Enhancing osteogenesis and angiogenesis functions for Ti-24Nb-4Zr-8Sn scaffolds with methacrylated gelatin and deferoxamine.

Repair of large bone defects remains challenge for orthopedic clinical treatment. Porous titanium alloys have been widely fabricated by the additive manufacturing, which possess the elastic modulus close to that of human cortical bone, good osteoconductivity and osteointegration. However, insufficient bone regeneration and vascularization inside the porous titanium scaffolds severely limit their capability for repair of large-size bone defects. Therefore, it is crucially important to improve the osteogenic function and vascularization of the titanium scaffolds. Herein, methacrylated gelatin (GelMA) were incorporated with the porous Ti-24Nb-4Zr-8Sn (Ti2448) scaffolds prepared by the electron beam melting (EBM) method (Ti2448-GelMA). Besides, the deferoxamine (DFO) as an angiogenic agent was doped into the Ti2448-GelMA scaffold (Ti2448-GelMA/DFO), in order to promote vascularization. The results indicate that GelMA can fully infiltrate into the pores of Ti2448 scaffolds with porous cross-linked network (average pore size: 120.2 ± 25.1 µm). Ti2448-GelMA scaffolds facilitated the differentiation of MC3T3-E1 cells by promoting the ALP expression and mineralization, with the amount of calcium contents ∼2.5 times at day 14, compared with the Ti2448 scaffolds. Impressively, the number of vascular meshes for the Ti2448-GelMA/DFO group (∼7.2/mm2) was significantly higher than the control group (∼5.3/mm2) after cultivation for 9 h, demonstrating the excellent angiogenesis ability. The Ti2448-GelMA/DFO scaffolds also exhibited sustained release of DFO, with a cumulative release of 82.3% after 28 days. Therefore, Ti2448-GelMA/DFO scaffolds likely provide a new strategy to improve the osteogenesis and angiogenesis for repair of large bone defects.

Enhanced Toughening of the Lamellar Structure in a Black Coral by Interlocking Spines.

The black corals possess a branched, tree-like skeleton that is composed of chitin fibrils embedded within a protein matrix. This skeleton exhibits growth rings interlocked by spines. The lamellae are tightly wrapped around the spines, creating a structure akin to an onion. The indentation hardness and Young's modulus of the spines are comparable to those of the chitin rings. The compressive stress and the fracture toughness are increased by approximately 14.6% and 32.2% at higher loading rate in the dry state, but remain comparable at different loading rates in the wet state. The lamellar interfaces have a tendency to resist sliding in the dry state. As a result, the lamellae that curve around the spines are prone to fracturing one by one, just like an onion being peeled. This allows the material to absorb more fracture energy, ensuring that the spines can effectively resist the lamellar delamination.

Construction of an Au12Cd2 nanocluster with circularly polarized luminescence by a metal- and ligand-exchange strategy.

Excellent luminescence properties and unique chiral structures enable nanoclusters to be a novel class of circularly polarized luminescence (CPL) materials, and their precise structures facilitate the clarification of structure-activity relationships. However, efficiently preparing nanoclusters with CPL properties is still a great challenge. In this work, the luminescent properties as well as the molecular symmetry were simultaneously manipulated to transform the centrosymmetric Au14Cd1 into a chiral Au12Cd2 nanocluster, which has CPL properties. In detail, Cd doping and chiral-ligand exchange were performed simultaneously on the Au14Cd1 nanocluster to realize its photoluminescence enhancement and chiral-framework construction by increasing the alloying degree which is defined as deep-alloying and chiral ligand induction at the same time, resulting in the formation of an Au12Cd2 nanocluster with CPL properties. Further investigations revealed an increased alloying degree in the structure-maintained M6 kernel of Au12Cd2, which results in a 15-fold enhancement in quantum yield.

Comparative studies on the anti-wear behavior of prismatic structures in different shell species.

