Utilizing systems genetics to enhance understanding into molecular targets of skin cancer.

Despite progress made with immune checkpoint inhibitors and targeted therapies, skin cancer remains a significant public health concern in the United States. The intricacies of the disease, encompassing genetics, immune responses, and external factors, call for a comprehensive approach. Techniques in systems genetics, including transcriptional correlation analysis, functional pathway enrichment analysis, and protein-protein interaction network analysis, prove valuable in deciphering intricate molecular mechanisms and identifying potential diagnostic and therapeutic targets for skin cancer. Recent studies demonstrate the efficacy of these techniques in uncovering molecular processes and pinpointing diagnostic markers for various skin cancer types, highlighting the potential of systems genetics in advancing innovative therapies. While certain limitations exist, such as generalizability and contextualization of external factors, the ongoing progress in AI technologies provides hope in overcoming these challenges. By providing protocols and a practical example involving Braf, we aim to inspire early-career experimental dermatologists to adopt these tools and seamlessly integrate these techniques into their skin cancer research, positioning them at the forefront of innovative approaches in combating this devastating disease.

In situ restoration of soil ecological function in a coal gangue reclamation area after 10 years of elm/poplar phytoremediation.

The soil ecological health risks and toxic effects of coal gangue accumulation were examined after 10 years of elm/poplar phytoremediation. The changes in soil enzyme activities, ionome metabolism, and microbial community structure were analyzed at shallow (5-15 cm), intermediate (25-35 cm), and deep (45-55 cm) soil depths. Soil acid phosphatase activity in the restoration area increased significantly by 4.36-7.18 fold (p < 0.05). Soil concentrations of the metal ions Cu, Pb, Ni, Co, Bi, U, and Th were significantly reduced, as were concentrations of the non-metallic element S. The repair effect was shallow > middle > deep. The soil community structure, determined by 16S diversity results, was changed significantly in the restoration area, and the abundance of microorganisms increased at shallow soil depths. Altererythrobacter and Sphingomonas species were at the center of the microbial weight network in the restoration area. Redundancy analysis (RDA) showed that S and Na are important driving forces for the microbial community distributions at shallow soil depths. The KEGG function prediction indicated enhancement of the microbial function of the middle depth soil layers in the restoration area. Overall, phytoremediation enhanced the biotransformation of soil phosphorus in the coal gangue restoration area, reduced the soil content of several harmful metal elements, significantly changed the structure and function of the microbial community, and improved the overall soil ecological environment.

Gut microbial characteristics of adult patients with allergy rhinitis.

BACKGROUND: Although recent studies have indicated that intestinal microbiota dweller are involved in the pathogenesis of allergy rhinitis (AR), the influence of gut microbiota on AR adult has not been fully elucidated yet. Hence, we carried out this study to uncover the distinctive bacterial taxa that differentiate allergy rhinitis patients from healthy individuals. Feces samples from thirty three AR patients and thirty one healthy individuals were analyzed by 16S rRNA gene sequencing. RESULTS: Results showed that the bacterial diversity in AR group was significantly higher than that of the non-AR group. Bacterial communities between AR and non-AR group were significantly differentiated as revealed by Principal coordinates analysis (PCoA) and the variation within non-AR were higher than that of the counterpart. Firmicutes, Fusobacteria, Actinobacteria, Cyanobacteria and Chloroflexi were the significantly differed phyla taxa and the top significantly distinguished bacterial genus included Prevotella_9, Phascolarctobacterium, Roseburia, Megamonas, Alistipes, Lachnoclostridium and Fusobacterium. The higher network complexity in AR group were dominated by taxa belonging to Firmicutes. The predicted function, alpha linolenic acid metabolism and bacterial invasion of epithelial cells pathway were higher in non-AR group while gonadotropin-releasing hormone (GnRH) signaling pathway, Fc γ-R mediated phagocytosis and endocytosis were higher in AR patients. Although the bacterial diversity between moderate and severe AR patients showed no significant difference, the significant correlation between featured genus and total nasal symptom score or rhinoconjunctivitis quality of life questionnaire, such as Butyricicoccus and Eisenbergiella, revealed the potential to intervene the AR status by means of gut microbiota. CONCLUSIONS: In conclusion, patients with allergy rhinitis had distinguished gut microbiota characteritics in comparison with healthy controls. The results suggest that gut microbiota might play crucial roles in influencing the course and different symptoms of AR. Trial registration ChiCTR, ChiCTR1900028613. Registered 29 December 2019, https://www.chictr.org.cn/showproj.aspx?proj=47650 .

