Let-7c-3p suppresses lens epithelial-mesenchymal transition by inhibiting cadherin-11 expression in fibrotic cataract.

Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.

Proteopathy Linked to Exon-Skipping Isoform of RGR-Opsin Contributes to the Pathogenesis of Age-Related Macular Degeneration.

Purpose: Proteopathy is believed to contribute to age-related macular degeneration (AMD). Much research indicates that AMD begins in the retinal pigment epithelium (RPE), which is associated with formation of extracellular drusen, a clinical hallmark of AMD. Human RPE produces a drusen-associated abnormal protein, the exon Ⅵ-skipping splice isoform of retinal G protein-coupled receptor (RGR-d). In this study, we investigate the detrimental effects of RGR-d on cultured cells and mouse retina. Methods: ARPE-19 cells were stably infected by lentivirus overexpressing RGR or RGR-d and were treated with MG132, sometimes combined with or without endoplasmic reticulum (ER) stress inducer, tunicamycin. RGR and RGR-d protein expression, degeneration pathway, and potential cytotoxicity were explored. Homozygous RGR-d mice aged 8 or 14 months were fed with a high-fat diet for 3 months and then subjected to ocular examination and histopathology experiments. Results: We confirm that RGR-d is proteotoxic under various conditions. In ARPE-19 cells, RGR-d is misfolded and almost completely degraded via the ubiquitin-proteasome system. Unlike normal RGR, RGR-d increases ER stress, triggers the unfolded protein response, and exerts potent cytotoxicity. Aged RGR-d mice manifest disrupted RPE cell integrity, apoptotic photoreceptors, choroidal deposition of complement C3, and CD86+CD32+ proinflammatory cell infiltration into retina and RPE-choroid. Furthermore, the AMD-like phenotype of RGR-d mice can be aggravated by a high-fat diet. Conclusions: Our study confirmed the pathogenicity of the RGR splice isoform and corroborated a significant role of proteopathy in AMD. These findings may contribute to greater comprehension of the multifactorial causes of AMD.

Boosting Antibacterial Photodynamic Therapy in a Nanosized Zr MOF by the Combination of Ag NP Encapsulation and Porphyrin Doping.

Antibacterial photodynamic therapy (aPDT) is regarded as one of the most promising antibacterial therapies due to its nonresistance, noninvasion, and rapid sterilization. However, the development of antibacterial materials with high aPDT efficacy is still a long-standing challenge. Herein, we develop an effective antibacterial photodynamic composite UiO-66-(SH)2@TCPP@AgNPs by Ag encapsulation and 4,4',4″,4‴-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid) (TCPP) dopant. Through a mix-and-match strategy in the self-assembly process, 2,5-dimercaptoterephthalic acid containing -SH groups and TCPP were uniformly decorated into the UiO-66-type framework to form UiO-66-(SH)2@TCPP. After Ag(I) impregnation and in situ UV light reduction, Ag NPs were formed and encapsulated into UiO-66-(SH)2@TCPP to get UiO-66-(SH)2@TCPP@AgNPs. In the resulting composite, both Ag NPs and TCPP can effectively enhance the visible light absorption, largely boosting the generation efficiency of reactive oxygen species. Notably, the nanoscale size enables it to effectively contact and be endocytosed into bacteria. Consequently, UiO-66-(SH)2@TCPP@AgNPs show a very high aPDT efficacy against Gram-negative and Gram-positive bacteria as well as drug-resistant bacteria (MRSA). Furthermore, the Ag NPs were firmly anchored at the framework by the high density of -SH moieties, avoiding the cytotoxicity caused by the leakage of Ag NPs. By in vitro experiments, UiO-66-(SH)2@TCPP@AgNPs show a very high antibacterial activity and good biocompatibility as well as the potentiality to promote cell proliferation.

QTL mapping and identification of candidate genes for cold tolerance at the germination stage in wild rice.

