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Rheumatoid arthritis (RA) is a severe autoimmune disease with symptoms including synovial inflammation, cartilage erosion, and bone loss in RA lesions, which eventually lead to joint deformity and function loss. Most current treatments fail to achieve satisfying therapeutic outcomes with some adverse effects. Extracellular vesicles derived from apoptotic cells (apoEVs) have emerged as important mediators in intercellular communication regulating diverse physiological and pathological processes. In this study, we investigated the therapeutic efficacy of macrophage-derived and osteoclast-derived apoEVs (Mφ-apoEVs and OC-apoEVs) on RA. The in vitroresults showed that both Mφ-apoEVs and OC-apoEVs induced macrophage repolarization toward the anti-inflammatory M2 phenotype, promoted chondrocyte functions and chondrogenesis, and inhibited osteoclast formation and maturation. In addition, OC-apoEVs promoted osteogenic differentiation. The in vivostudy on the CIA mouse model further demonstrated that apoEVs could couple various functions and exert synergistic effects on the joint with RA, as evidenced by the regression of synovial inflammation, the reversal of cartilage damage and bone erosion, and the preservation of joint structure. These findings demonstrated that Mφ-apoEVs and OC-apoEVs contributed to restoring the homeostasis of the overall microenvironment in the RA joint and highlighted their potential application as a promising alternative to treat RA.

Er/Zr and Sc/Zr were added into 5xxx series alloy to prepare welding wires, and the welding wires with the different compositions were used to weld 6xxx extruded alloy. The effects of different alloying additions on the microstructure and properties of welded joints were investigated. The results show that Al3(Sc1-x, Zrx) particles in the Al–Mg-Sc-Zr alloy welding wire can be used as heterogeneous nucleation site, which can effectively refine the grain structure and reduce the flow of low melting point elements to the PMZ of the joint. Compared with Al–Mg and Al–Mg–Er–Zr welding wire, the grain refinement in WZ is improved by 20.5 % and 13.8 %, and that in FZ is improved by 35.0 % and 8.1 %. At the same time, the refined grain structure can effectively eliminate the stress concentration of the joint and reduce the probability of liquation cracks. The joint welded by Al–Mg-Sc-Zr wire possesses the highest ultimate tensile strength of 249 MPa, while the joints welded by Al–Mg-Sc-Zr wire and Al–Mg wire possess ultimate tensile strength of 159 MPa and 128 MPa, respectively.

Dynamic hydrogels have attracted enormous interest for bone tissue engineering as they demonstrate reversible mechanics to better mimic biophysical cues of natural extracellular matrix (ECM) compared to traditional static hydrogels. However, the facile development of therapeutic dynamic hydrogels that simultaneously recapitulate the filamentous architecture of the ECM of living tissues and induce both osteogenesis and angiogenesis to augment vascularized bone regeneration remains challenging. Herein, we report a dual nanoengineered DNA dynamic hydrogel developed through the supramolecular coassembly of amyloid fibrils and clay nanosheets with DNA strands. The nanoengineered ECM-like fibrillar hydrogel network is facilely formed without a complicated and tedious molecular synthesis. Amyloid fibrils together with clay nanosheets synergistically enhance the mechanical strength and stability of the dynamic hydrogel and, more remarkably, endow the matrix with an array of tunable features, including shear-thinning, injectability, self-healing, self-supporting, and 3D printable properties. The QK peptide is further chemically grafted onto amyloid fibrils, and its sustainable release from the hydrogel matrix stimulates the tube formation and migration with human umbilical vein endothelial cells. Meanwhile, the nanoengineered hydrogel matrix promotes osteogenic differentiation of bone marrow mesenchymal stem cells due to the sustainable release of Si4+and Mg2+derived from clay nanosheets. Furthermore, the manipulation of enhanced vascularized bone regeneration by the dynamic hydrogel is revealed in a rat cranial bone defect model. This dual nanoengineered strategy envisions great promise in developing therapeutic dynamic hydrogels for improved and customizable bone regeneration.

Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall survival. On multivariable analysis, DEL/DHL, age >60 years, and >2 prior therapies, but not COO, were important prognostic factors for overall survival. When we explored the interaction of COO and BCL2 expression, patients with germinal center B-cell (GCB)/BCL2 (+) had inferior progression-free survival (PFS) compared to GCB/BCL2 (−) patients (HR, 4.97; P= 0.027). We conclude that the DEL/non-DHL and non-DEL/non-DHL subtypes of DLBCL have similar survival after ASCT. The negative impact of GCB/BCL2 (+) on PFS warrants future trials targeting BCL2 after ASCT. The inferior outcomes in DEL/DHL need to be verified in a larger number of patients.

Photoinitiators (PIs) are a family of anthropogenic chemicals used in polymerization systems that generate active substances to initiate polymerization reactions under certain radiations. Although polymerization is considered a green method, its wide application in various commercial products, such as UV-curable inks, paints, and varnishes, has led to ubiquitous environmental issues caused by PIs. In this study, we present an overview of the current knowledge on the environmental occurrence, human exposure, and toxicity of PIs and provide suggestions for future research based on numerous available studies. The residual concentrations of PIs in commercial products, such as food packaging materials, are at microgram per gram levels. The migration of PIs from food packaging materials to foodstuffs has been confirmed by more than 100 reports of food contamination caused by PIs. Furthermore, more than 20 PIs have been detected in water, sediment, sewage sludge, and indoor dust collected from Asia, the United States, and Europe. Human internal exposure was also confirmed by the detection of PIs in serum. In addition, PIs were present in human breast milk, indicating that breastfeeding is an exposure pathway for infants. Among the most available studies, benzophenone is the dominant congener detected in the environment and humans. Toxicity studies of PIs reveal multiple toxic end points, such as carcinogenicity and endocrine-disrupting effects. Future investigations should focus on synergistic/antagonistic toxicity effects caused by PIs coexposure and metabolism/transformation pathways of newly identified PIs. Furthermore, future research should aim to develop “greener” PIs with high efficiency, low migration, and low toxicity.

Organelle-targeted therapy guided by fluorescence imaging is promising for precise cancer treatment. However, most current organelle-targeted therapeutics can only destruct single organelles, which suffer from limited therapeutic efficacy. To address this challenge, a photoactivatable probe was developed for sequential photodynamic destruction of multiorganelles in cancer cells, including lysosomes, lipid droplets, and mitochondria. This photoactivatable probe not only exhibits efficient cancer cell eradication in vitrobut also can suppress tumor growth in vivo. Simultaneously, the photoactivatable probe enables sequential destruction of multiple organelles in cancer cells, which can be observed in situthrough the conversion of green-to-red fluorescence facilitated by a photooxidative dehydrogenation reaction. We believe this photoactivatable probe for sequential destruction of multiple organelles associated with fluorescence color conversion provides a new strategy for cancer treatment with greatly improved efficacy.

