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Moiré superlattices formed by twisted stacking in van der Waals materials have emerged as a new platform for exploring the physics of strongly correlated materials and other emergent phenomena1-5. However, there remains a lack of research on the mechanical properties of twisted-layer van der Waals materials, owing to a lack of suitable strategies for making three-dimensional bulk materials. Here we report the successful synthesis of a polycrystalline boron nitride bulk ceramic with high room-temperature deformability and strength. This ceramic, synthesized from an onion-like boron nitride nanoprecursor with conventional spark plasma sintering and hot-pressing sintering, consists of interlocked laminated nanoplates in which parallel laminae are stacked with varying twist angles. The compressive strain of this bulk ceramic can reach 14% before fracture, about one order of magnitude higher compared with traditional ceramics (less than 1% in general), whereas the compressive strength is about six times that of ordinary hexagonal boron nitride layered ceramics. The exceptional mechanical properties are due to a combination of the elevated intrinsic deformability of the twisted layering in the nanoplates and the three-dimensional interlocked architecture that restricts deformation from propagating across individual nanoplates. The advent of this twisted-layer boron nitride bulk ceramic opens a gate to the fabrication of highly deformable bulk ceramics.
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Grain boundaries (GBs), with their diversity in both structure and structural transitions, play an essential role in tailoring the properties of polycrystalline materials1-5. As a unique GB subset, {112} incoherent twin boundaries (ITBs) are ubiquitous in nanotwinned, face-centred cubic materials6-9. Although multiple ITB configurations and transitions have been reported7,10, their transition mechanisms and impacts on mechanical properties remain largely unexplored, especially in regard to covalent materials. Here we report atomic observations of six ITB configurations and structural transitions in diamond at room temperature, showing a dislocation-mediated mechanism different from metallic systems11,12. The dominant ITBs are asymmetric and less mobile, contributing strongly to continuous hardening in nanotwinned diamond13. The potential driving forces of ITB activities are discussed. Our findings shed new light on GB behaviour in diamond and covalent materials, pointing to a new strategy for development of high-performance, nanotwinned materials.
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Understanding the direct transformation from graphite to diamond has been a long-standing challenge with great scientific and practical importance. Previously proposed transformation mechanisms1-3, based on traditional experimental observations that lacked atomistic resolution, cannot account for the complex nanostructures occurring at graphite-diamond interfaces during the transformation4,5. Here we report the identification of coherent graphite-diamond interfaces, which consist of four basic structural motifs, in partially transformed graphite samples recovered from static compression, using high-angle annular dark-field scanning transmission electron microscopy. These observations provide insight into possible pathways of the transformation. Theoretical calculations confirm that transformation through these coherent interfaces is energetically favoured compared with those through other paths previously proposed1-3. The graphite-to-diamond transformation is governed by the formation of nanoscale coherent interfaces (diamond nucleation), which, under static compression, advance to consume the remaining graphite (diamond growth). These results may also shed light on transformation mechanisms of other carbon materials and boron nitride under different synthetic conditions.
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The root cap secretes mucilage and sheds border cells (border-like cells, BLCs) in Arabidopsis (Arabidopsis thaliana). These mucilage and root cap-derived cells form a defensive barrier against soil pathogens. BEARSKIN1 (BRN1) and BRN2 are 2 homologous NAM, ATAF1/2, and CUC2 (NAC) family transcription factors of Arabidopsis, and mucilage secretion is inhibited in the brn1/2 double mutant. BRN1 and BRN2 are also involved in the expression of a pectin-digesting enzyme, POLYGALACTURONASE (RCPG), that facilitates BLC shedding. To further explore the connection between mucilage secretion and BLC shedding, we examined mucilage production in Arabidopsis lines displaying altered BLC detachment. Inactivation of BRN2 blocked mucilage synthesis and secretion, while inactivation of BRN1 and RCPG did not. Interestingly, RCPG sorted into mucilage-carrying vesicles budding from the Golgi and inhibited mucilage secretion in brn2-delayed BLC detachment. The root cap of a germinating seedling is initially covered with a cuticle, which is replaced by mucilage from BLCs as the seedling begins to shed these cells. Ectopic expression of RCPG in germinating seedlings caused early BLC formation and accelerated the cuticle-to-mucilage transition, indicating that RCPG expression and mucilage secretion are co-regulated. Furthermore, brn2 roots exhibited slower growth and increased cell death when subjected to salt or osmotic stress. Our research suggests that BRN2-mediated mucilage secretion contributes to BLC release to build an extracellular defense zone surrounding the root cap.
