N-acetyl-l-methionine dietary supplementation improves meat quality by oxidative stability of finishing Angus heifers.

Methionine plays a vital role in protein synthesis, and regulation of antioxidant response in ruminants. This study aimed to assess the effects of dietary supplementation with N-acetyl-l-methionine (NALM), which serves a source of rumen-protected methionine, on growth performance, carcass traits, meat quality, and oxidative stability. Sixty Angus heifers (initial body weight = 408 ± 51.2 kg, 15-18 months) were stratified by body weight and randomly assigned to four dietary treatments: a control group (0% NALM), and experimental groups receiving diets containing 0.125%, 0.25%, and 0.50% NALM (dry matter (DM) basis), respectively. The experiment included a 2-week adaptation and a 22-week data and sample collection period. Results indicated that blood urea nitrogen in the plasma of the 0.25% NALM group was lower compared to the control and the 0.50% NALM groups (P = 0.02). The plasma methionine (P = 0.04), proline (P < 0.01), and tryptophan (P = 0.05) were higher in the 0.25% and 0.50% NALM groups, as well as the methionine and proline in the muscle of the 0.25% NALM group (P < 0.01). The muscle pH (P < 0.01) was increased by supplementing 0.25% and 0.50% NALM in diets but decreased the lactate (P < 0.01). The 0.25% NALM group also increased a* (P = 0.05), decreased L* (P = 0.05), drip loss (P = 0.01), and glycolytic potential in the muscle (P < 0.01). The total antioxidant capacity, superoxide dismutase, glutathione peroxidase, catalase, and glutathione in muscle of 0.25% NALM group were higher than that of the control (P < 0.01), and the malondialdehyde and protein carbonyl were lower (P < 0.01). In conclusion, the dietary supplement with NALM improves meat quality by enhancing the antioxidant effect of lipids and proteins.

Effect of Guanidinoacetic Acid Supplementation on Growth Performance, Rumen Fermentation, Blood Indices, Nutrient Digestion, and Nitrogen Metabolism in Angus Steers.

Guanidinoacetic acid (GAA) functions as a precursor for creatine synthesis in the animal body, and maintaining ample creatine reserves is essential for fostering rapid growth. This study aimed to explore the impact of GAA supplementation on growth performance, rumen fermentation, blood indices, nutrient digestion, and nitrogen metabolism in Angus steers through two experiments: a feeding experiment (Experiment 1) and a digestive metabolism experiment (Experiment 2). In Experiment 1, thirty-six Angus steers (485.64 ± 39.41 kg of BW) at 16 months of age were randomly assigned to three groups: control (CON), a conventional dose of GAA (CGAA, 0.8 g/kg), and a high dose of GAA (HGAA, 1.6 g/kg), each with twelve steers. The adaptation period lasted 14 days, and the test period was 130 days. Weighing occurred before morning feeding on days 0, 65, and 130, with rumen fluid and blood collected before morning feeding on day 130. Experiment 2 involved fifteen 18-month-old Angus steers (575.60 ± 7.78 kg of BW) randomly assigned to the same three groups as in Experiment 1, with a 7-day adaptation period and a 3-day test period. Fecal and urine samples were collected from all steers during this period. Results showed a significantly higher average daily gain (ADG) in the CGAA and HGAA groups compared to the CON group (p = 0.043). Additionally, the feed conversion efficiency (FCE) was significantly higher in the CGAA and HGAA groups than in the CON group (p = 0.018). The concentrations of acetate and the acetate:propionate ratio were significantly lower in the CGAA and HGAA groups, while propionate concentration was significantly higher (p < 0.01). Serum concentration of urea (UREA), blood ammonia (BA), GAA, creatine, and catalase (CAT) in the CGAA and HGAA groups were significantly higher than in the CON group, whereas malondialdehyde (MDA) concentrations were significantly lower (p < 0.05). Digestibility of dry matter (DM) and crude protein (CP) and the nitrogen retention ratio were significantly higher in the CGAA and HGAA groups than in the CON group (p < 0.05). In conclusion, dietary addition of both 0.8 g/kg and 1.6 g/kg of GAA increased growth performance, regulated rumen fermentation and blood indices, and improved digestibility and nitrogen metabolism in Angus steers. However, higher doses of GAA did not demonstrate a linear stacking effect.

