Systematic review on marine carbon source-mannitol: Applications in synthetic biology.

Mannitol, one of the most widespread sugar alcohols, has been integral to daily human life for two centuries. Global population growth and competition for freshwater, food, and land have prompted a shift in the fermentation industry from terrestrial to marine raw materials. Mannitol is a readily available carbohydrate in brown seaweed from the ocean and possess a higher reducing power than glucose, making it a promising substrate for biological manufacturing. This has spurred numerous explorations into converting mannitol into high-value chemicals. Researchers have engineered microorganisms to utilize mannitol in various synthetic biological applications, including: (1) employing mannitol as an inducer to control the activation and deactivation of genetic circuits; (2) using mannitol as a carbon source for synthesizing high-value chemicals through biomanufacturing. This review summarizes the latest advances in the application of mannitol in synthetic biology. AIM OF REVIEW: The aim is to present a thorough and in-depth knowledge of mannitol, a marine carbon source, and then use this carbon source in synthetic biology to improve the competitiveness of biosynthetic processes. We outlined the methods and difficulties of utilizing mannitol in synthetic biology with a variety of microbes serving as hosts. Furthermore, future research directions that could alleviate the carbon catabolite repression (CCR) relationship between glucose and mannitol are also covered. EXPECTED CONTRIBUTIONS OF REVIEW: Provide an overview of the current state, drawbacks, and directions for future study on mannitol as a carbon source or genetic circuit inducer in synthetic biology.

Advancing Bacillus licheniformis as a Superior Expression Platform through Promoter Engineering.

Bacillus licheniformis is recognised as an exceptional expression platform in biomanufacturing due to its ability to produce high-value products. Consequently, metabolic engineering of B. licheniformis is increasingly pursued to enhance its utility as a biomanufacturing vehicle. Effective B. licheniformis cell factories require promoters that enable regulated expression of target genes. This review discusses recent advancements in the characterisation, synthesis, and engineering of B. licheniformis promoters. We highlight the application of constitutive promoters, quorum sensing promoters, and inducible promoters in protein and chemical synthesis. Additionally, we summarise efforts to expand the promoter toolbox through hybrid promoter engineering, transcription factor-based inducible promoter engineering, and ribosome binding site (RBS) engineering.

The impact of NUMB on chicken abdominal adipogenesis: A comprehensive analysis.

Excessive abdominal fat deposition negatively impacts poultry meat production and carcass yield. Identification of novel adipogenesis regulators may help improve production performance declines caused by excessive fat deposition. NUMB Endocytic Adaptor Protein (NUMB) typically functions as a cell fate determinant and plays a significant role in cell development and various diseases. Here, we found that NUMB is abundantly expressed in chicken abdominal fat depots and is induced in cultured adipocytes following adipogenic treatment. The gain- and loss-of-function experiments demonstrated that NUMB promotes the proliferation and G1/S transition of chicken adipocytes, enhances adipocyte differentiation, and increases the expression of PPARγ1 transcript. Through mRNA-seq analysis and molecular experiments, we further confirmed that NUMB inhibits the transcriptional activation of the NOTCH1 pathway and the expression of the downstream transcription factor HES1 by inducing NOTCH1 degradation. Nevertheless, the inhibition of the NOTCH1/HES1 axis alone cannot fully explain NUMB's role in adipogenesis, as NUMB also regulates the expression of multiple adipogenic transcription factors such as E2F1, EGR2, and NR4A3. Our data suggest that NUMB is a potent activator of adipogenesis and enhances our understanding of its regulatory mechanisms in chicken abdominal fat deposition.

Environmentally relevant concentration PFNA promotes degradation of SMAD7 to drive progression of ovarian cancer via TGF-ß/SMADs signaling pathway.

