Investigation of guanidino acetic acid and rumen-protected methionine induced improvements in longissimus lumborum muscle quality in beef cattle.

This study examined the impact of dietary guanidino acetic acid (GAA) and rumen-protected methionine (RPM) on beef quality in Simmental bulls. For 140 days, forty-five bulls (453.43 ± 29.05 kg) were randomly divided into control (CON), 0.1% GAA (GAA), and 0.1% GAA + 0.1% RPM (GAM) groups with 15 bulls in each group and containing 3 pen with 5 bulls in each pen. Significant improvements in eye muscle area, pH48h, redness (a*) value, and crude protein (CP) content of longissimus lumborum (LL) muscles were observed in the GAA and GAM groups (P < 0.05). Conversely, the lightness (L*) value, drip loss, cooking loss, and moisture contents decreased (P < 0.05). Additionally, glutathione (GSH) and glutathione peroxidase (GSH-PX) concentrations of LL muscles in GAM were higher (P < 0.05), while malondialdehyde (MDA) content of LL muscles in GAA and GAM groups were lower (P < 0.05). Polyunsaturated fatty acids (PUFA) profiles were enriched in beef from GAM group (P < 0.05). The addition of GAA and RPM affected the expression of genes in LL muscle, such as HMOX1, EIF4E, SCD5, and NOS2, which are related to hypoxia metabolism, protein synthesis, and unsaturated fatty acid synthesis-related signaling pathways. In addition, GAA and RPM also affected the content of a series of metabolites such as L-tyrosine, L-tryptophan, and PC (O-16:0/0:0) involved in amino acid and lipid metabolism-related signaling pathways. In summary, GAA and RPM can improve the beef quality and its nutritional composition. These changes may be related to changes in gene expression and metabolic pathways related to protein metabolism and lipid metabolism in beef.

Human apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation.

Extracellular matrix (ECM) assembly/disassembly is a critical regulator for airway epithelial development and remodeling. Airway organoid is widely used in respiratory research, yet there is limited study to indicate the roles and mechanisms of ECM organization in epithelial growth and differentiation by using in vitro organoid system. Moreover, most of current Matrigel-based airway organoids are in basal-out orientation where accessing the apical surface is challenging. We present a human apical-out airway organoid using a biochemically defined hybrid hydrogel system. During human nasal epithelial progenitor cells (hNEPCs) differentiation, the gel gradually degrade, leading to the organoid apical surfaces facing outward. The expression and activity of ECM-degrading enzymes, matrix metalloproteinases (MMP7, MMP9, MMP10 and MMP13) increases during organoid differentiation, where inhibition of MMPs significantly suppresses the normal ciliation, resulting in increased goblet cell proportion. Moreover, a decrease of MMPs is found in goblet cell hyperplastic epithelium in inflammatory mucosa. This system reveals essential roles of epithelial-derived MMPs on epithelial cell fate determination, and provides an applicable platform enabling further study for ECM in regulating airway development in health and diseases.

Type 17 mucosal-associated invariant T cells contribute to neutrophilic inflammation in patients with nasal polyps.

BACKGROUND: Immune regulation in chronic rhinosinusitis with nasal polyps (CRSwNP) with a neutrophilic endotype remains unclear. Mucosal-associated invariant T (MAIT) cells are tissue-resident innate T lymphocytes that respond quickly to pathogens and promote chronic mucosal inflammation. OBJECTIVE: We aimed to investigate the roles of MAIT cells in neutrophilic CRSwNP. METHODS: Nasal tissues were obtained from 113 patients with CRSwNP and 29 control subjects. Peripheral and tissue MAIT cells and their subsets were analyzed by flow cytometry. Polyp-derived MAIT cells were analyzed by RNA sequencing to study their effects on neutrophils. RESULTS: Endotypes of CRSwNP were classified as paucigranulocytic (n = 21), eosinophilic (n = 29), neutrophilic (n = 39), and mixed granulocytic (n = 24). Frequencies of MAIT cells were significantly higher in neutrophilic (3.62%) and mixed granulocytic (3.60%) polyps than in control mucosa (1.78%). MAIT cell percentages positively correlated with local neutrophil counts. MAIT cells were more enriched in tissues than in matched PBMCs. The frequencies of MAIT1 subset or IFN-γ+ MAIT cells were comparable among control tissues and CRSwNP subtypes. The proportions of MAIT17 subset or IL-17A+ MAIT cells were significantly increased in neutrophilic or mixed granulocytic polyps compared with controls. RNA sequencing revealed type 17 and pro-neutrophil profiles in neutrophilic polyp-derived MAIT cells. In patients with neutrophilic CRSwNP, the proportions of MAIT and MAIT17 cells were positively correlated with local proinflammatory cytokines and symptom severity. In vitro experiments demonstrated that neutrophilic polyp-derived MAIT cells promoted neutrophil migration, survival, and activation. CONCLUSIONS: MAIT cells from neutrophilic CRSwNP demonstrate type 17 functional properties and promote neutrophil infiltration in nasal mucosa.

