Enhancing Antimicrobial Performance of Gauze via Modification by Ag-Loaded Polydopamine Submicron Particles.

Silver nanoparticles (AgNPs) are known for their antibacterial properties and their ability to promote wound healing. By incorporating silver nanoparticles into medical gauze, the resulting composite material shows promise as an advanced wound dressing. However, clinical applications are hindered by challenges related to the stability of silver nanoparticle loading on the gauze as nanoparticle leaching can compromise antibacterial efficacy. In this study, silver nanoparticles were immobilized onto polydopamine (PDA) submicron particles, which were then used to modify medical gauze. Energy dispersive spectroscopy (EDS) was employed to analyze the elemental distribution on the modified gauze, confirming successful surface modification. The antibacterial properties of the modified gauze were assessed using a laser scanning confocal microscope (CLSM). The results demonstrated a significant reduction in the adhesion rates of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by 99.1% and 63%, respectively, on the PDA-Ag-modified gauze. Optical density (OD) measurements at 590 nm indicated that the modified gauze effectively inhibited biofilm formation, underscoring its potent antimicrobial capabilities. Further antibacterial efficacy was evaluated by diluting and plating co-cultured bacterial solutions with the modified dressing, followed by 24 h incubation and colony counting. The gauze exhibited an antibacterial efficiency of 99.99% against E. coli and 99.8% against S. aureus. Additionally, cell compatibility tests, involving the co-culture of PDA-Ag composites with human cells, demonstrated excellent biocompatibility. These findings suggest that PDA-Ag-modified medical gauze holds significant potential for the treatment of infected wounds, offering a promising solution to improve wound care through enhanced antimicrobial activity and biocompatibility.

Novel method for recovering valuable metals from Sn ash: Vacuum carbothermal reduction-directional condensation.

Sn ash recycling is an industry with positive development prospects, as it provides better-protected resources, promotes sustainable development, and lays a solid foundation for future development. In this study, an innovative vacuum carbothermal reduction-directional condensation process was developed. The thermodynamic analysis results indicated that the initial reaction pressure and temperature for the carbothermal reduction of the system was 1-10 Pa and 998-1063 K, respectively. The saturation vapor pressure, separation coefficient, and condensation temperature of Sn, Pb, and Zn in the reduced products differed significantly, and their separation could be achieved by controlling the volatilization and condensation temperatures. A single-factor experiment investigated the effects of carbon ratio, temperature, and time on the reduction efficiency, direct yield, and recovery rate. The optimal experimental conditions were the ratio of MeO to C of 4:1, temperature of 1373 K, and time of 120 min. Sn, Pb, and Zn products were obtained at different positions. This process shortens the traditional process, reduces the reduction cost of Sn, and enables the implementation of the process, making it environmentally friendly.

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway.

BACKGROUND: Acute liver failure (ALF) is an unpredictable and life-threatening critical illness. The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure. METHODS: Animals were divided into 3 groups, normal, thioacetamide (TAA, ALF model) and TAA + AGK2. Cultured L02 cells were divided into 5 groups, normal, TAA, TAA + mitofusin 2 (MFN2)-siRNA, TAA + AGK2, and TAA + AGK2 + MFN2-siRNA groups. The liver histology was evaluated with hematoxylin and eosin staining, inositol-requiring enzyme 1 (IRE1), activating transcription factor 6ß (ATF6ß), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylated-PERK (p-PERK). C/EBP homologous protein (CHOP), reactive oxygen species (ROS), MFN2 and glutathione peroxidase 4 (GPX4) were measured with Western blotting, and cell viability and liver chemistry were also measured. Mitochondria-associated endoplasmic reticulum membranes (MAMs) were measured by immunofluorescence. RESULTS: The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis, which were reduced by AGK2 pre-treatment. In comparison to the normal group, apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ in the TAA-induced ALF model group were significantly increased, which were decreased by AGK2 pre-treatment. The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group, which were enhanced by AGK2 pre-treatment. Compared with the TAA-induced L02 cell, apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group. AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1, ATF6ß, p-PERK, CHOP, ROS and Fe2+ and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell. Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells. CONCLUSIONS: The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.

