A programmable targeted protein-degradation platform for versatile applications in mammalian cells and mice.

Myriad physiological and pathogenic processes are governed by protein levels and modifications. Controlled protein activity perturbation is essential to studying protein function in cells and animals. Based on Trim-Away technology, we screened for truncation variants of E3 ubiquitinase Trim21 with elevated efficiency (ΔTrim21) and developed multiple ΔTrim21-based targeted protein-degradation systems (ΔTrim-TPD) that can be transfected into host cells. Three ΔTrim-TPD variants are developed to enable chemical and light-triggered programmable activation of TPD in cells and animals. Specifically, we used ΔTrim-TPD for (1) red-light-triggered inhibition of HSV-1 virus proliferation by degrading the packaging protein gD, (2) for chemical-triggered control of the activity of Cas9/dCas9 protein for gene editing, and (3) for blue-light-triggered degradation of two tumor-associated proteins for spatiotemporal inhibition of melanoma tumor growth in mice. Our study demonstrates that multiple ΔTrim21-based controllable TPD systems provide powerful tools for basic biology research and highlight their potential biomedical applications.

Intergrative metabolomic and transcriptomic analyses reveal the potential regulatory mechanism of unique dihydroxy fatty acid biosynthesis in the seeds of an industrial oilseed crop Orychophragmus violaceus.

BACKGROUND: Orychophragmus violaceus is a potentially important industrial oilseed crop due to the two 24-carbon dihydroxy fatty acids (diOH-FA) that was newly identified from its seed oil via a 'discontinuous elongation' process. Although many research efforts have focused on the diOH-FA biosynthesis mechanism and identified the potential co-expressed diacylglycerol acyltranferase (DGAT) gene associated with triacylglycerol (TAG)-polyestolides biosynthesis, the dynamics of metabolic changes during seed development of O. violaceus as well as its associated regulatory network changes are poorly understood. RESULTS: In this study, by combining metabolome and transcriptome analysis, we identified that 1,003 metabolites and 22,479 genes were active across four stages of seed development, which were further divided into three main clusters based on the patterns of metabolite accumulation and/or gene expression. Among which, cluster2 was mostly related to diOH-FA biosynthesis pathway. We thus further constructed transcription factor (TF)-structural genes regulatory map for the genes associated with the flavonoids, fatty acids and diOH-FA biosynthesis pathway in this cluster. In particular, several TF families such as bHLH, B3, HD-ZIP, MYB were found to potentially regulate the metabolism associated with the diOH-FA pathway. Among which, multiple candidate TFs with promising potential for increasing the diOH-FA content were identified, and we further traced the evolutionary history of these key genes among species of Brassicaceae. CONCLUSION: Taken together, our study provides new insight into the gene resources and potential relevant regulatory mechanisms of diOH-FA biosynthesis uniquely in seeds of O. violaceus, which will help to promote the downstream breeding efforts of this potential oilseed crop and advance the bio-lubricant industry.

Mapping quantitative trait loci associated with self-(in)compatibility in goji berries (Lycium barbarum).

