The impact of high polymerization inulin on body weight reduction in high-fat diet-induced obese mice: correlation with cecal Akkermansia.

Obesity presents a significant public health challenge, demanding effective dietary interventions. This study employed a high-fat diet-induced obesity mouse model to explore the impacts of inulin with different polymerization degrees on obesity management. Our analysis reveals that high-degree polymerization inulin (HDI) exhibited a significantly higher oil binding capacity and smaller particle size compared to low-degree polymerization inulin (LDI) (p < 0.05). HDI was more effective than LDI in mitigating body weight gain in high-diet induced obese mice, although neither LDI nor HDI affected blood sugar levels when compared to the high-fat diet control group (p < 0.05). Both HDI and LDI administrations reduced liver weight and enhanced brown adipose tissue thermogenesis compared to the high-fat diet induced control group (p < 0.05). Additionally, HDI suppressed hepatic lipogenesis, resulting in a further reduction in liver triglycerides compared to the high-fat diet-induced obese mice (p < 0.05). Notably, HDI improved gut health by enhancing intestinal morphology and modulating gut microbiota structure. HDI administration notably increased the relative abundance of cecal Akkermansia, a gut microbe associated with improved metabolic health, while LDI showed limited efficacy (p < 0.05 and p > 0.05, respectively). These findings underscore the importance of the structural properties of inulin in its potential to combat obesity and highlight the strategic use of inulin with varying polymerization degrees as a promising dietary approach for obesity management, particularly in its influence on gut microbiota composition and hepatic lipid metabolism regulation.

ß-Cyclodextrin based magnetic hyper-crosslinked polymer: A recyclable adsorbent for effective preconcentration of triazine herbicides in complex sample matrices.

High efficiency enrichment and trace analysis of triazine herbicide residues are crucial for ensuring environmental and food safety. Herein, a series of magnetic hyper-crosslinked polymers (CD-gs-MHCPs) were synthesized with different crosslinkers, which might possess different pore structure and surface area, so they might dispay variable adsorption performance. CD-gs-MHCP2 with dichloroxylene as crosslinker delivered superior adsorption ability for triazine herbicides (THs). The synergistic effect of hydrogen bonds, hydrophobic interaction, π-π stacking interaction and pore adsorption were proved to be the main adsorption mechanism. Combined CD-gs-MHCP2 based magnetic solid-phase extraction (MSPE) with high-performance liquid chromatography, the quantitative analysis of THs in river water and vegetable samples (zucchini, pakchoi) was achieved. Under the optimal conditions, the enrichment factors for three different samples ranged from 94 to 244 and low detection limit (S/N = 3) of the four THs were obtained from 0.05 to 0.15 ng mL-1 for river water and 0.31-3.10 ng g-1 for vegetable samples. The method recoveries were in the range of 86.2 %-120 % with relative standard deviations lower than 7.4 %. This work not only offers a new strategy for fabrication ß-CD-based HCPs, but also provided a practical and effective method for efficient isolation and sensitive detection of trace THs residues in complex samples.

Identification and Analysis of Differentially Expressed Genes Associated with Ferroptosis an d HIV in PASMCs Based on Bioinformatics.

BACKGROUND: HIV-associated pulmonary arterial hypertension (HIV-PAH), a rare and fatal condition within the pulmonary arterial hypertension spectrum, is linked to HIV infection. While ferroptosis, an iron-dependent cell death form, is implicated in various lung diseases, its role in HIVPAH development remains unclear. METHODS: Leveraging Gene Expression Omnibus data, we identified differentially expressed genes (DEGs) in pulmonary arterial smooth muscle cells, including HIV-related DEGs (HIV-DEGs) and ferroptosis-related HIV-DEGs (FR-HIV-DEGs). PPI network analysis of FR-HIV-DEGs using CytoHubba in Cytoscape identified hub genes. We conducted functional and pathway enrichment analyses for FR-HIV-DEGs, HIV-DEGs, and hub genes. Diagnostic value assessment of hub genes utilized ROC curve analysis. Key genes were further screened, and external validation was performed. Additionally, we predicted a potential ceRNA regulatory network for key genes. RESULTS: 1372 DEGs were found, of which 228 were HIV-DEGs, and 20 were FR-HIV-DEGs. TP53, IL6, PTGS2, IL1B (downregulated), and PPARG (upregulated) were the five hub genes that were screened. TP53, IL6, and IL1B act as ferroptosis drivers, PTGS2 as a ferroptosis marker, and PPARG as a ferroptosis inhibitor. Enrichment analysis indicated biological processes enriched in "response to oxidative stress" and pathways enriched in "human cytomegalovirus infection." Key genes IL6 and PTGS2 exhibited strong predictive value via ROC curve analysis and external validation. The predicted ceRNA regulatory network identified miRNAs (has-mir-335-5p, has-mir-124-3p) targeting key genes and lncRNAs (XIST, NEAT1) targeting these miRNAs. CONCLUSION: This study advances our understanding of potential mechanisms in HIV-PAH pathogenesis, emphasizing the involvement of ferroptosis. The findings offer valuable insights for future research in HIV-PAH.

