The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.

Research on Risk Contagion in ESG Industries: An Information Entropy-Based Network Approach.

Sustainable development is a practical path to optimize industrial structures and enhance investment efficiency. Investigating risk contagion within ESG industries is a crucial step towards reducing systemic risks and fostering the green evolution of the economy. This research constructs ESG industry indices, taking into account the possibility of extreme tail risks, and employs VaR and CoVaR as measures of tail risk. The TENET network approach is integrated to to capture the structural evolution and direction of information flow among ESG industries, employing information entropy to quantify the topological characteristics of the network model, exploring the risk transmission paths and evolution patterns of ESG industries in an extreme tail risk event. Finally, Mantel tests are conducted to examine the existence of significant risk spillover effects between ESG and traditional industries. The research finds strong correlations among ESG industry indices during stock market crash, Sino-US trade frictions, and the COVID-19 pandemic, with industries such as the COAL, CMP, COM, RT, and RE playing key roles in risk transmission within the network, transmitting risks to other industries. Affected by systemic risk, the information entropy of the TENET network significantly decreases, reducing market information uncertainty and leading market participants to adopt more uniform investment strategies, thus diminishing the diversity of market behaviors. ESG industries show resilience in the face of extreme risks, demonstrating a lack of significant risk contagion with traditional industries.

Dzyaloshinskii-Moriya-Interaction-Like Behavior in Confined Permalloy Nanostructures via Coupled Magnetic Vortices.

Dzyaloshinskii-Moriya interaction (DMI), one of antisymmetric exchanges, originates from the combination of low structural symmetry and large spin-orbit coupling and favors magnetization rotations with fixed chirality. Herein, this work reports a DMI-like behavior in permalloy via coupled vortices in confined structures. Under the in-plane magnetic fields, continuous reversals of different coupled vortices are directly observed by in situ Lorentz transmission electron microscopy, and reproduced by complementary micromagnetic simulations. The statistical results show that coupled vortices with opposite chirality appear more frequently with the frequency up to about 60%. Such an asymmetric phenomenon mainly arises from a DMI-like behavior, associated with the increased total energy difference between different ground-state coupled vortices. Moreover, in the reversal process, the junction between disks accelerates the annihilation of vortices moving toward it and is also the starting point of vortex nucleation. These results provide an effective method to generate a DMI-like behavior in magnetic systems with symmetry breaking surface and benefit the future development of vortex-based spintronic devices.

Quinary High-Entropy-Alloy@Graphite Nanocapsules with Tunable Interfacial Impedance Matching for Optimizing Microwave Absorption.

Designing heterogeneous interfaces and components at the nanoscale is proven effective for optimizing electromagnetic wave absorption and shielding properties, which can achieve desirable dielectric polarization and ferromagnetic resonances. However, it remains a challenge for the precise control of components and microstructures via an efficient synthesis approach. Here, the arc-discharged plasma method is proposed to synthesize core@shell structural high-entropy-alloy@graphite nanocapsules (HEA@C-NPs), in which the HEA nanoparticles are in situ encapsulated within a few layers of graphite through the decomposition of methane. In particular, the HEA cores can be designed via combinations of various transition elements, presenting the optimized interfacial impedance matching. As an example, the FeCoNiTiMn HEA@C-NPs obtain the minimum reflection loss (RLmin ) of -33.4 dB at 7.0 GHz (3.34 mm) and the efficient absorption bandwidth (≤-10 dB) of 5.45 GHz ranging from 12.55 to 18.00 GHz with an absorber thickness of 1.9 mm. The present approach can be extended to other carbon-coated complex components systems for various applications.

SETD2 deficiency accelerates MDS-associated leukemogenesis via S100a9 in NHD13 mice and predicts poor prognosis in MDS.

SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation-seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.

Binding affinity and conformation of a conjugated AS1411 aptamer at a cationic lipid bilayer interface.

