Chronic sleep deprivation impairs retinal circadian transcriptome and visual function.

Sleep loss is common in modern society and is increasingly associated with eye diseases. However, the precise effects of sleep loss on retinal structure and function, particularly on the retinal circadian system, remain largely unexplored. This study investigates these effects using a chronic sleep deprivation (CSD) model in mice. Our investigation reveals that CSD significantly alters the retinal circadian transcriptome, leading to remarkable changes in the temporal patterns of enriched pathways. This perturbation extends to metabolic and immune-related transcriptomes, coupled with an accumulation of reactive oxygen species in the retina. Notably, CSD rhythmically affects the thickness of the ganglion cell complex, along with diurnal shifts in microglial migration and morphology within the retina. Most critically, we observe a marked decrease in both scotopic and photopic retinal function under CSD conditions. These findings underscore the broad impact of sleep deprivation on retinal health, highlighting its role in altering circadian gene expression, metabolism, immune response, and structural integrity. Our study provides new insights into the broader impact of sleep loss on retinal health.

Long-term high fructose intake reprograms the circadian transcriptome and disrupts homeostasis in mouse extra-orbital lacrimal glands.

This study aims to explore the effects of long-term high fructose intake (LHFI) on the structure, functionality, and physiological homeostasis of mouse extra-orbital lacrimal glands (ELGs), a critical component of ocular health. Our findings reveal significant reprogramming of the circadian transcriptome in ELGs following LHFI, alongside the activation of specific inflammatory pathways, as well as metabolic and neural pathways. Notably, LHFI resulted in increased inflammatory infiltration, enhanced lipid deposition, and reduced nerve fiber density in ELGs compared to controls. Functional assessments indicated a marked reduction in lacrimal secretion following cholinergic stimulation in LHFI-treated mice, suggesting impaired gland function. Overall, our results suggest that LHFI disrupts lacrimal gland homeostasis, potentially leading to dry eye disease by altering its structure and secretory function. These insights underscore the profound impact of dietary choices on ocular health and highlight the need for strategies to mitigate these risks.

[Chemical constituents and pharmacological effects of Nauclea officinalis and predictive analysis of its quality markers].

Nauclea officinalis is a Chinese medicinal material with a high medicinal value, which contains various chemical constituents such as alkaloids, pentacyclic triterpenoids and their saponins, organic phenolic acids and their glycosides, iridoids, and flavonoids. It has antiviral, antibacterial, antipyretic, analgesic, anti-inflammatory, and immunoregulatory functions. This article systematically reviewed the reported chemical constituents and pharmacological effects of N. officinalis. According to the concept of quality markers, the quality markers of N. officinalis were predicted and analyzed from the aspects of plant kinship, specificity of chemical constituents, traditional drug efficacy, measurability of chemical constituents, plasma components, and different producing areas and harvest times, in order to provide a basis for the quality evaluation of N. officinalis.

Long-term high fructose intake promotes lacrimal gland dysfunction by inducing gut dysbiosis in mice.

The lacrimal gland is essential for maintaining ocular surface health through the secretion of the aqueous layer of the tear film. It is therefore important to explore the intrinsic and extrinsic factors that affect the structure and function of the lacrimal gland and the mechanisms underlying them. With the prevalence of Westernized diets characterized by high sugar and fat content, the susceptibility to many diseases, including ocular diseases, is increased by inducing dysbiosis of the gut microbiome. Here, we found that the composition, abundance, and diversity of the gut microbiome was significantly altered in mice by drinking 15% high fructose water for one month, as determined by 16S rRNA sequencing. This was accompanied by a significant increase in lipid deposition and inflammatory cell infiltration in the extraorbital lacrimal glands (ELGs) of mice. Transcriptome analysis based on bulk RNA-sequencing revealed abnormal activation of some of several metabolic and immune-related pathways. In addition, the secretory response to stimulation with the cholinergic receptor agonist pilocarpine was significantly reduced. However, when the composition and diversity of the gut microbiome of high fructose intake (HFI)-treated mice were improved by transplanting feces from normal young healthy mice, the pathological alterations in ELG structure, inflammatory cell infiltration, secretory function and transcriptome analysis described above were significantly reversed compared to age-matched control mice. In conclusion, our data suggest that prolonged HFI may cause pathological damage to the structure and function of the ELG through the induction of gut dysbiosis. Restoration of intestinal dysbiosis in HFI-treated mice by fecal transplantation has a potential role in ameliorating these pathological impairments.

