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The development of perennial crops holds great promise for sustainable agriculture and food security. However, the evolution of the transition between perenniality and annuality is poorly understood. Here, using two Brassicaceae species, Crucihimalaya himalaica and Erysimum nevadense, as polycarpic perennial models, we reveal that the transition from polycarpic perennial to biennial and annual flowering behavior is a continuum determined by the dosage of three closely related MADS-box genes. Diversification of the expression patterns, functional strengths, and combinations of these genes endows species with the potential to adopt various life-history strategies. Remarkably, we find that a single gene among these three is sufficient to convert winter-annual or annual Brassicaceae plants into polycarpic perennial flowering plants. Our work delineates a genetic basis for the evolution of diverse life-history strategies in plants and lays the groundwork for the generation of diverse perennial Brassicaceae crops in the future.
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Brassicaceae , Flores , Regulação da Expressão Gênica de Plantas , Brassicaceae/genética , Brassicaceae/fisiologia , Produtos Agrícolas/genética , Flores/genética , Flores/fisiologia , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Fenômenos Fisiológicos Vegetais , Mapeamento Cromossômico , MutaçãoRESUMO
Efficient and accurate reactive force fields (e.g., ReaxFF) are pivotal for large-scale atomistic simulations to comprehend microscopic combustion processes. ReaxFF has been extensively utilized to describe chemical reactions in condensed phases, but most existing ReaxFF models rely on quantum mechanical (QM) data nearly two decades old, particularly in hydrocarbon systems, constraining their accuracy and applicability. Addressing this gap, we introduce a reparametrized ReaxFFCHO-S22 for C/H/O systems, tailored for studying the pyrolysis and combustion of hydrocarbon fuel. Our approach involves high-level QM benchmarks and large database construction for C/H/O systems, global ReaxFF parameter optimization, and molecular dynamics simulations of typical hydrocarbon fuels. Density functional theory (DFT) computations utilized the M06-2X functional at the meta-generalized gradient approximation (meta-GGA) level with a large basis set (6-311++G**). Our new ReaxFFCHO-S22 model exhibits a minimum 10% enhancement in accuracy compared to the previous ReaxFF models for a large variety of hydrocarbon molecules. This advanced ReaxFFCHO-S22 not only enables efficient large-scale studies on the microscopic chemical reactions of more complex hydrocarbon fuel but also can extend to biofuels, energetic materials, polymers, and other pertinent systems, thus serving as a valuable tool for studying chemical reaction dynamics of the large-scale hydrocarbon condensed phase at an atomistic level.
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What determines the rate at which a multicellular organism matures is a fundamental question in biology. In plants, the decline of miR156 with age serves as an intrinsic, evolutionarily conserved timer for the juvenile-to-adult phase transition. However, the way in which age regulates miR156 abundance is poorly understood. Here, we show that the rate of decline in miR156 is correlated with developmental age rather than chronological age. Mechanistically, we found that cell division in the apical meristem is a trigger for miR156 decline. The transcriptional activity of MIR156 genes is gradually attenuated by the deposition of the repressive histone mark H3K27me3 along with cell division. Our findings thus provide a plausible explanation of why the maturation program of a multicellular organism is unidirectional and irreversible under normal growth conditions and suggest that cell quiescence is the fountain of youth in plants.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Divisão Celular/genética , Meristema/genética , MicroRNAs/genética , Brotos de Planta/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica de Plantas/genética , Folhas de Planta/genética , Plantas Geneticamente Modificadas/genética , Fatores de Transcrição/genéticaRESUMO
Considering the challenge in the treatment of severe breast tumor patients, xonotlite nanowire-containing bioactive scaffolds (Fe3O4-CS-GelMA) were fabricated by the 3D-printing technique for the therapy of injured adipose tissue after surgery. Importantly, benefiting from the excellent magnetothermal performance of Fe3O4 microspheres, Fe3O4-CS-GelMA scaffolds could effectively kill tumor cells in vitro and suppress breast cancer in vivo under an alternating magnetic field, and the tumor did not recur in 2 weeks. In addition, attributed to the released bioactive inorganic ions, Fe3O4-CS-GelMA composite scaffolds could effectively promote the expression of adipogenesis-related genes and proteins of adipose-derived stem cells (ADSCs) via the PI3K-AKT signaling pathway in vitro. Furthermore, Fe3O4-CS-GelMA scaffolds with ADSCs could obviously stimulate the formation of adipose in vivo, compared with that of pure GelMA without inorganic components. Therefore, this study offers a promising strategy for the therapy of breast tumors after the surgical excision of breast carcinoma.
