The selective laser melting (SLM) process parameters significantly affect the bonding of melting powders and the substrate or deposited layer, and the microstructure of end-use components. In this ...study, single track, double track and cubic sample SLM experiments were carried out to investigate the effect of process parameters on the surface morphology of SLM-fabricated AlSi10Mg alloy. The hierarchical microstructures discriminated by the Si phase are observed in SLM-processed AlSi10Mg samples. The formation mechanism of the hierarchical microstructures is elucidated. The formula proved that the solidification rate (R) increases gradually from the boundary to the center of the melt pool. Coarse zones are formed by the instantaneous existence of an extremely high ratio of thermal gradient (G) and solidification rate at the melt pool boundary, where solidification microstructure grows planar. With the heat propagating, a gradual change of the G/R ratio appears and the microstructure turns to columnar-dendritic growth, creating the fine zones.
Metal FDM technology overcomes the problems of high cost, high energy consumption and high material requirements of traditional metal additive manufacturing by combining FDM and powder metallurgy and ...realizes the low-cost manufacturing of complex metal parts. In this work, 15-5PH stainless steel granules with a powder content of 90% and suitable for metal FDM were developed. The flowability and formability of the feedstock were investigated and the parts were printed. A two-step (solvent and thermal) debinding process is used to remove the binder from the green part. After being kept at 75 °C in cyclohexane for 24 h, the solvent debinding rate reached 98.7%. Following thermal debinding, the material’s weight decreased by slightly more than 10%. Sintering was conducted at 1300 °C, 1375 °C and 1390 °C in a hydrogen atmosphere. The results show that the shrinkage of the sintered components in the X-Y-Z direction remains quite consistent, with values ranging from 13.26% to 19.58% between 1300 °C and 1390 °C. After sintering at 1390 °C, the material exhibited a relative density of 95.83%, a hardness of 101.63 HRBW and a remarkable tensile strength of 770 MPa. This work realizes the production of metal parts using 15-5PH granules’ extrusion additive manufacturing, providing a method for the low-cost preparation of metal parts. And it provides a useful reference for the debinding and sintering process settings of metal FDM. In addition, it also enriches the selection range of materials for metal FDM.
Internal pore defects are inevitable during laser powder bed fusion (LPBF), which have a significant impact on the mechanical properties of the parts. Therefore, detecting pores and obtaining their ...morphology will contribute to the quality of LPBF parts. Currently, supervised models are used for defect image detection, which requires a large amount of LPBF sample data, image labeling, and computing power equipment during the training process, resulting in high detection costs. This study extensively collected LPBF sample data and proposed a method for pore defect classification by obtaining its morphological features while detecting pore defects in optical microscopy (OM) images under various conditions. Compared with other advanced models, the proposed method achieves better detection accuracy on pore defect datasets with limited data. In addition, quickly detecting pore defects in a large number of labeling ground truth images will also contribute to the development of deep learning. In terms of image segmentation, the average accuracy scores of this method in the test images exceed 85%. The research results indicate that the algorithm proposed in this paper is suitable for quickly and accurately identifying pore defects from optical microscopy images.
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•This study provided a strategy for synthesizing carrier-free curcumin, quercetin and resveratrol-based nanomedicines with one-pot method, that is overcoming the dilemma of complexity ...carrier synthesis and drug low loading rate.•Curcumin nanomedicines not only decreased the cytotoxicity of curcumin but also preserved its anti-inflammatory activity.•In the acute and chronic inflammation models, including sepsis, IBD, and liver fibrosis, nanomedicines showed a better therapeutic effect than free curcumin.
Hyperinflammation can lead to tissue injury, organ failure, and even fatalities by overproducing proinflammatory cytokines. The long-term safety and outstanding anti-inflammatory ability of natural products have attracted much attention, but the low solubility and bioavailability limit their application. In this study, PGDE was conjugated with aromatic hydroxy groups of curcumin, resveratrol, and quercetin to prepare polyphenolic nano-assemblies. The nano-assemblies showed a comparable capacity for scavenging DPPH and ABTS free radicals with curcumin. The modification not only decreased the cytotoxicity of curcumin but also the anti-inflammation activity was preserved successfully. In vivo tests, NCAs were preferentially located at the inflammatory sites and performed effective therapeutic effects on acute and chronic inflammation models including sepsis, IBD, and liver fibrosis models. The anti-inflammatory activities were primarily realized by suppressing the overproduction of TNF-α, IL-6 and IL-β cytokines, and down-regulating the ROS-related NOX-1 and NOX-4. Additionally, NCAs inhibited the activation of the TGF-α/Smad pathway and decreased the production of α-SMA to alleviate collagen deposition in fibrosis mice. This study described a simple method for preparing nano-assemblies of insoluble polyphenols via the carrier-free self-assembly method, which improved the therapeutic effect on inflammatory diseases and broadened the application field of insoluble natural active polyphenols.
