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1.
Pancreatology ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38853072

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the digestive malignancy with poor prognosis, and there is still a lack of effective diagnostic biomarkers. OBJECTIVE: We aimed to explore the diagnostic efficiency of DNA methylation in peripheral blood monocytes (PBMCs) in PDAC. METHODS: 850K BeadChips were used to detect genome-wide methylation of PBMCs. For the selected sites, MethylTarget assays was used for further verification. The support vector machine was used to establish the combined panel. RESULTS: A total of 167 PDAC patients and 113 healthy controls were included in this study and were divided into three sets. In the discovery set, we found 4625 differentially methylated positions (DMPs) between cancer group and healthy controls. ZFHX3 (0.16 ± 0.04 vs. 0.18 ± 0.04, P = 0.001), cg01904886 (0.84 ± 0.05 vs. 0.81 ± 0.04, P = 0.02) and NUMBL (0.96 ± 0.005 vs. 0.957 ± 0.005, P = 0.04) were found to be significantly different in training set. The locus with more significant differences, namely ZFHX3, was used for further validation and to establish a combined diagnostic panel with CA19-9. In the validation set, the ROC curve indicated that the AUC value of ZFHX3 was 0.75. The AUC value of the combined model (AUC = 0.92) was higher than that of CA19-9 alone (AUC = 0.88). In patients with normal CA19-9 levels, the ZFHX3 methylation biomarker still maintained good diagnostic efficacy (AUC = 0.71). CONCLUSION: Our study preliminarily suggests that ZFHX3 methylation combined with CA19-9 can improve the detection rate of PDAC. Especially in patients with normal CA19-9, ZFHX3 methylation can maintain stable diagnostic efficacy. The diagnostic value of ZFHX3 methylation still needs to be prospectively validated.

2.
Front Cell Infect Microbiol ; 14: 1374238, 2024.
Article in English | MEDLINE | ID: mdl-38774627

ABSTRACT

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system with the worst prognosis. Even after radical surgery, the majority of patients with GBC have difficulty achieving a clinical cure. The risk of tumor recurrence remains more than 65%, and the overall 5-year survival rate is less than 5%. The gut microbiota refers to a variety of microorganisms living in the human intestine, including bacteria, viruses and fungi, which profoundly affect the host state of general health, disease and even cancer. Over the past few decades, substantial evidence has supported that gut microbiota plays a critical role in promoting the progression of GBC. In this review, we summarize the functions, molecular mechanisms and recent advances of the intestinal microbiota in GBC. We focus on the driving role of bacteria in pivotal pathways, such as virulence factors, metabolites derived from intestinal bacteria, chronic inflammatory responses and ecological niche remodeling. Additionally, we emphasize the high level of correlation between viruses and fungi, especially EBV and Candida spp., with GBC. In general, this review not only provides a solid theoretical basis for the close relationship between gut microbiota and GBC but also highlights more potential research directions for further research in the future.


Subject(s)
Bacteria , Gallbladder Neoplasms , Gastrointestinal Microbiome , Humans , Gallbladder Neoplasms/microbiology , Bacteria/classification , Bacteria/isolation & purification , Animals , Dysbiosis/microbiology , Virulence Factors , Fungi/pathogenicity , Fungi/classification
3.
ACS Nano ; 18(21): 13818-13828, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38748457

ABSTRACT

Ion transport efficiency, the key to determining the cycling stability and rate capability of all-solid-state lithium metal batteries (ASSLMBs), is constrained by ionic conductivity and Li+-migration ability across the multicomponent phases and interfaces in ASSLMBs. Here, we report a robust strategy for the large-scale fabrication of a practical solid electrolyte composite with high-throughput linear Li+-transport channels by compositing an all-trans block copolymer PVDF-b-PTFE matrix with ferroelectric BaTiO3-TiO2 nanofiber films. The electrolyte shows a sustainable electromechanical-coupled deformability that enables the rapid dissociation of anions with Li+ to create more movable Li+ ions and spontaneously transform the battery internal strain into Li+-ion migration kinetic energy. The ceramic framework homogenizes the interfacial potential with electrodes, endowing the electrolyte with a high conductivity of 0.782 mS·cm-1 and stable ion transport ability in ASSLMBs at room temperature. The batteries of LiFePO4/Li can stably cycle 1000 times at 0.5 C with a high capacity retention of 96.1%, and Ah-grade pouch or high-voltage Li(Ni0.8Mn0.1Co0.1)O2/Li batteries also exhibit excellent rate capability and cycling performance.