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.

The Effect of Yucca schidigera Extract on Serum Metabolites of Angus Crossbreed Steers with Metabolomics.

This study was conducted to explore the potential effect of Yucca schidigera extract (YSE) on the metabolism of beef cattle. Thirty Angus crossbreed steers were selected, with an initial mean body weight of 506.6 ± 33.3 kg, and assigned to two treatments: a diet with no additives (CON group) and a diet supplemented with 1.75 g/kg of YSE (YSE group) (on a dry matter basis). The experiment lasted for 104 days, with 14 days for adaptation. The results showed that adding YSE could significantly improve the average daily gain (ADG) from 1 to 59 d (15.38%) (p = 0.01) and 1 to 90 d (11.38%) (p < 0.01), as well as dry matter digestibility (DMD) (0.84%) (p < 0.05). The contents of alanine aminotransferase, aspartate aminotransferase, and bilirubin and the total antioxidant capacity were increased and blood urea was reduced in the YSE group, compared to the CON group (p < 0.05). Both the glycerophospholipids and bile acids, including phosphocholine, glycerophosphocholine, PC(15:0/18:2(9Z,12Z)), PE(18:0/20:3(5Z,8Z,11Z)), PE(18:3(6Z,9Z,12Z)/P-18:0), LysoPC(15:0), LysoPC(17:0), LysoPC(18:0), LysoPC(20:5(5Z,8Z,11Z,14Z,17Z)), deoxycholic acid, glycocholic acid, and cholic acid, were upregulated by the addition of YSE. In summary, YSE may improve the ADG by increasing the blood total antioxidant capacity and glycerophospholipid synthesis, maintaining steers under a healthy status that is beneficial for growth. Furthermore, YSE may also increase the expression of bile acid synthesis, thereby promoting DMD, which, in turn, offers more nutrients available for growth.

Concentrate supplementation improves cold-season environmental fitness of grazing yaks: responsive changes in the rumen microbiota and metabolome.

Yak (Bos grunniens) is an important economic animal species on the Qinghai-Tibet Plateau. Yaks grazed in the cold season often suffer from nutritional stress, resulting in low production performance. This situation can be improved by properly feeding the grazing yaks in the cold season; however, there is still little information about the effect of different feeding levels on the intestinal microflora and metabolites of yaks. Therefore, this study aimed to explore the effect of feeding different doses of concentrate supplements on rumen bacterial communities and metabolites in grazing yaks during the cold season. Feed concentrate supplementation significantly improved the production performance and rumen fermentation status of grazing yaks during the cold season, and switched the type of ruminal fermentation from acetic acid fermentation to propionic acid fermentation. Ruminal fermentation parameters and ruminal bacterial abundance correlated strongly. At the phylum level, the abundance of Firmicutes increased with increasing concentrate supplementation, while the opposite was true for Bacteroidota. At the genus level, the abundance of Christensenellaceae_R-7_group, NK4A214_group, Ruminococcus, norank_f__Eubacterium_coprostanoligenes_group, norank_f__norank_o__ Clostridia_UCG-014, Lachnospiraceae_NK3A20_group, Acetitomaculum, and Family_XIII_AD3011_group increased with increasing concentrate supplementation, while the abundance of Rikenellaceae_RC9_gut_ group decreased. Dietary concentrate supplementation altered the concentration and metabolic mode of metabolites in the rumen, significantly affecting the concentration of metabolites involved in amino acid and derivative metabolism (e.g., L-aspartic acid, L-glutamate, and L-histidine), purine metabolism (e.g., guanine, guanosine, and hypoxanthine), and glycerophospholipid metabolism (e.g., phosphatidate, phosphatidylcholine, and phosphocholine), and other metabolic pathways. The strong correlation between yak rumen microorganisms and metabolites provided a more comprehensive understanding of microbial community composition and function. This study showed significant changes in the composition and abundance of bacteria and metabolites in the rumen of cool season grazing yaks fed with concentrate supplements. Changes in ruminal fermentation parameters and metabolite concentration also showed a strong correlation with ruminal bacterial communities. These findings will be helpful to formulate supplementary feeding strategies for grazing yaks in the cold season from the perspective of intestinal microorganisms.