[Optimization of ethanol precipitation process of Nauclea officinalis extract based on concept of quality by design(QbD)].

The ethanol precipitation process of Nauclea officinalis extract was optimized based on the concept of quality by design(QbD). Single factor tests were carried out to determine the levels of test factors. The ethanol volume fraction, pre-ethanol precipitation drug concentration, and ethanol precipitation time were taken as critical process parameters(CPPs). With the comprehensive scores of strictosamide transfer rate and solid removal rate as the critical quality attributes(CQAs), Box-Behnken design was employed to establish the mathematical models and space design between CPPs and CQAs, and the obtained optimal operating space was validated. The optimal operating space included ethanol volume fraction of 65%-70%, pre-ethanol precipitation drug concentration of 22-27 mg·mL~(-1), and ethanol precipitation time of 12 h. Based on the concept of QbD, this study adopted the design space to optimize the ethanol precipitation process of N. officinalis extract, which provided a reliable theoretical basis for the quality control in the production process of N. officinalis preparations. Moroever, this study provided a reference value for guiding the research and industrial production of traditional Chinese medicines.

Microbial Reconstitution Improves Aging-Driven Lacrimal Gland Circadian Dysfunction.

Lacrimal glands are highly susceptible to aging and exhibit age-related structural and functional alterations. However, the mechanisms by which aging affects the lacrimal glands are not well-established. The current study explores the crosstalk between the aging process, gut microbiota, and circadian rhythm in age-associated lacrimal gland dysfunction. C57BL/6J mice were divided into young, old, and fecal microbiota transplant (FMT)-treated old groups. The gut bacterial community diversity was analyzed by 16S rRNA sequencing. Exorbital lacrimal glands (ELGs) were collected at 3-hour intervals over a 24-hour circadian cycle, and total RNA was subjected to high-throughput sequencing. Rhythmic transcriptional data were analyzed using the Jonckheere-Terpstra-Kendall algorithm and bioinformatics analysis technology. Immunostaining was used to identify lymphocytic infiltration, lipid deposition, and nerve innervation in the ELGs. Compared with young mice, old mice underwent a significant gut microbial community shift. The rhythmically transcriptomic profile was significantly reprogrammed over a 24-hour cycle in the old ELG group. Intervention with serial FMT from young donors for 1 month rejuvinated the gut microbial community of the old mice. Most alterations in rhythmic transcriptomic profiling were improved. Furthermore, chronic inflammation, lipid deposition, and aberrant neural response of the aging lacrimal glands were significantly reduced. Thus, the study shows that reconstitution of age-associated gut dysbiosis with FMTs from young donors improves aging-driven lacrimal gland circadian dysfunction.

Recent advances in modulators of circadian rhythms: an update and perspective.

Circadian rhythm is a universal life phenomenon that plays an important role in maintaining the multiple physiological functions and regulating the adaptability to internal and external environments of flora and fauna. Circadian alignment in humans has the greatest effect on human health, and circadian misalignment is closely associated with increased risk for metabolic syndrome, cardiovascular diseases, neurological diseases, immune diseases, cancer, sleep disorders, and ophthalmic diseases. The recent description of clock proteins and related post-modification targets was involved in several diseases, and numerous lines of evidence are emerging that small molecule modulators of circadian rhythms can be used to rectify circadian disorder. Herein, we attempt to update the disclosures about the modulators targeting core clock proteins and related post-modification targets, as well as the relationship between circadian rhythm disorders and human health as well as the therapeutic role and prospect of these small molecule modulators in circadian rhythm related disease.

[Multi-correspondence analysis of the status and related factors of chronic diseases multimorbidity in middle-aged and elderly people in China in 2009].