Perfluorononanoic acid (PFNA), an acknowledged environmental endocrine disruptor, is increasingly utilized as a substitute for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Despite its growing use, limited research has been conducted to investigate its potential impact on tumorigenesis and progression, and the potential molecular mechanisms. Earlier studies linked perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure to breast and gynecological cancer progression in humans, lacking a clear understanding of the underlying mechanisms, notably in ovarian cancer. Our investigation into PFNA's effects at environmental concentrations (0.25-2 mM) showed no significant impact on cell proliferation but a notable increase in invasion and migration of ovarian cancer cells. This led to alterations in epithelial-mesenchymal transition (EMT) markers, including Claudin1, Vimentin, and Snail. Notably, PFNA exposure activated the TGF-ß/SMADs signaling pathway. Crucially, SMAD7 degradation through the ubiquitin-proteasome system emerged as PFNA's pivotal molecular target for inducing EMT, corroborated in mouse models. In summary, this study presented evidence that environmentally relevant concentrations of PFNA could induce SMAD7 degradation via the proteasome pathway, subsequently activating the TGF-ß/SMADs signaling pathway, and promoting EMT in ovarian cancer. These results illuminated the association between PFNA exposure and metastasis of ovarian cancer.

The Effects of Age and Reading Experience on the Lifespan Neurodevelopment for Reading Comprehension.

Reading comprehension is a vital cognitive skill that individuals use throughout their lives. The neurodevelopment of reading comprehension across the lifespan, however, remains underresearched. Furthermore, factors such as maturation and experience significantly influence functional brain development. Given the complexity of reading comprehension, which incorporates lower-level word reading process and higher-level semantic integration process, our study aims to investigate how age and reading experience influence the neurobiology underpinning these two processes across the lifespan. fMRI data of 158 participants aged from 7 to 77 years were collected during a passive word viewing task and a sentence comprehension task to engage the lower- and higher-level processes, respectively. We found that the neurodevelopment of the lower-level process was primarily influenced by age, showing increased activation and connectivity with age in parieto-occipital and middle/inferior frontal lobes related to morphological-semantic mapping while decreased activation in the temporoparietal regions linked to phonological processing. However, the brain function of the higher-level process was primarily influenced by reading experience, exhibiting a greater reliance on the frontotemporal semantic network with enhanced sentence-level reading performance. Furthermore, reading experience did not significantly affect the brain function of children, but had a positive effect on young adults in the lower-level process and on middle-aged and older adults in the higher-level process. These findings indicate that the brain function for lower- and higher-level processes of reading comprehension is differently affected by maturation and reading experience, and the experience effect is contingent on age regarding the two processes.

Compound probiotics can improve intestinal health by affecting the gut microbiota of broilers.

Probiotics, as a widely used additive, have played a unique advantage in replacing antibiotic products. As a result, the probiotic effects on broiler development, intestinal flora, intestinal barrier, and immunity were assessed by this investigation. Four hundred and eighty 1-day-old Arbor Acres broilers were randomly allotted to 4 groups of 5 replicates with 24 broilers each. The control was fed only a basal corn-soybean meal diet. Probiotics I, probiotics II, and probiotics III were fed basal diet and 1, 5, and 10 g/kg compound probiotics (Lactobacillus casei: Lactobacillus acidophilus: Bifidobacterium = 1:1:2), respectively. We found that broilers in the compound probiotic group exhibited better growth performance and carcass characteristics compared with control, especially among probiotics III group. The intestinal barrier-related genes relative expression of Claudin, Occludin, MUC2, and ZO-1 mRNA in the probiotic group increased at 21 and 42 d compared with control, especially among probiotics III group (P < 0.05). The early gut immune-related genes (TLR2, TLR4, IL-1ß, and IL-2) mRNA increased compared with control, while the trend at 42 d was completely opposite to that in the earlier stage (P < 0.05). Among them, probiotics III group showed the most significant changes compared to probiotics II group and probiotics I group. Select probiotics III group and control group for 16S rDNA amplicon sequencing analysis. The 16S rDNA amplicon sequencing results demonstrated that probiotics increased the relative abundance of beneficial microbes such as o_Bacteroidales, f_Rikenellaceae, and g_Alistipes and improved the cecum's gut microbiota of 42-day-old broilers. Additionally, adding the probiotics decreased the relative abundance of harmful microbes such as Proteobacteria. PICRUSt2 functional analysis revealed that most proteins were enriched in DNA replication, transcription, and glycolysis processes. Therefore, this study can provide theoretical reference value for probiotics to improve production performance, improve intestinal barrier, immunity, intestinal flora of broilers, and the application of probiotics.