Research Progress on Low-Surface-Energy Antifouling Coatings for Ship Hulls: A Review.

The adhesion of marine-fouling organisms to ships significantly increases the hull surface resistance and expedites hull material corrosion. This review delves into the marine biofouling mechanism on marine material surfaces, analyzing the fouling organism adhesion process on hull surfaces and common desorption methods. It highlights the crucial role played by surface energy in antifouling and drag reduction on hulls. The paper primarily concentrates on low-surface-energy antifouling coatings, such as organic silicon and organic fluorine, for ship hull antifouling and drag reduction. Furthermore, it explores the antifouling mechanisms of silicon-based and fluorine-based low-surface-energy antifouling coatings, elucidating their respective advantages and limitations in real-world applications. This review also investigates the antifouling effectiveness of bionic microstructures based on the self-cleaning abilities of natural organisms. It provides a thorough analysis of antifouling and drag reduction theories and preparation methods linked to marine organism surface microstructures, while also clarifying the relationship between microstructure surface antifouling and surface hydrophobicity. Furthermore, it reviews the impact of antibacterial agents, especially antibacterial peptides, on fouling organisms' adhesion to substrate surfaces and compares the differing effects of surface structure and substances on ship surface antifouling. The paper outlines the potential applications and future directions for low-surface-energy antifouling coating technology.

Antifouling applications and fabrications of biomimetic micro-structured surfaces: A review.

BACKGROUND: Since the inception of the term "Biomimetics" in 1991, the concept of utilizing natural solutions or deriving inspiration from nature to address contemporary engineering challenges has gained significant attention within the scientific community. Organisms, in order to thrive in harsh environments, have evolved a wide range of micro/nanostructured surfaces, which serve as a rich source of inspiration for the development of artificial micro/nano-structured surfaces. These natural adaptations provide valuable insights and novel pathways for fabricating such surfaces. AIM: To conclude recent advances in micro/nano-structured surfaces from four aspects: biomimetic micro-structured surfaces of plants and animals, properties and applications of biomimetic surfaces, methods of preparations, and their limitation. KEY SCIENTIFIC CONCEPTS: Artificial micro/nano-structured surfaces inspired by animals and plants are classified and demonstrated according to their living environment. The performances, principles and preparation techniques of natural superhydrophobic surfaces, slippery liquid-infused porous surfaces (SLIPS), anisotropic surfaces, etc. are described in detail. Moreover, the pros and cons of each preparation measures are compared and the challenges developing large-scale, cost-effective surface microstructure preparation processes are pointed out. In the end, the development trends of artificial micro/nano-structured surface are forecasted.

Research Progress on New Environmentally Friendly Antifouling Coatings in Marine Settings: A Review.

Any equipment submerged in the ocean will have its surface attacked by fouling organisms, which can cause serious damage. Traditional antifouling coatings contain heavy metal ions, which also have a detrimental effect on the marine ecological environment and cannot fulfill the needs of practical applications. As the awareness of environmental protection is increasing, new environmentally friendly and broad-spectrum antifouling coatings have become the current research hotspot in the field of marine antifouling. This review briefly outlines the formation process of biofouling and the fouling mechanism. Then, it describes the research progress of new environmentally friendly antifouling coatings in recent years, including fouling release antifouling coatings, photocatalytic antifouling coatings and natural antifouling agents derived from biomimetic strategies, micro/nanostructured antifouling materials and hydrogel antifouling coatings. Highlights include the mechanism of action of antimicrobial peptides and the means of preparation of modified surfaces. This category of antifouling materials has broad-spectrum antimicrobial activity and environmental friendliness and is expected to be a new type of marine antifouling coating with desirable antifouling functions. Finally, the future research directions of antifouling coatings are prospected, which are intended to provide a reference for the development of efficient, broad-spectrum and green marine antifouling coatings.

