Patterned cPCDH expression regulates the fine organization of the neocortex.

The neocortex consists of a vast number of diverse neurons that form distinct layers and intricate circuits at the single-cell resolution to support complex brain functions1. Diverse cell-surface molecules are thought to be key for defining neuronal identity, and they mediate interneuronal interactions for structural and functional organization2-6. However, the precise mechanisms that control the fine neuronal organization of the neocortex remain largely unclear. Here, by integrating in-depth single-cell RNA-sequencing analysis, progenitor lineage labelling and mosaic functional analysis, we report that the diverse yet patterned expression of clustered protocadherins (cPCDHs)-the largest subgroup of the cadherin superfamily of cell-adhesion molecules7-regulates the precise spatial arrangement and synaptic connectivity of excitatory neurons in the mouse neocortex. The expression of cPcdh genes in individual neocortical excitatory neurons is diverse yet exhibits distinct composition patterns linked to their developmental origin and spatial positioning. A reduction in functional cPCDH expression causes a lateral clustering of clonally related excitatory neurons originating from the same neural progenitor and a significant increase in synaptic connectivity. By contrast, overexpression of a single cPCDH isoform leads to a lateral dispersion of clonally related excitatory neurons and a considerable decrease in synaptic connectivity. These results suggest that patterned cPCDH expression biases fine spatial and functional organization of individual neocortical excitatory neurons in the mammalian brain.

Centrosome anchoring regulates progenitor properties and cortical formation.

Radial glial progenitor cells (RGPs) are the major neural progenitor cells that generate neurons and glia in the developing mammalian cerebral cortex1-4. In RGPs, the centrosome is positioned away from the nucleus at the apical surface of the ventricular zone of the cerebral cortex5-8. However, the molecular basis and precise function of this distinctive subcellular organization of the centrosome are largely unknown. Here we show in mice that anchoring of the centrosome to the apical membrane controls the mechanical properties of cortical RGPs, and consequently their mitotic behaviour and the size and formation of the cortex. The mother centriole in RGPs develops distal appendages that anchor it to the apical membrane. Selective removal of centrosomal protein 83 (CEP83) eliminates these distal appendages and disrupts the anchorage of the centrosome to the apical membrane, resulting in the disorganization of microtubules and stretching and stiffening of the apical membrane. The elimination of CEP83 also activates the mechanically sensitive yes-associated protein (YAP) and promotes the excessive proliferation of RGPs, together with a subsequent overproduction of intermediate progenitor cells, which leads to the formation of an enlarged cortex with abnormal folding. Simultaneous elimination of YAP suppresses the cortical enlargement and folding that is induced by the removal of CEP83. Together, these results indicate a previously unknown role of the centrosome in regulating the mechanical features of neural progenitor cells and the size and configuration of the mammalian cerebral cortex.

A proteomic atlas of ligand-receptor interactions at the ovine maternal-fetal interface reveals the role of histone lactylation in uterine remodeling.

Well-orchestrated maternal-fetal cross talk occurs via secreted ligands, interacting receptors, and coupled intracellular pathways between the conceptus and endometrium and is essential for successful embryo implantation. However, previous studies mostly focus on either the conceptus or the endometrium in isolation. The lack of integrated analysis impedes our understanding of early maternal-fetal cross talk. Herein, focusing on ligand-receptor complexes and coupled pathways at the maternal-fetal interface in sheep, we provide the first comprehensive proteomic map of ligand-receptor pathway cascades essential for embryo implantation. We demonstrate that these cascades are associated with cell adhesion and invasion, redox homeostasis, and the immune response. Candidate interactions and their physiological roles were further validated by functional experiments. We reveal the physical interaction of albumin and claudin 4 and their roles in facilitating embryo attachment to endometrium. We also demonstrate a novel function of enhanced conceptus glycolysis in remodeling uterine receptivity by inducing endometrial histone lactylation, a newly identified histone modification. Results from in vitro and in vivo models supported the essential role of lactate in inducing endometrial H3K18 lactylation and in regulating redox homeostasis and apoptotic balance to ensure successful implantation. By reconstructing a map of potential ligand-receptor pathway cascades at the maternal-fetal interface, our study presents new concepts for understanding molecular and cellular mechanisms that fine-tune conceptus-endometrium cross talk during implantation. This provides more direct and accurate insights for developing potential clinical intervention strategies to improve pregnancy outcomes following both natural and assisted conception.

