Combined analysis of mRNA and miRNA transcriptomes reveals the regulatory mechanism of Xanthomonas arboricola pv pruni resistance in Prunus persica.

BACKGROUND: Peach bacterial shot hole, caused by Xanthomonas arboricola pv pruni (Xap), is a global bacterial disease that poses a threat to the yield and quality of cultivated peach trees (Prunus persica). RESULTS: This study compared the mRNA and miRNA profiles of two peach varieties, 'Yanbao' (resistant) and 'Yingzui' (susceptible), after inoculation with Xap to identify miRNAs and target genes associated with peach tree resistance. mRNA sequencing results revealed that in the S0-vs-S3 comparison group, 1574 genes were upregulated and 3975 genes were downregulated. In the R0-vs-R3 comparison group, 1575 genes were upregulated and 3726 genes were downregulated. Through miRNA sequencing, a total of 112 known miRNAs belonging to 70 miRNA families and 111 new miRNAs were identified. Notably, some miRNAs were exclusively expressed in either resistant or susceptible varieties. Additionally, 59 miRNAs were downregulated and 69 miRNAs were upregulated in the R0-vs-R3 comparison group, while 46 miRNAs were downregulated and 52 miRNAs were upregulated in the S0-vs-S3 comparison group. Joint analysis of mRNA and miRNA identified 79 relationship pairs in the S0-vs-S3 comparison group, consisting of 48 miRNAs and 51 target genes. In the R0-vs-R3 comparison group, there were 58 relationship pairs, comprising 28 miRNAs and 20 target genes. Several target genes related to resistance, such as SPL6, TIFY6B, and Prupe.4G041800_v2.0.a1 (PPO), were identified through literature reports and GO/KEGG enrichment analysis. CONCLUSION: In conclusion, this study discovered several candidate genes involved in peach tree resistance by analyzing differential expression of mRNA and miRNA. These findings provide valuable insights into the mechanisms underlying resistance to Xap in peach trees.

PAD4 Inhibitor-Loaded Layered Double Hydroxide Nanosheets as a Multifunctional Nanoplatform for Photodynamic Therapy-Mediated Tumor Metastasis Treatment.

Photodynamic therapy (PDT) is demonstrated to be effective in inducing antitumor immune responses for tumor metastasis treatment. However, tumor hypoxia, inferior tissue penetration of light, and low singlet oxygen (1O2) quantum yield significantly hamper the efficacy of PDT, thus weakening its immune function. Moreover, PDT-mediated neutrophil extracellular traps (NETs) formation can further reduce the therapeutic effectiveness. Herein, the use of defect-rich CoMo-layered double hydroxide (DR-CoMo-LDH) nanosheets as a carrier to load a typical peptidyl arginine deiminase 4 inhibitor, i.e., YW4-03, to construct a multifunctional nanoagent (403@DR-LDH) for PDT/immunotherapy, is reported. Specifically, 403@DR-LDH inherits excellent 1O2 generation activity under 1550 nm laser irradiation and improves the half-life of YW4-03. Meanwhile, 403@DR-LDH plus 1550 nm laser irradiation can stimulate immunogenic cell death to promote the maturation of dendric cells and activation/infiltration of T cells and significantly downregulate H3cit protein expression to inhibit NETs formation, synergistically promoting the antitumor metastasis effect. Taken together, 403@DR-LDH can kill cancer cells and inhibit tumor growth/metastasis under 1550 nm laser irradiation. Single-cell analysis indicates that 403@DR-LDH can regulate the ratio of immune cells and immune-related proteins to improve the tumor immune microenvironment, showing strong efficacy to inhibit the tumor growth, metastasis, and recurrence.

Bifunctional Bismuth-Based Layered Double Hydroxide Sonosensitizer for Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy.

Novel inorganic sonosensitizers with excellent reactive oxygen species (ROS) generation activity and multifunctionality are appealing in sonodynamic therapy (SDT). Herein, amorphous bismuth (Bi)-doped CoFe-layered double hydroxide (a-CoBiFe-LDH) nanosheets are proposed via crystalline-to-amorphous phase transformation strategy as a new type of bifunctional sonosensitizer, which allows ultrasound (US) to trigger ROS generation for magnetic resonance imaging (MRI)-guided SDT. Importantly, a-CoBiFe-LDH nanosheets exhibit much higher ROS generation activity (≈6.9 times) than that of traditional TiO2 sonosensitizer under US irradiation, which can be attributed to the acid etching-induced narrow band gap, high electron (e-)/hole (h+) separation efficiency and inhibited e-/h+ recombination. In addition, the paramagnetic properties of Fe ion endow a-CoBiFe-LDH with excellent MRI contrast ability, making it a promising contrast agent for T2-weighted MRI. After modification with polyethylene glycol, a-CoBiFe-LDH nanosheets can function as a high-efficiency sonosensitizer to activate p53, MAPK, oxidative phosphorylation, and apoptosis-related signaling pathways, ultimately inducing cell apoptosis in vitro and tumor ablation in vivo under US irradiation, which shows great potential for clinical cancer treatment.