Evaluation on displacement risks of dismantling temporary lining in tunnel and optimization on temporary lining configuration.

In tunnel engineering, the temporary lining is adopted as an effective countermeasure in mitigating tunnel failure potential, often featured by extra-large cross-sections and/or driven through weak ground conditions. However, dismantling temporary linings negatively impacts primary linings. In this paper, the comprehensive research is conducted on the displacement risk caused by dismantling temporary lining based on two alternative tunneling methods (TM-1 and TM-2). Besides, the following three influence factors are taken into consideration: the axial forces in temporary linings, the thickness of preliminary linings, and the deformation modulus of ground. After that, the tunneling method optimization plan is proposed from the view of these three influence factors. The results show that TM-1 always induces invert uplift, whereas TM-2 mainly brings about invert uplift or sidewall bulging depending on which transverse or vertical linings are dominant in terms of axial force values. For TM-2, the axial force in transverse linings can suppress the development of maximum deformation increment (MDI) value at invert when the axial forces in transverse linings are smaller than those in vertical linings. It is also found that with the further increase of the axial force in transverse linings in TM-2, MDI relocates to the sidewall. Moreover, on the basis of the displacement risk evaluations, an optimization on the temporary lining configurations has been developed by replacing temporary linings with pre-tension anchor cables to reduce the risk of dismantling temporary linings. All the research results can provide some important reference for the similar tunnel engineering in the future.

PANoptosis: A Cell Death Characterized by Pyroptosis, Apoptosis, and Necroptosis.

PANoptosis is a new cell death proposed by Malireddi et al in 2019, which is characterized by pyroptosis, apoptosis and necroptosis, but cannot be explained by any of them alone. The interaction between pyroptosis, apoptosis and necroptosis is involved in PANoptosis. In this review, from the perspective of PANoptosis, we focus on the relationship between pyroptosis, apoptosis and necroptosis, the key molecules in the process of PANoptosis and the formation of PANoptosome, as well as the role of PANoptosis in diseases. We aim to understand the mechanism of PANoptosis and provide a basis for targeted intervention of PANoptosis-related molecules to treat human diseases.

Detection of myeloma cell-derived microvesicles: a tool to monitor multiple myeloma load.

The persistence of tumor load in multiple myeloma (MM) lead to relapse in patients achieving complete remission (CR). Appropriate and effective methods of myeloma tumor load monitoring are important for guiding clinical management. This study aimed to clarify the value of microvesicles in monitoring MM tumor load. Microvesicles in bone marrow and peripheral blood were isolated by differential ultracentrifugation and detected by flow cytometry. Western blotting was applied to assess myosin light chain phosphorylation levels. Flow cytometry to detect Ps+CD41a-, Ps+CD41a-CD138+, Ps+CD41a-BCMA+ microvesicles from bone marrow can be used to predict myeloma burden, furthermore, Ps+CD41a- microvesicles may as a potential index to MRD test. Mechanistically, the releasing of microvesicles from MM cell was regulated by Pim-2 Kinase via Phosphorylation of MLC-2 protein.

Convolutional neural network for detecting rib fractures on chest radiographs: a feasibility study.

