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It is of significance to construct the immunomodulatory and osteogenic microenvironment for three dimension (3D) regeneration of bone tissues. 3D scaffolds, with various chemical composition, macroporous structure and surface characteristics offer a beneficial microenvironment for bone tissue regeneration. However, there is a gap between the well-ordered surface microstructure of bioceramic scaffolds and immune microenvironment for bone regeneration. In this study, a gear-inspired 3D scaffold with well-ordered surface microstructure was successfully prepared through a modified extrusion-based 3D printing strategy for immunomodulation and bone regeneration. The prepared gear-inspired scaffolds could induce M2 phenotype polarization of macrophages and further promoted osteogenic differentiation of bone mesenchymal stem cells in vitro. The subsequent in vivo study demonstrated that the gear-inspired scaffolds were able to attenuate inflammation and further promote new bone formation. The study develops a facile strategy to construct well-ordered surface microstructure which plays a key role in 3D immunomodulatory and osteogenic microenvironment for bone tissue engineering and regenerative medicine. • A gear-inspired 3D bioceramic scaffold with highly well-ordered surface microstructure was successfully fabricated through a modified extrusion-based 3D printing technique. • The size and shape of the highly well-ordered microstructure could be readily modulated. • Taking advantage of good inducing effect of the well-ordered microstructure, the gear-inspired scaffold could be used as a satisfactory biomaterial, which could induce M2 phenotype polarization of macrophages and further promoted osteogenic differentiation of bone mesenchymal stem cells in vitro. • The gear-inspired scaffold could construct 3D immunomodulatory microenvironment to significantly attenuate inflammation and further promote new bone formation in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

The treatment of osteochondral defects remains a huge challenge in clinic. The thermotherapy in traditional Chinese medicine is widely used in treating joint disease because the mild heat stimulation can promote the nutrient circulation. Inspired by the function of thermotherapy, we design a new thermotherapy strategy by using black bioceramic scaffolds to build local mild hyperthermal environment for treating osteochondral defects. Herein, black akermanite (B-AKT) bioceramic scaffolds with micro/nano surface structure and excellent photothermal conversion property are successfully fabricated. The temperature of scaffolds can be precisely controlled by near infrared (NIR) irradiation to construct a mild hyperthermal environment (～41°C). The micro/nanostructure on the scaffolds surface well promoted the cell adhesion and nutrition absorption by activating integrins and focal adhesion kinase (FAK). Meanwhile, the mild hyperthermal environment constructed by B-AKT scaffolds can simultaneously induce the chondrogenesis and osteogenesis both in vitro and in vivo by activating the expression of cellular heat shock proteins (HSPs) and corresponding signaling pathways. Furthermore, in rabbit osteochondral defects, mild hyperthermal environment induced by B-AKT scaffolds exhibits stimulatory effects on the integrated regeneration of cartilage and bone. This study proposes a novel therapy strategy of constructing local mild hyperthermal environment by black bioceramic scaffolds to treat osteochondral defects and other joint diseases. [Display omitted] • The black bioceramic scaffolds with surface micro/nano structure and photothermal properties. • The micro/nano surface structure could promote the cells adhesion and nutrition adsorption. • The mild hyperthermal environment was proved to enhance cells differentiation in vitro and repair osteochondral defects in vivo. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hydroxytyrosol reduces flap necrosis and edema, enhancing skin flap survival. • Hydroxytyrosol decreases oxidative stress and apoptosis, while promoting angiogenesis. • SIRT1-mediated autophagy plays a key role in Hydroxytyrosol's protective mechanism. Surgical tissue reconstruction often uses random skin flaps, but ischemic necrosis at the distal end remains a problem. Hydroxytyrosol, a phenolic compound from olive oil, has anti-inflammatory and antioxidative properties. This study investigated whether hydroxytyrosol could promote flap survival and its underlying mechanisms using a mouse model with random skin flaps. Flap necrosis was assessed seven days after surgery, with angiogenesis, apoptosis, oxidative stress, and autophagy evaluated in flap specimens. Compared to controls, the hydroxytyrosol-treated group showed reduced necrotic areas and edema. Immunohistochemistry and Western blotting revealed decreased oxidative stress and apoptosis, with increased angiogenesis. Laser Doppler imaging confirmed enhanced angiogenesis with hydroxytyrosol treatment. The reversal of hydroxytyrosol's effects by 3-methyladenine underscores autophagy's role, mediated by SIRT1 activation. Our research indicates that hydroxytyrosol enhances random skin flap survival by activating SIRT1-mediated autophagy. [ABSTRACT FROM AUTHOR]

