MXene-based composite aerogels with bifunctional ferrous ions for the efficient degradation of phenol from wastewater.

Herein, MXene-based composite aerogel (MXene-Fe2+ aerogel) are constructed by a one-step freeze-drying method, using Ti3C2Tx MXene layers as substrate material and ferrous ion (Fe2+) as crosslinking agent. With the aid of the Fe2+ induced Fenton reaction, the synthesized aerogels are used as the particle electrodes to remove phenol from wastewater with three-dimensional electrode technology. Combined with the dual roles of Fe2+ and the highly conductive MXene, the obtained particle electrode possesses extremely effective phenol degradation. The effects of experiment parameters such as Fe2+ to MXene ratio, particle electrode dosage, applied voltage, and initial pH of solution on the removal of phenol are discussed. At pH = 2.5, phenol with 50 mg/L of initial concentration can be completely removed within 50 min at 10 V with the particle electrode dosage of 0.56 g/L. Finally, the mechanism of degradation is explored. This work provides an effective way for phenol degradation by MXene-based aerogel, which has great potential for the degradation of other organic pollutants in wastewater.

Design Synthesis of Low-Silica SAPO-34 Nanocrystals by Constructing Isomorphous Core-Shell Structure: An Effective Catalyst for Improving Catalytic Performances in Methanol-to-Olefins Reaction.

It is well known that low-silica SAPO-34, with an extra porosity (meso- and/or macropores) system, affords excellent catalytic performance in the methanol-to-olefins (MTO) reaction, while the direct synthesis of low-silica SAPO-34 with a hierarchical structure is difficult to achieve, principally because the crystal impurities are usually formed under a low silica content in a gel precursor. Herein, low-silica SAPO-34 nanocrystals were successfully fabricated for the first time by constructing an isomorphous core-shell structure in an epitaxial growth manner. In which, low-silica, ultrasmall nanosquare-shaped SAPO-34 crystals with the same growth orientation along the (100) crystal plane compactly grow on the monocrystal SAPO-34 cores. Crucially, the external surface acid properties of the core SAPO-34 with the Si-rich outer layer are effectively modified by the low-silica SAPO-34 shell. Furthermore, the growth process and Si-substitution mechanism of the shell zeolite were comprehensively investigated. It was found that with the prolonged crystallization time, more and more coordinated Si(4Al) and Si(3Al) structures via two substitution mechanisms (SM2 and SM3) are generated in the nanocrystalline SAPO-34 shell, which endow moderate acidity of the core-shell SAPO-34. Compared to the uncoated SAPO-34, the core-shell SAPO-34 performs a longer lifespan and a higher average selectivity of light olefins (ethylene plus propylene) when applied to the MTO reaction, which is attributed to the positive effects of the luxuriant interstitial pores offering a fast diffusion channel and the moderate acid density depressing the hydrogen transfer reaction of light olefins. This work provides new insights into the fabrication of low-silica SAPO-34 nanocrystals, which are based on the rational design of the isomorphous core-shell zeolite.

Pleosmaranes A-R, Isopimarane and 20-nor Isopimarane Diterpenoids with Anti-inflammatory Activities from the Mangrove Endophytic Fungus Pleosporales sp. HNQQJ-1.

Pleosmaranes A-R (1-18), 18 new isopimarane-type diterpenoids, together with four known analogs (19-22), were isolated from the mangrove endophytic fungus Pleosporales sp. HNQQJ-1. Their structures and absolute configurations were established by analysis of their spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-9 possess an unusual aromatic B ring and a 20-nor-isopimarane skeleton. Compounds 15-17 contain a unique 2-oxabicyclo[2.2.2]octane moiety. Compound 18 features an unexpected 2-oxabicyclo[3.2.1]octane moiety. Compounds 8 and 12 exhibited a moderate inhibitory effect against LPS-induced NO production, with IC50 values of 19 and 25 µM, respectively.

Kinome and phosphoproteome reprogramming underlies the aberrant immune responses in critically ill COVID-19 patients.