Microencapsulated Lactobacillus plantarum promotes intestinal development through gut colonization of layer chicks.

The effects of Lactobacillus plantarum in microencapsulation (LPM) on intestinal development in layer chicks were investigated in this study, as well as the colonization of L. plantarum in the gut. A total of 480 healthy Hy-Line Brown layer chicks at 0 d old were randomly divided into 4 groups (8 replicates each treatment), and the diets of these birds were supplemented with nothing (control), L. plantarum (0.02 g/kg feed; 109 CFU/kg feed), LPM (1.0 g/kg feed; 109 CFU/kg feed) and wall material of LPM (WM; 0.98 g/kg feed), respectively. Compared to control, LPM improved growth performance and intestinal development of layer chicks, evidenced by significantly increased body weight, average daily gain, average daily feed intake, villus height, villus height/crypt depth, as well as weight and length of the duodenum, jejunum and ileum (P < 0.05). These results could be attributed to the increased colonization of L. plantarum in the gut, which was verified by significant increases in lactic acid content, viable counts in chyme and mucosa (P < 0.05), as well as a visible rise in number of strains labeled with fluorescein isothiocyanate. Meanwhile, the relative abundances of Lactobacillus and Bifidobacterium significantly increased in response to microencapsulated L. plantarum supplementation (P < 0.05), accompanied by the significant up-regulation of colonization related genes (P < 0.05), encoding solute carrier family, monocarboxylate transporter, activin A receptor, succinate receptor and secretogranin II. To sum up, microencapsulated L. plantarum supplementation promoted intestinal development, which could be attributed to the enhancement of L. plantarum colonization in the intestine through the mutual assistance of Bifidobacterium and interactions with colonization related transmembrane proteins.

Comparison of the variability and diagnostic efficacy of respiratory-gated PET/CT based radiomics features with ungated PET/CT in lung lesions.

OBJECTIVES: To investigate the variability and diagnostic efficacy of respiratory-gated (RG) PET/CT based radiomics features compared to ungated (UG) PET/CT in the differentiation of non-small cell lung cancer (NSCLC) and benign lesions. METHODS: 117 patients with suspected lung lesions from March 2020 to May 2021 and consent to undergo UG PET/CT and chest RG PET/CT (including phase-based quiescent period gating, pQPG and phase-matched 4D PET/CT, 4DRG) were prospectively included. 377 radiomics features were extracted from PET images of each scan. Paired t test was used to compare UG and RG features for inter-scan variability analysis. We developed three radiomics models with UG and RG features (i.e. UGModel, pQPGModel and 4DRGModel). ROC curves were used to compare diagnostic efficiencies, and the model-level comparison of diagnostic value was performed by five-fold cross-validation. A P value < 0.05 was considered as statistically significant. RESULTS: A total of 111 patients (average age ± standard deviation was 59.1 ± 11.6 y, range, 29 - 88 y, and 63 were males) with 209 lung lesions were analyzed for features variability and the subgroup of 126 non-metastasis lesions in 91 patients without treatment before PET/CT were included for diagnosis analysis. 101/377 (26.8 %) 4DRG features and 82/377 (21.8 %) pQPG features showed significant difference compared to UG features (both P<0.05). 61/377 (16.2 %) and 59/377 (15.6 %) of them showed significantly better discriminant ability (ΔAUC% (i.e. (AUCRG - AUCUG) / AUCUG×100 %) > 0 and P<0.05) in malignant recognition, respectively. For the model-level comparison, 4DRGModel achieved the highest diagnostic efficacy (sen 73.2 %, spe 87.3 %) compared with UGModel (sen 57.7 %, spe 76.4 %) and pQPGModel (sen 63.4 %, spe 81.8 %). CONCLUSION: RG PET/CT performs better in the quantitative assessment of metabolic heterogeneity for lung lesions and the subsequent diagnosis in patients with NSCLC compared with UG PET/CT.