Platinum chemotherapy drugs, represented by cisplatin, have been widely used in cancer therapy. While they are effective, their use is limited by their adverse effects in long-term administration, especially the lack of selectivity and high systemic toxicity. Encouragingly, molecular-like platinum nanoclusters, as a bridge between nanomedical and small molecular drugs, provide an attractive opportunity to completely change the current status of cancer treatment, mainly due to their unique structural advantages, making them highly efficient and low toxic. Functional modifications offer a promising avenue to enhance template-modified platinum nanoclusters' selectivity and safety, addressing systemic toxicity concerns. Concurrently, leveraging tumor heterogeneity facilitates drug bioactivity via metabolism, thereby augmenting therapeutic efficacy. Herein, we utilized iRGD-modified bovine serum albumin (BSA-iRGD) as the protective molecule to construct platinum nanoclusters drug (Pt NC @BSA-iRGD) directly under mild conditions. The new type of chemotherapeutic drug Pt NC @BSA-iRGD exhibits excellent antitumor activity in vitro/vivo, in comparison to clinical commercial first-line carboplatin. This powerful antitumor effect is attributed to its selective uptake by tumor cells through receptor-mediated endocytosis. The release of platinum ions inhibits DNA replication by forming DNA-Pt complexes, activates apoptosis pathways, and ultimately induces tumor cell apoptosis. More impressively, compared to first-line platinum chemotherapy drugs, Pt NC @BSA-iRGD has superior biocompatibility while possessing higher tumor inhibitory activity in vivo during medication treatment. This feature compensates for the shortcomings of clinical chemotherapy platinum-based drugs. This study provides novel insights into exploring new forms of metal cluster-based platinum drugs with high efficiency for optimizing therapeutic efficacy while minimizing systemic toxicity. [Display omitted] • Developing a high-safety, atomically precise Pt NC @BSA-iRGD targeted drug. • In-depth investigation of the antitumor biological activities of Pt NC @BSA-iRGD drug both in vitro and in vivo. • Revealing the antitumor mechanism of atomically precise Pt NC @BSA-iRGD drugs. • Exploring new forms of metal cluster-based platinum drugs with high efficiency and low systemic toxicity. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA) is the main inorganic component of human bone. Inspired by nacre and cortical bone, hydroxyapatite-based coil scaffolds were successfully prepared. The scaffolds presented "brick and mortar" multi-layered structure of nacre and multi-layered concentric circular structure of cortical bone. Because of bioactive components and hierarchical structure, the scaffolds possessed good compressive strength (≈95 MPa), flexural strength (≈161 MPa) and toughness (≈1.1 MJ/m3). In addition, they showed improved angiogenesis and osteogenesis in rat and rabbit critical sized bone defect models. By mimicking co-biological systems, this work provided a feasible strategy to optimize the properties of traditional tissue engineering biological materials for vascularized bone regeneration. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Nitroreductases (NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide (NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para -nitrobenzyl substituted T 1 -weighted magnetic resonance imaging (MRI) contrast agent Gd-DOTA-PNB (probe 1 ) has been designed and explored for the possible detection of NTR. Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para -nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para -aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T 1 -weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections. [ABSTRACT FROM AUTHOR]

The significant guiding roles of nerves in bone formation and remodeling have been largely overlooked during the past decades when it comes to designing bone regeneration scaffolds. The requirement of intrabony nerve regeneration cannot be fulfilled by current therapeutic options, resulting in delayed innervation. Constructing a bone organoid which takes intrabony nerves into account can be a feasible approach. Herein, in combination with the nanocomposite bioinks and multicellular 3D bioprinting technology, a biomimetic neural-bone construct was successfully developed for innervated bone regeneration. Neural cells and bone-related cells were orderly printed to imitate the simplified spatial distribution of bone and nerves. Besides, inorganic calcium silicate (CS) nanowires were synthesized and incorporated into the bioinks to serve as "bioactive factors" to regulate multicellular behaviors. CS nanowires containing-bioinks could obviously promote the long-term survival and spreading as well as osteogenic and neurogenic differentiation of encapsulated cells. Furthermore, the in vivo results demonstrated that the CS nanowires containing-bioinks for 3D bioprinting of neural-bone constructs could simultaneously accelerate the new bone formation and ingrowth of nerve fibers. Taken together, this study offers a new concept by using inorganic nanomaterials as the bioactive components of bioinks for complex tissue regeneration, which represents a potential strategy for the fabrication of bone organoid with enhanced restoration of innervation and innervated bone tissues. A biomimetic neural-bone construct with the incorporation of inorganic calcium silicate nanowires is developed via multicellular 3D bioprinting technology, which can simultaneously promote innervation and bone regeneration. This study provides a potential strategy by using inorganic nanomaterials as the bioactive components for the fabrication of bone organoid with enhanced restoration of innervation and innervated bone tissues. [Display omitted] • Biomimetic neural-bone construct was developed for innervated bone regeneration by using 3D bioprinting technology. • Inorganic calcium silicate nanowires-based bioinks could simultaneously stimulating osteogenesis and neurogenesis. • 3D bioprinted construct with silicate biomaterials was a promising strategy for regeneration of innervated complex tissues. [ABSTRACT FROM AUTHOR]

