High-mobility group box 1 (HMGB1), a member of damage-associated molecular patterns (DAMPs), is involved in the immune regulation of several infectious diseases. Mycoplasma gallisepticum (MG) ...infection is proved to cause an abnormal immune response, but the role of HMGB1 in MG-induced chronic respiratory disease (CRD) is unclear. In this study, we found that HMGB1 was released from the nucleus to the extracellular in macrophages upon infection with MG. Extracellular HMGB1 bound to TLR2 activating the NF-κB pathway triggering a severe inflammatory storm and promoting the progression of MG infection. More importantly, TLR4 could be activated by HMGB1 to trigger immune disorders after TLR2 was silenced. This disease process could be interrupted by ethyl pyruvate (EP) inhibition of HMGB1 release or glycyrrhizic acid (GA). Furthermore, treatment of MG-infected chickens with GA significantly alleviated immune organ damage. In conclusion, we demonstrate that HMGB1 is secreted extracellularly to form an inflammatory environment upon MG infection, triggering a further cellular inflammatory storm in a positive feedback approach. Blocking MG-induced HMGB1 release or suppression downstream of the HMGB1-TLR2/TLR4 axis may be a promising novel strategy for the treatment of CRD. Furthermore, this study may provide a theoretical reference for understanding non-LPS-activated TLR4 events.
Nitrogen (N) limits plant productivity, and its uptake and assimilation may be regulated by N sources, N assimilating enzymes, and N assimilation genes. Mastering the regulatory mechanisms of N ...uptake and assimilation is a key way to improve plant nitrogen use efficiency (NUE). However, it is poorly known how these factors interact to influence the growth process of pecans. In this study, the growth, nutrient uptake and N assimilation characteristics of pecan were analyzed by aeroponic cultivation at varying
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ratios (0/0, 0/100,25/75, 50/50, 75/25,100/0 as CK, T1, T2, T3, T4, and T5). The results showed that T4 and T5 treatments optimally promoted the growth, nutrient uptake and N assimilating enzyme activities of pecan, which significantly increased aboveground biomass, average relative growth rate (RGR), root area, root activity, free amino acid (FAA) and total organic carbon (TOC) concentrations, nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), glutamate synthase (Fd-GOGAT and NADH-GOGAT), and glutamate dehydrogenase (GDH) activities. According to the qRT-PCR results, most of the N assimilation genes were expressed at higher levels in leaves and were mainly significantly up-regulated under T1 and T4 treatments. Correlation analysis showed that a correlation between N assimilating enzymes and N assimilating genes did not necessarily exist. The results of partial least squares path model (PLS-PM) analysis indicated that N assimilation genes could affect the growth of pecan by regulating N assimilation enzymes and nutrients. In summary, we suggested that the
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ratio of 75:25 was more beneficial to improve the growth and NUE of pecan. Meanwhile, we believe that the determination of plant N assimilation capacity should be the result of a comprehensive analysis of N concentration, N assimilation enzymes and related genes.
Cornus officinalis, a medicinal and edible plant known for its liver-nourishing properties, has shown promise in inhibiting the activation of hepatic stellate cells (HSCs), crucial indicators of ...hepatic fibrosis, especially when processed by high pressure wine steaming (HPWS). Herein, this study aims to investigate the regulatory effects of cornus officinalis, both in its raw and HPWS forms, on inflammation and apoptosis in liver fibrosis and their underlying mechanisms. In vivo liver fibrosis models were established by subcutaneous injection of CCl4, while in vitro HSCs were exposed to transforming growth factor-β (TGF-β). These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury, reduced the release of proinflammatory factors, and decreased collagen deposition in CCl4-induced rats compared to its raw form. Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) combined with network analysis, we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS, primarily centered on the adenosine phosphate (AMP)-activated protein kinase (AMPK) pathway. Of note, cornus officinalis activated AMPK and sirtuin 3 (SIRT3), promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3, caspase6 and caspase9. small interfering RNA (siRNA) experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3. In conclusion, cornus officinalis exhibited the ability to reduce inflammation and apoptosis, with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.
A schematic model showing that cornus officinalis exerts anti-inflammatory and apoptosis effect in liver fibrosis via activation of SIRT3-AMPK signaling. Display omitted
•Cornus officinalis both RAW and HPWS could ameliorate liver fibrosis.•Cornus officinalis with HPWS on liver fibrosis was better than that of it with RAW, which was associated with compounds change before and after HPWS.•Cornus officinalis with HPWS could promote apoptosis of activated HSCs through AMPK mediated caspase cascade.•SIRT3-AMPK axis is a potential mechanism of the anti-fibrosis synergistic effect of Cornus officinalis.