SARS-CoV-2 infection triggers extensive host immune reactions, leading to severe diseases in certain individuals. However, the molecular basis underlying the excessive yet non-productive immune responses in severe COVID-19 remains incompletely understood. In this study, we conducted a comprehensive analysis of the peripheral blood mononuclear cell (PBMC) proteome and phosphoproteome in sepsis patients positive or negative for SARS-CoV-2 infection, as well as healthy subjects, using quantitative mass spectrometry. Our findings demonstrate dynamic changes in the COVID-19 PBMC proteome and phosphoproteome during disease progression, with distinctive protein or phosphoprotein signatures capable of distinguishing longitudinal disease states. Furthermore, SARS-CoV-2 infection induces a global reprogramming of the kinome and phosphoproteome, resulting in defective adaptive immune response mediated by the B and T lymphocytes, compromised innate immune responses involving the SIGLEC and SLAM family of immunoreceptors, and excessive cytokine-JAK-STAT signaling. In addition to uncovering host proteome and phosphoproteome aberrations caused by SARS-CoV-2, our work recapitulates several reported therapeutic targets for COVID-19 and identified numerous new candidates, including the kinases PKG1, CK2, ROCK1/2, GRK2, SYK, JAK2/3, TYK2, DNA-PK, PKCδ, and the cytokine IL-12.

Preparation of highly dispersed Ni single-atom doped ultrathin g-C3N4 nanosheets by metal vapor exfoliation for efficient photocatalytic CO2 reduction.

Single-atom photocatalysts can modulate the utilization of photons and facilitate the migration of photogenerated carriers. However, the preparation of single-atom uniformly doped photocatalysts is still a challenging topic. Herein, we propose the preparation of Ni single-atom doped g-C3N4 photocatalysts by metal vapor exfoliation. The Ni vapor produced by calcining nickel foam at high temperature accumulates in between g-C3N4 layers and poses a certain vapor pressure to destroy the interlayer van der Waals forces of g-C3N4. Individual metal atoms are doped into the structure while exfoliating g-C3N4 into nanosheets by metal vapor. Upon optimization of Ni content, the Ni single atom doped g-C3N4 nanosheets with 2.81 wt% Ni exhibits the highest CO2 reduction performance in the absence of sacrificial agents. The generation rates of CO and CH4 are 19.85 and 1.73 µmol g-1h-1, respectively. The improved photocatalytic performance is attributed to the anchoring Ni of single atoms on g-C3N4 nanosheets, which increases both carrier separation efficiency and reaction sites. This work provides insight into the design of photocatalysts with highly dispersed single-atom.

Ultrafine PtCo alloy by pyrolysis etching-confined pyrolysis for enhanced hydrogen evolution.

Zeolitic imidazolate framework-67 (ZIF-67) has been widely used as a precursor to developing efficient PtCo alloy catalysts for hydrogen evolution reaction (HER). However, traditional in-situ pyrolysis strategies involve complicated interface structure modulating processes between ZIF-67 and Pt precursors, challenging large-scale synthesis. Herein, a "pyrolysis etching-confined pyrolysis" approach is developed to design confined PtCo alloy in porous frameworks of onion carbon derived from ZIF-67. The confined PtCo alloy with Pt content of only 5.39 wt% exhibits a distinct HER activity in both acid (η10: 5 mV and Tafel: 9 mV dec-1) and basic (η10: 33 mV and Tafel: 51 mV dec-1) media and a drastic enhancement in stability. Density functional theory calculations reveal that the strong electronic interaction between Pt and Co allows favorable electron redistribution, which affords a favorable hydrogen spillover on PtCo alloy compared with that of pristine Pt(111). Operational electrochemical impedance spectroscopy demonstrates that the Faraday reaction process is facilitated under acidic conditions, while the transfer of intermediates through the electric double-layer region under alkaline conditions is accelerated. This work not only offers a universal route for high-performance Pt-based alloy catalysts with metal-organic framework (MOF) precursors but also provides experimental evidence for the role of the electric double layer in electrocatalysis reactions.

SERS immunoassay analysis of Escherichia coli and Staphylococcus aureus based on sandwich-structured complex probe and target-induced strand displacement.