Morbidity of osteoporosis is increasing as the world population grows and ages, but bone mineral density (BMD) as a common-used diagnostic indicator is not omnipotent in predicting the bone fragility. According to the definition of osteoporosis by World Health Organization (WHO), the present hypothesis proposes an additional fractal-dimension indicator less than 3 to measure the structural change of bones, and further to diagnose osteoporotic patients with complications, to which BMD is insensitive. Literature reports support that the fractal dimension is more sensitive than BMD in specific cases. The hypothesis shows a promise not only in improving the accuracy of screening osteoporotic patients as a complementary indicator to BMD, but also in evaluating mechanical properties of osteoporotic bone and bone-repair effect of bone tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract: Given the current limitation of therapeutic approach for ischemic stroke, a leading cause of disability and mortality in the developed countries, to develop new therapeutic strategies for this devastating disease is urgently necessary. As a serine/threonine kinase, mammalian target of rapamycin (mTOR) activation can mediate broad biological activities that include protein synthesis, cytoskeleton organization, and cell survival. mTOR functions through mTORC1 and mTORC2 complexes and their multiple downstream substrates, such as eukaryotic initiation factor 4E-binding protein 1, p70 ribosomal S6 kinase, sterol regulatory element-binding protein 1, hypoxia inducible factor-1, and signal transducer and activator transcription 3, Yin Ying 1, Akt, protein kinase c-alpha, Rho GTPase, serum-and gucocorticoid-induced protein kinase 1, etc. Specially, the role of mTOR in the central nervous system has been attracting considerable attention. Based on the ability of mTOR to prevent neuronal apoptosis, inhibit autophagic cell death, promote neurogenesis, and improve angiogenesis, mTOR may acquire the capability of limiting the ischemic neuronal death and promoting the neurological recovery. Consequently, to regulate the activity of mTOR holds a potential as a novel therapeutic strategy for ischemic stroke. [Copyright &y& Elsevier]

Abstract: NMR spectroscopy combined with principal component analysis was applied to Arabidopsis thaliana treated with methyl jasmonate in order to obtain macroscopic metabolic changes caused by the treatment. As the first step several chromatographic and NMR spectroscopic techniques were utilized to identify metabolites of Arabidopsis. Sephadex LH-20 showed a high efficiency in the separation of phenolic metabolites in the plant. For identification of minor metabolites two-dimensional J-resolved NMR technique was directly applied to the plant extract and results in a number of elucidation of the metabolites of which signals overlap in 1H NMR spectra. The chemical structure of the identified metabolites were confirmed by various two-dimensional NMR spectroscopy including correlated spectroscopy, heteronuclear single quantum coherence, and heternuclear multiple bond correlation. As next step, a statistical approach, principal component analysis based on projected J-resolved NMR spectra was performed for metabolic alteration of methyl jasmonate-treated Arabidopsis. The results show that methyl jasmonate caused an increase of flavonoids, fumaric acid, sinapoyl malate, sinigrin, tryptophan, valine, threonine, and alanine and a decrease of malic acid, feruloyl malate, glutamine, and carbohydrates after 24h treatment. [Copyright &y& Elsevier]

The lack of traditional bioactivity in zirconia (ZrO 2) and limitations in the personalization capabilities of conventional manufacturing processes pose significant challenges for alveolar bone defect repair. This study aims to investigate whether ZrO 2 /CSi-Mgx scaffolds, produced by combining magnesium-doped calcium silicate (CSi–Mg) as a doping phase with ZrO 2 as the matrix, using projection-based 3D printing (3DPP) technology, exhibit favorable biocompatibility and mechanical properties at low sintering temperatures. The effect of CSi–Mg content (x%), pore structure and heating temperature on the strength of scaffolds were investigated systematically. Incorporation of CSi–Mg could readily adjust the sintering properties of the ZrO 2 scaffolds and the scaffolds with low (10–20 %) CSi–Mg possess much higher strength (74–92 MPa) after 1150 °C. Meanwhile, the ZrO 2 /CSi–Mg10 scaffolds with Triply periodic minimum surfaces (TPMS) pore structure had a compression strength of over 92 MPa and maintained a respectable strength (63 MPa) even after immersion in Tris buffer for 6 weeks. Concurrently, cellular experiments showed that incorporation of CSi–Mg could enhance cellular adhesion, proliferation, and migration of the ZrO 2 scaffolds and also promote the osteogenic property of the scaffolds. In conclusion, the ZrO 2 /CSi–Mg10 scaffold with TPMS pore structure showcases remarkable mechanical performance and bioactivity, holding the potential to facilitate in-situ bone regeneration within the alveolar bone. [ABSTRACT FROM AUTHOR]

