Skin characterization of diabetes mellitus revealed by polarization-sensitive optical coherence tomography imaging.

Significance: Diabetes can lead to the glycation of proteins and dysfunction of skin collagen. Skin lesions are a prevalent clinical symptom of diabetes mellitus (DM). Early diagnosis and assessing the efficacy of treatment for DM are crucial for patient health management. However, performing a non-invasive skin assessment in the early stages of DM is challenging. Aim: By using the polarization-sensitive optical coherent tomography (PS-OCT) imaging technique, it is possible to noninvasively assess the skin changes caused by diabetes. Approach: The PS-OCT was used to monitor the polarization characteristics of mouse skin at different stages of diabetes. Results: Based on a multi-layered adhesive tape model, we found that the polarization characteristics (retardation, optic axis, and polarization uniformity) were sensitive to the microstructure changes in the samples. Through this method, we observed significant changes in the polarization states of the skin as diabetes progressed. This was in line with the detected microstructure changes in skin collagen fibers using scanning electron microscopy. Conclusions: This study presents a highly useful approach for non-invasive skin assessment of diabetes.

The complete mitochondrial genome of the Anas platyrhynchos Linnaeus, 1758 breed Longshengcui and its phylogenetic analyses.

Duck breed Longshengcui (Anas platyrhynchos Linnaeus, 1758 breed Longshengcui, LSC) is one of the famous native breed of the Guangxi Zhuang Nationality Autonomous Region in China. In this study, we report the complete mitochondrial genome of LSC. The mitogenome (GenBank accession no. MZ895120) has 16,602 bp in length and consisted of the well-known 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and the control region. The phylogenetic analysis showed that LSC and Zhijiang duck have highly similar genetic relationship. These results are helpful for the conservation of genetic resources and phylogeny of this species.

Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Effect of muscle activation on dynamic responses of neck of pilot during emergency ejection: a finite element study.

To determine the effect of muscle activation on the dynamic responses of the neck of a pilot during simulated emergency ejections. A complete finite element model of the pilot's head and neck was developed and dynamically validated. Three muscle activation curves were designed to simulate different activation times and levels of muscles during pilot ejection: A is the unconscious activation curve of the neck muscles, B is the pre-activation curve, and C is the continuous activation curve. The acceleration-time curves obtained during ejection were applied to the model, and the influence of the muscles on the dynamic responses of the neck was investigated by analyzing both angles of rotation of the neck segments and disc stresses. Muscle pre-activation reduced fluctuations in the angle of rotation in each phase of the neck. Continuous muscle activation caused a 20% increase in the angle of rotation compared to pre-activation. Moreover, it resulted in a 35% increase in the load on the intervertebral disc. The maximum stress on the disc occurred in the C4-C5 phase. Continuous muscle activation increased both the axial load on the neck and the posterior extension angle of rotation of the neck. Muscle pre-activation during emergency ejection has a protective effect on the neck. However, continuous muscle activation increases the axial load and rotation angle of the neck. A complete finite element model of the pilot's head and neck was established and three neck muscle activation curves were designed to investigate the effects of muscle activation time and level on the dynamic response of the pilot's neck during ejection. This increased insights into the protection mechanism of neck muscles on the axial impact injury of the pilot's head and neck.

An optical clearing imaging window: Realization of mouse brain imaging and manipulation through scalp and skull.

Cortical visualization is essential to understand the dynamic changes in brain microenvironment under physiopathological conditions. However, the turbid scalp and skull severely limit the imaging depth and resolution. Existing cranial windows require invasive scalp excision and various subsequent skull treatments. Non-invasive in vivo imaging of skull bone marrow, meninges, and cortex through scalp and skull with high resolution yet remains a challenge. In this work, a non-invasive trans-scalp/skull optical clearing imaging window is proposed for cortical and calvarial imaging, which is achieved by applying a novel skin optical clearing reagent. The imaging depth and resolution are greatly enhanced in near infrared imaging and optical coherence tomography imaging. Combining this imaging window with adaptive optics, we achieve the visualization and manipulation of the calvarial and cortical microenvironment through the scalp and skull using two-photon imaging for the first time. Our method provides a well-performed imaging window and paves the way for intravital brain studies with the advantages of easy-operation, convenience and non-invasiveness.

GSCA: an integrated platform for gene set cancer analysis at genomic, pharmacogenomic and immunogenomic levels.