A direct and ultra-sensitive surface-enhanced Raman scattering (SERS) immunoassay method is introduced for the detection of Escherichia coli and Staphylococcus aureus. This methodology is based on a sandwich-structured complex probe (SCP) mechanism, combined with target-induced strand displacement. Moreover, by leveraging the amplified SERS signal from gold nanoparticles (AuNPs) corresponding to an increase in bacterial count, we achieve quantitative determination. The SCP demonstrates remarkable specificity, sensitivity, and anti-interference capability in bacterial detection. The detection limits for both bacterial strains are as low as 10 CFU/mL. In our selectivity tests, all peak intensities had standard deviations (n = 3) below 6%. Recoveries in normal human serum were 101-110% for E. coli and 96-101% for S. aureus. In milk, the recoveries were 102-105% for E. coli and 100-105% for S. aureus, respectively, demonstrating a high level of accuracy and resistance to interference. In addition, the SCP offers a dual-detection capability, enabling simultaneous diagnosis of multiple targets, which greatly simplifies the testing procedure. The findings underscore that this immunoassay platform fulfills the demand for rapid and precise pathogenic bacterial diagnosis, holding substantial potential for practical applications.

Intrinsic room-temperature ferromagnetism in a two-dimensional semiconducting metal-organic framework.

The development of two-dimensional (2D) magnetic semiconductors with room-temperature ferromagnetism is a significant challenge in materials science and is important for the development of next-generation spintronic devices. Herein, we demonstrate that a 2D semiconducting antiferromagnetic Cu-MOF can be endowed with intrinsic room-temperature ferromagnetic coupling using a ligand cleavage strategy to regulate the inner magnetic interaction within the Cu dimers. Using the element-selective X-ray magnetic circular dichroism (XMCD) technique, we provide unambiguous evidence for intrinsic ferromagnetism. Exhaustive structural characterizations confirm that the change of magnetic coupling is caused by the increased distance between Cu atoms within a Cu dimer. Theoretical calculations reveal that the ferromagnetic coupling is enhanced with the increased Cu-Cu distance, which depresses the hybridization between 3d orbitals of nearest Cu atoms. Our work provides an effective avenue to design and fabricate MOF-based semiconducting room-temperature ferromagnetic materials and promotes their practical applications in next-generation spintronic devices.

Advances in Magnetic Carbon Dots: A Theranostics Platform for Fluorescence/Magnetic Resonance Bimodal Imaging and Therapy for Tumors.

Theranostics technology that combines tumor diagnosis or monitoring with therapy is an important direction for the future development of tumor treatment. It takes advantage of efficiently observing tumor tissues, monitoring tumor treatment in real time, and significantly improving the cure efficiency. Magnetic carbon dots (CDs) are of wide interest as molecular imaging probes, drug carriers, photosensitizers, and radiosensitizers in the integration of tumor fluorescence/magnetic resonance bimodal diagnosis and treatment because of their small size, good optical stability, magnetic relaxation rate, and biocompatibility. This review first analyzes and compares the synthesis methods and physicochemical properties of magnetic CDs in recent years and then concludes their mechanism in tumor fluorescence/magnetic resonance bimodal imaging and therapy in details. Subsequently, the research progress of their application in tumor theranostics are summarized. Finally, the problems and challenges of magnetic CDs for development at this stage are prospected. This review provides new ideas for their controlled synthesis and application in efficient and precise therapy for tumors.

UroVysion™ fluorescence in situ hybridization (FISH) possibly has a high positive rate in carcinoma of non-urothelial lineages.

Background: Positive UroVysion™ fluorescence in situ hybridization (FISH) is generally considered as urothelial carcinoma (UC). We clarify if UroVysion™ FISH can be positive in carcinoma of non-urothelial lineages (CNUL), and verify the consistency of urine FISH and histological FISH in CNUL. Methods: All CNUL subjects detected by urine FISH assay due to haematuria from Tongji Hospital were screened. Meanwhile, 2 glandular cystitis and 2 urothelial carcinoma were served as negative or positive control. Paraffin-embedded tissue sections of all subjects were sent to the pathology department for histological FISH detection. Results: A total of 27 patients were included in this study, including 9 with adenocarcinomas, 11 with squamous cell carcinomas, and 7 with other tumour types. The overall positive rate in urine FISH was 64.00% (16/25) in patients with CNUL, 77.78% (7/9) in those with adenocarcinoma and 54.55% (6/11) in those with squamous carcinoma. There was a significant difference in the GLP p16 gene deletion rate between UC and CNUL (100% vs. 8.00%, p = 0.017). Histological FISH results showed that the histological results of 19 patients were consistent with their urine FISH results, and only one patient with stage Ⅲa urachal carcinoma had inconsistent histological FISH results (positive) and urine FISH (negative) results. Conclusion: We demonstrated for the first time the application value of FISH in CNUL on urine samples. Positive urine FISH tests indicate not only UC, but also CNUL. UroVysion™ FISH possibly has a high positive rate in CNUL. CNUL and UC have different genetic changes shown by FISH.