In bone fracture preoperative surgical planning, 3D fracture reduction is of great significance. However, segmenting 3D fracture bones into fragments and assembling the bone fragments to restore their original morphology are labor intensive and time consuming. Current works, however, omit their synergistic effects between reduction and segmentation, which, we envision, can significantly benefit the fracture reduction. To this end, a method is proposed to alternatively segment and assemble the fragments by incorporating the contralateral bone as template and leveraging the synergistic effect on segmentation and reduction. The 3D fracture model is initially segmented into separated outer surface of fragments. The reduction is then conducted by template matching, specifically, a whole-to-whole matching strategy through deep learning of dense features is employed. Thereafter, the segmentation is further refined with the assistance of the template. The process of reduction and segmentation is iterated until the algorithm converges. Experiments were conducted on simulated data and clinical data, the mean segmentation accuracy is 95.26%, the assembling translation error is 3.28 ± 3.01 mm, and the assembling rotation error is 1.62 ± 1.71°. Results demonstrated the superiority of our method over state-of-the-art methods, and it can be used as a feasible scheme for fracture reduction planning. Moreover, it is also proved that segmentation and reduction can promote each other. [Display omitted] • Synergistic effect is exploited between segmentation and reduction. • A novel whole-to-whole matching tactics is proposed for template-matching. • The SSM is leveraged to generate and label the training data. [ABSTRACT FROM AUTHOR]

Fractured object assembly is a fundamental problem across many disciplines such as digital archaeology, accident recovery, paleontology, cranio-facial and orthopaedic surgical repair, and many more. With advances in 3D acquisition devices and improved fidelity models of fractured pieces, a flurry of semi-automatic and automatic computational assembly solutions have been developed. These methods have the potential to reduce human labor in assembling fractured objects. The challenge is to balance the time efficiency with the fidelity of the reconstructed assembly. This paper introduces TAssembly , a data-driven approach to fractured object assembly. TAssembly leverages learned feature descriptors of the underlying objects. Its assembly pipeline seamlessly integrates multiple objective terms, including feature matching, rigid matching, and regularization for matching and stitching adjacent pieces. Many experimental results show that TAssembly significantly outperforms previous fractured object assembly methods. [Display omitted] • A data-driven method for 3D fracture bone assembly is proposed. • A latent shape descriptor space for matching features on fractured objects. • Using Stitching constraints to discourage self-penetration. • Feature extraction, feature matching, pairwise matching, consistent matching. [ABSTRACT FROM AUTHOR]

With the increasing incidence of osteoarthritis (OA) in elderly patients and the challenges posed by its multifaceted pathogenesis in developing effective treatments, this study explores the effective protein loading mode of Progranulin (PGRN) and its therapeutic potential for treating OA. GelMA hydrogels prepared with different concentrations of PGRN, employing AC-PEG-NHS as a crosslinking agent for drug encapsulation, were used to test the sustained release effect of the composite hydrogel drug delivery system. Additionally, we conducted in vitro assays to investigate the regulatory effects on rat bone marrow mesenchymal atromal cells (BMSCs), chondrocytes, and mouse macrophages - focusing on cell proliferation, and differentiation. For in vivo studies, histological staining techniques were utilized to assess inflammatory cell polarization and cartilage repair in a rat knee injury model. The results demonstrated that PGRN-loaded hydrogels significantly accelerated cell proliferation, enhance differentiation of BMSCs into chondrocytes, maintained a healthy chondrocyte phenotype, and induce M2-type polarization while inhibiting M1-type polarization in macrophages. Histological analyses also showed markedly improved tissue repair in the group treated with GelMA–NHS–PGRN hydrogels. As a result, these GelMA–NHS–PGRN hydrogels present a promising therapeutic approach for OA, potentially mitigating chronic inflammation and facilitating cartilage repair through controlled release of PGRN. PGRN, Osteoarthritis, Anti-inflammatory hydrogels, Cartilage regeneration. [ABSTRACT FROM AUTHOR]

• This retrospective study analysed the use of three-dimensional (3D)-printed antibiotic-loaded bone cement (ALBC) spacers when treating infection after hip replacement surgery. • Compared with traditional ALBC spacers (conventional group), the use of 3D-printed spacers improved functional mobility of the hip joint after surgery. • The health status was better for patients in the 3D-printing group compared with the conventional group after surgery. • Pain was less for patients in the 3D-printing group compared with the conventional group after surgery. To explore the effect of three-dimensional (3D) printing to create personalized antibiotic-loaded bone cement (ALBC) spacers to assist in treatment of periprosthetic infection after total hip arthroplasty (THA). The data of 40 patients with postoperative infection after THA were analysed retrospectively. The patients were divided into two groups: the 3D-printing group (age 47–78 years, n = 20) and the conventional group (age 57–78 years, n = 20). In stage I surgery, 3D-printed silicone moulds were used to create ALBC spacers for the 3D-printing group, while traditional manual methods were used to create spacers for the conventional group. After the infection was controlled, both groups underwent conventional hip revision surgery (stage II surgery). All patients were evaluated using the Harris Hip Score (HHS) (primary outcome) for hip function. All 40 patients had follow-up data from 3 months after stage I surgery and 12 months after stage II surgery. The intergroup difference in HHS was 11.25 points [97.5% confidence interval (CI) 7.92–14.58; P < 0.01] at 3 months after stage I surgery, and 9.15 points (97.5% CI 4.82–13.48; P < 0.01) at 12 months after stage II surgery. The overall difference between the two groups was 9.55 points (97.5% CI 5.83–13.27; P < 0.01), which was significant (P < 0.05). During the follow-up period, the hip function of the 3D-printing group was superior to that of the conventional group following the treatment of infections after THA. [ABSTRACT FROM AUTHOR]