BACKGROUND: Chest radiography is the standard investigation for identifying rib fractures. The application of artificial intelligence (AI) for detecting rib fractures on chest radiographs is limited by image quality control and multilesion screening. To our knowledge, few studies have developed and verified the performance of an AI model for detecting rib fractures by using multi-center radiographs. And existing studies using chest radiographs for multiple rib fracture detection have used more complex and slower detection algorithms, so we aimed to create a multiple rib fracture detection model by using a convolutional neural network (CNN), based on multi-center and quality-normalised chest radiographs. METHODS: A total of 1080 radiographs with rib fractures were obtained and randomly divided into the training set (918 radiographs, 85%) and the testing set (162 radiographs, 15%). An object detection CNN, You Only Look Once v3 (YOLOv3), was adopted to build the detection model. Receiver operating characteristic (ROC) and free-response ROC (FROC) were used to evaluate the model's performance. A joint testing group of 162 radiographs with rib fractures and 233 radiographs without rib fractures was used as the internal testing set. Furthermore, an additional 201 radiographs, 121 with rib fractures and 80 without rib fractures, were independently validated to compare the CNN model performance with the diagnostic efficiency of radiologists. RESULTS: The sensitivity of the model in the training and testing sets was 92.0% and 91.1%, respectively, and the precision was 68.0% and 81.6%, respectively. FROC in the testing set showed that the sensitivity for whole-lesion detection reached 91.3% when the false-positive of each case was 0.56. In the joint testing group, the case-level accuracy, sensitivity, specificity, and area under the curve were 85.1%, 93.2%, 79.4%, and 0.92, respectively. At the fracture level and the case level in the independent validation set, the accuracy and sensitivity of the CNN model were always higher or close to radiologists' readings. CONCLUSIONS: The CNN model, based on YOLOv3, was sensitive for detecting rib fractures on chest radiographs and showed great potential in the preliminary screening of rib fractures, which indicated that CNN can help reduce missed diagnoses and relieve radiologists' workload. In this study, we developed and verified the performance of a novel CNN model for rib fracture detection by using radiography.

Integration of Antifouling and Underwater Sound Absorption Properties into PDMS/MWCNT/SiO2 Coatings.

Any surface immersed in sea water will suffer from marine fouling, including underwater sound absorption coatings. Traditional underwater sound absorption coatings rely heavily on the use of toxic, biocide-containing paints to combat biofouling. In this paper, an environmentally-friendly nanocomposite with integrated antifouling and underwater sound absorption properties was fabricated by adopting MWCNTs-COOH and SiO2 into PDMS at different ratios. SEM, FTIR and XPS results demonstrated MWCNTs were mixed into PDMS, and the changes in elements were also analyzed. SiO2 nanoparticles in PDMS decreased the tensile properties of the coating, while erosion resistance was enhanced. Antibacterial properties of the coatings containing MWCNTs-COOH and SiO2 at a ratio of 1:1, 1:3, and 1:5 reached 62.02%, 72.36%, and 74.69%, respectively. In the frequency range of 1500-5000 Hz, the average sound absorption coefficient of PDMS increased from 0.5 to greater than 0.8 after adding MWCNTs-COOH and SiO2, which illustrated that the addition of nanoparticles enhanced the underwater sound absorption performance of the coating. Incorporating MWCNTs-COOH and SiO2 nanoparticles into the PDMS matrix to improve its sound absorption and surface antifouling properties provides a promising idea for marine applications.

NOD2-mediated HDAC6/NF-κb signalling pathway regulates ferroptosis induced by extracellular histone H3 in acute liver failure.

Acute liver failure (ALF) is life-threatening and often associated with high mortality rates. The aim of the present study was to investigate whether extracellular histone H3 could induce ferroptosis in hepatic macrophages in ALF and explore its potential mechanism. RAW264.7 macrophages and C57BL/6 mice were used in this study. LPS, D-galactosamine (D-Gal), histone H3, histone H3 antibody, NOD2 agonist Muramyl Dipeptide (MDP) and HDAC6-siRNA were administered in this study. The key molecules of ferroptosis, NOD2, HDAC6 and the NF-κb pathway, were detected. In vitro, histone H3 was released into the extracellular environment from cell nucleus after LPS exposure. In addition, histone H3 could induce ferroptosis in RAW264.7 macrophages with increased level of Fe2+ and ROS and decreased levels of GPX4 and GSH. MDP further aggravated ferroptosis in RAW264.7 macrophages stimulated by histone H3, which was accompanied by elevated NOD2, HDAC6, p-P65 and IκBα. HDAC6-siRNA ameliorated ferroptosis in RAW264.7 macrophages induced by histone H3, which was accompanied by decreased levels of HDAC6, p-P65 and IκBα. However, HDAC6-siRNA did not alter NOD2 levels in RAW264.7 macrophages administered histone H3. In vivo, the levels of NOD2, HDAC6 the NF-κb pathway and ferroptosis were increased in ALF mice, which were downregulated by histone H3 antibody and upregulated by histone H3. Extracellular histone H3 could induce ferroptosis in hepatic macrophages in ALF by regulating theNOD2-mediated HDAC6/NF-κb signalling pathway.

