Development and Validation of a Radiomics Model Based on Lymph-Node Regression Grading After Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

PURPOSE: The response to neoadjuvant chemoradiotherapy (nCRT) varies among patients with locally advanced rectal cancer (LARC), and the treatment response of lymph nodes (LNs) to nCRT is critical in implementing a watch-and-wait strategy. A robust predictive model may help personalize treatment plans to increase the chance that patients achieve a complete response. This study investigated whether radiomics features based on prenCRT magnetic resonance imaging nodes could predict treatment response in preoperative LARC LNs. METHODS AND MATERIALS: The study included 78 patients with clinical stage T3-T4, N1-2, and M0 rectal adenocarcinoma who received long-course neoadjuvant radiotherapy before surgery. Pathologists evaluated 243 LNs, of which 173 and 70 were assigned to training and validation cohorts, respectively. For each LN, 3641 radiomics features were extracted from the region of interest in high-resolution T2WI magnetic resonance imaging before nCRT. The least absolute shrinkage and selection operator regression model was used for feature selection and radiomics signature building. A prediction model based on multivariate logistic analysis, combining radiomics signature and selected LN morphologic characteristics, was developed and visualized by drawing a nomogram. The model's performance was assessed by receiver operating characteristic curve analysis and calibration curves. RESULTS: The radiomics signature consists of 5 selected features that were effectively discriminated within the training cohort (area under the curve [AUC], 0.908; 95% CI, 0.857%-0.958%) and the validation cohort (AUC, 0.865; 95% CI, 0.757%-0.973%). The nomogram, which consisted of radiomics signature and LN morphologic characteristics (short-axis diameter and border contours), showed better calibration and discrimination in the training and validation cohorts (AUC, 0.925; 95% CI, 0.880%-0.969% and AUC, 0.918; 95% CI, 0.854%-0.983%, respectively). The decision curve analysis confirmed that the nomogram had the highest clinical utility. CONCLUSIONS: The nodal-based radiomics model effectively predicts LNs treatment response in patients with LARC after nCRT, which could help personalize treatment plans and guide the implementation of the watch-and-wait approach in these patients.

Role of MRI­based radiomics in locally advanced rectal cancer (Review).

Colorectal cancer is the third most common type of cancer, with high morbidity and mortality rates. In particular, locally advanced rectal cancer (LARC) is difficult to treat and has a high recurrence rate. Neoadjuvant chemoradiotherapy (NCRT) is one of the standard treatment programs of LARC. If the response to treatment and prognosis in patients with LARC can be predicted, it will guide clinical decision­making. Radiomics is characterized by the extraction of high­dimensional quantitative features from medical imaging data, followed by data analysis and model construction, which can be used for tumor diagnosis, staging, prediction of treatment response and prognosis. In recent years, a number of studies have assessed the role of radiomics in NCRT for LARC. MRI­based radiomics provides valuable data and is expected to become an imaging biomarker for predicting treatment response and prognosis. The potential of radiomics to guide personalized medicine is widely recognized; however, current limitations and challenges prevent its application to clinical decision­making. The present review summarizes the applications, limitations and prospects of MRI­based radiomics in LARC.

A Novel Approach to Quantitative Evaluation of Outer Retinal Lesions Via a New Parameter "Integral" in Spectral Domain Optical Coherence Tomography.

Purpose: The purpose of this study was to design a new parameter "integral" to quantitatively evaluate the spatial cumulative reflectivity of the outer retinal layers in optical coherence tomography (OCT), and to investigate its role in the detection of outer retinal diseases. Methods: This was a cross-sectional study. Fovea-centered line OCT scans were performed on 60 eyes of 60 healthy volunteers and 44 eyes of 44 patients diagnosed with outer retinal diseases. The integrals of the ellipsoid zone (EZ) and interdigitation zone (IZ) were measured by respectively accumulating the grayscale values of all the pixels within the EZ and IZ at specified locations on the scanning lines, and were then adjusted by calculating their percentages on the outer retina. The integrals of the EZ and IZ were compared between the two groups. Results: The integrals of the EZ and IZ were stably and normally distributed in the healthy eyes, and were significantly lower in eyes with outer retinal lesions than in healthy ones (P < 0.05). Moreover, the integrals of the EZ and IZ were correlated with best corrected visual acuity (BCVA; adjusted R2 = 0.620) and the presence of outer retinal lesions (Nagelkerke R2 = 0.767). The area under the receiver operating characteristic (ROC) curve was 0.954 (95% confidence interval [CI] = 0.918-0.990) when the integral was selected as a diagnostic variable. Conclusions: Obtained from this novel quantification method, the new parameter integral was comparable between different individuals and had the potential to detect outer retinal abnormalities in reflectivity through OCT. Translational Relevance: Our work verified the feasibility of the new image analysis technique in the detection of the diseases affecting the outer retina.

Improvement of Black-Odor Water by Pichia Strain GW1 under Optimized NH3-N Degradation Conditions.