Dessert or Poison? The Roles of Glycosylation in Alzheimer's, Parkinson's, Huntington's Disease, and Amyotrophic Lateral Sclerosis.

Ministry of Education and Key Laboratory of Neurons and glial cells of the central nervous system (CNS) are modified by glycosylation and rely on glycosylation to achieve normal neural function. Neurodegenerative disease is a common disease of the elderly, affecting their healthy life span and quality of life, and no effective treatment is currently available. Recent research implies that various glycosylation traits are altered during neurodegenerative diseases, suggesting a potential implication of glycosylation in disease pathology. Herein, we summarized the current knowledge about glycosylation associated with Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS) pathogenesis, focusing on their promising functional avenues. Moreover, we collected research aimed at highlighting the need for such studies to provide a wealth of disease-related glycosylation information that will help us better understand the pathophysiological mechanisms and hopefully specific glycosylation information to provide further diagnostic and therapeutic directions for neurodegenerative diseases.

A systematic comparison of normalization methods for eQTL analysis.

Expression quantitative trait loci (eQTL) analysis has been widely used in interpreting disease-associated loci through correlating genetic variant loci with the expression of specific genes. RNA-sequencing (RNA-Seq), which can quantify gene expression at the genome-wide level, is often used in eQTL identification. Since different normalization methods of gene expression have substantial impacts on RNA-seq downstream analysis, it is of great necessity to systematically compare the effects of these methods on eQTL identification. Here, by using RNA-seq and genotype data of four different cancers in The Cancer Genome Atlas (TCGA) database, we comprehensively evaluated the effect of eight commonly used normalization methods on eQTL identification. Our results showed that the application of different methods could cause 20-30% differences in the final results of eQTL identification. Among these methods, COUNT, Median of Ratio (MED) and Trimmed Mean of M-values (TMM) generated similar results for identifying eQTLs, while Fragments Per Kilobase Million (FPKM) or RANK produced more differential results compared with other methods. Based on the accuracy and receiver operating characteristic (ROC) curve, the TMM method was found to be the optimal method for normalizing gene expression data in eQTLs analysis. In addition, we also evaluated the performance of different pairwise combinations of these methods. As a result, compared with single normalization methods, the combination of methods can not only identify more cis-eQTLs, but also improve the performance of the ROC curve. Overall, this study provides a comprehensive comparison of normalization methods for identifying eQTLs from RNA-seq data, and proposes some practical recommendations for diverse scenarios.

Genomic and metabonomic methods reveal the probiotic functions of swine-derived Ligilactobacillus salivarius.

BACKGROUND: As substitutes for antibiotics, probiotic bacteria protect against digestive infections caused by pathogenic bacteria. Ligilactobacillus salivarius is a species of native lactobacillus found in both humans and animals. Herein, a swine-derived Ligilactobacillus salivarius was isolated and shown to colonize the ileal mucous membrane, thereby promoting nutritional digestion, absorption, and immunity. To evaluate its probiotic role, the entire genome was sequenced, the genetic information was annotated, and the metabolic information was analyzed. RESULTS: The phylogenetic relationship indicated that the bacteria was closer to L. salivarius MT573555.1 and MT585431.1. Functional genes included transporters, membrane proteins, enzymes, heavy metal resistance proteins, and putative proteins; metabolism-related genes were the most abundant. The six types of metabolic pathways secreted by L. salivarius were mainly composed of secretory transmembrane proteins and peptides. The secretory proteins of L. salivarius were digestive enzymes, functional proteins that regulate apoptosis, antibodies, and hormones. Non-targeted metabolomic analysis of L. salivarius metabolites suggested that ceramide, pyrrolidone- 5- carboxylic acid, N2-acetyl-L-ornithine, 2-ethyl-2-hydroxybutyric acid, N-lactoyl-phenylalanine, and 12 others were involved in antioxidation, repair of the cellular membrane, anticonvulsant, hypnosis, and appetite inhibition. Metabolites of clavaminic acid, antibiotic X14889C, and five other types of bacteriocins were identified, namely phenyllactic acid, janthitrem G, 13-demethyl tacrolimus, medinoside E, and tertonasin. The adherence and antioxidation of L. salivarius were also predicted. No virulence genes were found. CONCLUSION: The main probiotic properties of L. salivarius were identified using genomic, metabonomic, and biochemical assays, which are beneficial for porcine feeding. Our results provided deeper insights into the probiotic effects of L. salivarius.