Heat stress mediates changes in fecal microbiome and functional pathways of laying hens.

Chicken gastrointestinal microbiota plays important roles in health, productivity, and disease. However, knowledge of the relationship between heat stress and the gut microbial ecosystem of poultry, especially laying hens, is still limited. Here, we aimed to provide important knowledge for heat stress intervention in the egg industry. We performed high-throughput sequencing metagenomics on fecal contents to unravel the microbial taxa and functional capacity of the gut microbiome of caged laying hens under heat stress. Results showed that the fecal microbial communities of laying hens were dominated by Firmicutes, Bacteroidetes, and Proteobacteria phyla. The Firmicutes were significantly decreased, and Bacteroidetes were increased in the fecal microbiota under heat stress. Functional prediction of these changes in microbiota revealed that metabolism-related pathways, including cysteine and methionine metabolism and benzoate degradation, were more abundant. Conversely, retinol metabolism and phenylpropanoid biosynthesis were decreased by heat stress, suggesting differences in metabolism between layers in different temperature environments. Clear contributions were identified between active taxa (genus level) and metabolic pathways, which were associated with the liver and intestinal dysfunction in layers. These data revealed that heat stress induced a significant taxonomic perturbation in the gut microbiome of caged laying hens. This was related to the negative effects of heat stress in poultry and provided important basic knowledge for heat stress intervention.

Probabilistic maps of the white matter tracts with known associated functions on the neonatal brain atlas: Application to evaluate longitudinal developmental trajectories in term-born and preterm-born infants.

Diffusion tensor imaging (DTI) has been widely used to investigate the development of the neonatal and infant brain, and deviations related to various diseases or medical conditions like preterm birth. In this study, we created a probabilistic map of fiber pathways with known associated functions, on a published neonatal multimodal atlas. The pathways-of-interest include the superficial white matter (SWM) fibers just beneath the specific cytoarchitectonically defined cortical areas, which were difficult to evaluate with existing DTI analysis methods. The Jülich cytoarchitectonic atlas was applied to define cortical areas related to specific brain functions, and the Dynamic Programming (DP) method was applied to delineate the white matter pathways traversing through the SWM. Probabilistic maps were created for pathways related to motor, somatosensory, auditory, visual, and limbic functions, as well as major white matter tracts, such as the corpus callosum, the inferior fronto-occipital fasciculus, and the middle cerebellar peduncle, by delineating these structures in eleven healthy term-born neonates. In order to characterize maturation-related changes in diffusivity measures of these pathways, the probabilistic maps were then applied to DTIs of 49 healthy infants who were longitudinally scanned at three time-points, approximately five weeks apart. First, we investigated the normal developmental pattern based on 19 term-born infants. Next, we analyzed 30 preterm-born infants to identify developmental patterns related to preterm birth. Last, we investigated the difference in diffusion measures between these groups to evaluate the effects of preterm birth on the development of these functional pathways. Term-born and preterm-born infants both demonstrated a time-dependent decrease in diffusivity, indicating postnatal maturation in these pathways, with laterality seen in the corticospinal tract and the optic radiation. The comparison between term- and preterm-born infants indicated higher diffusivity in the preterm-born infants than in the term-born infants in three of these pathways: the body of the corpus callosum; the left inferior longitudinal fasciculus; and the pathway connecting the left primary/secondary visual cortices and the motion-sensitive area in the occipitotemporal visual cortex (V5/MT+). Probabilistic maps provided an opportunity to investigate developmental changes of each white matter pathway. Whether alterations in white matter pathways can predict functional outcomes will be further investigated in a follow-up study.

Predicted functional analysis of rumen microbiota suggested the underlying mechanisms of the postpartum subacute ruminal acidosis in Holstein cows.

