Polyetheretherketone (PEEK) has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance. However, its biological inertness, poor osteoinduction, ...and weak antibacterial activity make the clinical applications in a dilemma. Inspired by the mussel adhesion mechanism, here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins (Mfps)-mimic peptide with clickable azido terminal. The peptide enables mussel-like adhesion on PEEK biomaterial surfaces, leaving azido groups for the further steps of biofunctionalizations. In this study, antimicrobial peptide (AMP) and osteogenic growth peptide (OGP) were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair. Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios, an optimal PEEK surface was finally obtained in this research, which could long-term inhibit bacterial growth, stabilize bone homeostasis and facilitate interfacial bone regeneration. In a word, this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants, in particular, achieving rational integration of multiple biofunctions to match clinical requirements.
A dual-effect of host defense and tissue repair can be rationally constructed by bioorthogonal conjugations of both anti-infective and osteo-inductive peptides on PEEK osteoimplants via an interlayer of mussel adhesive peptide with bioclickable properties. This study may provide a simple, efficient, and multi-functional surface strategy for improving the clinical outcomes of bio-inert medical implants. Display omitted
•An upgraded mussel-inspired surface strategy were developed.•A typical AMP and the active sequence of OGP were co-clicked on PEEK osteoimplants.•The coating can defend against bacterial invasion, facilitate osteogenesis.•The optimal dual-functional coating improves osseointegration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
All-inorganic halide perovskites have attracted significant attention because of their excellent photoelectric performance. However, several remaining challenges, including large-scale synthesis, ...strict limitations on the experimental conditions, and material stability, limit their practical application. In this study, we propose a simple ligand-assisted supersaturated recrystallization (LASR) procedure in order to prepare perovskite-related plum-pudding-like Cs4PbBr6/CsPbBr3 microcrystals (MCs) on a large scale and at room temperature. The LASR approach was proved to rely on the selection of an appropriate antisolvent. The synthesized Cs4PbBr6/CsPbBr3 MCs exhibit strong green emission at 520 nm with a narrow full-width at half-maximum (FWHM) value of 20 nm originating from the CsPbBr3 nanocrystals (NCs) embedded in the Cs4PbBr6 MCs. Additionally, the environmental stability experiment showed ∼20% PL intensity loss after storage under ambient conditions with 50% relative humidity (RH) for 2 months.
The 7075 aluminum alloy was an important structural material in the field of aeronautics and astronautics. With the development of this field, the requirements for its comprehensive properties were ...increasing. A novel casting method, the impact jet solid-liquid compound casting, was adopted to fabricate the 3A21/7075 aluminum alloy cladding material. Retrogression and reaging (RRA) treatment was further applied to the 3A21/7075 aluminum alloy cladding material in order to investigate the influence of RRA on microstructure and microhardness of the 3A21/7075 aluminum alloy cladding material. Then, the electron backscattered diffraction (EBSD) technique and the transmission electron microscope (TEM) together with the energy dispersive spectrometer (EDS) and the hardness test were utilized to analyze the influence of RRA treatment on microstructure and hardness of the 3A21/7075 aluminum alloy cladding material. The research results showed the 3A21/7075 aluminum alloy cladding material had better deformability. The amount of fine and dispersed phases precipitated in grains was in favor of improving the comprehensive mechanical properties of the 3A21/7075 aluminum alloy cladding material. This research might provide data and a theoretical approach for the engineering application of the 3A21/7075 aluminum alloy cladding material.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper studies the multi-depot joint distribution vehicle routing problem considering energy consumption with time-dependent networks (MDJDVRP-TDN). Aiming at the multi-depot joint distribution ...vehicle routing problem where the vehicle travel time depends on the variation characteristics of the road network speed in the distribution area, considering the influence of the road network on the vehicle speed and the relationship between vehicle load and fuel consumption, a multi-depot joint distribution vehicle routing optimization model is established to minimize the sum of vehicle fixed cost, fuel consumption cost and time window penalty cost. Traditional vehicle routing problems are modeled based on symmetric graphs. In this paper, considering the influence of time-dependent networks on routes optimization, modeling is based on asymmetric graphs, which increases the complexity of the problem. A hybrid genetic algorithm with variable neighborhood search (HGAVNS) is designed to solve the model, in which the nearest neighbor insertion method and Logistic mapping equation are used to generate the initial solution firstly, and then five neighborhood structures are designed to improve the algorithm. An adaptive neighborhood search times strategy is used to balance the diversification and depth search of the population. The effectiveness of the designed algorithm is verified through several groups of numerical instances with different scales. The research can enrich the relevant theoretical research of multi-depot vehicle routing problems and provide the theoretical basis for transportation enterprises to formulate reasonable distribution schemes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper considers