BACKGROUND: Goji (Lycium barbarum L.) is a perennial deciduous shrub widely distributed in arid and semiarid regions of Northwest China. It is highly valued for its medicinal and functional properties. Most goji varieties are naturally self-incompatible, posing challenges in breeding and cultivation. Self-incompatibility is a complex genetic trait, with ongoing debates regarding the number of self-incompatible loci. To date, no genetic mappings has been conducted for S loci or other loci related to self-incompatibility in goji. RESULTS: We used genome resequencing to create a high-resolution map for detecting de novo single-nucleotide polymorphisms (SNP) in goji. We focused on 229 F1 individuals from self-compatible '13-19' and self-incompatible 'new 9' varieties. Subsequently, we conducted a quantitative trait locus (QTL) analysis on traits associated with self-compatibility in goji berries. The genetic map consisted of 249,327 SNPs distributed across 12 linkage groups (LGs), spanning a total distance of 1243.74 cM, with an average interval of 0.002 cM. Phenotypic data related to self-incompatibility, such as average fruit weight, fruit rate, compatibility index, and comparable compatibility index after self-pollination and geitonogamy, were collected for the years 2021-2022, as well as for an extra year representing the mean data from 2021 to 2022 (2021/22). A total of 43 significant QTL, corresponding to multiple traits were identified, accounting for more than 11% of the observed phenotypic variation. Notably, a specific QTL on chromosome 2 consistently appeared across different years, irrespective of the relationship between self-pollination and geitonogamy. Within the localization interval, 1180 genes were annotated, including Lba02g01102 (annotated as an S-RNase gene), which showed pistil-specific expression. Cloning of S-RNase genes revealed that the parents had two different S-RNase alleles, namely S1S11 and S2S8. S-genotype identification of the F1 population indicated segregation of the four S-alleles from the parents in the offspring, with the type of S-RNase gene significantly associated with self-compatibility. CONCLUSIONS: In summary, our study provides valuable insights into the genetic mechanism underlying self-compatibility in goji berries. This highlights the importance of further positional cloning investigations and emphasizes the importance of integration of marker-assisted selection in goji breeding programs.

Prevalence and characteristics of amblyopia, strabismus, and refractive errors among patients aged 3-16 years in Shanghai, China: a hospital-based population study.

BACKGROUND: Functional visual impairments in children are primarily caused by amblyopia or strabismus. This study aimed to determine the prevalence and clinical profile of amblyopia and strabismus among individuals aged 3-16 years in Shanghai, China. METHODS: From February 2023 to February 2024, this hospital-based, cross-sectional study included data of children who visited the Ophthalmology Department of Shanghai General Hospital. Comprehensive ocular examinations included visual acuity measurement after cycloplegic refraction, slit lamp examination, cover test, and dilated fundus examination. Descriptive statistics were performed to estimate the proportion and clinical characteristics of amblyopia and strabismus. RESULTS: A total of 920 children were enrolled in our study. Among them, 223 (24.24%) children were identified as amblyopia. Unilateral amblyopia occupied 57.85%, and bilateral amblyopia occupied 42.15%. Most participants were within the age range of 5-10 years (75.97% for unilateral amblyopia, and 70.21% for bilateral amblyopia). Anisometropia was the primary cause of unilateral amblyopia (68.99%). Most amblyopic children have high hyperopia (38.76% for unilateral amblyopia, and 39.89% for bilateral amblyopia). 30 (3.26%) children were diagnosed with strabismus, and 19 (63.3%) of them were aged 5-10 years. Seven of the children had both strabismus and amblyopia. CONCLUSION: The proportion of patients with amblyopia and strabismus was determined as 24.24% and 3.26% in our study. Anisometropia was the leading cause of unilateral amblyopia, whereas high hyperopia was a crucial refractive error in the amblyopic population. These findings shed light on further longitudinal studies targeting the age-related changes in amblyopia, strabismus and refraction errors. Therefore, efforts should be made to manage uncorrected refractive errors, amblyopia, and strabismus among children in Shanghai.

Association between ambient air pollution and age-related macular degeneration: a meta-analysis.

BACKGROUND: Several epidemiological studies have investigated the association between ambient air pollution and age-related macular degeneration (AMD). However, a consensus has not yet been reached. Our meta-analysis aimed to clarify this association. METHODS: Databases, including PubMed, EMBASE, and Web of Science, were searched for relevant studies from 01 January 2000 to 30 January 2024. English-language, peer-reviewed studies using cross-sectional, prospective, or retrospective cohorts and case-control studies exploring this relationship were included. Two authors independently extracted data and assessed study quality. A random-effects model was used to calculate pooled covariate-adjusted odds ratios. Heterogeneity across studies was also tested. RESULTS: We identified 358 relevant studies, of which eight were included in the meta-analysis. Four studies evaluated the association between particulate matter less than 2.5 µm in diameter (PM2.5) and AMD, and three studies explored the relationship between nitrogen dioxide (NO2) or ozone (O3) and AMD. The pooled odds ratios were 1.16 (95% confidence interval [CI]: 1.11-1.21), 1.17 (95% CI: 1.09-1.25), and 1.06 (95% CI: 1.05-1.07), respectively. CONCLUSION: Current evidence suggests a concomitant positive but not causal relationship between PM2.5, NO2, or O3 and AMD risk.