For the first time, g-C 3 N 4 @α-Fe 2 O 3 /Co-Pi heterojunctional hollow spheres were successfully fabricated via thermal condensation method followed by solvothermal and photo-deposition treatment, which showed excellent photocatalytical property. Except for the Z-scheme charge transfer between α-Fe 2 O 3 and g-C 3 N 4 , the Co-Pi could further reduce the combination of photogenerated electrons and holes as a hole storage agent, resulting in remarkably enhanced visible-light photocatalytic water splitting activity with the H 2 production rate of 450 μmol h−1g−1, which is 15.7 times higher than that of g-C 3 N 4. Moreover, the photocatalytic activity of the prepared ternary hollow photocatalysts showed almost no significant weakness after five cycles, which indicated their good performance stability. The as-prepared g-C 3 N 4 @α-Fe 2 O 3 /Co-Pi also possessed good activity for overall water splitting with the hydrogen production rate reaching 9.8 μmol h−1g−1. This synthesized g-C 3 N 4 @α-Fe 2 O 3 /Co-Pi composite is expected to be a promising candidate for water splitting. Image 1 • Hollow g-C 3 N 4 @α-Fe 2 O 3 /Co-Pi (CFP) heterojunction spheres are fabricated. • CFP enhances visible-light photocatalytic activity for water splitting. • H 2 production rate of CFP is 15.7 times higher than that of g-C 3 N 4. • The ternary hollow photocatalysts have good performance stability. • Z-Scheme system forms between g-C 3 N 4 and α-Fe 2 O 3 , Co-Pi acts as hole storage agent. [ABSTRACT FROM AUTHOR]

Abstract It is difficult to achieve self-healing outcoming for the osteochondral defects caused by degenerative diseases. The simultaneous regeneration of both cartilage and subchondral bone tissues is an effective therapeutic strategy for osteochondral defects. However, it is challenging to design a single type of bioscaffold with suitable ionic components and beneficial osteo/chondral-stimulation ability for regeneration of osteochondral defects. In this study, we successfully synthesized a pure-phase lithium calcium silicate (Li 2 Ca 4 Si 4 O 13 , L 2 C 4 S 4) bioceramic by a sol-gel method, and further prepared L 2 C 4 S 4 scaffolds by using a 3D-printing method. The compressive strength of L 2 C 4 S 4 scaffolds could be well controlled in the range of 15–40 MPa when pore size varied from 170 to 400 μm. L 2 C 4 S 4 scaffolds have been demonstrated to possess controlled biodegradability and good apatite-mineralization ability. At a certain concentration range, the ionic products from L 2 C 4 S 4 significantly stimulated the proliferation and maturation of chondrocytes, as well as promoted the osteogenic differentiation of rBMSCs. L 2 C 4 S 4 scaffolds simultaneously promoted the regeneration of both cartilage and subchondral bone as compared to pure β-TCP scaffolds in rabbit osteochondral defects. These findings suggest that 3D-printed L 2 C 4 S 4 scaffolds with such specific ionic combination, high mechanical strength and good degradability as well as dual bioactivities, represent a promising biomaterial for osteochondral interface reconstruction. Graphical abstract 3D-printed Li 2 Ca 4 Si 4 O 13 scaffolds possess dual bioactivities and can biologically fulfill the requirements of both cartilage and subchondral bone interface reconstruction, which represents a feasible strategy for osteochondral reconstruction. Image 1 [ABSTRACT FROM AUTHOR]

[Display omitted] • Customized magnesium-doped wollastonite/nano-hydroxyapatite bioceramic scaffolds with precise porous structures were fabricated by 3D printing and coating technique. • Composite bioceramic scaffold with 15 μm coating thickness exhibited the highest mechanical properties. • Nano-hydroxyapatite coating can effectively inhibite the proliferation of human osteosarcoma cells. • Composite bioceramic scaffold had significantly enhanced osteogenic induction on Rat bone marrow stem cells. It is still a major challenge to remove tumor cells and fill bone defects after tumor resection. Combined with the 3D printing technology, the composite bioceramics scaffolds were fabricated with interconnected porous magnesium-doped wollastonite (CSi-Mg) scaffolds as the architecture and nano-hydroxyapatite (n -HA) as the surface. The influence of manufacturing process on the n -HA layer thickness and degradation performance, biological performance and anti-tumor performance of the composite scaffolds were investigated. The n -HA surface layer could effectively retard the degradation rate of CSi-Mg scaffolds and maintain high mechanical strength (over 90 MPa) after immersion in simulated body fluid for 3 weeks. Meanwhile, CSi-Mg/n-HA3 scaffold induced about 50 % of cell death for human osteosarcoma cells (MG-63) in vitro. CSi-Mg/ n -HAx (x = 1, 3) scaffolds could improve the osteogenic performance of Rat BMSC. These findings demonstrate that the bioceramic composite scaffold with high strength, good osteogenic performance and anti-tumor performance is promising for the treatment of tissue injury after resection of osteosarcoma. [ABSTRACT FROM AUTHOR]

