Incentive strategies for retired power battery closed-loop supply chain considering corporate social responsibility.

Global environmental concerns and resource scarcity are driving the growth in sales of electric vehicles (EVs). Reusing and recycling retired batteries from EVs has significant economic value and reduces the environmental burden. Rising raw material prices have intensified competition among recyclers; in particular, recyclers without corporate social responsibility (CSR) have been added. These observations lead to a game-theoretical model consisting of three players: a battery manufacturer, a recycler with CSR and a recycler without CSR (non-CSR). The non-CSR recycler enjoys a cost advantage over the CSR recycler, but may not be considered by the consumers with high environmental awareness (CEA). We explore the incentive strategies for CSR recyclers outperform, and how the equilibrium is affected by the recyclers' Stackelberg game. Results show that (1) the deposit- refund is the most profitable strategy for all members and the whole supply chain if raw material price rises high enough; otherwise, a contract strategy should be adopted. (2) Improving CEA and echelon utilization ratio is more conducive to the implementation of revenue-sharing contract. In addition, increasing CEA contributed to CSR recycler collects more retired batteries instead of non-CSR recycler. (3) Stackelberg game between recyclers may hurt supply chain. However, CSR recycler may benefit from the non-CSR recycler-led Stackelberg game. Our work provides the basis of incentive strategies for different participants in the closed-loop supply chain of retired batteries, in particular, to encourage retired batteries flow to CSR recyclers.

Nitrosonisoldipine is a selective inhibitor of inflammatory caspases and protects against pyroptosis and related septic shock.

Pyroptosis is a type of acute cell death that mainly occurs in immune cells. It is characterized with robust release of inflammatory cytokines and has emerged to play a critical role in the pathogenesis of sepsis-associated immune disorders. In this study, we screened for pyroptotic inhibitors with the ultimate goal to benefit sepsis treatments. Accidentally, we identified that nitrosonisoldipine (NTS), a photodegradation product of calcium channel inhibitor nisoldipine, inhibits noncanonical pyroptosis. Using murine immortalized BM-derived macrophage and human THP-1 cell line, we further discovered that NTS not only inhibits noncanonical pyroptosis mediated by caspase-11 or caspase-4 but also canonical pyroptosis mediated by caspase-1. Mechanistically, NTS directly inhibits the enzyme activities of these inflammatory caspases, and these inhibitory effects persist despite extensive washout of the drug. By contrast, apoptosis mediated by caspase-3/-7 was not affected by NTS. Mice pretreated with NTS intraperitoneally displayed improved survival rate and extended survival time in LPS- and polymicrobe-induced septic models, respectively. In conclusion, NTS is a selective inhibitor of inflammatory caspases that blocks both the noncanonical and canonical pyroptotic pathways. It is safe for intraperitoneal administration and might be used as a prototype to develop drugs for sepsis treatments.

Mn-SOD alleviates methotrexate-related hepatocellular injury via GSK-3ß affecting anti-oxidative stress of HO-1 and Drp1. / Mn-SOD通过GSK-3ß影响HO-1和Drp1的抗氧化应激减轻MTXç›¸å ³è‚ç»†èƒžæŸä¼¤.