Double-dose investigation of aflibercept in neovascular age-related macular degeneration (DIANA): a real-world study.

BACKGROUND: To investigate the clinical effects of double-dose (4 mg) aflibercept treatment in neovascular age-related macular degeneration (nAMD), compared with the standard-dose (2 mg) treatment. METHODS: A total of 108 eyes from 97 patients with nAMD and received intravitreal aflibercept 2 mg and/or 4 mg treatment were retrospectively reviewed. The changes of central macular thickness (CMT)/ pigmental epithelium detachment height and the recurrence rate of exudation during the 12-month follow-up were compared between the 2 mg group and the 4 mg group. Self-control comparisons (2 mg switch to 4 mg) were also made between two regimens. RESULTS: Compared with the 2 mg group, tendencies of lower intraretinal fluid incidence and more CMT reduction were observed in the 4 mg group. The later one was also observed when eyes switching from 2 mg to 4 mg regimen. The median remission interval was 5 months in the 4 mg group, 2 months longer than the 3 months in the 2 mg group (P = 0.452). Injections needed in the 4 mg group were 3.644 ± 1.670, less than the 4.286 ± 2.334 injections in the 2 mg group within 12 months as well (P = 0.151). However, no associated vision benefits were gained from the double-douse regimen. No markedly increased-intraocular pressure events, or other adverse events were found in two groups. CONCLUSIONS: Compared to the aflibercept 2 mg treatment in nAMD, tendencies of anatomic gains and relieving treatment burden were brought by the aflibercept 4 mg treatment. This study may have additional importance, given the further application of high-dose aflibercept in real-world settings.

Engineering genetic devices for in vivo control of therapeutic T cell activity triggered by the dietary molecule resveratrol.

Chimeric antigen receptor (CAR)-engineered T cell therapies have been recognized as powerful strategies in cancer immunotherapy; however, the clinical application of CAR-T is currently constrained by severe adverse effects in patients, caused by excessive cytotoxic activity and poor T cell control. Herein, we harnessed a dietary molecule resveratrol (RES)-responsive transactivator and a transrepressor to develop a repressible transgene expression (RESrep) device and an inducible transgene expression (RESind) device, respectively. After optimization, these tools enabled the control of CAR expression and CAR-mediated antitumor function in engineered human cells. We demonstrated that a resveratrol-repressible CAR expression (RESrep-CAR) device can effectively inhibit T cell activation upon resveratrol administration in primary T cells and a xenograft tumor mouse model. Additionally, we exhibit how a resveratrol-inducible CAR expression (RESind-CAR) device can achieve fine-tuned and reversible control over T cell activation via a resveratrol-titratable mechanism. Furthermore, our results revealed that the presence of RES can activate RESind-CAR T cells with strong anticancer cytotoxicity against cells in vitro and in vivo. Our study demonstrates the utility of RESrep and RESind devices as effective tools for transgene expression and illustrates the potential of RESrep-CAR and RESind-CAR devices to enhance patient safety in precision cancer immunotherapies.

Publication trends of vascular endothelial growth factor (VEGF) and anti-VEGF treatment in neovascular age-related macular degeneration during 2001-2020: a 20-year bibliometric study.