Strategies to improve the therapeutic efficacy of mesenchymal stem cell-derived extracellular vesicle (MSC-EV): a promising cell-free therapy for liver disease.

Liver disease has emerged as a significant worldwide health challenge due to its diverse causative factors and therapeutic complexities. The majority of liver diseases ultimately progress to end-stage liver disease and liver transplantation remains the only effective therapy with the limitations of donor organ shortage, lifelong immunosuppressants and expensive treatment costs. Numerous pre-clinical studies have revealed that extracellular vesicles released by mesenchymal stem cells (MSC-EV) exhibited considerable potential in treating liver diseases. Although natural MSC-EV has many potential advantages, some characteristics of MSC-EV, such as heterogeneity, uneven therapeutic effect, and rapid clearance in vivo constrain its clinical translation. In recent years, researchers have explored plenty of ways to improve the therapeutic efficacy and rotation rate of MSC-EV in the treatment of liver disease. In this review, we summarized current strategies to enhance the therapeutic potency of MSC-EV, mainly including optimization culture conditions in MSC or modifications of MSC-EV, aiming to facilitate the development and clinical application of MSC-EV in treating liver disease.

Ratiometric Fluorescence and Afterglow Lifetime Dual-Channel Nanoprobe for Simultaneous Imaging of HOCl and Temperature in Arthritis.

Arthritis is a joint disorder that potentially causes permanent joint damage and eventual disability without effective treatment. Clinical detection methods, including in vitro blood tests and anatomical imaging, still have limitations in achieving real-time in situ early detection of arthritis. In this work, a dual-channel luminescence nanoprobe (AGNPs-Cy7) is reported, which combines a cyanine dye and a photochemical reaction-based afterglow system for real-time in vivo imaging of arthritis. AGNPs-Cy7 simultaneously detect hypochlorous acid (HOCl) and temperature, two important indicators associated with the early development of arthritis, by monitoring the respective changes in independent ratiometric fluorescence and afterglow lifetime signals. The anti-interference properties of both the ratiometric fluorescence signal and afterglow lifetime signal enhance sensing accuracy compared to the single luminescence intensity. The developed probe successfully reveals the simultaneous increase in HOCl concentration and temperature in an arthritis mouse model.

Osseointegration of titanium implants after surface treatment with ultraviolet light or cold atmospheric plasma in vivo.

PURPOSE: To determine the histological effects of ultraviolet light and cold atmospheric plasma treatment on the osseointegration of titanium implants in vivo. MATERIALS AND METHODS: Six juvenile pigs were divided into three groups of two animals each. A total of 54 titanium implants were placed randomly in the pigs' calvarial bone (nine implants per pig). Of these, 18 implants served as untreated controls. The remaining 36 implants served as the experimental group and were treated with either ultraviolet light or argon plasma for 12 minutes each prior to insertion. Two pigs in each group were kept until 2, 4 and 8 weeks and then sacrificed. Resonance frequency analysis was conducted after implant placement and at the time of sacrifice. Osseointegration was evaluated using microcomputed tomography scans and histomorphometrical analysis. RESULTS: After initial loss, all implants showed a constant increase in implant stability quotient values over time without significant differences between the groups. The bone-implant contact values increased steadily for all implants over 8 weeks of healing. Surface-treated implants showed significantly higher bone-implant contact values compared to untreated implants at each time point. Bone area fraction occupancy values were almost always higher following both treatment methods; however, differences were only significant after 4 and 8 weeks for the cold atmospheric plasma group and after 4 weeks for the ultraviolet light group. CONCLUSIONS: Ultraviolet light and cold atmospheric plasma may improve histomorphometrical osseointegration of titanium implants significantly.

