B4GALT5 a sialylation-related genes associated with patient prognosis and immune microenvironment in ovarian cancer and pan-cancer.

BACKGROUND: Ovarian cancer (OC) is the predominant primary tumor in the human reproductive system. Abnormal sialylation has a significant impact on tumor development, metastasis, immune evasion, angiogenesis, and treatment resistance. B4GALT5, a gene associated with sialylation, plays a crucial role in ovarian cancer, and may potentially affect clinicopathological characteristics and prognosis. METHODS: We conducted a comprehensive search across TIMER, GEPIA2, GeneMANIA, and Metascape to obtain transcription profiling data of ovarian cancer from The Cancer Genome Atlas (TCGA). The expression of B4GALT5 was test by immunohistochemistry. To investigate the impact of B4GALT5 on growth and programmed cell death in OC cells, we performed transwell assays and western blots. RESULTS: The presence of B4GALT5 was strongly associated with an unfavorable outcome in OC. B4GALT5 significantly promoted the proliferation of OC cells. Upon analyzing gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), it was discovered that B4GALT5 played a crucial role in the extracellular matrix, particularly in collagen-containing structures, and exhibited correlations with ECM-receptor interactions, transcriptional dysregulation in cancer, as well as the interleukin-1 receptor signaling pathway. Furthermore, there is a clear link between B4GALT5 and the tumor immune microenvironment in OC. Moreover, B4GALT5 exhibits favorable expression levels across various types of cancers, including CHOL, KIRC, STAD and UCES. CONCLUSION: In conclusion, it is widely believed that B4GALT5 plays a pivotal role in the growth and progression of OC, with its heightened expression serving as an indicator of unfavorable outcomes. Moreover, B4GALT5 actively participates in shaping the cancer immune microenvironment within OC. This investigation has the potential to contribute significantly to a deeper understanding of the substantial involvement of B4GALT5 in human malignancies, particularly OCs.

Highly Dispersive Gold Nanoclusters Confined within Micropores of Defective UiO-66 for Highly Efficient Aldehyde Oxidation at Mild Conditions.

The oxidative esterification of aldehydes under mild conditions remains a significant challenge. This study introduces a unique defective UiO-66 to achieve gold nanoclusters (AuNCs) for efficient aldehyde oxidation under mild conditions. The construction and characterization of these materials are thoroughly investigated by techniques of XRD, SEM and TEM images, FT-IR, Raman, and XPS spectrum, emphasizing the unique microporous in defective UiO-66 are conducive to the fabrication of AuNCs. The catalytic performance of the prepared materials in aldehyde oxidation reactions is systematically evaluated, demonstrating the remarkable efficiency of dispersed Au@UiO-66-25 with high-content (9.09 wt%) Au-loading and ultra-small size (~2.7 nm). Moreover, mechanistic insights into the catalytic process under mild conditions (70 °C for 1 h) are provided, elucidating the determination of defective UiO-66 in the confined fabrication of AuNCs and subsequent furfural adsorption, which underlie the principles governing the observed enhancements. This study establishes the groundwork for the synthesis of highly dispersed and catalytically active metal nanoparticles using defective MOFs as a platform, advancing the catalytic esterification reaction of furfural to the next level.

Histological and molecular difference in albumen quality between post-adolescent hens and aged hens.

The decline in albumen quality resulting from aging hens poses a threat to the financial benefits of the egg industry. Exploring the underlying mechanisms from the perspective of cell molecules of albumen formation is significant for the efficient regulation of albumen quality. Two individual groups of Hy-Line Brown layers with ages of 40 (W40) and 100 (W100) wk old were used in the present study. Each group contained over 2,000 birds. This study assessed the egg quality, biochemical indicators and physiological status of hens between W40 and W100. Subsequently, a quantitative proteomic analysis was conducted to identify differences in protein abundance in magnum tissues between W40 and W100. In the W40 group, significant increases (P < 0.05) were notable for albumen quality (thick albumen solid content, albumen height, Haugh unit), serum indices (calcium, estrogen, and progesterone levels), magnum histomorphology (myosin light-chain kinase content, secretory capacity, mucosal fold, goblet cell count and proportion) as well as the total antioxidant capacity of the liver. However, the luminal diameter of the magnum, albumen gel properties and random coil of the albumen were increased (P < 0.05) in the W100 group. The activity of glutathione, superoxidase dismutase, and malondialdehyde in the liver, magnum, and serum did not vary (P > 0.05) among the groups. Proteomic analysis revealed the identification of 118 differentially expressed proteins between the groups, which comprised proteins associated with protein secretion, DNA damage and repair, cell proliferation, growth, antioxidants, and apoptosis. Furthermore, Kyoto Encyclopedia of Genes pathway analysis revealed that BRCA2 and FBN1 were significantly downregulated in Fanconi anemia (FA) and TGF-ß signaling pathways in W100, validated through quantitative real-time PCR (qRT-PCR). In conclusion, significant age-related variations in albumen quality, and magnum morphology are regulated by proteins involved in antioxidant capacity.