Bile components play a critical role in maintaining gut microbiota homeostasis. In cholestasis, bile secretion is impaired, leading to liver injury. However, it remains to be elucidated whether gut ...microbiota plays a role in cholestatic liver injury. Here, we performed a sham operation and bile duct ligation (BDL) in antibiotic-induced microbiome depleted (AIMD) mice and assessed liver injury and fecal microbiota composition in these mice. Significant reductions in gut microbiota richness and diversity were found in AIMD-sham mice when compared to sham controls. Three-day BDL leads to great elevation of plasma ALT, ALP, total bile acids, and bilirubin where reduced diversity of the gut microbiota was also found. AIMD further aggravated cholestatic liver injury evidenced by significantly higher levels of plasma ALT and ALP, associated with further reduced diversity and increased Gram-negative bacteria in gut microbiota. Further analyses revealed increased levels of LPS in the plasma of AIMD-BDL mice where elevated expression of inflammatory genes and decreased expression of hepatic detoxification enzymes were also found in liver when compared to the BDL group. These findings indicate that gut microbiota plays a critical role in cholestatic liver injury. Maintaining its homeostasis may alleviate liver injury in patients with cholestasis.
Bile acid transporters maintain bile acid homeostasis. Little is known about the functions of some transporters in cholestasis or their regulatory mechanism. We investigated the hepatic expression of ...solute carrier organic anion transporter family member 3A1 (SLCO3A1, also called OATP3A1) and assessed its functions during development of cholestasis.
We measured levels of OATP3A1 protein and messenger RNA and localized the protein in liver tissues from 22 patients with cholestasis and 21 patients without cholestasis, using real-time quantitative polymerase chain reaction, immunoblot, and immunofluorescence analyses. We performed experiments with Slco3a1-knockout and C57BL/6J (control) mice. Mice and Sprague-Dawley rats underwent bile duct ligation (BDL) or a sham operation. Some mice were placed on a 1% cholic acid (CA) diet to induce cholestasis or on a control diet. Serum and liver tissues were collected and analyzed; hepatic levels of bile acids and 7-α-C4 were measured using liquid chromatography/mass spectrometry. Human primary hepatocytes and hepatoma (PLC/PRF/5) cell lines were used to study mechanisms that regulate OATP3A1 expression and transport.
Hepatic levels of OATP3A1 messenger RNA and protein were significantly increased in liver tissues from patients with cholestasis and from rodents with BDL or 1% CA diet–induced cholestasis. Levels of fibroblast growth factor 19 (FGF19, FGF15 in rodents) were also increased in liver tissues from patients and rodents with cholestasis. FGF19 signaling activated the Sp1 transcription factor and nuclear factor κB to increase expression of OATP3A1 in hepatocytes; we found binding sites for these factors in the SLCO3A1 promoter. Slco3a1-knockout mice had shorter survival times and increased hepatic levels of bile acid, and they developed more liver injury after the 1% CA diet or BDL than control mice. In hepatoma cell lines, we found OATP3A1 to take prostaglandin E2 and thyroxine into cells and efflux bile acids.
We found levels of OATP3A1 to be increased in cholestatic liver tissues from patients and rodents compared with healthy liver tissues. We show that OATP3A1 functions as a bile acid efflux transporter that is up-regulated as an adaptive response to cholestasis.
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•HA-PEI actively targets the liver through the CD44 receptor to reduce the off-target effects of PEI (highest effect at 1000 K).•This study provided a therapeutic agent for late-stage ...liver injury induced by acetaminophen that outperforms the FDA-approved drug N-acetylcysteine.•HA-PEI could increase oxygen content, eliminate ROS, and maintain mitochondrial membrane potential to protect hepatocytes that are under oxidative stress and inhibit the secretion of inflammatory factors to block the migration of immune cells to the liver, safeguarding hepatocytes from secondary damage.