OBJECTIVES: Methotrexate (MTX) is the most common therapeutic agent that may have the risk of drug-induced liver injury. Its pathogenic mechanism is related to oxidative stress caused by mitochondrial dysfunction. Superoxide dismutase (SOD), including manganese-containing SOD (Mn-SOD), can exert its effect of anti-oxidative stress by scavenging superoxide free radicals. Accordingly, this study is performed to explore the underlying molecular mechanism via observing whether Mn-SOD could affect the damage of MTX to hepatocytes. METHODS: Human hepatocyte cell line L-02 was cultured in vitro and divided into 4 groups, including a blank group with the addition of the same volume of serum-free medium, a MTX group (40 µg/well MTX drug-treatment), a MTX+NC group (40 µg/well MTX drug-treatment+blank plasmid), and a MTX+SOD group (40 µg/well MTX drug-treatment+Mn-SOD plasmid). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and microRNA-122 (miR-122) in the supernatant of cell culture were respectively detected by automatic biochemical analytical instrument and real-time RT-PCR to evaluate the degree of hepatocyte damage in each group. MitoSOX fluorescent probe was used to label intracellular superoxide in each group, and cell apoptosis was detected by flow cytometry. Meanwhile, the contents of glycogen synthase kinase-3 beta (GSK-3ß), hemeoxygenase-1 (HO-1), mitochondrial fission-mediated protein of dynamin-related protein 1 (Drp1), and Mn-SOD were detected by Western blotting. RESULTS: Compared with the blank group, the levels of ALT, AST, and miR-122 in the supernatant of hepatocyte culture of the MTX group and MTX+NC group were significantly elevated (all P <0.05), and that in the MTX+SOD group were significantly decreased ( P <0.05) and equivalent to that in the blank group. MitoSOX staining revealed that the MTX group and MTX+NC had the most abundant superoxide; and the amount was significantly reduced in the MTX+SOD group, without a significant difference when compared with the blank group. Furthermore, the results of flow cytometry indicated that compared with the blank group, the MTX group and MTX+NC group showed significantly increased cell apoptosis ( P <0.05); while there was obviously reduced cell apoptosis in the MTX+SOD group than that in the MTX group and MTX+NC group ( P <0.05). According to the results of Western blotting, the blank group and MTX+SOD group had higher expressions of Mn-SOD, p-GSK-3ß, and HO-1; while the MTX group and MTX+NC group exhibited remarkably lower levels of Mn-SOD, p-GSK-3ß, and HO-1 than those in the blank group ( P <0.05). Besides, a completely opposite trend was found in the expression of Drp1, which was highly expressed in the MTX group and MTX+NC group, but lowly expressed in the blank group and the MTX+SOD group. CONCLUSIONS: MTX may induce hepatocyte damage, and one of the mechanisms may be due to the decrease of intracellular Mn-SOD level, which can cause the accumulation of superoxide, affect the levels of HO-1 and Drp1 through GSK-3ß leading to mitochondrial damage and cell apoptosis. High expression of Mn-SOD intracellularly through exogenous introduction can scavenge drug-produced superoxide, affect HO-1 and Drp1 levels through GSK-3ß, activate mitochondria, protect cells against damage from oxidative stress, and inhibit hepatocyte apoptosis eventually. So exogenous introduction of SOD may be a potential therapeutic approach to block or reverse MTX-related hepatocyte injury.

Hypertonic saccharide solution delays pyroptosis in murine macrophages regardless of the membrane binding of gasdermin D N-terminal.

Pyroptosis is a type of programmed lytic cell death that could be activated by either the canonical or noncanonical inflammasome pathway. In this study, we aimed to examine the effect of hypertonic solution on noncanonical pyroptosis in macrophage. We found that although hypertonic solution had a general inhibitory effect on noncanonical pyroptosis, the underlying mechanism varied by the solute causing hypertonicity. Specifically, hypertonic NaCl or KCl solution inhibited the cleavage of gasdermin D, the pore-forming protein in pyroptosis, whereas hypertonic saccharide solution did not affect the cleavage or membrane binding of gasdermin D. In this case, nevertheless, pyroptosis was still inhibited as evidenced by the preserved mitochondria activity and cell membrane permeability.

Epidermis-Activated Gasdermin-A3 Enhances Thermogenesis of Brown Adipose Tissue through IL-6/Stat3 Signaling.

Missense mutations in the gasdermin-A3 (Gsdma3) gene are associated with skin inflammation and hair loss in mice. However, the physiological function of Gsdma3 remains unclear. Herein, we reported that mice carrying the Gsdma3 Y344H mutation that encodes a presumptive activated form of Gsdma3 show increased heat production along with lower body fat percentages. Detailed analysis indicated that this metabolic phenotype is mediated by serum IL-6-induced up-regulation of thermogenesis in brown adipose tissue. The mutant form of Gsdma3 promotes the expression of IL-6 in the epidermis in a c-Jun N-terminal kinase (JNK) signaling-dependent manner. The higher whole-body heat production in alopecia and excoriation mice could be suppressed by an IL-6 receptor/GP130 inhibitor. Our results uncovered Gsdma3/IL-6-dependent cross talk between the skin and brown adipose tissue.