OBJECTIVE: To study the status of chronic disease multimorbidity of middle-aged and elderly people over 45 years old in China, and to analyze the influencing factors. METHODS: Using the data of the"China Health and Nutrition Survey(CHNS)", this survey has been carried out in 10 rounds nationwide since 1989. Multi-stage cluster random sampling was used to investigate rural and urban areas in 9 provinces and cities in China. In this study, the general socio-demographic characteristics, disease history, living habits and other information in the 2009 database were used to analyze the subjects who were collected blood samples. The prevalence of 8 common chronic diseases and multimorbidity such as hypertension, mixed-hyperlipidemia and hyperuricemia were described respectively. The Venn diagram in the R software package was used to calculate the multimorbidity of the disease. The χ~2 test and multiple correspondence analysis were used to explore the influencing factors of chronic disease multimorbidity in the middle-aged and elderly people in China. RESULTS: Among the 5316 subjects, the highest prevalence among 8 chronic diseases was hypertension(2143, 40. 3%). The lowest prevalence was myocardial infarction(87, 1. 4%). There were all together 1498 patients who had two kinds or more than two kinds of chronic diseases with a detection rate of 28. 18%. The most common multimorbidity were hypertension+hyperuricemia(199, 13. 30%), followed by hypertension + mixed-hyperlipidemia(191, 12. 77%). Hypertension+hyperuricemia+mixed-hyperlipidemia was the most common combination of the three chronic diseases(103, 6. 89%). Age(Kendull=0. 158, P<0. 001), region(χ~2=30. 129, P<0. 001), BMI(Kendull=0. 344, P<0. 001) and marital status(χ~2=21. 923, P<0. 001) were associated with the number of multimorbidities. Correspondence analysis showed that subjects aged 65 to 74, living in cities and sleeping less than 7 hours were more likely to have multimorbidity. CONCLUSION: The prevalence of chronic disease multimorbidity among middle-aged and elderly residents in China is high. Older age, unmarried, overweight and obesity, too little or too much sleep may increase the risk of multimorbidity.

Neck circumference may be a valuable tool for screening individuals with obesity: findings from a young Chinese population and a meta-analysis.

BACKGROUND: Central obesity and overweight/obesity can result in various chronic non-communicable diseases, such as cardiovascular disease, metabolic syndrome, and diabetes mellitus. Waist circumference (WC) and body mass index (BMI) are widely used to measure obesity despite their limitations. For example, WC and BMI cannot be measured in pregnant women and subjects with abdominal ascites or masses. Therefore, this study aims to determine the efficacy of neck circumference (NC) as a tool for screening central obesity and overweight/obesity. METHODS: A total of 1169 undergraduates aged 18-25 years were studied by a cross-sectional survey in China, 2016. Questionnaires and physical examinations were used to collect data. Receiver operator characteristic (ROC) curve was performed to determine the best threshold of NC for screening central obesity and overweight/obesity. Meanwhile, a meta-analysis was conducted to estimate the efficacy of NC for screening central obesity and overweight/obesity synthetically. RESULTS: NC was moderately correlated with WC and BMI. The ROC analysis showed that 37.1 cm for male and 32.6 cm for female were the best thresholds for central obesity, and 37.4 cm and 32.2 cm for overweight/obesity, respectively. The sensitivity, specificity, area under receiver operating curve (AUC) of central obesity and overweight/obesity were higher. In the meta-analysis, the pooled sensitivity, specificity, AUC and their 95%CI of NC for screening central obesity were 0.72 (0.68~ 0.75), 0.87 (0.74~ 0.94), 0.77 (0.73~ 0.80) for male and 0.73 (0.65~ 0.80), 0.80 (0.71~ 0.86), 0.82 (0.79~ 0.86) for female. For overweight/obesity, the pooled sensitivity, specificity, AUC and corresponding 95%CI were 0.83 (0.70~ 0.91), 0.77 (0.66~ 0.85), 0.86 (0.83~ 0.89) for male and 0.82 (0.71~ 0.90), 0.84 (0.61~ 0.95), 0.89 (0.86~ 0.92) for female. CONCLUSION: NC may not be a good tool for screening individuals with central obesity. But it may be a simple and valuable tool for screening individuals with overweight/obesity, especially in females.

[Relationship between serum magnesium concentration and obesity in Chinese adults].