Enhancing egg production and quality by the supplementation of probiotic strains (Clostridium and Brevibacillus) via improved amino acid digestibility, intestinal health, immune response, and antioxidant activity.

This study focused on evaluating the influence of Clostridium butyricum and Brevibacillus strains on egg production, egg quality, immune response and antioxidant function, apparent fecal amino acid digestibility, and jejunal morphology when supplemented as probiotics in the diets of laying hens in the peak phase. A total of 288 healthy 30-week-old Hy-Line Brown laying hens were arbitrarily assigned to four dietary groups, which included control diet and control diet supplemented with 0.02% C. butyricum zlc-17, C. butyricum lwc-13, or Brevibacillus zlb-z1, for 84 days. The results showed that dietary C. butyricum and Brevibacillus sp. exerted a positively significant influence (P ≤ 0.05) compared to the control group on the performance, egg quality, and physiological response of the birds. The diets could reduce mortality rate and enhance (P ≤ 0.05) egg weight and egg mass, egg production rate, and feed efficiency. Further analysis suggested that the probiotic strains can enhance (P ≤ 0.05) eggshell quality, Haugh unit, thick albumen content, and albumen height. Also, probiotics enhanced (P ≤ 0.05) the antioxidant status via increased antioxidant enzymes and jejunal morphology as evidenced by increased villi surface area (VSA), the ratio of villi height to crypt depth, villi width, and villi height, and a significant reduction in crypt depth. Besides, nutrient absorption and retention were enhanced, as apparent fecal amino acid digestibility of key essential amino acids was substantially improved in the diet-based group. The concentrations of immunoglobulin M and A (IgM and IgA) increased significantly (P ≤ 0.05) in the probiotics group and the same effect was notable for complement proteins (C3) and immune organ (Spleen). Conclusively, the supplementation of Clostridium butyricum zlc-17 in comparison to Clostridium butyricum lwc-13 and Brevibacillus zlb-z1 strains significantly (P ≤ 0.05) promoted the antioxidant status, modulated the intestinal structure, enhanced amino acid digestibility, and regulated the immunity index of the laying hens, which finally improves the laying performance and egg quality of the laying hens.

Dietary Fructooligosaccharides Effectively Facilitate the Production of High-Quality Eggs via Improving the Physiological Status of Laying Hens.

The focus of this study was to investigate the influence of prebiotics, such as fructooligosaccharides (FOS), on laying performance, egg quality, apparent fecal amino acid digestibility, jejunal morphology, hematological indices, immunological response, and antioxidant capacity in laying hens. A total of 216 healthy Hy-Line Brown laying hens aged 30 weeks were randomly assigned to one of three dietary treatments: basal diet, basal diet supplemented with 0.3 percent FOS, or 0.6 percent FOS. For 84 days, each treatment was fed the corresponding experimental diet. According to the findings, dietary supplementation with FOS enhanced laying performance and egg mass while lowering mortality rate. Albumen height, thick albumen content, Haugh unit, and eggshell thickness were also improved by the prebiotics. Prebiotics also boosted antioxidant status by increasing the activity of antioxidant enzymes, improved morphological development of the jejunum as demonstrated by significant increases in villi height, villi width, ratio of villi height to crypt depth, and reduced crypt depth. The prebiotics group showed a considerable increase in immunoglobulin M, G, and A (IgM, IgG, and IgA) levels, as well as a similar effect on complement proteins (C3). Furthermore, the apparent fecal amino acid digestibility of most essential amino acids was significantly enhanced. Conclusively, fructooligosaccharides at inclusion level of 0.6% efficiently enhanced laying performance and production of high-quality eggs while positively modulating amino acid digestibility, jejunal morphology, antioxidant status, and immune functions of the laying hens.

Invasive Pathobionts Contribute to Colon Cancer Initiation by Counterbalancing Epithelial Antimicrobial Responses.