Prismatic structure is mainly located in the outer layer of mollusk shells. However, there is limited studies on their resistance to wear and the underlying mechanisms. The Vicker's hardness and sliding anti-wear properties of prismatic structures in four species of mollusk shells were systematically investigated for comparisons in the present work. The crystalline types, organic matrix content, structural arrangement, and dimension of prisms are varied among different species. The hardness and wear properties of prismatic structures are, in the first place, determined by the crystalline type, i.e., the aragonite prismatic structures are harder and more wear-resisting than the calcite types. The primary failure mechanism in the prismatic structure during wear tests is three-body abrasion. The volume of the crushed prism particles is directly related to the thickness of organic interface and the hardness of prisms. The organic sheaths form organic films during sliding, and thus lubricate the friction interface to some extent, but higher organic content leads to a wider interface, resulting in a higher plough force at the edge of prisms. A higher plough force gives rise to a severe three-body abrasion. Long and straight prisms perpendicular to the shell surface present a higher wear resistance. Too thin prisms cannot bear the plough force. Therefore, the anti-wear properties of prismatic structures are governed by the joint action of crystalline types, organic matrix, structural arrangement and dimension of basic building blocks.

Preparation and biomedical applications of artificial cells.

Artificial cells have received much attention in recent years as cell mimics with typical biological functions that can be adapted for therapeutic and diagnostic applications, as well as having an unlimited supply. Although remarkable progress has been made to construct complex multifunctional artificial cells, there are still significant differences between artificial cells and natural cells. It is therefore important to understand the techniques and challenges for the fabrication of artificial cells and their applications for further technological advancement. The key concepts of top-down and bottom-up methods for preparing artificial cells are summarized, and the advantages and disadvantages of the bottom-up methods are compared and critically discussed in this review. Potential applications of artificial cells as drug carriers (microcapsules), as signaling regulators for coordinating cellular communication and as bioreactors for biomolecule fabrication, are further discussed. The challenges and future trends for the development of artificial cells simulating the real activities of natural cells are finally described.

Structure of the siphophage neck-Tail complex suggests that conserved tail tip proteins facilitate receptor binding and tail assembly.

Siphophages have a long, flexible, and noncontractile tail that connects to the capsid through a neck. The phage tail is essential for host cell recognition and virus-host cell interactions; moreover, it serves as a channel for genome delivery during infection. However, the in situ high-resolution structure of the neck-tail complex of siphophages remains unknown. Here, we present the structure of the siphophage lambda "wild type," the most widely used, laboratory-adapted fiberless mutant. The neck-tail complex comprises a channel formed by stacked 12-fold and hexameric rings and a 3-fold symmetrical tip. The interactions among DNA and a total of 246 tail protein molecules forming the tail and neck have been characterized. Structural comparisons of the tail tips, the most diversified region across the lambda and other long-tailed phages or tail-like machines, suggest that their tail tip contains conserved domains, which facilitate tail assembly, receptor binding, cell adsorption, and DNA retaining/releasing. These domains are distributed in different tail tip proteins in different phages or tail-like machines. The side tail fibers are not required for the phage particle to orient itself vertically to the surface of the host cell during attachment.

Robust photogalvanic effect, full spin polarization and pure spin current in the BiC photodetector by vacancy- and substitution-doping.

The photogalvanic effects (PGEs) in low-dimensional devices have attracted great interests recently. Herein, based on non-equilibrium Green's function combined with density functional theory, we investigated spin-dependent PGE phenomena in the BiC photodetector for the case of linearly polarized light and zero bias. Due to the presence of strong spin-orbital interaction (SOI) and C3v symmetry for the BiC monolayer, the armchair and zigzag BiC photodetectors produce robust spin-dependent PGEs which possess the cos(2θ) and sin(2θ) relations on the photon energies. Especially, the armchair and Bi-vacancy armchair BiC photodetector can produce fully spin polarization, and pure spin current was found in the armchair and zigzag BiC photodetector. Furthermore, after introducing the Bi-vacancy, C-vacancy, Bi-doping and C-doping respectively, corresponding armchair and zigzag BiC photodetector can produce higher spin-dependent PGEs for their Cs symmetry. Moreover, the behaviors of spin-dependent photoresponse are highly anisotropic and can be tuned by the photon energy. This work suggested great potential applications of the BiC monolayer on PGE-driven photodetectors in low energy-consumption optoelectronics and spintronic devices. .