Probiotics, as a green and pollution-free feed additive, can improve the production performance and economic benefits of broilers. Previous studies have found that the effect of multi-strain assistance is superior to that of a single strain. Therefore, to conduct our research, we added 1, 5, and 10 g/kg compound probiotics (Lactobacillus casei:Lactobacillus acidophilus:Bifidobacterium = 1:1:2) to the diet. The density of viable probiotics was 1 × 1010 CFU/g. We have found that adding 10 g/kg compound probiotics has better effects on production performance, intestinal immunity, and intestinal barrier function compared with adding 1 and 5 g/kg compound probiotics. Further sequencing analysis of gut microbiota revealed that by influencing the community structure and function of the cecum's microbiota, compound probiotics can enhance the intestinal barrier and immune performance of broilers, which in turn improves their growth performance and carcass attributes.

The co-regulation of the gut microbiome and host genes might play essential roles in metformin gastrointestinal intolerance.

Metformin is commonly used, but approximately 20% of patients experience gastrointestinal intolerance, leading to medication discontinuation for unclear reasons and a lack of effective management strategies. In this study, the 18 fecal and blood samples were analyzed using 16S rRNA and mRNA transcriptome, respectively. These samples included 3 fecal and 4 blood from metformin-tolerant T2D patients before and after metformin treatment (T and Ta), 3 fecal and 5 blood from metformin-intolerant T2D patients before and after treatment (TS and TSa), and 6 fecal samples from healthy controls. The results showed that certain anti-inflammatory gut bacteria and gene, such as Barnesiella (p = 0.046), Parabacteroides goldsteinii (p = 0.016), and the gene JUND (p = 0.0002), exhibited higher levels in metformin-intolerant patients, and which decreased after metformin treatment (p < 0.05). This potentially invalidates patients' anti-inflammatory effect and intestinal mucus barrier protection, which may lead to alterations in intestinal permeability, decreased gut barrier function, and gastrointestinal symptoms, including diarrhea, bloating, and nausea. After metformin treatment, primary bile acids (PBAs) production species: Weissella confusa, Weissella paramesenteroides, Lactobacillus brevis, and Lactobacillus plantarum increased (p < 0.05). The species converting PBAs to secondary bile acids (SBAs): Parabacteroides distasonis decreased (p < 0.05). This might result in accumulation of PBAs, which also may lead to anti-inflammatory gene JUND and SQSTM1 downregulated. In conclusion, this study suggests that metformin intolerance may be attributed to a decrease in anti-inflammatory-related flora and genes, and also alterations in PBAs accumulation-related flora. These findings open up possibilities for future research targeting gut flora and host genes to prevent metformin intolerance.

Heat stress exposure cause alterations in intestinal microbiota, transcriptome, and metabolome of broilers.

Introduction: Heat stress can affect the production of poultry through complex interactions between genes, metabolites and microorganisms. At present, it is unclear how heat stress affects genetic, metabolic and microbial changes in poultry, as well as the complex interactions between them. Methods: Thus, at 28 days of age a total of 200 Arbor Acres broilers with similar body weights were randomly divided into the control (CON) and heat stress treatment (HS). There were 5 replicates in CON and HS, respectively, 20 per replication. From the 28-42 days, the HS was kept at 31 ± 1°C (9:00-17:00, 8 h) and other time was maintained at 21 ± 1°C as in the CON. At the 42nd day experiment, we calculated the growth performance (n = 8) of broilers and collected 3 and 6 cecal tissues for transcriptomic and metabolomic investigation and 4 cecal contents for metagenomic investigation of each treatment. Results and discussion: The results indicate that heat stress significantly reduced the average daily gain and body weight of broilers (value of p < 0.05). Transcriptome KEGG enrichment showed that the differential genes were mainly enriched in the NF-kB signaling pathway. Metabolomics results showed that KEGG enrichment showed that the differential metabolites were mainly enriched in the mTOR signaling pathway. 16S rDNA amplicon sequencing results indicated that heat stress increased the relative abundance of Proteobacteria decreased the relative abundance of Firmicutes. Multi-omics analysis showed that the co-participating pathway of differential genes, metabolites and microorganisms KEGG enrichment was purine metabolism. Pearson correlation analysis found that ornithine was positively correlated with SULT1C3, GSTT1L and g_Lactobacillus, and negatively correlated with CALB1. PE was negatively correlated with CALB1 and CHAC1, and positively with g_Alistipes. In conclusion, heat stress can generate large amounts of reactive oxygen and increase the types of harmful bacteria, reduce intestinal nutrient absorption and antioxidant capacity, and thereby damage intestinal health and immune function, and reduce growth performance indicators. This biological process is manifested in the complex regulation, providing a foundational theoretical basis for solving the problem of heat stress.