BACKGROUND: The relationships between the postpartum subacute ruminal acidosis (SARA) occurrence and predicted bacterial functions during the periparturient period are still not clear in Holstein cows. OBJECTIVES: The present study was performed to investigate the alterations of rumen fermentation, bacterial community structure, and predicted bacterial functional pathways in Holstein cows. METHODS: Holstein cows were divided into the SARA (n = 6) or non-SARA (n = 4) groups, depending on whether they developed SARA during the first 2 weeks after parturition. Reticulo-ruminal pH was measured continuously during the study period. Reticulo-ruminal fluid samples were collected 3 weeks prepartum, and 2 and 6 weeks postpartum, and blood samples were collected 3 weeks before, 0, 2, 4 and 6 weeks postpartum. RESULTS: The postpartum decline in 7-day mean reticulo-ruminal pH was more severe and longer-lasting in the SARA group compared with the non-SARA group. Changes in predicted functional pathways were identified in the SARA group. A significant upregulation of pathway "PWY-6383" associated with Mycobacteriaceae species was identified at 3 weeks after parturition in the SARA group. Significantly identified pathways involved in denitrification (DENITRIFICATION-PWY and PWY-7084), detoxification of reactive oxygen and nitrogen species (PWY1G-0), and starch degradation (PWY-622) in the SARA group were downregulated. CONCLUSIONS: The postpartum SARA occurrence is likely related to the predicted functions of rumen bacterial community rather than the alterations of rumen fermentation or fluid bacterial community structure. Therefore, our result suggests the underlying mechanisms, namely functional adaptation of bacterial community, causing postpartum SARA in Holstein cows during the periparturient period.

The effect of graphene photocatalysis on microbial communities in Lake Xingyun, southwestern China.

Graphene photocatalysis is a new method for harmful algae and water pollution control. However, microbial communities undergoing graphene photocatalysis treatment in freshwater lakes have been poorly studied. Here, using 16S rRNA and 18S rRNA gene high-throughput sequencing, the responses of microbial communities to graphene photocatalysis were analyzed in the eutrophic lake, Lake Xinyun, southwestern China. For microeukaryotes, we found that Arthropoda was dominant in summer, while its abundant level declined in spring under natural conditions. The evident reduction of Arthropods was observed after graphene photocatalysis treatment in summer and then reached a relatively stable level. For bacteria, Cyanobacteria decreased in summer due to the graphene photocatalysis-mediated inactivation. However, Cyanobacteria was higher in the treated group in spring with a genera group-shift. Functional analysis revealed that microeukaryotes showed higher potential for fatty acid oxidation and TCA cycle in the treated group in summer, but they were more abundant in control in spring. Pathways of starch and sucrose metabolism and galactose metabolism were more abundant in control in summer, while they were enriched in the treated group in spring for bacteria. This study offers insights into the effects of graphene photocatalysis on microbial communities and their functional potential in eutrophic lake.

Diurnal changes of the oral microbiome in patients with alcohol dependence.

Background: Saliva secretion and oral microbiota change in rhythm with our biological clock. Dysbiosis of the oral microbiome and alcohol consumption have a two-way interactive impact, but little is known about whether the oral microbiome undergoes diurnal changes in composition and function during the daytime in patients with alcohol dependence (AD). Methods: The impact of alcohol consumption on the diurnal salivary microbiome was examined in a case-control study of 32 AD patients and 21 healthy control (HC) subjects. We tested the changes in microbial composition and individual taxon abundance by 16S rRNA gene sequencing. Results: The present study is the first report showing that alcohol consumption enhanced the richness of the salivary microbiome and lowered the evenness. The composition of the oral microbiota changed significantly in alcohol-dependent patients. Additionally, certain genera were enriched in the AD group, including Actinomyces, Leptotrichia, Sphaerochaeta and Cyanobacteria, all of which have pathogenic effects on the host. There is a correlation between liver enzymes and oral microbiota. KEGG function analysis also showed obvious alterations during the daytime. Conclusion: Alcohol drinking influences diurnal changes in the oral microbiota, leading to flora disturbance and related functional impairment. In particular, the diurnal changes of the oral microbiota may open avenues for potential interventions that can relieve the detrimental consequences of AD.

Characterizing the supragingival microbiome of healthy pregnant women.