Ligilactobacillus Salivarius improve body growth and anti-oxidation capacity of broiler chickens via regulation of the microbiota-gut-brain axis.

Certain strains of probiotic bacteria can secret functional substances namely digestive enzymes and functional peptides to regulate physiological conditions such as digestion and anti-oxidation, which are often incorporated in industrial broiler chick production. However, few studies have detailed the action mechanisms and effects of these bacteria on regulating growth and anti-oxidation levels in broiler chickens. Ligilactobacillus salivarius is a strain of probiotic bacteria used as dietary supplement. In the present study, Ligilactobacillus salivarius was evaluated for its secreted digestive enzymes in vitro. To detailed evaluate the action mechanisms and effects of gastrointestinal tract (GIT) microbiota on alleviating anti-oxidation levels of broiler chickens through the gut-brain axis. Ligilactobacillus salivarius was cultured and supplemented in the food of broilers to evaluate the probiotic effect on growth and anti-oxidation by modulation of gut microbial composition and its functional metabolites using metagenomic and metabolomic assays. Biochemical results showed that Ligilactobacillus salivarius secreted digestive enzymes: protease, lipase, and amylase. Broiler chickens with Ligilactobacillus salivarius supplemented for 42 days, showed increased body weights, a reduced oxidative status, decreased malondialdehyde levels, and improved activities rates of total superoxide dismutase, glutathione peroxidase IIand IV improved. The microbial composition of caecum was more abundant than those broiler without probiotics supplementation, owing 400 of total number (489) of bacterial operational taxonomic units (OTU). The genera of Lactobacillus, Megamonas, Ruminoccoccaceae, Ruminococcus, Alistipes and Helicobacter shared the dominant proportion of Candidatus _Arthromitus compared with the control chickens. These functional bacteria genera assisted in the transportation and digestion of amino acids, carbohydrates, and ions, synthesis of cellular membranes, and anti-oxidation. Uncultured_organism_g_ Anaerosporobacter, Lactobacillus salivarius, uncultured_bacterium_g_ Ruminococcaceae_UCG-014, uncultured_bacterium_g_ Peptococcus were strongly and positively correlated with body growth performance and anti-oxidation. A metabonomic assay suggested that the secreted of gamma-aminobutyric acid and monobactam was metabolized according to the Kyoto Encyclopedia of Genes and Genomes analysis. In conclusion, Ligilactobacillus salivarius optimized microbial composition of the caecum and secreted functional peptides through gut-brain axis to improve the body growth and antioxidation of broiler chicken.

Antidiabetic activity of Tartary buckwheat protein-derived peptide AFYRW and its effects on protein glycosylation of pancreas in mice.

Diabetes Mellitus (DM) is one of the most important public health problems, and new antidiabetic drugs with fewer side effects are urgently needed. Here, we measured the antidiabetic effects of an antioxidant peptide (Ala-Phe-Tyr-Arg-Trp, AFYRW) from Tartary Buckwheat Albumin (TBA) in a high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mouse model. The data showed that AFYRW suppressed hepatocyte steatosis and triglycerides while ameliorating insulin resistance in mice. Successively, the influence of AFYRW on aberrant protein glycosylation in diabetic mice was further investigated by lectin microarrays. The results suggested AFYRW could restore the expression of GalNAc, GalNAcα1-3Gal and GalNAcα1-3Galß1-3/4Glc recognized by PTL-I, Siaα2-3Galß1-4Glc(NAc)/Glc, Siaα2-3Gal, Siaα2-3 and Siaα2-3GalNAc recognized by MAL-II, terminating in GalNAcα/ß1-3/6Gal recognized by WFA and αGalNAc, αGal, anti-A and B recognized by GSI-I to normal levels in the pancreas of HFD-STZ-induced diabetic mice. This work may provide new targets for the future discovery of potential biomarkers to evaluate the efficacy of food-derived antidiabetic drugs based on precise alterations of glycopatterns in DM.