The classical 3D-printed scaffolds have attracted enormous interests in bone regeneration due to the customized structural and mechanical adaptability to bone defects. However, the pristine scaffolds still suffer from the absence of dynamic and bioactive microenvironment that is analogous to natural extracellular matrix (ECM) to regulate cell behaviour and promote tissue regeneration. To address this challenge, we develop a black phosphorus nanosheets-enabled dynamic DNA hydrogel to integrate with 3D-printed scaffold to build a bioactive gel-scaffold construct to achieve enhanced angiogenesis and bone regeneration. The black phosphorus nanosheets reinforce the mechanical strength of dynamic self-healable hydrogel and endow the gel-scaffold construct with preserved protein binding to achieve sustainable delivery of growth factor. We further explore the effects of this activated construct on both human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) as well as in a critical-sized rat cranial defect model. The results confirm that the gel-scaffold construct is able to promote the growth of mature blood vessels as well as induce osteogenesis to promote new bone formation, indicating that the strategy of nano-enabled dynamic hydrogel integrated with 3D-printed scaffold holds great promise for bone tissue engineering.

• Bionic hierarchical scaffold fabricated by 3D-printing and surface mineralization. • The obtained biomimetic multi-structured scaffolds facilitate bone regeneration. • Regulation of cell fate in activated PI3K/AKT/mTOR signaling were confirmed. • Hydroxyapatite coating accelerates osseointegration and enhance bone-augmentation. • A two-step method enriches and guides the design of modified bone graft materials. The architecture and surface modifications have been regarded as effective methods to enhance the biological response of biomaterials in bone tissue engineering. The porous architecture of the implantation was essential conditions for bone regeneration. Meanwhile, the design of biomimetic hydroxyapatite (HAp) coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis. However, bioactive bio-ceramics such as β-tricalcium phosphate (β-TCP) and calcium silicate (CS) with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp. Hence in this study, 3D-printed interconnected porous bioactive ceramics β-TCP/CS scaffold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction, and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells (mBMSCs) and the potential mechanisms were explored. The results indicated that HAp apatite coating enhanced cell proliferation, alkaline phosphatase (ALP) activity, and osteogenic gene expression. Furthermore, PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions. The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were activated after the biomimetic hydroxyapatite coating were constructed on the 3D-printed ceramic scaffolds. Besides, the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358. In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality. These results suggest that biomimetic HAp coating constructed on the 3D-printed bioactive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration. [ABSTRACT FROM AUTHOR]

The process of bone repair is highly regulated by a large number of bioactive factors. Thus, a “cocktail” of bioactive factors supplemented to the defect sites is desirable for bone repair. In this regard, small extracellular vesicles (sEVs) derived from mesenchymal stem cells hold great potential in tissue repair. Nevertheless, the poor homing and retention of sEVs greatly limited their possible clinical application. In the present work, DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs (CREKA-sEVs), which could target fibrin to accumulate and retain in bone defects. Our results showed that CREKA-sEVs, like sEVs, promoted the osteogenic differentiation of BMSCs, the angiogenic property of HUVECs, and modulated the polarization of macrophages in vitro. Furthermore, due to the improved fibrin-binding and retention capacity of CREKA-sEVs, they enhanced the bone repair substantially in the rat femoral defect model. This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair.

/Objective: Tissue engineering involves scaffolds, cells and growth factors, among which growth factors have limited applications due to potential safety risks and high costs. Therefore, an alternative approach to exogenously induce osteogenesis is desirable. Considering that osteogenesis and angiogenesis are coupled, a system of human umbilical vein endothelial cells (HUVECs) and human bone mesenchymal stem cells (hBMSCs) coculture is more biologically adapted to the microenvironment in vivoand can mediate osteogenesis and angiogenesis viaparacrine signalling. Hence, in this study, a HUVECs/hBMSCs coculture system with appropriate cell and medium proportions was established. The substrate for the coculture system was a 3D-printed composite bioceramic scaffold (β-TCP/CaSiO3) based on a previous study. The aim of this study was to explore the potential of this system for bone tissue engineering.

There are many interdependent computers available in distributed networks. In such schemes, overall ownership costs comprise facilities, such as computers, controls, etc.; buying hardware; and running expenses such as wages, electrical charges, etc. Strom use is a large part of operating expenses. AI-assisted dynamic modelling for data management (AI-DM) framework is proposed. The high percentage of power use is connected explicitly to inadequate planning of energy. This research suggests creating a multi-objective method to plan the preparation of multi-criteria software solutions for distributed systems using the fuzzy TOPSIS tool as a comprehensive guide to multi-criteria management. The execution results demonstrate that this strategy could then sacrifice requirements by weight.

Calcium phosphate bio-ceramics are osteo-conductive, but it remains a challenge to promote the induction of bone augmentation and capillary formation. The surface micro/nano-topography of materials can be recognized by cells and then the cell fate are mediated. Traditional regulation methods of carving surface structures on bio-ceramics employ mineral reagents and organic additives, which might introduce impurity phases and affect the biological results. In a previous study, a facile and novel method was utilized with ultrapure water as the unique reagent for hydrothermal treatment, and a uniform hydroxyapatite (HAp) surface layer was constructed on composite ceramics (β-TCP/CaSiO3) in situ. Further combined with 3D printing technology, biomimetic hierarchical structure scaffolds were fabricated with interconnected porous composite ceramic scaffolds as the architecture and micro/nano-rod hybrid HAp as the surface layer. The obtained HAp surface layer favoured cell adhesion, alleviated the cytotoxicity of precursor scaffolds, and upregulated the cellular differentiation of mBMSCs and gene expression of HUVECs in vitro. In vivostudies showed that capillary formation, bone augmentation and new bone matrix formation were upregulated after the HAp surface layer was obtained, and the results confirmed that the fabricated biomimetic hierarchical structure scaffold could be an effective candidate for bone regeneration.

Sulfate corrosion is an important cause of accelerated structural failure in concrete structures in coastal and saline alkali areas. High ductility concrete has good tensile and durability properties, and is therefore widely used for the repair and reinforcement of damaged structures. To investigate the flexural performance of high ductility concrete on ordinary concrete structures in saline alkali environments, experimental methods were used to test it. The experimental data validated that the bearing capacity of the 10 mm specimen reinforced with high ductility concrete before and after corrosion is 125 kN and 117 k, respectively. After reinforcement and corrosion, the bearing capacities of the specimens were 115 kN, 129 kN, and 139 kN, respectively. In addition, sodium sulfate reduced the deformation capacity of the original specimen by 13.9 %, but after reinforcement, the deformation capacity of the specimen increased by at least 97.1 %. Compared to reinforced specimens in non saline alkali environments, the deformation capacity of reinforced specimens in saline alkali environments decreases by no more than 23 %. Compared to unreinforced specimens, the strain capacity of reinforced concrete and longitudinal bars in sulfate environments increased by at least 28.1 % and 34.5 %, respectively. However, compared to reinforced specimens in conventional environments, the strain capacity of reinforced specimens in sulfate environments decreased by no more than 19 %. The above results indicate that high ductility concrete can effectively improve the bending resistance of specimens, while also slowing down the corrosion of sulfates on specimens and effectively extending the service life of concrete structures.