PURPOSE: This study sought to provide an overview of the current research and further analyze publication trends in the field of vascular endothelial growth factor (VEGF) and anti-VEGF treatment for neovascular age-related macular degeneration (NVAMD). METHODS: We downloaded all related publications from 2001 to 2020 from the Web of Science Core Collection and conducted a bibliometric analysis using the bibiometrix package in R programming software. RESULTS: A total of 3717 publications were included in the analysis. The USA contributed the largest number of publications (1443), and achieved the highest number of citations (74,946) and H-index value (28). Johns Hopkins University, USA, was the top institution with the most publications, and Peter A. Campochiaro was the most productive professor at The Wilmer Eye Institute, USA. 9.60% of the total publications were from the Journal of Retinal and Vitreous Diseases. Trend analysis demonstrated that anti-VEGF therapy was introduced in early 2000 after steroids, and the last 2 decades have witnessed the blossom of several anti-VEGF agents. "Treat-and-extend" and "resistance" were two popular trend topics in recent years. CONCLUSIONS: The USA occupies a dominant position in the research field of VEGF and anti-VEGF treatments in NVAMD. Steroid administration, photodynamic therapy, and anti-VEGF therapy have been pivotal advances in the treatment of NVAMD patients over the past 2 decades. Limited acting period and resistance are potential investigation directions in future studies.

Demographic History and Natural Selection Shape Patterns of Deleterious Mutation Load and Barriers to Introgression across Populus Genome.

Hybridization and resulting introgression are important processes shaping the tree of life and appear to be far more common than previously thought. However, how the genome evolution was shaped by various genetic and evolutionary forces after hybridization remains unresolved. Here we used whole-genome resequencing data of 227 individuals from multiple widespread Populus species to characterize their contemporary patterns of hybridization and to quantify genomic signatures of past introgression. We observe a high frequency of contemporary hybridization and confirm that multiple previously ambiguous species are in fact F1 hybrids. Seven species were identified, which experienced different demographic histories that resulted in strikingly varied efficacy of selection and burdens of deleterious mutations. Frequent past introgression has been found to be a pervasive feature throughout the speciation of these Populus species. The retained introgressed regions, more generally, tend to contain reduced genetic load and to be located in regions of high recombination. We also find that in pairs of species with substantial differences in effective population size, introgressed regions are inferred to have undergone selective sweeps at greater than expected frequencies in the species with lower effective population size, suggesting that introgression likely have higher potential to provide beneficial variation for species with small populations. Our results, therefore, illustrate that demography and recombination have interplayed with both positive and negative selection in determining the genomic evolution after hybridization.

m6A methyltransferase METTL3 programs CD4+ T-cell activation and effector T-cell differentiation in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder in which excessive CD4+ T-cell activation and imbalanced effector T-cell differentiation play critical roles. Recent studies have implied a potential association between posttranscriptional N6-methyladenosine (m6A) modification and CD4+ T-cell-mediated humoral immunity. However, how this biological process contributes to lupus is not well understood. In this work, we investigated the role of the m6A methyltransferase like 3 (METTL3) in CD4+ T-cell activation, differentiation, and SLE pathogenesis both in vitro and in vivo. METHODS: The expression of METTL3 was knocked down and METTL3 enzyme activity was inhibited using siRNA and catalytic inhibitor, respectively. In vivo evaluation of METTL3 inhibition on CD4+ T-cell activation, effector T-cell differentiation, and SLE pathogenesis was achieved using a sheep red blood cell (SRBC)-immunized mouse model and a chronic graft versus host disease (cGVHD) mouse model. RNA-seq was performed to identify pathways and gene signatures targeted by METTL3. m6A RNA-immunoprecipitation qPCR was applied to confirm the m6A modification of METTL3 targets. RESULTS: METTL3 was defective in the CD4+ T cells of SLE patients. METTL3 expression varied following CD4+ T-cell activation and effector T-cell differentiation in vitro. Pharmacological inhibition of METTL3 promoted the activation of CD4+ T cells and influenced the differentiation of effector T cells, predominantly Treg cells, in vivo. Moreover, METTL3 inhibition increased antibody production and aggravated the lupus-like phenotype in cGVHD mice. Further investigation revealed that catalytic inhibition of METTL3 reduced Foxp3 expression by enhancing Foxp3 mRNA decay in a m6A-dependent manner, hence suppressing Treg cell differentiation. CONCLUSION: In summary, our findings demonstrated that METTL3 was required for stabilizing Foxp3 mRNA via m6A modification to maintain the Treg differentiation program. METTL3 inhibition contributed to the pathogenesis of SLE by participating in the activation of CD4+ T cells and imbalance of effector T-cell differentiation, which could serve as a potential target for therapeutic intervention in SLE.