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Neoplasias da Mama , Nanofios , Humanos , Feminino , Alicerces Teciduais , Osteogênese , Diferenciação Celular , Neoplasias da Mama/tratamento farmacológico , Fosfatidilinositol 3-Quinases , Nanofios/uso terapêutico , Impressão Tridimensional , Tecido Adiposo , Engenharia Tecidual/métodosRESUMO
Dual-Active-Sites Single-Atom catalysts (DASs SACs) are not only the improvement of SACs but also the expansion of dual-atom catalysts. The DASs SACs contains dual active sites, one of which is a single atomic active site, and the other active site can be a single atom or other type of active site, endowing DASs SACs with excellent catalytic performance and a wide range of applications. The DASs SACs are categorized into seven types, including the neighboring mono metallic DASs SACs, bonded DASs SACs, non-bonded DASs SACs, bridged DASs SACs, asymmetric DASs SACs, metal and nonmetal combined DASs SACs and space separated DASs SACs. Based on the above classification, the general methods for the preparation of DASs SACs are comprehensively described, especially their structural characteristics are discussed in detail. Meanwhile, the in-depth assessments of DASs SACs for variety applications including electrocatalysis, thermocatalysis and photocatalysis are provided, as well as their unique catalytic mechanism are addressed. Moreover, the prospects and challenges for DASs SACs and related applications are highlighted. The authors believe the great expectations for DASs SACs, and this review will provide novel conceptual and methodological perspectives and exciting opportunities for further development and application of DASs SACs.
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Due to the limited resources and high cost of noble metals, boosting their catalytic activities is highly desired in the current catalysis industry. Here, we report a synergetic catalyst, combining Pd2+ and Pd0 species in a nitrogen-doped porous carbons (NPC), which shows boosted catalytic activities in hydrogenation reactions of organic nitro compounds (nitrobenzene, 4-nitrophenol, 1-nitronaphthalene and 1-nitropropane) under near ambient conditions. This synergetic catalyst NPC-[Pd] was synthesized by partial reduction of a palladium-loaded NPC. The catalytic activities and selectivity of NPC-[Pd] for hydrogenation were enhanced significantly compared with those of NPC-Pd2+ or NPC-Pd0 nanoparticles. Theoretical calculations show that H2 preferentially dissociates on Pd nanoparticles, and then organic molecules (nitrobenzene) can be captured and react with the dissociated H atom on Pd2+ sites. Similar reaction procedure also occur on Pt or Rh. Hydrogenation of different aromatic compounds with different functional groups (naphthalene, 4-nitrochlorobenzene, benzaldehyde and acetophenone) confirmed the broad excellent catalytic activity of this synergistic catalyst.
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The electrochemical sensing of nitric oxide (NO) molecules by metal-organic framework (MOF) catalysts has been impeded, to a large extent, owing to their poor electrical conductivity and weak NO adsorption. In this work, incomplete in situ conversion of V2 CTx (T = terminal atoms) MXene to MOF is adopted, forming MOF@MXene heterostructures, which outperform MXene and MOF monocomponents toward electrochemical NO sensing. Density functional theory (DFT) calculation results indicate metal-like electronic characters for the heterostructure benefiting from the dominating contribution of the V 3d orbitals of the metallic MXene. Moreover, plane-averaged charge density difference shows substantial charge redistribution occurs at the heterointerfaces, producing a built-in field, which facilitates charge transfer. Besides, molecular mechanics-based simulated annealing calculation reveals greatly enhanced adsorption energies of NO molecules on the heterointerfaces than that on separate MOFs and MXenes. Hence, the facilitated charge transfer and preferential NO adsorption are responsible for the dramatically promoted performance toward NO sensing. The prudent design of MOF@MXene heterostructure may spur advanced electrocatalysts for electrochemical sensing.