In the blown film industry, the nonuniformity in films has been one of the most important problems, and the existing structures of blown films dies have many disadvantages, such as long thermal process and complex structure. This work proposes a novel flow channel structure of blown film die via theoretical modeling and verified by numerical simulations. The results show that the new structure is simple without the mandrel structure that is commonly used in the blown film die, capable of achieving the circumferential uniformity of the film at outlet in an ultrashort flow distance, which can largely avoid the polymer degradation and is well adaptable to different polymers. This work has successfully constructed a special geometry of flow channel without any other complicated elements to achieve uniform discharge, which provides new strategies to deal with the problem of nonuniform film thickness.

ABSTRACTDiffuse large B-cell lymphoma (DLBCL) is one of the most common causes of cancer death worldwide, and responds poorly to the existing treatments. Thus, identifying novel therapeutic targets of DLBCL is urgently needed. In this study, we found that T-lymphokine-activated killer cell-originated protein kinase (TOPK) was highly expressed in DLBCL cells and tissues. Data from the GEPIA database also indicated that TOPK was highly expressed in DLBCL tissues. The high expression levels of proteins were identified via Western blots and immunohistochemistry (IHC). TOPK knockdown inhibited cell growth and induced apoptosis of DLBCL cells with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium (MTS) and flow cytometry. Further experiments demonstrated that acetylshikonin, a compound that targeted TOPK, could attenuate cell growth and aggravate cell apoptosis through TOPK/extracellular signal-regulated kinase (ERK)-1/2 signaling, as shown by MTS, flow cytometry and Western blots. In addition, we demonstrated that TOPK modulated the effect of acetylshikonin on cell proliferation and apoptosis in U2932 and OCI-LY8 cells using MTS, flow cytometry and Western blots. Taken together, the present study suggests that acetylshikonin suppresses the growth of DLBCL cells by attenuating TOPK signaling, and the targeted inhibition of TOPK by acetylshikonin may be a promising approach for the treatment of DLBCL.

Boron-based catalysts have attracted attention in recent years, due to their high selectivity for light olefins in the catalytic oxidative dehydrogenation of propane (ODHP). But they still face drawbacks such as low activity at mild reaction temperature and more or less boron leaching from the catalyst surface during the reaction. Hence, it is necessary to exploit more efficient boron-based catalysts with higher stability. In this study, metal borate catalysts (CoB4O7and Ni3B2O6) were prepared by a co-precipitation method and evaluated for the ODHP. Reaction tests showed that both metal borates could catalyze propane dehydrogenation efficiently at 450–540 °C with high selectivity and stability. In particular, the CoB4O7catalyst, after activation at 490 °C for 70 h, exhibited rather high stability with propane conversion of 17.6% and an appreciable selectivity for light olefins of 91.4% during the subsequent reaction run. The structural stability and active sites of the metal borate catalysts were investigated by SEM, TEM, XRD, FTIR, ICP-MS and XPS. The results showed that the morphology and crystal structure of the catalysts as well as the composition of bulk and surface elements changed little after reaction, showing excellent structural stability. Besides, the M–B–O (M = Co, Ni) and B–OH species on the catalysts surface were considered to be the active sites, which gradually increased and reached an abundant content without boron leaching during the induction period of the catalysts, affording the high catalytic activity and selectivity for light olefins.

CCAAT/enhancer binding protein zeta (C/EBPZ) was differentially expressed in abdominal adipose tissues of fat and lean broilers and regulated adipogenesis in chicken. The objective of this study was to elucidate the transcriptional regulation of C/EBPZgene in chicken adipose tissue. A 2,031-base pair (bp) chicken C/EBPZsequence (2,025 nucleotides upstream to 6 nucleotides downstream from the initiator codon, -2,025/+6) was studied. The sequence exhibited a significant promoter activity (P< 0.05) and had some cis-acting elements, notably, a core promoter was identified in nucleotides −94 to +6. Additionally, DNA pull-down assay showed that proteins interacted with chicken C/EBPZpromoter (−173/+6) in preadipocytes were implicated in transcription, post-transcriptional regulation and translation. In addition, KLF2 facilitated the activities of chicken C/EBPZpromoter (−2,025/+6, −1,409/+6, −793/+6, −485/+6, −173/+6, and −94/+6) in preadipocytes (P< 0.05). The expression levels of KLF2and C/EBPZin chicken abdominal adipose tissue were substantially associated (r= 0.5978278, P< 0.0001), and KLF2 increased C/EBPZexpression in vitro(P< 0.05). Additionally, chromatin immunoprecipitation (ChIP)-PCR analysis revealed that KLF2 has the ability to interact with the chicken C/EBPZpromoter regions at least at the positions −1,245/−1,048 and −571/−397. Mutation analysis showed that the CGCAGCGCCCG motif located in the chicken C/EBPZpromoter at positions -45 to -35 is involved in regulating transcription and facilitates trans activation by KLF2. These results provided some information of transcription control of C/EBPZin chicken adipose tissue.

The presence of anthropogenically emitted chlorinated paraffins (CPs) has been reported in the pristine regions, providing evidence of their long-range transport. This study comprehensively analyzed the short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in both gas and particle phases at King George Island, West Antarctica (the Chinese Great Wall Station), from 2014 to 2018. The atmospheric levels of CPs ranged between 71.4 and 4230 pg/m3, with an increasing temporal trend during the sampling time. Three different models (J–P model, H–B model, and L–M–Y model) were built to estimate the progress of gas/particle partitioning of CPs at the measurement site. Furthermore, we compared the measured data of the gas/particle partitioning with the data estimated using three different models. We found that the steady-state model (L–M–Y model) was more suitable for investigating the gas/particle partitioning of CPs instead of equilibrium state models (J–P model and H–B model). The result indicated that steady-state approximation rather than the equilibrium state represents the most predominant contribution to the transport of CPs to the Antarctic region. The steady-state further made it conducive to sustaining the levels of CPs for a more extended period in the atmosphere of West Antarctica.

Bone is an important part of the human body structure and plays a vital role in human health. A microfluidic chip that can simulate the structure and function of bone will provide a platform for bone-related biomedical research. Hydroxyapatite (HA), a bioactive ceramic material, has a similar structure and composition to bone mineralization products. In this study, we used HA as a microfluidic chip component to provide a highly bionic bone environment. HA substrates with different microchannel structures were printed by using ceramic stereolithography (SLA) technology, and the minimum trench width was 50 μm. The HA substrate with microchannels was sealed by a thin polydimethylsiloxane (PDMS) layer to make a HA-PDMS microfluidic chip. Cell culture experiments demonstrated that compared with PDMS, HA was more conducive to the proliferation and osteogenic differentiation of the human foetal osteoblast cell line (hFOB). In addition, the concentration gradient of the model drug doxorubicin hydrochloride (DOX) was successfully generated on a Christmas tree structure HA-PDMS chip, and the half maximal inhibitory concentration (IC50) of DOX was determined. The findings of this study indicate that the HA-PDMS microfluidic chip has great potential in the field of high-throughput bone-related drug screening and bone-related research.

