Synthesis of [1,2,3]Triazolo-[1,5-a]quinoxalin-4(5H)-ones through Photoredox-Catalyzed [3 + 2] Cyclization Reactions with Hypervalent Iodine(III) Reagents.

An efficient synthesis of a variety of [1,2,3]triazolo-[1,5-a]quinoxalin-4(5H)-ones via a [3 + 2] cyclization reaction by photoredox catalysis between quinoxalinones and hypervalent iodine(III) reagents is reported. A range of quinoxalinones and hypervalent iodine(III) reagents were tolerated well. This cyclization reaction allows access to structurally diverse [1,2,3]triazolo-[1,5-a]quinoxalin-4(5H)-ones in moderate to good yields.

The prevalence of lower eyelid epiblepharon and its association with refractive errors in Chinese preschool children: a cross-sectional study.

BACKGROUND: To assess the prevalence and demographics of lower eyelid epiblepharon in Chinese preschool children and to evaluate its association with refractive errors. METHODS: In this population-based, cross-sectional study, a total of 3170 children aged 3 to 6 years from Beijing, China underwent examinations including weight, height, cycloplegic autorefraction and slit-lamp examination of external eyes. The prevalence of lower eyelid epiblepharon in preschool children was evaluated and its association with age, sex, body mass index (BMI), and refractive errors was analyzed using logistic regression analysis. RESULTS: The prevalence of lower eyelid epiblepharon was 26.2%, which decreased with age, with prevalence in 3-, 4-, 5-, and 6-year-olds of 30.6, 28.0, 15.0, and 14.3%, respectively. Boys had a higher risk of having epiblepharon than girls (OR = 1.41; 95%CI, (1.20-1.66)) and no significant correlation was detected between BMI and epiblepharon after adjusting for age and sex (p = 0.062). Epiblepharon was significantly associated with a higher risk of refractive errors, including astigmatism (OR = 3.41; 95% CI, (2.68-4.33)), myopia (OR = 3.55; 95% CI, (1.86-6.76)), and hyperopia (OR = 1.53; 95% CI, (1.18-1.99)). CONCLUSIONS: There is a high prevalence of lower eyelid epiblepharon in Chinese preschool children, particularly among boys and younger children. Preschoolers with lower eyelid epiblepharon are subject to a higher risk of developing astigmatism, myopia, and hyperopia, than those without. Increased attention should be paid to this eyelid abnormality in the preschool population.

Constraints on the Velocity and Spin Dependent Exotic Interaction at the Micrometer Range.

We report on an experimental test of the velocity and spin dependent exotic interaction that can be mediated by new light bosons. The interaction is searched by measuring the force between a gold sphere and a microfabricated magnetic structure using a cantilever. The magnetic structure consists of stripes with antiparallel electron spin polarization so that the exotic interaction between the polarized electrons in the magnetic structure and the unpolarized nucleons in the gold sphere varies periodically, which helps to suppress the spurious background signals. The experiment sets the strongest laboratory constraints on the coupling constant between electrons and nucleons at the micrometer range with f_{⊥}<5.3×10^{-8} at λ=5 µm.

The N-terminal His-tag affects the triglyceride lipase activity of hormone-sensitive lipase in testis.

The sterility of hormone-sensitive lipase (HSL) knockout mice clearly shows the link between lipid metabolism and spermatogenesis. However, which substrate or product of this multifunctional lipase affects spermatogenesis is unclear. We found that an HSL protein with a His-tag at the N-terminus preserved the normal hydrolase activity of cholesteryl ester (CE) but the triglyceride lipase (TG) activity significantly decreased in vitro. Therefore, mice with this functionally incomplete HSL (His-HSL) were produced on a background of HSL deficiency (HSL-/- h). As a result, HSL-/- h testis has an 8.65-fold higher CE activity than wild-type testis but a twofold higher TG activity than wild-type testis. To compare His-HSL and wild-type HSL in vitro and in vivo, we confirmed that the His-tag significantly suppressed HSL TG activity. From our results, we believe that TG activity was affected by the His-tag insertion, but CE activity was not influenced. Furthermore, the His-tag protected HSL from binding to the inhibitor BAY. From our study, TG activity and BAY binding sites were affected by N-terminal His-tag insertion.