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CO2 reduction by H2 using metal-free catalysts is highly challenging. Frustrated Lewis pairs (FLPs) have been considered potential metal-free catalysts for this reaction. However, most FLPs are unstable, which limits their practical applications. In this study, a class of novel metal-free catalysts composed of K3-nHnPO4 (n = 0, 1, 2) and B(C6F5-mHm)3 (m = 0, 3, 5) were prepared and identified as effective catalysts for CO2 hydrogenation to formate by density functional theory (DFT) calculations. The simulations show that the B-H bond formation is the rate-determining step (RDS). The acid/base strength and repulsive steric interactions affect the corresponding energy barrier. Therefore, the catalytic performance can be improved by choosing a suitable Lewis acid or base. Among these catalysts, the B(C6H5)3-KH2PO4 pair, with the lowest barrier height (26.3 kcal mol-1) in RDS, is suggested as a promising metal-free catalyst for CO2 hydrogenation. This study may provide strategies for designing new LP-based metal-free catalysts.
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The hydrogenation of CO2 into valuable chemical fuels reduces the atmospheric CO2 content and also has broad economic prospects. Support is essential for catalysts, but many of the reported support materials cannot meet the requirements of accessibility and durability. Herein, we theoretically designed a series of single-atom noble metals anchored on a SiO2 surface for CO2 hydrogenation using density functional theory (DFT) calculations. Through theoretical evaluation of the formation energy, hydrogen dissociation capacity, and activity of CO2 hydrogenation, we found that Ru@SiO2 is a promising candidate for CO2 hydrogenation to formic acid. The energy barrier of the rate-determining step of the entire conversion process is 23.9 kcal mol-1; thus, the reaction can occur under mild conditions. In addition, active and stable origins were revealed through electronic structure analysis. The charge of the metal atom is a good descriptor of the catalytic activity. The Pearson correlation coefficient (PCC) between metal charge and its CO2 hydrogenation barrier is 0.99. Two solvent models were also used to investigate hydrogen spillover processes and the reaction path was searched by the climbing image nudged-elastic-band (CI-NEB) method. The results indicated that the explicit solvent model could not be simplified into a few solvent molecules, leading to a large difference in the reaction paths. This work will serve as a reference for the future design of more efficient catalysts for CO2 hydrogenation.
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Lithium-sulfur (Li-S) batteries suffer from multiple complex and often interwoven issues, such as the low electronic conductivity of sulfur and Li2S/Li2S2, shuttle effect, and sluggish electrochemical kinetics of lithium polysulfides (LiPSs). Guided by theoretical calculations, a multifunctional catalyst of isolated single-atom nickel in an optimal Ni-N5 active moiety incorporated in hollow nitrogen-doped porous carbon (Ni-N5/HNPC) is constructed and acts as an ideal host for a sulfur cathode. The host improved electrical conductivity, enhanced physical-chemical dual restricting capability toward LiPSs, and, more importantly, boosted the redox reaction kinetics by the Ni-N5 active moiety. Therefore, the Ni-N5/HNPC/S cathode exhibits superior rate performance, long-term cycling stability, and good areal capacity at high sulfur loading. This work highlights the important role of the coordination number of active centers in single-atom catalysts and provides a strategy to design a hollow nanoarchitecture with single-atom active sites for high-performance Li-S batteries.
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Imines are important intermediates in drug synthesis. Photocatalytic aerobic oxidative coupling of amines has been considered as a clean and promising way to produce imines and has attracted great attention. Herein, we designed and synthesized a novel two-dimensional porphyrin-based covalent organic framework (Por-BC-COF) which adopts an AA stacking mode with excellent crystallinity, high Brunauer-Emmett-Teller surface areas (1200â m2 g-1 ), wide light absorption range (200-1300â nm) and good stability in a variety of organic solvents. Por-BC-COF can be used as a metal-free heterogeneous photocatalyst for the photocatalytic oxidation of amines to imines under visible light and red light with a high yield (97 %). This work presents a novel and efficient COF photocatalyst in the application of light-driven organic synthesis.