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The para-crystalline structures of prolamellar bodies (PLBs) and light-induced etioplast-to-chloroplast transformation have been investigated via electron microscopy. However, such studies suffer from chemical fixation artifacts and limited volumes of 3D reconstruction. Here, we examined Arabidopsis thaliana cotyledon cells by electron tomography (ET) to visualize etioplasts and their conversion into chloroplasts. We employed scanning transmission ET to image large volumes and high-pressure freezing to improve sample preservation. PLB tubules were arranged in a zinc blende-type lattice-like carbon atoms in diamonds. Within 2 h after illumination, the lattice collapsed from the PLB exterior and the disorganized tubules merged to form thylakoid sheets (pre-granal thylakoids), which folded and overlapped with each other to create grana stacks. Since the nascent pre-granal thylakoids contained curved membranes in their tips, we examined the expression and localization of CURT1 (CURVATURE THYLAKOID1) proteins. CURT1A transcripts were most abundant in de-etiolating cotyledon samples, and CURT1A was concentrated at the PLB periphery. In curt1a etioplasts, PLB-associated thylakoids were swollen and failed to form grana stacks. In contrast, PLBs had cracks in their lattices in curt1c etioplasts. Our data provide evidence that CURT1A is required for pre-granal thylakoid assembly from PLB tubules during de-etiolation, while CURT1C contributes to cubic crystal growth in the dark.
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Arabidopsis , Tilacoides , Arabidopsis/genética , Arabidopsis/metabolismo , Carbono/metabolismo , Cloroplastos/metabolismo , Cotilédone , Diamante/análise , Diamante/metabolismo , Tomografia com Microscopia Eletrônica , Tilacoides/metabolismo , Zinco/metabolismoRESUMO
The accurate diagnosis of diabetic nephropathy relies on achieving ultrasensitive biosensing for biomarker detection. However, existing biosensors face challenges such as poor sensitivity, complexity, time-consuming procedures, and high assay costs. To address these limitations, we report a WS2-based plasmonic biosensor for the ultrasensitive detection of biomarker candidates in clinical human urine samples associated with diabetic nephropathy. Leveraging plasmonic-based electrochemical impedance microscopy (P-EIM) imaging, we observed a remarkable charge sensitivity in monolayer WS2 single crystals. Our biosensor exhibits an exceptionally low detection limit (0.201 ag/mL) and remarkable selectivity in detecting CC chemokine ligand 2 (CCL2) protein biomarkers, outperforming conventional techniques such as ELISA. This work represents a breakthrough in traditional protein sensors, providing a direction and materials foundation for developing ultrasensitive sensors tailored to clinical applications for biomarker sensing.
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Biomarcadores , Técnicas Biossensoriais , Quimiocina CCL2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/urina , Nefropatias Diabéticas/diagnóstico , Técnicas Biossensoriais/métodos , Quimiocina CCL2/urina , Biomarcadores/urina , Limite de Detecção , Técnicas Eletroquímicas/métodosRESUMO
Hydrides are promising candidates for achieving room-temperature superconductivity, but a formidable challenge remains in reducing the stabilization pressure below a megabar. In this study, we successfully synthesized a ternary lanthanum borohydride by introducing the nonmetallic element B into the La-H system, forming robust B-H covalent bonds that lower the pressure required to stabilize the superconducting phase. Electrical transport measurements confirm the presence of superconductivity with a critical temperature (Tc) of up to 106 K at 90 GPa, as evidenced by zero resistance and Tc shift under an external magnetic field. X-ray diffraction and transport measurements identify the superconducting compound as LaB2H8, a nonclathrate hydride, whose crystal structure remains stable at pressures as low as â¼ half megabar (59 GPa). Stabilizing superconductive stoichiometric LaB2H8 in a submegabar pressure regime marks a substantial advancement in the quest for high-Tc superconductivity in polynary hydrides, bringing us closer to the ambient pressure conditions.