Hormone-sensitive lipase deficiency alters gene expression and cholesterol content of mouse testis.

Hormone-sensitive lipase-knockout (HSL-/-) mice exhibit azoospermia for unclear reasons. To explore the basis of sterility, we performed the following three experiments. First, HSL protein distribution in the testis was determined. Next, transcriptome analyses were performed on the testes of three experimental groups. Finally, the fatty acid and cholesterol levels in the testes with three different genotypes studied were determined. We found that the HSL protein was present from spermatocyte cells to mature sperm acrosomes in wild-type (HSL+/+) testes. Spermiogenesis ceased at the elongation phase of HSL-/- testes. Transcriptome analysis indicated that genes involved in lipid metabolism, cell membrane, reproduction and inflammation-related processes were disordered in HSL-/- testes. The cholesterol content was significantly higher in HSL-/- than that in HSL+/+ testis. Therefore, gene expression and cholesterol ester content differed in HSL-/- testes compared to other testes, which may explain the sterility of male HSL-/- mice.

[Macular thickness in unilateral amblyopia as measured by optical coherence tomography: a meta analysis].

OBJECTIVE: To offer a clue for the etiology of amblyopia by systematically comparing the macular thickness measured by optical coherence tomography (OCT) between the amblyopic eye and the fellow normal eye in patients with unilateral amblyopia. METHODS: Databases including Wanfang, PubMed and others were searched, and data were extracted after quality assessment, then the Meta analysis was performed by the RevMan 5.02 software. RESULTS: Four studies using the time-domain OCT (TD-OCT) were enrolled in the analysis and all those were anisometropic amblyopic patients. The only one study showed that the foveal minimum thickness is thicker in the amblyopic eyes than the fellow ones (P = 0.045). The meta analysis indicated the amblyopic eyes were 6.82 µm (P < 0.05, 95% CI: 2.81-10.83) thicker in the fovea (1 mm diameter region ). Five trials using the spectral-domain OCT (SD-OCT) were included in the analysis. It showed no significant difference in the foveal minimum thickness between amblyopic and fellow eyes. Also, no significant difference were detected in either anisometropic or strabismic subgroup (P = 0.50). Amblyopic eyes were 7.38 µm thicker in the fovea (1 mm diameter region) (P < 0.05, 95% CI: 3.13 -11.63) and significant difference in the anisometropic subgroup while no significant difference in the strabismic subgroup were detected. CONCLUSIONS: The macular fovea is thicker in the amblyopic eyes than the fellow ones by the use of OCT, so it is effective to measure the macular thickness of amblyopia in searching evidence for the etiology of amblyopia.

Novel pathogenic variants of SLC38A8 gene and literature review.

PURPOSE: This study aimed to analyze the clinical and genetic characteristics of 6 Chinese patients with foveal hypoplasia (FH) caused by the variants of solute carrier family 38 member 8 (SLC38A8), and to describe the genotype and phenotype of SLC38A8 variants from previous literature. METHODS: All subjects underwent comprehensive ophthalmic examinations. Optical coherence tomography (OCT) was performed to evaluate the structural grade of FH. Pathogenic variants of SLC38A8 gene were identified using panel-based next-generation sequencing and direct Sanger sequencing techniques. Further, all previously reported cases of SLC38A8 variants were re-analyzed together with the novel ones identified in this study. RESULTS: Nystagmus and FH were present in 6 patients with variants of SLC38A8 gene, accompanied by a normal anterior segment. Grade 4 FH was identified in 4 patients. A total of 12 variants of SLC38A8 gene were identified, including 9 novel variants. Systematical analysis revealed that half of the variants (30/60) were missense, the majority of which (23/30) were distributed in the transmembrane (TM) domains. Grade 4 FH was detected in the majority of patients (66%, 23/35). There was no statistical difference in the clinical features between the subgroups of patients with 0, 1 and 2 missense variants. CONCLUSION: Severe arrest of foveal development was identified in patients with variants of SLC38A8. This study provides a brief summary of the clinical and genetic characteristics of the pathogenic SLC38A8 variants, which is helpful in the differentiation diagnosis of FH.