Cancer initiation and progression are likely caused by the dysregulation of biological pathways. Gene set analysis (GSA) could improve the signal-to-noise ratio and identify potential biological insights on the gene set level. However, platforms exploring cancer multi-omics data using GSA methods are lacking. In this study, we upgraded our GSCALite to GSCA (gene set cancer analysis, http://bioinfo.life.hust.edu.cn/GSCA) for cancer GSA at genomic, pharmacogenomic and immunogenomic levels. In this improved GSCA, we integrated expression, mutation, drug sensitivity and clinical data from four public data sources for 33 cancer types. We introduced useful features to GSCA, including associations between immune infiltration with gene expression and genomic variations, and associations between gene set expression/mutation and clinical outcomes. GSCA has four main functional modules for cancer GSA to explore, analyze and visualize expression, genomic variations, tumor immune infiltration, drug sensitivity and their associations with clinical outcomes. We used case studies of three gene sets: (i) seven cell cycle genes, (ii) tumor suppressor genes of PI3K pathway and (iii) oncogenes of PI3K pathway to prove the advantage of GSCA over single gene analysis. We found novel associations of gene set expression and mutation with clinical outcomes in different cancer types on gene set level, while on single gene analysis level, they are not significant associations. In conclusion, GSCA is a user-friendly web server and a useful resource for conducting hypothesis tests by using GSA methods at genomic, pharmacogenomic and immunogenomic levels.

Biological Pathway-Derived TMB Robustly Predicts the Outcome of Immune Checkpoint Blockade Therapy.

Although immune checkpoint blockade (ICB) therapies have achieved great progress, the patient response varies among cancers. In this study, we analyzed the potential genomic indicators contributing to ICB therapy response. The results showed that high tumor mutation burden (TMB) failed to predict response in anti-PD1 treated melanoma. SERPINB3 was the most significant response-related gene in melanoma and mutations in either SERPINB3 or PEG3 can serve as an independent risk factor in melanoma. Some recurrent mutations in CSMD3 were only in responders or non-responders, indicating their diverse impacts on patient response. Enrichment scores (ES) of gene mutations in 12 biological pathways were significantly higher in responders or non-responders. Next, the P-TMB calculated from genes in these pathways was significantly related to patient response with prediction AUC 0.74-0.82 in all collected datasets. In conclusion, our work provides new insights into the application of TMB in predicting patient response, which will benefit to immunotherapy research.

Effects of Lecithin Supplementation in Feed of Different fat Levels on Serum Indexes and Liver Health of Laying Hens.

The aim of this experiment was to investigate the effect of soy lecithin on serum-related indicators and liver health in laying hens under the influence of high-fat diets. 180 peak laying hens at 40 weeks of age were randomly assigned to one of the four diets using a 2 × 2 factorial and fed for 5 weeks. The results showed that compared to the low-fat group, the high-fat group had lower egg production (p < 0.05) and higher average daily feed intake and feed-to-egg ratio (p < 0.05). At the 21st day, the serum levels of triglyceride (TC) and superoxide dismutase (SOD) were higher (p < 0.05), high-density lipoproteins cholesterol (HDL-C) levels were lower (p < 0.01), catalase (CAT) activity was lower (p < 0.05), TC and malondialdehyde (MDA) levels in liver were higher (p < 0.01) and SOD activity in liver was lower (p < 0.05) in layers supplemented with soy lecithin. CAT activity in serum was increased (p < 0.01) and total antioxidant capacity (T-AOC) activity in the liver was decreased (p < 0.05) after increasing the dietary fat concentration. The addition of soy lecithin and the increase in dietary fat concentration had a highly significant interaction on serum CAT activity and liver TC content in layers (p < 0.01). At the 35th day, the serum alanine aminotransferase (ALT) activity was higher (p < 0.01), serum glutathione peroxidase (GSH-Px) and CAT activity were higher (p < 0.05), and serum triglyceride (TG) content and total T-AOC capacity activity were lower (p < 0.05) in layers supplemented with soy lecithin. Increasing dietary fat concentration decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and GSH-Px activity in serum (p < 0.05). However, it increased TG and MDA content in liver (p < 0.05), and highly decreased SOD content in liver (p < 0.01) in layers. The addition of soy lecithin and increasing dietary fat concentration had a highly significant reciprocal effect on serum ALT viability and CAT viability (p < 0.01) and liver TG and MDA content and SOD viability (p < 0.05) in layers. In conclusion, feeding high-fat diets will adversely affect the laying performance of laying hens, while long-term addition of lecithin can improve the blood lipids and liver lipids of laying hens, enhance the antioxidant capacity of the liver, and maintain liver health.

EVAtool: an optimized reads assignment tool for small ncRNA quantification and its application in extracellular vesicle datasets.