Biomaterial surface chemistry engenders profound consequences on cell adhesion and the ultimate tissue response by adsorbing proteins from extracellular matrix, where vitronectin (Vn) is involved as one of the crucial mediator proteins. Deciphering the adsorption behaviors of Vn in molecular scale provides a useful account of how to design biomaterial surfaces. But the details of structural dynamics and consequential biological effect remain elusive. Herein, both experimental and computational approaches were applied to delineate the conformational and orientational evolution of Vn during adsorption onto self-assembled monolayers (SAMs) terminating with -COOH, -NH2, -CH3and -OH. To unravel the interplay between cell binding and the charge and wettability of material surface, somatomedin-B (SMB) domain of Vn holding the RGD cell-binding motif was employed in molecular dynamics (MD) simulations, with orientation initialized by Monte Carlo (MC) method. Experimental evidences including protein adsorption, cell adhesion and integrin gene expressions were thoroughly investigated. The adsorption of Vn on different surface chemistries showed very complex profiles. Cell adhesion was enabled on all Vn-adsorbed surfaces but with distinct mechanisms mostly determined by conformational change induced reorientation. Higher amount of Vn was observed on negatively charged surface (COOH) and hydrophobic surface (CH3). However, advantageous orientations defined by RGD loop conditions were only obtained on the charged surfaces (COOH and NH2). Specifically, COOH surface straightened up the Vn molecules and accumulated them into a higher density, whereas CH3surface squashed Vn and stacked them into higher density multilayer by tracking adsorption but with the RGD loops restrained. These findings may have a broad implication on the understanding of Vn functionality and would help develop new strategies for designing advanced biomaterials.

Materials research usually relies on lengthy and largely trial-and-error methods, high-throughput technology has thereby emerged as an alternative method which is proven to be a simple, rapid, accurate and sensitive technique. Here, we presented a microfluidic platform with a set of 6 × 6 microarray chips for high-throughput synthesis and rapid screening the reaction conditions of biomedical materials. The core design of this platform is to generate concentration gradient inside microarray chips. Considering that calcium phosphates (CaP) are the most important inorganic constituents of biological hard tissues, different phases of calcium phosphates particles were synthesized with various morphogenesis when the reaction conditions such as Ca/P concentration ratio, NaOH concentration were screened using our platform. And this platform is universal and expected to apply to other systems for high-throughput screening and synthesis.

The leakage mechanism of the clamp connector for submarine pipeline is investigated. The contact seal of a clamp connector is regarded as a half-cylinder squeezing a plane. Moreover, mean stress of the contact region is used to calculate the permeability, based on an observation length-dependent mechanic model and a new fractal porous media model. The analysis yields insight into the effects of surface fractal parameters on the permeability, when mean stress rises within the yield limit. Compared with experiment results, the prediction of this model shows well consistency in the trend.

Phosphorous-containing biopolymers have been applied to expedite the regeneration of damaged bone tissue by stimulating the function of phosphorous groups in natural bones. However, the underlying mechanism of phosphorous-containing biopolymers in promoting osteogenic differentiation is unclarified. Herein, we synthesized phosphorylated chitosan hydrogels by incorporating phosphocreatine into chitosan molecular chains under mild conditions. The introduction of phosphate groups improved properties of protein adsorption and calcium deposition without affecting the morphology of hydrogels. Our results showed that phosphorylated chitosan hydrogels could not only promote alkaline phosphatase activity and mineralization but also upregulate the expression of osteogenic-related genes and proteins. Meanwhile, application of c-Jun N-terminal kinase inhibitor SP600125 and p38 mitogen-activated protein kinase inhibitor SB203580 repressed the expression of osteogenic-related markers in gene and protein levels. To the best of our knowledge, it is reported for the first time that phosphorous-containing biopolymers promote osteogenic differentiation of osteoblasts via JNK and p38 signaling pathways.

Hydroxyapatite (HA) micro/nano particles show great promise as artificial bone and dental substitutes, or drug carrier systems. However, the precise regulation of hydroxyapatite micro/nano particles with controllable physicochemical properties (such as hierarchical structure, particle size, potential and crystallinity) is still a challenge. Furthermore, the effects of different hierarchical structures on biological responses have been rarely reported. Herein, the HA particles with a precisely tailored micro/nano hierarchical structure have been developed using an elaborate biomimetic synthesis technology. Three representative particles, namely, micro/nano needle-like HA particles, micro/nano rod-like HA particles, and micro/nano flake-like HA particles, were featured to evaluate their biological responses to stem cells. The pore structure facilitated the adsorption of serum adhesive proteins, which together with the unique hierarchical architecture of micro/nano flake-like HA particles remarkably promoted the endocytosis efficiency in a concentration-dependent manner. The qRT-PCR together with RNA-seq and western blot analyses showed that micro/nano flake-like HA particles more significantly up-regulated the expression of genes and production of proteins related to osteogenic differentiation among the three particles through the activated ERK/MAPK signalling pathway. RNA-seq further revealed a complex mechanism of cell interface events, suggesting that the hierarchical architecture of HA particles is of crucial importance for the regulation of actin cytoskeleton involved in the modulation of cell adhesion which positively stimulated osteogenic differentiation of stem cells. Moreover, the endocytosis of particles into lysosomes resulted in an increase in the intracellular Ca2+levels, which activated possible intracellular Ca2+-mediated signaling cascades (Ras/cAMP/Rap1/MAPK signaling pathways) related to osteogenic differentiation of stem cells. Our findings shed light on the effects of different hierarchical structures of HA particles on stem cell differentiation and contribute to the optimal design of implant materials.

To address the uneven nutrient distribution within three-dimensional (3D) tissue models and organoids currently used in medical research, this study introduces a microvascular network based on the Hilbert curve. Our aim was to develop innovative solutions for enhancing nutrient supply in thick tissue models in vitro. By using 3D bioprinting, we engineered microvascular networks of varying Hilbert orders and validated their efficacy in enhancing nutrient uniformity through numerical simulations and experiments. These networks facilitated broader and more uniform nutrient distribution throughout the thick tissue models, particularly the 2° Hilbert microvascular structure, which occupies less space and significantly reduces regions of cellular death. Furthermore, we explored the potential of assembling larger tissue constructs using the 2° Hilbert microvascular network, showcasing its applicability in constructing large-scale biological models. The findings suggest that the 2° Hilbert microvascular structure is particularly effective in ensuring adequate nutrient delivery, thus enhancing the viability and functionality of large-volume tissue models. These innovations hold significant promise for advancing the fields of tissue engineering and regenerative medicine by improving nutrient delivery to in vitrothick tissue block models. This provides a robust foundation for future in vitroresearch and clinical applications, potentially leading to more effective treatments and interventions in the medical field. The development of these microvascular networks represents a crucial step forward in overcoming the limitations of current 3D tissue models and organoids, paving the way for more sophisticated and reliable biomedical research tools.