Euphorbia pekinensis (EP) is a commonly used Chinese medicine treating edema with potential hepatorenal toxicity. However, its toxic mechanism and prevention are remained to be explored. Oleanolic ...acid (OA) is a triterpene acid with potential hepatorenal protective activities. We investigated the protective effect and potential mechanism of OA on EP-induced hepatorenal toxicity. In this study, rats were given total diterpenes from EP (TDEP, 16 mg/kg) combined with OA (10, 20, 40 mg/kg) by gavage for 4 weeks. The results showed that TDEP administration could lead to a 3-4-fold increasement in hepatorenal biochemical parameters with histopathological injuries, while OA treatment could ameliorate them in a dose-dependent manner. At microbial and metabolic levels, intestinal flora and host metabolism were perturbed after TDEP administration. The disturbance of bile acid metabolism was the most significant metabolic pathway, with secondary bile acids increasing while conjugated bile acids decreased. OA treatment can improve the disorder of intestinal flora and metabolic bile acid spectrum. Further correlation analysis screened out that Escherichia-Shigella, Phascolarctobacterium, Acetatifactor, and Akkermansia were closely related to the bile acid metabolic disorder. In conclusion, oleanolic acid could prevent hepatorenal toxicity induced by EP by regulating bile acids metabolic disorder via intestinal flora improvement.
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•Luteolin inhibits Mycoplasma gallisepticum colonization and ensures the safety of chicken meat.•Luteolin restores Mycoplasma gallisepticum-induced immunocompromise.•Luteolin ...alleviates Mycoplasma gallisepticum-induced production performance degradation and inflammatory responses.•Luteolin inhibits the MG-activated IL-17/ NF-kB pathway.•Luteolin can be used as a safe and effective antibiotic alternative drug to treat chronic respiratory disease.
Mycoplasma gallisepticum (MG) is a major pathogen causing chronic respiratory disease (CRD) in chickens. Exposure to MG poses a constant threat to chicken health and causes substantial economic losses. Antibiotics are the main treatment for MG infections, but have to struggle with antibiotic residues and MG resistance. To date, no safe and more effective prevention or treatment for MG infections has been identified. Luteolin (Lut) is a natural flavonoid compound known for its excellent anti-viral, anti-bacterial, immunoregulatory, and anti-inflammatory pharmacological activities. Herein, we established an MG-infected model using partridge shank chickens and chicken-like macrophages (HD11 cells) to investigate the effect and potential mechanism of Lut against MG-induced immune damage.
According to our findings, Lut significantly inhibited the expression of MG adhesion protein (pMGA1.2) in vivo and in vitro. Lut effectively mitigated the MG-induced decrease in body weight gain, feed conversion ratio, survival rate, and serum IgG and IgA levels. Lut directly repaired MG-induced spleen and thymus damage by histopathological analysis. Furthermore, network pharmacology analysis revealed that Lut most probably resisted MG infection through the IL-17/NF-kB pathway. In vivo and in vitro experiments, Lut significantly suppressed the increase in key protein IL-17A, TRAF6, p-p65, and p-IkBα in the IL-17/NF-kB pathway. Meanwhile, Lut markedly alleviated MG-induced the increase of pro-inflammatory cytokines TNF-α, IL-6, IL-1β, pro-apoptotic genes caspase3 and caspase9, while promoting the expression of anti-apoptotic genes Bcl-2 and Bcl-XL.
In summary, Lut effectively suppressed MG colonization, alleviated MG-induced the production performance degradation, inflammatory responses, and immune damage by inhibiting the IL-17/ NF-kB pathway. This study indicates Lut can serve as a safe and effective antibiotic alternative drug for preventing and treating MG-induced CRD. It also provides new evidence to explore the molecular mechanisms of MG infection.
The recent development of tough tissue adhesives has stimulated intense interests among material scientists and medical doctors. However, these adhesives have seldom been tested in clinically ...demanding surgeries. Here we demonstrate adhesive anastomosis in organ transplantation. Anastomosis is commonly conducted by dense sutures and takes a long time, during which all the vessels are occluded. Prolonged occlusion may damage organs and even cause death. We formulate a tough, biocompatible, bioabsorbable adhesive that can sustain tissue tension and pressurized flow. We expose the endothelial surface of vessels onto a gasket, press two endothelial surfaces to the adhesive using a pair of magnetic rings, and reopen the bloodstream immediately. The time for adhesive anastomosis is shortened compared to the time for sutured anastomosis. We have achieved adhesive anastomosis of a great vein in transplanting the liver of a pig. After the surgery, the adhesive is absorbed, the vein heals, and the pig lives for over one month.