A novel TPD52L2-ROS1 gene fusion expanding the molecular alterations in inflammatory myofibroblastic tumor: case report and literature review.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a distinctive tumor composed of spindle cells accompanied by mixed inflammatory cells, and immunohistochemical positivity for ALK (anaplastic lymphoma kinase protein) can be detected in half of IMTs. The diagnosis of ALK-negative IMT could be a challenge. Recently, the fusions of some kinase genes, such as RET, NTRK1, ROS1, etc., are revealed in ALK-negative IMT. CASE PRESENTATION: A 19-year-old woman presented with swelling of the left upper arm. Magnetic resonance imaging (MRI) scan revealed a tumor in the left postbrachium extended to the left axillary, serratus anterior muscle, and latissimus dorsi muscle. Histopathologically, the irregular-circumscribed tumor was composed of dense spindle-shaped cells with eosinophilic abundant cytoplasm and hyalinized mesenchyme in an inflammatory background. Immunohistochemically (IHC), tumor cells were positive for SMA, MDM2, and p16; the cells were negative for desmin, MyoD1, Myogenin, pan-cytokeratin, S100, SOX10, HMB45, Malen-A, CD34, CD31, CD99, and ALK. By RNA-based NGS, a novel fusion between TPD52L2 3' end of exon 1-4 and ROS1 5' end of exon 36-43 was revealed. ROS1 IHC staining was negative. The final diagnosis of IMT with TPD52L2-ROS1 fusion was made. Subsequently, the patient experienced a good clinical response to Crizotinib, and clinical follow-up showed stable disease after 9 months. CONCLUSION: This report expands the spectrum of ROS1 gene rearrangements in the IMT and highlights the importance of molecular analysis of IMT for getting a diagnostic clue and determining potential therapeutic strategies.

Effect of SH2B1 on glucose metabolism during pressure overload-induced cardiac hypertrophy and cardiac dysfunction.

This study mainly explored the effect and mechanism of Src homology 2 (SH2) B adaptor protein 1 (SH2B1) on cardiac glucose metabolism during pressure overload-induced cardiac hypertrophy and dysfunction. A pressure-overloaded cardiac hypertrophy model was constructed, and SH2B1-siRNA was injected through the tail vein. Haematoxylin and eosin (H&E) staining was used to detect myocardial morphology. ANP, BNP, ß-MHC and the diameter of myocardial fibres were quantitatively measured to evaluate the degree of cardiac hypertrophy, respectively. GLUT1, GLUT4, and IR were detected to assess cardiac glucose metabolism. Cardiac function was determined by echocardiography. Then, glucose oxidation and uptake, glycolysis and fatty acid metabolism were assessed in Langendorff perfusion of hearts. Finally, PI3K/AKT activator was used to further explore the relevant mechanism. The results showed that during cardiac pressure overload, with the aggravation of cardiac hypertrophy and dysfunction, cardiac glucose metabolism and glycolysis increased, and fatty acid metabolism decreased. After SH2B1-siRNA transfection, cardiac SH2B1 expression was knocked down, and the degree of cardiac hypertrophy and dysfunction was alleviated compared with the Control-siRNA transfected group. Simultaneously, cardiac glucose metabolism and glycolysis were reduced, and fatty acid metabolism was enhanced. The SH2B1 expression knockdown mitigated the cardiac hypertrophy and dysfunction by reducing cardiac glucose metabolism. After using PI3K/AKT activator, the effect of SH2B1 expression knockdown on cardiac glucose metabolism was reversed during cardiac hypertrophy and dysfunction. Collectively, SH2B1 regulated cardiac glucose metabolism by activating the PI3K/AKT pathway during pressure overload-induced cardiac hypertrophy and cardiac dysfunction.

CHI3L1 promotes myocardial fibrosis via regulating lncRNA TUG1/miR-495-3p/ETS1 axis.

