Modelling the impact of precaution on disease dynamics and its evolution.

In this paper, we introduce the notion of practically susceptible population, which is a fraction of the biologically susceptible population. Assuming that the fraction depends on the severity of the epidemic and the public's level of precaution (as a response of the public to the epidemic), we propose a general framework model with the response level evolving with the epidemic. We firstly verify the well-posedness and confirm the disease's eventual vanishing for the framework model under the assumption that the basic reproduction number R 0 < 1 . For R 0 > 1 , we study how the behavioural response evolves with epidemics and how such an evolution impacts the disease dynamics. More specifically, when the precaution level is taken to be the instantaneous best response function in literature, we show that the endemic dynamic is convergence to the endemic equilibrium; while when the precaution level is the delayed best response, the endemic dynamic can be either convergence to the endemic equilibrium, or convergence to a positive periodic solution. Our derivation offers a justification/explanation for the best response used in some literature. By replacing "adopting the best response" with "adapting toward the best response", we also explore the adaptive long-term dynamics.

Enhancing Few-Shot Learning in Lightweight Models via Dual-Faceted Knowledge Distillation.

In recent computer vision research, the pursuit of improved classification performance often leads to the adoption of complex, large-scale models. However, the actual deployment of such extensive models poses significant challenges in environments constrained by limited computing power and storage capacity. Consequently, this study is dedicated to addressing these challenges by focusing on innovative methods that enhance the classification performance of lightweight models. We propose a novel method to compress the knowledge learned by a large model into a lightweight one so that the latter can also achieve good performance in few-shot classification tasks. Specifically, we propose a dual-faceted knowledge distillation strategy that combines output-based and intermediate feature-based methods. The output-based method concentrates on distilling knowledge related to base class labels, while the intermediate feature-based approach, augmented by feature error distribution calibration, tackles the potential non-Gaussian nature of feature deviations, thereby boosting the effectiveness of knowledge transfer. Experiments conducted on MiniImageNet, CIFAR-FS, and CUB datasets demonstrate the superior performance of our method over state-of-the-art lightweight models, particularly in five-way one-shot and five-way five-shot tasks.

Macular and peripapillary Choroidal Vascularity Index in children with different refractive status.

OBJECTIVES: To characterize choroidal vascular changes in children with different refractive status. METHODS: A study including 5864 children aged 6-9 years was performed to investigate the choroidal vascular index (CVI) in myopic, emmetropic and hyperopic eyes. Each participant had a comprehensive ocular examination with cycloplegic autorefraction performed, axial length (AL) measured and Swept Source-Optical Coherence Tomography (SS-OCT) scans acquired. Choroidal thickness (ChT) was measured by built-in software, and CVI was calculated using a previously validated self-developed algorithm. RESULTS: The mean ChT and CVI were 275.88 ± 53.34 µm and 34.91 ± 3.83 in the macula region, and 191.96 ± 46.28 µm and 32.35 ± 4.21 in the peripapillary region. CVI was significantly lowest for myopes, followed by emmetropes and hyperopes (P < 0.001). CVI varied between different sectors separated by the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid (P < 0.001). Macular CVI decreased horizontally from nasal to temporal quadrant with lowest in center fovea, and vertically from superior to inferior quadrants. Peripapillary CVI was highest in the nasal and lowest in the inferior sector. Multiple regression showed that spherical equivalent (SE), AL, intraocular pressure (IOP), ChT, age, and gender were significantly related to CVI (P < 0.05). CONCLUSIONS: In children, the distribution of CVI in the posterior pole is not uniform. A decreased CVI was observed from hyperopia to myopia and was associated with decreased SE, elongated AL, and choroidal thinning. Further study of changes in CVI during myopia onset and progression is required to better understand the role of the choroidal vasculature in myopia development.

Clinical Characteristics and Immune Responses in Children with Primary Ciliary Dyskinesia during Pneumonia Episodes: A Case-Control Study.