Electrocatalytic Synthesis of Pyridine Oximes using in Situ Generated NH2 OH from NO species on Nanofiber Membranes Derived from NH2 -MIL-53(Al).

Pyridine oximes produced from aldehyde or ketone with hydroxylamine (NH2 OH) have been widely applied in pharmaceutics, enzymatic and sterilization. However, the important raw material NH2 OH exhibits corrosive and unstable properties, leading to substantial energy consumption during storage and transportation. Herein, this work presents a novel method for directly synthesizing highly valuable pyridine oximes using in situ generated NH2 OH from electrocatalytic NO reduction with well-design nanofiber membranes (Al-NFM) derived from NH2 -MIL-53(Al). Particularly, 2-pyridinealdoxime, the precursor of antidote pralidoxime (2-PAM) for nerve agents suffering from scarcity and high cost, was achieved with a Faraday efficiency up to 49.8 % and a yield of 92.1 %, attributing to the high selectivity of NH2 OH production on Al-NFM, further easily reacted with iodomethane to produce 2-PAM. This study proposes a creative approach, having wide universality for synthesizing pyridine and other oximes with a range of functional groups, which not only facilitates the conversion of exhaust gas (NO) and waste water (NO2 - ) into valuable chemicals especially NH2 OH production and in situ utilization through electrochemistry, but also holds significant potential for synthesis of neuro detoxifying drugs to humanity security.

Tumor Lysis Syndrome with CD20 Monoclonal Antibodies for Chronic Lymphocytic Leukemia: Signals from the FDA Adverse Event Reporting System.

BACKGROUND AND OBJECTIVE: Although tumor lysis syndrome was reported with obinutuzumab and rituximab, the association with CD20 monoclonal antibodies for chronic lymphocytic leukemia is unclear. METHODS: A disproportionality analysis was conducted to investigate the link between CD20 monoclonal antibodies and tumor lysis syndrome by accounting for known confounders and comparing with other anticancer drugs, using data from the US Food and Drug Administration Adverse Event Reporting System. Reporting odds ratios and the information component were calculated as disproportionality measures. A stepwise sensitivity analysis was conducted to test the robustness of disproportionality signals. Bradford Hill criteria were adopted to globally assess the potential causal relationship. RESULTS: From 2004 to 2022, 197, 368, 41, and 14 tumor lysis syndrome reports were detected for obinutuzumab, rituximab, ofatumumab, and alemtuzumab (CD52 monoclonal antibody), respectively. Disproportionality signals were found for the above four monoclonal antibodies when compared with other anticancer drugs. Sensitivity analyses confirmed robust disproportionality signals for obinutuzumab, rituximab, and ofatumumab. The median onset time was 4.5, 1.5, and 2.5 days for rituximab, obinutuzumab, and ofatumumab, respectively. A potential causal relationship was fulfilled by assessing Bradford Hill criteria. CONCLUSIONS: This pharmacovigilance study on the FDA Adverse Event Reporting System detected a plausible association between CD20 monoclonal antibodies (but not CD52) and tumor lysis syndrome by assessing the adapted Bradford Hill criteria. Urgent clarification of drug- and patient-related risk factors is needed through large comparative population-based studies.

Exploring the rumen microbiota of Hu lambs in response to diet with paper mulberry.