High-energy 2 µm pulsed vortex beam excitation from a Q-switched Tm:LuYAG laser.

We report on the first, to the best of our knowledge, direct generation of pulsed vortex beams at 2 µm from a ${ Q}$Q-switched Tm:LuYAG laser. High-energy Laguerre-Gaussian (${{\rm LG}_{0,l}}$LG0,l) pulsed laser beams with well-defined handedness are selectively excited through spatially matched pump gain distribution and asymmetric cavity loss without using any intracavity handedness-selective optical elements. Pulse energies of 1.48 mJ for the ${{\rm LG}_{0, + 1}}$LG0,+1 mode and 1.51 mJ for the ${{\rm LG}_{0, - 1}}$LG0,-1 mode, respectively, are achieved at a repetition rate of 500 Hz. The pulsed laser beams with helical wavefronts are potentially useful for studying orbital angular momentum transformation dynamics, generation of mid-IR vortex beams, and nanostructuring of organic materials.

MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway.

BACKGROUND: MicroRNA-148b (miR-148b) has been detected in various types of tumors, and is generally viewed as a tumor suppressor. Our previous study found the decreased expression of miR-148b in human non small cell lung cancer (NSCLC) specimens and cell lines. However, the underlying mechanisms of miR-148b in regulating tumor progression remain unclear. METHODS: Firstly animal experiments were performed to verify whether miR-148b could inhibit the tumor growth. Then, the underlying mechanisms were studied by transfecting recombinant plasmids containing a miR-148b mimic or a negative control (NC) mimic (shRNA control) into NSCLC cell lines PC14/B and A549 cells. Tumor cells transfected with unpackaged lentiviral vectors was used as blank control. Cell proliferation capabilities were measured by using CCK-8 kit and colony formation assay. Cell cycle arrest was compared to clarify the mechanism underlying the tumor cell proliferation. Annexin V-FITC Apoptosis Detection kit was applied to investigate the effect of miR-148b on cell apoptosis. Furthermore, western blot analysis were performed to study the targeting pathway. RESULTS: We found that over-expression of miR148b could significantly inhibit tumor growth, while knocking down miR148b could obviously promote tumor growth. Further experiment showed that miR-148b inhibited tumor cell proliferation. Besides, over-expression of miR148b decreased the G2/M phase population of the cell cycle by preventing NSCLC cells from entering the mitotic phase and enhanced tumor cell apoptosis. Further western blot analysis indicated that miR148b could inhibit mitogen-activated protein kinase/Jun N-terminal kinase (MAPK/JNK) signaling by decreasing the expression of phosphorylated (p) JNK. CONCLUSIONS: These results demonstrate that miR-148b could inhibit the tumor growth and act as tumor suppressor by inhibiting the proliferation and inducing apoptosis of NSCLC cells by blocking the MAPK/JNK pathway.

High-power nanosecond pulse generation from an integrated Tm-Ho fiber MOPA over 2.1 µm.

In this paper, we report on high-power stable nanosecond pulse generation at ~2.1 µm from an integrated Tm-Ho all-fiber master oscillator power amplifier (MOPA) system. A total output power of 128.5 W is generated from the Tm-Ho hybrid MOPA, with an average power of 99.1 W from Ho emission at 2116 nm; the corresponding pulse repetition frequency and pulse width are 161 kHz and 322 ns, respectively, leading to a peak power of 1.91 kW. The Tm-Ho integrated master oscillator is designed to operate at 1980 and 2116 nm, where the former wavelength serves as the pump of the Ho-doped fiber. Stable laser pulses are generated from both the Tm and Ho oscillators owing to mutual modulation of emission from the two lasers. The prospects for further scaling in output power at ~2.1 µm using Tm-Ho integrated MOPA system are discussed.