Elder and booster vaccination associates with decreased risk of serious clinical outcomes in comparison of Omicron and Delta variant: A meta-analysis of SARS-CoV-2 infection.

Background: The COVID-19 pandemic brings great pressure to the public health systems. This meta-analysis aimed to compare the clinical outcomes among different virus variants, to clarify their impact on medical resources and to provide evidence for the formulation of epidemic prevention policies. Methods: A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases using the key words "Omicron" and "Delta." The adjusted Risk ratios (RRs), Odds ratios (ORs) and Hazard ratios (HRs) were extracted, and RRs and Rate difference % (RD%) were used to interpret the risk estimates of the outcomes ultimately. Results: Forty-three studies were included, with 3,812,681 and 14,926,841 individuals infected with SARS-CoV-2 Delta and Omicron variant, respectively. The relative risks of hospitalization, death, ICU admission, and mechanical ventilation use after infection with the Omicron variant were all significantly reduced compared those after infection with the Delta variant (RRhospitalization = 0.45, 95%CI: 0.40-0.52; RRdeath = 0.37, 95%CI: 0.30-0.45; RRICU = 0.35, 95%CI: 0.29-0.42; RRmechanical ventilation = 0.33, 95%CI: 0.25-0.44). The change of both absolute and relative risks for hospitalization was more evident (RR = 0.47, 95%CI: 0.42-0.53；RD% =10.61, 95%CI: 8.64-12.59) and a significant increase was observed for the absolute differences in death in the elderly (RD% = 5.60, 95CI%: 4.65-6.55); the change of the absolute differences in the risk of hospitalization and death were most markedly observed in the patients with booster vaccination (RD%hospitalization = 8.60, 95CI%: 5.95-11.24; RD%death = 3.70, 95CI%: 0.34-7.06). Conclusion: The ability of the Omicron variant to cause severe clinical events has decreased significantly, as compared with the Delta variant, but vulnerable populations still need to be vigilant. There was no interaction between the vaccination doses and different variants.

hsa-mir-(4328, 4422, 548z and -628-5p) in diabetic retinopathy: diagnosis, prediction and linking a new therapeutic target.

AIMS: Growing evidence suggests that microRNAs (miRNAs) are crucial in controlling how diabetic retinopathy (DR) develops. We intend to mine miRNAs with diagnostic and predictive value for DR and to investigate new drug therapeutic targets. METHODS: After performing a differential analysis on the miRNA and mRNA datasets for DR and neovascularization (NEO), miRNA-mRNA networks were created. Combine the results of enrichment analysis, Protein-Protein Interaction Networks (PPI), and Cytoscape to identify key miRNAs. DrugBank was used to find drugs that interacted with transcription factors (TF) predicted by TransmiR. Finally, whole blood and clinical data were collected from 58 patients with type 2 diabetes mellitus (T2DM), and RT-qPCR, logistic analysis, and ROC were used to verify the value of key miRNAs. RESULTS: Differential analysis indicated the presence of genes and miRNAs that co-regulate DR and NEO. Enrichment analysis showed that key genes are inextricably linked to neovascularization. Combining the results of PPI and Cytoscape identified four key miRNAs, namely hsa-mir-(4328, 4422, 548z and -628-5p). RT-qPCR, logistic, and ROC results showed that decreased expression levels of hsa-mir-(4328, 4422, 548z and -628-5p) signal the risk of evolution to DR in T2DM patients. Finally, we constructed a TF-miRNA network to find the 15 TFs and the 35 drugs that interact with these TFs. CONCLUSION: hsa-mir-(4328, 4422, 548z and -628-5p) in whole blood are protective factors for DR as novel biomarkers for diagnosis and prediction. In addition, our research provides new drug directions for the treatment of DR, such as Diosmin, Atorvastatin, and so on.