4.
J Environ Manage ; 360: 121108, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38754189

ABSTRACT

A novel air-lifting loop reactor combines anoxic, oxic, and settling zones to achieve organic and nutrient removal, as well as solid-liquid separation. To address sludge settling ability and operation stability issues caused by low dissolved oxygen in aerobic zones, this study proposes using modified polypropylene carriers to establish a fixed-film activated sludge (IFAS) system. A pilot-scale demonstration of the IFAS-based air-lifting loop reactor is conducted, and the results show successful operation for approximately 300 days. The pilot-scale reactor achieves a maximum aerobic granulation ratio of 16% in the bulk liquid. The IFAS system contributes to efficient removal of organic matter (96%) and nitrogen (94%) by facilitating simultaneous nitrification and denitrification, as well as fast solid-liquid separation with a low sludge volume index of 34 mL/g. Microbial analysis reveals enrichment of functional bacteria involved in nitrification, denitrification, and flocculation throughout the operation process.


Subject(s)
Bioreactors , Nitrogen , Sewage , Waste Disposal, Fluid , Wastewater , Waste Disposal, Fluid/methods , Wastewater/chemistry , Denitrification , Nitrification , Pilot Projects
5.
Front Endocrinol (Lausanne) ; 15: 1281622, 2024.
Article in English | MEDLINE | ID: mdl-38524630

ABSTRACT

Background: CXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4. Methods: This study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis. Results: 100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P<0.001), and Carcinoembryonic Antigen (CEA) elevation (P=0.008) between neuroendocrine tumor (NET) G3 and neuroendocrine carcinoma (NEC). CXCR4 was highly expressed only in tumors, low or no expressed in adjacent tissues (P<0.001). The expression level of CXCR4 in NEC was significantly higher than that in NET G3 (P=0.038). The K-M curves showed that there was no significant difference in overall survival between patients with high CXCR4 expression and patients with low CXCR4 expression, either in GEP-NEN G3 or NEC (P=0.920, P=0.842. respectively). Conclusion: Differential expression of CXCR4 was found between tumor and adjacent tissues and between NET G3 and NEC. Our results demonstrated that CXCR4 can be served as a new IHC diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multi-center, large sample size and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis.


Subject(s)
Carcinoma, Neuroendocrine , Intestinal Neoplasms , Neuroendocrine Tumors , Pancreatic Neoplasms , Stomach Neoplasms , Humans , Receptors, CXCR4 , Retrospective Studies , Intestinal Neoplasms/pathology , Stomach Neoplasms/pathology , Pancreatic Neoplasms/pathology , Neuroendocrine Tumors/pathology , Carcinoma, Neuroendocrine/pathology
7.
Front Microbiol ; 15: 1275865, 2024.
Article in English | MEDLINE | ID: mdl-38419639

ABSTRACT

Introduction: The dietary protein level plays a crucial role in maintaining the equilibrium of rumen microbiota in yaks. To explore the association between dietary protein levels, rumen microbiota, and muscle metabolites, we examined the rumen microbiome and muscle metabolome characteristics in yaks subjected to varying dietary protein levels. Methods: In this study, 36 yaks were randomly assigned to three groups (n = 12 per group): low dietary protein group (LP, 12% protein concentration), medium dietary protein group (MP, 14% protein concentration), and high dietary protein group (HP, 16% protein concentration). Results: 16S rDNA sequencing revealed that the HP group exhibited the highest Chao1 and Observed_species indices, while the LP group demonstrated the lowest. Shannon and Simpson indices were significantly elevated in the MP group relative to the LP group (P < 0.05). At the genus level, the relative abundance of Christensenellaceae_R-7_group in the HP group was notably greater than that in the LP and MP groups (P < 0.05). Conversely, the relative abundance of Rikenellaceae_RC9_gut_group displayed an increasing tendency with escalating feed protein levels. Muscle metabolism analysis revealed that the content of the metabolite Uric acid was significantly higher in the LP group compared to the MP group (P < 0.05). The content of the metabolite L-(+)-Arabinose was significantly increased in the MP group compared to the HP group (P < 0.05), while the content of D-(-)-Glutamine and L-arginine was significantly reduced in the LP group (P < 0.05). The levels of metabolites 13-HPODE, Decanoylcarnitine, Lauric acid, L-(+)-Arabinose, and Uric acid were significantly elevated in the LP group relative to the HP group (P < 0.05). Furthermore, our observations disclosed correlations between rumen microbes and muscle metabolites. The relative abundance of NK4A214_group was negatively correlated with Orlistat concentration; the relative abundance of Christensenellaceae_R-7_group was positively correlated with D-(-)-Glutamine and L-arginine concentrations. Discussion: Our findings offer a foundation for comprehending the rumen microbiome of yaks subjected to different dietary protein levels and the intimately associated metabolic pathways of the yak muscle metabolome. Elucidating the rumen microbiome and muscle metabolome of yaks may facilitate the determination of dietary protein levels.