Comprehensive analysis of the differential expression of mRNAs, lncRNAs, and miRNAs in Zi goose testis with high and low sperm mobility.

Sperm mobility (SM) is an objective index for measuring sperm motility; however, the mechanisms underlying its regulation in geese remain unclear. The present study sought to elucidate the genetic mechanism underlying SM traits in Zi geese (Anser cygnoides L.). To this end, three successive experiments were performed. In Experiment I, SM was determined in 40 ganders; the 3 ganders with the highest mobility and three with the lowest mobility were assigned to the high and low sperm mobility rank (SMR) groups, respectively. In Experiment II, the differences in fertility between the two SMR groups were assessed within two breeding flocks comprising the selected six ganders from Experiment I and 30 females (each flock had 3 ganders and 15 females). In Experiment III, the testes of the 6 ganders were harvested for histological observation and whole-transcriptome sequencing. Results revealed better fertility, well-developed seminiferous tubules, and abundant mature sperm in the high-SMR-flock compared to those of the low-SMR-flock (89 vs. 81%) (P < 0.05). Differential expression (DE) analysis identified 76 mRNAs, 344 lncRNAs, and 17 miRNAs between the SMR groups, with LOC106049708, XPNPEP3, GNB3, ADCY8, PRKAG3, oha-miR-182-5p, and ocu-miR-10b-5p identified as key mRNAs and miRNAs contributing to SM. Enrichment analysis implicated these DE RNAs in pathways related to ATP binding, cell metabolism, apelin signaling, Wnt signaling, and Adherens junctions. Additionally, competing endogenous RNA (ceRNA) networks comprising 9 DE mRNAs, 17 DE miRNAs, and 169 DE lncRNAs were constructed. Two ceRNA network pathways (LOC106049708-oha-miR-182-5p-MSTRG.2479.6 and PRKAG3-ocu-miR-10b-5p-MSTRG.9047.14) were identified as key regulators of SM in geese. These findings offer crucial insights into the identification of key genes and ceRNA pathways influencing sperm mobility in geese.

Detection of malignant lesions in cytologically indeterminate thyroid nodules using a dual-layer spectral detector CT-clinical nomogram.

Purpose: To evaluate the capability of dual-layer detector spectral CT (DLCT) quantitative parameters in conjunction with clinical variables to detect malignant lesions in cytologically indeterminate thyroid nodules (TNs). Materials and methods: Data from 107 patients with cytologically indeterminate TNs who underwent DLCT scans were retrospectively reviewed and randomly divided into training and validation sets (7:3 ratio). DLCT quantitative parameters (iodine concentration (IC), NICP (IC nodule/IC thyroid parenchyma), NICA (IC nodule/IC ipsilateral carotid artery), attenuation on the slope of spectral HU curve and effective atomic number), along with clinical variables, were compared between benign and malignant cohorts through univariate analysis. Multivariable logistic regression analysis was employed to identify independent predictors which were used to construct the clinical model, DLCT model, and combined model. A nomogram was formulated based on optimal performing model, and its performance was assessed using receiver operating characteristic curve, calibration curve, and decision curve analysis. The nomogram was subsequently tested in the validation set. Results: Independent predictors associated with malignant TNs with indeterminate cytology included NICP in the arterial phase, Hashimoto's Thyroiditis (HT), and BRAF V600E (all p < 0.05). The DLCT-clinical nomogram, incorporating the aforementioned variables, exhibited superior performance than the clinical model or DLCT model in both training set (AUC: 0.875 vs 0.792 vs 0.824) and validation set (AUC: 0.874 vs 0.792 vs 0.779). The DLCT-clinical nomogram demonstrated satisfactory calibration and clinical utility in both training set and validation set. Conclusion: The DLCT-clinical nomogram emerges as an effective tool to detect malignant lesions in cytologically indeterminate TNs.