Mitigating greenhouse gas emissions by replacing inorganic fertilizer with organic fertilizer in wheat-maize rotation systems in China.

Combining organic and inorganic fertilizer applications can help reduce inorganic fertilizer use and increase soil fertility. However, the most suitable proportion of organic fertilizer is unknown, and the effect of combining organic and inorganic fertilizers on greenhouse gas (GHG) emissions is inconclusive. This study aimed to identify the optimum ratio of inorganic fertilizer to organic fertilizer in a winter wheat-summer maize cropping system in northern China to achieve high grain yields and low GHG intensities. The study compared six fertilizer treatments: no fertilization (CK), conventional inorganic fertilization (NP), and constant total nitrogen input with 25% (25%OF), 50% (50%OF), 75% (75%OF), or 100% (100%OF) organic fertilizer. The results showed that the 75%OF treatment increased the winter wheat and summer maize yields the most, by 7.2-25.1% and 15.3-16.7%, respectively, compared to NP. The 75%OF and 100%OF treatments had the lowest nitrous oxide (N2O) emissions, 187.3% and 200.2% lower than the NP treatment, while all fertilizer treatments decreased methane (CH4) absorption (by 33.1-82.0%) compared to CK. Carbon dioxide flux increased in the summer maize growing season (by 7.7-30.5%) compared to CK but did not significantly differ between fertilizer treatments. The average global warming potential (GWP) rankings across two wheat-maize rotations were NP > 50%OF > 25%OF > 100%OF > 75%OF > CK, and greenhouse gas intensity (GHGI) rankings were NP > 25%OF > 50%OF > 100%OF > 75%OF > CK. We recommend using 75% organic fertilizer/25% inorganic fertilizer to reduce GHG emissions and ensure high crop yields in wheat-maize rotation systems in northern China.

CAVIN2/SDPR Functioned as a Tumor Suppressor in Lung Adenocarcinoma from Systematic Analysis of Caveolae-Related Genes and Experimental Validation.

Background: Caveolae-Related Genes include caveolins and cavins, which are the main component of the fossa and, play important roles in a variety of physiological and pathological processes. Although increasing evidence indicated that caveolins (CAVs) and cavins (CAVINs) are involved in carcinogenesis and progression, their clinical significance and biological function in lung cancer are still limited. Methods: We investigated the expression of CAVs and CAVINs at transcriptional levels using Oncomine and Gene Expression Profiling Interactive Analysis. The protein and mRNA expression levels of CAVs and CAVINs were determined by the human protein atlas website and our surgically resected samples, respectively. The clinical value of prognostic prediction based on the expression of CAVs and CAVINs was also assessed. cBioPortal, GeneMANIA and STRING were used to analyze the molecular characteristics of CAVs and CAVINs in lung adenocarcinoma (LUAD) comprehensively. Finally, we investigated the effect of CAVIN2/SDPR (serum deprivation protein response) on LUAD cells with biological experiments in vitro. Results: The expression of CAV1/2 and CAVIN1/2/3 were significantly downregulated in LUAD and lung squamous cell carcinoma (LUSC). The patients with high expression of CAV1, CAV2, CAV3, CAVIN1 and CAVIN2/SDPR were tightly correlated with a better prognosis in LUAD, while no statistical significances in LUSC. Further, our results found that CAVIN2/SDPR can be identified as a prognostic biomarker independent of other CAVINs in patients with LUAD. Mechanically, the overexpression of CAVIN2/SDPR inhibited cell proliferation and migration owing to the cell apoptosis induction and cell cycle arrest at S phase in LUAD cells. Conclusions: CAVIN2/SDPR functioned as a tumor suppressor, and was able to serve as prognostic biomarkers in precision medicine of LUAD. Mechanically, overexpression of CAVIN2/SDPR inhibited cell proliferation by inducing cell apoptosis and S phase arrest in LUAD cells.