A pan-cancer analysis revealing the role of LFNG, MFNG and RFNG in tumor prognosis and microenvironment.

BACKGROUND: Fringe is a glycosyltransferase involved in tumor occurrence and metastasis. However, a comprehensive analysis of the Fringe family members lunatic fringe (LFNG), manic fringe (MFNG), radical fringe (RFNG) in human cancers is lacking. METHODS: In this study, we performed a pan-cancer analysis of Fringe family members in 33 cancer types with transcriptomic, genomic, methylation data from The Cancer Genome Atlas (TCGA) project. The correlation between Fringe family member expression and patient overall survival, copy number variation, methylation, Gene Ontology enrichment, and tumor-infiltrating lymphocytes (TILs) was investigated by using multiple databases, such as cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2. In vitro experiments and immunohistochemical assays were performed to validate our findings. RESULTS: High expression levels of LFNG, MFNG, RFNG were closely associated with poor overall survival in multiple cancers, particularly in pancreatic adenocarcinoma (PAAD), uveal melanoma (UVM), and brain lower-grade glioma (LGG). Copy number variation analysis revealed that diploid and gain mutations of LFNG was significantly increased in PAAD and stomach adenocarcinoma (STAD), and significantly associated with the methylation levels in promoter regions. Significant differential genes between high and low expression groups of these Fringe family members were found to be consistently enriched in immune response and T cell activation pathway, extracellular matrix adhesion pathway, RNA splicing and ion transport pathways. Correlation between the abundance of tumor-infiltrating lymphocytes (TILs) and LFNG, MFNG, and RFNG expression showed that high LFNG expression was associated with lower TIL levels, particularly in PAAD. In vitro experiment by using pancreatic cancer PANC1 cells showed that LFNG overexpression promoted cell proliferation and invasion. Immunohistochemical assay in 90 PAAD patients verified the expression level of LFNG and its relationship with the prognosis. CONCLUSIONS: Our study provides a relatively comprehensive understanding of the expression, mutation, copy number, promoter methylation level changes along with prognosis values of LFNG, MFNG, and RFNG in different tumors. High LFNG expression may serve as a poor prognosis molecular marker for PAAD.

Local environmental engineering for highly stable single-atom Pt1/CeO2catalysts: first-principles insights.

Single-atom Pt1/CeO2catalysts may cope with the high cost and durability issues of fuel cell electrocatalysts. In the present study, the stability and underlying interaction mechanisms of the Pt1/CeO2system are systematically investigated using first-principles calculations. The Pt adsorption energy on CeO2surfaces can be divided into chemical interaction and surface deformation parts. The interaction energy, mainly associated with the local chemical environment, i.e. the number of Pt-O bonds, plays a major role in Pt1/CeO2stability. When forming a Pt-4O configuration, the catalytic system has the highest stability and Pt is oxidized to Pt2+. An electronic metal-support interaction mechanism is proposed for understanding Pt1/CeO2stability. In addition, our calculations show that the Pt1/CeO2(100) system is dynamically stable, and the external O environment can promote the further oxidation of Pt to Ptn+(2 ≤n< 4). The present study provides useful guidance for the experimental development of highly stable and efficient electrocatalysts for fuel cell applications.

Chaotic medical image encryption method using attention mechanism fusion ResNet model.