The ecological characteristics and changes of the supragingival plaque microbial community during pregnancy are poorly understood. This study compared the microbial community characteristics of supragingival plaque in pregnant and non-pregnant women, with the aim of identifying specific microbial lineages and genera that may be associated with pregnancy. Thirty pregnant women were randomly selected from the First Affiliated Hospital of Xinjiang Medical University and divided into groups based on pregnancy trimester: first trimester (group P1, n=10, ≤12 weeks), second trimester (group P2, n=10, 13-27 weeks), and third trimester (group P3, n=10, 28-40 weeks). Ten healthy non-pregnant women (group N) were enrolled as the control group. Supragingival plaque samples of all subjects were collected and oral microbial composition was surveyed using a 16S rRNA gene sequencing approach. Statistical analysis was performed using a nonparametric test. The Chao 1 index of P3 was significantly lower compared with that of N, P1, and P2 (P<0.05). The Simpson indices of P2 and P3 were significantly higher than that of N (P<0.05). The Shannon index of P2 was significantly higher compared with that of N (P<0.05). Principal coordinate analysis (PCoA) showed different clustering according to the pregnancy status. Linear discriminant analysis effect size (LEfSe) revealed that the microbial species in group N that were significantly different from those of other groups were concentrated in the genus Neisseria. Species in P1 that were significantly different from those of other groups were concentrated in the genus Tannerella, while those in P2 and P3 were concentrated in the genus Leptotrichia. A total of 172 functional pathways were predicted for the bacterial communities in this study using PICRUSt2. Principal Component Analysis (PCA) showed that most predicted functional pathways clustered together in N and P1 and in P2 and P3. LEfSe analysis revealed that 11 pathways played a discriminatory role in the four groups. This work suggests a potential role of pregnancy in the formation of supragingival plaque microbiota and indicates that physiological changes during pregnancy may convert supragingival plaque into entities that could cause harm, which may be a risk factor for maternal health. Furthermore, findings from the study provide a basis for etiological studies of pregnancy-associated oral ecological disorders.

Bacterial Community Dynamics in Kumamoto Oyster Crassostrea sikamea Hatchery During Larval Development.

Increasing evidence indicates that microbes colonized in early life stages have a long-term effect on animal wellbeing in later life stages. Related research is still limited in aquatic animals, particularly in bivalve mollusks. In this study, we analyzed the dynamics of the bacterial composition of the pelagic larval stages (fertilized egg, trochophore, D-stage, veliger, and pediveliger) and the sessile postlarval stage (spat) of Kumamoto oyster (Crassostrea sikamea) and their relationships with the rearing water bacterioplankton in a hatchery by using Illumina sequencing of bacterial 16S rRNA gene. Both bacterioplankton and larval bacterial communities changed greatly over larval development, and the two communities remarkably differed (r = 0.956, P < 0.001), as highlighted by the differences in the dominant taxa and bacterial diversity. Ecological processes of larval bacterial communities were measured by abundance-unweighted and abundance-weighted standardized effect sizes of the mean nearest taxon distance (ses.MNTD). The unweighted ses.MNTD analysis revealed that the deterministic process constrained the larval bacterial assembly, whereas the weighted ses.MNTD analysis showed that larval bacterial composition was initially governed by stochasticity and then gradually by determinism in the later stages. SourceTracker analysis revealed that the larval bacteria were primarily derived from an internal source, mainly from larvae at the present stage. Additionally, the abundances of larval bacterial-mediated functional pathways that were involved in the amino acid, energy, lipid and carbohydrate metabolisms significantly altered with the larval development. These findings suggest that bacteria assemble into distinct communities in larvae and rearing water in the hatchery system, and the dynamics of bacterial community composition in larvae is likely associated with larval developmental stages.

Alterations and Correlations of Gut Microbiota and Fecal Metabolome Characteristics in Experimental Periodontitis Rats.