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Exploring efficient and cost-effective catalysts to replace precious metal catalysts, such as Pt, for electrocatalytic oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) holds great promise for renewable energy technologies. Herein, we prepare a type of Co catalyst with single-atomic Co sites embedded in hierarchically ordered porous N-doped carbon (Co-SAS/HOPNC) through a facile dual-template cooperative pyrolysis approach. The desirable combination of highly dispersed isolated atomic Co-N4 active sites, large surface area, high porosity, and good conductivity gives rise to an excellent catalytic performance. The catalyst exhibits outstanding performance for ORR in alkaline medium with a half-wave potential (E1/2) of 0.892 V, which is 53 mV more positive than that of Pt/C, as well as a high tolerance of methanol and great stability. The catalyst also shows a remarkable catalytic performance for HER with distinctly high turnover frequencies of 0.41 and 3.8 s-1 at an overpotential of 100 and 200 mV, respectively, together with a long-term durability in acidic condition. Experiments and density functional theory (DFT) calculations reveal that the atomically isolated single Co sites and the structural advantages of the unique 3D hierarchical porous architecture synergistically contribute to the high catalytic activity.
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Exploring high-performance electrocatalysts, especially non-noble metal electrocatalysts, for the oxygen evolution reaction (OER) is critical to energy storage and conversion. Herein, we report for the first time that conjugated microporous polymers (CMPs) incorporating salen can be used as OER electrocatalysts with outstanding performances. The best OER electrocatalyst (salen-CMP-Fe-3) exhibits a low Tafel slope of 63â mV dec-1 and an overpotential of 238â mV at 10â mA cm-2 . DFT and Grand Canonical Monte Carlo calculations confirmed that the significantly improved electrocatalytic properties can be attributed to the intrinsic catalytic activity of the salen moiety and the enrichment effect of the pore structures. This work demonstrates that salen-based conjugated polymers are a type of metal-coordinated porous polymer that show excellent catalyst performance.
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The relation between a catalytic center and the surrounding carbon-oxygen groups influences the catalytic activity in various reactions. However, the impact of this relation on catalysis is usually discussed separately. For the first time, we proved that carbon-oxygen groups increased the reducibility of Fe-C bonds toward NO reduction. Experimentally, we compared the reductive activities of materials with either one or both factors, i.e., carbon-oxygen groups and Fe-C bonds. As a result, graphene oxide-supported Fe (with both factors) showed the best activity, duration of activity, and selectivity. This material reduced 100% of NO to N2 at 300 °C. Moreover, theoretical calculations revealed that the adsorption energy of graphene for NO increased from -13.51 (physical adsorption) to -327.88 kJ/mol (chemical adsorption) after modification with Fe-C. When the graphene-supported Fe was further modified with carboxylic acid groups, the ability to transfer charge increased dramatically from 0.109 to 0.180 |e-|. Therefore, the carbon-oxygen groups increased the reducibility of Fe-C. The main results will contribute to the understanding of NO reduction and the design of effective catalysts.
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Carbono , Oxigênio , Catálise , Ferro , OxirreduçãoRESUMO
BACKGROUND: The aim of the present study is to explore the impact of butorphanol in combination with ketamine via nasal inhalation (NI) on neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve in a rat model. METHODS: CCI rats (n = 12) were equally randomized to four groups based on the treatments received as follows: 100 µL of 0.9% normal saline via NI (NS/NI group); 100 µg of butorphanol plus 1 mg of ketamine via NI (B + K/NI group); 100 µg of butorphanol alone via NI (B/NI group); and 100 µg of butorphanol plus 1 mg of ketamine via subcutaneous injection (B + K/SC group). Mechanical pain threshold was measured at 10 min, 30 min, 2 h, 4 h, and 6 h after drug administration. RESULTS: The mechanical pain threshold in the B + K/NI group was improved significantly 4 h after drug administration as compared with that in the B/NI or B + K/SC group (P < 0.05). The onset and intensity of drug action in the B + K/NI group were better than those of the other two groups, but the duration of drug action was not prolonged. CONCLUSIONS: NI of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in a rat neuropathic pain model induced by CCI to the sciatic nerve.