Tartary buckwheat protein-derived peptide AFYRW alleviates H2O2-induced vascular injury via the PI3K/AKT/NF-κB pathway.

Tartary buckwheat protein-derived peptide (Ala-Phe-Tyr-Arg-Trp, AFYRW) is a natural active peptide that hampers the atherosclerosis process, but the underlying role of AFYRW in angiogenesis remains unknown. Here, we present a system-based study to evaluate the effects of AFYRW on H2O2-induced vascular injury in human umbilical vein endothelial cells (HUVECs). HUVECs were co-incubated with H2O2 for 2 h in the vascular injury model, and AFYRW was added 24 h in advance to investigate the protective mechanism of vascular injury. We identified that AFYRW inhibits oxidative stress, cell migration, cell invasion, and angiogenesis in H2O2-treated HUVECs. In addition, we found H2O2-induced upregulation of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), phosphorylation of nuclear factor-κB (NF-κB) p65 and nuclear translocation of NF-κB decreased by AFYRW. Taken together, AFYRW attenuated H2O2-induced vascular injury through the PI3K/AKT/NF-κB pathway. Thereby, AFYRW may serve as a therapeutic option for vascular injuries.

Animal-APAdb: a comprehensive animal alternative polyadenylation database.

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism that recognizes different polyadenylation signals on transcripts, resulting in transcripts with different lengths of 3' untranslated regions and thereby influencing a series of biological processes. Recent studies have highlighted the important roles of APA in human. However, APA profiles in other animals have not been fully recognized, and there is no database that provides comprehensive APA information for other animals except human. Here, by using the RNA sequencing data collected from public databases, we systematically characterized the APA profiles in 9244 samples of 18 species. In total, we identified 342 952 APA events with a median of 17 020 per species using the DaPars2 algorithm, and 315 691 APA events with a median of 17 953 per species using the QAPA algorithm in these 18 species, respectively. In addition, we predicted the polyadenylation sites (PAS) and motifs near PAS of these species. We further developed Animal-APAdb, a user-friendly database (http://gong_lab.hzau.edu.cn/Animal-APAdb/) for data searching, browsing and downloading. With comprehensive information of APA events in different tissues of different species, Animal-APAdb may greatly facilitate the exploration of animal APA patterns and novel mechanisms, gene expression regulation and APA evolution across tissues and species.

Ion release and biocompatibility of Co-Cr alloy fabricated by selective laser melting from recycled Co-Cr powder: An in vitro study.

STATEMENT OF PROBLEM: As the cobalt chromium (Co-Cr) powder used in selective laser melting (SLM) is costly, reusing the remaining powder after multiple cycles provides an economic and environmental benefit. However, knowledge of the cytotoxic effect of the alloy fabricated from recycled powder is lacking. PURPOSE: The purpose of this in vitro study was to evaluate the biological effects of the Co-Cr ions released from the alloy fabricated from the recycled powder on the human gingival fibroblasts (HGFs) and normal oral keratinocytes (NOKs). MATERIAL AND METHODS: Disk-shaped Co-Cr specimens were fabricated by using the SLM technique from powders with different proportions of recycled to unused and from different recycling times. Co and Cr ions released from the disks immersed in the Dulbecco Modified Eagle Medium (DMEM) for 24 hours or 7 days were measured by inductively coupled plasma mass spectrometry (ICP-MS). Biocompatibility of Co-Cr alloy was detected by incubation of HGFs and NOKs in DMEM containing Co and Cr ions for 24 hours. The ANOVA test was used to evaluate statistically significant differences among different groups (α=.05). RESULTS: Compared with the alloy fabricated from 100% unused powder, the concentrations of Co and Cr ions increased with the increase of recycled to unused powder ratio or with the increase in the recycling times. HGFs and NOKs showed an increase in apoptosis, intracellular oxidative stress (ROS), hypoxia-inducing factor1α (HIF-1α), and proinflammatory cytokines (tumor necrosis factor alpha [TNF- α], interleukin 6 [IL-6], interleukin 8 [IL-8], and vascular endothelial growth factor [VEGF]) with the increase of Co-Cr ions in a concentration-dependent manner. A significant reduction in cell proliferation was found with the increase in the concentrations of Co and Cr ions (P<.05). CONCLUSIONS: The results of this study indicated that Co-Cr alloy fabricated from partially recycled powder or powder with different recycling times released significantly more Co and Cr ions and showed higher cytotoxicity to HGFs and NOKs than the alloy fabricated from unused powder.