8.
J Gene Med ; 26(1): e3649, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38282155

ABSTRACT

BACKGROUND: Ovarian cancer is one of the most common cancers in women. Profiles changes of microRNAs (miRNAs) are closely linked to malignant tumors. In the present study, we investigated expression of miR-451a in high-grade serous ovarian cancer (HGSOC). We also investigated the potential pathological roles and the likely mechanism of miR-451a in the development of HGSOC using animal models and cell lines. METHODS: Using bioinformatics techniques and a real-time PCR, we analyzed differently expressed miRNAs in HGSOC compared to normal tissue. MTT (i.e. 3-[4, 5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide), EDU (i.e. 5-ethynyl-2'-deoxyuridine) and transwell assays were performed to investigate the effect of miR-451a on the proliferation and migration of HGSOC SKOV-3 cells. A dual luciferase reporter assay was performed to verify the targeting relationship of miR-451 and RAB5A (one of the Rab GTPase proteins that regulates endocytosis and vesicle transport). Also, we analyzed levels of the RAB5A mRNA and protein by real-time PCR, western blotting and immunohistochemistry assays in HGSOC cells and tissues. Finally, we performed in vivo experiments using HGSOC mice. RESULTS: miR-451a was substantially upregulated in HGSOC and associated with favorable clinical characteristics. miR-451a knockdown significantly increased growth and metastasis of HGSOC cell line SKOV-3 through Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. In addition, RAB5A, an early endosome marker, was shown to be a direct target of miR-451a. Moreover, RAB5A is correlated with unfavorable clinical features and shows independent prognostic significance in HGSOC. CONCLUSIONS: We found that the miR-451a/RAB5A axis is associated with tumorigenesis and progression through the Ras/Raf/MEK/ERK pathway, providing prognostic indicators and therapeutic targets for patients with HGSOC.


Subject(s)
MicroRNAs , Ovarian Neoplasms , rab5 GTP-Binding Proteins , Animals , Female , Humans , Mice , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Expression Regulation, Neoplastic , MAP Kinase Signaling System/genetics , MicroRNAs/genetics , Mitogen-Activated Protein Kinase Kinases/genetics , Ovarian Neoplasms/genetics , rab5 GTP-Binding Proteins/genetics
11.
J Environ Manage ; 351: 119869, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38142596

ABSTRACT

The stacking of phosphogypsum has caused considerable phosphorus pollution in water bodies near phosphogypsum yards through surface runoff and underground infiltration. The phosphate oxygen isotope (δ18Op) tracing method has served as a valuable tool for tracing phosphorus pollution in water. However, the existing δ18Op enrichment and purification methods are complex, costly, and inefficient for phosphate recovery, particularly for phosphogypsum leachate with complex compositions. Herein, a simplified and optimized pretreatment method for δ18Op measurement in phosphogypsum leachate was developed. Zirconium/polyvinyl alcohol (Zr/PVA) gel beads showed good selectivity for phosphate enrichment from water at different initial phosphate concentrations with appropriate Zr/PVA dosage. The optimal enrichment pH value was <7, and the concentrated phosphate on the Zr/PVA gel beads could be effectively eluted in an alkaline environment. Compared with the traditional Fe or Mg coprecipitation enrichment methods, impurities in the solution showed no obvious adverse effects on the phosphate enrichment process. Further, the phosphate solution eluted from the Zr/PVA gel beads was purified by a simple adjustment of the pH instead of cation exchange in the traditional purification process. Magnesium ions in the solution could be completely removed when the pH ranged from 3.17 to 6.15, and the phosphate recovery rate could reach 98.66% when the eluent pH was 5.02. Fourier-transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy revealed that similar to traditional pretreatment method, the proposed method can obtain high-purity Ag3PO4 solids for δ18OP measurement and no isotope fractionation of δ18OP was observed. Therefore, this study provides a promising and reliable pretreatment method for δ18OP measurement, especially in complex phosphogypsum leachate.