Chlorinated paraffins (CPs) are a class of compounds that are currently produced and used in large amounts in commercial products worldwide. In this study, food, indoor air, indoor dust, and drinking water samples were collected to evaluate the external exposure levels of CPs and possible pathway for the general population in Beijing, China. Short chain CPs (SCCPs) and medium chain CPs (MCCPs) in 199 samples were analyzed using a gas chromatography tandem time-of-flight high-resolution mass spectrometry (GC-TOF-HR-MS) method. High levels of CPs were observed in the indoor environment from residential houses, offices, and student dormitories. The geometric mean concentrations (GM) of ∑SCCPs and ∑MCCPs in indoor dust were 92 μg g–1and 82 μg g–1, respectively, while in indoor air, the concentrations were 80 ng m–3and 3.4 ng m–3, respectively. The GM of ∑SCCPs and ∑MCCPs in the diet were 83 ng g–1dry weight (dw) and 56 ng g–1dw, respectively. The most important external exposure routes to CPs to the general populations in Beijing were food intake and indoor dust ingestion. Indoor dust and indoor air posed higher risks for toddlers and infants than for adults.

Bioadaptability, proposed earlier to accentuate the biomaterial-host interactivity, incites the development of adaptable biomaterials. Esser-Kahn et al.3recently reported a biomaterial that can self-adapt to its mechanical environment as potential bone implants. Such endeavors allow “precise bioadaptability” for fueling precision medicine.

The use of antimicrobial peptides (AMPs)-functionalized titanium implants is an efficient method for preventing bacterial infection. However, the attachment of AMPs to the surface of titanium implants remains a challenge. In this study, a “clickable” titanium surface was developed by using a silane coupling agent with an alkynyl group. The antimicrobial titanium implant was then constructed through the reaction between the “clickable” surface and azido-AMPs (PEG-HHC36:N3-PEG12-KRWWKWWRR) via click chemistry of Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Such an antimicrobial titanium implant, with an AMP density of 897.4 ± 67.3 ng/cm2(2.5 ± 0.2 molecules per nm2) on the surface, exhibited good and stable antimicrobial activity, inhibited 90.2% of Staphylococcus aureusand 88.1% of Escherichia coliafter 2.5 h of incubation, and even inhibited 69.5% of Staphylococcus aureusafter 4 days of degradation. The CCK-8 assay indicated that the antimicrobial titanium implant exhibited negligible cytotoxicity to mouse bone mesenchymal stem cells. In vivoassay illustrated that this implant could kill 78.8% of Staphylococcus aureusafter 7 days. This method has great potential for the preparation of antimicrobial titanium implants and the prevention of infections in the clinic.

Mesenchymal stem cells (MSCs) have broad therapeutic potential due to their ability to secrete bioactive factors that are immunomodulatory and trophic (regenerative). In this study, polyacrylamide (PAAm) hydrogels with different stiffness are used as a model to explore the effects of substrate stiffness on the paracrine function of human mesenchymal stem cells (hMSCs). Human MSCs cultured on soft substrates produced significantly higher levels of immunomodulatory and trophic factors compared with hMSCs cultured on rigid substrates. The enhanced paracrine function of hMSCs is further confirmed by the M2 phenotypic polarization observed in macrophages, as well as the accelerated chemotactic migration and angiogenesis capacity observed in human umbilical vein endothelial cells (HUVECs) after treatment with conditioned media (CM) collected from hMSCs cultured on soft substrates. Furthermore, the inhibited secretion of immunosuppressive and trophic factors by hMSCs cultured on rigid substrates is largely rescued by treatment with Lat.A, a cytoskeletal polymerization inhibitor. Similar results are observed after treatment with either myosin (Blebbi) or ROCK (Y27632) inhibitors. These results demonstrate that substrate stiffness is a key modulator of the paracrine function of hMSCs and highlight the potential utility of promoting tissue repair through stiffness-regulated paracrine signaling in MSCs.

Natural polysaccharides and proteins have been widely explored for the preparation of hydrogel matrices due to their promising biocompatibility and biodegradability. However, it is challenging to achieve multiple functions of the hydrophilic matrix through convenient functionalization strategies. Herein we report the facile engineering of a natural matrix with black phosphorus (BP) nanosheets as building blocks to generate a therapeutic nanocomposite hydrogel (BP/Gel) with an array of promising features. BP nanosheets could reinforce the crosslinking networks and significantly promote their capabilities of mineralization. The BP/Gel nanocomposite hydrogel exhibits excellent near infrared (NIR) photothermal performance and good biocompatibility in vitroand in vivo. Upon NIR irradiation, the nanocomposite hydrogel demonstrates efficient photothermal antibacterial features. More remarkably, the BP nanosheet engineered hydrogel matrix is capable of promoting in vitroosteogenesis in the absence of osteoinductive factors, and in the meantime demonstrates significant newborn cranial bone tissue formation in a Sprague-Dawley rat model. These results demonstrate that BP nanosheets could endow the natural matrix with multiple functions including reinforced networks, photothermal performance, enhanced mineralization and bone regeneration, which provides a facile and highly efficient therapeutic strategy for bone tissue engineering.

Natural polymer hydrogels are one of the best biomaterials for soft tissue repair because of their excellent biocompatibility, biodegradability and low immune rejection. However, they lack mechanical strength matching that of natural tissue and desired functionality (e.g., self-healing and 3D-printability). To solve these problems, we developed a host–guest supramolecule (HGSM) with three arms covalently crosslinked with a natural polymer to construct a novel hydrogel with non-covalent bonds integrated into a covalently crosslinked network. This unique structure enabled the hydrogel to exhibit improved mechanical properties and show both self-healing and 3D printing capabilities. The three-armed HGSM was first prepared viaefficient non-covalent host–guest inclusion interactions between isocyanatoethyl acrylate-modified β-cyclodextrin (β-CD-AOI2) and acryloylated tetra-ethylene glycol-modified adamantane (A-TEG-Ad). Subsequently, a host–guest supramolecular hydrogel (HGGelMA) was obtained through copolymerization between the arms of the HGSM and gelatin methacryloyl (GelMA) to form a covalently crosslinked network. The HGGelMA was robust, fatigue resistant, reproducible and rapidly self-healing. In the HGGelMA, the covalent crosslinking maintained its overall shape, whereas the weak reversible non-covalent host–guest interactions reinforced its mechanical properties and enabled it to rapidly self-heal upon fracturing. The reversible non-covalent interactions could be re-established upon breaking, so as to heal the hydrogel and dissipate energy to prevent catastrophic fracture propagation. Furthermore, the precursors of the HGGelMA were sufficiently viscous and could be rapidly photocrosslinked to produce a robust scaffold with an exquisite internal structure through 3D printing. The 3D-printed HGGelMA hydrogel scaffold was biocompatible, promoted cell adhesion and proliferation, and supported tissue in-growth. Our strategy of integrating a non-covalently linked HGSM into a covalently linked hydrogel network represents a new approach to the development of natural polymers into biocompatible hydrogels with improved strength as well as desired self-healing and 3D-printability.