Wavelength- and OAM-tunable vortex laser with a reflective volume Bragg grating.

Vortex beams carrying orbital angular momentum (OAM) have been recently investigated intensely in optical communication systems, as using OAM mode multiplexing simultaneously with other conventional multiplexing techniques is the key to further expand data capacity. This article demonstrates a wavelength- and OAM-tunable vortex laser at 1.6 µm in an Er:YAG system. For the first time to the best of our knowledge, a reflective volume Bragg grating (VBG) was theoretically and experimentally proved to be an effective OAM-preserving wavelength selector inside the laser cavity. A z-shaped laser cavity employing a VBG as a folding mirror was constructed for the direct generation of vortex beams, and we finally obtained wavelength-tunable beams of five OAM states (0, ± h, and ± 2h) with a narrow bandwidth less than 0.04 nm. This laser supplies a new way for optical communication by combining the spatial degree of freedom for multiplexing information channels with the conventionally used wavelength domains in packable and robust resonant cavity.

~1 mJ pulsed vortex laser at 1645 nm with well-defined helicity.

We report on a millijoule level Er:YAG ceramic pulsed vortex laser resonantly pumped by an annular beam at 1532 nm. By means of an uncoated YAG crystal plate inserting into the cavity and a proper thermal gradient on the ceramic, 1.03 mJ LG0,-1 mode and 0.97 mJ LG0, + 1 mode were respectively produced, and no vortex mode instability problem was observed. We believe the directly generated millijoule level optical vortex with well-defined helicity will have potential applications in material modification and processing, high-field laser physics, and nonlinear optics, etc.

Integration of helicity-control and pulse-modulation for vortex laser based on a black phosphorus plate.

Using a home-made black phosphorus plate (BPP) as handedness controller and Q-switch modulator synchronously, a ~1.6 µm pulsed vortex laser with well-determined handedness is demonstrated in this letter. Stable vortex pulses of LG0, + 1, LG0,-1, LG0, + 2 and LG0,-2 modes were respectively achieved from compact resonant cavities in this experiment. Such pulsed vortex laser should have promising applications in various fields based on its simple structure, controllable handedness, and carried orbital angular momentum.

Short pulse-width gain-switched Ho:YAG ceramic laser at ∼2.09 µm.

This paper presents a short pulse-width gain-switched Ho:YAG ceramic laser at 2089 nm resonantly pumped by a homemade Q-switched Tm:fiber laser at ∼1908 nm. We generated stable pulses of 44-103 ns duration and 0.13-2 kW peak power at 20 kHz of pulse repetition frequency when the incident pump pulse energy increased from ∼0.1 to 0.3 mJ. We also obtained an average output power of 1.76 W under an incident pump power of 6 W, corresponding to a slope efficiency of 41.8%. Finally, this paper discusses the prospects to further improve the results with even a shorter pulse-width and higher peak power.

Effects of intrahippocampal GABAB receptor antagonist treatment on the behavioral long-term potentiation and Y-maze learning performance.

GABAB receptor is present at pre- and post-synaptic sites and participates in many brain functions including cognition, reward and anxiety. Although a lot of research has shown that activation or blockade of GABAB receptor may produce different even opposing effects on long-term potentiation (LTP) and cognitive function, there is little information available concerning the effect of GABAB receptor on behavioral LTP, a learning-induced LTP model. Herein, we firstly examined the effects of 2-OH saclofen, a GABAB receptor antagonist, on the induction of behavioral LTP and Y-maze learning performance. In addition, GABAB receptor has been reported to be present on cholinergic terminals and to regulate the ACh release. Therefore, we also investigated the effect of 2-OH saclofen on the impairments in behavioral LTP and cognitive function induced by scopolamine, an acetylcholine receptor antagonist. We found that intrahippocampal application of 2-OH saclofen could significantly enhance the population spike (PS) amplitude with a dose-response relationship, and 20 µM 2-OH saclofen evidently facilitated the formation of behavioral LTP in the perforant pathway to the dentate gyrus (PP-DG) and led to an obvious improvement in maze learning performance. Furthermore, intrahippocampal 20 µM 2-OH saclofen administration could markedly reverse the scopolamine-induced impairments in behavioral LTP and maze performance. Our data demonstrate that blockade of GABAB receptor displays a facilitatory role in the induction of behavioral LTP and maze learning task, and the antagonist of GABAB receptor seems to exert the potentially therapeutic value in the cognitive defect induced by cholinergic dysfunction.