OBJECTIVE: This study explored the clinical features and immune responses of children with primary ciliary dyskinesia (PCD) during pneumonia episodes. METHODS: The 61 children with PCD who were admitted to hospital because of pneumonia were retrospectively enrolled into this study between April 2017 and August 2022. A total of 61 children with pneumonia but without chronic diseases were enrolled as the control group. The clinical characteristics, levels of inflammatory indicators, pathogens, and imaging features of the lungs were compared between the two groups. RESULTS: The PCD group had higher levels of lymphocytes (42.80% versus 36.00%, p = 0.029) and eosinophils (2.40% versus 1.25%, p = 0.020), but lower neutrophil counts (3.99 versus 5.75 × 109/L, p = 0.011), percentages of neutrophils (46.39% versus 54.24%, p = 0.014), CRP (0.40 versus 4.20 mg/L, p < 0.001) and fibrinogen (257.50 versus 338.00 mg/dL, p = 0.010) levels. Children with PCD and children without chronic diseases were both most commonly infected with Mycoplasma pneumoniae (24.6% versus 51.9%). Children with PCD had significantly more common imaging features, including mucous plugging (p = 0.042), emphysema (p = 0.007), bronchiectasis (p < 0.001), mosaic attenuation (p = 0.012), interstitial inflammation (p = 0.015), and sinusitis (p < 0.001). CONCLUSION: PCD is linked to immune system impairment, which significantly contributes to our understanding of the pathophysiology of this entity.

Myopic maculopathy among Chinese children with high myopia and its association with choroidal and retinal changes: the SCALE-HM study.

AIMS: To investigate myopic maculopathy in Chinese children with high myopia and its association with choroidal and retinal changes. METHODS: This cross-sectional study included Chinese children aged 4-18 years with high myopia. Myopic maculopathy was classified by fundus photography and retinal thickness (RT) and choroidal thickness (ChT) in the posterior pole were measured by swept-source optical coherence tomography. A receiver operation curve was used to determine the efficacy of fundus factors in classifying myopic maculopathy. RESULTS: In total, 579 children aged 12.8±3.2 years with a mean spherical equivalent of -8.44±2.20 D were included. The proportions of tessellated fundus and diffuse chorioretinal atrophy were 43.52% (N=252) and 8.64% (N=50), respectively. Tessellated fundus was associated with a thinner macular ChT (OR=0.968, 95% CI: 0.961 to 0.975, p<0.001) and RT (OR=0.977, 95% CI: 0.959 to 0.996, p=0.016), longer axial length (OR=1.545, 95% CI: 1.198 to 1.991, p=0.001) and older age (OR=1.134, 95% CI: 1.047 to 1.228, p=0.002) and less associated with male children (OR=0.564, 95% CI: 0.348 to 0.914, p=0.020). Only a thinner macular ChT (OR=0.942, 95% CI: 0.926 to 0.959, p<0.001) was independently associated with diffuse chorioretinal atrophy. When using nasal macular ChT for classifying myopic maculopathy, the optimal cut-off value was 129.00 µm (area under the curve (AUC)=0.801) and 83.85 µm (AUC=0.910) for tessellated fundus and diffuse chorioretinal atrophy, respectively. CONCLUSION: A large proportion of highly myopic Chinese children suffer from myopic maculopathy. Nasal macular ChT may serve as a useful index for classifying and assessing paediatric myopic maculopathy. TRIAL REGISTRATION NUMBER: NCT03666052.

Monitoring weed mechanical and chemical damage stress based on chlorophyll fluorescence imaging.