Integrative analysis of transcriptome and metabolome reveals probiotic effects on cecal metabolism in broilers.

BACKGROUND: Probiotics play an important role in the host and have attracted widespread attention as an alternative to antibiotics. Arbor Acres broilers were used in the present experiment and fed different doses of compound probiotics at 1, 5, and 10 g kg-1 . The effects of compound probiotics on broiler growth performance and cecal transcriptome and metabolome were investigated. RESULTS: We discovered 425 differentially expressed genes (DEGs; upregulated: 256; downregulated: 169) in the cecal transcriptome study. These DEGs were assigned to fat metabolic pathways, such as the peroxisome proliferator-activated receptor (PPAR) signaling pathway, according to KEGG analysis. Probiotics downregulated LPL and upregulated PPARα expression in the cecum. In metabolome analysis of the cecum of cecum, we screened 86 differential metabolites and performed KEGG enrichment analysis of these metabolites. The KEGG analysis showed that these differentially expressed metabolites were annotated to nucleotide metabolism-related pathways, such as purine metabolism. In the cecum, probiotics upregulated the content of guanine, AMP, 3'-AMP, adenylosuccinate, deoxyguanosine, and ADP-ribose, whereas they downregulated the content of 5-hydroxyisourate. Comprehensive transcriptome and metabolome analysis revealed that glycolysis, gluconeogenesis, and glycerophospholipid metabolism pathways were jointly enriched in cecum of broilers fed a probiotic-containing diet. CONCLUSION: This study provides valuable information for studying the regulation and gene metabolism network of probiotics on cecal metabolism in broilers. © 2022 Society of Chemical Industry.

Transcriptome and metabolome analyses reveal the regulatory effects of compound probiotics on cecal metabolism in heat-stressed broilers.

The effect of compound probiotics on the caecum of broilers under heat stress was assessed in this study. A total of 400 twenty-eight-day-old AA male broilers were randomly divided into 4 treatment groups, where each group had 5 replicates of 20 broilers. The 4 treatment groups were a heat stress control group (broilers receiving a normal diet) and groups HP I, HP II, and HP Ⅲ, consisting of broilers receiving 1, 5, and 10 g of compound probiotics added to each kilogram of feed, respectively. Compound probiotics (L. casei, L. acidophilus, and B. lactis at a ratio of 1:1:2) were used to formulate a compound probiotic powder, with 1 × 1010 CFU/g of effective viable bacteria. Heat stress treatment was performed at 32 ± 1°C from 9:00 to 17:00 every day from 28 d to 42 d. In d 28 to 42, compared with the HC group, the ADG of broilers in the HP II and III groups was significantly increased (P < 0.05); the ADFI difference between groups was not significant (P > 0.05); the FCR of HP II and III broilers was significantly decreased (P < 0.05); and the FCR of the HP I group increased, but the difference was not significant (P > 0.05). Transcriptome results demonstrate that 665 differential genes were screened (DEGs; upregulated: 366, downregulated: 299). The DEGs were enriched in the B cell receptor signaling pathway, the intestinal immune network for IgA synthesis, the Fc epsilon RI signaling pathway, and other signaling pathways, according to KEGG enrichment analysis. Metabolome analysis identified 92 differential metabolites (DAMs; upregulated: 48, downregulated: 44). KEGG enrichment analysis indicated significant enrichment of Pantothenate and CoA biosynthesis and beta-Alanine metabolism. The combined transcriptome and metabolome analysis revealed that the DAMs and DEGs were mostly involved in beta-alanine metabolism, arginine biosynthesis, amino sugar and nucleotide sugar, and alanine, aspartate, and glutamate metabolism. The results of this study suggest that the addition of compound probiotics has a positive effect on intestinal metabolites, improving the growth performance and contributing to the overall health of broilers under heat stress.

WGCNA Analysis of Important Modules and Hub Genes of Compound Probiotics Regulating Lipid Metabolism in Heat-Stressed Broilers.