Inspired by the constitution of things in the natural world, three-dimensional (3D) nanofiber scaffold/cells complex was constructed via the combination of electrospinning technology and origami techniques. The nanofiber boxes prepared by origami provided a limited space for the layer-by-layer nanofiber films, and the human fetal osteoblasts (hFOBs) seeded on the both sides of the nanofiber films were expected to facilitate the bonding of the adjacent nanofiber films through the secretion of extracellular matrix. Specifically, the hFOBs presented 3D distribution in the nanofiber scaffold, and they can stretch across the gaps between the adjacent nanofiber films, forming the cell layers and filling the whole 3D nanofiber scaffold. Eventually, a 3D block composed of electrospun nanofiber scaffold and cells was obtained, which possesses potential applications in bone tissue engineering. Interestingly, we also created 3D nanofiber structures that range from simple forms to intricate architectures via origami, indicating that the combination of electrospinning technology and origami techniques is a feasible method for the 3D construction of tissue engineering scaffolds.

Introduction:In recent years, increasing evidence suggests an important role of tumor-infiltrating B lymphocytes (TIL-Bs) in cancer immunity. In various types of solid tumors, high density of TIL-Bs and presence of mature tertiary lymphoid structures consistently correlate with better prognosis and response to immune checkpoint blockade therapies. Diffuse large B-cell lymphoma (DLBCL) is a type of aggressive lymphoma arising from mature B cells. TIL-Bs have been identified in DLBCL based on single-cell gene-expression data in several previous studies, but their prognostic significance in DLBCL is unknown. In this study, we determined the clinical significance of TIL-B abundance and investigated the potential underlying mechanisms.

Ce and F were added to MCM-48 molecular sieve by hydrothermal synthesis, and Pd/Ce(F)-MCM-48 metal acid bifunctional catalysts were prepared by impregnation method. The physical and chemical properties of Ce(F)-MCM-48 and Pd/Ce(F)-MCM-48 were characterized by X-ray diffraction, scanning electron microscope, NH3temperature programmed desorption instrument, Fourier infrared spectrometer, and X-ray photoelectronic spectrometer characterization methods. The results showed that when the molar ratio of the raw materials was n(Ce):n(TEOS) = 0.02 and n(NaF):n(TEOS) = 0.10, Ce(F)-MCM-48-0.10 molecular sieve had a high degree of order and large specific surface area and pore volume, the total acid content increased, and the acid strength also increased. And it had an acidic center and generated certain oxygen vacancies. The catalyst prepared after Pd impregnation had good dispersibility. 0.4% Pd/Ce(F)-MCM-48-0.10 catalyst still maintained the crystalline phase of MCM-48 molecular sieve. A micro-reaction device was used to examine the catalytic performance of n-heptane isomerization of Pd/Ce(F)-MCM-48-0.10 catalysts. When the hydrogen flow rate was 30 mL·min−1, reduction temperature was 300°C, reduction time was 4 h, weight hourly space velocity was 7.6 h−1, and reaction temperature was 280°C, 0.4% Pd/Ce(F)-MCM-48-0.10 catalyst was used in the heptane isomerization reaction, where the conversion of n-heptane was 67.3% and the selectivity of isoheptane was 96.5%.

Insoluble metal bisphosphonates (BPs) are considered an ideal alternative to the soluble counterparts in regenerative medicine due to their increased BP release profile, but still present undesired properties (e.g., low stability, uncontrolled degradation, and poor biocompatibility). Through a simple crystallization on a solid calcium hydroxyapatite (HA)‐based substrate from a BP precursor solution in 30 days, a series of insoluble calcium BP (CaBP) crystals are developed. These crystals, including calcium alendronate (CaAln), calcium pamidronate (CaPam), calcium incadronate (CaInc), calcium risedronate (CaRis), calcium zoledronate (CaZol), and calcium di‐minodronate (Ca(Min)2), present high purity, regular morphologies and excellent biodegradability. It is demonstrated that these CaBPs can induce osteogenic differentiation of adipose‐derived mesenchymal stem cells in vitro in the absence of other osteogenic inducers. It is further found that CaBP induces bone formation more effectively in a femur defect rabbit model in three months but with a lower in vivo hematotoxicity than the clinically used HA during osteogenesis. It is believed that these desired biological properties arise from the capability of the insoluble CaBPs in releasing BPs in a sustained manner for stimulating osteogenesis. This work provides a significant strategy for turning CaBPs into novel biomaterials for tissue regeneration and demonstrates their great potential in the clinic. Crystallization on a solid calcium hydroxyapatite‐based substrate results in the formation of a series of insoluble calcium bisphosphonate (CaBP) crystals with high purity, regular morphologies and excellent biodegradability. The CaBP materials can release bisphosphonate ions in a sustained manner, allowing them to induce osteogenic differentiation of stem cells in vitro and promote bone formation to repair bone defect in vivo.

Titanium (Ti) alloy implants can repair bone defects at load-bearing sites. However, they mechanically mismatch with the natural bone and lack customized adaption with the irregularly major-sized load-bearing bone defects, resulting in the failure of implant fixation. Mineralized collagen (MC), a building block in bone, can induce angiogenesis and osteogenesis, and 3D printing technology can be employed to prepare scaffolds with an overall shape customized to the bone defect. Hence, we induced the formation of MC, made of hydroxyapatite (HAp) nanocrystals and collagen fibers, in 3D-printed porous Ti6Al4V (PT) scaffolds through in situ biomimetic mineralization. The resultant MC/PT scaffolds exhibited a bone-like Young’s modulus and were customized to the anatomical contour of actual bone defects of rabbit model. We found that the biocompatibility and osteogenic differentiation are best when the mass ratio between HAp nanocrystals and collagen fibers is 1 in MC. We then implanted the MC/PT scaffolds into the customized radius defect rabbit model and found that the MC/PT scaffolds significantly improved the vascularized bone tissue formation and integration between new bone and the implants. Therefore, a combination of 3D printing and biomimetic mineralization could lead to customized 3D PT scaffolds for enhanced angiogenesis, osteogenesis, and osteointegration. Such scaffolds represent novel patient-specific implants for precisely repairing irregular major-sized load-bearing bone defects.