Acute liver injury (ALI) is one of the most important causes of liver failure, and there are no FDA-approved drugs that could therapy late-stage ALI. It has been shown in this study that HA-PEI, a molecule formed by covalently combining HA and PEI, can effectively treat advanced ALI. Through the CD44 receptor, HA-PEI could target the liver actively, with the highest liver-targeting effect confirmed at 1000 K. The underlying mechanism of protection of HA-PEI is by increasing oxygen content, reducing ROS, and maintaining mitochondrial membrane potential. HA-PEI also inhibits the secretion of inflammatory factors and blocks the migration of immune cells to the liver, protecting the hepatocytes not suffer from secondary damage. More importantly, for late-stage ALI, NAC, as the only FDA-approved drug, is completely ineffective, whereas HA-PEI has an excellent therapeutic effect. This work provides a new safe therapeutic agent for ALI, which has a bright application prospect.
Glomerulonephritis (GN) is the most common cause of end-stage renal failure worldwide; in most cases, it cannot be cured and can only delay the progression of the disease. At present, the main ...treatment methods include symptomatic therapy, immunosuppressive therapy, and renal replacement therapy. However, effective treatment of GN is hindered by issues such as steroid resistance, serious side effects, low bioavailability, and lack of precise targeting. With the widespread application of nanoparticles in medical treatment, novel methods have emerged for the treatment of kidney diseases. Targeted transportation of drugs, nucleic acids, and other substances to kidney tissues and even kidney cells through nanodrug delivery systems can reduce the systemic effects and adverse reactions of drugs and improve treatment effectiveness. The high specificity of nanoparticles enables them to bind to ion channels and block or enhance channel gating, thus improving inflammation. This review briefly introduces the characteristics of GN, describes the treatment status of GN, systematically summarizes the research achievements of nanoparticles in the treatment of primary GN, diabetic nephropathy and lupus nephritis, analyzes recent therapeutic developments, and outlines promising research directions, such as gas signaling molecule nanodrug delivery systems and ultrasmall nanoparticles. The current application of nanoparticles in GN is summarized to provide a reference for better treatment of GN in the future.
Linear discriminant analysis (LDA) often suffers from the small sample size problem when dealing with high-dimensional face data. Random subspace can effectively solve this problem by random sampling ...on face features. However, it remains a problem how to construct an optimal random subspace for discriminant analysis and perform the most efficient discriminant analysis on the constructed random subspace. In this paper, we propose a novel framework, random discriminant analysis (RDA), to handle this problem. Under the most suitable situation of the principal subspace, the optimal reduced dimension of the face sample is discovered to construct a random subspace where all the discriminative information in the face space is distributed in the two principal subspaces of the within-class and between-class matrices. Then we apply Fisherface and direct LDA, respectively, to the two principal subspaces for simultaneous discriminant analysis. The two sets of discriminant analysis features from dual principal subspaces are first combined at the feature level, and then all the random subspaces are further integrated at the decision level. With the discriminating information fusion at the two levels, our method can take full advantage of useful discriminant information in the face space. Extensive experiments on different face databases demonstrate its performance.
Non-alcoholic fatty liver disease (NAFLD) is characterized by the abnormal buildup of lipids in the liver tissue. Non-alcoholic fatty liver (NAFL) may progress to non-alcoholic steatohepatitis. ...Triglycerides in the liver can originate from various sources, including de novo lipogenesis (DNL). Research indicates that DNL significantly escalates in NAFLD, worsening steatosis. However, the precise regulatory mechanism of DNL in the development of this disease is not fully understood. Therefore, the targeted reduction of DNL could be a crucial therapeutic strategy. Currently, numerous pharmaceutical agents targeting DNL have been developed, attracting significant attention. This review examines the mechanism of DNL upregulation in NAFLD, assessing its potential as a therapeutic target for hepatic steatosis. Furthermore, we thoroughly examine hepatocellular lipotoxicity and provide an extensive review of the application and limitations of relevant therapeutic drugs, with a focus on key enzymes involved in DNL. The implementation of these pharmacological strategies is expected to significantly improve the management and overall outcomes for patients with NAFLD.
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