Subject(s)
Calcium Sulfate , Phosphates , Phosphorus , Oxygen Isotopes , Phosphorus/chemistry , Water
12.
Sci Rep ; 13(1): 21501, 2023 12 06.
Article in English | MEDLINE | ID: mdl-38057444

ABSTRACT

Polyethylene glycol-coated magnetic nanoparticles (PEGylated MNPs) have demonstrated prominent advantages in cancer diagnosis and hyperthermia therapy. However, there is currently lack of standard mode and sufficient toxicity data for determining the delayed risk of PEGylated MNPs. Nevertheless, the toxicity potentials, especially those associated with the oxidative stress, were ubiquitously reported. In this study, PEGylated MNPs and p-PEGylated MNPs were administrated to SD (Sprague Dawley) rats by single intravenously injection, and various toxicity indicators were monitored till 56 days post-administration for a comprehensive toxicity evaluation. We revealed that both nanoparticles could be rapidly cleared from plasma and enter tissues, such as, liver, kidneys and spleen, and p-PEGylated MNP is less prone to be accumulated in the tissues, indicating a lower toxicity risk. PEGylated MNPs were more likely to up-regulate the expression levels of Th2 type cytokines and trigger inflammatory pathways, but no related pathological change was found. Both MNPs are not mutagenic, while recoverable mild DNA damage associated with the presence of nanoparticles might also be observed. This study demonstrated a research approach for the non-clinical safety evaluation of nanoparticles. It also provided comprehensive valuable safety data for PEGylated and p-PEGylated MNPs, for promoting the clinical application and bio-medical translation of such MNPs with PEG modifications in the cancer diagnosis and therapy.


Subject(s)
Magnetite Nanoparticles , Neoplasms , Rats , Animals , Magnetite Nanoparticles/therapeutic use , Rats, Sprague-Dawley , Liver , Polyethylene Glycols
13.
J Transl Int Med ; 11(4): 401-409, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38130646

ABSTRACT

Background and Objectives: Non-hepatic hyperammonemia can damage the central nervous system (CNS), and possible prognostic factors are lacking. This study aimed to investigate the prognostic and risk factors for patients admitted to the intensive care unit (ICU). Materials and Methods: This prospective, observational, multicenter study was conducted between November and December 2019 at 11 ICUs in the Chinese Heilongjiang province. Changes in blood ammonia level during and after ICU admission were continuously monitored and expressed as the high level (H-), mean level (M-), and initial level (I-) of ammonia. The risk factors of poor prognosis were investigated by conducting univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive ability of Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE-II) score, lactic acid, total bilirubin (TBil), and M-ammonia. Results: A total of 1060 patients were included in this study, of which 707 (67%) had a favorable prognosis and 353 (33%) had a poor prognosis. As shown by univariate models, a poor prognosis was associated with elevated serum levels of lactic acid, TBil, and ammonia (P < 0.05) and pathologic scores from three assessments: APACHE-II, Glasgow Coma Scale (GCS), and Sequential Organ Failure Assessment (SOFA). Multivariate analysis revealed that circulating mean ammonia levels in ICU patients were independently associated with a poor prognosis (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.07-2.80, P = 0.02). However, the APACHE-II score (area under the curve [AUC]: 0.714, sensitivity: 0.86, specificity: 0.68, P < 0.001) remained the most predictive factor for patient prognosis by ROC analysis. Conclusion: Elevated serum levels of ammonia in the blood were independently prognostic for ICU patients without liver disease.