BACKGROUND: Cold damage stress significantly affects rice growth (germination and seedling) and causes serious losses in yield in temperate and high-altitude areas around the globe. OBJECTIVE: This study aimed to explore the cold tolerance (CT) locus of rice and create new cold-tolerant germplasm. We constructed a chromosome segment substitution line (CSSL) with strong CT and fine mapped quantitative trait loci (QTLs) associated with CT by performing the whole-genome resequencing of CSSL with phenotypes under cold treatment. METHODS: A chromosome CSSL, including 271 lines from a cross between the cold-tolerant wild rice Y11 (Oryza rufipogon Griff.) and the cold-sensitive rice variety GH998, was developed to map QTLs conferring CT at the germination stage. The whole-genome resequencing was performed on CSSL for mapping QTLs of associated with CT at the germination stage. RESULTS: A high-density linkage map of the CSSLs was developed using the whole-genome resequencing of 1484 bins. The QTL analysis using 615,466 single-nucleotide polymorphisms (SNPs) led to the identification of 2 QTLs related to germination rate at low-temperature on chromosome 8 (qCTG-8) and chromosome 11 (qCTG-11). The qCTG-8 and qCTG-11 explained 14.55% and 14.31% of the total phenotypic variation, respectively. We narrowed down qCTG-8 and qCTG-11 to 195.5 and 78.83-kb regions, respectively. The expression patterns of important candidate genes in different tissues, and of RNA-sequencing (RNA-seq) in CSSLs, were identified based on gene sequences in qCTG-8 and qCTG-11 cold-induced expression analysis. LOC_Os08g01120 and LOC_Os08g01390 were identified as candidate genes in qCTG-8, and LOC_Os11g32880 was identified as a candidate gene in qCTG-11. CONCLUSIONS: This study demonstrated a general method that could be used to identify useful loci and genes in wild rice and aid in the future cloning of candidate genes of qCTG-8 and qCTG-11. The CSSLs with strong CT were supported for breeding cold-tolerant rice varieties.

Cervical and endometrial cancers of intestinal origin diagnosed 18 years after vaginal replacement with a sigmoid colon segment: a case report and review of the literature.

Background: Sigmoid colpoplasty is a surgical method for the treatment of vagina agenesis. Malignant tumors of neovaginas derived from sigmoid colons are rare. Case presentation: We report a 33-year-old woman who underwent sigmoid colpoplasty for vaginal agenesis and presented 18 years later with vaginal bleeding. Examination revealed cancer of the neovagina with involvement of the cervix and endometrium. The patient was administered four cycles of chemotherapy because she refused surgery. Conclusions: Patients with a history of colpoplasty should undergo long-term comprehensive testing after reconstruction, including regular gynecological, colposcopic, and gastrointestinal examinations. In patients with cancer of the neovagina, a comprehensive treatment plan should be developed in consultation with gynecologists and surgeons. There is no standard treatment, although surgery plus chemotherapy or radiotherapy appears to be effective.

In situ exopolysaccharides from Lactobacillus helveticus MB2-1 in Sayram ketteki yoghurt: Set yoghurts properties and interactions with sodium caseinate.

The effects of high exopolysaccharides (EPS) - producing Lactobacillus helveticus MB2-1 on the structure and storage stability of set yoghurts, and the interactions between its EPS (molecular weight 9.34 × 104 Da) from Sayram ketteki yoghurt (SKY) and sodium caseinate (CAS) were studied. The rheology, microstructure, texture and storage stability of the three set yoghurts including control yoghurt (Control), adding-probiotic yoghurt (APY) and SKY were investigated, which showed that the SKY exhibited less shear thinning than the Control and APY, and the textural indexes and storage stability of the SKY were significantly better than that of other two yoghurts (p < 0.05). Moreover, the increased turbidity, decreased ζ potential and surface hydrophobicity of EPS/CAS complex coacervation were determined at EPS/CAS mass ratio of 3 (corresponding to 0.33 g/L of CAS and 1 g/L of EPS), mainly owing to the electrostatic attraction of the two biopolymers to form aggregates. Besides, the higher sizes and more aggregation of EPS/CAS complexes were formed at pH 3.5. Taken together, the results indicated that the high EPS-producing characteristic of L. helveticus MB2-1 could positively influence the qualities of set yoghurts, and the EPS/CAS complex coacervation in dairy products was closely related to the EPS/CAS mass ratio and pH condition.