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Analgésicos Opioides/administração & dosagem , Butorfanol/administração & dosagem , Ketamina/administração & dosagem , Neuralgia/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Nervo Isquiático/lesões , Administração por Inalação , Animais , Masculino , RatosRESUMO
BACKGROUND: Typically, the overexpressed keratin 7 (KRT7) is considered a validated therapeutic target and prognosis marker in bladder cancer. However, the crucial roles of KRT7 in the clinical prognosis and immune microenvironment in bladder cancer remain unclear. METHODS: Initially, the expression levels of KRT7 in public databases were analyzed that is,Tumor Immune Estimation Resource (TIMER) 2.0 and Gene Expression Profiling Interactive Analysis (GEPIA). Further, the clinical tissue samples from patients (n = 10 pairs) were collected to confirm the expression trends of KRT7 and detected by immunohistochemistry (IHC) analysis. Meanwhile, the relationship between KRT7 and the prognosis of bladder cancer patients was analyzed by Kaplan-Meier plotter estimation and Cox regression analysis. Finally, TIMER 2.0 and IHC staining analyses were performed to calculate the infiltration abundances of three kinds of immune cells in eligible bladder tumor samples. RESULTS: The TIMER 2.0 and GEPIA datasets suggested the differences in the expression levels of KRT7 in tumors, in which KRT7 was significantly upregulated in bladder cancer. The KRT7 expression was closely associated with patients' gender, tumor histologic subtypes, T status, and American Joint Committee on Cancer stages. Notably, the increased KRT7 indicated poor overall survival and disease-free survival rates. Moreover, KRT7 expression could be responsible for immune infiltration in the cancer microenvironment of the bladder. Finally, the high expression level of KRT7 increased the presence of regulatory T cells (Tregs) but reduced the infiltration of CD8+ T and natural killer cells. CONCLUSION: KRT7 as a biomarker potentiated the prediction of bladder cancer prognosis and the immune microenvironment.
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Queratina-7 , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/imunologia , Prognóstico , Queratina-7/metabolismo , Queratina-7/genética , Feminino , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Masculino , Microambiente Tumoral , Pessoa de Meia-Idade , Relevância ClínicaRESUMO
The process of CH4 cracking into H2 and carbon has gained wide attention for hydrogen production. However, traditional catalysis methods suffer rapid deactivation due to severe carbon deposition. In this study, we discover that effective CH4 cracking can be achieved at 450 °C over a Re/Ni single-atom alloy via ball milling. To explore single-atom alloy catalysis, we construct a library of 10,950 transition metal single-atom alloy surfaces and screen candidates based on C-H dissociation energy barriers predicted by a machine learning model. Experimental validation identifies Ir/Ni and Re/Ni as top performers. Notably, the non-noble metal Re/Ni achieves a hydrogen yield of 10.7 gH2 gcat-1 h-1 with 99.9% selectivity and 7.75% CH4 conversion at 450 °C, 1 atm. Here, we show the mechanical energy boosts CH4 conversion clearly and sustained CH4 cracking over 240 h is achieved, significantly surpassing other approaches in the literature.