[Colloidal gold immunochromatographic test strip for virus detection: a review].

Colloidal gold immunochromatographic strip is a fast, sensitive and accurate solid-phase labeling detection technology, which has the advantages of low price, easy operation, rapid detection and high specificity, with the potential to qualitatively detect the relevant viruses in a short time with desired sensitivity and accuracy. It effectively addresses the disadvantages of long detection time, equipment inconvenience and professionalism requirement of the traditional detection methods used in the medical, veterinary, animal, plant virus detection, pesticide residue detection and other areas. Presently, the technology has been applied in the detection of bacterial diseases, viral diseases and prevention of extensive spread of infectious diseases, and has sufficient room for further development. This review summarizes the application of colloidal gold immunochromatography strip for biological virus detection, followed by prospecting future perspectives.

Transcription-independent regulation of STING activation and innate immune responses by IRF8 in monocytes.

Sensing of cytosolic DNA of microbial or cellular/mitochondrial origin by cGAS initiates innate immune responses via the adaptor protein STING. It remains unresolved how the activity of STING is balanced between a productive innate immune response and induction of autoimmunity. Here we show that interferon regulatory factor 8 (IRF8) is essential for efficient activation of STING-mediated innate immune responses in monocytes. This function of IRF8 is independent of its transcriptional role in monocyte differentiation. In uninfected cells, IRF8 remains inactive via sequestration of its IRF-associated domain by its N- and C-terminal tails, which reduces its association with STING. Upon triggering the DNA sensing pathway, IRF8 is phosphorylated at Serine 151 to allow its association with STING via the IRF-associated domain. This is essential for STING polymerization and TBK1-mediated STING and IRF3 phosphorylation. Consistently, IRF8-deficiency impairs host defense against the DNA virus HSV-1, and blocks DNA damage-induced cellular senescence. Bone marrow-derived mononuclear cells which have an autoimmune phenotype due to deficiency of Trex1, respond to IRF-8 deletion with reduced pro-inflammatory cytokine production. Peripheral blood mononuclear cells from systemic lupus erythematosus patients are characterized by elevated phosphorylation of IRF8 at the same Serine residue we find to be important in STING activation, and in these cells STING is hyper-active. Taken together, the transcription-independent function of IRF8 we describe here appears to mediate STING activation and represents an important regulatory step in the cGAS/STING innate immune pathway in monocytes.

Characterization of the pathogenesis and immune response to a highly virulent Edwardsiella tarda strain responsible for mass mortality in the hybrid snakehead (Channa maculate ♀ × Channa argus ♂).

Edwardsiella tarda is reported as the causative agent of the systemic disease Edwardsiellosis in fish, which lead to huge economic losses in aquaculture. The pathogenicity and immune response to a highly virulent E. tarda isolate responsible for mass mortality in hybrid snakehead were performed. After species identification, morphology and virulence gene detection of Edwardsiella isolated from hybrid snakehead, the pathogenicity of the strain and histopathological changes in infected fish were analyzed. The infected fish exhibited typical acute hemorrhagic symptoms and enlarged internal organs. Histopathology revealed that the liver, spleen, kidney and intestinal tissues of diseased fish exhibited marked inflammatory with vacuolar degeneration and cell necrosis. Subsequently, humoral immune factors such as superoxide dismutase, lysozyme and acid phosphatase activities were detected as serum indicators, and real-time quantitative PCR was used to investigate immune-related genes (STAT1, HSP70, IgM, IL-6, IL-8, TRAF2, CD40, HLA-DMA and LCK) expression patterns in liver, spleen and head kidney. The results showed that these enzyme activity indicators and immune-related gene expression were significantly activated compared with healthy fish. These data provide insight into the pathogenic mechanisms and host immune responses of E. tarda, which could be useful for the future prevention and treatment of Edwardsiellosis in fish.