Abnormal levels of CHI3L1 and lnc TUG1 are often associated with myocardial fibrosis, and their specific expressions may be closely related to the process of myocardial fibrosis. In addition, CHI3L1 was found to significantly up-regulate the expression of lncTUG1. Therefore, this study further explored the major role of CHI3L1 in regulating the progression of myocardial fibrosis. Myocardial fibrosis in mice was established using an angiotensin (Ang II) model, and the degree of myocardial fibrosis was assessed by qPCR, western blot and pathological techniques. HL-1 cells with overexpression and silencing of CHI3L1 were constructed, and the cell migration ability was detected using the Transwell method. Biological information was used to predict the potential target miRNA of lnc TUG1, and the interaction between them was verified by dual luciferase reporter assay. Using functional rescue assay and the rAAV9 technique, CHI3L1 was verified to affect the fibrotic process of myocardial cells by regulating the lnc TUG1/miR-495-3p/ETS1 axis in vitro and in vivo. The myocardial fibrosis index in the model group was significantly upregulated, and expression of both CHI3L1 and lnc TUG1 was upregulated. Pathological results revealed fibrosis and collagen deposition in the myocardium. Overexpression of lnc TUG1 reversed the inhibitory effect of CHI3L1 silencing on myocardial fibrosis. Mechanistically, CH3L1 upregulates the expression of lnc TUG1, and lnc TUG1 weakens the inhibition of ETS1 through sponge absorption of miR-495-3p, promoting the process of myocardial fibrosis.

Embedding TiO2microspheres into the active layer as light scatterers in a perovskite photodetector to boost light harvesting.

Here, TiO2microspheres with particle sizes of 200-400 nm are embedded in p-i-n perovskite photodetectors, which are used as light scatterers. This approach was implemented to change the light transfer path in the perovskite layer, which gives the device higher photon-capture ability in a specific incident wavelength range. Compared with a pristine device, the photocurrent and responsivity of the device based on such a structure are obviously enhanced in the ranges of 560-610 nm and 730-790 nm. The photocurrent under 590 nm incident light wavelength illumination (light intensityP= 31.42µW·cm-2) increases from 1.45µA to 1.71µA, with an increase of 17.93%, and the responsivity reaches 0.305 A·W-1. In addition, the introduction of TiO2has no additional negative impact on the carrier extraction and the dark current. Also, the response time of the device did not deteriorate. Finally, the role of TiO2as light scatterers is further verified by embedding microspheres into mixed-halide perovskite devices.

CircUBXN7 Impedes Apoptosis to Alleviate Myocardial Infarction Injury by Regulating the miR-582-3p/MARK3 Axis.

OBJECTIVE: The role of CircUBXN7 has been described in various disorders, including hypoxia/reoxygenation-induced cardiomyocyte injury. However, the detailed mechanisms underlying myocardial infarction (MI) remain unclear. METHODS: CircUBXN7, microtubule affinity regulating kinase 3 (MARK3), and miR-582-3p expression was analyzed in patients with MI, in an ischemia/reperfusion (I/R) rat model, and in hypoxia-induced H9c2 cells using quantitative reverse transcription polymerase chain reaction analysis. The myocardial infarction (MI) area was assessed using triphenyltetrazolium chloride staining, whereas the TUNEL assay and western blotting were performed to assess apoptosis. The relationships of miR-582-3p with circUBXN7 and MARK3 3'UTR were ascertained through luciferase reporter experiments. RESULTS: Both circUBXN7 and MARK3 were poorly expressed, whereas miR-582-3p was upregulated in patients with MI, the I/R rat model, and hypoxia-induced H9c2 cells. CircUBXN7 overexpression hampered hypoxia-induced apoptosis in H9c2 cells and mitigated MI-resulting myocardial injury. CircUBXN7 targeted miR-582-3p, and circUBXN7 overexpression abolished the pro-apoptotic influence of miR-582-3p overexpression in hypoxia-induced H9c2 cells. Nevertheless, the circUBXN7 target, MARK3, could abrogate the effect of the miR-582-3p mimic. CONCLUSION: CircUBXN7 impedes apoptosis and reduces MI injury by regulating the miR-582-3p/MARK3 axis.

Synthesis, Structures, and Photophysical Properties of Zigzag BNBNB-Embedded Anthracene-Fused Fluoranthene.