Extracellular vesicles (EVs) carrying various small non-coding RNAs (sncRNAs) play a vital roles in cell communication and diseases. Correct quantification of multiple sncRNA biotypes simultaneously in EVs is a challenge due to the short reads (<30 bp) could be mapped to multiple sncRNA types. To address this question, we developed an optimized reads assignment algorithm (ORAA) to dynamically map multi-mapping reads to the sncRNA type with a higher proportion. We integrated ORAA with reads processing steps into EVAtool Python-package (http://bioinfo.life.hust.edu.cn/EVAtool) to quantify sncRNAs, especially for sncRNA-seq from EV samples. EVAtool allows users to specify interested sncRNA types in advanced mode or use default seven sncRNAs (microRNA, small nucleolar RNA, PIWI-interacting RNAs, small nuclear RNA, ribosomal RNA, transfer RNA and Y RNA). To prove the utilities of EVAtool, we quantified the sncRNA expression profiles for 200 samples from cognitive decline and multiple sclerosis. We found that more than 20% of short reads on average were mapped to multiple sncRNA biotypes in multiple sclerosis. In cognitive decline, the proportion of Y RNA is significantly higher than other sncRNA types. EVAtool is a flexible and extensible tool that would benefit to mine potential biomarkers and functional molecules in EVs.

Effect of Ramie on the Production Performance of Laying Hens, and the Quality, Nutrient Composition, Antioxidation of the Eggs.

Ramie (Boehmeria nivea), which is rich in protein, fatty acid, vitamins and minerals, has become a potential alternative feed resource for poultry, and has attracted more and more attentions in nutrition research. The objective of this study is to evaluate the effect of dietary ramie at different concentrations on the production performance of the hens, and the quality, nutrient composition, and antioxidation of the eggs. A total of 432 34-week-old Lohmann commercial laying hens were divided into four groups, that were fed with corn-soybean meal-based control diet, control mixed with ramie at concentrations of 3, 6, or 9% separately for 8 weeks. Results showed that dietary ramie did not affect production performance. And egg yolk color gradually deepened as the inclusion levels of ramie increased. Ramie at tested concentration could significantly reduce the content of malondialdehyde (MDA) (p = 0.002) and 3% ramie supplementation significantly increased total antioxidative capacity (T-AOC) concentrations in egg yolk compared to the control group (p = 0.033). In addition, dietary supplementation with 6% ramie significantly reduced total cholesterol (T-CHO) content (p < 0.05) compared with controls. For egg nutrient composition, compared with the control group, the addition of 6% ramie significantly increased (p < 0.05) total omega-3 polyunsaturated fatty acids (n-3PUFA) and phenylalanine (Phe) in yolk. In conclusion, dietary inclusion of 6% ramie was most effective in improving the color, antioxidative capability, and reducing T-CHO contents of the egg yolks without any negative impacts on the production performance of the hens.

A Long-Term Clearing Cranial Window for Longitudinal Imaging of Cortical and Calvarial Ischemic Injury through the Intact Skull.

Skull is a reservoir for supplying immune cells that mediate brain immune surveillance. However, during intravital optical imaging of brain, conventional cranial windows requiring skull thinning or removal disrupt brain immunity integrity. Here, a novel long-term clearing cranial window (LCCW) based on the intact skull, dedicated to chronic skull transparency maintenance, is proposed. It significantly improves optical imaging resolution and depth, by which the cortical and calvarial vascular injury and regeneration processes after ischemic injury are longitudinally monitored in awake mice. Results show that calvarial blood vessels recover earlier than the cortex. And the transcriptome analysis reveals that gene expression patterns and immune cells abundances exist substantial differences between brain and skull after ischemic injury, which may be one of the causes for the time lag between their vascular recovery. These findings bring great enlightenment to vascular regeneration and reconstruction. Moreover, LCCW provides a minimally invasive approach for imaging the brain and skull bone marrow.

Effect of Dietary Ramie Powder (Boehmeria nivea) at Various Levels on Growth Performance, Carcass and Meat Qualities, Biochemical Indices, and Antioxidative Capacity of Linwu Ducks.