14.
Heliyon ; 9(10): e20546, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37867853

ABSTRACT

Background: The use of noninvasive ventilation (NIV) during and after extubation is common. We designed this study to determine the optimal strategy to compensate for mask leaks and achieve effective ventilation during NIV by comparing commonly used operating room ventilator systems and a regular facemask. Methods: We tested four operating room ventilator systems (Dägger Zeus, Dägger Apollo, Dägger Fabius Tiro, and General Electric Healthcare Carestation 650) on a lung model with normal compliance and airway resistance and evaluated pressure control ventilation (PCV), volume control ventilation (VCV), and AutoFlow mode (VAF). We set the O2 flow at 10 L/min and the maximal flow at 13, 16, or 26 L/min. We simulated five leak levels, from no leak to over 40 L/min (I to V levels), using customized T-pieces placed between the lung model and the breathing circuit. We recorded the expired tidal volume (Vte) from the lung model and peak inspiratory pressure via two flow/pressure sensors that were placed distally and proximally to the T-pieces. Results: 1. Comparison of four ventilators: with any given ventilation mode, an increase in leak level caused a decrease in Vte. With PCV, only Zeus produced Vte larger than 150 ml at leak level V. 2. Effect of ventilation mode on Vte: across all four ventilators, PCV resulted in a higher Vte than VCV and VAF (P < 0.01). PCV mode with all ventilators at leak level II provided Vte values that were equal to or greater than those obtained with no leak. 3. Effect of O2 flow on Vte Using PCV mode: only Carestation 650 Vte at leak level II during PCV were significantly greater with 16 L/min O2 flow compared with 10 L/min O2 flow (P < 0.01). 4. Actual leak: increasing the O2 flow from 10 L/min to the maximum O2 flow dramatically increased the real leak with all 4 ventilators at any fixed leak level (P < 0.01). 5. Preset PIP vs. actual PIP with PCV: at low preset PIP and leak levels such as leak II and III, the discrepancy between preset PIP and actual PIP was small. The disparity between the preset and actual PIP grew when the target PIP and the leak level were raised. Conclusion: For NIV using a mask, the ventilator is preferred whose Pressure generator is Turbine, the PCV mode is preferred in the ventilation mode and the oxygen flow is set to 10 L/min or maximum oxygen flow.

15.
Inorg Chem ; 62(41): 16825-16831, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37779255

ABSTRACT

By harnessing the power of coordination self-assembly, crystalline materials can act as carriers for photoacids. Unlike their solution-based counterparts, these photoacids are capable of altering the properties of the crystalline material under light and can even generate proton transfer in a solid-state environment. Due to the photoinduced proton transfer and charge transfer processes within this functional material, this crystal exhibits powerful absorption spanning the visible to near-infrared spectrum upon light irradiation. This feature enables reproducible, significant chromatic variation, near-infrared photothermal conversion, and photocontrollable conductivity for this photoresponsive material. The findings suggest that the synthesis of pyranine photoacid-based crystalline materials via coordination self-assembly can not only enhance light-harvesting efficiency but also enable excited-state proton transfer processes within solid crystalline materials, thereby maintaining and even improving the properties of photoacids.

16.
Free Radic Biol Med ; 209(Pt 1): 70-83, 2023 11 20.
Article in English | MEDLINE | ID: mdl-37806597

ABSTRACT

The gut microbiota plays a crucial role in maintaining host nutrition, metabolism, and immune homeostasis, particularly in extreme environmental conditions. However, the regulatory mechanisms of the gut microbiota in animal organisms hypobaric hypoxia exposure require further study. We conducted a research by comparing SD rats treated with an antibiotic (ABX) cocktail and untreated SD rats that were housed in a low-pressure oxygen chamber (simulating low pressure and hypoxic environment at 6000 m altitude) for 30 days. After the experiment, blood, feces, and lung tissues from SD rats were collected for analysis of blood, 16S rRNA amplicon sequencing, and non-targeted metabolomics. The results demonstrated that the antibiotic cocktail-treated SD rats exhibited elevated counts of neutrophil (Neu) and monocyte (Mon) cells, an enrichment of sulfate-reducing bacteria (SBC), reduced levels of glutathione, and accumulated phospholipid compounds. Notably, the accumulation of phospholipid compounds, particularly lysophosphatidic acid (LPA), lipopolysaccharide (LPS), and lysophosphatidylcholine (LPC), along with the aforementioned changes, contributed to heightened oxidative stress and inflammation in the organism. In addition, we explored the resistance mechanisms of SD rats in low-oxygen and low-pressure environments and found that increasing the quantity of the Prevotellaceae and related beneficial bacteria (especially Lactobacillus) could reduce oxidative stress and inflammation. These findings offer valuable insights into enhancing the adaptability of low-altitude animals under hypobaric hypoxia exposure.