Currently, mechanical and chemical damage is the main way to carry out weed control. The use of chlorophyll fluorescence (CF) technology to nondestructively monitor the stress physiological state of weeds is significant to reveal the damage mechanism of mechanical and chemical stresses as well as complex stresses. Under simulated real field environmental conditions, different species and leaf age weeds (Digitaria sanguinalis 2-5 leaf age, and Erigeron canadensis 5-10 leaf age) were subjected to experimental treatments for 1-7 days, and fluorescence parameters were measured every 24 h using a chlorophyll fluorometer. The aim of this study was to investigate the changes in CF parameters of different species of weeds (Digitaria sanguinalis, Erigeron canadensis) at their different stress sites under chemical, mechanical and their combined stresses. The results showed that when weeds (Digitaria sanguinalis and Erigeron canadensis) were chemically stressed in different parts, their leaf back parts were the most severely stressed after 7 days, with photosynthetic inhibition reaching R=75%. In contrast, mechanical stress differs from its changes, and after a period of its stress, each parameter recovers somewhat after 1 to 2 days of stress, with heavy mechanical stress R=11%. Complex stress had the most significant effect on CF parameters, mainly in the timing and efficiency of changes in Fv/Fm, Fq'/Fm', ETR, Rfd, NPQ and Y(NO), with R reaching 71%-73% after only 3-4 days of complex stress, and its changes in complex stress were basically consistent with the pattern of changes in its chemical stress. The results of the study will help to understand the effects of mechanical and chemical stresses and combined stresses on CF parameters of weeds and serve as a guide for efficient weed control operations and conducting weed control in the future.

Modeling of and Experimenting with Concentric Tube Robots: Considering Clearance, Friction and Torsion.

Concentric tube robots (CTRs) are a promising prospect for minimally invasive surgery due to their inherent compliance and ability to navigate in constrained environments. Existing mechanics-based kinematic models typically neglect friction, clearance, and torsion between each pair of contacting tubes, leading to large positioning errors in medical applications. In this paper, an improved kinematic modeling method is developed. The effect of clearance on tip position during concentric tube assembly is compensated by the database method. The new kinematic model is mechanic-based, and the impact of friction moment and torsion on tubes is considered. Integrating the infinitesimal torsion of the concentric tube robots eliminates the errors caused by the interaction force between the tubes. A prototype is built, and several experiments with kinematic models are designed. The results indicate that the error of tube rotations is less than 2 mm. The maximum error of the feeding experiment does not exceed 0.4 mm. The error of the new modeling method is lower than that of the previous kinematic model. This paper has substantial implications for the high-precision and real-time control of concentric tube robots.

Dexterity enhancement of continuum robot for natural orifice transluminal endoscopic surgery in the dual-manipulator collaborative space.

BACKGROUND: Suturing and knotting in Natural Orifice Transluminal Endoscopic Surgery (NOTES) requires the robot not only to be able to work with multiple manipulators but also to have a high degree of dexterity. However, little attention has been paid to the design and enhancement of dexterity in multi-manipulated robots. METHODS: In this paper, the dexterity of a new dual-manipulator collaborative continuum robot in collaborative space is analyzed and enhanced. A kinematic model of the continuum robot was developed. The dexterity function of the robot is evaluated based on the concepts of the low-Degree-of-Freedom Jacobian matrix. Then an Adaptive Parameter Gray Wolf Coupled Cuckoo Optimization Algorithm with faster convergence and higher accuracy is innovatively proposed to optimize the objective function. Finally, experiments demonstrate that the dexterity of the optimized continuum robot is enhanced. RESULTS: The optimization results show that the optimized dexterity is 24.91% better than the initial state. CONCLUSION: Through the work of this paper, the robot for NOTES can perform suturing and knot more dexterously, which has significant implications for the treatment of digestive tract diseases.

Machine Learning-Based Integration of Metabolomics Characterisation Predicts Progression of Myopic Retinopathy in Children and Adolescents.

Myopic retinopathy is an important cause of irreversible vision loss and blindness. As metabolomics has recently been successfully applied in myopia research, this study sought to characterize the serum metabolic profile of myopic retinopathy in children and adolescents (4-18 years) and to develop a diagnostic model that combines clinical and metabolic features. We selected clinical and serum metabolic data from children and adolescents at different time points as the training set (n = 516) and the validation set (n = 60). All participants underwent an ophthalmologic examination. Untargeted metabolomics analysis of serum was performed. Three machine learning (ML) models were trained by combining metabolic features and conventional clinical factors that were screened for significance in discrimination. The better-performing model was validated in an independent point-in-time cohort and risk nomograms were developed. Retinopathy was present in 34.2% of participants (n = 185) in the training set, including 109 (28.61%) with mild to moderate myopia. A total of 27 metabolites showed significant variation between groups. After combining Lasso and random forest (RF), 12 modelled metabolites (mainly those involved in energy metabolism) were screened. Both the logistic regression and extreme Gradient Boosting (XGBoost) algorithms showed good discriminatory ability. In the time-validation cohort, logistic regression (AUC 0.842, 95% CI 0.724-0.96) and XGBoost (AUC 0.897, 95% CI 0.807-0.986) also showed good prediction accuracy and had well-fitted calibration curves. Three clinical characteristic coefficients remained significant in the multivariate joint model (p < 0.05), as did 8/12 metabolic characteristic coefficients. Myopic retinopathy may have abnormal energy metabolism. Machine learning models based on metabolic profiles and clinical data demonstrate good predictive performance and facilitate the development of individual interventions for myopia in children and adolescents.