Objective The goal of this study was to detect early changes in the cartilage matrix caused by immobilization in a rabbit model of immobilization-induced osteoarthritis (OA) by T2 mapping with 7.0 T MRI. Materials and methods Left knee joints of 28 mature rabbits were immobilized at 180° of extension with orthopedic casting tape for 1, 2, or 3 weeks ( n = 7 rabbits each). No immobilization was performed in the control group ( n = 7 rabbits). T2 mapping was performed after 1, 2, and 3 weeks. Osteochondral specimens harvested from the trochlea groove (TG) and medial femoral condyle (MFC) were subjected to histologic, immunohistochemical, and microscopic evaluation, followed by biochemical assays for water, glycosaminoglycan (GAG), and collagen. The ability of T2 mapping to reveal changes in the cartilage matrix was further assessed. Results Rabbits demonstrated elevated T2 values (9.9% in TG, 10.6% in MFC), a dulled cartilage surface, reduced Safranin-O staining, and decreased GAG content (14.2% in TG and MFC) after 2 weeks, with cartilage surface softening, irregularity, and markedly reduced GAG content by 3 weeks. T2 values were correlated positively with water (r = 0.836 in TG, r = 0.821 in MFC) and negatively with GAG content (r = − 0.945 in TG, r = − 0.957 in MFC), but had no discernible relationship with collagen content (r = − 0.196 in TG, r = − 0.213 in MFC). Conclusions 7.0 T MRI T2 mapping can be used to detect early changes of the cartilage matrix caused by immobilization in an immobilization-induced OA model. [ABSTRACT FROM AUTHOR]

Local corrosion of coated Mg alloys appears as aggressive solutions penetrate the coating-substrate interface, which might accelerate the premature failure of coated Mg alloys. In this work, Mg corrosion by-products, including pH increase and Mg2+ enrichment, were attempted to act as dual stimuli for coating self-healing. We prepared DCPD/H x Phy (dicalcium phosphate dihydrate/phytic acid) hybrid coating as anti-corrosive self-healing coatings for regulating Mg degradation. pH increase stimulated Ca2+ and PO 4 3- ion release from DCPD and apatite formation for local corrosion elimination. Besides, H x Phy-containing compounds were regulated by Mg2+ ion enrichment and transformed into Mg-H x Phy chelate compounds for enhanced self-healing behavior. [Display omitted] • Mg corrosion by-products (pH increase and Mg2+ enrichment) were acted as dual stimuli. • DCPD/H x Phy coatings were prepared on Mg as anti-corrosive self-healing coatings. • pH increase stimulated DCPD dissolution and promoted apatite formations. • Mg2+ ion enrichment promoted Mg-H x Phy chelate for enhanced self-healing. [ABSTRACT FROM AUTHOR]

Highlights: [•] Three new cucurbitane triterpenoids were isolated from Hemsleya penxianensis. [•] Cytotoxic activities of the isolated compounds was evaluated. [•] A new compound with aldehyde group showed the strongest cytotoxicities. [Copyright &y& Elsevier]

Fig. 2 The recognition mechanism of sensor 9b and gallic acid. [Display omitted] • Gallic acid is involved in many important biological events and has a variety of biological properties. • Boronic acid-based fluorescence sensors can specifically recognize compounds with 1, 2-diol structure. • Guanidine group synergizes with boronic acid group to enhance the binding affinity, selectivity and water solubility of sensor 9b. • We discussed the fluorescence response characteristics of sensor 9b with gallic acid and its application in actual samples. As one of the widespread phenols in nature, gallic acid (GA) has attracted a subject of attention due to its extensive biological properties. It is very important and significant to develop a sensitive and selective gallic acid sensor. In recent years, owing to their reversible covalent binding with Lewis bases and polyols, boronic acid compounds have been widely reported as fluorescence sensors for the identification of carbohydrates, ions and hydrogen peroxide, etc. However, boronic acid sensors for specific recognition of gallic acid have not been reported. Herein, a novel water-soluble boronic acid sensor with double recognition sites is reported. When the concentration of gallic acid added was 1.1 × 10−4 M, the fluorescence intensity of sensor 9b decreased by 80%, followed by pyrogallic acid and dopamine. However, the fluorescence of the sensor 9b combined with other analytes such as ATP, sialic acid, and uridine was basically unchanged, indicating that the sensor 9b had no ability to recognize these analytes. Also, sensor 9b has a fast response time to gallic acid at room temperature, and has a high binding constant (12355.9 ± 156.89 M−1) and low LOD (7.30 × 10−7 M). Moreover, gallic acid content of real samples was also determined, and the results showed that this method has a higher recovery rate. Therefore, sensor 9b can be used as a potential tool for detecting biologically significant gallic acid in actual samples such as food, medicine, and environmental analysis samples. [ABSTRACT FROM AUTHOR]