In situ exopolysaccharides produced by Lactobacillus helveticus MB2-1 and its effect on gel properties of Sayram ketteki yoghurt.

In order to study the mechanism of high viscosity of Sayram ketteki yoghurt, the growth, acidification properties, in situ exopolysaccharides (EPS) production of Lactobacillus helveticus MB2-1 in milk medium were investigated. The microstructure of the yoghurt was analyzed. The characteristics of in situ EPS produced by this strain in yoghurt were studied by high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible (UV-vis) analysis. The amount of in situ EPS produced could be up to 689.47 mg/L. The micrographs of Sayram ketteki yoghurt demonstrated that the in situ EPS secreted by ropy L. helveticus MB2-1 were closely connected with proteins, effectively filling the three-dimensional network structure of casein clusters, thereby resulting in high viscosity of yoghurt. Besides, the molecular weight of in situ EPS was 9.34 × 104 Da, and the in situ EPS was determined to be a new heteropolysaccharide, containing fucose, which made it unique. Moreover, the set yoghurts added with in situ EPS were demonstrated fine effects on the texture improvement. These results illustrated that L. helveticus MB2-1 could be set as a good starter and the in situ EPS could be considered as a probiotic stabilizer substitute for fermented dairy products.

Systemic side effects of glaucoma medications.

Glaucoma is a progressive loss of retinal ganglion cells leading to visual field loss. Lowering intraocular pressure is currently the only modifiable risk factor to slow glaucoma progression. Intraocular pressure-lowering options include topical and systemic medications, lasers, and surgical procedures. Glaucoma eye drops play a major role in treating this blinding disease. Similar to all medications, the glaucoma medications have their own adverse effects. The majority of glaucoma medications work by stimulating or inhibiting adrenergic, cholinergic, and prostaglandin receptors, which are distributed all over the body. Therefore, the glaucoma medications can affect organs other than the eye. This review will discuss the systemic adverse effects of carbonic anhydrase inhibitors, sympathomimetics, para-sympathomimetics, beta blockers, prostaglandin analogs, hyperosmotic agents, and novel glaucoma medications with a stress on pregnant patients, breastfeeding mothers, and paediatric patients.

Dose-Related Structural Effects of Photodynamic Therapy on Rabbit Choroidal Structure.

INTRODUCTION: Photodynamic therapy with verteporfin (vPDT) has been shown to be effective against central serous chorioretinopathy (CSC) and was the preferred therapeutic for CSC treatment. However, alterations in choroidal structure after PDT were reported, and these effects were dose-dependent. This study aimed to compare the changes in choroidal structure after PDT with different doses of verteporfin in rabbits and may provide individualized therapeutic guidance for patients who failed to respond to initial half-dose vPDT. METHODS: The full dose of verteporfin used in CSC was 6 mg/m2, which was used in patients with neovascular age-related macular degeneration. Laser fluence was 50 J/cm2 (irradiance, 600 mW/cm2, 83 s). There were 4 different dose groups in this study (100%, 70%, 50%, and 30%). The alterations were examined at 1 day, 1 week, and 1 month after vPDT using color fundus imaging, indocyanine green angiography, and histopathology analysis. RESULTS: Various degrees of choroidal alterations were demonstrated at different dose groups. Examinations on day 1 showed that gradually reduced verteporfin dose tended to decrease photochemical reactions to the choroid in terms of the number of occlusion vessels and area of the lesion. After 1 month, choroid vessel alteration persisted in high-dose groups (100% and 70%); nevertheless, alterations of low-dose groups (50% and 30%) returned to normal. CONCLUSIONS: vPDT can induce photochemical reactions of the choroid, high dose causes permanent change, and low dose causes recoverable change. The dose-dependent alterations need to be considered for the individual therapeutic plan according to the situation of a patient with CSC.