Current experiment was designed to check the effect of dietary supplementation of ramie powder on the growth performance, carcass and meat qualities and antioxidative capacity of Linwu ducks. A total of 312 ducks at 21-day-age were equally divided into 4 groups, fed with control diet, control diet supplemented of 3, 6, or 12% ramie powder, respectively. The results showed that dietary supplementation of 6 and 12% ramie powder increased the final weight and daily body weight gain (P < 0.05), and dietary supplementation of 6% ramie improved the cooking loss of the leg meat 45-mins-postmortem compared with the control group (P < 0.05). Moreover, dietary supplementation of 6% ramie powder promoted the antioxidative capacity of the ducks by increasing the serum activities of superoxide dismutase and glutathione (P < 0.05), as well as the mRNA expressions of glutathione peroxidase 1 in the breast meat and superoxide dismutase 1 in the leg meat (P < 0.05). This experiment demonstrated that dietary supplementation of ramie powder showed beneficial efficacy on the growth performance of Linwu ducks. It corroborated the potential of dietary ramie being used as poultry feed ingredient and suggested that 6% was the proper supplementation rate of ramie powder in Linwu ducks' feed.

CBX2 and EZH2 cooperatively promote the growth and metastasis of lung adenocarcinoma.

The disruption of epigenetic regulation is common in tumors; the abnormal expression of epigenetic factors leads to cancer occurrence and development. In this study, to investigate the potential function of histone methylation regulators in lung adenocarcinoma (LUAD), we performed differential expression analysis using RNA-seq data downloaded from The Cancer Genome Atlas (TCGA) database, and identified CBX2 and EZH2 as obviously upregulated histone methylation regulators. CBX2 knockdown significantly inhibited LUAD cell growth and metastasis in vitro and in vivo. The combined high expression of CBX2 and EZH2 was an indicator of poor prognosis in LUAD. The inhibition of both CBX2 and EZH2 exerted cooperative suppressive effects on the growth and metastasis of LUAD cells. Mechanistically, we revealed that CBX2 and EZH2 downregulated several PPAR signaling pathway genes and tumor suppressor genes through binding to their promoter cooperatively or separately. Furthermore, knockdown of CBX2 improved the therapeutic efficiency of EZH2 inhibitor on A549 cells. Our study reveals the cooperative oncogenic role of CBX2 and EZH2 in promoting LUAD progression, thereby providing potential targets for LUAD diagnosis and therapy.

EVAtlas: a comprehensive database for ncRNA expression in human extracellular vesicles.

Extracellular vesicles (EVs) packing various molecules play vital roles in intercellular communication. Non-coding RNAs (ncRNAs) are important functional molecules and biomarkers in EVs. A comprehensive investigation of ncRNAs expression in EVs under different conditions is a fundamental step for functional discovery and application of EVs. Here, we curated 2030 small RNA-seq datasets for human EVs (1506 sEV and 524 lEV) in 24 conditions and over 40 diseases. We performed a unified reads dynamic assignment algorithm (RDAA) considering mismatch and multi-mapping reads to quantify the expression profiles of seven ncRNA types (miRNA, snoRNA, piRNA, snRNA, rRNA, tRNA and Y RNA). We constructed EVAtlas (http://bioinfo.life.hust.edu.cn/EVAtlas), a comprehensive database for ncRNA expression in EVs with four functional modules: (i) browse and compare the distribution of ncRNAs in EVs from 24 conditions and eight sources (plasma, serum, saliva, urine, sperm, breast milk, primary cell and cell line); (ii) prioritize candidate ncRNAs in condition related tissues based on their expression; (iii) explore the specifically expressed ncRNAs in EVs from 24 conditions; (iv) investigate ncRNA functions, related drugs, target genes and EVs isolation methods. EVAtlas contains the most comprehensive ncRNA expression in EVs and will be a key resource in this field.

A comprehensive survey for human transcription factors on expression, regulation, interaction, phenotype and cancer survival.

Transcription factors (TFs) act as key regulators in biological processes through controlling gene expression. Here, we conducted a systematic study for all human TFs on the expression, regulation, interaction, mutation, phenotype and cancer survival. We revealed that the average expression levels of TFs in normal tissues were lower than 50% expression of non-TFs, whereas TF expression was increased in cancers. TFs that are specifically expressed in an individual tissue or cancer may be potential marker genes. For instance, TGIF2LX/Y were preferentially expressed in testis and NEUROG1, PRDM14, SRY, ZNF705A and ZNF716 were specifically highly expressed in germ cell tumors. We found different distributions of target genes and TF co-regulations in different TF families. Some small TF families have huge protein interaction pairs, suggesting their central roles in transcriptional regulation. The bZIP family is a small family involving many signaling pathways. Survival analysis indicated that most TFs significantly affect survival of one or more cancers. Some survival-related TFs were also specifically highly expressed in the corresponding cancer types, which may be potential targets for cancer therapy. Finally, we identified 43 TFs whose mutations were closely correlated to survival, suggesting their cancer-driven roles. The systematic analysis of TFs provides useful clues for further investigation of TF regulatory mechanisms and the role of TFs in diseases.