Three simple fluorescence turn-on sensors have been designed for the selective detection of adenosine (AD) based on a boronic acid receptor and a coumarin fluorophore (NLC, NJC, NDC). In the absence of AD, the fluorescence emission intensity of the sensors was relatively weak due to the effective electronic transfer from the to the coumarin to the boronic acid moiety. When the AD was introduced into the system, an obvious fluorescence enhancement was observed. It was attributed to the boronic acid covalently binding to the cis -diol unit of the AD resulting in the electronic transfer process being inhibited. Under the optimal conditions, these fluorescent sensors not only could perform good selectivity and fast response (< 30 s), but also show good water solubility. Finally, the proposed sensor NLC has been utilized for the AD determination in urine without any complicated pretreatment and the recovery was in the range of 95–103%. As a result, it is promising for application on the AD detection in complex biological samples. Moreover, there are no small molecular sensors detecting AD have been reported, yet, it is promising for providing a new platform to detect AD by small molecular sensor. [Display omitted] • Fluorescence turn on sensors for specific detection of adenosine (AD) in urine. • The first synthesized small molecular sensor for detecting AD. • The sensors operated by phenylboronic acid as the recognition group and coumarin as the luminescent group. • Sensor NLC has a low detection limit when detecting AD (6.87 μM). [ABSTRACT FROM AUTHOR]

In this work, a facile hemicyanine-naphthalene-based fluorescent sensor for colorimetric and ratiometric sensing of pH was constructed via a simple synthesis process. Significantly, sensor 3 showed a high sensitivity to extremely alkaline solution and had a notably large Stokes shift (145 nm). Its absorbance and fluorescence enhanced or quenched obviously in the pH range of 5.0–12.0, accompanying with colour change. In addition, the fluorescence intensity increased 727-fold (F 440 /F 710) when the pH was adjusted to 12, indicating that sensor 3 showed great potential in the detection of extremely alkaline solution. • A novel colorimetric and ratiometric pH sensor was constructed via a simple synthesis process. • It shows a high sensitivity to pH in range of 5.0–12.0, especially in extremely alkaline solution. • Sensor 3 has a notably large Stokes shift (≥145 nm). • The fluorescence intensity of sensor 3 increased 727-fold (F 440 /F 710) when the pH was adjusted to 12. [ABSTRACT FROM AUTHOR]

Sphingosine kinases (SphKs) are lipid kinases that catalyze the phosphorylation of sphingosine (Sph) to sphingosine-1-phosphate (S1P). As a bioactive lipid, S1P plays a role outside and inside the cell to regulate biological processes. The overexpression of SphKs is related to a variety of pathophysiological conditions. Targeting the S1P signaling pathway is a potential treatment strategy for many diseases. SphKs are key kinases of the S1P signaling pathway. The SphK family includes two isoforms: SphK1 and SphK2. Determination of the co-crystal structure of SphK1 with various inhibitors has laid a solid foundation for the development of small molecule inhibitors targeting SphKs. This paper reviews the differences and connections between the two isoforms and the structure of SphK1 crystals, especially the structure of its Sph " J -shaped" channel binding site. This review also summarizes the recent development of SphK1 and SphK2 selective inhibitors and the exploration of the unresolved SphK2 structure. Image 1 • The biological role of sphingosine kinases and inhibitors were introduced. • The structural properties of SphK1 crystal structure and the co-crystal structures of some inhibitors were introduced. • The advances in rational design of new inhibitors based on the co-crystal structures of SphK1 were introduced. • Compare the differences of " J -shaped" binding sites; analyze the changes in selectivity induced by structural changes. • A comparative study of SphK1 and SphK2 in mice and humans. [ABSTRACT FROM AUTHOR]

Small-molecule reactive species, such as reactive oxygen species, catecholamines, ions, sialic acid and gas signal molecules, are involved in many important biological events. For example, abnormal reactive oxygen species levels can lead to a range of cell dysfunctions and eventually cancer and neurodegenerative diseases. Therefore, the development of sensors for detecting small-molecule reactive species is of great significance for disease prevention, diagnosis and treatment. Boronic acid has been widely used for the selective recognition of sugars due to their obvious fluorescence change after combining with sugar, easily structure modification and good light stability. In recent years, a large number of boronic acid-based sensors that can selectively recognize small-molecule reactive species have been reported, however, there are few systematic reviews in this field, and lack of in-depth understanding of the identification mechanism and structure-activity relationship. In this review, boronic acid-based sensors detecting small-molecule reactive species (such as reactive oxygen species (H 2 O 2 , ONOO−, CLO−), catecholamines (dopamine, norepinephrine), sialic acid and sialic acid derivatives (sialic acid, sialic Lewis X, sialic Lewis Y) and ions (F−, Fe3+, Cu2+)) over the recent years (2015–2020) will be discussed, focusing on the fluorescence characteristics of the sensors and their potential in disease detection, and we are aiming to provide researchers with better inspiration. • Small-molecule reactive species are involved in many important biological events. • Boronic acid-based fluorescent sensors are widely used to detect small-molecule reactive species in organisms. • We review boronic acid-based sensors for small-molecule reactive species imaging. • We discuss the characteristic and response mechanism of the sensors. [ABSTRACT FROM AUTHOR]