Electrical Generation and Deletion of Magnetic Skyrmion-Bubbles via Vertical Current Injection.

The magnetic skyrmion is a topologically protected spin texture that has attracted much attention as a promising information carrier because of its distinct features of suitability for high-density storage, low power consumption, and stability. One of the skyrmion devices proposed so far is the skyrmion racetrack memory, which is the skyrmion version of the domain-wall racetrack memory. For application in devices, skyrmion racetrack memory requires electrical generation, deletion, and displacement of isolated skyrmions. Despite the progress in experimental demonstrations of skyrmion generation, deletion, and displacement, these three operations have yet to be realized in one device. Here, a route for generating and deleting isolated skyrmion-bubbles through vertical current injection with an explanation of its microscopic origin is presented. By combining the proposed skyrmion-bubble generation/deletion method with the spin-orbit-torque-driven skyrmion shift, a proof-of-concept experimental demonstration of the skyrmion racetrack memory operation in a three-terminal device structure is provided.

Programmable Dynamics of Exchange-Biased Domain Wall via Spin-Current-Induced Antiferromagnet Switching.

Magnetic domain wall (DW) motion in perpendicularly magnetized materials is drawing increased attention due to the prospect of new type of information storage devices, such as racetrack memory. To augment the functionalities of DW motion-based devices, it is essential to improve controllability over the DW motion. Other than electric current, which is known to induce unidirectional shifting of a train of DWs, an application of in-plane magnetic field also enables the control of DW dynamics by rotating the DW magnetization and consequently modulating the inherited chiral DW structure. Applying an external bias field, however, is not a viable approach for the miniaturization of the devices as the external field acts globally. Here, the programmable exchange-coupled DW motion in the antiferromagnet (AFM)/ferromagnet (FM) system is demonstrated, where the role of an external in-plane field is replaced by the exchange bias field from AFM layer, enabling the external field-free modulations of DW motions. Interestingly, the direction of the exchange bias field can also be reconfigured by simply injecting spin currents through the device, enabling electrical and programmable operations of the device. Furthermore, the result inspires a prototype DW motion-based device based on the AFM/FM heterostructure, that could be easily integrated in logic devices.

Retinitis pigmentosa-associated anterior subcapsular cataract: morphological features and visual performance.

PURPOSE: To investigate the morphological features and surgical outcomes of retinitis pigmentosa (RP)-associated anterior subcapsular cataract (ASC). METHODS: Consecutive RP-associated ASC cases were reviewed, and one hundred patients (171 eyes) were included. Anterior segment photographed images by slit-lamp microscope were reviewed. Best-corrected visual acuity (BCVA) was recorded. The cases were classified according to preoperative best BCVA, the area (central, midperipheral and peripheral) and the density (Grade 1, vacuolar/bubble-like; Grade 2, plaque-like/translucent; and Grade 3, fibrotic/opaque) of ASC; subgroup analysis of surgical outcomes was then performed. RESULTS: The mean age was 52.1 ± 13.7 years, and the 41-50-year group had the best BCVA. 13.5% of eyes had BCVA better than 20/63, 30.4% were between 20/400 and 20/63, and 56.1% were worse than 20/400. The percentage of ASCs in the central, midperipheral and peripheral areas was 55.0%, 37.4% and 7.6%, respectively. Postoperative BCVA was improved in the central and midperipheral groups (P < 0.001) but was not in the peripheral group (P = 0.07). The percentage of ASCs in density of Grade 1, 2 and 3 was 11.1%, 38.6% and 50.3%, respectively. Grade 2 and 3 achieved improved postoperative BCVA (P < 0.001), but Grade 1 did not (P = 0.693). CONCLUSIONS: Mostly, ASC is located at the center of the pupillary area and affected the residual vision of RP patients. The patients benefited from cataract removal except for those with ASC extended to peripheral area. Surgery was also recommended for RP with ASC developed to be plaque-like and even fibrotic.