In this study, a yeast strain with an outstanding NH3-N degradation ability was isolated from the sediment of a black-odor water channel in Guangdong Province, China. Based on phenotypic and phylogenetic analysis, this strain was identified as Pichia kudriavzevii GW1. The optimum conditions for NH3-N degradation by the GW1 strain were as follows: 0.3% inoculum concentration, 1.5 L/min aeration, pH 7, and a temperature of 35°C. Under optimized conditions, the GW1 strain degraded 95.5% of the NH3-N. The strain was then added to simulated black-odor water under optimal degradation conditions to investigate changes to the bacterial community over time. 16S rRNA sequencing of samples collected on days 0, 7, 14, and 21 showed that, in the presence of the GW1 strain, the relative abundances of the phyla Proteobacteria, Bacteroidetes, Chloroflexi, and Firmicutes increased in the black-odor water. In addition, the relative abundance of Propionivibrio, a known NH3-N degrading genus, increased. This study will facilitate the use of microbiological methods to repair black-odor water.

Circular RNA HIPK3 regulates human lens epithelial cells proliferation and apoptosis by targeting the miR-193a/CRYAA axis.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs generated from back splicing. Accumulating evidence has demonstrated their vital regulation in several biological processes and ocular diseases. However, the role of circRNAs in age-related cataract (ARC), the leading cause of visual impairment worldwide, is still unknown. CircRNA sequencing reveals that 101 circRNAs are differentially expressed between the capsules of transparent and ARC lenses, including 75 down-regulated circRNAs and 26 up-regulated circRNAs transcripts. Eight of 10 differentially expressed circRNAs are further verified by quantitative RT-PCRs. One highly conserved circRNA, circHIPK3, is significantly down-regulated in all cortical, nuclear and posterior subcapsular subtypes of ARC. The silencing of circHIPK3, but not HIPK3 mRNA, significantly accelerates apoptosis development upon oxidative stress and decreases cell viability and proliferation in primary cultured human lens epithelial cells (HLECs). The expression of α-SMA and vimentin was downregulated, while the expression of E-cadherin and ZO-1was upregulated, suggesting the repression of epithelial-mesenchymal transition after circHIPK3 knockdown. CircHIPK3 silencing increases miR-193a expression. miR-193a regulates CRYAA expression by targeting the binding site within the 3'UTR. Moreover, miR-193a decreases the viability and proliferation, and increases the apoptosis of HLECs upon oxidative stress. This study suggests that circRNAs are the potential regulators in cataractogenesis. CircHIPK3 regulates HLECs function through miR-193a-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of ARC.

High-level expression, purification, and enzymatic characterization of truncated human plasminogen (Lys531-Asn791) in the methylotrophic yeast Pichia pastoris.

BACKGROUND: Plasmin is a serine protease that plays a critical role in fibrinolysis, which is a process that prevents blood clots from growing and becoming problematic. Recombinant human microplasminogen (rhµPlg) is a derivative of plasmin that solely consists of the catalytic domain of human plasmin and lacks the five kringle domains found in the native protein. Developing an industrial production method that provides high yields of this protein with high purity, quality, and potency is critical for preclinical research. RESULTS: The human microplasminogen gene was cloned into the pPIC9K vector, and the recombinant plasmid was transformed into Pichia pastoris strain GS115. The concentration of plasmin reached 510.1 mg/L of culture medium. Under fermentation conditions, the yield of rhµPlg was 1.0 g/L. We purified rhµPlg to 96% purity by gel-filtration and cation-exchange chromatography. The specific activity of rhµPlg reached 23.6 U/mg. The K m of substrate hydrolysis by recombinant human microplasmin was comparable to that of human plasmin, while rhµPlm had higher k cat /Km values than plasmin. The high purity and activity of the rhµPlg obtained here will likely prove to be a valuable tool for studies of its application in thrombotic diseases and vitreoretinopathies. CONCLUSIONS: Reliable rhµPlg production (for use in therapeutic applications) is feasible using genetically modified P. pastoris as a host strain. The successful expression of rhµPlg in P. pastoris lays a solid foundation for its downstream application.

The GluN2B subunit of N-methy-D-asparate receptor regulates the radial migration of cortical neurons in vivo.

The formation of layered structure of the mammalian neocortex requires a fine organized migration of post-mitotic neurons during early development. However, whether the radial migration is regulated by NMDA receptor and specific subunits remains contradictory and unknown. Here, we reported that in the developing rat cortex, migration of presumptive layer II/III neurons to their deserved destination was regulated by NMDA receptors with GluN2B but not GluN2A subunit. Using in utero electroporation of small interference RNA (siRNA) of distinct NMDA receptor subunits, we found that knockdown GluN1 and GluN2B subunits dramatically delayed the neuronal migration to proper layer II/III, while improperly stayed at lower layers or even the germinal regions, without changing the cell fate. In contrast, knockdown of GluN2A subunit did not impair the neuronal migration. Additionally, the ecotopic neurons by GluN2B RNAi developed to well dendritic differentiation, while the ones by GluN1 RNAi still kept morphology of migrating neurons. Therefore, GluN2B subunit of NMDA receptor plays an essential role in regulating proper neuronal migration and cortical lamination.