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.

Spatiotemporal Patterns of the Omicron Wave of COVID-19 in the United States.

COVID-19 has undergone multiple mutations, with the Omicron variant proving to be highly contagious and rapidly spreading across many countries. The United States was severely hit by the Omicron variant. However, it was still unclear how Omicron transferred across the United States. Here, we collected daily COVID-19 cases and deaths in each county from 1 December 2021 to 28 February 2022 as the Omicron wave. We adopted space-time scan statistics, the Hoover index, and trajectories of the epicenter to quantify spatiotemporal patterns of the Omicron wave of COVID-19. The results showed that the highest and earliest cluster was located in the Northeast. The Hoover index for both cases and deaths exhibited phases of rapid decline, slow decline, and relative stability, indicating a rapid spread of the Omicron wave across the country. The Hoover index for deaths was consistently higher than that for cases. The epicenter of cases and deaths shifted from the west to the east, then southwest. Nevertheless, cases were more widespread than deaths, with a lag in mortality data. This study uncovers the spatiotemporal patterns of Omicron transmission in the United States, and its underlying mechanisms deserve further exploration.

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.

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.

Chinese Consumer Assessment of Australian Sheep Meat Using a Traditional Hotpot Cooking Method.

Hotpot is a widely popular cooking method for sheepmeat in China. This study measured the sensory responses of 720 untrained Chinese consumers to Australian sheepmeat cooked using a hotpot technique with methods based on Meat Standards Australia protocols. Shoulder and leg cuts of 108 lambs and 109 yearlings were scored on tenderness, juiciness, flavour and overall liking with linear mixed effects models used to analyse the influence of muscle type and animal factors on these scores. On average, shoulder cuts were more palatable than legs cuts for all sensory traits (p < 0.01) and lambs compared to yearlings (p < 0.05). Intramuscular fat and muscularity were identified as strong drivers of eating quality (p < 0.05), with greater palatability for both cuts as intramuscular fat increased (range 2.5 to 7.5%), and muscularity decreased (as measured through loin weight adjusted for hot carcase weight). Consumers were unable to detect differences between animal sire type and sex in sheepmeat hotpot. These findings suggest shoulder and leg cuts performed comparatively well in hotpot compared to previously tested sheepmeat cooking methods and emphasise the importance of balanced selection for quality and yield traits to ensure that consumer satisfaction is maintained.

Intrarenal Doppler approaches in hemodynamics: A major application in critical care.

The treatment of severe cases usually requires multimodality hemodynamic monitoring approaches, particularly for tissue and organ perfusion tracking. Currently, only a few studies have investigated renal perfusion status at the bedside. Ultrasound has become increasingly utilized to guide the hemodynamic management of severe patients. Similarly, intrarenal Doppler (IRD) is widely used to assess renal perfusion from both the intrarenal artery and vein perspectives. The renal resistive index (RRI), which reflects the renal arterial blood flow profile, is often applied to predict the reversibility of renal dysfunction and to titrate hemodynamic support. Intrarenal venous flow (IRVF) patterns and the renal venous stasis index (RVSI), which reflects the intrarenal vein blood flow profile, are now being used to assess intravenous congestion. They may also be useful in predicting the risk of acute kidney injury and avoiding fluid overload. IRD can provide diverse and supplemental information on renal perfusion and may help to establish the early diagnosis in severe patients. This review focused on the specific operational methods, influencing factors, and applications of IRD in hemodynamics.

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.

Dietary Concentrate-to-Forage Ratio Affects Rumen Bacterial Community Composition and Metabolome of Yaks.