Objectives: Periodontitis affects the progression of many diseases, while its detailed mechanism remains unclear. This study hopes to provide new ideas for exploring its mechanism by analyzing the gut microbiota and fecal metabolic characteristics of experimental periodontitis rats. Methods: A total of 10 rats were randomly divided into ligature-induced experimental periodontitis (EP) group and healthy control group. After 4 weeks of the experiment, the feces of all rats were collected for sequencing through 16S ribosomal DNA (rDNA) sequencing technology and liquid chromatography-mass spectrometry (LC-MS). Results: 16S rDNA sequencing results showed that the ß-diversity of gut microbiota was significantly different between the EP and control group, and the levels of dominant genera were different. Compared with the control group, Ruminococcus, Escherichia, and Roseburia were significantly enriched in EP, and Coprococcus, Turicibacter, Lachnospira were significantly decreased. Correlation analysis showed that Roseburia exhibited the highest correlation within the genus. Of 3,488 qualitative metabolites, 164 metabolites were upregulated and 362 metabolites were downregulated in EP. Enrichment analysis showed that periodontitis significantly changed 45 positive/negative ion metabolic pathways. Five KEGG pathways, protein digestion and absorption, tyrosine metabolism, glycolysis/gluconeogenesis, niacin and nicotinamide metabolism, and oxidative phosphorylation, are enriched in both the microbiome and metabolome. Correlation analysis showed that the genera with significant differences in periodontitis were usually significantly correlated with more metabolites, such as Roseburia, Lachnospira, Escherichia, Turicibacter, and Ruminococcus. The genera with the same changing trend tended to have a similar correlation with some certain metabolites. In addition, vitamin D2 and protoporphyrin IX have the most significant correlations with microorganisms. Conclusion: Our study reveals that periodontitis alters gut microbiota and fecal metabolites. The correlation analysis of microbiota and metabolome provides a deeper understanding of periodontitis, and also provides a direction for the study of periodontitis affecting other diseases.

Global Transcriptional Profiling of Granulosa Cells from Polycystic Ovary Syndrome Patients: Comparative Analyses of Patients with or without History of Ovarian Hyperstimulation Syndrome Reveals Distinct Biomarkers and Pathways.

Ovarian hyperstimulation syndrome (OHSS) is often a complication of polycystic ovarian syndrome (PCOS), the most frequent disorder of the endocrine system, which affects women in their reproductive years. The etiology of OHSS is multifactorial, though the factors involved are not apparent. In an attempt to unveil the molecular basis of OHSS, we conducted transcriptome analysis of total RNA extracted from granulosa cells from PCOS patients with a history of OHSS (n = 6) and compared them to those with no history of OHSS (n = 18). We identified 59 significantly dysregulated genes (48 down-regulated, 11 up-regulated) in the PCOS with OHSS group compared to the PCOS without OHSS group (p-value < 0.01, fold change >1.5). Functional, pathway and network analyses revealed genes involved in cellular development, inflammatory and immune response, cellular growth and proliferation (including DCN, VIM, LIFR, GRN, IL33, INSR, KLF2, FOXO1, VEGF, RDX, PLCL1, PAPPA, and ZFP36), and significant alterations in the PPAR, IL6, IL10, JAK/STAT and NF-κB signaling pathways. Array findings were validated using quantitative RT-PCR. To the best of our knowledge, this is the largest cohort of Saudi PCOS cases (with or without OHSS) to date that was analyzed using a transcriptomic approach. Our data demonstrate alterations in various gene networks and pathways that may be involved in the pathophysiology of OHSS. Further studies are warranted to confirm the findings.

Comparison of the effects of acetic acid bacteria and lactic acid bacteria on the microbial diversity of and the functional pathways in dough as revealed by high-throughput metagenomics sequencing.

Knowledge of the effects of various strains of acetic acid bacteria (AAB) on sourdough remains limited. In this study, the diversity of microbial taxa in sourdoughs fermented by different starters was assessed and their functional capacity was evaluated via high-throughput metagenomics sequencing. Results showed that Erwinia (29.43%), Pantoea (45.89%), and Enterobacter (9.16%) were predominant in the blank CK treatment. Lactobacillus (91.40%), Saccharomyces (6.13%), as well as the AAB genus Acetobacter (0.61%) were the dominant microbial genera in the sourdoughs started by yeast and a strain of lactic acid bacteria (YL treatment). By contrast, the dominant genera in the sourdoughs started by yeasts and various LAB and AAB strains (YLA treatment) were Komagataeibacter (0.39%) except for the inoculated Lactobacillus (68.37%), Acetobacter (20.17%), and Saccharomyces (8.31%) species. Functional prediction of these changes in microbial community and diversity revealed that various metabolism-related pathways, including alanine, aspartate, and glutamate metabolism (21.95%), as well as amino acid biosynthesis (19.14%), were predominant in the sourdoughs started by yeast and an AAB strain (YA treatment). Moreover, arginine biosynthesis (11.65%) were the dominant pathways in the YL treatment. The fermented dough added with sourdoughs started with yeast + AAB and yeast + AAB + LAB strains had substantially higher contents (more than 48.58% in total) of essential amino acids than the dough added with sourdoughs started with yeast + LAB strain. These results demonstrated that amino acid biosynthesis has a beneficial effect on sourdoughs inoculated with an AAB strain.