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The nerve guidance conduits incorporated with stem cells, which can differentiate into the Schwann cells (SCs) to facilitate myelination, shows great promise for repairing the severe peripheral nerve injury. The innovation of advanced hydrogel materials encapsulating stem cells, is highly demanded for generating supportive scaffolds and adaptive microenvironment for nerve regeneration. Herein, this work demonstrates a novel strategy in regulating regenerative microenvironment for peripheral nerve repair with a biodegradable conductive hydrogel scaffold, which can offer multifunctional capabilities in immune regulation, enhancing angiogenesis, driving SCs differentiation, and promoting axon regrowth. The biodegradable conductive hydrogel is constructed by incorporation of polydopamine-modified silicon phosphorus (SiP@PDA) nanosheets into a mixture of methacryloyl gelatin and decellularized extracellular matrix (GelMA/ECM). The biomimetic electrical microenvironment performs an efficacious strategy to facilitate macrophage polarization toward a pro-healing phenotype (M2), meanwhile the conductive hydrogel supports vascularization in regenerated tissue through sustained Si element release. Furthermore, the MSCs 3D-cultured in GelMA/ECM-SiP@PDA conductive hydrogel exhibits significantly increased expression of genes associated with SC-like cell differentiation, thus facilitating the myelination and axonal regeneration. Collectively, both the in vitro and in vivo studies demonstrates that the rationally designed biodegradable multifunctional hydrogel significantly enhances nerve tissues repair.
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Hidrogéis , Regeneração Nervosa , Hidrogéis/química , Animais , Regeneração Nervosa/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Gelatina/química , Polímeros/química , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Células de Schwann/citologia , Células de Schwann/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Camundongos , Alicerces Teciduais/química , Células-Tronco/citologia , Condutividade Elétrica , Indóis/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , MetacrilatosRESUMO
Ultrasensitive detection of biomarkers, particularly proteins, and microRNA, is critical for disease early diagnosis. Although surface plasmon resonance biosensors offer label-free, real-time detection, it is challenging to detect biomolecules at low concentrations that only induce a minor mass or refractive index change on the analyte molecules. Here an ultrasensitive plasmonic biosensor strategy is reported by utilizing the ferroelectric properties of Bi2O2Te as a sensitive-layer material. The polarization alteration of ferroelectric Bi2O2Te produces a significant plasmonic biosensing response, enabling the detection of charged biomolecules even at ultralow concentrations. An extraordinary ultralow detection limit of 1 fm is achieved for protein molecules and an unprecedented 0.1 fm for miRNA molecules, demonstrating exceptional specificity. The finding opens a promising avenue for the integration of 2D ferroelectric materials into plasmonic biosensors, with potential applications spanning a wide range.
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Técnicas Biossensoriais , Ressonância de Plasmônio de Superfície , Técnicas Biossensoriais/métodos , Ressonância de Plasmônio de Superfície/métodos , Bismuto/química , MicroRNAs/análiseRESUMO
Glycine-rich RNA-binding proteins (GRPs) have been implicated in the responses of plants to environmental stresses, but the function of GRP genes involved in salt stress and the underlying mechanism remain unclear. In this study, we identified BpGRP1 (glycine-rich RNA-binding protein), a Betula platyphylla gene that is induced under salt stress. The physiological and molecular responses to salt tolerance were investigated in both BpGRP1-overexpressing and suppressed conditions. BpGRF3 (growth-regulating factor 3) was identified as a regulatory factor upstream of BpGRP1. We demonstrated that overexpression of BpGRF3 significantly increased the salt tolerance of birch, whereas the grf3-1 mutant exhibited the opposite effect. Further analysis revealed that BpGRF3 and its interaction partner, BpSHMT, function upstream of BpGRP1. We demonstrated that BpmiR396c, as an upstream regulator of BpGRF3, could negatively regulate salt tolerance in birch. Furthermore, we uncovered evidence showing that the BpmiR396c/BpGRF3 regulatory module functions in mediating the salt response by regulating the associated physiological pathways. Our results indicate that BpmiR396c regulates the expression of BpGRF3, which plays a role in salt tolerance by targeting BpGRP1.