Mapping intellectual structures and research hotspots in the application of artificial intelligence in cancer: A bibliometric analysis.

Background: Artificial intelligence (AI) is more and more widely used in cancer, which is of great help to doctors in diagnosis and treatment. This study aims to summarize the current research hotspots in the Application of Artificial Intelligence in Cancer (AAIC) and to assess the research trends in AAIC. Methods: Scientific publications for AAIC-related research from 1 January 1998 to 1 July 2022 were obtained from the Web of Science database. The metrics analyses using bibliometrics software included publication, keyword, author, journal, institution, and country. In addition, the blustering analysis on the binary matrix was performed on hot keywords. Results: The total number of papers in this study is 1592. The last decade of AAIC research has been divided into a slow development phase (2013-2018) and a rapid development phase (2019-2022). An international collaboration centered in the USA is dedicated to the development and application of AAIC. Li J is the most prolific writer in AAIC. Through clustering analysis and high-frequency keyword research, it has been shown that AI plays a significantly important role in the prediction, diagnosis, treatment and prognosis of cancer. Classification, diagnosis, carcinogenesis, risk, and validation are developing topics. Eight hotspot fields of AAIC were also identified. Conclusion: AAIC can benefit cancer patients in diagnosing cancer, assessing the effectiveness of treatment, making a decision, predicting prognosis and saving costs. Future AAIC research may be dedicated to optimizing AI calculation tools, improving accuracy, and promoting AI.

ZNF384-ZEB1 feedback loop regulates breast cancer metastasis.

BACKGROUND: Breast cancer has become the most frequently diagnosed cancer worldwide. Increasing evidence indicated that zinc finger proteins (ZNFs), the largest family of transcription factors, contribute to cancer development and progression. Although ZNF384 is overexpressed in several types of human cancer, the role of ZNF384 in breast cancer remains unknown. Therefore, our research focused on ZNF384 regulation of the malignant phenotype of breast cancer and the underlying molecular mechanisms. METHODS: CCK-8 and colony formation assays were used to evaluate cell proliferation. Transwell and scratch assays were used to evaluate the cell migration and invasion. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were used to confirm the target relationship between ZNF384 and zinc finger E-box binding homeobox 1 (ZEB1). Xenografts were used to monitor the targets in vivo effects. RESULTS: We noted that ZNF384 was significantly overexpressed in breast cancer and highlighted the oncogenic mechanism of ZNF384. ZNF384 transactivated ZEB1 expression and induced an epithelial and mesenchymal-like phenotype, resulting in breast cancer metastasis. Furthermore, ZNF384 may be a target of miR-485-5p, and ZEB1 can up-regulate ZNF384 expression by repressing miR-485-5p expression. Together, we unveiled a feedback loop of ZNF384-ZEB1 in breast cancer metastasis. CONCLUSIONS: The findings suggest that ZNF384 can serve as a prognostic factor and a therapeutic target for breast cancer patients.

Analysis of Clinicopathological Characteristics and Prognosis of Carcinosarcoma of the Breast.