Ginseng and ginsenosides are known for their remarkable effects on the central nervous system. However, pharmacokinetic studies have suggested that the Ginsenoside Rg1 (Rg1) cannot be efficiently transported through the blood–brain barrier. To investigate the effects of Rg1 in combination with mannitol protects neurons against glutamate-induced ER stress via the PERK-eIF2 -ATF4 signaling pathway. Rg1, along with the BBB permeabilizer mannitol, exhibited a potent neuroprotective effect by significantly reducing the neurological scores and infarct volume in rats exposed to middle cerebral artery occlusion. We evaluated the effect of Rg1 on neuroprotection after MCAO, and also explored its potential mechanism of action. Our results show that Rg1 reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive neurons. This neuroprotection may be dependent, at least in part, on the preservation of the endoplasmic reticulum and mitochondrial function. Ischemia-induced brain injury is largely caused by the excessive release of glutamate, which results in excitotoxicity and cell death. Neurons were pretreated with Rg1 before inducing endoplasmic reticulum stress with glutamate. A reduction in the expression of Bax and a concomitant increase in Bcl2 expression prevented the induction of apoptosis. Furthermore, Rg1 downregulated the expression of endoplasmic reticulum stress genes. Our results indicate that Rg1 modulation of stress-responsive genes helps prevent glutamate-induced endoplasmic reticulum stress in neurons through the PERK-eIF2-α-ATF4 signaling pathway. [ABSTRACT FROM AUTHOR]

Specifically inhibiting the proliferation of activated macrophages and clearing the high levels of reactive oxygen species (ROS) secreted by macrophages is crucial for osteoarthritis (OA) treatment. Moreover, if the clearance of these high levels of ROS can be simultaneously used to induce oxidation-responsive release of anti-inflammatory drugs, the therapeutic effect of OA may be further improved. Here, a multifunctional anti-inflammatory drug (CPHs) based on a peptide dendrimer nanogel was constructed by physically encapsulating CORM-401 and wrapping its surface with folic acid (FA)-modified hyaluronic acid (HA). CPHs is capable of efficiently entering activated macrophages via FA- and HA-mediated specific targeting effects and then rapidly release large amounts of CO by massive consumption of H 2 O 2. The generated CO effectively suppresses the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α by inhibiting cell proliferation; inducing the activation of heme oxygenase (HO-1), and downregulating the expression of p38 MAPK, NF-kB (p50/p65) and TLR-2. In vivo experiments further confirmed that CPHs can massively deplete ROS in OA joints and effectively suppress the degradation of articular cartilage and their extracellular matrix. More importantly, CPHs is non-toxic to normal macrophages, and the high levels of CO generated in the joints do not result in notable changes in the HbCO levels in blood. Together, these results show that CPHs is an effective and safe anti-inflammatory drug and has essential application prospects in OA treatment. Image 1 [ABSTRACT FROM AUTHOR]

Abstract: A new sesquiterpenoid, namely Linerenone (1), together with three known sesquiterpenoids (2–4), were isolated from the fruits of Lindera communis. Their structures were determined by extensive spectroscopic analysis including 1D, 2D-NMR and HR-MS spectra. Compound 1 showed significant cytotoxic activity against H460, ES2 and DU145 cancer cells with IC50 of 2.1μg/mL, 2.8μg/mL and 3.0μg/mL, respectively. [Copyright &y& Elsevier]

A boronic acid-based sensor was reported selectively to recognize Pd2+ ion, which has a low limit of detection (38 nM) and exhibits the potential for the development of Pd2+ recognition in practical environments. Herein, a boronic acid-based sensor was reported selectively to recognize Pd2+ ion. The fluorescence intensity increased 36-fold after sensor binding with 2.47 × 10−5 M of Pd2+ ion. It was carried out in the 99% aqueous solution for binding tests, indicating sensor having good water solubility. In addition, it is discernible that Pd2+ ion turned on the blue fluorescence of sensor under a UV–lamp (365 nm), while other ions (Ag+, Al3+, Ba2+, Ca2+, Cr2+, Cd2+, Co2+, Cs2+, Cu2+, Fe2+, Fe3+, K+, Li+, Mg2+, Mn2+, Na+, Ni2+ and Zn2+) did not show the similar change. Furthermore, sensor has a low limit of detection (38 nM) and high selectivity, which exhibits the potential for the development of Pd2+ recognition in practical environments. [ABSTRACT FROM AUTHOR]