Systematic analysis of inflammation and pain pathways in a mouse model of gout.

Gout is a prevalent and painful inflammatory arthritis, and its global burden continues to rise. Intense pain induced by gout attacks is a major complication of gout. However, systematic studies of gout inflammation and pain are lacking. Using a monosodium urate (MSU) crystal-induced gout model, we performed genome-wide transcriptome analysis of the inflamed ankle joint, dorsal root ganglion (DRG), and spinal cord of gouty mice. Our results revealed important transcriptional changes, including highly elevated inflammation and broad activation of immune pathways in both the joint and the nervous system, in gouty mice. Integrated analysis showed that there was a remarkable overlap between our RNAseq and human genome-wide association study (GWAS) of gout; for example, the risk gene, stanniocalcin-1 (STC1) showed significant upregulation in all three tissues. Interestingly, when compared to the transcriptomes of human osteoarthritis (OA) and rheumatoid arthritis (RA) joint tissues, we identified significant upregulation of cAMP/cyclic nucleotide-mediated signaling shared between gouty mice and human OA with high knee pain, which may provide excellent drug targets to relieve gout pain. Furthermore, we investigated the common and distinct transcriptomic features of gouty, inflammatory pain, and neuropathic pain mouse models in their DRG and spinal cord tissues. Moreover, we discovered distinct sets of genes with significant differential alternative splicing or differential transcript usage in each tissue, which were largely not detected by conventional differential gene expression analysis approaches. Based on these results, our study provided a more accurate and comprehensive depiction of transcriptomic alterations related to gout inflammation and pain.

Electrochemical Sulfonylation-Induced Lactonization of Alkenes: Synthesis of Sulfonyl Phthalides.

An electrochemical cascade sulfonylation and lactonization process of alkenes and a most widely used arylsulfonylation reagent─sulfonyl hydrazines─was developed for the first time. This electrochemical sulfonyl lactonization avoided the use of toxic metal catalysts or stoichiometric oxidants and was carried out under mild conditions. The target product γ-sulfonylated phthalides with broad and excellent substrate tolerance were achieved.

Animal-ImputeDB: a comprehensive database with multiple animal reference panels for genotype imputation.

Animal-ImputeDB (http://gong_lab.hzau.edu.cn/Animal_ImputeDB/) is a public database with genomic reference panels of 13 animal species for online genotype imputation, genetic variant search, and free download. Genotype imputation is a process of estimating missing genotypes in terms of the haplotypes and genotypes in a reference panel. It can effectively increase the density of single nucleotide polymorphisms (SNPs) and thus can be widely used in large-scale genome-wide association studies (GWASs) using relatively inexpensive and low-density SNP arrays. However, most animals except humans lack high-quality reference panels, which greatly limits the application of genotype imputation in animals. To overcome this limitation, we developed Animal-ImputeDB, which is dedicated to collecting genotype data and whole-genome resequencing data of nonhuman animals from various studies and databases. A computational pipeline was developed to process different types of raw data to construct reference panels. Finally, 13 high-quality reference panels including ∼400 million SNPs from 2265 samples were constructed. In Animal-ImputeDB, an easy-to-use online tool consisting of two popular imputation tools was designed for the purpose of genotype imputation. Collectively, Animal-ImputeDB serves as an important resource for animal genotype imputation and will greatly facilitate research on animal genomic selection and genetic improvement.

ncRNA-eQTL: a database to systematically evaluate the effects of SNPs on non-coding RNA expression across cancer types.