the price conflict problem between the online channel of a food processing factory and the offline channel of the food retailers in food supply chains by analyzing the pricing ...decisions and coordination mechanisms between the food processing factory and food retailers under the influence of a food quality information service. First, the Stackelberg game method and the Bertrand game method are used to optimize the pricing decisions with the goal of maximizing the profits of the food processing factory and retailer. The analysis shows that the food quality information service level is positively correlated with the price of the factory’s own channel, and the influence of the food quality information service level on the price of the food processing factory’s or the food retailer’s own channel is stronger than its influence on the price of a competitor’s channel. Second, the food supply chain members’ pricing decisions are analyzed using the case analysis method by considering practical problems in the food supply chain. The results indicate that the food processing factory should use the Stackelberg game to make pricing decisions. However, it is optimal for the food retailer to make pricing decisions under the Bertrand game, and the total profit of the food supply chain is optimized under centralized decision making. Finally, we use both the quantitative discount mechanism and the Stackelberg game method to analyze the profits obtained by the food processing factory and retailer. The results indicate that the food processing factory should implement a quantitative discount mechanism when the quantity discount coefficient is greater than 0.4, and the retailer should implement a quantity discount mechanism when the quantity discount coefficient is in the range of 0.25 to 0.4.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The immune responses are involved in every stage after implantation but the reported immune-regulated materials only work at the beginning without fully considering the different phases of bone ...healing. Here, poly(aryl-ether-ether-ketone) (PEEK) is coated with a programmed surface, which rapidly releases interleukin-10 (IL-10) in the first week and slowly delivers dexamethasone (DEX) up to 4 weeks. Owing to the synergistic effects of IL-10 and DEX, an aptly weak inflammation is triggered within the first week, followed by significant M2 polarization of macrophages and upregulation of the autophagy-related factors. The suitable immunomodulatory activities pave the way for osteogenesis and the steady release of DEX facilitates bone regeneration thereafter. The sequential immune-mediated process is also validated by an 8-week implementation on a rat model. This is the first attempt to construct implants by taking advantage of both immune-mediated modulation and sequential regulation spanning all bone regeneration phases, which provides insights into the fabrication of advanced biomaterials for tissue engineering and immunological therapeutics.
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•A programed surface is designed and fabricated for immune-mediated osteogenesis•The degradation of PTMC coating enables a sequential release of IL-10 and DEX•Initially, osteoimmunomodulation is achieved by IL-10 and a small amount of DEX•Afterwards, sustained release of DEX fosters the peri-implant bone regeneration
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aiming at the time-dependent green vehicle routing problem with fuzzy demand, this paper comprehensively considers the dispatch costs, time window penalty costs, fuel costs, and the effects of ...vehicle travel speed, road gradient, and vehicle load on fuel consumption, a mixed integer programming model is formulated based on pre-optimization and re-optimization strategies. The traditional vehicle routing problems are modeled based on a symmetric graph. In this paper, considering the influence of time-dependent networks on route optimization, modeling is based on an asymmetric graph, which increases the complexity of the problem. In the pre-optimization stage, a pre-optimization scheme is generated based on the credibility measure theory; in the re-optimization stage, a new re-optimization strategy was used to deal with the service failure node In order to solve this problem, we developed a chaotic genetic algorithm with variable neighborhood search, pseudo-randomness of chaos was introduced to ensure the diversity of initial solutions, and adaptive neighborhood search times strategy and inferior solution acceptance mechanism were proposed to improve the performance of the algorithm. The numerical results show that the model and algorithm we proposed are effective.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cancer cells selectively promote translation of specific oncogenic transcripts to facilitate cancer survival and progression, but the underlying mechanisms are poorly understood. Here, we find that ...N7-methylguanosine (m7G) tRNA modification and its methyltransferase complex components, METTL1 and WDR4, are significantly upregulated in intrahepatic cholangiocarcinoma (ICC) and associated with poor prognosis. We further reveal the critical role of METTL1/WDR4 in promoting ICC cell survival and progression using loss- and gain-of-function assays in vitro and in vivo. Mechanistically, m7G tRNA modification selectively regulates the translation of oncogenic transcripts, including cell-cycle and epidermal growth factor receptor (EGFR) pathway genes, in m7G-tRNA-decoded codon-frequency-dependent mechanisms. Moreover, using overexpression and knockout mouse models, we demonstrate the crucial oncogenic function of Mettl1-mediated m7G tRNA modification in promoting ICC tumorigenesis and progression in vivo. Our study uncovers the important physiological function and mechanism of METTL1-mediated m7G tRNA modification in the regulation of oncogenic mRNA translation and cancer progression.