A Passively Conforming Soft Robotic Gripper with Three-Dimensional Negative Bending Stiffness Fingers.

Robot grippers that lack physical compliance have a difficult time dealing with uncertainty, such as fragile objects that may not have well-defined shapes. Existing soft robotic grippers require a large empty workspace for their actuated fingers to curl around the objects of interest, limiting their performance in clutter. This article presents a three-dimensional structure that exhibits negative stiffness in every bending direction used as fingers in a class of soft robotic grippers. Our approach exploits a compliant mechanism in a conical shape such that a transverse external contact force causes the fingers to bend toward the contact, enabling passive conformation for an adaptive grasp, even in clutter. We show analytically and experimentally that the proposed fingers have a negative bending response and that they conform to objects of various diameters. We demonstrate a soft robotic gripper with three self-conforming fingers performing the following: (1) fingertip grasping, (2) power grasping, and (3) semipassive grasping in clutter. Grasping experiments focus on picking fruits, which exemplify delicate objects with unmodeled shapes with significant variation. The experimental results reveal the ability of the self-conforming structure to smoothly envelope a broad range of objects and demonstrate a 100% grasp success rate in the experiments performed. The proposed passively conforming fingers enable picking of complex and unknown geometries without disturbing nearby objects in clutter and without the need for complex grasping algorithms. The proposed structures can be tailored to deform in desired ways, enabling a robust strategy for the engineering of physical compliance for adaptive soft structures.

Higher-order aberrations and their association with axial elongation in highly myopic children and adolescents.

BACKGROUND: Vision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and the relationship between HOA components and 1-year axial eye growth. METHODS: Baseline cycloplegic ocular and corneal HOAs, axial length (AL), spherical equivalent (SE), astigmatism and interpupillary distance (IPD) were determined for the right eyes of 458 highly myopic (SE ≤-5.0D) subjects. HOAs were compared among baseline age groups (≤12 years, 13-15 years and 16-18 years). Ninety-nine subjects completed the 1-year follow-up. Linear mixed model analyses were applied to determine the association between HOA components, other known confounding variables (age, gender, SE, astigmatism and IPD) and axial growth. A comparison with data from an early study of moderate myopia were conducted. RESULTS: Almost all ocular HOAs and few corneal HOAs exhibited significant differences between different age groups (all p<0.05). After 1 year, only ocular HOA components was significantly negative associated with a longer AL, including secondary horizontal comatic aberration (p=0.019), primary spherical aberration (p<0.001) and spherical HOA (p=0.026). Comparing with the moderate myopia data, the association of comatic aberration with AL growth was only found in high myopia. CONCLUSION: In highly myopic children and adolescents, lower levels of annual ocular secondary horizontal comatic aberration changes, besides spherical aberrations, were associated with axial elongation. This suggests that ocular HOA plays a potential role in refractive development in high myopia.

Role of corneal radius of curvature in early identification of fundus tessellation in children with low myopia.