Boosting the sonodynamic performance of CoBiMn-layered double hydroxide nanoparticles via tumor microenvironment regulation for ultrasound imaging-guided sonodynamic therapy.

Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO2 sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e-/h+) separation. More importantly, the presence of Mn4+ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H2O2 into O2 for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.

A MgAl-LDH-CuS nanosheet-based thermo-responsive composite hydrogel with nir-responsive angiogenesis inhibitor releasing capability for multimode starvation therapy.

The rapid proliferation of tumors is highly dependent on the nutrition supply of blood vessels. Cutting off the nutrient supply to tumors is an effective strategy for cancer treatment, known as starvation therapy. Although various hydrogel-based biomaterials have been developed for starvation therapy through glucose consumption or intravascular embolization, the limitations of single-mode starvation therapy hinder their therapeutic effects. Herein, we propose a dual-function nutrition deprivation strategy that can block the nutrients delivery through extravascular gelation shrinkage and inhibit neovascularization through angiogenesis inhibitors based on a novel NIR-responsive nanocomposite hydrogel. CuS nanodots-modified MgAl-LDH nanosheets loaded with angiogenesis inhibitor (sorafenib, SOR) are incorporated into the poly(n-isopropylacrylamide) (PNIPAAm) hydrogel by radical polymerization to obtain the composite hydrogel (SOR@LDH-CuS/P). The SOR@LDH-CuS/P hydrogel can deliver hydrophobic SOR with a NIR-responsive release behavior, which could decrease the tumor vascular density and accelerate cancer cells apoptosis. Moreover, the SOR@LDH-CuS/P hydrogel exhibits higher (3.5 times) compressive strength than that of the PNIPAAm, which could squeeze blood vessels through extravascular gelation shrinkage. In vitro and in vivo assays demonstrate that the interruption of nutrient supply by gelation shrinkage and the prevention of angiogenesis by SOR is a promising strategy to inhibit tumor growth for multimode starvation therapy.

Layered double hydroxide-based nanomaterials for biomedical applications.

Against the backdrop of increased public health awareness, inorganic nanomaterials have been widely explored as promising nanoagents for various kinds of biomedical applications. Layered double hydroxides (LDHs), with versatile physicochemical advantages including excellent biocompatibility, pH-sensitive biodegradability, highly tunable chemical composition and structure, and ease of composite formation with other materials, have shown great promise in biomedical applications. In this review, we comprehensively summarize the recent advances in LDH-based nanomaterials for biomedical applications. Firstly, the material categories and advantages of LDH-based nanomaterials are discussed. The preparation and surface modification of LDH-based nanomaterials, including pristine LDHs, LDH-based nanocomposites and LDH-derived nanomaterials, are then described. Thereafter, we systematically describe the great potential of LDHs in biomedical applications including drug/gene delivery, bioimaging diagnosis, cancer therapy, biosensing, tissue engineering, and anti-bacteria. Finally, on the basis of the current state of the art, we conclude with insights on the remaining challenges and future prospects in this rapidly emerging field.

Preparation of Dye Molecule-Intercalated MoO3 Organic/Inorganic Superlattice Nanoparticles for Fluorescence Imaging-Guided Catalytic Therapy.

Intercalation of organic molecules into the van der Waals gaps of layered materials allows for the preparation of organic/inorganic superlattices for varying promising applications. Herein, the preparation of a series of dye molecule/MoO3 organic/inorganic superlattice nanoparticles by aqueous intercalation of several dye molecules into layered MoO3 for fluorescence imaging-guided catalytic therapy is reported. The long MoO3 nanobelts are treated by ball milling and subsequent aqueous intercalation followed by a cation ion exchange to obtain the dye molecule-intercalated MoO3 organic/inorganic superlattices. Importantly, because of the activation induced by organic intercalation, the Nile blue (NB)-intercalated MoO3-x (NB-MoO3-x ) nanoparticles show excellent catalytic activity for the generation of reactive oxygen species, that is, hydroxyl radical (·OH) and superoxide anion (·O2- ), through catalyzing H2 O2 and O2 , respectively. Moreover, the intense fluorescence of the intercalated NB molecules endows NB-MoO3-x with the in vivo fluorescence imaging capability. Thus, the polyvinylpyrrolidone-modified NB-MoO3-x nanoparticles can be used for tumor-specific catalytic therapy to realize efficient cancer cell elimination in vitro and fluorescence imaging-guided tumor ablation in vivo.