Associations Between Gut Microbiota and Asthma Endotypes: A Cross-Sectional Study in South China Based on Patients with Newly Diagnosed Asthma.

OBJECTIVE: This study aimed to investigate the gut microbiome profile in different inflammatory phenotypes of treatment-naive newly diagnosed asthmatic adults, to gain insight on the associations between intestinal microbiota and phenotypic features that characterize asthma heterogeneity to develop new treatments for asthma. METHODS: Fresh stool samples were obtained from 20 healthy subjects and 47 newly diagnosed asthmatic patients prior to any interventions. The asthmatics were divided into allergic and non-allergic cohorts. Intestinal microbiota was analyzed by 16S rRNA next-generation sequencing. Demographic and clinical parameters were collected. Alpha and beta diversity analysis were calculated to detect differences within sample phylotype richness and evenness between controls and asthmatic patients. Statistically significant differences between samples were analyzed for all used metrics, and features of gut bacterial community structure were evaluated in relation to extensive clinical characteristics of asthmatic patients. RESULTS: Gut microbial compositions were significantly different between asthmatic and healthy groups. Alpha-diversity of the gut microbiome was significantly lower in asthmatics than in controls. The microbiome between allergic and non-allergic asthmatic patients were also different, and 28 differential species were identified. PPAR signaling pathway, carotenoid biosynthesis, and flavonoid biosynthesis were significantly positively correlated with allergy-associated clinical index, including FENO value, blood eosinophil counts, and serum IgE and IL-4 levels. A combination of Ruminococcus bromii, Brevundimonas vesicularis, and Clostridium disporicum showed an AUC of 0.743 in the specific allergic/non-allergic cohort. When integrating C. disporicum, flavone, flavonol biosynthesis, and serum IL-4 values, the AUC achieved 0.929 to classify asthmatics. At the same time, C. colinum and its associated functional pathway exhibited an AUC of 0.78 to distinguish allergic asthmatics from those without allergies. CONCLUSION: We demonstrated a distinct taxonomic composition of gut microbiota in different asthmatic phenotypes, highlighting their significant relationships. Our study may support considerations of intestinal microbial signatures in delineating asthma phenotypes.

Early social contact alters the community structure and functions of the faecal microbiome in suckling-growing piglets.

Social contact during suckling, in an enriched social environment, can reduce the aggressive behaviours of piglets during regrouping at weaning, and improve their production performance and welfare. The aim of this study was to determine the possible impact of suckling social contact on gut microbes. We performed 16S rRNA sequencing to measure the faecal microbial structure and function in piglets experiencing social contact. Eighteen-litter piglets were allocated to two treatments: an early continuous social contact (CSC) group where piglets from adjacent pens shared a mutual pen starting at 14 days postpartum and a control (CON) group where piglets had no contact with individuals from adjacent pens during the suckling period. The piglets were regrouped at 36 days of age. The litter weights at 35 and 63 days of age were measured. Faecal samples were randomly collected at 16, 35, 42, and 63 days of age and faecal DNA was determined. The results showed that the litter weight of piglets in the CSC group was significantly decreased at 63 days compared with the CON group. Continuous social contact also significantly decreased the microbial richness at 16 and 35 days of age (P < 0.05). Firmicutes was the most abundant bacterial phylum in both groups at all detected time-points and the abundance increased with social contact. At the genus level, Lactobacillus was the most abundant bacterium after weaning and the abundance increased in the piglets with social contact. Compared with the faecal microbiota of control piglets, a total of 22 genera at 16 days, 20 genera at 35 days, 12 genera at 42 days, and 27 genera at 63 days in the faeces of CSC piglets were observed to be significantly different in abundance (linear discriminant analysis score > 3, P < 0.05). Furthermore, functional analysis of the microbial composition showed that the changes induced by early CSC mainly altered the relative abundance of metabolic and related pathways. The social contact notably had an effect on the abundance of microbial pathways for amino acid and carbohydrate metabolism. In conclusion, CSC changed the microbial composition in the faeces of piglets, which might have a negative effect on nutrient metabolism for the suckling-growing piglets. Our study provided new insight into the influence of social contact on the suckling-growing piglets.