BACKGROUND & AIMS: Microbiota dysbiosis and mucosa-associated bacteria are involved in colorectal cancer progression. We hypothesize that an interaction between virulent pathobionts and epithelial defense promotes tumorigenesis. METHODS: Chemical-induced CRC mouse model was treated with antibiotics at various phases. Colonic tissues and fecal samples were collected in a time-serial mode and analyzed by gene microarray and 16S rRNA sequencing. Intraepithelial bacteria were isolated using a gentamicin resistance assay, and challenged in epithelial cultures. RESULTS: Our study showed that antibiotic treatment at midphase but not early or late phase reduced mouse tumor burden, suggesting a time-specific host-microbe interplay. A unique antimicrobial transcriptome profile showing an inverse relationship between autophagy and oxidative stress genes was correlated with a transient surge in microbial diversity and virulence emergence in mouse stool during cancer initiation. Gavage with fimA/fimH/htrA-expressing invasive Escherichia coli isolated from colonocytes increased tumor burden in recipient mice, whereas inoculation of bacteria deleted of htrA or triple genes did not. The invasive E.coli suppressed epithelial autophagy activity through reduction of microtubule-associated protein 1 light-chain 3 transcripts and caused dual oxidase 2-dependent free radical overproduction and tumor cell hyperproliferation. A novel alternating spheroid culture model was developed for sequential bacterial challenge to address the long-term changes in host-microbe interaction for chronic tumor growth. Epithelial cells with single bacterial encounter showed a reduction in transcript levels of autophagy genes while those sequentially challenged with invasive E.coli showed heightened autophagy gene expression to eliminate intracellular microbes, implicating that bacteria-dependent cell hyperproliferation could be terminated at late phases. Finally, the presence of bacterial htrA and altered antimicrobial gene expression were observed in human colorectal cancer specimens. CONCLUSIONS: Invasive pathobionts contribute to cancer initiation during a key time frame by counterbalancing autophagy and oxidative stress in the colonic epithelium. Monitoring gut microbiota and antimicrobial patterns may help identify the window of opportunity for intervention with bacterium-targeted precision medicine.

Pharmacokinetics of Tinidazole in Chinese subjects: comparison of Mongolian, Korean, Hui, Uighur and Han nationalities.

PURPOSE: This study investigated the pharmacokinetics of tinidazole in subjects of five different Chinese nationalities (Han, Mongolian, Korean, Hui, and Uighur). METHODS: Fifty healthy subjects (five male and five female of each nationality) were recruited for the study, and each received 1 g tinidazole. A total of 14 blood samples were collected over a 72-hour period after administration. RESULTS: Pharmacokinetic profiles, including area under the curve from time zero to infinity (AUC0-inf), peak plasma concentration (Cmax), time to reach Cmax (tmax), oral clearance (CL/F), elimination rate constant (Ke), and elimination half-life (t1/2), were determined following a single oral dose of tinidazole. The respective pharmacokinetic properties of Han, Mongolian, Korean, Hui, and Uighur nationalities were: half-life (h): 16.94+/-2.40, 16.40+/-1.79, 16.63+/-1.82, 16.81+/-1.56, 14.34+/-1.92; Cmax (microg/mL): 19.04+/-2.42, 19.22+/-4.93, 20.83+/-3.33, 20.25+/-4.05, 18.81+/-3.10; AUC0-inf (h*microg/mL): 483.13+/-65.65, 479.70+/-99.74, 511.07+/-53.47, 514.25+/-130.78, 388.58+/-37.37. The t1/2 and AUC0-inf of Uighur subjects were significantly lower (p =0.023, 0.011) and the CL/F and Ke were significantly higher (p = 0.003, 0.013) than those of other nationalities. After normalization by weight, the differences in AUC0-inf and CL/F between Uigur subjects and those of other races were still significant. CONCLUSIONS: The results indicate that ethnicity had significant impact on the pharmacokinetics of tinidazole after a single oral dose in healthy volunteers of different nationalities in China.

Contribution of fucose-containing capsules in Klebsiella pneumoniae to bacterial virulence in mice.

Bacterium Klebsiella pneumoniae (KP) contains a prominent capsule. Clinical infections usually are associated with pneumonia or urinary tract infection (UTI). Emerging evidence implicates KP in severe liver abscess especially in diabetic patients. The goal of this study was to investigate the capsular polysaccharides from KP of liver abscess (hepatic-KP) and of UTI-KP. The composition of capsular polysaccharides was analyzed by capillary high-performance liquid chromatography (HPLC, Dionex system). The terminal sugars were assayed by binding ability to lectins. The results showed that the capsule of a hepatic KP (KpL1) from a diabetic patient contained fucose, while the capsule from UTI-KP (KpU1) did not. The absence of fucose was verified by the absence of detectable polymerase chain reaction (PCR) fragment for fucose synthesis genes, gmd and wcaG in KpU1. Mice infected with the KpL1 showed high fatality, whereas those infected with the KpU1 showed high survival rate. The KpL1 capsule was reactive to lectins AAA and AAL, which detect fucose, while the KpU1 capsule was reactive to lectin GNA, which detects mannose. Phagocytosis experiment in mouse peritoneal cavity indicated that the peritoneal macrophages could interact with KpU1, while rare association of KpL1 with macrophages was observed. This study revealed that different polysaccharides were displayed on the bacterial capsules of virulent KpL1 as compared with the less virulent KpU1. Interaction of KpU1 with mice peritoneal macrophages was more prominent than that of KpL1. The possession of fucose might contribute to KpL1 virulence by avoiding phagocytosis since fucose on bacteria had been implicated in immune evasion.