A Se Nanoparticle/MgFe-LDH Composite Nanosheet as a Multifunctional Platform for Osteosarcoma Eradication, Antibacterial and Bone Reconstruction.

Despite advances in treating osteosarcoma, postoperative tumor recurrence, periprosthetic infection, and critical bone defects remain critical concerns. Herein, the growth of selenium nanoparticles (SeNPs) onto MgFe-LDH nanosheets (LDH) is reported to develop a multifunctional nanocomposite (LDH/Se) and further modification of the nanocomposite on a bioactive glass scaffold (BGS) to obtain a versatile platform (BGS@LDH/Se) for comprehensive postoperative osteosarcoma management. The uniform dispersion of negatively charged SeNPs on the LDH surface restrains toxicity-inducing aggregation and inactivation, thus enhancing superoxide dismutase (SOD) activation and superoxide anion radical (·O2 -)-H2O2 conversion. Meanwhile, Fe3+ within the LDH nanosheets can be reduced to Fe2+ by depleting glutathione (GSH) in the tumor microenvironments (TME), which can catalyze H2O2 into highly toxic reactive oxygen species. More importantly, incorporating SeNPs significantly promotes the anti-bacterial and osteogenic properties of BGS@LDH/Se. Thus, the developed BGS@LDH/Se platform can simultaneously inhibit tumor recurrence and periprosthetic infection as well as promote bone regeneration, thus holding great potential for postoperative "one-stop-shop" management of patients who need osteosarcoma resection and scaffold implantation.

A LDH-Derived Metal Sulfide Nanosheet-Functionalized Bioactive Glass Scaffold for Vascularized Osteogenesis and Periprosthetic Infection Prevention/Treatment.

Periprosthetic infection and prosthetic loosing stand out as prevalent yet formidable complications following orthopedic implant surgeries. Synchronously addressing the two complications is long-time challenging. Herein, a bioactive glass scaffold (BGS) functionalized with MgCuFe-layered double hydroxide (LDH)-derived sulfide nanosheets (BGS/MCFS) is developed for vascularized osteogenesis and periprosthetic infection prevention/treatment. Apart from the antibacterial cations inhibiting bacterial energy and material metabolism, the exceptional near-infrared-II (NIR-II) photothermal performance empowers BGS/MCFS to eliminate periprosthetic infections, outperforming previously reported functionalized BGS. The rough surface topography and the presence of multi-bioactive metal ions bestow BGS/MCFS with exceptional osteogenic and angiogenic properties, with 8.5-fold and 2.3-fold enhancement in bone mass and neovascularization compared with BGS. Transcriptome sequencing highlights the involvement of the TGF-ß signaling pathway in these processes, while single-cell sequencing reveals a significant increase in osteoblasts and endothelial cells around BGS/MCFS compared to BGS.

PAD4 Inhibitor-Functionalized Layered Double Hydroxide Nanosheets for Synergistic Sonodynamic Therapy/Immunotherapy Of Tumor Metastasis.

Sonodynamic therapy (SDT) is demonstrated to trigger the systemic immune response of the organism and facilitate the treatment of metastatic tumors. However, SDT-mediated neutrophil extracellular traps (NETs) formation can promote tumor cell spread, thus weakening the therapeutic effectiveness of metastatic tumors. Herein, the amorphous CoW-layered double hydroxide (a-CoW-LDH) nanosheets are functionalized with a peptidyl arginine deiminase 4 (PAD4) inhibitor, i.e., YW3-56, to construct a multifunctional nanoagent (a-LDH@356) for synergistic SDT/immunotherapy. Specifically, a-CoW-LDH nanosheets can act as a sonosensitizer to generate abundant reactive oxygen species (ROS) under US irradiation. After loading with YW3-56, a-LDH@356 plus US irradiation not only effectively induces ROS generation and immunogenic cell death, but also inhibits the elevation of citrullinated histone H3 (H3cit) and the release of NETs, enabling a synergistic enhancement of anti-tumor metastasis effect. Using 4T1 tumor model, it is demonstrated that combining a-CoW-LDH with YW3-56 stimulates an anti-tumor response by upregulating the proportion of immune-activated cells and inducing polarization of M1 macrophages, and inhibits immune escape by downregulating the expression of PD-1 on immune cells under US irradiation, which not only arrests primary tumor progression with a tumor inhibition rate of 69.5% but also prevents tumor metastasis with the least number of lung metastatic nodules.