Paper mulberry (Broussonetia papyrifera), as a new woody forage with high-protein characteristic, is being widely used in ruminant feeding. However, little is known about the comprehensive microbiota picture of whole ruminal niches (liquid, solid, and epithelium) under paper mulberry diet. To gain a better understanding of feeding paper mulberry on the rumen microbiota, the effects of fresh paper mulberry, paper mulberry silage, or a conventional high-protein alfalfa silage on rumen fermentation products and microbiota in rumen niches of Hu lambs were studied. Forty-five Hu lambs were randomly divided into 3 treatments with 15 replicates in each treatment. No significant difference was observed among treatments in the average daily gain (ADG). The fresh paper mulberry treatment had lower (P < 0.05) pH and higher (P < 0.05) total volatile fatty acids (TVFA) compared with silage treatments, but the fermentation parameters did not show significant differences between paper mulberry silage and alfalfa silage treatments. The Shannon index did not show a significant difference (P < 0.05) among treatments except between fresh paper mulberry and alfalfa silage treatment in rumen epithelial niches. Butyrivibrio and Treponema were the predominant genera in the rumen epithelial fraction, while Prevotella and Rikenellaceae_RC9 dominated in both rumen liquid and solid fractions. These results indicated the paper mulberry supplement did not have distinct impact on the microbial diversity and growth performance compared with alfalfa silage, especially for paper mulberry silage, which might help us develop an alternative animal feeding strategy of replacing alfalfa with paper mulberry. KEY POINTS: • Feeding paper mulberry silage did not show significant impact on the growth performance compared with alfalfa silage treatment. • Feeding fresh paper mulberry reduced rumen pH value and increased total volatile fatty acid. • The microbial diversity did not show significant difference among treatments.

Preparation of hypercrosslinked porous polymer with manifold functional groups for sensitive determination of phenylurea herbicides in beverages and celtuce samples.

Wide use of phenylurea herbicide has caused serious residue problem and threaten human health. It is important to develop viable method for their sensitive determination. Herein, a multi-functionalized porous polymer was prepared by crosslinking hexafluorobisphenol A with pyromellitic dianhydride. Using the multi-functionalized porous polymer as solid phase extraction sorbent, combined with high performance liquid chromatography, a sensitive method was established for determining phenylurea herbicides in beverages and celtuces. High sensitivity was achieved, with method detection limit (S/N = 3) of 0.01---0.025 ng mL-1 for beverages, 1.70 ng g-1 for celtuce, and quantitation limits of 0.03---0.10 ng mL-1 for beverages, 5.00 ng g-1 for celtuce. The method recoveries were 80.5---120.0 % with relative standard deviations lower than 6.1%. Adsorption mechanism mainly involved F-π, F-O, π-π, polar interactions and hydrogen-bonding interactions. This study offers a simple protocol to develop multi-functional sorbents for extraction of organic pollutants.

Tunable Afterglow System via Controllable Photoenergy Storage and Release.

Afterglow luminescence has garnered significant attention due to its excellent optical properties. Currently, most afterglow phenomena are produced by persistent luminescence following cessation of the excitation light. However, it remains a challenge to control the afterglow luminescence process due to rapid photophysical or photochemical changes. Here, we develop a new strategy to control the afterglow luminescence process by introducing pyridones as singlet oxygen (1O2) storage reagents (OSRs), where 1O2 can be stored in covalent bonds at relatively low temperatures and released upon heating. The afterglow luminescence properties, including afterglow intensity, decay rate, and decay process, can be tuned flexibly by regulating temperature or OSR structures. Based on the controllable luminescence properties, we devise a new strategy for information security. We believe that such an excellent luminescent system also holds remarkable potential for applications in many other fields.

Design of hydroxyl-functionalized nanoporous organic polymer with tunable hydrophilic-hydrophobic surface for solid phase extraction of neonicotinoid insecticides.

As being widely used insecticides, neonicotinoid residues are toxic and harmful to human health and aquatic ecosystems. Thus, the sensitive monitoring of neonicotinoids in water and food samples is highly desirable to reduce their risks to humans. Herein, four novel hydroxyl-functionalized nanoporous organic frameworks (OH-NOP1, OH-NOP2, OH-NOP3 and OH-NOP4) with tunable hydrophilic-hydrophobic surface have been designed and fabricated for the first time by employing luteolin as monomer and 4,4'-bis(chloromethyl)-1,1'-biphenyl as crosslinker at the molar ratio of 3:1, 1:1, 1:3 and 1:6, respectively. When the molar ratio of luteolin to crosslinker was 1:3, OH-NOP3 was obtained and it presented the highest affinity with excellent adsorption performance towards the studied neonicotinoids. The adsorption mechanism was proposed to be the strong hydrogen bond, polar interaction, Lewis acid-base interaction and pore adsorption between OH-NOP3 and neonicotinoids. Then, utilizing OH-NOP3 as sorbent for solid phase extraction cartridges, an effective method for extraction and preconcentration of neonicotinoids followed by high performance liquid chromatography analysis has been developed for quantitative detection of neonicotinoids from water and edible fungi. The method provided good linearity over the range of 0.06-100.0 ng mL-1 for lake water, 1.5-100.0 ng g-1 for pleurotus eryngii and sea-shroom. Low detection limit (at the signal to noise ratio of 3) was achieved in the range of 0.02-0.08 ng mL-1 for water, 0.50-0.60 ng g-1 for pleurotus eryngii and 0.50-0.80 ng g-1 for sea-shroom, while the limit of quantification was 0.06-0.25 ng mL-1, 1.50-1.80 ng g-1 and 1.50-2.50 ng g-1, respectively. Satisfactory method recoveries (85.1-112%) were obtained, with relative standard deviations below 8.2%. This study offered a new strategy for designing efficient sorbents to adsorb or remove organic pollutants based on the structure and properties of substrates.