Introduction: With the rapid advancement of artificial intelligence (AI) technology, the protection of patient medical image privacy and security has become a critical concern in current research on image privacy protection. However, traditional methods for encrypting medical images have faced criticism due to their limited flexibility and inadequate security. To overcome these limitations, this study proposes a novel chaotic medical image encryption method, called AT-ResNet-CM, which incorporates the attention mechanism fused with the ResNet model. Methods: The proposed method utilizes the ResNet model as the underlying network for constructing the encryption and decryption framework. The ResNet's residual structure and jump connections are employed to effectively extract profound information from medical images and expedite the model's convergence. To enhance security, the output of the ResNet model is encrypted using a logistic chaotic system, introducing randomness and complexity to the encryption process. Additionally, an attention mechanism is introduced to enhance the model's response to the region of interest within the medical image, thereby strengthening the security of the encrypted network. Results: Experimental simulations and analyses were conducted to evaluate the performance of the proposed approach. The results demonstrate that the proposed method outperforms alternative models in terms of encryption effectiveness, as indicated by a horizontal correlation coefficient of 0.0021 and information entropy of 0.9887. Furthermore, the incorporation of the attention mechanism significantly improves the encryption performance, reducing the horizontal correlation coefficient to 0.0010 and increasing the information entropy to 0.9965. These findings validate the efficacy of the proposed method for medical image encryption tasks, as it offers enhanced security and flexibility compared to existing approaches. Discussion: In conclusion, the AT-ResNet-CM method presents a promising solution to address the limitations of traditional encryption techniques in protecting patient medical images. By leveraging the attention mechanism fused with the ResNet model, the method achieves improved security and flexibility. The experimental results substantiate the superiority of the proposed method in terms of encryption effectiveness, horizontal correlation coefficient, and information entropy. The proposed method not only addresses the shortcomings of traditional methods but also provides a more robust and reliable approach for safeguarding patient medical image privacy and security.

Association of Tumor Cell Metabolic Subtype and Immune Response With the Clinical Course of Hepatocellular Carcinoma.

AIM: Tumor metabolism plays an important role in tumorigenesis and tumor progression. This study evaluated the potential association of tumor cell metabolism and immune cell tumor infiltration with the clinical course of hepatocellular carcinoma (HCC). METHODS: Gene-wise normalization and principal component analysis were performed to evaluate the metabolic system. A tumor microenvironment score system of tumor immune cell infiltration was constructed to evaluate its association with metabolic subtypes. Finally, we analyzed the impact of metabolism and immune cell infiltration on the clinical course of HCC. RESULTS: A total of 673 HCC patients were categorized into cholesterogenic (25.3%), glycolytic (14.6%), mixed (10.4%), and quiescent (49.8%) types based on glycolysis and cholesterol biosynthesis gene expression. The subgroups including the glycolytic genotyping expression (glycolytic and mixed types) showed a higher mortality rate. The glycolytic, cholesterogenic, and mixed types were positively correlated with M0 macrophage, resting mast cell, and naïve B-cell infiltration (P = .013, P = .019, and P = .006, respectively). In TCGA database, high CD8+ T cell and low M0 macrophage infiltration were associated with prolonged overall survival (OS, P = .0017 and P < .0001, respectively). Furthermore, in glycolytic and mixed types, patients with high M0 macrophage infiltration had a shorter OS (P = .03 and P = .013, respectively), and in quiescent type, patients with low naïve B-cell infiltration had a longer OS (P = .007). CONCLUSIONS: Tumor metabolism plays a prognostic role and correlates with immune cell infiltration in HCC. M0 macrophage and CD8+ T cell appear to be promising prognostic biomarker for HCC. Finally, M0 macrophages may represent a useful immunotherapeutic target in patients with HCC.

Insights into the effect of regulation of molecular composition on the properties of (AuAg)9 clusters.

