Association of macular outward scleral height with axial length, macular choroidal thickness and morphologic characteristics of the optic disc in Chinese adults.

PURPOSE: To identify the relationship of macular outward scleral height (MOSH) with axial length (AL), macular choroidal thickness (ChT), peripapillary atrophy (PPA), and optic disc tilt in Chinese adults. METHODS: In this cross-sectional study, 1088 right eyes of 1088 participants were enrolled and assigned into high myopia (HM) and non-HM groups. MOSH was measured in the nasal, temporal, superior, and inferior directions using swept-source optical coherence tomography images. The clinical characteristics of MOSH and the association of MOSH with AL, macular ChT, PPA, and tilt ratio were analysed. RESULTS: The mean age of participants was 37.31 ± 18.93 years (range, 18-86 years), and the mean AL was 25.78 ± 1.79 mm (range, 21.25-33.09 mm). MOSH was the highest in the temporal direction, followed by the superior, nasal, and inferior directions (all p < 0.001). The MOSH of HM eyes was significantly higher than that of non-HM eyes, and it was positively correlated with AL in the nasal, temporal, and superior directions (all p < 0.001). Macular ChT was independently associated with the average MOSH (B = -0.190, p < 0.001). Nasal MOSH was positively associated with the PPA area and the presence of a tilted optic disc (both p < 0.01). Eyes with a higher MOSH in the superior (odds ratio [OR] = 1.008; p < 0.001) and inferior directions (OR = 1.006; p = 0.009) were more likely to have posterior staphyloma. CONCLUSION: MOSH is an early indicator of scleral deformation, and it is correlated positively with AL and negatively with ChT. A higher nasal MOSH is associated with a larger PPA area and the presence of a tilted optic disc. Higher MOSH values in the superior and inferior directions were risk factors for posterior staphyloma. CLINICAL TRIAL REGISTRATION: The study was registered at www. CLINICALTRIALS: gov (Reg. No. NCT03446300).

Phosphorylation by ATR triggers FANCD2 chromatin loading and activates the Fanconi anemia pathway.

The Fanconi anemia (FA) pathway repairs DNA interstrand crosslinks (ICLs) in humans. Activation of the pathway relies on loading of the FANCD2/FANCI complex onto chromosomes, where it is fully activated by subsequent monoubiquitination. However, the mechanism for loading the complex onto chromosomes remains unclear. Here, we identify 10 SQ/TQ phosphorylation sites on FANCD2, which are phosphorylated by ATR in response to ICLs. Using a range of biochemical assays complemented with live-cell imaging including super-resolution single-molecule tracking, we show that these phosphorylation events are critical for loading of the complex onto chromosomes and for its subsequent monoubiquitination. We uncover how the phosphorylation events are tightly regulated in cells and that mimicking their constant phosphorylation leads to an uncontrolled active state of FANCD2, which is loaded onto chromosomes in an unrestrained fashion. Taken together, we describe a mechanism where ATR triggers FANCD2/FANCI loading onto chromosomes.

Potential Choroidal Mechanisms Underlying Atropine's Antimyopic and Rebound Effects: A Mediation Analysis in a Randomized Clinical Trial.

Purpose: To investigate whether choroidal vascularity participates in high-dose atropine's antimyopia and rebound mechanisms. Methods: A mediation analysis was embedded within a randomized controlled trial. In total, 207 myopic children were assigned randomly to group A/B. Participants in group A received 1% atropine weekly (phase 1) and 0.01% atropine daily (phase 2) for 6 months each. Those in group B received 0.01% atropine daily for 1 year. Four plausible intervention mediators were assessed: total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI). Results: In group A, LA, SA, and TCA increased significantly after receiving 1% atropine for 6 months. The increment diminished after tapering to 0.01% atropine. In group B, those parameters remained stable. TCA mediated approximately one-third of 1% atropine's effect on spherical equivalent progression in both phases. In phase 1, the mediation effect of TCA was shared by LA and SA, while only that of LA remained significant in phase 2. No mediation effect of CVI was found. Conclusions: One percent atropine induced choroidal thickening by increasing both LA and SA, while 0.01% atropine had little choroidal response. The choroidal changes following 1% atropine treatment diminished after switching to 0.01% atropine. TCA, but not CVI, partially explains atropine's antimyopic and myopic-rebound mechanisms. SA may serve as a potential biomarker to predict the postrebound treatment efficacy of high-dose atropine. (ClinicalTrials.gov number, NCT03949101.).

Efficacy and Safety of Consecutive Use of 1% and 0.01% Atropine for Myopia Control in Chinese Children: The Atropine for Children and Adolescent Myopia Progression Study.