Support Vector Machine for Lung Adenocarcinoma Staging Through Variant Pathways.

Lung adenocarcinoma (LUAD) is one of the most common malignant tumors. How to effectively diagnose LUAD at an early stage and make an accurate judgement of the occurrence and progression of LUAD are still the focus of current research. Support vector machine (SVM) is one of the most effective methods for diagnosing LUAD of different stages. The study aimed to explore the dynamic change of differentially expressed genes (DEGs) in different stages of LUAD, and to assess the risk of LUAD through DEGs enriched pathways and establish a diagnostic model based on SVM method. Based on TMN stages and gene expression profiles of 517 samples in TCGA-LUAD database, coefficient of variation (CV) combined with one-way analysis of variance (ANOVA) were used to screen out feature genes in different TMN stages after data standardization. Unsupervised clustering analysis was conducted on samples and feature genes. The feature genes were analyzed by Pearson correlation coefficient to construct a co-expression network. Fisher exact test was conducted to verify the most enriched pathways, and the variation of each pathway in different stages was analyzed. SVM networks were trained and ROC curves were drawn based on the predicted results so as to evaluate the predictive effectiveness of the SVM model. Unsupervised hierarchical clustering analysis results showed that almost all the samples in stage III/IV were clustered together, while samples in stage I/II were clustered together. The correlation of feature genes in different stages was different. In addition, with the increase of malignant degree of lung cancer, the average shortest path of the network gradually increased, while the closeness centrality gradually decreased. Finally, four feature pathways that could distinguish different stages of LUAD were obtained and the ability was tested by the SVM model with an accuracy of 91%. Functional level differences were quantified based on the expression of feature genes in lung cancer patients of different stages, so as to help the diagnosis and prediction of lung cancer. The accuracy of our model in differentiating between stage I/II and stage III/IV could reach 91%.

High-temperature exposure alters the community structure and functional features of the intestinal microbiota in Shaoxing ducks (Anas platyrhynchos).

The gut microbiome is a complex ecosystem that contributes to host nutrition and health. However, our current knowledge of the relationship between ambient temperature and gut microbiota of poultry is still limited. The objective of the present study was to characterize the intestinal microbiota of ducks exposed to high ambient temperature. Sixty 60-day-old Shaoxing ducks were allocated to control and heat-treated groups. The ducks in the control group were kept at 25°C, and the ducks in the heat treatment group were raised at 30-40°C, which simulated the temperature change of day and night in summer. After 15 D, the intestinal contents of the duodenum, jejunum, and ileum were obtained from 6 ducks of each group. Genomic DNA was extracted and amplified based on the V4-V5 hypervariable region of 16S rRNA. The results showed that Firmicutes was the dominant bacterial phylum with the highest abundance in the contents of the small intestine of ducks, and the relative abundance of the phylum Firmicutes in all 3 intestinal segments was increased by high temperature. At the genus level, Lactobacillus was found to be the most dominant bacterial genus across 3 gut segments, and its abundance was increased in ducks under heat treatment. Compared with the corresponding intestine segment of control ducks, a total of 36 genera in the duodenum, 19 genera in the jejunum, and 6 genera in the ileum of heat-treated ducks were found to be significantly different in the abundance (linear discriminant analysis score >3.0, P < 0.05). Functional prediction of gut microbiota revealed that high temperature caused changes in the abundance of metabolism and transcription-related pathways. It is noteworthy that most of the altered pathways are related to metabolism. In conclusion, high temperature induced remarkable taxonomic changes in the gut microbiome of ducks, which might be related to the negative effects of high temperature in ducks. Our present study provided an important theoretical ground for high-temperature intervention.