OBJECTIVE: To explore the relationship between concentration of serum magnesium with overweight/obesity and abdominal obesity in Chinese adults. METHODS: Data from China Health and Nutrition Survey investigated in 2009 was analyzed. Rank correlation analysis, univariate analysis and binary Logistic regression analysis were performed to analyze influence of serum magnesium concentrations, regions and gender on the prevalence of overweight/obesity and abdominal obesity. RESULTS: The prevalence of overweight/obesity was 40. 2%. The concentration of serum magnesium in people withoverweight/obesity was higher than that in people with non-overweight/obesity( 0. 95 mmol/L vs. 0. 93 mmol/L, t = 7. 021, P < 0. 001). The prevalence of overweight/obesity was 33. 2%. The concentration of serum magnesium in people with abdominal obesity was higher than that in people with non-abdominal obesity( 0. 95 mmol/L vs. 0. 93 mmol/L, t = 5. 712, P < 0. 001). The serum magnesium concentration, prevalence of overweight/obesity and abdominal obesity were higher in magnesium-rich area than in the nonmagnesium-rich areas, which showed significant differences between two groups( serum magnesium: t = 8. 012, P < 0. 001; overweight/obesity: χ~2= 138. 252, P < 0. 001;abdominal obesity: χ~2= 134. 999, P < 0. 001). The rank correlation coefficients between serum magnesium concentration and prevalence of overweight/obesity and abdominal obesity were 0. 952 and 0. 796 in male, and 0. 794 and 0. 903 in female, respectively. Serum magnesium concentration was divided into four grades according to quartiles. The risk of overweight/obesity increased by 1. 207 times( 95% CI 1. 138-1. 281) when the serum magnesium increased a level, and the risk of abdominal obesity increased by 1. 187 times( 95% CI 1. 114-1. 266). CONCLUSION: Higher serum magnesium concentration may be a risk factor for overweight/obesity and abdominal obesity. Serum magnesium concentration is moderately and even highly correlated with prevalence of obesity, and there is a gender difference in this relationship.

Genetic insights and emerging therapeutics in diabetic retinopathy: from molecular pathways to personalized medicine.

Diabetic retinopathy (DR) is a major complication of diabetes worldwide, significantly causing vision loss and blindness in working-age adults, and imposing a substantial socioeconomic burden globally. This review examines the crucial role of genetic factors in the development of DR and highlights the shift toward personalized treatment approaches. Advances in genetic research have identified specific genes and variations involved in angiogenesis, inflammation, and oxidative stress that increase DR susceptibility. Understanding these genetic markers enables early identification of at-risk individuals and the creation of personalized treatment plans. Incorporating these genetic insights, healthcare providers can develop early intervention strategies and tailored treatment plans to improve patient outcomes and minimize side effects. This review emphasizes the transformative potential of integrating genetic information into clinical practice, marking a paradigm shift in DR management and advancing toward a more personalized and effective healthcare model.

A Retrospective Analysis of Corneal Dermoid.

BACKGROUND: Corneal dermoid is a congenital benign tumor and ocular malformation, often diagnosed at birth or in early childhood. Its treatment and long-term prognosis remain under-researched, necessitating further investigation. PURPOSE: This study aims to investigate the epidemiological and clinical characteristics of corneal dermoid, evaluate the efficacy of different surgical methods, and identify factors influencing treatment outcomes. METHODS: A retrospective analysis was conducted on the clinical data of 58 patients treated for corneal dermoid at our hospital from 2017 to 2021. Patients' demographic information, tumor characteristics, surgical methods, and postoperative outcomes were collected and analyzed. Descriptive statistics, independent sample t-test, chi-square (χ 2) test, and Spearman correlation analysis were used to evaluate the distribution characteristics and intergroup differences of corneal dermoid. RESULTS: The average age of the patients was 6.3 years, with 55.2% being male and 44.8% female. The right eye was affected in 63.8% of cases, with the temporal limbus being the most common site (75.9%). Pathological examination revealed tumors covered by squamous epithelium, containing hair follicles, sebaceous glands, adipose tissue, and fibrous tissue; some cases also had cartilage and glandular tissue. Surgical methods included corneal dermoid excision (100%), lamellar keratoplasty (37.9%), amniotic membrane grafting (31.0%), and autologous limbal stem cell transplantation (8.6%). None of the 50 followed up patients experienced tumor recurrence. Postoperative vision improved in 58.0% of patients, with more females (61.9%) experiencing visual impairment compared to males (38.1%) (χ²=4.711, p=0.030). CONCLUSIONS: This study analyzed 58 corneal dermoid patients treated from 2017 to 2021, focusing on epidemiological and clinical characteristics, surgical efficacy, and treatment outcomes. It identified common pathological features and effective surgical methods, with no tumor recurrence in followed up patients. The study highlights the need for further research with larger sample sizes and longer follow-up periods.