The precise tuning of cluster composition helps us to understand the relationship between clusters and their properties. In this context, on the basis of [Au4Ag5(SAdm)6(Dppm)2](BPh4) (HSAdm is 1-adamantanethiol, C10H15SH; Dppm is bis(diphenylphosphino)methane, Ph2PCH2PPh2), the control of the internal metal, surface thiol, and surface phosphine ligand was accomplished, with the formations of [Au6.5Ag2.5(SAdm)6(Dppm)2](BPh4), [Au4Ag5(S-c-C6H11)6(Dppm)2](BPh4) and [Au4Ag5(SAdm)6(VDPP-2H)2](BPh4) (HS-c-C6H11 is cyclohexanethiol; VDPP is 1,1-bis(diphenylphosphino)ethylene, (Ph2P)2CCH2; and VDPP-2H is 1,1-bis(diphenylphosphine) ethane derived from the reduction of VDPP, (Ph2P)2CHCH3). The structures of [Au6.5Ag2.5(SAdm)6(Dppm)2](BPh4) and [Au4Ag5(S-c-C6H11)6(Dppm)2](BPh4) were determined by single-crystal X-ray crystallography (SC-XRD), while that of [Au4Ag5(SAdm)6(VDPP-2H)2](BPh4) was confirmed via ESI-MS measurements. The control of the metal, thiol and phosphine ligand affects the electronic structure and optical properties of the [Au4Ag5(SAdm)6(Dppm)2](BPh4) cluster. Overall, the nanoclusters [Au4Ag5(SAdm)6(Dppm)2](BPh4), [Au6.5Ag2.5(SAdm)6(Dppm)2](BPh4), [Au4Ag5(S-c-C6H11)6(Dppm)2](BPh4) and [Au4Ag5(SAdm)6(VDPP-2H)2](BPh4) provide a chance to explore the effect of regulation of metals and surface ligands on electronic and optical properties.

NFL-TBS.40-63 Peptide Gold Complex Nanovector: A Novel Therapeutic Approach to Increase Anticancer Activity by Breakdown of Microtubules in Pancreatic Adenocarcinoma (PDAC).

The role of the NFL-TBS.40-63 peptide is to destroy the microtubule network of target glioma cancer cells. Recently, we have conceived a gold-complex biotinylated NFL-TBS.40-63 (BIOT-NFL) to form a hybrid gold nanovector (BIOT-NFL-PEG-AuNPs). This methodology showed, for the first time, the ability of the BIOT-NFL-PEG-AuNPs to target the destruction of pancreatic cancer cells (PDAC) under experimental conditions, as well as detoxification and preclinical therapeutic efficacy regulated by the steric and chemical configuration of the peptide. For this aim, a mouse transplantation tumor model induced by MIA-PACA-2 cells was applied to estimate the therapeutic efficacy of BIOT-NFL-PEG-AuNPs as a nanoformulation. Our relevant results display that BIOT-NFL-PEG-AuNPs slowed the tumor growth and decreased the tumor index without effects on the body weight of mice with an excellent antiangiogenic effect, mediated by the ability of BIOT-NFL-PEG-AuNPs to alter the metabolic profiles of these MIA-PACA-2 cells. The cytokine levels were detected to evaluate the behavior of serum inflammatory factors and the power of BIOT-NFL-PEG-AuNPs to boost the immune system.

Correction: CTL-doxorubicin (DOX)-gold complex nanoparticles (DOX-AuGCs): from synthesis to enhancement of therapeutic effect on liver cancer model.

[This corrects the article DOI: 10.1039/D0NA00758G.].

A Capsid Structure of Ralstonia solanacearum podoviridae GP4 with a Triangulation Number T = 9.

GP4, a new Ralstonia solanacearum phage, is a short-tailed phage. Few structures of Ralstonia solanacearum phages have been resolved to near-atomic resolution until now. Here, we present a 3.7 Å resolution structure of the GP4 head by cryo-electron microscopy (cryo-EM). The GP4 head contains 540 copies of major capsid protein (MCP) gp2 and 540 copies of cement protein (CP) gp1 arranged in an icosahedral shell with a triangulation number T = 9. The structures of gp2 and gp1 show a canonical HK97-like fold and an Ig-like fold, respectively. The trimeric CPs stick on the surface of the head along the quasi-threefold axis of the icosahedron generating a sandwiched three-layer electrostatic complementary potential, thereby enhancing the head stability. The assembly pattern of the GP4 head provides a platform for the further exploration of the interaction between Ralstonia solanacearum and corresponding phages.