AIM: To assess the role of the corneal radius of curvature (CR) in the identification of fundus tessellation in children with low myopia. METHODS: In the cross-sectional study, students aged 9-12 years from 24 primary schools in Shanghai were enrolled by cluster sampling. Participants underwent measurements including cycloplegic refraction and axial length. Fundus images and choroidal thickness were obtained by swept-source optical coherence tomography. Fundus tessellation was classified into four grades according to fundus photographs. RESULTS: A total of 1127 children with low myopia (spherical equivalence (SE) >-3.00 dioptre (D) but ≤-0.50 D) were included, with a mean age of 10.29±0.60 years and a mean SE of -1.44±0.69 D. Fundus tessellation was found in 591 (52.4%) cases (grade 1: 428, 38.0%; grade 2: 128, 11.4%; grade 3: 35, 3.1%). Choroidal thickness decreased as fundus tessellation grade increased (p trend <0.001). According to regression analysis, higher fundus tessellation grade was independently associated with larger CR (OR, 7.499; 95% CI 2.279 to 24.675, p=0.001). For those with CR >7.9 mm, along with CR, degree and proportion of fundus tessellation increased sharply. CONCLUSION: Fundus tessellation existed in more than half of children with low myopia. Preliminary fundus photography conducted in children with low myopia with large CR would be necessary and beneficial to the early management of myopic fundus changes. Trial registration number NCT02980445.

Effect of Ocular Magnification on Macular Choroidal Thickness Measurements Made Using Optical Coherence Tomography in Children.

PURPOSE: To evaluate the relationship between ocular magnification correction and macular choroidal thickness (ChT) measurements in children, and to demonstrate when ocular magnification correction is necessary. METHODS: Chinese children aged 6-9 years with various refractive statuses were included. Swept-source optical coherence tomography was used to measure macular ChT. A self-designed program was adopted to simulate ChT changes in each sector of the ETDRS grid in the macula under various simulated axial lengths (ALs). RESULTS: ChT measurements were not affected for all simulated ALs in over 95% of the individuals in the central fovea. In the inferior, superior, and temporal parafoveal sectors, the extent of AL that may include 95% of the individuals narrowed from approximately 22.0 mm to 27.2 mm. In the nasal parafoveal sector and inferior, superior, and temporal perifoveal sectors, the extent of AL that may include 95% of the individuals became even narrower, from approximately 22.8 mm to 26.0 mm. The narrowest extent was observed in the perifoveal nasal sector, ranging from 23.3 mm to 25.5 mm. The effect of ocular magnification was more significant in hyperopes than in myopes in the inferior parafoveal sector and temporal, superior, and nasal perifoveal sectors. CONCLUSION: During macular ChT measurements, ocular magnification correction is not necessary in the central fovea. However, ocular magnification should be corrected normally in the nasal perifoveal region and in individuals with ALs shorter than 22.8 mm or longer than 26.0 mm in the remaining macular regions.

A new perspective on infection forces with demonstration by a DDE infectious disease model.

In this paper, we revisit the notion of infection force from a new angle which can offer a new perspective to motivate and justify some infection force functions. Our approach can not only explain many existing infection force functions in the literature, it can also motivate new forms of infection force functions, particularly infection forces depending on disease surveillance of the past. As a demonstration, we propose an SIRS model with delay. We comprehensively investigate the disease dynamics represented by this model, particularly focusing on the local bifurcation caused by the delay and another parameter that reflects the weight of the past epidemics in the infection force. We confirm Hopf bifurcations both theoretically and numerically. The results show that, depending on how recent the disease surveillance data are, their assigned weight may have a different impact on disease control measures.

Effects of environmental factors on refractive development of children and adolescents in different pubertal stages / 中国学校卫生

Objective@#To explore the effect of puberty on refractive development of children and adolescents and its interaction with outdoor activities, near work and the use of electronic products, so as to provide a reference for strategies for intervening myopia.@*Methods@#Cluster sampling method was used to select 776 students aged 7-13 from a nine year consistent school in Shanghai to participate and were followed up for 2 years. All participants underwent cycloplegic refraction and ocular axial length measurement once a year, as well as pubertal development, average daily outdoor time, near work time and time of electronic products usage. The influencing factors and interaction effects of refractive parameters in different puberty stages were analyzed by generalized estimation equation.@*Results@#At baseline, 634 children participated in cycloplegic refraction, of which 350 were myopic (55.2%). There were significant differences in axial length, average daily outdoor time, near work time and time of using electronic products at different stages of puberty ( F = 4.10 ，4.24，5.54，9.20， P <0.05). There was interaction between puberty and outdoor time on axial length development ( β =0.133, P < 0.05), and the interaction between puberty and the time of near work or using electronic products was not statistically significant ( P >0.05).@*Conclusion@#Puberty may play a regulatory role in the relationship between outdoor time and refractive development among Chinese children and adolescents.