Transcriptomic and functional pathway features were associated with survival after pathological complete response to neoadjuvant chemotherapy in breast cancer.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) has been proposed as a surrogate endpoint for the prediction of long-term survival in breast cancer (BC); however, an increased pCR rate has not clearly correlated with improved survival. We hypothesized that some transcriptomic and functional pathway features correlate with survival after pCR in BC. We utilized 2 published NAC cohorts, 105 women with gene expression data before, "Baseline", and that changed during NAC, "Delta", and TCGA database with 1068 BC patients to investigate the relationship between the efficacy of NAC and survival utilizing differentially expressed-mRNAs, construction and analysis of the mRNA-hub gene network, and functional pathway analysis. In mRNA expression profiling, S100A8 was a gene involved in survival after pCR in Baseline and NDP was a gene involved in recurrence after pCR in Delta. In functional pathway analysis, we found multiple pathways involved in survival after pCR. In mRNA-hub gene analysis, HSP90AA1, EEF1A1, APP, and HSPA4 were related to recurrence in BC patients with pCR due to NAC. TP53, EGFR, CTNNB1, ERBB2, and HSPB1 may play a significant role in survival for patients with pCR. Interestingly, high HSP90AA1, HSPA4, S100A8, and TP53, and low EEF1A1, EGFR, and CTNNB1 expressing tumors have significantly worse overall survival in TCGA BC cohort. We demonstrated the genes and functional pathway features associated with pCR and survival utilizing the bioinformatics approach to public BC cohorts. Some genes involved in recurrence after pCR due to NAC also served as prognostic factors in primary BC.

In Vitro Evaluation of the Effects of Commercial Prebiotic GOS and FOS Products on Human Colonic Caco-2 Cells.

Prebiotic oligosaccharides are widely used as human and animal feed additives for their beneficial effects on the gut microbiota. However, there are limited data to assess the direct effect of such functional foods on the transcriptome of intestinal epithelial cells. The purpose of this study is to describe the differential transcriptomes and cellular pathways of colonic cells directly exposed to galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS). We have examined the differential gene expression of polarized Caco-2 cells treated with GOS or FOS products and their respective mock-treated cells using mRNA sequencing (RNA-seq). A total of 89 significant differentially expressed genes were identified between GOS and mock-treated groups. For FOS treatment, a reduced number of 12 significant genes were observed to be differentially expressed relative to the control group. KEGG and gene ontology functional analysis revealed that genes up-regulated in the presence of GOS were involved in digestion and absorption processes, fatty acids and steroids metabolism, potential antimicrobial proteins, energy-dependent and -independent transmembrane trafficking of solutes and amino acids. Using our data, we have established complementary non-prebiotic modes of action for these frequently used dietary fibers.

Differential dynamics of hepatic protein expressions with long-term cultivated hepatitis C virus infection.

BACKGROUND: The liver maintains blood chemical homeostasis by active uptake and secretion through endocytosis, exocytosis, and intracellular trafficking between the plasma and intracellular membranes. Hepatitis C virus (HCV) infection affects the host membrane architecture and might thus impair the regulation of the cellular transportation machinery. Additionally, the hepatic expressions of differential protein dynamics with long-term HCV infection remain fully recover. METHODS: In this study, comparative proteomic analysis was performed in HCV-infected and mock-control Huh7 cells according to the viral dynamics of exponential, plateau, declined, and silencing phases at the acute stage, and the chronic stage. The proteins with <0.8-fold and ≥1.25-fold changes in expression were analyzed using functional pathway clustering prediction. RESULTS: The combined experimental repetitions identified full-spectrum cellular proteins in each of 5 sample sets from acute exponential, plateau, declined, and silencing phases, and the chronic stage. The clustering results revealed that HCV infection might differentiate regulatory pathways involving extracellular exosome, cadherin, melanosome, and RNA binding. Overall host proteins in HCV-infected cells exhibited kinetic pattern 1, in which cellular expression was downregulated from the acute exponential to plateau phases, reached a nadir, and was then elevated at the chronic stage. The proteins involved in the membrane-budding pathway exhibited kinetic pattern 2, in which their expressions were distinctly downregulated at the chronic stage. CONCLUSION: The current comparative proteomics revealed the differential regulatory effects of HCV infection on host intracellular transport functional pathways, which might contribute to the pathogenic mechanisms of HCV in hepatocytes that sustain long-term infection.