Analysis of the heterogeneity and complexity of murine extraorbital lacrimal gland via single-cell RNA sequencing.

PURPOSE: The lacrimal gland is essential for maintaining ocular surface health and avoiding external damage by secreting an aqueous layer of the tear film. However, a healthy lacrimal gland's inventory of cell types and heterogeneity remains understudied. METHODS: Here, 10X Genome-based single-cell RNA sequencing was used to generate an unbiased classification of cellular diversity in the extraorbital lacrimal gland (ELG) of C57BL/6J mice. From 43,850 high-quality cells, we produced an atlas of cell heterogeneity and defined cell types using classic marker genes. The possible functions of these cells were analyzed through bioinformatics analysis. Additionally, the CellChat was employed for a preliminary analysis of the cell-cell communication network in the ELG. RESULTS: Over 37 subclasses of cells were identified, including seven types of glandular epithelial cells, three types of fibroblasts, ten types of myeloid-derived immune cells, at least eleven types of lymphoid-derived immune cells, and five types of vascular-associated cell subsets. The cell-cell communication network analysis revealed that fibroblasts and immune cells play a pivotal role in the dense intercellular communication network within the mouse ELG. CONCLUSIONS: This study provides a comprehensive transcriptome atlas and related database of the mouse ELG.

Screening marker genes of type 2 diabetes mellitus in mouse lacrimal gland by LASSO regression.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and a relative deficiency of insulin. This study aims to screen T2DM-related maker genes in the mouse extraorbital lacrimal gland (ELG) by LASSO regression.C57BLKS/J strain with leptin db/db homozygous mice (T2DM, n = 20) and wild-type mice (WT, n = 20) were used to collect data. The ELGs were collected for RNA sequencing. LASSO regression was conducted to screen marker genes with the training set. Five genes were selected from 689 differentially expressed genes by LASSO regression, including Synm, Elovl6, Glcci1, Tnks and Ptprt. Expression of Synm was downregulated in ELGs of T2DM mice. Elovl6, Glcci1, Tnks, and Ptprt were upregulated in T2DM mice. Area under receiver operating curve of the LASSO model was 1.000(1.000-1.000) and 0.980(0.929-1.000) in the training set and the test set, respectively. The C-index and the robust C-index of the LASSO model were 1.000 and 0.999, respectively, in the training set, and 1.000 and 0.978, respectively, in the test set. In the lacrimal gland of db/db mice, Synm, Elovl6, Glcci1, Tnks and Ptprt can be used as marker genes of T2DM. Abnormal expression of marker genes is related to lacrimal gland atrophy and dry eye in mice.

Mechanisms of Extraorbital Lacrimal Gland Aging in Mice: An Integrative Analysis of the Temporal Transcriptome.

Purpose: This study used high-throughput RNA sequencing (RNA-Seq) and bioinformatics analysis to investigate the altered transcriptome profile of aging lacrimal glands in mice that occurs over the course of a 24-hour cycle. Methods: Male C57BL/6J mice aged 12 weeks (young) and 20 months (aging) were housed in a pathogen-free setting with a 12-hour light/12-hour dark cycle. Throughout a 24-hour cycle, mouse extraorbital lacrimal glands (ELGs) were collected at eight time points at three-hour intervals. To prepare for the high-throughput RNA-Seq, whole mRNA was extracted. Differentially expressed genes (DEGs) in the young and aging groups were subjected to bioinformatic analysis based on diurnal patterns. Furthermore, the cell populations in which significant DEGs express and signaling pathways occur were validated at the single-cell RNA sequencing (scRNA-seq) level. Results: The total transcriptome composition was significantly altered in aging ELGs compared with that in young mouse ELGs at eight time points during the 24-hour cycle, with 864 upregulated and 228 downregulated DEGs, which were primarily enriched in inflammatory pathways. Further comparative analysis of the point-to-point transcriptome revealed that aging ELGs underwent alterations in the temporal transcriptome profile in several pathways, including the inflammation-related, metabolism-related, mitochondrial bioenergetic function-associated, synaptome neural activity-associated, cell processes-associated, DNA processing-associated and fibrosis-associated pathways. Most of these pathways occurred separately in distinct cell populations. Conclusions: Transcriptome profiles of aging lacrimal glands undergo considerable diurnal time-dependent changes; this finding offers a comprehensive source of information to better understand the pathophysiology of lacrimal gland aging and its underlying mechanisms.