Aptamers have been widely used in the detection, diagnosis, and treatment of cancer. Owing to their special binding affinity toward cancer-related biomarkers, aptamers can be used for targeted drug delivery or bio-sensing/bio-imaging in various scenarios. The interfacial properties of aptamers play important roles in controlling the surface charge, recognition efficiency, and binding affinity of drug-delivering lipid-based carriers. In this research, the interfacial behaviors, such as surface orientation, molecular conformation, and adsorption kinetics of conjugated AS1411 molecules at different cationic lipid bilayer interfaces were investigated by sum frequency generation vibrational spectroscopy (SFG-VS) in situ and in real-time. It is shown that the conjugated AS1411 molecules at the DMTAP bilayer interface show a higher binding affinity but with slower binding kinetics compared to the DMDAP bilayer interface. The analysis results also reveal that the thymine residues of cholesteryl conjugated AS1411 molecules show higher conformational ordering compared to the thymine residues of the alkyl chain conjugated AS1411 molecules. These understandings provide unique molecular insight into the aptamer-lipid membrane interactions, which may help researchers to improve the efficiency and safety of aptamer-related drug delivery systems.

Different roles of E proteins in t(8;21) leukemia: E2-2 compromises the function of AETFC and negatively regulates leukemogenesis.

The AML1-ETO fusion protein, generated by the t(8;21) chromosomal translocation, is causally involved in nearly 20% of acute myeloid leukemia (AML) cases. In leukemic cells, AML1-ETO resides in and functions through a stable protein complex, AML1-ETO-containing transcription factor complex (AETFC), that contains multiple transcription (co)factors. Among these AETFC components, HEB and E2A, two members of the ubiquitously expressed E proteins, directly interact with AML1-ETO, confer new DNA-binding capacity to AETFC, and are essential for leukemogenesis. However, the third E protein, E2-2, is specifically silenced in AML1-ETO-expressing leukemic cells, suggesting E2-2 as a negative factor of leukemogenesis. Indeed, ectopic expression of E2-2 selectively inhibits the growth of AML1-ETO-expressing leukemic cells, and this inhibition requires the bHLH DNA-binding domain. RNA-seq and ChIP-seq analyses reveal that, despite some overlap, the three E proteins differentially regulate many target genes. In particular, studies show that E2-2 both redistributes AETFC to, and activates, some genes associated with dendritic cell differentiation and represses MYC target genes. In AML patients, the expression of E2-2 is relatively lower in the t(8;21) subtype, and an E2-2 target gene, THPO, is identified as a potential predictor of relapse. In a mouse model of human t(8;21) leukemia, E2-2 suppression accelerates leukemogenesis. Taken together, these results reveal that, in contrast to HEB and E2A, which facilitate AML1-ETO-mediated leukemogenesis, E2-2 compromises the function of AETFC and negatively regulates leukemogenesis. The three E proteins thus define a heterogeneity of AETFC, which improves our understanding of the precise mechanism of leukemogenesis and assists development of diagnostic/therapeutic strategies.

3D nitrogen-doped graphene created by the secondary intercalation of ethanol with enhanced specific capacity.

Here, we report an improved synthesis strategy for 3D nitrogen-doped graphene to increase the specific capacity of supercapacitors. Ethanol replaces the strong oxidant hydrogen peroxide in the improved Hummers method, and the loose porous structure is conducive to charge transfer. N-doped porous 3D graphene was synthesized from RGO-C prepared by ethanol secondary intercalation modification of functional groups. Ammonia was selected as the dopant; the microstructure and electrochemical performance of samples synthesized at different temperatures were examined. The results demonstrate that the 3D nitrogen-doped graphene (N-RGO-5) had a layered tuple shape with a sheet thickness of 0.612 nm.The specific surface area of the 3D N-RGO-5, which was prepared at 190°C, was 258.371 m2g-1, which was higher than that (5.877 m2g-1) of the original graphite. The 3D N-RGO-5 exhibited a specific capacitance of 236 F g-1and an energy density of 32.78 Wh kg-1at a current density of 1 A g-1, which is 27% higher than the specific capacitance of RGO. The 3D N-RGO-5 demonstrated an excellent capacity retention rate of 93.6% after 5000 cycles at a current density of 1 A g-1. This study demonstrates that the unique 3D structure and N-doping of N-RGO considerably improved the overall energy storage performance of graphene-based nanomaterials.