Background: Few cases of carcinosarcoma of the breast have been reported because of its low incidence rate and rapid progression. Seeking effective therapeutic methods becomes urgent in clinical practice. This study was aimed to investigate the clinical characteristics of carcinosarcoma of the breast and to explore proper therapeutic methods for patients with this rare tumor. Methods: We conducted a retrospective analysis on 47 patients with carcinosarcoma of the breast receiving treatment in our hospital from 2003 to 2020. Most of these patients received primary surgery followed by adjuvant chemotherapy, while four patients had lumpectomy only. Statistics showed no preference in age and menopausal status of patients. Results: The overall survival rate and progression-free survival rate of all patients at a median follow-up time of 33 months were 63.8% and 57.4%, respectively. Tumor size at diagnosis and chemotherapy strategies were both significant prognostic factors in reference to disease-free survival (DFS) and overall survival (OS) of the patients (tumor size: p=0.023 for DFS and p=0.021 for OS; therapeutic method: p=0.041 for DFS and p=0.024 for OS). N stage at diagnosis was significant only with reference to overall survival of the patients (p=0.009). EGFR expression was positive in some patients. Conclusions: Our results elucidated that the patients received comprehensive therapy, especially adjuvant chemotherapy was indispensable for better outcomes. Early detection and treatment were necessary for a higher survival rate when the tumor size was less than 5 cm without lymph node metastasis. Prospective outcomes with novel strategies targeting EGFR need to be further investigated.

Type 2 and Type 17 Invariant Natural Killer T Cells Contribute to Local Eosinophilic and Neutrophilic Inflammation and Their Function Is Regulated by Mucosal Microenvironment in Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by heterogeneous inflammatory endotypes of unknown etiology. Invariant natural killer T (iNKT) cells are multifunctional innate T cells that exhibit Th1-, Th2-, and Th17-like characteristics. We investigated functional relationships between iNKT cells and inflammatory subtypes of CRSwNP. Eighty patients with CRSwNP and thirty-two control subjects were recruited in this study. Flow cytometry was used to analyze the frequencies and functions of iNKT cells and their subsets in peripheral blood mononuclear cells (PBMCs) and tissues. Polyp tissue homogenates were used to study the multifunctionality of iNKT cells. iNKT cells were significantly increased in polyps (0.41%) than in control mucosa (0.12%). iNKT cells were determined in the paucigranunlocytic (n=20), eosinophilic (n=22), neutrophilic (n=23), and mixed granulocytic (n=13) phenotypes of CRSwNP. The percentages of iNKT cells and HLA-DR+PD-1+ subsets were lower in eosinophilic or mixed granulocytic polyps than those of other phenotypes. iNKT cells and subsets were enriched in polyp tissues than in matched PBMCs. The evaluation of surface markers, transcription factors, and signature cytokines indicated that the frequencies of iNKT2 and iNKT17 subsets were significantly increased in eosinophilic and neutrophilic polyps, respectively, than in the paucigranulocytic group. Moreover, the production of type 2 (partially dependent on IL-7) and type 17 (partially dependent on IL-23) iNKT cells could be stimulated by eosinophilic and neutrophilic homogenates, respectively. Our study revealed that type 2 and type 17 iNKT cells were involved in eosinophilic and neutrophilic inflammation, respectively, in CRSwNP, while different inflammatory microenvironments could modulate the functions of iNKT cells, suggesting a role of iNKT cells in feedback mechanisms and local inflammation.

The functions and prognostic value of Krüppel-like factors in breast cancer.

BACKGROUND: Krüppel-like factors (KLFs) are zinc finger proteins which participate in transcriptional gene regulation. Although increasing evidence indicate that KLFs are involved in carcinogenesis and progression, its clinical significance and biological function in breast cancer are still limited. METHODS: We investigated all the expression of KLFs (KLF1-18) at transcriptional levels by using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). The mRNA and protein expression levels of KLFs were also determined by using RT-qPCR and immunohistochemistry, respectively. CBioPortal, GeneMANIA and STRING were used to comprehensive analysis of the molecular characteristics of KLFs. The clinical value of prognostic prediction based on the expression of KLFs was determined by using the KM plotter. The relevant molecular pathways of KLFs were further analyzed by using Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Finally, we investigated the effect of KLF2 and KLF15 on biological behavior of breast cancer cells in vitro. RESULTS: The expression of KLF2/4/6/8/9/11/15 was significantly down-regulated in breast cancer. The patients with high KLF2, KLF4 or KLF15 expression had a better outcome, while patients with high KLF8 or KLF11 had a poor prognosis. Furthermore, our results showed that KLF2 or KLF15 can be used as a prognostic factor independent on the other KLFs in patients with breast cancer. Overexpression of KLF2 or KLF15 inhibited cell proliferation and migration, and blocked cell cycle at G0/G1 phase, resulting in cell apoptosis. CONCLUSIONS: KLF2 and KLF15 function as tumor suppressors in breast cancer and are potential biomarkers for prognostic prediction in patients with breast cancer.