Human RGR Gene and Associated Features of Age-Related Macular Degeneration in Models of Retina-Choriocapillaris Atrophy.

Age-related macular degeneration (AMD) is a progressive eye disease and the most common cause of blindness among the elderly. AMD is characterized by early atrophy of the choriocapillaris and retinal pigment epithelium (RPE). Although AMD is a multifactorial disease with many environmental and genetic risk factors, a hallmark of the disease is the origination of extracellular deposits, or drusen, between the RPE and Bruch membrane. Human retinal G-protein-coupled receptor (RGR) gene generates an exon-skipping splice variant of RGR-opsin (RGR-d; NP_001012740) that is a persistent component of small and large drusen. Herein, the findings show that abnormal RGR proteins, including RGR-d, are pathogenic in an animal retina with degeneration of the choriocapillaris, RPE, and photoreceptors. A frameshift truncating mutation resulted in severe retinal degeneration with a continuous band of basal deposits along the Bruch membrane. RGR-d produced less severe disease with choriocapillaris and RPE atrophy, including focal accumulation of abnormal RGR-d protein at the basal boundary of the RPE. Degeneration of the choriocapillaris was marked by a decrease in endothelial CD31 protein and choriocapillaris breakdown at the ultrastructural level. Fundus lesions with patchy depigmentation were characteristic of old RGR-d mice. RGR-d was mislocalized in cultured cells and caused a strong cell growth defect. These results uphold the notion of a potential hidden link between AMD and a high-frequency RGR allele.

Xylitol enhances synthesis of propionate in the colon via cross-feeding of gut microbiota.

BACKGROUND: Xylitol, a white or transparent polyol or sugar alcohol, is digestible by colonic microorganisms and promotes the proliferation of beneficial bacteria and the production of short-chain fatty acids (SCFAs), but the mechanism underlying these effects remains unknown. We studied mice fed with 0%, 2% (2.17 g/kg/day), or 5% (5.42 g/kg/day) (weight/weight) xylitol in their chow for 3 months. In addition to the in vivo digestion experiments in mice, 3% (weight/volume) (0.27 g/kg/day for a human being) xylitol was added to a colon simulation system (CDMN) for 7 days. We performed 16S rRNA sequencing, beneficial metabolism biomarker quantification, metabolome, and metatranscriptome analyses to investigate the prebiotic mechanism of xylitol. The representative bacteria related to xylitol digestion were selected for single cultivation and co-culture of two and three bacteria to explore the microbial digestion and utilization of xylitol in media with glucose, xylitol, mixed carbon sources, or no-carbon sources. Besides, the mechanisms underlying the shift in the microbial composition and SCFAs were explored in molecular contexts. RESULTS: In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro. Cross-feeding, a relationship in which one organism consumes metabolites excreted by the other, was observed among Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol. At the molecular level, we revealed that xylitol dehydrogenase (EC 1.1.1.14), xylulokinase (EC 2.7.1.17), and xylulose phosphate isomerase (EC 5.1.3.1) were key enzymes in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Therefore, they are considered keystone bacteria in xylitol digestion. Also, xylitol affected the metabolic pathway of propionate, significantly promoting the transcription of phosphate acetyltransferase (EC 2.3.1.8) in Bifidobacterium and increasing the production of propionate. CONCLUSIONS: Our results revealed that those key enzymes for xylitol digestion from different bacteria can together support the growth of micro-ecology, but they also enhanced the concentration of propionate, which lowered pH to restrict relative amounts of Escherichia and Staphylococcus. Based on the cross-feeding and competition among those bacteria, xylitol can dynamically balance proportions of the gut microbiome to promote enzymes related to xylitol metabolism and SCFAs. Video Abstract.

Vitamin B12 Enriched in Spinach and its Effects on Gut Microbiota.

