. METHODS: We used an experimental autoimmune uveitis (EAU) animal model and characterized the comprehensive immune landscape of KU-treated EAU mice using single-cell RNA sequencing (scRNA-seq). The retina and lymph nodes were analyzed. The siRNAs and selective inhibitors were used to study the signaling pathway. The effect of KU on peripheral blood mononuclear cells (PBMCs) from uveitis patients was also examined. RESULTS: We found that KU relieved chorioretinal lesions and immune cell infiltration in EAU model mice. Subsequent single-cell analysis revealed that KU downregulated the EAU-upregulated expression of inflammatory and autoimmune-related genes and suppressed pathways associated with immune cell differentiation, activation, and migration in a cell-specific manner. KU was implicated in restoring T helper 17 (Th17)/regulatory T (Treg) cell balance by alleviating inflammatory injury and elevating the expression of modulatory mediators in Tregs, while simultaneously ameliorating excessive inflammation by Th17 cells. Furthermore, Rac1 and the Id2/Pim1 axis potentiated the pathogenicity of Th17 cells during EAU, which was inhibited by KU treatment, contributing to the amelioration of EAU-induced inflammation and treatment of AU. In addition, KU suppressed inflammatory cytokine production in activated human PBMCs by inhibiting Rac1. Integration of the glucocorticoid-treated transcriptome suggests that KU has immunomodulatory effects on lymphocytes. CONCLUSION: Our study constructed a high-resolution atlas of the immunoregulatory effects of KU treatment on EAU and identified its potential therapeutic mechanisms, which hold great promise in treating autoimmune disorders.

An Association Between Pediatric Bronchiolitis and Atopic Dermatitis: A Multi-Institutional Electronic Medical Records Database Study From Taiwan.

Atopic dermatitis (AD) is triggered by many environmental factors. We sought to determine the relationship between birth weight, infectious diseases, and AD. This retrospective cohort study analyzed data from the CGR Database for the period 2004 through 2015 in Taiwan. All diseases were classified using the International Classification of Disease codes. Logistic regression adjusted for birth weights and comorbidities were analyzed by SAS (version 9.4). P < .05 were considered statistically significant. In children with AD, bronchiolitis was significantly associated with the development of AD, whether the patients were aged < 2 years (odds ratio [OR] = 1.497; P = .014) or ≥ 2 years (OR = 1.882; P = .022). There was also no difference in the association between AD and different birth weights. We conclude that AD is associated with a previous history of bronchiolitis in children, regardless of age (less than or greater than 2 years).

Conformal Human-Machine Integration Using Highly Bending-Insensitive, Unpixelated, and Waterproof Epidermal Electronics Toward Metaverse.

Efficient and flexible interactions require precisely converting human intentions into computer-recognizable signals, which is critical to the breakthrough development of metaverse. Interactive electronics face common dilemmas, which realize high-precision and stable touch detection but are rigid, bulky, and thick or achieve high flexibility to wear but lose precision. Here, we construct highly bending-insensitive, unpixelated, and waterproof epidermal interfaces (BUW epidermal interfaces) and demonstrate their interactive applications of conformal human-machine integration. The BUW epidermal interface based on the addressable electrical contact structure exhibits high-precision and stable touch detection, high flexibility, rapid response time, excellent stability, and versatile "cut-and-paste" character. Regardless of whether being flat or bent, the BUW epidermal interface can be conformally attached to the human skin for real-time, comfortable, and unrestrained interactions. This research provides promising insight into the functional composite and structural design strategies for developing epidermal electronics, which offers a new technology route and may further broaden human-machine interactions toward metaverse.

Risk factors for osteoporosis in chronic schizophrenia on long-term treatment with antipsychotics: a cross-sectional study.