Dynamic changes in the yak rumen eukaryotic community and metabolome characteristics in response to feed type.

With diversification of yak breeding, it is important to understand the effects of feed type on the rumen, especially microbiota and metabolites. Due to the unique characteristics of yak, research on rumen microbes and metabolites is limited. In this study, the effects of two diet types on rumen eukaryotic microflora and metabolites were evaluated using the Illumina MiSeq platform and liquid chromatography-mass spectrometry (LC-MS). All identified protozoa belonged to Trichostomatia. At the genus level, the relative abundance of Metadinium and Eudiplodinium were significantly (p < 0.05) higher in the roughage group than that of concentrate group, while the concentrate group harbored more Isotricha. Ascomycota, Basidiomycota, and Neocallimastigomycota were the main fungal phyla, and the Wallemia, Chordomyces, Chrysosporium, Cladosporium, Scopulariopsis, and Acremonium genera were significantly (p < 0.05) more abundant in the roughage group than the concentrate group, while the concentrate group harbored more Aspergillus, Neocallimastix, Thermoascus, and Cystofilobasidium (p < 0.05). Metabolomics analysis showed that feed type significantly affected the metabolites of rumen protein digestion and absorption (L-proline, L-phenylalanine, L-tryosine, L-leucine, L-tryptophan, and ß-alanine), purine metabolism (hypoxanthine, xanthine, guanine, guanosine, adenosine, and adenine), and other metabolic pathway. Correlation analysis revealed extensive associations between differential microorganisms and important metabolites. The results provide a basis for comprehensively understanding the effects of feed types on rumen microorganisms and metabolites of yaks. The findings also provide a reference and new directions for future research.

Ultrasound-Guided Continuous Thoracic Paravertebral Infusion of Methylene Blue in the Treatment of Postherpetic Neuralgia: A Prospective, Randomized, Controlled Study.

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster. Methylene blue (MB) is an inhibitor of nitric oxide synthesis with potentially analgesic and anti-inflammatory properties. Studies have demonstrated that thoracic paravertebral single MB injection is effective in treating chronic pain. However, there are rare reports of the efficacy of continuous thoracic paravertebral infusion of MB for pain management in PHN patients. The purpose of this study was to evaluate the therapeutic effects of continuous thoracic paravertebral infusion of MB on PHN. METHODS: A total of 104 PHN patients were randomly divided into two groups: the control group (continuous thoracic paravertebral infusion of 5% lidocaine in a total volume of 300 ml) and the MB group (continuous thoracic paravertebral infusion of 5% lidocaine plus 0.2% MB in a total volume of 300 ml). All patients were evaluated using the Numerical Rating Scale (NRS), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), 36-Item Short-Form Health Survey (SF-36), and medication doses before and after the procedure. The effective treatment rate and adverse complications were recorded 6 months after the procedure. RESULTS: In both groups, the NRS scores, ISI scores, PHQ-9 scores, and rescue medication dosages were significantly decreased at different time points after treatment compared to baseline, while the SF-36 scores were evidently improved at different time points after treatment compared to baseline. Compared with the control group, the MB group had significantly reduced NRS scores, ISI scores, PHQ-9 scores, and rescue medication dosages at each observation time point. Furthermore, the SF-36 scores in the MB group were significantly higher than those in the control group at each observation time point. The total effective treatment rate of the MB group was higher than that of the control group 6 months after the procedure. No severe adverse complications were observed in either group. CONCLUSIONS: Ultrasound-guided continuous thoracic paravertebral infusion with MB is a safe and effective therapy for PHN. Continuous infusion with MB can significantly reduce pain intensity, improve pain-related depression, increase quality of life, and decrease the amount of rescue medicine with no serious adverse complications.