Meat and fermented foods are the main source of vitamin B12 (cobalamin) for human beings. Therefore, daily cobalamin intake is a big problem for vegans. In this study, cyanocobalamin (CNCBL) was added to the culture broth for cobalamin enrichment in spinach. After 36 h of cultivation, the accumulated CNCBL in the spinach leaves (wet weight) was as high as 0.48% (concentration), and the leaves still contained 0.94 ± 0.11 µg/g CNCBL after boiling, which could provide consumer daily requirement of CNCBL. Because CNCBL supplementation had adverse effects on gut microbiota, this study focused on the effect of the combination of spinach and CNCBL on gut microbiota as well. After the boiled leaves were passed through an in vitro gastrointestinal tract simulation system, it was found that the spinach protected CNCBL against the low-pH gastric acid. Moreover, compared with the CNCBL supplement group, the relative abundances of Bacteroides and Firmicutes increased, and the relative abundance of Proteobacteria, especially Escherichia spp., reduced. Analysis of short-chain fatty acids (SCFAs) showed that cobalamin-rich spinach was positively correlated with Bacteroides, propionate, and butyrate. The results showed that the method of enriching spinach with CNCBL was effective and had beneficial effects on gut microbiota and SCFAs.

Gut microbiota affect the formation of calcium oxalate renal calculi caused by high daily tea consumption.

Kidney stones are a common and frequently occurring disease worldwide. Stones can cause urinary tract obstruction, pain, haematuria, and other symptoms. In this study, the relationship between calcium oxalate renal calculi and gut microbiota was considered. The dietary habits of 30 patients with calcium oxalate kidney stones and 30 healthy people were investigated. The 16S rDNA sequences and short-chain fatty acids (SCFAs) in their stool samples were analysed. We identified 5 genera of the gut microbiota as biomarkers for calcium oxalate renal calculi, namely, Bacteroides, Phascolarctobacterium, Faecalibacterium, Akkermansia, and Lactobacillus, with a receiver operating characteristic (ROC) curve value of 0.871 (95% confidence interval (CI) 0.785-0.957). Phascolarctobacterium and Faecalibacterium showed a positive relationship with SCFA synthesis to reduce the risk of kidney stones. Meanwhile, according to the analysis, Lactobacillus spp. made the largest contribution (79%) to prevent kidney stones caused by tea consumption, since tea offers the great parts of oxalate in kidney stone formation. Three strains of Lactobacillus spp. were isolated from stools of a healthy person with a high level of tea consumption who did not suffer from kidney stones. All these strains survived in the colon with supplementation of high concentrations of tea and efficiently degraded oxalic acid (Ca. 50%) in an in vitro colonic simulation. Therefore, a suitable adjustment of the gut microbiota or SCFA concentration enhanced the degradation of oxalate from food, which can be applied to prevent the formation of calcium oxalate renal calculi caused by tea. KEY POINTS: • Five genera, including Lactobacillus, were identified as biomarkers for calcium oxalate renal calculi. • Lactobacillus is a potential gut bacterium associated with preventing kidney stone formation. • Isolated Lactobacillus strains have the ability to degrade oxalic acid in vitro.

Identification and Validation of Angiogenesis-Related Gene Expression for Predicting Prognosis in Patients With Ovarian Cancer.

Ovarian cancer (OC) is a highly heterogeneous disease with different cellular origins reported; thus, precise prognostic strategies and effective new therapies are urgently needed for patients with OC. A growing number of studies have shown that most malignancies have intensive angiogenesis and rapid growth. Therefore, angiogenesis plays an important role in the development of tumor metastasis. However, the prognostic value of angiogenesis-related genes (ARGs) in OC remains to be further elucidated. In this study, the expression data and corresponding clinical data from patients with OC and normal control samples were downloaded with UCSC XENA. A total of 1,960 differentially expressed ARGs were screened and functionally annotated through Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Univariate Cox regression analysis was performed to identify ARGs associated with prognosis. New ARGs signatures (including ESM1, CXCL13, TPCN2, PTPRD, FOXO1, and ELK3) were constructed for the prediction of overall survival (OS) in OC based on the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. Patients were divided based on their median risk score. In the The Cancer Genome Atlas (TCGA) training dataset, the survival analysis showed that overall survival was lower in the high-risk group than that in the low-risk group (p < 0.0001). The International Cancer Genome Consortium (ICGC) database was used for validation, and the receiver operating characteristic (ROC) curves showed good performance. Univariate and multivariate Cox analyses were conducted to identify independent predictors of OS. The nomogram, including the risk score, age, stage, grade, and position, can not only show good predictive ability but also can explore the correlation analysis based on ARGs for immunogenicity, immune components, and immune phenotypes with risk score. Risk scores were correlated strongly with the type of immune infiltration. Furthermore, homologous recombination defect (HRD), NtAIscore, LOH score, LSTm score, stemness index (mRNAsi), and stromal cells were significantly correlated with risk score. The present study suggests that the novel signature constructed from six ARGs may serve as effective prognostic biomarkers for OC and contribute to clinical decision making and personalized prognostic monitoring of OC.