Numerous studies indicate that non-coding RNAs (ncRNAs) have critical functions across biological processes, and single-nucleotide polymorphisms (SNPs) could contribute to diseases or traits through influencing ncRNA expression. However, the associations between SNPs and ncRNA expression are largely unknown. Therefore, genome-wide expression quantitative trait loci (eQTL) analysis to assess the effects of SNPs on ncRNA expression, especially in multiple cancer types, will help to understand how risk alleles contribute toward tumorigenesis and cancer development. Using genotype data and expression profiles of ncRNAs of >8700 samples from The Cancer Genome Atlas (TCGA), we developed a computational pipeline to systematically identify ncRNA-related eQTLs (ncRNA-eQTLs) across 33 cancer types. We identified a total of 6 133 278 and 721 122 eQTL-ncRNA pairs in cis-eQTL and trans-eQTL analyses, respectively. Further survival analyses identified 8312 eQTLs associated with patient survival times. Furthermore, we linked ncRNA-eQTLs to genome-wide association study (GWAS) data and found 262 332 ncRNA-eQTLs overlapping with known disease- and trait-associated loci. Finally, a user-friendly database, ncRNA-eQTL (http://ibi.hzau.edu.cn/ncRNA-eQTL), was developed for free searching, browsing and downloading of all ncRNA-eQTLs. We anticipate that such an integrative and comprehensive resource will improve our understanding of the mechanistic basis of human complex phenotypic variation, especially for ncRNA- and cancer-related studies.

SNP2APA: a database for evaluating effects of genetic variants on alternative polyadenylation in human cancers.

Alternative polyadenylation (APA) is an important post-transcriptional regulation that recognizes different polyadenylation signals (PASs), resulting in transcripts with different 3' untranslated regions, thereby influencing a series of biological processes and functions. Recent studies have revealed that some single nucleotide polymorphisms (SNPs) could contribute to tumorigenesis and development through dysregulating APA. However, the associations between SNPs and APA in human cancers remain largely unknown. Here, using genotype and APA data of 9082 samples from The Cancer Genome Atlas (TCGA) and The Cancer 3'UTR Altas (TC3A), we systematically identified SNPs affecting APA events across 32 cancer types and defined them as APA quantitative trait loci (apaQTLs). As a result, a total of 467 942 cis-apaQTLs and 30 721 trans-apaQTLs were identified. By integrating apaQTLs with survival and genome-wide association studies (GWAS) data, we further identified 2154 apaQTLs associated with patient survival time and 151 342 apaQTLs located in GWAS loci. In addition, we designed an online tool to predict the effects of SNPs on PASs by utilizing PAS motif prediction tool. Finally, we developed SNP2APA, a user-friendly and intuitive database (http://gong_lab.hzau.edu.cn/SNP2APA/) for data browsing, searching, and downloading. SNP2APA will significantly improve our understanding of genetic variants and APA in human cancers.

Multi-Level Cycle-Consistent Adversarial Networks with Attention Mechanism for Face Sketch-Photo Synthesis.

The synthesis between face sketches and face photos has important application values in law enforcement and digital entertainment. In cases of a lack of paired sketch-photo data, this paper proposes an unsupervised model to solve the problems of missing key facial details and a lack of realism in the synthesized images of existing methods. The model is built on the CycleGAN architecture. To retain more semantic information in the target domain, a multi-scale feature extraction module is inserted before the generator. In addition, the convolutional block attention module is introduced into the generator to enhance the ability of the model to extract important feature information. Via CBAM, the model improves the quality of the converted image and reduces the artifacts caused by image background interference. Next, in order to preserve more identity information in the generated photo, this paper constructs the multi-level cycle consistency loss function. Qualitative experiments on CUFS and CUFSF public datasets show that the facial details and edge structures synthesized by our model are clearer and more realistic. Meanwhile the performance indexes of structural similarity and peak signal-to-noise ratio in quantitative experiments are also significantly improved compared with other methods.