Activation of peroxymonosulfate by iron-biochar composites: Comparison of nanoscale Fe with single-atom Fe.

A convenient and efficient method to fabricate isolated Fe single-atom catalysts deposited on Myriophyllum aquaticum-based biochar (ISA-Fe/MC) is reported for peroxymonosulfate-based organics degradation. Firstly, the Fe nanoparticles anchored on the hierarchical porous biochar (nano-Fe/MC) can be obtained by utilizing K2FeO4 as a synchronous activation and graphitization agent. Subsequently, ISA-Fe/MC was achieved by HCl etching of nano-Fe/MC to remove the excess Fe nanoparticles. Compared with nano-Fe/MC, ISA-Fe/MC demonstrated outperformed catalytic capacity towards PMS activation for phenol degradation. The combination of super high surface area, hierarchical porous structure, graphitization structure and atomically dispersed Fe species should be responsible for prominent catalytic oxidation ability and outstanding resistance to common anions and humic acid. Based on the chemical scavengers, EPR experiments and electrochemistry tests, the SO4•- dominated radical degradation pathway for nano-Fe/MC and electron transfer reigned non-radical degradation pathway for ISA-Fe/MC was revealed. In contrast to nano-Fe/MC, density functional theory calculations demonstrated the enhanced density of states around Fermi level in ISA-Fe/MC meaning the increased catalytic performance and more electron transfer between single-atom Fe to adjacent graphitic C and N which could serve as electron transfer channel for PMS activation.

[The role of palatovaginal canal and sphenopalatine artery in the localization of vidian canal during vidian neurotomy].

Objective:To explore the role of palatovaginal canal and sphenopalatine artery in the localization of pterygoid canal during pterygoid neurotomy. Method:55 patients with or without nasal polyps were divided into two groups: group A（twenty-nine cases, anterior wall approach of sphenoid sinus） and group B（twenty-six cases, middle nasal meatus approach）. All patients underwent unilateral vidian neurectomy under nasal endoscope. The vidian canal was located by palatal canal and sphenopalatine artery in group A and B, respectively. Result:The vidian canal was located successfully in all patients, with small wound, fast postoperative recovering. There was no irreversible complication. Conclusion:The relationship between the palatovaginal canal, sphenopalatine artery and the external orifice of vidian canal is constant, which can be used as an anatomical marker of vidian neurotomy.

The expression and prognostic role of EBP1 and relationship with AR in HER2+ breast cancer.

Human epidermal growth factor receptor (HER)-2 positive (HER2+) breast cancer (BC) has a poor survival rate and is more aggressive in nature. HER2-targeting agents could be beneficial for patients with HER2+ BC. In addition, targeted therapy and chemotherapy have been successfully used. However, a few patients are resistant to treatment. ErbB3 binding protein 1 (EBP1) binds to HER3 and inhibits the proliferation and invasive potential of tumor cells. However, its role in HER2+ BC has not been demonstrated. In this study, we aimed to analyze the relationship between androgen receptor (AR) and EBP1 expression in HER2+ BC. A total of 282 cases (140 cases of HER2+ invasive BC and 142 HER2-negative invasive BC) were included in this study. We performed immunohistochemistry (IHC) to analyze the expression of AR and EBP1; thereafter, we evaluated the relationship between these two biomarkers and estrogen receptor (ER), progesterone receptor (PR), HER2, p53, Ki67 expression, and other clinicopathological parameters. Of the HER2+ cases, 67 (47.9%) showed high expression of EBP1 (EBP1high) and 73 (52.1%) showed low/no expression of EBP1 (EBP1low/no). EBP1 expression was correlated with AR expression, histological grade, and lymphatic metastasis (p < 0.001, < 0.001, and 0.013, respectively). Kaplan-Meier analysis revealed that AR+ and EBP1low/no group had poorer overall survival (OS) and disease-free survival (DFS) compared with other groups (AR- and EBP1low/no, AR+ and EBP1high, and AR- and EBP1high). AR+ and EBP1low/no expression were independent prognostic factors for OS and DFS in HER2+ BC. This study showed the clinicopathological role of EBP1 and AR in HER2+ BC. Targeting EBP1 may be an effective treatment strategy for patients with AR+ HER2+ BC.