Bone-strengthening effects and safety of compound peptides from skin of Chiloscyllium plagiosum and Mustelus griseus.

Fish processing produces a lot of by-products highly containing large amount of proteins which mainly consist of collagen, implying great potential value for application as nutraceutical ingredients. In present study, two kinds of sharks, Chiloscyllium plagiosum and Mustelus griseus, were used as raw material to gain three kinds of "compound peptides" (CPs) by enzymolysis, FCP (CPs from the flesh of C. plagiosum), SCP (CPs from the skin of C. plagiosum), and SMG (CPs from the skin of M. griseus). According to a series of constituent analysis, the molecule weights of FCP, SCP, and SMG were under 800 Da; amino acids composition analysis of FCP, SCP, and SMG showed that there were high glycine, proline, and hydroxyproline and low cysteine contents in SCP and SMG, which is the characteristic of collagen peptides; their total protein contents were 87.500%, 91.875%, and 95.625%, respectively; and heavy metal contents of CPs were all beneath national standards. After three kinds of CPs were administrated intragastrically to C57BL/6 mice at a total dosage of 15 g/kg, bone-strengthening effects of SCP and SMG were manifested by osteoblasts activity promotion, bone mineral density (BMD) increase, and marrow adipocyte number decrease, yet nonsignificant effects were shown in FCP group. No index showed toxicity of SCP and SMG in subacute toxicology trial, indicating their safety as functional foods. Herein, industrial application foundation of the skins from these two sharks was explored but more efforts should subsequently be implemented for further exploitation.

A computerized resolution visual acuity test in preschool and school age children.

AIM: To develop a novel approach called the Autoacuity Tester, and to evaluate its validity, especially the sensitivity and specificity for detecting amblyopia. METHODS: Children aged from 3 to 12y (n=552) were enrolled in the study. The validity of the Autoacuity Tester was evaluated by comparing it to the Tumbling E Early Treatment Diabetic Retinopathy Study (ETDRS) acuity chart for school age children, and Lea Symbols and Teller acuity card (TAC) for preschool children. The repeatability was assessed by coefficient of repeatability (COR). The sensitivity and specificity for detecting amblyopia were calculated. RESULTS: The mean difference (95% limits of agreement) between the Autoacuity Tester and the ETDRS tests were -0.03 (-0.24, 0.19) logMAR for the school age group. In preschool children, the mean difference was 0.04 (-0.14, 0.21) logMAR between the Autoacuity Tester and the TAC and 0.00 (-0.17, 0.18) logMAR between the Autoacuity Tester and the Lea Symbols. For the school age group, the COR was 0.20 logMAR for the Autoacuity Tester and 0.18 logMAR for the ETDRS. For the preschool group, the COR was 0.13 logMAR for the Autoacuity Tester and 0.21 logMAR for TAC. The Autoacuity Tester (88%) is more sensitive than TAC (72%) in detecting amblyopia (P=0.04), while had similar specificity (92% vs 90%, P=0.20). CONCLUSION: The Autoacuity Tester provides a reliable alternative for assessing visual acuity, and offers advantage of higher testability and repeatability for preschool children.