Effect of roughness and acidic medium on wear behavior of dental resin composite.

BACKGROUND: The aim of the study was to investigate whether the citric acid and rough surface have a synergistic effect leading to severe wear behavior of resin composite. MATERIALS AND METHODS: Disk-shaped (Ø15 × 1.5 mm) specimens of resin composite (n = 12) with different initial roughness were prepared. Reciprocating ball-on-flat wear tests were performed under distilled water and citric acid (pH = 5.5) respectively. The coefficient of friction (COF), wear volume loss, and duration of the running-in period were quantified to assess the wear performance. And the values were analyzed with one-way ANOVA (α = 0.05). Regression analysis was applied to examine the influence of Ra values and mediums on the wear data. The wear morphology was analyzed by scanning electron microscopy and a 3D profilometer. RESULTS: The average COF was higher in distilled water than in citric acid but was independent of the surface roughness. For the composite, the volume loss of worn area and running-in period increased with surface roughness when tested under distilled water. However, these increasing trends were not found in citric acid. All specimens exhibited mild wear behavior with low COF and less superficial abrasion in acidic medium. CONCLUSIONS: The effect of initial roughness on wear behavior depends on the medium. In distilled water, resin composites with high initial roughness exhibit a longer running-in time, which eventually leads to a significant increase in material loss. The adverse effects of high roughness can be alleviated by the lubrication of citric acid, which can maintain a mild wear behavior regardless of initial surface roughness.

Landscape of immune cell infiltration in clear cell renal cell carcinoma to aid immunotherapy.

The tumor microenvironment, comprised of tumor cells and tumor-infiltrating immune cells, is closely associated with the clinical outcome of clear cell renal cell carcinoma (ccRCC) patients. However, the landscape of immune infiltration in ccRCC has not been fully elucidated. Herein, we applied multiple computational methods and various datasets to reveal the immune infiltrative landscape of ccRCC patients. The tumor immune infiltration (TII) levels of 525 ccRCC patients using a single-sample gene were examined and further categorized into immune infiltration subgroups. The TII score was characterized by distinct clinical traits and showed a significant divergence based on gender, grade, and stage. A high TII score was associated with the ERBB signaling pathway, the TGF-ß signaling pathway, and the MTOR signaling pathway, as well as a better prognosis. Furthermore, patients with high TII scores exhibited greater sensitivity to pazopanib. The low TII score was characterized by a high immune infiltration level of CD8+ T cells, T follicular helper cells, and regulatory T cells (Tregs). Moreover, the immune check point genes, including CTLA-4, LAG3, PD-1, and IDO1, presented a high expression level in the low TII score group. Patients in the high TII score group demonstrated significant therapeutic advantages and clinical benefits. The findings in this study have the potential to assist in the strategic design of immunotherapeutic treatments for ccRCC.

Role of sialylated glycans on bovine lactoferrin against influenza virus.

Influenza is a worldwide plague caused by the influenza virus (IAV) infection, which is initiated by specific recognition with sialic acids on host cell surface. Bovine lactoferrin (bLf) is a sialoglycoprotein belonging to the transferrin family, and it plays an important role in immune regulation. It also shows toxicity against cancer cells and pathogenic microorganisms including bacteria, fungi, and virus. The purpose of this study is to assess the roles of the sialylated glycans on bLf against IAV. To this end, bLf were first treated with sodium periodate to destroy its sialylated glycans. Then, the binding activity of native or desialylated bLf with various IAV was assessed by blotting assay. Finally, their ability to inhibit IAV attachment to host cells was analyzed in vitro. Our result showed that the sialylated glycans on bLf were almost completely destroyed by sodium periodate treatment. Furthermore, the binding activity of desialylated bLf to IAV and the ability to inhibit IAV mimics binding to MDCK cells were significantly reduced compared to that of native bLf. These results demonstrated that the sialylated glycans on bLf could serve as competitive substrates to block IAV attachment to host cells during the early stages of viral infection. Our findings make an important contribute for the fully understanding of the mechanism of bLf in the prevention of IAV infections and their possible applications in antiviral infection.