3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus.

OBJECTIVES: Three-dimensional (3D) genome alterations can dysregulate gene expression by rewiring physical interactions within chromosomes in a tissue-specific or cell-specific manner and lead to diseases. We aimed to elucidate the 3D genome structure and its role in gene expression networks dysregulated in systemic lupus erythematosus (SLE). METHODS: We performed Hi-C experiments using CD4+ T cells from 7 patients with SLE and 5 age-matched and sex-matched healthy controls (HCs) combined with RNA sequencing analysis. Further integrative analyses, including transcription factor motif enrichment, SPI1 knockdown and histone modifications (H3K27ac, H3K4me1, H3K4me3), were performed for altered loop-associated gene loci in SLE. RESULTS: We deciphered the 3D chromosome organisation in T cells of patients with SLE and found it was clearly distinct from that of HCs and closely associated with the disease activity of SLE. Importantly, we identified loops within chromosomes associated with the disease activity of SLE and differentially expressed genes and found some key histone modifications close to these loops. Moreover, we demonstrated the contribution of the transcription factor SPI1, whose motif is located in the altered loop in SLE, to the overexpression of interferon pathway gene. In addition, we identified the potential influences of genetic variations in 3D genome alterations in SLE. CONCLUSIONS: Our results highlight the 3D genome structure alterations associated with SLE development and provide a foundation for future interrogation of the relationships between chromosome structure and gene expression control in SLE.

The potential bidirectional association between Helicobacter pylori infection and gallstone disease in adults: A two-cohort study.

BACKGROUND: Previous studies have suggested that Helicobacter pylori (H. pylori) may act as a precipitating factor in gallstone formation, and the potential association between H. pylori infection and gallstone disease (GD) is still unclear and controversial. This study aimed to clarify the potential bidirectional relationship between H. pylori infection and GD. METHODS: This retrospective cohort study was performed in a population that underwent health checkups at the hospital between 2013 and 2018. H. pylori infection status was evaluated by urea breath test (UBT), and GD was diagnosed via ultrasound. Cox regression and propensity score matching (PSM) were used. RESULTS: Among 1011 participants without H. pylori infection at baseline, 134 participants were infected with H. pylori. Among 1192 participants without gallstones or cholecystectomy at baseline, 60 participants developed gallstones or cholecystectomy. The hazard ratio (HR) (95% CI) for incident H. pylori infection comparing the GD versus the no GD group was 1.84 (1.19, 2.85). The age- and sex-adjusted HR (95% CI) for incident GD comparing H. pylori-positive subjects to H. pylori-negative subjects was 1.74 (1.01, 2.98). Consistent results were also found with PSM and multivariate analysis. CONCLUSIONS: This cohort study demonstrated a potential bidirectional association between H. pylori infection and GD, which provides a basis for indicating the risk of GD and implementing the clinical strategies for GD. For the prevention and treatment of GD, H. pylori infection should be carefully considered and evaluated.

The value of contrast-enhanced harmonic endoscopic ultrasound in differential diagnosis and evaluation of malignant risk of gastrointestinal stromal tumors (<50mm).