Ternary NiCoTi-layered double hydroxide nanosheets as a pH-responsive nanoagent for photodynamic/chemodynamic synergistic therapy.

Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O2-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situ pH-responsive PDT. Moreover, due to the effective conversion between Co3+ and Co2+ caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (·OH) from H2O2 through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO2 nanoparticles at pH 6.5. In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination.

Synergistic Interaction between Metal Single-Atoms and Defective WO3- x Nanosheets for Enhanced Sonodynamic Cancer Therapy.

Although metal single-atom (SA)-based nanomaterials are explored as sonosensitizers for sonodynamic therapy (SDT), they normally exhibit poor activities and need to combine with other therapeutic strategies. Herein, the deposition of metal SAs on oxygen vacancy (OV)-rich WO3- x nanosheets to generate a synergistic effect for efficient SDT is reported. Crystalline WO3 and OV-rich WO3- x nanosheets are first prepared by simple calcination of the WO3·H2O nanosheets under an air and N2 atmosphere, respectively. Pt, Cu, Fe, Co, and Ni metal SAs are then deposited on WO3- x nanosheets to obtain metal SA-decorated WO3- x nanocomposites (M-WO3- x). Importantly, the Cu-WO3- x sonosensitizer exhibits a much higher activity for ultrasound (US)-induced production of reactive oxygen species than that of the WO3- x and Cu SA-decorated WO3, which is also higher than other M-WO3- x nanosheets. Both the experimental and theoretical results suggest that the excellent SDT performance of the Cu-WO3- x nanosheets should be attributed to the synergistic effect between Cu SAs and WO3- x OVs. Therefore, after polyethylene glycol modification, the Cu-WO3- x can quickly kill cancer cells in vitro and effectively eradicate tumors in vivo under US irradiation. Transcriptome sequencing analysis and further molecular validation suggest that the Cu-WO3- x-mediated SDT-activated apoptosis and TNF signaling pathways are potential drivers of tumor apoptosis induction.

Study on UV-shielding mechanism of layered double hydroxide materials.

The development of UV-shielding materials has attracted considerable attention in the field of coatings and sunscreen. This paper reports the UV-shielding mechanism of layered double hydroxide (LDH) materials in terms of chemical composition, structure and morphology, by using (LDH/PAA)n films (n stands for bilayer number) through alternate LBL assembly of LDH nanoparticles and poly(acrylic acid) (PAA) on quartz substrates as a model system. A combination investigation based on experimental and theoretical study demonstrates that the maximum UV scattering can be achieved when λ/d ≈ 1.98; the introduction of Zn element is an effective way to tune the electron structure, band gap, transition mode and resulting UV-shielding property of LDH materials. A UV-shielding efficiency as high as 95% can be obtained by modulating the particle size, composition and thickness of the LDHs. Furthermore, the UV anti-aging capacity of LDH-modified bitumen was studied, which demonstrates a large improvement in UV-resistance performance of bitumen by the incorporation of LDH materials. Therefore, this work systematically discloses the relationship between UV-shielding property and chemical/structural parameters of LDH materials, which can be potentially used as anti-aging agents in various organic matrices and polymer areas.

Layered Double Hydroxides: A Novel Promising 2D Nanomaterial for Bone Diseases Treatment.

Bone diseases including bone defects, bone infections, osteoarthritis, and bone tumors seriously affect life quality of the patient and bring serious economic burdens to social health management, for which the current clinical treatments bear dissatisfactory therapeutic effects. Biomaterial-based strategies have been widely applied in the treatment of orthopedic diseases but are still plagued by deficient bioreactivity. With the development of nanotechnology, layered double hydroxides (LDHs) with adjustable metal ion composition and alterable interlayer structure possessing charming physicochemical characteristics, versatile bioactive properties, and excellent drug loading and delivery capabilities arise widespread attention and have achieved considerable achievements for bone disease treatment in the last decade. However, to the authors' best knowledge, no review has comprehensively summarized the advances of LDHs in treating bone disease so far. Herein, the advantages of LDHs for orthopedic disorders treatment are outlined and the corresponding state-of-the-art achievements are summarized for the first time. The potential of LDHs-based nanocomposites for extended therapeutics for bone diseases is highlighted and perspectives for LDHs-based scaffold design are proposed for facilitated clinical translation.