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Betula , Tolerância ao Sal , Tolerância ao Sal/genética , Betula/genética , Betula/metabolismo , Estresse Fisiológico/genética , Glicina , Regulação da Expressão Gênica de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Proteínas de Plantas/metabolismoRESUMO
Traditional ceramics or metals cannot simultaneously achieve ultrahigh strength and high electrical conductivity. The elemental carbon can form a variety of allotropes with entirely different physical properties, providing versatility for tuning mechanical and electrical properties in a wide range. Here, by precisely controlling the extent of transformation of amorphous carbon into diamond within a narrow temperature-pressure range, we synthesize an in situ composite consisting of ultrafine nanodiamond homogeneously dispersed in disordered multilayer graphene with incoherent interfaces, which demonstrates a Knoop hardness of up to ~53 GPa, a compressive strength of up to ~54 GPa and an electrical conductivity of 670-1,240 S m-1 at room temperature. With atomically resolving interface structures and molecular dynamics simulations, we reveal that amorphous carbon transforms into diamond through a nucleation process via a local rearrangement of carbon atoms and diffusion-driven growth, different from the transformation of graphite into diamond. The complex bonding between the diamond-like and graphite-like components greatly improves the mechanical properties of the composite. This superhard, ultrastrong, conductive elemental carbon composite has comprehensive properties that are superior to those of the known conductive ceramics and C/C composites. The intermediate hybridization state at the interfaces also provides insights into the amorphous-to-crystalline phase transition of carbon.
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The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.
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Regeneração Óssea , Fosfatos de Cálcio , Osteogênese , Osteossarcoma , Alicerces Teciduais , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Animais , Regeneração Óssea/efeitos dos fármacos , Alicerces Teciduais/química , Coelhos , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Osteogênese/efeitos dos fármacos , Poliésteres/química , Humanos , Diferenciação Celular/efeitos dos fármacos , Neoplasias Ósseas/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Células de Schwann/efeitos dos fármacos , Nanofibras/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Selênio/química , Selênio/farmacologiaRESUMO
Mechanical properties of covalent materials can be greatly enhanced with strategy of nanostructuring. For example, the nanotwinned diamond with an isotropic microstructure of interweaved nanotwins and interlocked nanograins shows unprecedented isotropic mechanical properties. How the anisotropic microstructure would impact on the mechanical properties of diamond has not been fully investigated. Here, we report the synthesis of diamond from superaligned multiwalled carbon nanotube films under high pressure and high temperature. Structural characterization reveals preferentially oriented diamond nanotwin bundles with an average twin thickness of ca. 2.9 nm, inherited from the directional nanotubes. This diamond exhibits extreme mechanical anisotropy correlated with its microstructure (e.g., the average Knoop hardness values measured with the major axis of the indenter perpendicular and parallel to nanotwin bundles are 233 ± 8 and 129 ± 9 GPa, respectively). Molecular dynamics simulation reveals that, in the direction perpendicular to the nanotwin bundles, the dense twin boundaries significantly hinder the motion of dislocations under indentation, while such a resistance is much weaker in the direction along the nanotwin bundles. Current work verifies the hardening effect in diamond via nanostructuring. In addition, the mechanical properties can be further tuned (anisotropy) with microstructure design and modification.
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Plasmonic biosensing is a label-free detection method that is commonly used to measure various biomolecular interactions. However, one of the main challenges in this approach is the ability to detect biomolecules at low concentrations with sufficient sensitivity and detection limits. Here, 2D ferroelectric materials are employed to address the issues with sensitivity in biosensor design. A plasmonic sensor based on Bi2 O2 Se nanosheets, a ferroelectric 2D material, is presented for the ultrasensitive detection of the protein molecule. Through imaging the surface charge density of Bi2 O2 Se, a detection limit of 1 fM is achieved for bovine serum albumin (BSA). These findings underscore the potential of ferroelectric 2D materials as critical building blocks for future biosensor and biomaterial architectures.