INTRODUCTION: The purpose of this study was to investigate the efficacy and safety of consecutive use of 1% and 0.01% atropine compared with 0.01% atropine alone over 1 year. METHODS: A total of 207 participants aged 6-12 years with myopia of - 0.50 to - 6.00 D in both eyes were enrolled in this randomized, controlled, non-masked trial and randomly assigned (1:1) to groups A and B. Group A received 1% atropine weekly and were tapered to 0.01% atropine daily at the 6-month visit, and group B received 0.01% atropine daily for 1 year. RESULTS: Of the 207 participants, 109 were female (52.7%) and the mean (± standard deviation) age was 8.92 ± 1.61 years. Ninety-one participants (87.5%) in group A and 80 participants (77.7%) in group B completed the 1-year treatment. Group A exhibited less refraction progression (- 0.53 ± 0.49 D vs. - 0.74 ± 0.52 D; P = 0.01) and axial elongation (0.26 ± 0.17 mm vs. 0.36 ± 0.21 mm; P < 0.001) over 1 year compared with group B. The changes in refraction (- 0.82 ± 0.45 D vs. - 0.46 ± 0.35 D; P < 0.001) and axial length (0.29 ± 0.12 mm vs. 0.17 ± 0.11 mm; P < 0.001) during the second 6 months in group A were greater than those in group B, with 72.5% of participants presenting refraction rebound. No serious adverse events were reported. CONCLUSIONS: The 1-year results preliminarily suggest that consecutive use of 1% and 0.01% atropine confers an overall better effect in slowing myopia progression than 0.01% atropine alone, despite myopia rebound after the concentration switch. Both regimens were well tolerated. The long-term efficacy and rebound after the concentration switch and regimen optimization warrant future studies to determine. TRIAL REGISTRATION NUMBER: Clinical Trials.gov PRS (Registration No. NCT03949101).

[Effects and pathophysiological significance of intestinal flora on the enteric neuro-endocrine-immune system].

Interactions among the nervous, the endocrine and the immune systems enable the gut to respond to the dietary products, pathogens and microbiota, which maintains the homeostasis of the body. However, dysbiosis may induce or aggravate the gastrointestinal (GI) and extra-GI diseases through changing the activities of enteric nervous system (ENS), enteroendocrine cells and enteric immune cells. Here we review recent advances in the understandings on how intestinal flora may impact the enteric neuro-endocrine-immune system in the gut, thereby contributing to the regulation of pathophysiological processes.

Identification of an essential regulator controlling the production of raw-starch-digesting glucoamylase in Penicillium oxalicum.

BACKGROUND: Raw-starch-digesting glucoamylases (RSDGs) from filamentous fungi have great commercial values in starch processing; however, the regulatory mechanisms associated with their production in filamentous fungi remain unknown. Penicillium oxalicum HP7-1 isolated by our laboratory secretes RSDG with suitable properties but at low production levels. Here, we screened and identified novel regulators of RSDG gene expression in P. oxalicum through transcriptional profiling and genetic analyses. RESULTS: Penicillium oxalicum HP7-1 transcriptomes in the presence of glucose and starch, respectively, used as the sole carbon source were comparatively analyzed, resulting in screening of 23 candidate genes regulating the expression of RSDG genes. Following deletion of 15 of the candidate genes in the parental P. oxalicum strain ∆PoxKu70, enzymatic assays revealed five mutants exhibiting significant reduction in the production of raw-starch-digesting enzymes (RSDEs). The deleted genes (POX01907, POX03446, POX06509, POX07078, and POX09752), were the first report to regulate RSDE production of P. oxalicum. Further analysis revealed that ∆POX01907 lost the most RSDE production (83.4%), and that POX01907 regulated the expression of major amylase genes, including the RSDG gene POX01356/PoxGA15A, a glucoamylase gene POX02412, and the α-amylase gene POX09352/Amy13A, during the late-stage growth of P. oxalicum. CONCLUSION: Our results revealed a novel essential regulatory gene POX01907 encoding a transcription factor in controlling the production of RSDE, regulating the expression of an important RSDG gene POX01356/PoxGA15A, in P. oxalicum. These results provide insight into the regulatory mechanism of fungal amylolytic enzyme production.

The underlying pathway involved in inter-subspecific hybrid male sterility in rice.

f5 locus in rice (Oryza sativa L.) confers significant effects on hybrid male sterility and segregation distortion. BC14F2 plants with f5-i/i, f5-j/j and f5-i/j genotypes were used to dissect the underlying pathway of f5-caused hybrid male sterility via comparative transcriptome analysis. A total of 350, 421, and 480 differentially expressed genes (DEGs) were identified from f5-i/j vs f5-j/j, f5-j/j vs f5-i/i, and f5-i/j vs f5-i/i, respectively. 145 DEGs were identified simultaneously in f5-i/j vs f5-j/j and f5-i/j vs f5-i/i. Enrichment analysis indicated that stress and cell control related processes were enriched. The expression of ascorbate peroxidase (APX) and most of the heat shock proteins (HSPs) were decreased, which might result in higher sensitivity to various stresses in pollen cells. A model was proposed to summarize the underlying process for f5-caused hybrid male sterility. These results would provide significant clues to further dissecting the molecular mechanism of f5-caused inter-subspecific reproductive isolation.