Transmembrane Protein CMTM6 Alleviates Ocular Inflammatory Response and Improves Corneal Epithelial Barrier Function in Experimental Dry Eye.

Purpose: To investigate the impact of transmembrane protein CMTM6 on the pathogenesis of dry eye disease (DED) and elucidate its potential mechanisms. Methods: CMTM6 expression was confirmed by database analysis, real-time polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. Tear secretion was measured using the phenol red thread test. Immune cell infiltration was assessed through flow cytometry. Barrier function was evaluated by fluorescein sodium staining, immunofluorescence staining of zonula occludens 1 (ZO-1), and electric cell-substrate impedance sensing (ECIS) assessment. For silencing CMTM6 expression, siRNA and shRNA were employed, along with lentiviral vector-mediated overexpression of CMTM6. Proinflammatory cytokine levels were analyzed by RT-PCR and cytometric bead array (CBA) analysis. Results: CMTM6 showed high expression in healthy human and mouse corneal and conjunctival epithelium but was notably reduced in DED. Notably, this downregulation was correlated with disease severity. Cmtm6-/- dry eye (DE) mice displayed reduced tear secretion, severe corneal epithelial defects, decreased conjunctival goblet cell density, and upregulated inflammatory response. Additionally, Cmtm6-/- DE mice and CMTM6 knockdown human corneal epithelial cell-transformed (HCE-T) cells showed more severe barrier disruption and reduced expression of ZO-1. Knockdown of CMTM6 in HCE-T cells increased inflammatory responses induced by hyperosmotic stress, which was significantly mitigated by CMTM6 overexpression. Moreover, the level of phospho-p65 in hyperosmolarity-stimulated HCE-T cells increased after silencing CMTM6. Nuclear factor kappa B (NF-κB) p65 inhibition (JSH-23) reversed the excessive inflammatory responses caused by hyperosmolarity in CMTM6 knockdown HCE-T cells. Conclusions: The reduction in CMTM6 expression on the ocular surface contributes to the pathogenesis of DED. The CMTM6-NF-κB p65 signaling pathway may serve as a promising therapeutic target for DED.

CMTM6 promotes hepatocellular carcinoma progression through stabilizing ß-catenin.

CMTM6, a regulator of PD-L1 stability, has been implicated in the development of various cancers. However, the expression and role of CMTM6 in hepatocellular carcinoma (HCC) remains controversial. Our study revealed a negative correlation between CMTM6 expression and HCC prognosis through bioinformatics analysis and immunofluorescence staining. CMTM6 expression was also positively associated with alpha-fetoprotein (AFP) levels, supporting its potential as a prognostic marker for HCC. Using Cmtm6 knockout mice, we found that Cmtm6 deficiency inhibited HCC formation and cell proliferation in primary liver cancer models induced by DEN and DEN/CCl4. In HCC cell lines, CMTM6 promoted cell proliferation and interacted with ß-catenin, stabilizing it by preventing ubiquitination. In conclusion, our study suggested that CMTM6 upregulation promotes HCC cell proliferation through the ß-catenin pathway, making it a potential therapeutic target for HCC treatment.