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Clinical treatment of osteosarcoma encounters great challenges of postsurgical tumor recurrence and extensive bone defect. To develop an advanced artificial bone substitute that can achieve synergistic bone regeneration and tumor therapy for osteosarcoma treatment, a multifunctional calcium phosphate composite enabled by incorporation of bioactive FePSe3 -nanosheets within the cryogenic-3D-printed α-tricalcium phosphate scaffold (TCP-FePSe3 ) is explored. The TCP-FePSe3 scaffold exhibits remarkable tumor ablation ability due to the excellent NIR-II (1064 nm) photothermal property of FePSe3 -nanosheets. Moreover, the biodegradable TCP-FePSe3 scaffold can release selenium element to suppress tumor recurrence by activating of the caspase-dependent apoptosis pathway. In a subcutaneous tumor model, it is demonstrated that tumors can be efficiently eradicated via the combination treatment with local photothermal ablation and the antitumor effect of selenium element. Meanwhile, in a rat calvarial bone defect model, the superior angiogenesis and osteogenesis induced by TCP-FePSe3 scaffold have been observed in vivo. The TCP-FePSe3 scaffold possesses improved capability to promote the repair of bone defects via vascularized bone regeneration, which is induced by the bioactive ions of Fe, Ca, and P released during the biodegradation of the implanted scaffolds. The TCP-FePSe3 composite scaffolds fabricated by cryogenic-3D-printing illustrate a distinctive strategy to construct multifunctional platform for osteosarcoma treatment.
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Neoplasias Ósseas , Osteossarcoma , Selênio , Ratos , Animais , Alicerces Teciduais , Recidiva Local de Neoplasia , Osteogênese , Regeneração Óssea , Fosfatos de Cálcio/farmacologia , Osteossarcoma/terapia , Impressão Tridimensional , Neoplasias Ósseas/terapiaRESUMO
2D materials with low symmetry are explored in recent years because of their anisotropic advantage in polarization-sensitive photodetection. Herein the controllably grown hexagonal magnetic semiconducting α-MnTe nanoribbons are reported with a highly anisotropic (100) surface and their high sensitivity to polarization in a broadband photodetection, whereas the hexagonal structure is highly symmetric. The outstanding photoresponse of α-MnTe nanoribbons occurs in a broadband range from ultraviolet (UV, 360 nm) to near infrared (NIR, 914 nm) with short response times of 46 ms (rise) and 37 ms (fall), excellent environmental stability, and repeatability. Furthermore, due to highly anisotropic (100) surface, the α-MnTe nanoribbons as photodetector exhibit attractive sensitivity to polarization and high dichroic ratios of up to 2.8 under light illumination of UV-to-NIR wavelengths. These results demonstrate that 2D magnetic semiconducting α-MnTe nanoribbons provide a promising platform to design the next-generation polarization-sensitive photodetectors in a broadband range.
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Floquet (periodic) driving has recently emerged as a powerful technique for engineering quantum systems and realizing nonequilibrium phases of matter. A central challenge to stabilizing quantum phenomena in such systems is the need to prevent energy absorption from the driving field. Fortunately, when the frequency of the drive is significantly larger than the local energy scales of the many-body system, energy absorption is suppressed. The existence of this so-called prethermal regime depends sensitively on the range of interactions and the presence of multiple driving frequencies. Here, we report the observation of Floquet prethermalization in a strongly interacting dipolar spin ensemble in diamond, where the angular dependence of the dipolar coupling helps to mitigate the long-ranged nature of the interaction. Moreover, we extend our experimental observation to quasi-Floquet drives with multiple incommensurate frequencies. In contrast to a single-frequency drive, we find that the existence of prethermalization is extremely sensitive to the smoothness of the applied field. Our results open the door to stabilizing and characterizing nonequilibrium phenomena in quasiperiodically driven systems.