Development and validation of a model for predicting the expression of Ki-67 in pancreatic ductal adenocarcinoma with radiological features and dual-energy computed tomography quantitative parameters.

OBJECTIVE: To construct and validate a model based on the dual-energy computed tomography (DECT) quantitative parameters and radiological features to predict Ki-67 expression levels in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Data from 143 PDAC patients were analysed. The variables of clinic, radiology and DECT were evaluated. In the arterial phase and portal venous phase (PVP), the normalized iodine concentration (NIC), normalized effective atomic number and slope of the spectral attenuation curves were measured. The extracellular volume fraction (ECVf) was measured in the equilibrium phase. Univariate analysis was used to screen independent risk factors to predict Ki-67 expression. The Radiology, DECT and DECT-Radiology models were constructed, and their diagnostic effectiveness and clinical applicability were obtained through area under the curve (AUC) and decision curve analysis, respectively. The nomogram was established based on the optimal model, and its goodness-of-fit was assessed by a calibration curve. RESULTS: Computed tomography reported regional lymph node status, NIC of PVP, and ECVf were independent predictors for Ki-67 expression prediction. The AUCs of the Radiology, DECT, and DECT-Radiology models were 0.705, 0.884, and 0.905, respectively, in the training cohort, and 0.669, 0.835, and 0.865, respectively, in the validation cohort. The DECT-Radiology nomogram was established based on the DECT-Radiology model, which showed the highest net benefit and satisfactory consistency. CONCLUSIONS: The DECT-Radiology model shows favourable predictive efficacy for Ki-67 expression, which may be of value for clinical decision-making in PDAC patients. CRITICAL RELEVANCE STATEMENT: The DECT-Radiology model could contribute to the preoperative and non-invasive assessment of Ki-67 expression of PDAC, which may help clinicians to screen out PDAC patients with high Ki-67 expression. KEY POINTS: • Dual-energy computed tomography (DECT) can predict Ki-67 in pancreatic ductal adenocarcinoma (PDAC). • The DECT-Radiology model facilitates preoperative and non-invasive assessment of PDAC Ki-67 expression. • The nomogram may help screen out PDAC patients with high Ki-67 expression.

Diagnostic accuracy of dual-energy computed tomography-based nomogram for differentiating papillary thyroid microcarcinomas from micronodular goiters.

Background: The misdiagnosis of papillary thyroid microcarcinoma (PTMC) and micronodular goiter (MNG) may lead to overtreatment and unnecessary medical expenditure by patients. This study developed and validated a dual-energy computed tomography (DECT)-based nomogram for the preoperative differential diagnosis of PTMC and MNG. Methods: This retrospective study analyzed the data of 366 pathologically confirmed thyroid micronodules, of which 183 were PTMCs and 183 were MNGs, from 326 patients who underwent DECT examinations. The cohort was divided into the training (n=256) and validation cohorts (n=110). The conventional radiological features and DECT quantitative parameters were analyzed. The iodine concentration (IC), normalized iodine concentration (NIC), effective atomic number, normalized effective atomic number, and slope of the spectral attenuation curves in the arterial phase (AP) and venous phase (VP) were measured. A univariate analysis and stepwise logistic regression analysis were performed to screen the independent indicators for PTMC. A radiological model, DECT model, and DECT-radiological nomogram were constructed, and the performances of the 3 models were assessed using the receiver operating characteristic curve, DeLong test, and a decision curve analysis (DCA). Results: The IC in the AP [odds ratio (OR) =0.172], NIC in the AP (OR =0.003), punctate calcification (OR =2.163), and enhanced blurring (OR =3.188) were identified as independent predictors in the stepwise-logistic regression. The areas under the curve with 95% confidence intervals (CIs) of the radiological model, DECT model, and DECT-radiological nomogram were 0.661 (95% CI: 0.595-0.728), 0.856 (95% CI: 0.810-0.902), and 0.880 (95% CI: 0.839-0.921), respectively, in the training cohort; and 0.701 (95% CI: 0.601-0.800), 0.791 (95% CI: 0.704-0.877), and 0.836 (95% CI: 0.760-0.911), respectively, in the validation cohort. The diagnostic performance of the DECT-radiological nomogram was better than that of the radiological model (P<0.05). The DECT-radiological nomogram was found to be well calibrated and had a good net benefit. Conclusions: DECT provides valuable information for differentiating between PTMC and MNG. The DECT-radiological nomogram could serve as an easy-to-use, noninvasive, and effective method for differentiating between PTMC and MNG and help clinicians in decision-making.