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•Use tough hydrogel to achieve adhesive anastomosis of a great vein in porcine liver transplantation.•The time for adhesive anastomosis is shortened compared to the time for sutured anastomosis.•The tough hydrogel can be bioabsorbed and enable the vessel to heal.
With much consideration on the stability of Ni-rich LiNixCoyMn1−x−yO2 (x > 0.5) cathode materials at high voltage, we use polyimides (PIs), a kind of mechanical, thermal and electrochemical ...performance all outstanding polymers, to coat LiNi0.6Co0.2Mn0.2O2 (NCM622) cathode materials via the self-growing method. The common cognition for the advantages of PI coatings is mainly about reduced interfacial side reactions, little transition metal dissolutions and a small amount of oxygen release, which prohibits the degradation of cathode materials and enhances electrochemical performance. However, the true state of PI coatings in LIBs at high voltage is not clear. Therefore, we resort to the electrochemically characterizing techniques combined with TEM, SEM, EDS, in-situ XRD and XPS to reveal the root cause of PI coatings. We find that the increment of electrochemical performance is the physical barrier interactions of PI coatings. Even at high voltage, PI coatings are stable without structural changes. These findings provide robust support for PI materials applied in LIBs, especially for coating high‑nickel materials to promote their commercialization.
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•PI@NCM622 cathode materials are prepared by the self-growing method and thermal imidized at 300 °C for 2 h.•PI@NCM622 cathode materials show excellent electrochemical performance by adding 4 wt% precursors.•PI coatings are stable without structural changes at high voltage and play the role of physical barriers.
A low-cost and minimal-processing-step method is demonstrated to synthesize Yb2O3-ZrO2 system by laser excitation catalyzed solid-state reaction. With 980 nm CW laser irradiating, near-resonant ...excitation of Yb3+ ions can obviously enhance solid state reaction. As the molar content of Yb2O3 rises from 12.5% to 50%, the lattice parameter of Yb2O3-ZrO2 ceramic increases distinctly. Among them, high crystal quality of Yb2Zr2O7 and Yb0.2Zr0.8O1.9 are synthesized at the laser power of 400 W for 10 s. Two obvious Raman peaks of Yb2Zr2O7 represent increased Raman activity. X-ray photoelectron spectroscopy (XPS) and Impedance spectroscopy demonstrate the huge amount of the oxygen vacancies in Yb0.2Zr0.8O1.9. Yb2Zr2O7 shows lowest thermal conductivity among all the ceramics studied, within the range of 0.497-0.730 W mK−1 from 25 °C to 1200 °C, which indicates a promising thermal barrier material.
A novel design method for absorber is presented, based on pixelated FSS with common effect of metallic pixels and lumped resistors. Considering the relative position of resistors and pixelated ...patches, the estimation of distribution algorithm is firstly employed to optimize the absorbing performance. Optimization process demonstrates its availability and high-efficiency. An absorption band (3.08-6.00 GHZ) below -6 dB formed with two strong absorption peaks is achieved, compared with the poor absorption performance in pixelated FSS without resistors. The simulated surface current distributions suggest that the loaded resistors are the main source for energy loss of incident electromagnetic wave, and provide an intuitive explanation to the correlation of optimized unit cell geometry and corresponding absorption peaks. The designed absorber is fabricated and the measured reflectivity curve fits well with the simulated results, which indicates that the availability of novel design method.
Abstract
Hypoxia and hydrogen peroxide (H
2
O
2
) accumulation form the profibrogenic liver environment, which involves fibrogenesis and chronic stimulation of hepatic stellate cells (HSCs). Catalase ...(CAT) is the major antioxidant enzyme that catalyzes H
2
O
2
into oxygen and water, which loses its activity in different liver diseases, especially in liver fibrosis. Clinical specimens of cirrhosis patients and liver fibrotic mice are collected in this work, and results show that CAT decrease is closely correlated with hypoxia-induced transforminmg growth factor β1 (TGF-β1). A multifunctional nanosystem combining CAT-like MnO
2
and anti-fibrosis Saikosaponin b1 (Ssb1) is subsequently constructed for antifibrotic therapy. MnO
2
catalyzes the accumulated H
2
O
2
into oxygen, thereby ameliorating the hypoxic and oxidative stress to prevent activation of HSCs, and assists to enhance the antifibrotic pharmaceutical effect of Ssb1. This work suggests that TGF-β1 is responsible for the diminished CAT in liver fibrosis, and our designed MnO
2
@PLGA/Ssb1 nanosystem displays enhanced antifibrotic efficiency through removing excess H
2
O
2
and hypoxic stress, which may be a promising therapeutic approach for liver fibrosis treatment.
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