Subject(s)
Hypoxia , Oxidative Stress , Rats , Animals , RNA, Ribosomal, 16S/genetics , Rats, Sprague-Dawley , Hypoxia/drug therapy , Hypoxia/metabolism , Oxygen , Inflammation , Phospholipids
18.
Front Microbiol ; 14: 1247251, 2023.
Article in English | MEDLINE | ID: mdl-37700865

ABSTRACT

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.

19.
Cancer Lett ; 575: 216403, 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37741433

ABSTRACT

Obesity is an essential risk factor for pancreatic cancer (PC). Macrophage-induced inflammation plays a pivotal role in obesity-associated carcinogenesis and disease progression; however, the underlying molecular mechanisms remain unclear. In this study, we found that fatty acid-binding protein 4 (FABP4) overexpressed in serum of obese patients and was associated with poor overall survival. In vivo and in vitro experiments have revealed that FABP4 induces macrophage-related inflammation to promote cancer cell migration, invasion and metastasis under obese conditions. Mechanistically, FABP4 participates in transferring saturated fatty acid to induce macrophages pyroptosis in a caspase-1/GSDMD-dependent manner and mediates NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/IL-1ß axis in macrophages, which further regulates epithelial-mesenchymal transition signals to promote the migration, invasion, and metastasis of PC cells. Our results suggest that FABP4 in macrophages is a crucial regulator of the NLRP3/IL-1ß axis to promote the progression of PC under obese conditions, which could act as a promising molecular target for treating of PC patients with obesity.

20.
Microorganisms ; 11(8)2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37630524

ABSTRACT

A relatively stable microbial ecological balance system in the rumen plays an important role in rumen environment stability and ruminant health maintenance. No studies have reported how rumen fluid transplantation (RFT) affects the composition of rumen microorganisms and yak growth performance. In this experiment, we transplanted fresh rumen fluid adapted to house-feeding yaks to yaks transitioned from natural pastures to house-feeding periods to investigate the effects of rumen fluid transplantation on rumen microbial community regulation and production performance. Twenty yaks were randomly divided into the control group (CON; n = 10) and the rumen fluid transplantation group (RT; n = 10). Ten yaks that had been adapted to stall fattening feed in one month were selected as the rumen fluid donor group to provide fresh rumen fluid. Ruminal fluid transplantation trials were conducted on the 1st, 3rd, and 5th. Overall, 1 L of ruminal fluid was transplanted to each yak in the RT and CON group. The formal trial then began with both groups fed the same diet. After this, growth performance was measured, rumen fluid was collected, and rumen microbial composition was compared using 16s rRNA sequencing data. The results showed that rumen fluid transplantation had no significant effect on yak total weight gain or daily weight gain (p > 0.05), and feed efficiency was higher in the RT group than in the CON group at 3 months (treatment × month: p < 0.01). Ruminal fluid transplantation significantly affected rumen alpha diversity (p < 0.05). Up to day 60, the RT group had significantly higher OTU numbers, Shannon diversity, and Simpson homogeneity than the CON group. Principal coordinate analysis showed that the rumen microbiota differed significantly on days 4 and 7 (p < 0.05). Bacteroidota, Firmicutes, Proteobacteria, and Spirochaetes were the most abundant phyla in the rumen. The relative abundances of Bacteroidota, Proteobacteria, and Spirochaetes were lower in the RT group than in the CON group, with a decrease observed in Bacteroidota in the RT group on days 7 and 28 after rumen fluid transplantation (p = 0.013), while Proteobacteria showed a decreasing trend in the CON group and an increasing trend in RT; however, this was only at day 4 (p = 0.019). The relative abundance of Firmicutes was significantly higher in the RT group than in the CON group on days 4, 7, and 28 (p = 0.001). Prevotella and Rikenellaceae_RC9_gut_group were the predominant genera. In conclusion, our findings suggest that rumen fluid transplantation improves yak growth performance and rumen microbial reshaping. The findings of this study provide new insights into yak microbial community transplantation and a reference for improving feed efficiency in the yak industry.

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