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) has been used in the differential diagnosis of benign and malignant tumors by visualization of tumor microcirculation and perfusion. However, its diagnostic role in submucosal tumors (SMTs), especially leiomyomas and gastric submucosal tumors (GISTs) was rarely studied. The aim of this study was to analyze the diagnostic role of CEH-EUS for SMTs (<50 mm) and the value of assessing the malignant potential of GISTs. MATERIALS AND METHODS: We retrospectively included patients with tumors <50 mm in diameter who underwent preoperative EUS and CEH-EUS examination and had pathologically confirmed as leiomyomas and GISTs. To analyze the imaging features of CEH-EUS with pathological diagnosis as the gold standard and evaluate its diagnostic value. RESULTS: This study included 10 cases of leiomyomas and 38 cases of GISTs. Under CEH-EUS detection, 86.9% of GISTs showed hyper-enhancement, 89.5% showed diffuse enhancement, 39.5% showed non-enhancing spots, and 97.4% showed obvious capsule enhancement. In contrast, the leiomyoma cases mostly showed hypo-enhancement (50.0%) or non-enhancement (30.0%) (p < 0.05). Then, the value of CEH-EUS in the differential diagnosis of benign and malignant tumors based on blood flow is significantly higher than that of B-EUS. Signal appearance time was significantly faster in the intermediate-high risk GISTs than in the very low-low risk group (5.1 s versus 15.5 s, p < 0.05), and the AUROC values predicted the risk at this time to be 0.903 (0.763-0.975). Heterogeneous perfusion and non-enhancing spots were also more common in the intermediate-high risk group. Univariate and multivariate analysis revealed that intratumoral irregularitie was an independent predictor of moderate to high risk (OR 3.99, 95%CI 1.04-90.95), with sensitivity, specificity and accuracy of 73.33%, 91.30% and 84.21%, respectively. CONCLUSIONS: Through this study, CEH-EUS has a good differential diagnostic ability for leiomyomas and GISTs, and has a high value in predicting the risk of GISTs.

Risk Factors Related to Polyp Miss Rate of Short-Term Repeated Colonoscopy.

BACKGROUND: Colonoscopy is regarded as the gold standard for colorectal cancer screening and surveillance. However, previous studies have reported large numbers of polyps were missed during routine colonoscopy. AIMS: To evaluate polyp miss rate in short-term repeated colonoscopy and explore the related risk factors. METHODS: A total of 3695 patients and 12,412 polyps were included in our studies. We calculated the miss rate for polyps of different sizes, pathologies, morphologies and locations, and patients of different characteristics. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors related to miss rate. RESULTS: The polyp miss rate was 26.3% and the adenoma miss rate was 22.4% in our study. The advanced adenoma miss rate was 11.0% and the proportion of missed advanced adenomas in missed adenomas sized > 5 mm was up to 22.8%. Polyps sized < 5 mm had a significantly higher miss rate. The miss rate of pedunculated polyps was lower than that of flat or sessile polyps. Polyps in the right colon were prone to be missed than that in the left colon. For older men, current smokers, individuals with multiple polyps detected in the first colonoscopy, the risk of missing polyps was significantly higher. CONCLUSION: Nearly a quarter of polyps were missed during routine colonoscopy. Diminutive, flat, sessile, and right-side colon polyps were at higher risk of missing. The risk of missing polyps was higher in older men, current smokers, and individuals with multiple polyps detected in the first colonoscopy than their counterparts.

Identification and Validation of an Aging-Associated circRNA-miRNA-mRNA Network in Neovascular Age-Related Macular Degeneration.

INTRODUCTION: Neovascular age-related macular degeneration (NVAMD) is a leading cause of severe vision impairment in the elderly. Aging is one of the most pivotal underlying molecular mechanisms of NVAMD. METHODS: In this study, we identified the potential aging-related genes involved in NVAMD. Considering that noncoding RNAs are vital regulators of NVAMD progression, we further explored and constructed an aging-originated circRNA-miRNA-mRNA network of NVAMD. Differential expression of 23 aging-associated genes was identified based on sequencing data and the Human Aging Genomic Resources tool at a threshold of p < 0.05, and log2|fold change| > 1. RESULTS: We screened 12 microRNAs (miRNAs) using public datasets and miRNet database. A total of 13 circRNAs were subsequently mined using the starBase tool. Merging these 13 circRNAs, 12 miRNAs, and 15 genes together, we obtained 281 pairs of circRNA-miRNA and 30 pairs of miRNA-mRNA. CONCLUSION: We created an aging-related circRNA-miRNA-mRNA network, which could be a promising target for future AMD treatments.