Chinese medicine in the treatment of non-alcoholic fatty liver disease based on network pharmacology: a review.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by abnormalities in hepatic fat deposition, the incidence of which has been increasing year by year in recent years. It has become the largest chronic liver disease globally and one of the important causes of cirrhosis and even primary liver cancer formation. The pathogenesis of NAFLD has not yet been fully clarified. Modern medicine lacks targeted clinical treatment protocols for NAFLD, and most drugs lack efficacy and have high side effects. In contrast, Traditional Chinese Medicine (TCM) has significant advantages in the treatment and prevention of NAFLD, which have been widely recognized by scholars around the world. In recent years, through the establishment of a "medicine-disease-target-pathway" network relationship, network pharmacology can explore the molecular basis of the role of medicines in disease prevention and treatment from various perspectives, predicting the pharmacological mechanism of the corresponding medicines. This approach is compatible with the holistic view and treatment based on pattern differentiation of TCM and has been widely used in TCM research. In this paper, by searching relevant databases such as PubMed, Web of Science, and Embase, we reviewed and analyzed the relevant signaling pathways and specific mechanisms of action of single Chinese medicine, Chinese medicine combinations, and Chinese patent medicine for the treatment of NAFLD in recent years. These related studies fully demonstrated the therapeutic characteristics of TCM with multi-components, multi-targets, and multi-pathways, which provided strong support for the exact efficacy of TCM exerted in the clinic. In conclusion, we believe that network pharmacology is more in line with the TCM mindset of treating diseases, but with some limitations. In the future, we should eliminate the potential risks of false positives and false negatives, clarify the interconnectivity between components, targets, and diseases, and conduct deeper clinical or experimental studies.

Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway.

Homeostasis of the skin barrier is essential for maintaining normal skin function. Gasdermin A (GSDMA) is highly expressed in the skin and is associated with many skin diseases, such as melanoma and psoriasis. In mice, GSDMA is encoded by three gene homologues, namely Gsdma1, Gsdma2, and Gsdma3. Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation, Gsdma3-deficient mice show no phenotypes in skin or hair structures. To explore the physiological function of GSDMA, we generated conventional Gsdma1/2/3 knockout (KO) mice. We found that Gsdma1/2/3 KO mice showed significantly decreased epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate (PMA). Furthermore, we found that the alleviation of epidermal hyperplasia depends on Gsdma1/2/3 expressed specifically in keratinocytes. Mechanistically, Gsdma1/2/3 depletion downregulated epidermal growth factor receptor (EGFR) ligands, leading to decreased EGFR-Stat3/Akt signalling. These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR-Stat3/Akt pathway.

Fecal microbiota transplantation improves chicken growth performance by balancing jejunal Th17/Treg cells.

BACKGROUND: Intestinal inflammation has become a threatening concern in chicken production worldwide and is closely associated with Th17/Treg cell imbalance. Several studies described that gut microbiota is significantly implicated in chicken growth by modulating intestinal immune homeostasis and immune cell differentiation. Whether reshaping gut microbiota by fecal microbiota transplantation (FMT) could improve chicken growth by balancing Th17/Treg cells is an interesting question. RESULTS: Here, the chickens with significantly different body weight from three different breeds (Turpan cockfighting × White Leghorn chickens, white feather chickens, and yellow feather chickens) were used to compare Th17 and Treg cells. qPCR and IHC staining results indicated that Th17 cell-associated transcriptional factors Stat3 and rorγt and cytokines IL-6, IL-17A, and IL-21 were significantly (P < 0.05) higher in the jejunum of low body weight chickens, while Treg cell-associated transcriptional factor foxp3 and cytokines TGF-ß and IL-10 were significantly (P < 0.05) lower in the jejunum of low body weight chickens, indicating imbalanced Th17/Treg cells were closely related to chicken growth performance. Transferring fecal microbiota from the healthy donor with better growth performance and abundant Lactobacillus in feces to 1-day-old chicks markedly increased growth performance (P < 0.001), significantly decreased Th17 cell-associated transcriptional factors and cytokines, and increased Treg cell-associated transcriptional factors and cytokines in the jejunum (P < 0.05). Furthermore, FMT increased the abundance of Lactobacillus (FMT vs Con; 84.98% vs 66.94%). Besides, the metabolites of tryptophan including serotonin, indole, and 5-methoxyindoleacetate were increased as well, which activated their receptor aryl-hydrocarbon-receptor (AhR) and expressed more CYP1A2 and IL-22 to maintain Th17/Treg cell balance and immune homeostasis. CONCLUSION: These findings suggested that imbalanced Th17/Treg cells decreased chicken growth performance, while FMT-reshaped gut microbiota, i.e., higher Lactobacilli, increased chicken growth performance by balancing Th17/Treg cells. Video Abstract.