BACKGROUND: Little is known about the laboratory variable risks with bone mineral density (BMD) in patients with schizophrenia. This study was designed to fully investigate the related risk factors for decreased BMD in schizophrenia, as well as evaluate the gender difference of BMD. METHOD: The BMD of the forearm of 211 patients (males/females = 140/71) who met the diagnostic criteria for DSM-5 schizophrenia was measured by dual-energy X-ray absorptiometry. Basic demographic information, clinical assessments, and laboratory variables (regarding nutrition, hormones, metabolism, and inflammatory markers) were comprehensively collected. RESULTS: Among 211 subjects, seventy-four (35%) patients had low BMD. Males had a significantly lower BMD T-score than females (P = 0.002). Multiple regression analyses showed that the independent risks with low BMD were lower folate, glycosylated hemoglobin levels, higher age, serum ferritin, and follicle-stimulating hormone (FSH) levels. In female patients, the BMD was mainly associated with age and serum hormones (FSH and testosterone), while the BMD of male patients was primarily related to age, microelements (serum ferritin and 25-OH-VD), and parathyroid hormone. CONCLUSION: Our study found several meaningful correlations between osteoporosis and schizophrenia, especially regarding laboratory measures, which may provide new clues to identifying or preventing osteoporosis in clinical patients.

Progesterone attenuates Th17-cell pathogenicity in autoimmune uveitis via Id2/Pim1 axis.

BACKGROUND: Autoimmune uveitis (AU) is the most common ophthalmic autoimmune disease (AD) and is characterized by a complex etiology, high morbidity, and high rate of blindness. AU remission has been observed in pregnant female patients. However, the effects of progesterone (PRG), a critical hormone for reproduction, on the treatment of AU and the regulatory mechanisms remain unclear. METHODS: To this end, we established experimental autoimmune uveitis (EAU) animal models and constructed a high-dimensional immune atlas of EAU-model mice undergoing PRG treatment to explore the underlying therapeutic mechanisms of PRG using single-cell RNA sequencing. RESULTS: We found that PRG ameliorated retinal lesions and inflammatory infiltration in EAU-model mice. Further single-cell analysis indicated that PRG reversed the EAU-induced expression of inflammatory genes (AP-1 family, S100a family, and Cxcr4) and pathological processes related to inflammatory cell migration, activation, and differentiation. Notably, PRG was found to regulate the Th17/Treg imbalance by increasing the reduced regulatory functional mediators of Tregs and diminishing the overactivation of pathological Th17 cells. Moreover, the Id2/Pim1 axis, IL-23/Th17/GM-CSF signaling, and enhanced Th17 pathogenicity during EAU were reversed by PRG treatment, resulting in the alleviation of EAU inflammation and treatment of AD. CONCLUSIONS: Our study provides a comprehensive single-cell map of the immunomodulatory effects of PRG therapy on EAU and elaborates on the possible therapeutic mechanisms, providing novel insights into its application for treating autoimmune diseases.

Sleep loss potentiates Th17-cell pathogenicity and promotes autoimmune uveitis.

BACKGROUND: Sleep loss (SL) is a health issue associated with the higher risk of autoimmune and inflammatory disorders. However, the connection between SL, the immune system, and autoimmune diseases remains unknown. METHODS: We conducted mass cytometry, single-cell RNA sequencing, and flow cytometry to analyze how SL influences immune system and autoimmune disease development. Peripheral blood mononuclear cells from six healthy subjects before and after SL were collected and analyzed by mass cytometry experiments and subsequent bioinformatic analysis to identify the effects of SL on human immune system. Sleep deprivation and experimental autoimmune uveitis (EAU) mice model were constructed, and scRNA-seq data from mice cervical draining lymph nodes were generated to explore how SL influences EAU development and related autoimmune responses. RESULTS: We found compositional and functional changes in human and mouse immune cells after SL, especially in effector CD4+ T and myeloid cells. SL upregulated serum GM-CSF levels in healthy individuals and in patients with SL-induced recurrent uveitis. Experiments in mice undergoing SL or EAU demonstrated that SL could aggravate autoimmune disorders by inducing pathological immune cell activation, upregulating inflammatory pathways, and promoting intercellular communication. Furthermore, we found that SL promoted Th17 differentiation, pathogenicity, and myeloid cells activation through the IL-23Th17GM-CSF feedback mechanism, thus promoting EAU development. Lastly, an anti-GM-CSF treatment rescued SL-induced EAU aggravation and pathological immune response. CONCLUSIONS: SL promoted Th17 cells pathogenicity and autoimmune uveitis development, especially through the interaction between Th17 and myeloid cells involving GM-CSF signaling, providing possible therapeutic targets for the SL-related pathological disorders.