This study aimed to study compound probiotics' (Lactobacillus casei, Lactobacillus acidophilus and Bifidobacterium) effects on production performance, lipid metabolism and meat quality in heat-stressed broilers. A total of 400 one-day-old AA broilers were randomly divided into four groups, each containing the same five replicates, with 20 broilers in each replicate. The control (21 °C) and experiment 2 were fed a basic corn−soybean meal diet. Experiment 1 (21 °C) and experiment 3 were fed a basic corn−soybean meal diet with 10 g/kg compound probiotics on days 7 and 28, respectively. The ambient temperature of experiment 2 and experiment 3 was increased to 30−32 °C (9:00−17:00) for 28−42 days, while the temperature for the other time was kept at 21 °C. The results showed that, compared with the control, the production performance and the content of high-density lipoprotein cholesterol in experiment 1 and triglyceride (TG) in experiment 2 increased (p < 0.05). Compared with experiment 2, TG decreased and the production performance increased in experiment 3 (p < 0.05). However, there was no significant change in meat quality indicators. Weighted gene co-expression network analysis (WGCNA) was used to analyze the intramuscular fat, abdominal fat and five blood lipid indicators. We found five related modules. Fatty acid biosynthesis, glycerolipid metabolism, and fat digestion and absorption were the pathways for KEGG enrichment. Additionally, NKX2-1, TAS2R40, PTH, CPB1, SLCO1B3, GNB3 and AQP7 may be the hub genes of compound probiotics regulating lipid metabolism in heat-stressed broilers. In conclusion, this study identified the key genes of compound probiotics regulating lipid metabolism and provided a theoretical basis for the poultry breeding industry to alleviate heat stress.

Developmental differences of large-scale functional brain networks for spoken word processing.

A dual-stream dissociation for separate phonological and semantic processing has been implicated in adults' language processing, but it is unclear how this dissociation emerges with development. By employing a graph-theory based brain network analysis, we compared functional interaction architecture during a rhyming and meaning judgment task of children (aged 8-12) with adults (aged 19-26). We found adults had stronger functional connectivity strength than children between bilateral inferior frontal gyri and left inferior parietal lobule in the rhyming task, between middle frontal gyrus and angular gyrus, and within occipital areas in the meaning task. Meanwhile, adults but not children manifested between-task differences in these properties. In contrast, children had stronger functional connectivity strength or nodal degree in Heschl's gyrus, superior temporal gyrus, and subcortical areas. Our findings indicated spoken word processing development is characterized by increased functional specialization, relying on the dorsal and ventral pathways for phonological and semantic processing respectively.

Effects of three probiotics and their interactions on the growth performance of and nutrient absorption in broilers.

The purpose of this study was to investigate the effects of three probiotics and their interactions on growth performance, intestinal digestion and absorption, and nutrient transporters in broilers. A total of 350 one-day-old male Arbor Acres broilers were randomly divided into seven groups: the control group (broilers receiving normal drinking water), groups P1, P2 and P3 (broilers receiving drinking water with 1% Lactobacillus casei, Lactobacillus acidophilus and Bifidobacterium lactis , respectively) and groups CP1, CP2 and CP3 (broilers receiving drinking water with a 1% compound probiotic mixture in 2:1:1, 1:2:1, 1:1:2 ratios, respectively). The feeding period was divided into two experimental periods: 1∼21 days and 22∼42 days. Compared to those in the control group, the broiler slaughter indexes and average daily feed intakes in the probiotics groups were not significantly different (P > 0.05), but the villus height in the small intestine increased significantly, and the crypt depth decreased significantly (P < 0.05). In the 1- to 21-day, experimental period, the broiler average daily gains in groups CP2 and CP3 were significantly greater than that in the control group. Amylase, lipase, and trypsin activities in the jejunum in groups CP and P3 increased significantly. GLUT2 mRNA expression in the probiotics group was significantly incresaed compared with that in the control group (P < 0.05). In the 22- to 42-day period, the average daily gain in the CP group was significantly greater than that in the control group. Amylase activity in the CP2 group, and lipase and trypsin activities in the CP, P1 and P3 groups increased significantly. The GLUT2 mRNA expression in the CP group increased significantly (P < 0.05). In summary, three probiotics and their interactions improved the digestibility and absorption of nutrients by increasing the activities of digestive enzymes, improving the morphology of the digestive tract, and upregulating the expression of GLUT2 mRNA in the intestinalcell membrane to improve the production performance in broilers.