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•METTL1-mediated m7G tRNA modification promotes ICC cancer progression•METTL1-mediated m7G tRNA modification regulates tRNA expression and mRNA translation•m7G tRNA selectively modulates translation in a codon-dependent manner•Oncogenic function of m7G tRNA modification is verified in multiple ICC mouse models
Dai et al. show that METTL1-mediated m7G tRNA modification selectively regulates the translation of certain oncogenic transcripts and promotes intrahepatic cholangiocarcinoma progression in vitro and in vivo. The selective translation mechanism is regulated at the tRNA-mRNA codon recognition step in a codon-frequency-dependent manner.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Hepatitis B virus (HBV) infection is one of the most common risk factors for intrahepatic cholangiocarcinoma (ICC). However, there is no direct evidence of a causal relationship between ...HBV infection and ICC. In this study, we attempted to prove that ICC may originate from hepatocytes through a pathological study involving ICC tissue-derived organoids.
Method
The medical records and tumor tissue samples of 182 patients with ICC after hepatectomy were collected. The medical records of 182 patients with ICC were retrospectively analyzed to explore the prognostic factors. A microarray of 182 cases of ICC tumor tissue and 6 cases of normal liver tissue was made, and HBsAg was stained by immunohistochemistry (IHC) to explore the factors closely related to HBV infection. Fresh ICC tissues and corresponding adjacent tissues were collected to make paraffin sections and organoids. Immunofluorescence (IF) staining of factors including HBsAg, CK19, CK7, Hep-Par1 and Albumin (ALB) was performed on both fresh tissues and organoids. In addition, we collected adjacent nontumor tissues of 6 patients with HBV (+) ICC, from which biliary duct tissue and normal liver tissue were isolated and RNA was extracted respectively for quantitative PCR assay. In addition, the expression of HBV-DNA in organoid culture medium was detected by quantitative PCR and PCR electrophoresis.
Results
A total of 74 of 182 ICC patients were HBsAg positive (40.66%, 74/182). The disease-free survival (DFS) rate of HBsAg (+) ICC patients was significantly lower than that of HBsAg (−) ICC patients (
p
= 0.0137). IF and IHC showed that HBsAg staining was only visible in HBV (+) ICC fresh tissues and organoids, HBsAg expression was negative in bile duct cells in the portal area. Quantitative PCR assay has shown that the expression of HBs antigen and HBx in normal hepatocytes were significantly higher than that in bile duct epithelial cells. Combined with the IF and IHC staining, it was confirmed that HBV does not infect normal bile duct epithelial cells. In addition, IF also showed that the staining of bile duct markers CK19 and CK7 were only visible in ICC fresh tissue and organoids, and the staining of hepatocyte markers Hep-Par1 and ALB was only visible in normal liver tissue fresh tissue. Real-time PCR and WB had the same results. High levels of HBV-DNA were detected in the culture medium of HBV (+) organoids but not in the culture medium of HBV (−) organoids.
Conclusion
HBV-related ICC might be derived from hepatocytes. HBV (+) ICC patients had shorter DFS than HBV (−) ICC patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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