Effect of anti-inflammatory compounds or antibiotic administration on receiving performance and physiological responses of transported heifers.

The objectives of this experiment was to evaluate the effects of products with anti-inflammatory properties (yeast product [YEA; 20 g/heifer daily] or astragalus polysaccharide [APS; 20 g/heifer daily]) or an antibiotic (TUL, tulathromycin; 0.025 mL/kg body weight [BW]) on receiving performance and stress responses of transported heifers. Angus heifers (n = 80) were ranked by BW (315 ± 6 kg) and assigned to one of four treatments (five pens per treatment, four heifers per pen) 7 d before shipping 1,400 km (day -7): 1) fed a basal diet of ad libitum hay and concentrate supplement (CON) from day -7 to day 29; 2) YEA in supplemental concentrate from day -7 to day 7 (YEA); 3) APS in supplemental concentrate from day -7 to day 7 (APS); 4) administration of TUL at loading for shipping (day 0; TUL). Upon arrival at the receiving facility (day 1), heifers within each treatment were ranked by BW and assigned to 20 feedlot pens in the same manner as pre-transport. Daily dry matter intake (DMI) was recorded from day 1 to day 28. Full BW was recorded on days -7, -1, 0, 1, 28, and 29. Blood samples were collected on days -7, -1, 1, 4, 7, 14, and 28. Over the receiving period, average daily gain (ADG) and gain: feed did not differ (P ≥ 0.19) for YEA, APS, and TUL, which were greater (P ≤ 0.01) than CON. Average daily gain was also lower (P < 0.01) for CON vs. YEA, APS, and TUL from day -7 to day 28. During the first week of receiving, hay, concentrate, and total DMI were lower (P < 0.01) in CON than the YEA, APS, and TUL, but did not differ (P ≥ 0.13) among these three groups. Hay and total DMI were still lower (P < 0.01) in CON vs. TUL in the second week. Total DMI was greater (P = 0.01) for TUL vs. YEA, and greater (P < 0.01) for YEA vs. CON. Serum nonesterified fatty acid concentrations were greater (P ≤ 0.05) for CON and TUL vs. YEA and APS on day 1. Plasma cortisol concentrations were greater (P ≤ 0.05) for YEA and CON vs. APS and TUL on day 1. Serum tumor necrosis factor-α concentrations were lower (P ≤ 0.05) for APS vs. CON, YEA, and TUL on days 1 and 4. Plasma haptoglobin concentrations were greater (P ≤ 0.05) for CON vs. YEA, APS, and TUL on days 1 and 4, greater (P ≤ 0.05) for YEA, APS vs. TUL on day 1, and greater (P = 0.03) for YEA vs. TUL on day 4. Plasma ceruloplasmin concentrations were greater (P ≤ 0.05) for CON vs. YEA, APS and TUL vs. APS on days 1, 4, and 7. In conclusion, YEA, APS, and TUL modulated the physiological stress responses and alleviated the performance losses caused by long-distance transportation.

Effect of steam explosion of oil palm frond and empty fruit bunch on nutrient composition and ruminal fermentation characteristics.

In this study, we evaluated the effect of steam explosion of oil palm frond (OPF) and oil palm empty fruit bunch (EFB) on nutrient composition and ruminal fermentation characteristics in vitro. The results showed that steam explosion decreased NDF (P < 0.01), ADF (P < 0.01), and hemicellulose content (P < 0.01) in OPF and EFB. Steam explosion improved the effective energy value of OPF and EFB. In vitro fermentation results revealed that 72-h gas production capacity of OPF and EFB increased by 12.60and 85.06% (P < 0.01), respectively, after steam explosion. Steam explosion had a tendency to improve the concentration of total volatile fatty acids (TVFA) (P = 0.082). In conclusion, steam explosion of OPF and EFB reduced NDF, ADF, and hemicellulose content and increased gas production and TVFA concentration.