Vector optical field with the polarization varying along an arbitrary circular trajectory on the Poincaré sphere.

As an inherent feature of vector optical field, the spatial distribution of polarization brings additional degrees of freedom to engineer the optical field and control the interaction between light and matters. Here we focus on the variation of polarization in single vector optical field, which can be defined by the trajectory on the Poincaré sphere. Based on the amplitude-phase-polarization joint modulation method we propose, vector optical field, whose variation of polarization follows arbitrary circular trajectory on the Poincaré sphere, can be generated. Moreover, the tightly focusing behaviors of the vector optical fields with the polarization varying along parallel circles on the Poincaré sphere are compared. Relations between the circular trajectory and the central intensity of the hollow focal field are concluded.

MiR-590-5p inhibits pathological hypertrophy mediated heart failure by targeting RTN4.

Heart failure (HF) is a rising epidemic and public health burden in modern society. It is of great need to find new biomarkers to ensure a timely diagnosis and to improve treatment and prognosis of the disease. The mouse model of HF was established by thoracic aortic constriction. Color Doppler ultrasound was performed to detect left ventricular end-diastolic diameter. Hematoxylin and eosin staining was conducted to observe the pathological changes of mouse myocardium. The RT-qPCR analysis was performed to detect miR-590-5p and RTN4 expression levels. Western blot was conducted to detect protein levels of the indicated genes. We found that the expression of miR-590-5p was downregulated in cardiac tissues of HF mice. Injection of AAV-miR-590-5p attenuated myocardium hypertrophy and myocyte apoptosis. Additionally, miR-590-5p overexpression promoted viability, inhibited apoptosis, and decreased ANF, BNP and beta-MHC protein levels in H9c2 cell. Mechanistically, miR-590-5p binds to RTN4 3'-untranslated region, as predicted by starBase online database and evidenced by luciferase reporter assay. Furthermore, miR-590-5p negatively regulates RTN4 mRNA expression and suppresses its translation. The final rescue experiments revealed that miR-590-5p modulated cardiomyocyte phenotypes by binding to RTN4. In conclusion, miR-590-5p modulates myocardium hypertrophy and myocyte apoptosis in HF by downregulating RTN4.

Prevalence, Causes, and Factors Associated with Visual Impairment in a Chinese Elderly Population: The Rugao Longevity and Aging Study.

PURPOSE: This study aimed to explore the current prevalence, causes, and factors associated with visual impairment in a Chinese elderly population. METHODS: A random sample of 2164 candidates aged ≥70 years was selected. Among them, 1914 participants (response rate: 88.4%) underwent comprehensive eye examinations. The prevalence and causes of visual impairment were estimated, and the associated factors were identified. RESULTS: The standardized prevalence of mild visual impairment (<6/12 to ≥6/18), moderate to severe visual impairment (MSVI) (<6/18 to ≥3/60), and blindness (<3/60) in the better eye were 20.5%, 25.8%, and 3.4%, respectively. The leading cause of visual impairment was cataract (49.7%), followed by uncorrected refractive error (26.5%), myopic maculopathy (5.8%), and posterior capsular opacification (5.5%). Optical coherence tomography revealed that vitreoretinal interface abnormalities were the third most common cause of monocular mild visual impairment (2.2%) and MSVI (4.4%) in the elderly population. A large number of patients with visual impairment (81.7%) were amenable to undergo the interventions. Visual impairment was associated with advanced age (odds ratio [OR], 1.09 per year; p<0.001), female sex (OR, 1.59; p=0.003), self-reported visual impairment (OR, 1.91; p<0.001), cognitive impairment (OR, 1.40, p=0.005), and high educational level (OR, 0.75; primary, p=0.045; and OR, 0.53, secondary or higher; p<0.001). CONCLUSION: Visual impairment was common in the Chinese elderly population and a severe health and social problem. Practicable policies are urgently needed to popularize eye health knowledge and promote treatments for visual impairment in elderly people in rural China.