Hematopoietic Stem Cell Activity Is Regulated by Pten Phosphorylation Through a Niche-Dependent Mechanism.

The phosphorylated form of Pten (p-Pten) is highly expressed in >70% of acute myeloid leukemia samples. However, the role of p-Pten in normal and abnormal hematopoiesis has not been studied. We found that Pten protein levels are comparable among long-term (LT) hematopoietic stem cells (HSCs), short-term (ST) HSCs, and multipotent progenitors (MPPs); however, the levels of p-Pten are elevated during the HSC-to-MPP transition. To study whether p-Pten is involved in regulating self-renewal and differentiation in HSCs, we compared the effects of overexpression of p-Pten and nonphosphorylated Pten (non-p-Pten) on the hematopoietic reconstitutive capacity (HRC) of HSCs. We found that overexpression of non-p-Pten enhances the LT-HRC of HSCs, whereas overexpression of p-Pten promotes myeloid differentiation and compromises the LT-HRC of HSCs. Such phosphorylation-regulated Pten functioning is mediated by repressing the cell:cell contact-induced activation of Fak/p38 signaling independent of Pten's lipid phosphatase activity because both p-Pten and non-p-Pten have comparable activity in repressing PI3K/Akt signaling. Our studies suggest that, in addition to repressing PI3K/Akt/mTor signaling, non-p-Pten maintains HSCs in bone marrow niches via a cell-contact inhibitory mechanism by inhibiting Fak/p38 signaling-mediated proliferation and differentiation. In contrast, p-Pten promotes the proliferation and differentiation of HSCs by enhancing the cell contact-dependent activation of Src/Fak/p38 signaling. Stem Cells 2016;34:2130-2144.

Reply to the 'Comment on "Observation of mutual diffusion of macromolecules in PS/PMMA binary films by confocal Raman microscopy"' by J. Pablo Tomba, Soft Matter, 2016, 12, DOI: 10.1039/C5SM02735G.

We greatly appreciate Tomba's valuable comments on our paper appearing in Soft Matter (2012, 8, 4780). Our responses are listed below to provide additional information for academic discussion.

Structural evolution analysis and cold-crystallization kinetics of spherical crystals in poly(trimethylene terephthalate) film using Raman spectroscopy.

Dynamic processes and the structural evolution of cold-crystallized poly(trimethylene terephthalate) (PTT) film were investigated using Raman spectroscopy. Raman scattering of C[double bond, length as m-dash]O stretching vibration was related to the molecular chain movement and structure evolution in PTT during cold crystallization. In particular, information about each phase of crystallization, including induction, nucleation, nucleus growth, and secondary crystallization, was thoroughly revealed. The experimental results indicated that the kinetic parameters measured by the Raman method were in good agreement with those obtained by differential scanning calorimetry (DSC) and infrared spectroscopy. The blue-shifted C[double bond, length as m-dash]O stretching vibration resulting from the crystallization process is a popular phenomenon and may therefore have many potential applications in a wide range of areas.

Highly anisotropic Fe3C microflakes constructed by solid-state phase transformation for efficient microwave absorption.

Soft magnetic materials with flake geometry can provide shape anisotropy for breaking the Snoek limit, which is promising for achieving high-frequency ferromagnetic resonances and microwave absorption properties. Here, two-dimensional (2D) Fe3C microflakes with crystal orientation are obtained by solid-state phase transformation assisted by electrochemical dealloying. The shape anisotropy can be further regulated by manipulating the thickness of 2D Fe3C microflakes under different isothermally quenching temperatures. Thus, the resonant frequency is adjusted effectively from 9.47 and 11.56 GHz under isothermal quenching from 700 °C to 550 °C. The imaginary part of the complex permeability can reach 0.9 at 11.56 GHz, and the minimum reflection loss (RLmin) is -52.09 dB (15.85 GHz, 2.90 mm) with an effective absorption bandwidth (EAB≤-10 dB) of 2.55 GHz. This study provides insight into the preparation of high-frequency magnetic loss materials for obtaining high-performance microwave absorbers and achieves the preparation of functional materials from traditional structural materials.

SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis.

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

Electric, magnetic, and shear field-directed assembly of inorganic nanoparticles.

Ordered assemblies of inorganic nanoparticles (NPs) have shown tremendous potential for wide applications due to their unique collective properties, which differ from those of individual NPs. Various assembly methods, such as external field-directed assembly, interfacial assembly, template assembly, biomolecular recognition-mediated assembly, confined assembly, and others, have been employed to generate ordered inorganic NP assemblies with hierarchical structures. Among them, the external field-directed assembly method is particularly fascinating, as it can remotely assemble NPs into well-ordered superstructures. Moreover, external fields (e.g., electric, magnetic, and shear fields) can introduce a local and/or global field intensity gradient, resulting in an additional force on NPs to drive their rotation and/or translation. Therefore, the external field-directed assembly of NPs becomes a robust method to fabricate well-defined functional materials with the desired optical, electronic, and magnetic properties, which have various applications in catalysis, sensing, disease diagnosis, energy conversion/storage, photonics, nano-floating-gate memory, and others. In this review, the effects of an electric field, magnetic field, and shear field on the organization of inorganic NPs are highlighted. The methods for controlling the well-ordered organization of inorganic NPs at different scales and their advantages are reviewed. Finally, future challenges and perspectives in this field are discussed.

Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma.

The patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have poor prognosis, and a novel and effective therapeutic strategy for these patients is urgently needed. Although ubiquitin-specific protease 1 (USP1) plays a key role in cancer, the carcinogenic effect of USP1 in B-cell lymphoma remains elusive. Here we found that USP1 is highly expressed in DLBCL patients, and high expression of USP1 predicts poor prognosis. Knocking down USP1 or a specific inhibitor of USP1, pimozide, induced cell growth inhibition, cell cycle arrest and autophagy in DLBCL cells. Targeting USP1 by shRNA or pimozide significantly reduced tumor burden of a mouse model established with engraftment of rituximab/chemotherapy resistant DLBCL cells. Pimozide significantly retarded the growth of lymphoma in a DLBCL patient-derived xenograft (PDX) model. USP1 directly interacted with MAX, a MYC binding protein, and maintained the stability of MAX through deubiquitination, which promoted the transcription of MYC target genes. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.

ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.

Enhancement of photoresponse properties of conjugated polymers/inorganic semiconductor nanocomposites by internal micro-magnetic field.

In this paper, the effect of the internal micro-magnetic field (IMMF) on the photocurrent property of conjugated polymer/inorganic semiconductor nanocomposites is reported and analyzed. By using the redox reaction, magnetic Fe(3)O(4) nanoparticles were coated on the surface of highly active nanorods of conjugated polyaniline (PANI), forming an internal micro-magnetic electron donor (i.e., Fe(3)O(4)@PANI). After subsequent incorporation of CdS nanoparticles (serving as electron acceptors), the power conversion efficiency (PCE) of the system (Fe(3)O(4)@PANI-CdS) was found to be as high as 3.563%, contrasting sharply with the value (1.135%) of the hybrid without Fe(3)O(4) (PANI-CdS). This obvious enhancement originated from the fact that the IMMF increased the number of singlet polaron pairs through field-dependent intersystem crossing (ISC), giving a positive contribution to the photocurrent generation. Additionally, the dependence of the photocurrent on the remnant magnetization of the Fe(3)O(4)@PANI-CdS nanocomposites was investigated. A percolation behavior was observed, which was due to the appearance of interpenetrating networks consisting of donor and acceptor phases, leading to the recombination of charge carriers through trapping. The outcomes of the present work might help to produce a new family of conjugated organic/inorganic semiconductor nanocomposites with designed optoelectronic performances.

In Situ Growth of MnO2 Nanosheets on a Graphite Flake as an Effective Binder-Free Electrode for High-Performance Supercapacitors.