Changes in dietary composition affect the rumen microbiota in ruminants. However, information on the effects of dietary concentrate-to-forage ratio changes on yak rumen bacteria and metabolites is limited. This study characterized the effect of three different dietary concentrate-to-forage ratios (50:50, C50 group; 65:35, C65 group; 80:20, C80 group) on yak rumen fluid microbiota and metabolites using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analyses. Rumen fermentation parameters and the abundance of rumen bacteria were affected by changes in the dietary concentrate-to-forage ratio, and there was a strong correlation between them. At the genus level, higher relative abundances of norank_f__F082, NK4A214_group, Lachnospiraceae_NK3A20_group, Acetitomaculum, and norank_f__norank_o__Clostridia_UCG-014 were observed with a high dietary concentrate-to-forage ratio (P < 0.05). Combined metabolomic and enrichment analyses showed that changes in the dietary concentrate-to-forage ratio significantly affected rumen metabolites related to amino acid metabolism, protein digestion and absorption, carbohydrate metabolism, lipid metabolism, and purine metabolism. Compared with the C50 group, 3-methylindole, pantothenic acid, D-pantothenic acid, and 20-hydroxy-leukotriene E4 were downregulated in the C65 group, while spermine and ribose 1-phosphate were upregulated. Compared to the C50 group, Xanthurenic acid, tyramine, ascorbic acid, D-glucuronic acid, 6-keto-prostaglandin F1a, lipoxin B4, and deoxyadenosine monophosphate were upregulated in the C80 group, while 3-methylindole and 20-hydroxy-leukotriene E4 were downregulated. All metabolites (Xanthurenic acid, L-Valine, N-Acetyl-L-glutamate 5-semialdehyde, N-Acetyl-L-glutamic acid, Tyramine, 6-Keto-prostaglandin F1a, Lipoxin B4, Xanthosine, Thymine, Deoxyinosine, and Uric acid) were upregulated in the C80 group compared with the C65 group. Correlation analysis of microorganisms and metabolites provided new insights into the function of rumen bacteria, as well as a theoretical basis for formulating more scientifically appropriate feeding strategies for yak.

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.

Small Intestine Microbiome and Metabolome of High and Low Residual Feed Intake Angus Heifers.

The gastrointestinal tract (GIT) contains complex microbial communities and plays an essential role in the overall health of the host. Previous studies of beef cattle feed efficiency have primarily concentrated on the ruminal microbiota because it plays a key role in energy production and nutrient supply in the host. Although the small intestine is the important site of post-ruminal digestion and absorption of nutrients, only a few studies have explored the relationship between the microbial populations in the small intestine and feed efficiency. Moreover, variations in GIT metabolites contribute to differences in feed efficiency. The objective of this study was to investigate relationships among bacterial populations of duodenum, jejunum, ileum; microbial metabolites; and RFI phenotype of beef cattle. We carried out by using Illumina MiSeq sequencing of the 16S rRNA V3-V4 region and liquid chromatography-mass spectrometry (LC-MS). In the duodenum, the relative abundances of Firmicutes ( p < 0.01), Lachnospiraceae, Ruminococcaceae, Family_XIII, Christensenellaceae, Christensenellaceae_R-7_group ( p < 0.05), and Lachnospiraceae_NK3A20_group ( p < 0.05) were higher in the low residual feed intake (LRFI) group compared with the high residual feed intake (HRFI) group, whereas the HRFI group had higher abundances of Proteobacteria and Acinetobacter ( p < 0.01). In the jejunum, the relative abundances of Lachnospiraceae and Lachnospiraceae_NK3A20_group were higher in the LRFI group ( p < 0.05). In the ileum, the relative abundances of Ruminococcaceae ( p < 0.01), Christensenellaceae, Christensenellaceae_R-7_group, and Ruminococcus_2 were also higher in the LRFI group ( p < 0.05). Moreover, the genera Lachnospiraceae_NK3A20_group, Christensenellaceae_R-7_group, and Ruminococcus_2 were negatively associated with RFI, while the genus Acinetobacter was positively associated with RFI. The metabolomics analysis revealed that the LRFI group significantly improved protein digestion and absorption, as well as glycerophospholipid metabolism in the duodenum, jejunum, ileum. The correlation between intestinal microorganisms and metabolites revealed that some microorganisms play an important role in amino acid metabolism, glycerophospholipid metabolism, nutrient digestion and absorption, and antioxidant enhancement. The present study provides a better understanding of the small intestinal microbiota and metabolites of beef cattle with different RFI phenotypes and the relationships among them, which are potentially important for the improvement of beef cattle feed efficiency.

Microglia-derived TNF-α inhibiting GABAergic neurons in the anterior lateral bed nucleus of the stria terminalis precipitates visceral hypersensitivity induced by colorectal distension in rats.

