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Uterine surgical scarring is an increasing risk factor for adverse pregnant consequences that threaten fetal-maternal health. BRD7389 The detailed molecular features of scar implantation remain largely unknown. We aim to study the pathologic features of uterine surgical scarring and the mechanisms of compromised pregnancy outcomes of scar implantation. We generated a mouse model of uterine surgical scarring with a uterine incision penetrating the myometrium to endometrium to examine the pathologic changes and transcriptome profiles of uterine scarring at various postsurgery (PS) time points, as well as features of the feto-maternal interface during scar implantation. We found that uterine surgical scar recovery was consistently poor at PS3 until PS90, as shown by a reduced number of endometrial glands, inhibition of myometrial smooth muscle cell growth but excessive collagen fiber deposition, and massive leukocyte infiltration. Transcriptome annotation indicated significant chronic inflammation at the scarring site. At the peri-implantation and postimplantation stages, abnormal expression of various steroid-responsive genes at the scarring site was in parallel with lumen epithelial cell hyperplasia, inappropriate luminal closure, and disorientation of the implanted embryo, restricted stromal cell proliferation, and defective decidualization. High embryonic lethality (around 70%) before E10.5 was observed, and the small amount of survival embryos at E10.5 exhibited restricted growth and aberrant placenta defects including overinvasion of trophoblast cells into the decidua and insufficient fetal blood vessel branching in the labyrinth. The findings indicate that chronic inflammation and compromised responses to steroids in uterine scar tissues are the pivotal molecular basis for adverse pregnancy consequences of scar implantation.

Protein fold recognition is a key step for template-based modeling approaches to protein structure prediction. Although closely related folds can be easily identified by sequence homology search in sequence databases, fold recognition is notoriously more difficult when it involves the identification of distantly related homologues. Recent progress in residue-residue contact and distance prediction opens up the possibility of improving fold recognition by using structural information contained in predicted distance and contact maps.

Here we propose to use the congruence coefficient as a metric of similarity between maps. We prove that this metric has several interesting mathematical properties which allow one to compute in polynomial time its exact mean and variance over all possible (exponentially many) alignments between two symmetric matrices, and assess the statistical significance of similarity between aligned maps. We perform fold recognition tests by recovering predicted target contact/distance maps from the two most recent CASP editions and over 27,000 non-homologous structural templates from the ECOD database. On this large benchmark, we compare fold recognition performances of different alignment tools with their own similarity scores against those obtained using the congruence coefficient. We show that the congruence coefficient overall improves fold recognition over other methods, proving its effectiveness as a general similarity metric for protein map comparison.

The congruence coefficient software CCpro is available as part of the SCRATCH suite at http//scratch.proteomics.ics.uci.edu/.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

To increase our understanding of the mechanisms underlying hydroxychloroquine (HCQ) retinopathy, analyses by quantitative fundus autofluorescence (qAF) and near-infrared fundus autofluorescence (NIR-AF) were compared to results obtained by recommended screening tests.

Thirty-one patients (28 females, 3 males) were evaluated with standard automated perimetry and spectral domain optical coherence tomography (SD-OCT); 28 also had multifocal electroretinography (mfERG). Measurement of short-wavelength fundus autofluorescence (SW-AF) by qAF involved the use of an internal fluorescent reference and intensity measurements in eight concentric segments at 7° to 9° eccentricity. For semiquantitative analysis of NIR-AF, intensities were acquired along a vertical axis through the fovea.

Four of 15 high-dose (total dose >1000 g, daily dose >5.0 mg/kg) patients and one of 16 low-dose (total dose <1000 g, daily dose 4.4 mg/kg) patients were diagnosed with HCQ-associated retinopathy based on abnormal 10-2 visual fields, SD-OCT, and SW-AF imaging. Three of the high-dose patients also had abnormal mfERG results. Of the five patients exhibiting retinopathy, two had qAF color-coded images revealing higher intensities inferior, nasal, and lateral to the fovea. The abnormal visual fields also exhibited superior-inferior differences. Mean NIR-AF gray-level intensities were increased in four high-dose patients with no evidence of retinopathy. In two patients with retinopathy, NIR-AF intensity within the parafovea was below the normal range. One high-dose patient (6.25 mg/kg) had only abnormal mfERG results.

These findings indicate that screening for HCQ retinopathy should take into consideration superior-inferior differences in susceptibility to HCQ retinopathy.

These findings indicate that screening for HCQ retinopathy should take into consideration superior-inferior differences in susceptibility to HCQ retinopathy.

The purpose of this study was to investigate the relationship between circadian rhythm and intraocular pressure (IOP), and to explore whether electrical stimulation of cervical sympathetic ganglia (SCG) can regulate IOP via neurotransmitter distribution around the Schlemm's canal (SC) in rats.

Sprague Dawley rats were housed under normal (N-normal), constant dark (N-dark), and constant light (N-light) rhythms (n = 6 per group). Electrical stimulation (intermittent wave [20 hertz Hz, 2 mA, 10 minutes]) was used to stimulate the SCG. Atropine sulfate eye gel was applied three times a day. DiI was injected into the SCG and anterior chamber. The cross-sectional area and circumference of SC were evaluated using hematoxylin-eosin staining. Immunofluorescence staining was used to evaluate dopamine-β-hydroxylase (DβH) expression in SC endothelial (SCE) cells.

N-Dark increased the IOP, decreased the cross-sectional area of SC, and increased DβH levels in SCE cells. Nerve projection between SC and SCG was detected, and electrical stimulation of SCG upregulated DβH expression in SCE cells.

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