Three zigzag BNBNB-embedded anthracene-fused fluoranthenes are synthesized from 1,3,2-benzodiazaboroles through an indole-type N-directed C-H borylation reaction. Single-crystal X-ray diffraction analyses confirm the double bond character of all four alternating B-N bonds and reveal the five-center four-π-electron nature of the BNBNB group. Experimental spectra and density functional theory calculations indicate that borylation remarkably enhances the planarity, extends π-conjugation, and leads to a bathochromic shift in the absorption and emission bands, with remarkable fluorescence quantum yields in solution (92%).

A theoretical study on the line defects in ß12-borophene: enhanced direct-current and alternating-current conductances.

Using density functional theory and the non-equilibrium Green's function method, we theoretically investigated the structures, stabilities, electronic properties, and the direct-current (DC) and alternating-current (AC) transport properties of the line defects in two-dimensional material ß12-borophene. Our results suggest that there exist six line defects that can enhance the stability of ß12-borophene and the line defects have profound influences on the electronic structure of ß12-borophene. Along the zigzag direction, the line defects can change the atomic orbital components of the Dirac cones in perfect ß12-borophene, but the line defects along the armchair direction have complicated influences on the Dirac cones. In the case of DC transport, some of the line defects lead to the constant DC phenomenon and the negative differential resistance effect, and enhance the DC conductances since the line defects exhibit typical one-dimensional characteristics. In the case of AC transport, some of the line defects enhance the AC conductances in the medium-frequency and high-frequency ranges through the photon-assisted tunneling effect. The microscopic mechanisms of the enhanced DC and AC conductances are different. In addition, for a low-frequency range, the equivalent circuits of ß12-borophene and the line defects were also suggested, which will be beneficial for designing borophene-based functional nanodevices.

One-Step Synthesis of White-Light-Emitting Carbon Dots for White LEDs with a High Color Rendering Index of 97.

White-light-emitting carbon dots (WCDs) show innate advantages as phosphors in white light-emitting diodes (WLEDs). For WLEDs, the color rendering index (CRI) is the most important metric to evaluate its performance. Herein, WCDs are prepared by a facile one-step solvothermal reaction of trimellitic acid and o-phenylenediamine. It consists of four CDs identified by column chromatography as blue, green, yellow, red, and thus white light is a superposition of these four types of light. The mixture of the four CDs undergoes Förster resonance energy transfer to induce the generation of white light. The photoluminescence of WCDs originates from the synergistic effect of carbon core and surface states. Thereinto, the carbon core states dominate in RCDs, and the increase of amide contents and degree of conjugation promote the redshift of the emission spectra, which is further confirmed by theoretical calculations. In addition, a high CRI of 97 is achieved when the WCDs are used as phosphors to fabricate WLEDs, which is almost the highest value up to now. The multicolor LEDs can also be fabricated by using the four multicolor CDs as phosphors, respectively. This work provides a novel approach to explore the rapid preparation of low-cost, high-performance WCDs and CDs-based WLEDs.

Carbonized ZIF-8/chitosan biomass imprinted hybrid carbon aerogel for phenol selective removal from wastewater.

In this work, carbonized ZIF-8/chitosan imprinted hybrid carbon aerogel (MIP@CZIF-8/CS) is constructed. The introduction of CZIF-8 effectively optimizes the specific surface area (664 m2 g-1) of imprinted matrix and further enhances the nitrogen atom doping, leading the increased adsorption sites and the formation of superhydrophilic surface. MIP@CZIF-8/CS exhibits a remarkable phenol adsorption capacity (246.6 mg g-1) at pH of 7 and shows excellent selective adsorption towards phenol against its structural analogues. The adsorption kinetics and isotherms of MIP@CZIF-8/CS follow pseudo-second-order and Langmuir-Freundlich models, respectively. Besides, MIP@CZIF-8/CS with monolithic structure can support about 4167 times its own weight. Thanks to its monolithic structure and excellent mechanical stability, MIP@CZIF-8/CS maintains 94 % adsorption capacity after 10 cycle tests and does not contaminate application system. In addition, MIP@CZIF-8/CS can realize the dynamic filtration of phenol in fixed bed column system. The effluent phenol concentration conforms to GB8978-1996, proving its practical application potential.