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INTRODUCTION: This study aimed to elucidate the coagulation disorders in non-ICU patients with acute kidney injury (AKI) and their contribution to clotting-related outcomes of intermittent kidney replacement therapy (KRT). METHODS: We included non-ICU-admitted patients with AKI requiring intermittent KRT, clinically having a risk of bleeding and against systemic anticoagulant use during KRT between April and December 2018. The premature termination of treatment due to circuit clotting was considered a poor outcome. We analyzed the characteristics of thromboelastography (TEG)-derived and traditional coagulation parameters and explored the potential-affecting factors. RESULTS: In total, 64 patients were enrolled. Hypocoagulability was detected in 4.7%-15.6% of patients by a combination of the traditional parameters, i.e., prothrombin time (PT)/international normalized ratio, activated partial PT, and fibrinogen. No patient had hypocoagulability observed on TEG-derived reaction time; only 2.1%, 3.1%, and 10.9% of patients had hypocoagulability on TEG-derived kinetic time (K-time), α-angle, and maximum amplitude (MA), respectively, which were also platelet-related coagulation parameters, despite 37.5% of the cohort having thrombocytopenia. In contrast, hypercoagulability was more prevalent, involving 12.5%, 43.8%, 21.9%, and 48.4% of patients on TEG K-time, α-angle, MA, and coagulation index (CI), respectively, although thrombocytosis was only in 1.5% of the cohort. Patients with thrombocytopenia showed lower fibrinogen level (2.6 vs. 4.0 g/L, p = 0.00), α-angle (63.5° vs. 73.3°, p = 0.00), MA (53.5 vs. 66.1 mm, p = 0.00), and CI (1.8 vs. 3.6, p = 0.00) but higher thrombin time (17.8 vs. 16.2 s, p = 0.00) and K-time (2.0 vs. 1.2 min, p = 0.00) than those with a platelet count over 100 × 109/L. 41 patients were treated with heparin-free protocol, and 23 were treated with regional citrate anticoagulation (RCA). The premature termination rate was 41.5% on heparin-free patients, while 8.7% of patients underwent an RCA protocol (p = 0.006). Heparin-free protocol was the strongest adverse factor to poor outcomes. A heparin-free subgroup analysis found that the circuit clotting risk was increased by 61.7% with a 10 × 109/L elevation in platelet count (odds ratio [OR] = 1.617, p = 0.049) and decreased by 67.5% following a second increase of PT (OR = 0.325, p = 0.041). No significant correlation was found between TEG parameters and premature circuit clotting. CONCLUSIONS: Most non-ICU-admitted patients with AKI had normal-to-enhanced hemostasis and activated platelet function based on TEG results, as well as a high rate of premature circuit clotting when receiving heparin-free protocol despite thrombocytopenia. Further studies are needed to better determine the use of TEG in respect to management of anticoagulation and bleeding complications in AKI patients with KRT.
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Injúria Renal Aguda , Trombocitopenia , Trombose , Humanos , Tromboelastografia/métodos , Estudos de Coortes , Fibrinogênio , Heparina , Trombocitopenia/complicações , Trombocitopenia/diagnóstico , Ácido Cítrico , Anticoagulantes/uso terapêutico , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologiaRESUMO
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BACKGROUND: Hepatocellular carcinoma (HCC) is a long-term malignancy that causes high morbidities and mortalities worldwide. Notably, long non-coding RNAs (LncRNAs) have been identified as candidate targets for malignancy treatments. METHODS: LncRNA LINC01116 and its Pearson-correlated genes (PCGs) were identified and analyzed in HCC patients. The diagnostic and prognostic value of the lncRNA was evaluated using data from The Cancer Genome Atlas (TCGA). Further, we explored the target drugs of LINC01116 for clinical application. Relationships between immune infiltration and PCGs, methylation and PCGs were explored. The diagnostic potentials were then validated by Oncomine cohorts. RESULTS: LINC01116 and the PCG OLFML2B are differentially and highly expressed in tumor tissues (both P ≤ 0.050). We found that LINC01116, TMSB15A, PLAU, OLFML2B, and MRC2 have diagnostic potentials (all AUC ≥ 0.700, all P ≤ 0.050) while LINC01116 and TMSB15A have prognostic significance (both adjusted P ≤ 0.050). LINC01116 was enriched in the vascular endothelial growth factor (VEGF) receptor signaling pathway, mesenchyme morphogenesis, etc. After that, candidate target drugs with potential clinical significance were identified: Thiamine, Cromolyn, Rilmenidine, Chlorhexidine, Sulindac_sulfone, Chloropyrazine, and Meprylcaine. Analysis of immune infiltration revealed that MRC2, OLFML2B, PLAU, and TMSB15A are negatively associated with the purity but positively associated with the specific cell types (all P < 0.050). Analysis of promoter methylation demonstrated that MRC2, OLFML2B, and PLAU have differential and high methylation levels in primary tumors (all P < 0.050). Validation results of the differential expressions and diagnostic potential of OLFML2B (Oncomine) were consistent with those obtained in the TCGA cohort (P < 0.050, AUC > 0.700). CONCLUSIONS: Differentially expressed LINC01116 could be a candidate diagnostic and an independent prognostic signature in HCC. Besides, its target drugs may work for HCC therapy via the VEGF receptor signaling pathway. Differentially expressed OLFML2B could be a diagnostic signature involved in HCC via immune infiltrates.