Effects of Dietary Ramie Powder at Various Levels on the Production Performance, Serum Biochemical Indices, Antioxidative Capacity, and Intestinal Development of Laying Hens.

The purpose of this study was to investigate the effects of ramie (0, 3, 6, and 9%) included in diets on production performance, antioxidative capacity, serum biochemical indices, and intestinal development of laying hens. A total of 432 Lohmann commercial laying hens were randomly allotted to one of four dietary treatments and fed for 6 weeks. The results showed that the inclusion of ramie had no negative effects on laying performance, and increased (quadratic, P < 0.05) the laying rate with the highest value in the 6% ramie group. However, ramie content in the diet up to 9% reduced the apparent metabolic energy, dry matter, and organic matter apparent digestibility of laying hens compared with those in the 3% ramie group. The content of high-density lipoprotein (HDL-C) in serum was increased (P < 0.05), but the activity of aspartate aminotransferase (AST) was decreased (P < 0.05) by dietary ramie supplementation. As the dietary ramie level increased, the activity of serum glutathione peroxidase (GSH-Px) was increased quadratically (P < 0.05). Compared with control, 3% ramie group significantly increased (P < 0.01) liver total superoxide dismutase (SOD) activity. Meanwhile, the addition of 3∼6% ramie powder increased (P < 0.05) villus height of jejunum and villus height/crypt depth (V/C) of ileum, which reflected the intestinal promotional effect of ramie powder. In conclusion, ramie in a diet of less than 9% might protect the liver and improve the antioxidative capacity with no detrimental impacts on the laying hens. Moreover, it could promote the intestinal mucosal structure and have a positive impact on the intestine health of the laying hens.

Expression profile of immune checkpoint genes and their roles in predicting immunotherapy response.

Immune checkpoint genes (ICGs) play critical roles in circumventing self-reactivity and represent a novel target to develop treatments for cancers. However, a comprehensive analysis for the expression profile of ICGs at a pan-cancer level and their correlation with patient response to immune checkpoint blockade (ICB) based therapy is still lacking. In this study, we defined three expression patterns of ICGs using a comprehensive survey of RNA-seq data of tumor and immune cells from the functional annotation of the mammalian genome (FANTOM5) project. The correlation between the expression patterns of ICGs and patients survival and response to ICB therapy was investigated. The expression patterns of ICGs were robust across cancers, and upregulation of ICGs was positively correlated with high lymphocyte infiltration and good prognosis. Furthermore, we built a model (ICGe) to predict the response of patients to ICB therapy using five features of ICG expression. A validation scenario of six independent datasets containing data of 261 patients with CTLA-4 and PD-1 blockade immunotherapies demonstrated that ICGe achieved area under the curves of 0.64-0.82 and showed a robust performance and outperformed other mRNA-based predictors. In conclusion, this work revealed expression patterns of ICGs and underlying correlations between ICGs and response to ICB, which helps to understand the mechanisms of ICGs in ICB signal pathways and other anticancer treatments.

miRNASNP-v3: a comprehensive database for SNPs and disease-related variations in miRNAs and miRNA targets.

MicroRNAs (miRNAs) related single-nucleotide variations (SNVs), including single-nucleotide polymorphisms (SNPs) and disease-related variations (DRVs) in miRNAs and miRNA-target binding sites, can affect miRNA functions and/or biogenesis, thus to impact on phenotypes. miRNASNP is a widely used database for miRNA-related SNPs and their effects. Here, we updated it to miRNASNP-v3 (http://bioinfo.life.hust.edu.cn/miRNASNP/) with tremendous number of SNVs and new features, especially the DRVs data. We analyzed the effects of 7 161 741 SNPs and 505 417 DRVs on 1897 pre-miRNAs (2630 mature miRNAs) and 3'UTRs of 18 152 genes. miRNASNP-v3 provides a one-stop resource for miRNA-related SNVs research with the following functions: (i) explore associations between miRNA-related SNPs/DRVs and diseases; (ii) browse the effects of SNPs/DRVs on miRNA-target binding; (iii) functional enrichment analysis of miRNA target gain/loss caused by SNPs/DRVs; (iv) investigate correlations between drug sensitivity and miRNA expression; (v) inquire expression profiles of miRNAs and their targets in cancers; (vi) browse the effects of SNPs/DRVs on pre-miRNA secondary structure changes; and (vii) predict the effects of user-defined variations on miRNA-target binding or pre-miRNA secondary structure. miRNASNP-v3 is a valuable and long-term supported resource in functional variation screening and miRNA function studies.