A MgFe-LDH Nanosheet-Incorporated Smart Thermo-Responsive Hydrogel with Controllable Growth Factor Releasing Capability for Bone Regeneration.

Although growth factor (GF)-loaded hydrogels have been explored as promising materials in repairing bone defects, it still remains challenging to construct smart hydrogels with excellent gelation/mechanical properties as well as controllable GF releasing capability. Herein, the incorporation of bone morphogenetic protein 2 (BMP-2)-functionalized MgFe-layered double hydroxide (LDH) nanosheets into chitosan/silk fibroin (CS) hydrogels loaded with platelet-derived growth factor-BB (PDGF-BB) to construct a smart injectable thermo-responsive hydrogel (denoted as CSP-LB), which can achieve a burst release of PDGF-BB and a sustained release of BMP-2, for highly efficient bone regeneration is reported. The incorporation of MgFe-LDH in CS hydrogel not only shortens the gelation time and decreases sol-gel transition temperature, but also enhances the mechanical property of the hydrogel. Because of the sequential release of dual-GFs and sustained release of bioactive Mg2+ /Fe3+ ions, the in vitro experiments prove that the CSP-LB hydrogel exhibits excellent angiogenic and osteogenic properties compared with the CS hydrogel. In vivo experiments further prove that the CSP-LB hydrogel can significantly enhance bone regeneration with higher bone volume and mineral density than that of the CS hydrogel. This smart thermo-sensitive CSP-LB hydrogel possesses excellent gelation capability and angiogenic and osteogenic properties, thus providing a promising minimally invasive solution for bone defect treatment.

Boosting the Sonodynamic Cancer Therapy Performance of 2D Layered Double Hydroxide Nanosheet-Based Sonosensitizers Via Crystalline-to-Amorphous Phase Transformation.

Sonodynamic therapy (SDT) has been a promising therapeutic modality for cancer because of its superior advantages compared with other therapeutic strategies. However, the current sonosensitizers used for SDT normally exhibit low activity for ultrasound (US)-induced reactive oxygen species (ROS) generation. Herein, the crystalline-to-amorphous phase transformation is reported as a simple but powerful strategy to engineer ultrathin 2D CoW-LDH and NiW-LDH nanosheets as highly efficient sonosensitizers for SDT. The phase transformation of CoW-LDH and NiW-LDH nanosheets from polycrystalline to amorphous ones is achieved through a simple acid etching treatment. Importantly, compared with the polycrystalline one, the amorphous CoW-LDH (a-CoW-LDH) nanosheets possess higher ROS generation activity under US irradiation, which is ≈17 times of the commercial TiO2 sonosensitizer. The results suggest that the enhanced performance of ultrathin a-CoW-LDH nanosheets for US-induced ROS generation may be attributed to the phase transformation-induced defect generation and electronic structure changes. After polyethylene glycol modification, the a-CoW-LDH nanosheets can serve as a high-efficiency sonosensitizer for SDT to achieve cell death in vitro and tumor eradication in vivo under US irradiation.

Coupling Probiotics with 2D CoCuMo-LDH Nanosheets as a Tumor-Microenvironment-Responsive Platform for Precise NIR-II Photodynamic Therapy.

Photodynamic therapy (PDT) has become a promising cancer treatment approach with superior advantages. However, it remains a grand challenge to develop tumor microenvironment (TME)-responsive photosensitizers (PSs) for tumor-targeting precise PDT. Herein, the coupling Lactobacillus acidophilus (LA) probiotics with 2D CoCuMo layered-double-hydroxide (LDH) nanosheets (LA&LDH) is reported as a TME-responsive platform for precise NIR-II PDT. The CoCuMo-LDH nanosheets loaded on LA can be transformed from crystalline into amorphous through etching by the LA-metabolite-enabled low pH and overexpressed glutathione. The TME-induced in situ amorphization of CoCuMo-LDH nanosheets can boost its photodynamic activity for singlet oxygen (1 O2 ) generation under 1270 nm laser irradiation with relative 1 O2 quantum yield of 1.06, which is the highest among previously reported NIR-excited PSs. In vitro and in vivo assays prove that the LA&LDH can effectively achieve complete cell apoptosis and tumor eradication under 1270 nm laser irradiation. This study proves that the probiotics can be used as a tumor-targeting platform for highly efficient precise NIR-II PDT.