A 12-week personalised physical activity and dietary protein intervention for older adults undergoing peritoneal dialysis: A feasibility study.

This single-arm observational study explored the feasibility and efficacy of a 12-week personalised physical activity and dietary protein intervention programme for older adults undergoing peritoneal dialysis. Older adults undergoing peritoneal dialysis received eight individualised nutrition and physical activity advice sessions provided by trained nurses. Protein intake and physical activity were regarded as primary outcomes. All data were collected at baseline and at week 12. The enrolment rate was 78.4%. Twenty-nine patients participated in the study. Of these, 86.2% (25/29) completed the intervention. There was a significant increase in protein intake (t = -4.453, P< 0.001) and physical activity levels (Z = -2.929, P = 0.004). Of the participants, 56.0% achieved the targeted protein goal, and 41.4% met the physical activity goal. The timed up-and-go performance (t = 4.135, P = 0.001) increased after intervention. Trained nurses can successfully implement personalised diet and physical activity advice, and achieve promising patient outcomes.

Fusobacterium nucleatum promotes the development of acute liver failure by inhibiting the NAD+ salvage metabolic pathway.

BACKGROUND: Acute liver failure (ALF) patients are often accompanied by severe energy metabolism abnormalities and intestinal microecological imbalance. The intestinal mucosal barrier is severely damaged. Intestinal endotoxin can induce intestinal endotoxemia through the "Gut-Liver axis". More and more evidence shows that members of the gut microbiota, especially Fusobacterium nucleatum (F. nucleatum), are related to inflammatory bowel disease, but whether F. nucleatum is involved in the development of ALF and whether it affects the liver energy metabolism is unclear. METHODS: This study first detected the abundance of F. nucleatum and its effect on ALF disease, and explored whether F. nucleatum aggravated liver inflammation in vitro and in vivo. RESULTS: Our data showed that liver tissues of ALF patients contained different abundances of F. nucleatum, which were related to the degree of liver inflammation. In addition, we found that F. nucleatum infection affected the energy metabolism of the liver during the development of ALF, inhibited the synthesis pathway of nicotinamide adenine dinucleotide (NAD+)'s salvage metabolism, and promoted inflammatory damage in the liver. In terms of mechanism, F. nucleatum inhibited NAD+ and the NAD+-dependent SIRT1/AMPK signaling pathway, and promoted liver damage of ALF. CONCLUSIONS: Fusobacterium nucleatum coordinates a molecular network including NAD+ and SIRT1 to control the progress of ALF. Detection and targeting of F. nucleatum and its related pathways may provide valuable insights for the treatment of ALF.

Construction of PIK3C3 Transgenic Pig and Its Pathogenesis of Liver Damage.