Modification of implants by antimicrobial peptides (AMPs) can improve the antimicrobial activity of the implants. However, AMPs have some cytotoxicity in vivo when they are exposed at body temperature. To tackle this challenge, we propose to develop a new approach to generating a smart antimicrobial surface through exposure of AMPs on the surface. A polydopamine film was first formed on the substrates, followed by the conjugation of a temperature-sensitive polymer, poly(N-isopropylacrylamide) (pNIPAM), to the film through atom transfer radical polymerization (ATRP). Then, AMPs were conjugated to the NIPAM on the resultant pNIPAM-modified surface through a click chemistry reaction. Because of the temperature-sensitive property of pNIPAM, the AMPs motif was more exposed to the external environment at room temperature (25 °C) than at body temperature (37 °C), making the surface present a higher antimicrobial activity at room temperature than at body temperature. More importantly, such a smart behavior is accompanied with the increased biocompatibility of the surface at body temperature when compared to the substrates unmodified or modified by AMPs or pNIPAM alone. Our in vivo study further verified that pNIPAM-AMP dual modified bone implants showed increased biocompatibility even when they were challenged with the bacteria at room temperature before implantation. These results indicate that the implants are antibacterial at room temperature and can be safely employed during surgery, resulting in no infection after implantations. Our work represents a new promising strategy to fully explore the antimicrobial property of AMPs, while improving their biocompatibility in vivo. The higher exposure of AMPs at room temperature (the temperature for storing the implants before surgery) will help decrease the risk of bacterial infection, and the lower exposure of AMPs at body temperature (the temperature after the implants are placed into the body by surgery) will improve the biocompatibility of AMPs.

The orientation and conformation of adhesive proteins after adsorption play a central role in cell-binding bioactivity. Fibronectin (Fn) holds two peptide sequences that favor cell adhesion: the Arg–Gly–Asp (RGD) loop on the tenth type-III domain (Fn-III10) and the Pro–His–Ser–Arg–Asn (PHSRN) synergy site on the ninth type-III domain (Fn-III9). Herein, adsorption of Fn fragments (Fn-III10and Fn-III9–10) on self-assembled monolayers (SAMs) carrying various functional groups (−COOH, −NH2, −CH3, and −OH) was investigated by the Monte Carlo method and molecular dynamics simulation in order to understand its mediation effect on cell adhesion. The results demonstrated that Fn-III9could enhance the stiffness of the Fn molecule and further fix the adsorption orientation. The RGD site of the Fn fragment appeared to be deactivated on hydrophobic surfaces (CH3-SAM) because of the binding of adjacent nonpolar residues on surfaces, whereas charged surfaces (COOH-SAM and NH2-SAM) and hydrophilic surfaces (OH-SAM) were conducive to the formation of cell-binding-favorable orientation for Fn fragments. The cell adhesion capability of Fn fragments was highly improved on positively charged surfaces (NH2-SAM) and hydrophilic surfaces because of the advantageous steric structure and orientation of both RGD and PHSRN sites. This work provides an insight into the interplay at the atomic scale between protein adsorption and surface chemistry for designing biologically responsive substrate surfaces.

As a group of new persistent organic pollutants, short-chain chlorinated paraffins (SCCPs) and medium-chain CP (MCCPs) have attracted extensive worldwide interest in recent years. However, the data regarding to the environmental behavior, especially in atmospheric transfer and air–seawater exchange, are still sparse. In this study, seasonal marine boundary layer air and seawater samples were collected from Chinese Bohai sea and a fugacity model was built to evaluate the air–seawater diffusion and deposition flux of CPs. Generally, the total CP levels in atmosphere and seawater samples in summer were higher than those in spring, and CPs existed mostly in the gaseous phase in air and the dissolved phase in seawater. For SCCPs, C10and C11components were the most abundant homologue groups. For MCCPs, the C14homologue dominated in the particle phase of atmosphere and particulate phase of seawater. The logarithmic fugacity ratios (log fa/fw) of higher chlorinated congeners (Cl8to Cl10: 0.71 to 1.32 in May and 1.38 to 2.29 in August) indicated that net deposition was the predominant process, whereas lower chlorinated congeners, especially Cl5homologue groups in August, showed a trend of net volitization (log fa/fw< −0.5). The results of diffusion and dry deposition fluxes indicated that air–seawater gas exchange of CPs was significantly higher than dry deposition in the sampling areas.

Yttrium is a main kind of rare earth elements (REEs) with wide applications in modern industry and farming. Phosphorus, an essential element of algae, is used as the nutrients and also one of the main factors of eutrophication. To investigate the effects of yttrium and phosphorus on Microcystis aeruginosa(M. aeruginosa), the growth and physiological changes were studied by lab cultured experiments. In the experiment, exogenous yttrium was tested by a concentration gradient (0.0, 0.1, 0.3, 0.5, 1.0 mg/L), meanwhile, phosphorus was tested by three concentrations (0.0, 0.02, 0.2 mg/L). The results show that the contents of chlorophyll a(chl-a) and soluble protein increase compared with the control and they have certain correlation with algal cells density. The growth status of algae is stimulated by initial yttrium concentration ≤0.3 and 0.2 mg/L phosphorus, while it is inhabited by 0.5 and 1.0 mg/L yttrium. Besides, the activity of superoxide dismutase (SOD) of algae increases with addition of yttrium dose (0–0.3 mg/L) when phosphorus dose is 0.2 mg/L. Furthermore, when yttrium dose is 0.5 and 1.0 mg/L, the vitality of SOD presents a sharp decline. The malondialdehyde (MDA) contents increase with time and addition of yttrium dose, 0.2 mg/L phosphorus weakens the accumulation of MDA.

In this study, we developed a simple approach for the controllable growth of whitlockite (WH) on a β-tricalcium phosphate surface and investigated its cell viability via CCK-8, its live-dead staining and its alkaline phosphatase activity. Herein, WH with controllable morphologies was prepared by regulating the hydrothermal reaction conditions. The results of scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy indicated that pure hexagonal plates of WH were prepared successfully. In vitro cell experiments showed that WH possessed excellent biocompatibility and effectively promoted the adhesion and proliferation of mouse bone mesenchymal stem cells. The osteogenesis of the WH was also enhanced. The obtained WH was expected to be utilized for promising applications as implantable block materials for bone repair. [ABSTRACT FROM AUTHOR]

Multidrug resistant bacterial infection has become one of the most serious threats to human health. Antimicrobial peptides (AMPs) have been identified as potential alternatives to antibiotics owing to their excellent bactericidal activity. However, the complicated bactericidal mechanism of AMPs is still poorly understood. Fluorescence imaging has many advantages in terms of dynamic monitoring, easy operation, and high sensitivity. In this study, we developed an aggregation-induced emission (AIE)-active probe AMP-2HBT by decorating the antimicrobial peptide HHC36 (KRWWKWWRR) with an AIEgen of 2-(2-hydroxyphenyl)benzothiazole (HBT). This AIE-active probe exhibited an excellent light-up fluorescence after binding with bacteria, enabling a real-time monitoring of the binding process. Moreover, a similar time-dependent bactericidal kinetics was observed for the AIE-active probe and HHC36 peptide, which indicated that the bactericidal activity of the peptide was not compromised by decorating with the AIEgen. The bactericidal mechanism of HHC36 peptide was further investigated by super-resolution fluorescence microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM), which suggested that the probe tended to accumulate on the bacterial membrane and efficiently disrupt the membrane structure to kill both Gram-positive and -negative bacteria. This AIE-active probe thus provided a convenient tool to investigate the bactericidal mechanism of AMPs.