Ultra-long Near-infrared Repeatable Photochemical Afterglow Mediated by Reversible Storage of Singlet Oxygen for Information Encryption.

Photochemical afterglow systems have drawn considerable attention in recent years due to their regulable photophysical properties and charming application potential. However, conventional photochemical afterglow suffered from its unrepeatability due to the consumption of energy cache units as afterglow photons are emitted. Here we report a novel strategy to realize repeatable photochemical afterglow (RPA) through the reversible storage of 1 O2 by 2-pyridones. Near-infrared afterglow with a lifetime over 10 s is achieved, and its initial intensity shows no significant reduction over 50 excitation cycles. A detailed mechanism study was conducted and confirmed the RPA is realized through the singlet oxygen-sensitized fluorescence emission. Furthermore, the generality of this strategy is demonstrated and tunable afterglow lifetimes and colors are achieved by rational design. The developed RPA is further applied for attacker-misleading information encryption, presenting a repeatable-readout.

An electrochemical sensor based on MOF-derived porous carbon/graphene composite for sensitive determination of carbendazim.

A sensitive electrochemical sensor for the determination of carbendazim (CBZ) was developed with Ni-doping nanoporous carbon-graphene composite (G-Ni/C) as the electrode material. The combination of graphene and Ni-doping nanoporous carbon not only prevented the aggregation of graphene, but also improved electric conductivity and substantially enhanced the electro catalytic activity for CBZ sensing. The electrochemical characterization of G-Ni/C towards CBZ determination was conducted by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) . The sensor based on G-Ni/C/GCE exhibits good electroanalytical activity towards the electro-oxidation of CBZ at the potential of + 0.6 V vs Ag/AgCl. Some key factors including sample pH, scan rates, accumulation potential, and accumulation time were investigated. The method offered a wide linear range of 0.04 to 10.0 µM with a detection limit of 8.9 nM. The obtained sensor was successfully employed for the determination of CBZ in pond water and juice samples with RSD < 5.7% and recoveries in the range 91.3-111%. In the present work, Ni-doping nanoporous carbon-graphene composite (G-Ni/C) was prepared by directly pyrolysis of GO/Ni-MOF. The electrochemical sensor based on G-Ni/C /GCE was applied for sensitive determination of carbendazim (CBZ) in pond water, peach, and lemon juices samples.

Facile synthesis of BiOI/MXene heterostructure as a superior photoelectrochemical sensor for sensitive detection of glucose.

A MXene-based heterostructure (BiOI/Ti3C2TX) was synthesized via simple hydrothermal synthesis strategy. The BiOI/Ti3C2TX exhibited distinctly enhanced photoelectrochemical (PEC) activity, excellent durability and high selectivity because the introduction of Ti3C2TX could facilitate the separation of photogenerated electron-hole pairs. Since the redox process of glucose resulted in a decreasing photocurrent of BiOI/Ti3C2TX, a BiOI/Ti3C2TX based signal-off PEC sensing platform was constructed to sensitively determine glucose for the first time. Under the optimal conditions, the BiOI/Ti3C2TX sensor displayed a good linearity ranging from 0.03 µΜ to 1500 µΜ with the limit of detection down to 0.02 µΜ. The sensor was successfully applied for the glucose detection in human urine with satisfactory accuracy and repeatability, confirming its practical applicability and good serviceability. Moreover, the BiOI/Ti3C2TX sensor also exhibited superb selectivity and stability, providing a great potential application in the development of glucose sensor.