Adaptive predefined-time prescribed performance control for spacecraft systems.

The high-accuracy attitude maneuvering problem for spacecraft systems is investigated. A prescribed performance function and a shifting function are first employed to ensure the predefined-time stability of attitude errors and eliminate the constraints on tracking errors at the incipient stage. Subsequently, a novel predefined-time control scheme is developed by combining prescribed performance control and backstepping control procedures. Radial basis function neural network and minimum learning parameter techniques are introduced to model the function of lumped uncertainty including inertial uncertainties, actuator faults and virtual control law derivatives. According to the rigorous stability analysis, the preset tracking precision can be achieved within a predefined time and the fixed-time boundedness of all closed-loop signals is established. Finally, the efficacy of the propounded control scheme is manifested through numerical simulation results.

Relapse in patients with schizophrenia and amisulpride-induced hyperprolactinemia or olanzapine-induced metabolic disturbance after switching to other antipsychotics.

Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.

Basal stem cell progeny establish their apical surface in a junctional niche during turnover of an adult barrier epithelium.

Barrier epithelial organs face the constant challenge of sealing the interior body from the external environment while simultaneously replacing the cells that contact this environment. New replacement cells-the progeny of basal stem cells-are born without barrier-forming structures such as a specialized apical membrane and occluding junctions. Here, we investigate how new progeny acquire barrier structures as they integrate into the intestinal epithelium of adult Drosophila. We find they gestate their future apical membrane in a sublumenal niche created by a transitional occluding junction that envelops the differentiating cell and enables it to form a deep, microvilli-lined apical pit. The transitional junction seals the pit from the intestinal lumen until differentiation-driven, basal-to-apical remodelling of the niche opens the pit and integrates the now-mature cell into the barrier. By coordinating junctional remodelling with terminal differentiation, stem cell progeny integrate into a functional, adult epithelium without jeopardizing barrier integrity.

Social support and quality of life among chronically homeless patients with schizophrenia.

This study aimed to describe the sociodemographic characteristics, social support received, and quality of life of chronically homeless patients with schizophrenia in China. A self-prepared sociodemographic questionnaire, the Social Support Rating Scale (SSRS), European Five-dimensional Health Scale (EQ-5D), and Eysenck Personality were administrated to 3,967 chronically homeless and 3,724 non-homeless patients from the Department of Xiangtan Fifth People's Hospital, Hunan, China, between April 2011 and October 2016. Results indicated that the homeless patients were more likely to live outside the city and be ethnic minorities compared with non-homeless patients. Although the married proportion was higher among homeless patients, they had a higher rate of being divorced or widowed. Notably, the homeless patients had higher employment rates before illness, despite significantly lower education (P < 0.001). Chronically homeless patients with schizophrenia showed a lower score in the SSRS (30.29 ± 7.34 vs. 26.16 ± 10.04, p < 0.001); they had significantly lower objective support, subject support, social support, and EQ-Visual Analog Scale, Eysenck Personality Questionnaire-Psychoticism, and Eysenck Personality-Neuroticism scores (p < 0.001). Homeless patients may be worse off, and could be assisted by providing accommodation, family intervention, medical services (such as pain medication), and other comprehensive measures.

JAK-STAT signaling pathway in non-infectious uveitis.

Non-infectious uveitis (NIU) refers to various intraocular inflammatory disorders responsible for severe visual loss. Cytokines participate in the regulation of ocular homeostasis and NIU pathological processes. Cytokine receptors transmit signals by activating Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins. Increasing evidence from human NIU and experimental models reveals the involvement of the JAK-STAT signaling pathway in NIU pathogenesis. Several small-molecule drugs that potentially inhibit multiple cytokine-dependent pathways are under investigation for treating autoimmune diseases, implicating possible applications for NIU treatment. This review summarizes the current understanding of the diverse roles of the JAK-STAT signaling pathway in ocular homeostasis and NIU pathology, providing a rationale for targeting JAKs and STATs for NIU treatment. Moreover, available evidence for the safety and efficacy of JAK inhibitors for refractory uveitis and potential approaches for treatment optimization are discussed.

Predictability effects and parafoveal processing of compound words in natural Chinese reading.