Sperm mobility is predictive of the relative genetic contribution among competing mating geese, as determined by microsatellite genotype identification of potential sires.

The low reproductive efficiency (RE) of geese limits their production in the poultry industry. To select ganders with high breeding potential, the effect of 3 sperm mobility ranks (SMRs; high-, medium-, and low-SMR) on the RE of naturally mating geese was determined. To exclude the confounding effect of social rank (SR) on RE in naturally mating flocks, a 2-factor nested experimental design was used to differentiate the effects of SMR and SR on RE. Twenty-seven ganders and 135 geese (Zi geese, Anser cygnoides L.) at approximately 1 yr of age were divided into 3 flocks, each of which included the 3 SMR groups. Each SMR group included 3 ganders and 15 female geese. Relative genetic contribution (RGC) is defined as the number of offspring sired by 1 male as a percentage of the entire goslings in each flock, and it was used to compare the differences in RE among ganders. The frequency of agonistic behavioral interactions (ABIs) among the ganders was video recorded in each SMR group, and the SR of each gander was determined. In total, 1,026 eggs were incubated, and 609 goslings hatched. Parent-offspring relationships among 771 individuals from the 2 generations were identified using 20 microsatellite markers, and the RGC was calculated. Results showed that the SMR and SR had significant effects on RGC in naturally mating geese (P = 0.001 and P = 0.000, respectively). Significant differences in RGC were observed among the high- and medium- and low-SMR groups, with average RGCs of 14.3, 10.6, and 8.4%, respectively. The high-SMR group had the highest RGCs in each flock, and the ganders with high SR had the highest RGCs among the 3 SMRs. The study showed that in a naturally mating geese population, selecting for the sperm mobility traits of a gander can effectively improve the RE.

Feasibility of a CT-based lymph node radiomics nomogram in detecting lymph node metastasis in PDAC patients.

Objectives: To investigate the potential value of a contrast enhanced computed tomography (CECT)-based radiological-radiomics nomogram combining a lymph node (LN) radiomics signature and LNs' radiological features for preoperative detection of LN metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Materials and methods: In this retrospective study, 196 LNs in 61 PDAC patients were enrolled and divided into the training (137 LNs) and validation (59 LNs) cohorts. Radiomic features were extracted from portal venous phase images of LNs. The least absolute shrinkage and selection operator (LASSO) regression algorithm with 10-fold cross-validation was used to select optimal features to determine the radiomics score (Rad-score). The radiological-radiomics nomogram was developed by using significant predictors of LN metastasis by multivariate logistic regression (LR) analysis in the training cohort and validated in the validation cohort independently. Its diagnostic performance was assessed by receiver operating characteristic curve (ROC), decision curve (DCA) and calibration curve analyses. Results: The radiological model, including LN size, and margin and enhancement pattern (three significant predictors), exhibited areas under the curves (AUCs) of 0.831 and 0.756 in the training and validation cohorts, respectively. Nine radiomic features were used to construct a radiomics model, which showed AUCs of 0.879 and 0.804 in the training and validation cohorts, respectively. The radiological-radiomics nomogram, which incorporated the LN Rad-score and the three LNs' radiological features, performed better than the Rad-score and radiological models individually, with AUCs of 0.937 and 0.851 in the training and validation cohorts, respectively. Calibration curve analysis and DCA revealed that the radiological-radiomics nomogram showed satisfactory consistency and the highest net benefit for preoperative diagnosis of LN metastasis. Conclusions: The CT-based LN radiological-radiomics nomogram may serve as a valid and convenient computer-aided tool for personalized risk assessment of LN metastasis and help clinicians make appropriate clinical decisions for PADC patients.