Bone tissue engineering for treating osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a devastating and complicated disease with an unclear etiology. Femoral head-preserving surgeries have been devoted to delaying and hindering the collapse of the femoral head since their introduction in the last century. However, the isolated femoral head-preserving surgeries cannot prevent the natural progression of ONFH, and the combination of autogenous or allogeneic bone grafting often leads to many undesired complications. To tackle this dilemma, bone tissue engineering has been widely developed to compensate for the deficiencies of these surgeries. During the last decades, great progress has been made in ingenious bone tissue engineering for ONFH treatment. Herein, we comprehensively summarize the state-of-the-art progress made in bone tissue engineering for ONFH treatment. The definition, classification, etiology, diagnosis, and current treatments of ONFH are first described. Then, the recent progress in the development of various bone-repairing biomaterials, including bioceramics, natural polymers, synthetic polymers, and metals, for treating ONFH is presented. Thereafter, regenerative therapies for ONFH treatment are also discussed. Finally, we give some personal insights on the current challenges of these therapeutic strategies in the clinic and the future development of bone tissue engineering for ONFH treatment.

Catalyzing Generation and Stabilization of Oxygen Vacancies on CeO2-x Nanorods by Pt Nanoclusters as Nanozymes for Catalytic Therapy.

Although CeO2 nanomaterials have been widely explored as nanozymes for catalytic therapy, they still suffer from relatively low activities. Herein, the catalyzing generation and stabilization of oxygen vacancies on CeO2 nanorods by Pt nanoclusters via H2 gas reduction under mild temperature (350 °C) to obtain Pt/CeO2- x , which can serve as a highly efficient nanozyme for catalytic cancer therapy, is reported. The deposited Pt on CeO2 by the atomic layer deposition technique not only can serve as the catalyst to generate oxygen vacancies under mild temperature reduction through the hydrogen spillover effect, but also can stabilize the generated oxygen vacancies. Meanwhile, the oxygen vacancies also provide anchoring sites for Pt forming strong metal-support interactions and thus preventing their agglomerations. Importantly, the Pt/CeO2- x reduced at 350 °C (Pt/CeO2- x -350R) exhibits excellent enzyme-mimicking catalytic activity for generation of reactive oxygen species (e.g., ·OH) as compared to other control samples, including CeO2 , Pt/CeO2 , and Pt/CeO2- x reduced at other temperatures, thus achieving excellent performance for tumor-specific catalytic therapy to efficiently eliminate cancer cells in vitro and ablate tumors in vivo. The excellent enzyme-mimicking catalytic activity of Pt/CeO2- x -350R originates from the good catalytic activities of oxygen vacancy-rich CeO2- x and Pt nanoclusters.

Preparation of 2D Polyaniline/MoO3- x Superlattice Nanosheets via Intercalation-Induced Morphological Transformation for Efficient Chemodynamic Therapy.

Organic intercalation of layered nanomaterials is an attractive strategy to fabricate organic/inorganic superlattices for a wide range of promising applications. However, the synthesis of 2D organic/inorganic superlattice nanosheets remains a big challenge. Herein, the preparation of 2D polyaniline/MoO3- x (PANI/MoO3- x ) superlattice nanosheets via intercalation-induced morphological transformation from MoO3  nanobelts, as efficient Fenton-like reagents for chemodynamic therapy (CDT), is reported. Micrometer-long MoO3  nanobelts are co-intercalated with Na+ /H2 O followed by the guest exchange with aniline monomer for in situ polymerization to obtain PANI/MoO3- x nanosheets. Intriguingly, the PANI intercalation can induce the morphological transformation from long MoO3  nanobelts to 2D PANI/MoO3- x nanosheets along with the partial reduction of Mo6+ to Mo5+ , and generation of rich oxygen vacancies. More importantly, thanks to the PANI intercalation-induced activation, the PANI/MoO3- x nanosheets exhibit excellent Fenton-like catalytic activity for generation of hydroxyl radical (·OH) by decomposing H2 O2  compared with the MoO3  nanobelts. It is speculated that the good conductivity of PANI can facilitate electron transport during the Fenton-like reaction, thereby enhancing the efficiency of CDT. Thus, the polyvinylpyrrolidone-modified PANI/MoO3- x nanosheets can function as Fenton-like reagents for highly efficient CDT to kill cancer cells and eradicate tumors.