Androgens drive sexual dimorphism in liver metastasis by promoting hepatic accumulation of neutrophils.

The liver is one of the most-favored distant metastatic sites for solid tumors, and interactions between cancer cells and components of the hepatic microenvironment are essential for liver metastasis (LM). Although sex is one of the determinants for primary liver cancer, sexual dimorphism in LM (SDLM) and the underlying mechanisms remain unclear. We herein demonstrate a significant male-biased SDLM, which is attributed to host androgen/androgen receptor (Ar) signaling that promotes hepatic seeding of tumor cells and subsequent outgrowth in a neutrophil-dependent manner. Mechanistically, androgen/Ar signaling promotes hepatic accumulation of neutrophils by promoting proliferation and development of neutrophil precursors in the bone marrow, as well as modulating hepatic recruitment of neutrophils and their functions. Antagonizing the androgen/Ar/neutrophil axis significantly mitigates LM in males. Our data thus reveal an important role of androgen in LM and suggest that androgen/Ar modulation represents a promising target for LM therapy in men.

Exploring the Effects of Different Bacteria Additives on Fermentation Quality, Microbial Community and In Vitro Gas Production of Forage Oat Silage.

Bacterial inoculants are considered as a good choice for successful ensiling, playing a key role in improving the silage quality. However, the potential of different bacteria, especially the propionic acid bacteria, in forage oat ensiling is yet to be explored. Therefore, the purpose of this study was to investigate the regulation effects of different bacterial additives on the fermentation quality of forage oat silage. Four additives (Lactiplantibacillus plantarum F1, LP; Lacticaseibacillus 0rhamnosus XJJ01, LR; Lacticaseibacillus paracasei XJJ02, LC; and Propionibacterium acidipropionici 1.1161, PP; without additives, CK) were inoculated in forage oat silage, and the fermentation quality and organic compounds were determined after 60 days of ensiling. Notably, LR showed higher dry matter preservation compared to other additives and CK. In addition, LP and LR showed strong lactic acid synthesis capacity, resulting in lower pH compared to other additives and CK. The treatments of PP and LC increased the bacterial diversity in silage, while the bacterial community in the LR group was different from that in other groups. In addition, the PP- and LC-treated oat silage showed significantly lower total in vitro gas production and a lower methane content. These results suggest that LP is more favorable for producing high-quality oat silage than LR, LC, or PP. Both the PP- and LC- treated oat silage may reduce rumen greenhouse gas emissions.

Hepatocyte-derived VEGFA accelerates the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via activating hepatic stellate cells.

Non-alcoholic fatty liver disease (NAFLD) is emerging as an epidemic risk factor for hepatocellular carcinoma (HCC). The progression of NAFLD to HCC is closely associated with paracrine communication among hepatic cells. Vascular endothelial growth factor A (VEGFA) plays a key role in NAFLD and HCC; however, the cellular communication of VEGFA in the pathological transition from NAFLD to HCC remains unclear. Here, we found that VEGFA elevation was considerably distributed in hepatocytes of clinical and murine NAFLD-HCC specimens. Notably, progression from NAFLD to HCC was attenuated in hepatocyte-specific deletion of Vegfa (VegfaΔhep) mice. Mechanistically, VEGFA activated human hepatic stellate cell (HSC) LX2 into a fibrogenic phenotype via VEGF-VEGFR signaling in fatty acid medium, and HSC activation was largely attenuated in VegfaΔhep mice during NAFLD-HCC progression. Additionally, a positive correlation between VEGFA and hepatic fibrosis was observed in the NAFLD-HCC cohort, but not in the HBV-HCC cohort. Moreover, LX2 cells could be activated by conditioned medium from NAFLD-derived organoids, but not from HBV livers, whereas this activation was blocked by a VEGFA antibody. In summary, our findings reveal that hepatocyte-derived VEGFA contributes to NAFLD-HCC development by activating HSCs and highlight the potential of precisely targeting hepatocytic VEGFA as a promising therapeutic strategy for NAFLD-HCC.