Circadian Clock Disruption Suppresses PDL1+ Intraepithelial B Cells in Experimental Colitis and Colitis-Associated Colorectal Cancer.

BACKGROUND & AIMS: The circadian clock is crucial for physiological homeostasis including gut homeostasis. Disorder of the circadian clock may contribute to many diseases including inflammatory bowel disease (IBD). However, the role and the mechanisms of circadian clock involvement in IBD still are unclear. METHODS: Disorder of the circadian clock including chronic social jet lag and circadian clock gene deficiency mice (Bmal1-/-, and Per1-/-Per2-/-) were established. Dextran sulfate sodium (DSS) and/or azoxymethane were used to induce mouse models of colitis and its associated colorectal cancer. Flow cytometry, immunohistochemistry, immunofluorescence, Western blot, and reverse-transcription quantitative polymerase chain reaction were used to analyze the characteristics of immune cells and their related molecules. RESULTS: Mice with disorders of the circadian clock including chronic social jet lag and circadian clock gene deficiency were susceptible to colitis. Functionally, regulatory B (Breg) cells highly expressing Programmed cell death 1 ligand 1 (PDL1) in intestinal intraepithelial lymphocytes (IELs) helped to alleviate the severity of colitis after DSS treatment and was dysregulated in DSS-treated Bmal1-/- mice. Notably, interleukin 33 in the intestinal microenvironment was key for Bmal1-regulated PDL1+ Breg cells and interleukin 33 was a target of Bmal1 transcriptionally. Dysregulated PDL1+ B cells induced cell death of activated CD4+ T cells in DSS-treated Bmal1-/- mice. Consequently, circadian clock disorder was characterized as decreased numbers of Breg+ PDL1+ cells in IELs and dysfunction of CD4+ T cells promoted colitis-associated colorectal cancer (CRC) in mice. In clinical samples from CRC patients, low expression of Bmal1 gene in paracancerous tissues and center area of tumor was associated closely with a poorer prognosis of CRC patients. CONCLUSIONS: Our study uncovers the importance of the circadian clock regulating PDL1+ Breg+ cells of IELs in IBD and IBD-associated CRC.

Prevalence of fundus tessellation and its associated factors in Chinese children and adolescents with high myopia.

PURPOSE: To investigate the prevalence and associated factors of fundus tessellation in highly myopic children and adolescents. METHODS: A total of 513 high myopes (spherical equivalent [SE] ≤ -5.0 D, 4-19 years of age) without any advanced pathological myopic lesions were enrolled. Fundus photographs and choroidal thickness (ChT) data were collected by SS-OCT. A novel grading approach was adopted to classify fundus tessellation into four categories on colour fundus photography, referring to the location of tessellation divided by an Early Treatment Diabetic Retinopathy Study grid centred on the fovea, through which closer to the fovea represents higher grades of fundus tessellation. Peripapillary atrophy (PPA) area and ovality index were also measured. RESULTS: Among the participants, with a mean age of 13.47 ± 3.13 years and mean SE of - 8.34 ± 1.91 D, there were 29 (5.7%), 95 (18.5%), 233 (45.4%) and 156 (30.4%) participants with grade 0 to grade 3 fundus tessellation, respectively. The ChT in both the macular and peripapillary area was negatively correlated with the fundus tessellation grade (R = -0.763 and -0.537, respectively, all p < 0.001). Higher grades of fundus tessellation were independently associated with thinner macular ChT (OR = 1.734, 95% CI: 1.621-1.856, p < 0.001), longer axial length (OR = 1.368, 95% CI: 1.105-1.695, p = 0.004), larger PPA area (OR = 1.391, 95% CI: 1.073-1.802, p = 0.013) and the female sex (OR = 1.605, 95% CI: 1.092-2.359, p = 0.016). CONCLUSION: The fundus tessellation grade could reflect the ChT, representing the severity of myopic maculopathy among young high myopes who rarely had any advanced lesions of pathological myopia. Fundus tessellation grade might be a potential index for assessing early-stage myopic maculopathy in children and adolescents.