Identification of Cuproptosis-Related circRNA-miRNA-mRNA Network in Laser-Induced Choroidal Neovascularization Models and in Peripheral Blood Mononuclear Cells of Patients with Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The aims of this study were to investigate the molecular alterations of cuproptosis-related genes and to construct the cuproptosis-related circular RNA (circRNA)-microRNA (miRNA)-mRNA networks in neovascular age-related macular degeneration (nAMD). METHODS: The transcriptional profiles of laser-induced choroid neovascularization (CNV) mouse models and nAMD patient samples were obtained from sequencing and from the GEO database (GSE146887), respectively. The expression levels of ten cuproptosis-related genes (FDX1, DLAT, LIAS, DLD, PDHB, MTF1, CDKN2A, GLS, LIPT1, and PDHA1) were extracted and verified in both mouse CNV models and patient peripheral blood mononuclear cells (PBMCs) samples. The cuproptosis-related circRNA-miRNA-mRNA network was further constructed based on miRNet database, the dataset GSE131646 of small RNA expression profile, and the dataset GSE140178 of circRNA expression profile in mouse CNV models. RESULTS: The significant upregulation of Cdkn2a and Mtf1 and the downregulation of other 5 cuproptosis-related genes were verified in the mouse CNV model, but only CDKN2A significantly upregulated in PBMCs of patients with nAMD. Four miRNAs were detected in the intersection between miRNet prediction and sequencing data: miR-129-5p, miR-129-2-3p, miR-182-5p, and miR-615-3p. There were 9 circRNAs at the intersection of hsa-miR-182-5p and hsa-miR-615-3p predictions, one circRNA predicted by hsa-miR-129-5p and GSE140178 (hsa-circASH1L), and one circRNA predicted by hsa-miR-182-5p and hsa-miR-615-3p (hsa-circNPEPPS). CONCLUSION: This study suggested the repression of cuproptosis in nAMD pathologies and constructed a cuproptosis-related network of 8 cuproptosis-related genes, 4 miRNAs, and 11 circRNAs.

Predicting postoperative delirium after hip arthroplasty for elderly patients using machine learning.

BACKGROUND: Postoperative delirium (POD) is a common and severe complication in elderly hip-arthroplasty patients. AIM: This study aims to develop and validate a machine learning (ML) model that determines essential features related to POD and predicts POD for elderly hip-arthroplasty patients. METHODS: The electronic record data of elderly patients who received hip-arthroplasty surgery between January 2017 and April 2021 were enrolled as the dataset. The Confusion Assessment Method (CAM) was administered to the patients during their perioperative period. The feature section method was employed as a filter to determine leading features. The classical machine learning algorithms were trained in cross-validation processing, and the model with the best performance was built in predicting the POD. Metrics of the area under the curve (AUC), accuracy (ACC), sensitivity, specificity, and F1-score were calculated to evaluate the predictive performance. RESULTS: 476 Arthroplasty elderly patients with general anesthesia were included in this study, and the final model combined feature selection method mutual information (MI) and linear binary classifier using logistic regression (LR) achieved an encouraging performance (AUC = 0.94, ACC = 0.88, sensitivity = 0.85, specificity = 0.90, F1-score = 0.87) on a balanced test dataset. CONCLUSION: The model could predict POD with satisfying accuracy and reveal important features of suffering POD such as age, Cystatin C, GFR, CHE, CRP, LDH, monocyte count, history of mental illness or psychotropic drug use and intraoperative blood loss. Proper preoperative interventions for these factors could reduce the incidence of POD among elderly patients.

Correlation between B-cell lymphoma 6 with the balance of T helper-1/2 and severity of allergic rhinitis.