Chicken cecal microbiota reduces abdominal fat deposition by regulating fat metabolism.

Cecal microbiota plays an essential role in chicken health. However, its contribution to fat metabolism, particularly in abdominal fat deposition, which is a severe problem in the poultry industry, is still unclear. Here, chickens at 1, 4, and 12 months of age with significantly (p < 0.05) higher and lower abdominal fat deposition were selected to elucidate fat metabolism. A significantly (p < 0.05) higher mRNA expression of fat anabolism genes (ACSL1, FADS1, CYP2C45, ACC, and FAS), a significantly (p < 0.05) lower mRNA expression of fat catabolism genes (CPT-1 and PPARα) and fat transport gene APOAI in liver/abdominal fat of high abdominal fat deposition chickens indicated that an unbalanced fat metabolism leads to excessive abdominal fat deposition. Parabacteroides, Parasutterella, Oscillibacter, and Anaerofustis were found significantly (p < 0.05) higher in high abdominal fat deposition chickens, while Sphaerochaeta was higher in low abdominal fat deposition chickens. Further, Spearman correlation analysis indicated that the relative abundance of cecal Parabacteroides, Parasutterella, Oscillibacter, and Anaerofustis was positively correlated with abdominal fat deposition, yet cecal Sphaerochaeta was negatively correlated with fat deposition. Interestingly, transferring fecal microbiota from adult chickens with low abdominal fat deposition into one-day-old chicks significantly (p < 0.05) decreased Parabacteroides and fat anabolism genes, while markedly increased Sphaerochaeta (p < 0.05) and fat catabolism genes (p < 0.05). Our findings might help to assess the potential mechanism of cecal microbiota regulating fat deposition in chicken production.

MicroRNA-34b-5p binds enhancer of zeste 2 to inhibit milk fat globule-EGF factor 8 expression, affecting liver fibrosis.

Activated hepatic stellate cells (HSCs) are considered the major drivers in the process of hepatic fibrosis. This study intends to explore the mechanism underlying microRNA (miR)-34b-5p effects over liver fibrosis through the enhancer of zeste 2 (EZH2)/milk fat globule-EGF factor 8 (MFGE8) axis in HSCs. A liver fibrosis model was generated by carbon tetrachloride (CCl4) in C57BL/6 J mice and subjected to histological examinations and detection of HSC activation and miR-34b-5p/EZH2/MFGE8 expression. Primary HSCs were treated with transforming growth factor (TGF)-ß and tested for proliferation, activation, and expression of fibrosis-related factors. A dual luciferase reporter assay was performed for confirming the targeted relationship between miR-34b-5p and EZH2. Chromatin immunoprecipitation was used to measure EZH2 enrichment in the MFGE8 promoter region. We found that miR-34b-5p was lowly expressed in the CCl4-induced mouse model. Overexpression of miR-34b-5p suppressed both TGF-ß-induced HSC proliferation and the expression of fibrosis-related factors and HSC activation markers. A dual luciferase assay showed a binding relationship between miR-34b-5p and EZH2. Overexpression of miR-34b-5p reduced TGF-ß-induced HSC activation by inhibiting EZH2 to promote MFGE8 expression. Overexpression of miR-34b-5p inhibited liver fibrosis in vivo through the EZH2/MFGE8 axis. Conclusively, overexpressing miR-34b-5p reduced TGF-ß-induced HSC activation by inhibiting EZH2 and thereby promoting MFGE8 expression, and inhibited liver fibrosis in vivo through the EZH2/MFGE8 axis.