In this work, manganese dioxide (MnO2) nanosheets in situ loaded on a high-purity graphite flake (GF) were prepared by one-step hydrothermal deposition. It was found that the specific capacitance value of a single MnO2/GF electrode was 882 F/g at a current density of 1.0 A/g in a KOH electrolyte, and the specific capacitance retention of the MnO2/GF electrode can reach about 90.1% after 5000 charge-discharge cycles at a current density of 10 A/g. Furthermore, a MnO2/GF∥MnO2/GF symmetric supercapacitor device was fabricated with two pieces of MnO2/GF electrodes and ordinary filter paper with a 1 M KOH/PVA gel electrolyte as a separator. The single symmetric device displayed a high energy density of 64.2 Wh/kg at a power density of 400 W/kg within an applied voltage of 1.6 V, and this value was superior to those of previously reported MnO2-based systems. A tandem device consisting of a five-series tandem device (the applied voltage of a single device was 0.7 V) and a three-series tandem device (the applied voltage of a single device was 1.6 V) was prepared to drive a red light-emitting diode (LED). These findings open up application prospects for MnO2-based composite electrode materials for high-performance supercapacitors.

Assembly of long silver nanowires into highly aligned structure to achieve uniform "Hot Spots" for Surface-enhanced Raman scattering detection.

Silver nanowires (AgNWs) as a promising surface-enhanced Raman spectroscopy (SERS) substrate could be used in the analytical science due to its high sensitivity. However, it is difficult for the randomly-distributed silver nanowires to offer uniform "hot spots" to achieve the SERS signal reproducibility of small molecules detection. Herein, the evaporation-induced aggregation had been used to assemble long silver nanowires into highly aligned structure to achieve uniform "hot spots" for SERS detection. The normal glass slide with well-aligned silver nanowires could act as a high sensitivity and excellent reproducibility SERS substrate to provide a versatile platform for detecting analytes. Rhodamine 6G (R6G) is used to evaluate the sensitivity and reproducibility of these AgNWs SERS substrates. Even the low concentration of the R6G was 10-10 mol/L, the SERS features of R6G could be still observed clearly, and the uniform distribution of enhancement factor (EF) was higher than 0.8 × 104 accounting for about 75 % in the observed mapping area. Moreover, the relative standard deviation (RSD) of SERS intensity at the band of 610 cm-1 was used to estimate the signal reproducibility, and the calculated RSD value of aligned AgNWs substrate was about 3.6%, which was much higher than that of the randomly distributed AgNWs (26.8%) because of the highly aligned structure of silver nanowires with abundant and uniform inherent "hot spots". In addition, potential SERS detection of other small molecule, e.g. melamine was also demonstrated in the micromolar range.

Fabrication of Large Aerogel-Like Carbon/Carbon Composites with Excellent Load-Bearing Capacity and Thermal-Insulating Performance at 1800 °C.

Carbon aerogels (CAs) are attractive candidates for the thermal protection of aerospace vehicles due to their excellent thermostability and thermal insulation. However, the brittleness and low mechanical strength severely limits their practical applications, and no significant breakthroughs in large CAs with a high strength have been made. We report a high-pressure-assisted polymerization method combined with ambient pressure drying to fabricate large, strong, crack-free carbon/carbon (C/C) composites with an excellent load-bearing capacity, thermal stability, and thermal insulation. The composites are comprised of an aerogel-like carbon matrix and a low carbon crystallinity fiber reinforcement, featuring overlapping nanoparticles, macro-mesopores, large particle contact necks, and strong fiber/matrix interfacial bonding. The resulting C/C composites with a medium density of 0.6 g cm-3 have a very high compressive strength (80 MPa), in-plane shear strength (20 MPa), and specific strength (133 MPa g-1 cm3). Moreover, the C/C composites of 7.5-12.0 mm in thickness exposed to an oxyacetylene flame at 1800 °C for 900 s display very low back-side temperatures of 778-685 °C and even better mechanical properties after the heating. This performance makes the composites ideal for the ultrahigh temperature thermal protection of aerospace vehicles where both excellent thermal-insulating and load-bearing capacities are required.