We report a boundary paradigm eye movement experiment to investigate whether the predictability of the second character of a two-character compound word affects how it is processed prior to direct fixation during reading. The boundary was positioned immediately prior to the second character of the target word, which itself was either predictable or unpredictable. The preview was either a pseudocharacter (nonsense preview) or an identity preview. We obtained clear preview effects in all conditions, but more importantly, skipping probability for the second character of the target word and the whole target word from pretarget was greater when it was predictable than when it was not predictable from the preceding context. Interactive effects for later measures on the whole target word (gaze duration and go-past time) were also obtained. These results demonstrate that predictability information from preceding sentential context and information regarding the likely identity of upcoming characters are used concurrently to constrain the nature of lexical processing during natural Chinese reading.

Sex Differences in Psychological Status and Fatigue of Frontline Staff After the COVID-19 Outbreak in China: A Cross-Sectional Study.

Background: The coronavirus disease 2019 (COVID-19) is spreading globally, and it is significant to pay attention to the mental health of frontline staff in this pandemic. This study is aimed to explore the sex difference among the frontline staff in demographics, characteristics of mental state, and the potential relationship between them. Method: A total of 2,614 Chinese frontline staff were recruited. The Self-Rating Anxiety Scale (SAS) and the Patient Health Questionnaire-9 (PHQ-9) were used for assessing the mental status of frontline staff, and the Fatigue Self-Assessment Scale (FSAS) was used for detecting fatigue. Result: The prevalence rate of anxiety for female frontline staff is higher than that of male (P = 0.003), and the prevalence rate of depression is similar between them (P = 0.091). After comparing the risk factors of unhealthy mental state between different sexes, it is found that family income below 100,000 [depression: odds ratio (OR) 1.37; 95% CI, 1.08-1.73; anxiety: OR 1.99; 95% CI, 1.44-2.75], unsupported of family (depression: OR 10.94; 95% CI, 1.39-85.79; anxiety: OR 11.92; 95% CI, 3.80-37.36), and marriage (depression: OR 1.67; 95% CI, 1.15-2.43) are risk factors for male, and total fatigue (depression: OR 2.96; 95% CI, 1.46-6.02) is risk factor for female. Conclusions: This study found that depression and anxiety are widespread among the frontline staff of COVID-19, and anxiety showed a higher prevalence rate among female frontline staff. From the sex difference in risk factors, the focus of psychological interventions may differ between genders. Men with low family income, unsupported by family or marriage, and women with a high score of total fatigue required particular attention to their psychological status.

Prealbumin and Retinol-Binding Protein 4: The Promising Inflammatory Biomarkers for Identifying Endoscopic Remission in Crohn's Disease.

OBJECTIVE: Endoscopic remission is the primary therapeutic target and associated with clinical outcome in Crohn's disease (CD). Non-invasive and accurate biomarkers are important in monitoring endoscopic remission frequently. Our study aimed at investigating the predictive capacity of prealbumin and retinol-binding protein 4 (RBP4) for identifying endoscopic remission. METHODS: From June 2018 to December 2020, 515 endoscopy procedures (332 in the training cohort and 183 in the validation cohort) were enrolled in this multicentre retrospective cohort study. Blood samples were collected for prealbumin or RBP4 testing with 7 days before the endoscopy. A simple Endoscopic Score for CD (SES-CD) was performed to evaluate endoscopic activity and defined endoscopic remission. The area under receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value and negative predictive value were performed to assess the predictive capacity of the biomarkers. RESULTS: Serum concentration of prealbumin and RBP4 was demonstrated to be higher in patients with endoscopic remission and significantly negatively correlated with SES-CD in the training cohort. The AUROC of prealbumin and specificity of prealbumin and RBP4 were larger than that of C-reactive protein in the training cohort and the validation cohort. The model combining prealbumin and faecal calprotectin had the largest AUROC (0.842 [95% CI: 0.775-0.908]). Furthermore, in both cohorts, prealbumin had a larger AUROC than C-reactive protein for identifying endoscopic remission in patients with anti-tumour necrosis factor therapy. CONCLUSION: Prealbumin and RBP4 were promising biomarkers for identifying endoscopic remission, especially in patients with anti-tumour necrosis factor therapy.