OBJECTIVE: Allergic rhinitis (AR) is a prevailing immune disorder affecting the nasal mucosa. B-cell lymphoma 6 (BCL6) imposes essential roles in immunity. This study probed into the serum expression of BCL6 and its effect on AR diagnosis and patients' quality of life (QOL). METHODS: A total of 113 patients with AR including 38 cases with mild AR (MAR) and 75 cases with moderate-severe AR (MSAR) were enrolled, with 101 healthy people enrolled as control. Serum expression of BCL6 was detected by RT-qPCR and the diagnostic efficacy of BCL6 for AR was analyzed using the receiver operating characteristic curve. The proportion of T helper-1/2 (Th1/Th2) cells in CD4+ T cells in peripheral blood mononuclear cells was detected using flow cytometry. The correlation between BCL6 and Th1/Th2 cells and the effects of BCL6 expression on patients' QOL were assessed by Pearson analysis and Mini-RQLQ questionnaire. RESULTS: BCL6 was downregulated in patients with AR, serum BCL6 level < 0.8450 had certain auxiliary diagnostic values for AR, and serum BCL6 level < 0.5400 could assist the diagnosis of AR severity. Th1 cell proportion in CD4+ T cells was decreased, whereas Th2 cell proportion was increased with AR severity. BCL6 was positively-linked with Th1 cells but inversely-correlated with Th2 cells in patients with AR. Patients with AR with low BCL6 expression had a poorer QOL compared with high BCL6 expression. The domains most affected by BCL6 expression were practical problems, nasal symptoms, and lacrimation. CONCLUSION: Serum BCL6 is downregulated and low BCL6 expression greatly deteriorates QOL in patients with AR.

Ultrafast Time-Resolved Pump-Probe Investigation of Nanosecond Extreme Ultraviolet-Light-Induced Damage Dynamics on B4C/Ru Nano-Bilayer Film.

An ultrafast time-resolved pump-probe setup with both high temporal and spatial resolution is developed to investigate the transient interaction between a nanosecond extreme ultraviolet (EUV) pulse and matter. By using a delayed femtosecond probe pulse, the pattern evolution of surface modification induced by an EUV pump at a wavelength of 13.5 nm can be imaged at different delay times, which provides deep insight into the EUV-induced damage dynamics and damage mechanisms. As a demonstration, single-shot EUV damage on a B4C(6.0 nm)/Ru(30.4 nm)/D263 nano-bilayer optical film is studied using this pump-probe method. A recoverable phenomenon is found during the evolution process of the dome-shaped damage region. This is explained by the elastic and plastic deformations resulting from the huge compressive stress difference at the Ru-substrate interface with the help of simulations on the thermal effects and mechanical responses. This damage mechanism is further proven by the complementary experiments at a higher EUV fluence at 13.5 nm.

Full-Length RNA Sequencing Provides Insights into Goldfish Evolution under Artificial Selection.

Goldfish Carassius auratus is an ideal model for exploring fish morphology evolution. Although genes underlying several ornamental traits have been identified, little is known about the effects of artificial selection on embryo gene expression. In the present study, hybrid transcriptome sequencing was conducted to reveal gene expression profiles of Celestial-Eye (CE) and Ryukin (RK) goldfish embryos. Full-length transcriptome sequencing on the PacBio platform identified 54,218 and 54,106 transcript isoforms in CE and RK goldfish, respectively. Of particular note was that thousands of alternative splicing (AS) and alternative polyadenylation (APA) events were identified in both goldfish breeds, and most of them were inter-breed specific. RT-PCR and Sanger sequencing showed that most of the predicted AS and APA were correct. Moreover, abundant long non-coding RNA and fusion genes were detected, and again most of them were inter-breed specific. Through RNA-seq, we detected thousands of differentially expressed genes (DEGs) in each embryonic stage between the two goldfish breeds. KEGG enrichment analysis on DEGs showed extensive differences between CE and RK goldfish in gene expression. Taken together, our results demonstrated that artificial selection has led to far-reaching influences on goldfish gene expression, which probably laid the genetic basis for hundreds of goldfish variations.