Efficient delivery of cargo into target cells is a formidable challenge in modern medicine. Despite the great promise of biomimetic hydroxyapatite (HA) particles in tissue engineering, their potential applications in bone tumor therapy, particularly their structure–function relationships in cargo delivery to target cells, have not yet been well explored. In this study, biomimetic multifunctional composite microparticles (Bm‐cMPs) are developed by integrating an amphiphilic prodrug of curcumin with hierarchically structured HA microspheres (Hs‐hMPs). Then, the effects of the hierarchical structure of vehicles on the integration and delivery of cargo as well as the anti‐osteosarcoma (OS) effect of the composite are determined. Different hierarchical structures of the vehicles strongly influence the self‐assembly behavior of the prodrug. The flake‐like crystals of Hs‐hMPs enable the highest loading capacity and enhance the stability of the cargo. Compared to the normal cells, OS cells exhibit 3.56‐times better uptake of flake‐like Hs‐hMPs, facilitating the selective anti‐tumor effect of the prodrug. Moreover, Bm‐cMPs suppress tumor growth and metastasis by promoting apoptosis and inhibiting cell proliferation and tumor vascularization. The findings shed light on the potential application of Bm‐cMPs and suggest a feasible strategy for developing an effective targeted therapy platform using hierarchically structured minerals for OS treatment. This study introduces a multifunctional particle integrating amphiphilic drug with hierarchically structured hydroxyapatite particle. The multifunctional particle exhibits selective anti‐tumor effect on osteosarcoma cells through the enhanced uptake of hierarchical structure, and suppresses the tumor growth and metastasis in vivo. This composite also supports the attachment and proliferation of stem cells, and has promising effect on stimulating osteogenesis.

For patients with liver failure, bilirubin (BR) is one of the endogenous toxins in their blood. Although blood purification can remove the bilirubin from the body in clinics, the detoxification system needs to be improved, and the cost needs to be decreased. In the present study, we developed a recyclable model surface that can strongly remove bilirubin. We first prepared adamantane(Ad) on a model gold surface by self-assembly. Then, we integrated the β-cyclodextrin dimer(CDD) onto the surface with host–guest interactions between one of the CD cavities in the CDDand Ad. We characterized the surface with XPS, static contact angle measurements, and AFM. In addition, we employed QCM-D to characterize the preparation process as well as the detoxification of the surface. We demonstrated that this modified surface could strongly adsorb bilirubin through host–guest interactions between the CD cavities in the CDDand bilirubin and that the detoxification was improved 1.7 times (compared to the surface only with Ad). Interestingly, after characterization with QCM-D, this surface could be recycled due to the thermoresponsive property of the host–guest interaction between the CDDand Ad. After adsorbing the toxin and increasing the temperature to 45 °C, the CDDwith bilirubin could be removed from the surface. Then, the refreshed surface with CDDcould be prepared again at room temperature. This cycle could be repeated at least 3 times. Additionally, during each cycle, the modified surface exhibited good detoxification to bilirubin. This modified surface also showed strong resistance to plasma proteins, decreasing the adsorption of human serum albumin (HSA) and fibrinogen (Fg). An in vitro platelet adhesion assay showed that the adhesion of the platelets on the modified surface decreased and that the platelets were in an inactivated state. The hemolysis assay showed that this surface exhibited no hemolysis activity in the samples to red blood cells (RBCs). The CCK-8 assay showed that this surface had negligible cytotoxicity to L929 cells. This work has taken advantage of the host–guest self-assembly between β-CD and BR/Ad for special recognizing adsorption, as well as the thermoresponse of β-CD-Ad inclusion for recyclable application, and these results demonstrate that this technology has great potential for removing bilirubin and decreasing clinic costs.

The stall and surge directly impact on the safety and reliability of compressors. The spike-type and modal-type stall inception exist in compressors. At present, few studies pay attention to the stall inception of centrifugal compressor, such as the formation reason for the stall inception and the action by the volute tongue on the stall precursor. This paper investigated the stall characteristics of a high-speed small-flow centrifugal compressor and illustrated the relationship between the volute tongue and the location of stall inception. In addition, the mechanism of stall inception was also clarified. Both the analysis of initial flow structures and the comparison of the frequency spectrum characteristics at different monitoring points show that the spike-type stall occurs at about 115° circumferential position in this centrifugal compressor. The nonaxisymmetric geometry structure of the volute leads to the uneven circumferential pressure distribution. The blockade effect of the volute tongue results in high static pressure area near the volute tongue. The disturbance caused by high static pressure adversely propagates into the diffuser, resulting in the static pressure peak value at different radii. As the pressure peaks adversely migrate to the impeller inlet and induce the leading edge spillover near the corresponding blade, the spike-type stall occurs. Therefore, the volute tongue both induces the stall inception and determines the circumferential position of the stall inception at the centrifugal compressor inlet.

Osteopontin (OPN) is a key mediator of cell interactions with biomaterials. However, few studies have been dedicated to studying cell adhesion on OPN-adsorbed substrates with controlled charge and wettability. Here, amino–carboxyl (NH2/COOH) and hydroxyl–methyl (OH/CH3) mixed self-assembled monolayers (SAMs) of varying charges and wettability, respectively, were used as controllable model surfaces to study OPN adsorption and subsequent mesenchymal stem cell (MSC) adhesion. The amount of OPN adsorbed onto the NH2/COOH mixed SAMs appeared to monotonically depend on the surface charge, whereas only a moderately hydrophilic surface was conducive to OPN adsorption on OH/CH3mixed SAMs. The results correlated well with cell spreading on OPN-coated surfaces in a serum-free medium culture. In addition, the OH/CH3mixed SAMs with moderate wettability tended to promote β1, β3, αvand α5integrins, indicating that wettability may guide cell adhesion by mediating the integrins signaling pathway. This work will have reference value for designing biologically responsive substrate surfaces.

Synthetic antioxidants, including synthetic phenolic antioxidants (SPAs), amine antioxidants (AAs), and organophosphite antioxidants (OPAs), are essential additives for preventing oxidative aging in various industrial and consumer products. Increasing attention has been paid to the environmental contamination caused by these chemicals, but our understanding of synthetic antioxidants is generally limited compared to other emerging contaminants such as plasticizers and flame retardants. Many people spend a significant portion (normally greater than 80%) of their time indoors, meaning that they experience widespread and persistent exposure to indoor contaminants. Thus, this Perspective focuses on the problem of synthetic antioxidants as indoor environmental contaminants. The wide application of antioxidants in commercial products and their demonstrated toxicity make them an important family of indoor contaminants of emerging concern. However, significant knowledge gaps still need to be bridged: novel synthetic antioxidants and their related transformation products need to be identified in indoor environments, different dust sampling strategies should be employed to evaluate human exposure to these contaminants, geographic scope and sampling scope of research on indoor contamination should be broadened, and the partition coefficients of synthetic antioxidants among different media need to be investigated.