Gut microbiota and differential genes-maintained homeostasis is key to maintaining health of individuals with Yang-deficiency constitution.

OBJECTIVE: Yang-deficiency constitution (YADC) is a common unbalanced constitution that predisposes individuals to certain diseases. However, not all people with YADC manifest develop diseases. This calls for delineation of the underlying molecular mechanisms. Previous studies suggested that the gut microbiota and gene differential expression should be considered. METHODS: In the present study, we compared profiles of gut microbiota between four healthy YADC individuals and those of five healthy balanced constitution (BC) counterparts, based on 16S rRNA gene sequence analysis. Furthermore, YADC relevant genes identified by comparing 62 healthy YADC and 58 healthy BC individuals in total to perform intersection analysis, functional clustering and pathway enrichment analyses. RESULTS: The levels of harmful gut microbiota (Prevotellaceae, LDA score > 4.0, P = 0.0141) and beneficial gut microbiota (Ruminococcaceae, LDA score > 4.0, P = 0.0025, Faecalibacterium, LDA score > 4.0, P = 0.0484) were both elevated in healthy YADC individuals. Also, we found that the specific metabolic pathway with 2, 6-Dichloro-p-hydroquinone 1, 2-Dioxygenase (PcpA) as the core in gut microbiota and the glutathione transferase activity has been enriched by YADC relevant genes in healthy YADC individuals were both responsible for the detoxification of halogenated aromatic hydrocarbon substances. CONCLUSIONS: Both beneficial and harmful factors had been detected in healthy YADC individuals, functionally, they may have triggered homeostasis to maintain the health of individuals with YADC. The homeostasis may be maintained by beneficial and harmful factors from gut flora and genes. Future studies are expected to focus on halogenated aromatic hydrocarbons and their detoxification processes.

The genes for sensory perception of sound should be considered in gene diagnosis of congenital sensorineural hearing loss and microtia.

Congenital sensorineural hearing loss (CSHL) and microtia are development-related diseases, sharing some factors and affecting children's hearing. However, genetic tests only focus on CSHL. We try to identify the common molecular mechanism of CSHL and microtia as candidates combining gene diagnosis biomarkers. Whole-exon sequencing (WES), Sanger sequencing, qPCR, and bioinformatics analyses were performed in microtia family (F1), family two, whose proband suffered from microtia and CSHL (F2), five microtia, and four CSHL individuals, respectively. We found that 40% microtia and 40% CSHL relevant genes were detected in F1 and a sharing pathway: the sensory perception of sound was identified. Moreover, the copy number variation in proband F2 was identified in one gene of the sharing pathway: EYA1. Meanwhile, two variants of BUB3 were identified in F1 data. BUB3 is related to development, dog ear type, direct and indirect interaction with microtia, and CSHL relevant genes. Notably, although the allele frequency of two variants of BUB3 showed significant differences between microtia and CSHL, the special microtia-relevant genotype also could be detected in one CSHL sample. These results suggest that the sensory perception of sound and the development of relevant pathways may be the common pathways of microtia and CSHL. Genes of these pathways can be used as candidates combining gene diagnosis biomarkers.

Low-dose mono(2-ethylhexyl) phthalate promotes ovarian cancer development through PPARα-dependent PI3K/Akt/NF-κB pathway.