Irritable bowel syndrome (IBS) is a common and debilitating gastrointestinal disorder that is exacerbated by stress and characterized by abdominal pain. Although microglia in the CNS have been implicated as an important mediator of the stress response, the role of microglia and microglia-GABAergic neuron interactions in the limbic area, most notably BNST, in the development of colorectal hypersensitivity has not been determined. We established a neonatal colorectal distension-induced chronic visceral hyperalgesia model in rats. The results showed that the frequency of spontaneous discharges of alBNST GABAergic neurons and the expression of GAD65/67 were significantly decreased in rats with chronic visceral pain. Moreover, ablation of BNST GABAergic neurons significantly reduced the visceral pain threshold in normal rats. Meanwhile, the number of M1 proinflammatory microglia and the expression of the M1 proinflammatory microglia-derived cytokines IL-6 and TNF-α were increased in the alBNST of rats with chronic visceral pain. Furthermore, alBNST infusion of the microglial inhibitor minocycline or IL-6 and TNF-α neutralizing antibodies significantly increased the visceral pain threshold. The decreased frequency of spontaneous discharges of alBNST GABAergic neurons in rats with chronic visceral pain was mimicked by a bath perfusion of TNF-α, but not IL-6, and was abolished by a perfusion of the microglial inhibitor minocycline. In addition, the alBNST infusion of the microglial inhibitor minocycline upregulated the expression of GAD65/67. Moreover, ablation of BNST GABAergic neurons significantly decreased the visceral pain threshold in normal rats, which was not reversed by a subsequent infusion of the microglial inhibitor minocycline. Our findings revealed this microglia-GABAergic neuron circuit in the alBNST, and this microglia-driven disinhibitory mechanism is essential for brain and gut dysfunction in stressful condition, providing a novel potential target for treating patients with IBS presenting visceral pain that is worsened during episodes of stress.

Rumen Microbiome and Metabolome of High and Low Residual Feed Intake Angus Heifers.

Feed cost is the greatest expense during cattle production; therefore, reducing it is critical to increasing producer profits. In ruminants, the microbial population is important to nutrient digestion and absorption in the rumen. The objective of this study was to investigate the relationships among rumen bacteria, rumen metabolites, and the residual feed intake (RFI) phenotype of beef cattle. Twelve Angus heifers were selected to be sampled and divided into high RFI (HRFI; n = 6) group and low RFI (LRFI; n = 6) group according to their RFI classification determined during the feedlot-finishing period. After the ruminal liquid samples were collected at slaughter, Illumina MiSeq sequencing of the 16S rRNA V3-V4 region and liquid chromatography-mass spectrometry (LC-MS) were performed to determine their bacterial composition and metabolites, respectively. At the phylum level, the relative abundance of Proteobacteria was higher in the LRFI group than in the HRFI group (P < 0.01). At the family level, the relative abundances of Rikenellaceae (P < 0.01), Ruminococcaceae, Bacteroidales_S24-7_group, and Lachnospiraceae (P < 0.05) were significantly higher in the LRFI group. At the genus level, the relative abundances of Rikenellaceae_RC9_gut_group and Ruminiclostridium_1 were higher in the LRFI group (P < 0.01), as were the relative abundances of norank_f__Bacteroidales_S24-7_group, Lachnospiraceae_ND3007_group, and Lachnospiraceae_NK3A20_group (P < 0.05). Moreover, the genera Rikenellaceae_RC9_gut_group, Ruminococcaceae_NK4A214_group, Christensenellaceae_R-7_group, Ruminococcaceae_UCG-010, Lachnospiraceae_ND3007_group, Ruminiclostridium_1, and Lachnospiraceae_NK3A20_group were negatively associated with the RFI; both foundational and key species are associated with feed efficiency phenotype. In addition, rumen metabolomics analysis revealed that the RFI was associated with significantly altered concentrations of rumen metabolites involved in protein digestion and absorption, Linoleic acid metabolism, Lysine degradation, and Fatty acid degradation. Correlation analysis revealed the potential relationships between the significantly differential ruminal metabolites and the genera ruminal bacteria. The present study provides a better understanding of rumen bacteria and metabolites of beef cattle with different RFI phenotypes and the relationships among them, which are potentially important for the improvement of beef cattle feed efficiency.