High-fat intake reshapes the circadian transcriptome profile and metabolism in murine meibomian glands.

Background: Nutritional and food components reshape the peripheral clock and metabolism. However, whether food challenges affect the circadian clock and metabolism of meibomian glands (MGs) has not been fully explored. This study was designed to analyze alterations in the rhythmic transcriptome and metabolism of MGs of murine fed a balanced diet or a high-fat diet (HFD). Methods: Male C57BL/6J mice were maintained on a 12/12 h light/dark cycle and fed ad libitum on normal chow (NC) or HFD for 4 weeks. MGs were collected from sacrificed animals at 3-h intervals throughout a 24-h circadian cycle. The circadian transcriptome of MGs was analyzed via bioinformatics approaches using high-throughput RNA sequencing (RNA-seq). In addition, circadian oscillations of lipid components in MGs were analyzed. Results: Meibomian glands displayed robust transcriptome rhythmicity. HFD feeding significantly altered the circadian transcriptome profile of MGs-including composition and phase-and spatiotemporally affected the enriched signaling pathways. In addition, HFD feeding significantly altered the normal rhythmic oscillations of lipid components in MGs. Conclusion: Our data show that HFD significantly affects MGs' rhythmicity, which reveals a high sensitivity of MGs' clocks to lipid composition in food.

Efficacy of artificial intelligence-based screening for diabetic retinopathy in type 2 diabetes mellitus patients.

AIM: To explore the efficacy of artificial intelligence (AI)-based screening for diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) patients. METHODS: Data were obtained from 549 T2DM patients who visited the Fundus Disease Center at Henan Provincial People's Hospital from 2018/10-2020/09. DR identification and grading were conducted by two retina specialists, EyeWisdom®DSS and EyeWisdom®MCS, with ophthalmologist grading as reference standard, efficacy of EyeWisdom was evaluated according to sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: Ophthalmologists detected 324 DR cases. Among them, there were 43 of mild non-proliferative DR (NPDR), 79 of moderate NPDR, 61 of severe NPDR, and 141 of proliferative DR (PDR). EyeWisdom®DSS detected 337 DR and EyeWisdom®MCS detected 264 DR. Sensitivity and specificity of EyeWisdom®DSS were 91.0%(95 %CI: 87.3%-93.8%) and 81.3% (95 %CI: 75.5%-86.1%), while EyeWisdom®MCS correctly identified 76.2%(95 %CI: 71.1%-80.7%) of patients with DR and 92.4%(95 %CI: 87.9%-95.4%) of patients without DR. EyeWisdom®DSS showed 76.5%(95 %CI: 69.6%-82.3%) sensitivity and 78.4%(95 %CI: 73.7%-82.5%) specificity for detecting NPDR and 64.5%(95 %CI: 56.0%-72.3%) sensitivity and 93.1%(95 %CI: 90.1%-95.3%) specificity for diagnosing PDR. CONCLUSION: EyeWisdom®DSS is effective in screening for DR, and the accuracy of EyeWisdom®MCS was higher for identifying patients without DR. It is valuable to carry out AI-based DR screening in poorer regions.

High-Fat Nutritional Challenge Reshapes Circadian Signatures in Murine Extraorbital Lacrimal Glands.