Effects of different CT angiography technology-based nursing methods on patients with coronary artery heart diseases.

To study the nursing effects of different CT angiography (CTA) technology-based nursing methods on patients with coronary artery heart diseases (CHD), CHD patients treated in Dongying People's Hospital were selected as the research objects and were divided into the control group and the observation group. Different coronary CTA nursing methods, i.e. the routine nursing and the psychological nursing, were performed to the control group and the observation group respectively. During the experiment, patients performed self-evaluations, which included the Self-rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS). Biological indicators of patients, including heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP), were measured before and after patients accepted different nursing methods. In addition, the quality of coronary CTA images was evaluated. The results showed that HR, DBP, SBP, SAS scores, and SDS scores of patients in the observation group were obviously lower than those in the control group, and the differences were statistically significant, besides, the image quality of the observation group was significantly greater than that of the control group, which was helpful for diagnosis and had statistical significances. Therefore, it is proved that the psychological nursing of CHD patients can effectively reduce the negative emotions of patients, such as anxiety and depression, which is conducive to CTA and can assist clinical diagnosis. The results provide a basis and ideas for more accurate research in the future.

Ube2s stabilizes ß-Catenin through K11-linked polyubiquitination to promote mesendoderm specification and colorectal cancer development.

The canonical Wnt/ß-Catenin signaling pathway is widely involved in regulating diverse biological processes. Dysregulation of the pathway results in severe consequences, such as developmental defects and malignant cancers. Here, we identified Ube2s as a novel activator of the Wnt/ß-Catenin signaling pathway. It modified ß-Catenin at K19 via K11-linked polyubiquitin chain. This modification resulted in an antagonistic effect against the destruction complex/ß-TrCP cascade-orchestrated ß-Catenin degradation. As a result, the stability of ß-Catenin was enhanced, thus promoting its cellular accumulation. Importantly, Ube2s-promoted ß-Catenin accumulation partially released the dependence on exogenous molecules for the process of embryonic stem (ES) cell differentiation into mesoendoderm lineages. Moreover, we demonstrated that UBE2S plays a critical role in determining the malignancy properties of human colorectal cancer (CRC) cells in vitro and in vivo. The findings in this study extend our mechanistic understanding of the mesoendodermal cell fate commitment, and provide UBE2S as a putative target for human CRC therapy.

Macular measurements using spectral-domain optical coherence tomography in Chinese myopic children.

PURPOSE: To evaluate the macular thickness/volume in Chinese myopic children using spectral-domain optical coherence tomography (SD-OCT) and assess its correlation with spherical equivalent refraction (SER), axial length (AL), sex, and age. METHODS: A total of 194 eyes from 194 children (aged 6-17 years old) with emmetropia (-0.5 diopters [D] < SER ≤ 0.5 D), low myopia (-3.0 D < SER ≤ -0.5 D), and moderate to high myopia (SER ≤ -3.0 D) were recruited in the study. Each child underwent standardized ophthalmic examinations including visual acuity (VA), cycloplegic refraction, and AL measurement. The macular thickness for the nine Early Treatment Diabetic Retinopathy Study (ETDRS) regions and the average macular thickness/volume were measured and calculated. RESULTS: Analyses of macular thickness for the ETDRS regions showed that the fovea was the thinnest of the nine regions, followed by the outer ring; the inner ring was the thickest. When compared to children with emmetropia or low myopia, children with moderate to high myopia tended to have greater foveal thickness, thinner quadrant-specific thickness in the outer ring, and smaller average macular thickness/volume. Also, there were significant differences in foveal, superior outer, inferior outer, and temporal outer quadrants among lowest, middle, and highest AL groups. Boys were found to have greater macular thickness than girls in fovea and inner ring regions. CONCLUSIONS: Our study highlights the variations and sex differences of macular thickness/volume in Chinese myopic children using SD-OCT.