The plasticizer di(2-ethylhexyl) phthalate (DEHP) and its hydrolysate mono(2-ethylhexyl) phthalate (MEHP) are major toxicants from plastics, but their association with hormone-dependent cancers has been controversial. We treated the human ovarian cancer cell lines SKOV3 and A2780 with low concentrations of DEHP/MEHP, and found that although no significant effect on cell proliferation was observed, ovarian cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT) were promoted by submicromolar MEHP but not DEHP. Next, ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were obtained and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) supported enrichment and Kaplan-Meier survival analyses, which identified PI3K/Akt pathway as a pivotal signaling pathway in ovarian cancer. We found that 500 nM MEHP treatment significantly increased PIK3CA expression, which could be reversed by the knockdown of peroxisome proliferator-activated receptor alpha (PPARα). Silencing PIK3CA significantly suppressed the MEHP-induced migration, invasion and EMT. In addition, we validated that MEHP treatment promoted phosphorylation of Akt and degradation of IκB-α, thereby activating NF-κB and enhancing NF-κB nuclear translocation. In nude mice, MEHP exposure significantly promoted the metastasis of ovarian cancer xenografts, which could be suppressed by the treatment of PPARα inhibitor GW6471. Our findings showed that low-dose MEHP promoted ovarian cancer progression through activating PI3K/Akt/NF-κB pathway, in a PPARα-dependent manner.

Supplementation of probiotics in water beneficial growth performance, carcass traits, immune function, and antioxidant capacity in broiler chickens.

This study aims to investigate the effects of commercial probiotic supplementation in water on the performance parameters, carcass traits, immune function, and antioxidant capacity of broiler chicks. In the experiment, 120 Arbor Acres (AA) broilers (60 male and 60 female) were randomly allocated into four groups (G) - G1: basal diet and G2, G3, and G4: basal diet with 1% Lactobacillus casei, 1% L. acidophilus, and 1% Bifidobacterium in the water, lasting 42 days. The experimental results revealed that probiotic additives produced positive impacts on body weight, average daily feed intake (ADFI), and average daily weight gain for female chicks, whereas these probiotics significantly reduced ADFI and the feed conversion ratio of male chicks (P < 0.05). Probiotics efficiently improved eviscerated yield and breast yield while reducing the abdominal fat (P < 0.05) for the male broiler chicks. A marked increase was observed in the weight of the spleen, bursa of Fabricius, and thymus in the treatment group (P < 0.05). Besides, probiotics produced a significant effect on the concentrations of immune-related proteins (P < 0.05) and markedly increased the concentrations of antioxidase and digestive enzymes when compared with the control (P < 0.05). The addition of probiotics dramatically reduced the total counts of Escherichia coli and Salmonella and increased the quantity of Lactobacilli (P < 0.05). The results of the present study demonstrated an increase in growth performance, carcass traits, immune function, gut microbial population, and antioxidant capacity by supplementing 1% probiotics (L. casei, L. acidophilus, and Bifidobacterium) in the water for broilers.

Aconiti lateralis Radix Praeparata inhibits Alzheimer's disease by regulating the complex regulation network with the core of GRIN1 and MAPK1.

CONTEXT: Current medicine for Alzheimer's disease (AD) cannot effectively reverse or block nerve injury. Traditional Chinese Medicine practice and research imply Aconiti lateralis Radix Praeparata (Fuzi) may meet this goal. OBJECTIVE: Analysing the anti-AD effect of Fuzi and its potential molecular mechanism. MATERIALS AND METHODS: AD model cells were treated with Fuzi in 0-300 mg/mL for 24 h in 37 °C. The cell viability (CV) and length of cell projections (LCP) for each group were observed, analysed, and standardised using control as a baseline (CVs and LCPs). The Fuzi and AD relevant genes were identified basing on databases, and the molecular mechanism of Fuzi anti-AD was predicted by network analysis. RESULTS: Experiment results showed that Fuzi in 0.4 mg/mL boosted LCP (LCPs = 1.2533, p ≤ 0.05), and in 1.6-100 mg/mL increased CV (CVs from 1.1673 to 1.3321, p ≤ 0.05). Bioinformatics analysis found 17 Fuzi target genes (relevant scores ≥ 20), showing strong AD relevant signals (RMS_p ≤ 0.05, related scores ≥ 5), enriched in the pathways regulating axon growth, synaptic plasticity, cell survival, proliferation, apoptosis, and death (p ≤ 0.05). Especially, GRIN1 and MAPK1 interacted with APP protein and located in the key point of the "Alzheimer's disease" pathway. DISCUSSION AND CONCLUSIONS: These results suggest that Fuzi may have therapeutic and prevention potential in AD, and GRIN1 and MAPK1 may be the core of the pathways of the Fuzi anti-AD process. Fuzi should be studied more extensively, especially for the prevention of AD.