Purpose: A high-fat diet (HFD) increases the risk of developing many systemic diseases; however, the effects of high fat intake on lacrimal gland functions and the molecular mechanisms underlying these effects are unknown. We explored the effects of an HFD on the circadian rhythms of the extraorbital lacrimal glands (ELGs). Methods: Male C57BL/6J mice maintained on a 12/12-hour light/dark cycle were fed an ad libitum HFD or normal chow (NC) for 2 weeks. The ELGs were collected from euthanized animals every 3 hours throughout the circadian cycle (24 hours). Using high-throughput RNA-sequencing (RNA-Seq), we studied the circadian transcriptomic profile of the ELGs. Circadian oscillations in cell size, secretion response, lipid deposition, and immune cell trafficking of the ELGs were also analyzed. Results: An HFD modulated the circadian transcriptomic profile of the ELGs, including the composition, phase, and amplitude of cyclical transcript oscillations, and affected the associated signaling pathways at spatiotemporal levels. HFD feeding significantly altered the normal rhythmic oscillations of ELG cell size, immune cell trafficking, secretion response, and lipid deposition. After dietary reversal in HFD-fed animals, the activity, core temperature, and lipid accumulation in lacrimal glands recovered partially to the level of NC-fed animals. However, the average cell size of the ELGs, the recruitment of immune cells, and the rhythm of lacrimal secretion did not return to the levels of the NC-fed group. Conclusions: HFD perturbation interferes with the cyclical transcriptomic profile, cell size, immune cell trafficking, and secretion function of the ELGs with a strikingly high sensitivity.

Sleep Loss Causes Dysfunction in Murine Extraorbital Lacrimal Glands.

Purpose: Sleep loss markedly affects the structure and function of the lacrimal gland and may cause ocular surface disease as a common public health problem. This study aims to investigate the circadian disturbance caused by sleep loss leading to dysfunction of extraorbital lacrimal glands (ELGs). Methods: A mouse sleep deprivation (SD) model for sleep loss studies was built in C57BL/6J male mice. After four weeks, the ELGs were collected at three-hour intervals during a 24-hour period. The Jonckheere-Terpstra-Kendall algorithm was used to determine the composition, phase, and rhythmicity of transcriptomic profiles in ELGs. Furthermore, we compared the non-sleep-deprived and SD-treated mouse ELG (i) reactive oxygen species (ROS) by fluorescein staining, (ii) DNA damage by immunostaining for γ-H2Ax, and (iii) circadian migration of immune cells by immunostaining for CD4, CD8, γδ-TCR, CD64, and CX3CR1. Finally, we also evaluated (i) the locomotor activity and core body temperature rhythm of mice and (ii) the mass, cell size, and tear secretion of the ELGs. Results: SD dramatically altered the composition and phase-associated functional enrichment of the circadian transcriptome, immune cell trafficking, metabolism, cell differentiation, and neural secretory activities of mouse ELGs. Additionally, SD caused the ROS accumulation and consequent DNA damage in the ELGs, and the ELG dysfunction caused by SD was irreversible. Conclusions: SD damages the structure, function, and diurnal oscillations of ELGs. These results highlight comprehensive characterization of insufficient sleep-affected ELG circadian transcriptome that may provide a new therapeutic approach to counteract the effects of SD on ELG function.

Relationship between renal and liver function with diabetic retinopathy in patients with type 2 diabetes mellitus: a study based on cross-sectional data.

This study aims to explore the relationship between abnormal renal- and liver-function and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). A total of 994 T2DM patients who received inpatient treatment in the Endocrinology Department of Henan Province People's Hospital were included in the study. Logistic regression was performed to identify the relationship between abnormal renal and liver function with DR. Receiver operator characteristic analysis was performed to explore the efficacy of risk factors in predicting DR. Higher urine albumin [OR(95%CI) = 3.344(1.921-5.822), P < 0.001] and urine albumin/creatinine ratio [OR (95%CI) = 2.901(1.911-5.822), P < 0.001] were closely related to the occurrence of DR. People with low TP had a 1.624-times higher risk (95%CI: 1.008-2.617) of developing DR than those with normal total protein (P = 0.046). The more risk factors that are present, the greater the risk of DR. For every one-point incremental increase in the risk-factor score, the risk of DR increased by 31.0% (P < 0.001). The area under receiver operating curve of risk-factor score was 0.839 (0.812, 0.866), with a sensitivity of 81.9% and a specificity of 74.8%. The risk of developing DR increased with an increased risk-factor score. These findings are potentially valuable for DR screening and early diagnosis in patients with T2DM.