As a member of the PIKs family, PIK3C3 participates in autophagy and plays a central role in liver function. Several studies demonstrated that the complete suppression of PIK3C3 in mammals can cause hepatomegaly and hepatosteatosis. However, the function of PIK3C3 overexpression on the liver and other organs is still unknown. In this study, we successfully generated PIK3C3 transgenic pigs through somatic cell nuclear transfer (SCNT) by designing a specific vector for the overexpression of PIK3C3. Plasmid identification was performed through enzyme digestion and transfected into the fetal fibroblasts derived from Diannan miniature pigs. After 2 weeks of culturing, six positive colonies obtained from a total of 14 cell colonies were identified through PCR. One positive cell line was selected as the donor cell line for SCNT for the construction of PIK3C3transgenic pigs. Thirty single blastocysts were collected and identified as PIK3C3 transgenic-positive blastocysts. Two surrogates became pregnant after transferring the reconstructed embryos into four surrogates. Fetal fibroblasts of PIK3C3-positive fetuses identified through PCR were used as donor cells for SCNT to generate PIK3C3 transgenic pigs. To further explore the function of PIK3C3 overexpression, genotyping and phenotyping of the fetuses and piglets obtained were performed by PCR, immunohistochemical, HE, and apoptosis staining. The results showed that inflammatory infiltration and vacuolar formation in hepatocytes and apoptotic cells, and the mRNA expression of NF-κB, TGF-ß1, TLR4, TNF-α, and IL-6 significantly increased in the livers of PIK3C3 transgenic pigs when compared with wild-type (WT) pigs. Immunofluorescence staining showed that LC3B and LAMP-1-positive cells increased in the livers of PIK3C3 transgenic pigs. In the EBSS-induced autophagy of the porcine fibroblast cells (PFCs), the accumulated LC3II protein was cleared faster in PIK3C3 transgenic (PFCs) thanWT (PFCs). In conclusion, PIK3C3 overexpression promoted autophagy in the liver and associated molecular mechanisms related to the activation of ULK1, AMBR1, DRAM1, and MTOR, causing liver damage in pigs. Therefore, the construction of PIK3C3 transgenic pigs may provide a new experimental animal resource for liver diseases.

Sirtuin1 attenuates acute liver failure by reducing reactive oxygen species via hypoxia inducible factor 1α.

BACKGROUND: The occurrence and development of acute liver failure (ALF) is closely related to a series of inflammatory reactions, such as the production of reactive oxygen species (ROS). Hypoxia inducible factor 1α (HIF-1α) is a key factor that regulates oxygen homeostasis and redox, and the stability of HIF-1α is related to the ROS level regulated by Sirtuin (Sirt) family. The activation of Sirt1 will lead to a powerful antioxidant defense system and therapeutic effects in liver disease. However, little is known about the relationship between HIF-1α and Sirt1 in the process of ALF and the molecular mechanism. AIM: To investigate whether HIF-1α may be a target of Sirt1 deacetylation and what the effects on ALF are. METHODS: Mice were administrated lipopolysaccharide (LPS)/D-gal and exposed to hypoxic conditions as animal model, and resveratrol was used as an activator of Sirt1. The cellular model was established with L02 cells stimulated by LPS. N-acetyl-L-cysteine was used to remove ROS, and the expression of Sirt1 was inhibited by nicotinamide. Western blotting was used to detect Sirt1 and HIF-1α activity and related protein expression. The possible signaling pathways involved were analyzed by immunofluorescent staining, co-immunoprecipitation, dihydroethidium staining, and Western blotting. RESULTS: Compared with mice stimulated with LPS alone, the expression of Sirt1 decreased, the level of HIF-1α acetylation increased in hypoxic mice, and the levels of carbonic anhydrase 9 and Bcl-2-adenovirus E1B interacting protein 3 increased significantly, which was regulated by HIF-1α, indicating an increase of HIF-1α activity. Under hypoxia, the down-regulation of Sirt1 activated and acetylated HIF-1α in L02 cells. The inhibition of Sirt1 significantly aggravated this effect and the massive production of ROS. The regulation of ROS was partly through peroxisome proliferator-activated receptor alpha or AMP-activated protein kinase. Resveratrol, a Sirt1 activator, effectively relieved ALF aggravated by hypoxia, the production of ROS, and cell apoptosis. It also induced the deacetylation of HIF-1α and inhibited the activity of HIF-1α. CONCLUSION: Sirt1 may have a protective effect on ALF by inducing HIF-1α deacetylation to reduce ROS.