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Carbonates represent major sedimentary rocks in on the continental and oceanic crust of Earth and are often closely related to microbial activities. However, the origin of magnesium-containing carbonates, such as dolomites, has not yet been fully resolved and was debated for many years. In order to reveal the specific role of organic components and microbes on the precipitation of magnesium ions, different dolomitization experiments were carried out with various setups for the presence of eight amino acids and microbes. The Gibbs free energy for dehydration of Mg[6(H2O)]2+ and organicmagnesium complexes (OMC) at the calcite (101¯4) step edges were calculated by density functional theory (DFT). Combined results of X-ray diffraction (XRD), scanning electron microscope-energy disperse spectroscopy (SEM-EDS), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR) and high resolution transmission electron microscopy (HRTEM) indicated that magnesium ions were incorporated into the crystal lattice of calcite after calcite reacting with organicmagnesium solutions (OMS). Dolomite was formed on the surface of calcite under the presence of microbes. The Gibbs free energy barrier of asp, glu, gly, thr, tyr, lys, ser, and ala bonding to Mg[6(H2O)]2+ were 17.8, 16.2, 14.8, 16.5, 19.2, 14.5, 19.0, 17.0 kcal/mol, those are lower than that of the direct dehydration of Mg[6(H2O)]2+ of 19.45 kcal/mol. The Gibbs free barrier of OMC bonding at the acute step ([481¯] and [4¯41]) of 29.7/34.25 kcal/mol are lower than that of Mg[6(H2O)]2+ of 32.45/36.7 kcal/mol and the Gibbs free barrier of OMC bonding at the obtuse step ([481¯] and [4¯41]) of 42.07/47.6 kcal/mol are lower than that of Mg[6(H2O)]2+ of 55.4/60.34 kcal/mol. The enhancing effects of organic components and microbes on the precipitation of magnesium ions were collectively determined through experimental and theoretical calculation, thus setting up a new direction for future studies of dolomitization with a focus on microbial- mineral interactions.
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AIMS: To assess the effect of the translocator protein 18 kDa (TSPO) on postpartum depression and explore its mechanism. METHODS: Postpartum depression (PPD) mouse model was established, and flow cytometry, immunofluorescence, Western blot analysis, real-time quantitative PCR, adeno-associated virus (AAV), co-immunoprecipitation-mass spectrometry and immunofluorescence co-staining were used to detect the effect of TSPO ligand ZBD-2 on PPD mice. RESULTS: ZBD-2 inhibits the overactivation of microglia in the hippocampus and amygdala of PPD model mice. ZBD-2 not only inhibited the inflammation but also repressed the burst of reactive oxygen species (ROS) and mitochondrial ROS (mtROS). Meanwhile, ZBD-2 protects mitochondria from LPS-induced damages through inhibiting the influx of calcium. ZBD-2 modulated the calcium influx by increasing the level of translocase of the outer mitochondrial membrane 40 (TOM40) and reducing the interaction of TSPO and TOM40. In addition, the effect of ZBD-2 was partially dependent on anti-oxidative process. Knockdown of TOM40 by adeno-associated virus (AAV) in the hippocampus or amygdala dramatically reduced the effect of ZBD-2 on PPD, indicating that TOM40 mediates the effect of ZBD-2 on PPD. CONCLUSIONS: TOM40 is required for the effect of ZBD-2 on treating anxiety and depression in PPD mice. This study reveals the role of microglia TSPO in PPD development and provides the new therapeutic strategy for PPD.
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Depressão Pós-Parto , Microglia , Animais , Feminino , Camundongos , Cálcio/metabolismo , Proteínas de Transporte , Depressão Pós-Parto/tratamento farmacológico , Depressão Pós-Parto/metabolismo , Homeostase , Microglia/metabolismo , Membranas Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de GABA/metabolismoRESUMO
Regeneration of severe bone defects remains an enormous challenge in clinic. Developing regenerative scaffolds to directionally guide bone growth is a potential strategy to overcome this hurdle. Conch, an interesting creature widely spreading in ocean, has tough spiral shell that can continuously grow along the spiral direction. Herein, inspired by the physiological features of conches, a conch-like (CL) scaffold based on ß-TCP bioceramic material was successfully prepared for guiding directional bone growth via digital light processing (DLP)-based 3D printing. Benefiting from the spiral structure, the CL scaffolds significantly improved cell adhesion, proliferation and osteogenic differentiation in vitro compared to the conventional 3D scaffolds. Particularly, the spiral structure in the scaffolds could efficiently induce cells to migrate from the bottom to the top of the scaffolds, which was like "cells climbing stairs". Furthermore, the capability of guiding directional bone growth for the CL scaffolds was demonstrated by a special half-embedded femoral defects model in rabbits. The new bone tissue could consecutively grow into the protruded part of the scaffolds along the spiral cavities. This work provides a promising strategy to construct biomimetic biomaterials for guiding directional bone tissue growth, which offers a new treatment concept for severe bone defects, and even limb regeneration.