Neoadjuvant Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is characterized by low resection and high postoperative recurrence rates, and conventional treatment strategies have failed to meet clinical needs. Neoadjuvant therapy (NAT) is widely employed in the routine management of several solid tumors because it increases resectability and reduces the rate of postoperative recurrence. However, a consensus has not been reached regarding the effects of NAT on HCC. As systemic therapy, particularly targeted therapy and immunotherapy, is given for HCC treatment, accumulating evidence shows that the "spring" of NAT for HCC is imminent. In the future, HCC researchers should focus on identifying biomarkers for treatment response, explore the mechanisms of resistance, and standardize the endpoints of NAT.

DOTAREM (DOTA)-Gold-Nanoparticles: Design, Spectroscopic Evaluation to Build Hybrid Contrast Agents to Applications in Nanomedecine.

Introduction: The realization of MRI contrast agents through chemical protocols of functionalization is a strong domain of research. In this work, we developed and formulated a novel hybrid gold nanoparticle system in which a gold salt (HAuCl4) is combined with dotarem, an MRI contrast agent (DOTA) by chelation (Method IN) and stabilized by a lactose-modified chitosan polymer (CTL; Chitlac) to form DOTA IN-CTL AuNPs. Result and Discussion: The authors demonstrate the biological efficiency of these nanoparticles in the case of three cell lines: Mia PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line). DOTA IN-CTL AuNPs are stable under physiological conditions, are nontoxic, and are very efficient as PTT agents. The highlights, such as high stability and preliminary MRI in vitro and in vivo models, may be suitable for diagnosis and therapy. Conclusion: We proved that DOTA IN-CTL AuNPs have several advantages: i) Biological efficacy on three cell lines: MIA PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line); ii) high stability, and no-toxicity; iii) high efficiency as a PPT agent. The study conducted on MRI in vitro and in vivo models will be suitable for diagnosis and therapy.

Multi-Image Encryption Method via Computational Integral Imaging Algorithm.

Under the framework of computational integral imaging, a multi-image encryption scheme based on the DNA-chaos algorithm is proposed. In this scheme, multiple images are merged to one image by a computational integral imaging algorithm, which significantly improves the efficiency of image encryption. Meanwhile, the computational integral imaging algorithm can merge images at different depth distances, thereby the different depth distances of multiple images can also be used as keys to increase the security of the encryption method. In addition, the high randomness of the chaos algorithm is combined to address the outline effect caused by the DNA encryption algorithm. We have experimentally verified the proposed multi-image encryption scheme. The entropy value of the encrypted image is 7.6227, whereas the entropy value of the merge image with two input images is 3.2886, which greatly reduces the relevance of the image. The simulation results also confirm that the proposed encryption scheme has high key security and can protect against various attacks.

Improving Biological Functions of Three-Dimensional Printed Ti2448 Scaffolds by Decoration with Polydopamine and Extracellular Matrices.

Extracellular matrices (ECMs) provide important cues for cell proliferation and differentiation in the complex environment, which show a significant influence on cell functions. Herein, cell-derived ECMs were deposited on the polydopamine (PDA)-decorated porous Ti-24Nb-4Zr-8Sn (Ti2448) scaffolds fabricated by the electron beam melting method in order to improve biological functions. The influence of PDA-ECM coatings on cell functions was further investigated. The results demonstrated that the PDA-ECM coating facilitated adhesion, proliferation, and migration of MC3T3-E1 cells on Ti2448 scaffolds. Moreover, Ti2448-PDA-ECM scaffolds promoted osteogenesis differentiation of cells indicated by greater alkaline phosphatase activity and further mineralization, compared to the plain Ti2448 group. Meanwhile, Ti2448-PDA-ECM scaffolds enhanced bone growth after implantation for one month in rabbit femoral bone defects. Our findings suggest that the bioinspired PDA-ECM coating can be implemented on the porous Ti2448 scaffolds, which significantly improve the biological functions of orthopedic implants.