A high AR:ERα or PDEF:ERα ratio predicts a sub-optimal response to tamoxifen therapy in ERα-positive breast cancer.

PURPOSE: Approximately 30% oestrogen receptor alpha (ERα)-positive breast cancer (BC) patients exhibit intrinsic or recurrent resistance to adjuvant endocrine therapy with tamoxifen. The androgen receptor (AR) is expressed in about 90% of ERα-positive patients, with particularly high expression in tamoxifen-resistant tumours. Prostate-derived Ets factor (PDEF), which is a co-regulator of AR, plays a role in tamoxifen resistance in ERα-positive BC. The purpose of this research was to analyse the potential roles of AR, PDEF and ERα levels in the response to tamoxifen resistance in ERα-positive BC. METHODS: The nuclear AR:ERα and PDEF:ERα ratios were examined immunohistochemically in a cohort of 225 ERα-positive pre-menopausal BC patients who had received adjuvant tamoxifen therapy. RESULTS: For both AR:ERα and PDEF:ERα ratios, the optimal cutoff value was 2.0. Patients receiving adjuvant tamoxifen treatment who had a high AR:ERα (≥ 2.0) (HR = 3.90) or PDEF:ERα ratio (≥ 2.0) (HR = 2.77) had a beyond twofold increased risk of failure. Both the AR:ERα ratio (P = 0.001) and PDEF:ERα ratio (P = 0.002) were independently associated with the risk of tamoxifen treatment failure. Furthermore, both a high ratio of AR:ERα (≥ 2.0) and PDEF:ERα (≥ 2.0) were associated with shorter disease-free survival (DFS) and shorter disease-specific survival (DSS). In addition, both the AR:ERα ratio and PDEF:ERα ratio were independent predictors of DFS (both P < 0.0001) and DSS (P = 0.001 and P < 0.0001, respectively). CONCLUSIONS: AR:ERα and PDEF:ERα ratios are independent predictors of the response to conventional ERα-directed tamoxifen endocrine therapy.

ß-Catenin nuclear localization positively feeds back on EGF/EGFR-attenuated AJAP1 expression in breast cancer.

BACKGROUND: Adherent junction associated protein 1 (AJAP1), a typical molecule of adherent junctions, has been found to be a tumor suppressor in many cancer types. Aberrant activation of ß-catenin has been demonstrated to be associated with malignant biological properties of tumors including breast cancer. This study aimed to investigate the function and mechanism of AJAP1-mediated ß-catenin activity of breast cancer lines in vitro and in breast cancer patients. METHODS: AJAP1 and ß-catenin expressions in breast cancer tissues and cell lines were detected by immunohistochemistry, western blotting and qRT-PCR. The EGF/EGFR axis-mediated AJAP1 attenuated ß-catenin nuclear location was measured by western blotting, immunofluorescence assay, co-immunoprecipitation, luciferase assay and ubiquitination assays. Furthermore, the function of AJAP1 and ß-catenin regulated breast cancer progression was explored both in vivo and in vitro. RESULTS: It was found that AJAP1 had a high negative correlation with ß-catenin nuclear expression and was a novel tumor suppressor in breast cancer. AJAP1 loss can mediate ß-catenin accumulated in cytoplasm and then transferred it to the nucleus, activating ß-catenin transcriptional activity and downstream genes. Additionally, ß-catenin can reverse the invasion, proliferation ability and tumorigenicity of the depletion of AJAP1 caused both in vivo and in vitro. Besides, EGF/EGFR also involved in the process of AJAP1-depiction induced ß-catenin transactivation to the nucleus. More importantly, EGFR depletion/AJAP1 knocked down promoted the progression of breast cancer by regulating the activity of ß-catenin nuclear transactivation. CONCLUSION: This study demonstrated that AJAP1 acted as a putative tumor suppressor while ß-catenin nuclear localization positively fed back on EGF/EGFR-attenuated AJAP1 expression in breast cancer, which might be beneficial to develop new therapeutic targets for decreasing nuclear ß-catenin-mediated malignancy in breast cancer.