Designing Atomic Interface in Sb2 S3 /CdS Heterojunction for Efficient Solar Water Splitting.

In the emerging Sb2 S3 -based solar energy conversion devices, a CdS buffer layer prepared by chemical bath deposition is commonly used to improve the separation of photogenerated electron-hole pairs. However, the cation diffusion at the Sb2 S3 /CdS interface induces detrimental defects but is often overlooked. Designing a stable interface in the Sb2 S3 /CdS heterojunction is essential to achieve high solar energy conversion efficiency. As a proof of concept, this study reports that the modification of the Sb2 S3 /CdS heterojunction with an ultrathin Al2 O3 interlayer effectively suppresses the interfacial defects by preventing the diffusion of Cd2+ cations into the Sb2 S3 layer. As a result, a water-splitting photocathode based on Ag:Sb2 S3 /Al2 O3 /CdS heterojunction achieves a significantly improved half-cell solar-to-hydrogen efficiency of 2.78% in a neutral electrolyte, as compared to 1.66% for the control Ag:Sb2 S3 /CdS device. This work demonstrates the importance of designing atomic interfaces and may provide a guideline for the fabrication of high-performance stibnite-type semiconductor-based solar energy conversion devices.

The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification.

CONTEXT: Huangqi Guizhi Wuwu Decoction (HGWD) is effective in treating ischaemic stroke (IS). However, its mechanism of action is still unclear. OBJECTIVE: Network pharmacology integrated with in vivo experiments were used to clarify the underlying mechanisms of HGWD for treating IS. MATERIALS AND METHODS: TCMSP, GeneCards, OMIM and STRING were used to retrieve and construct visual protein interaction networks for the key targets. The AutoDock tool was used for molecular docking between key targets and active compounds. The neuroprotective effect of HGWD were verified in a middle cerebral artery occlusion (MCAO) model rat. The Sprague-Dawley (SD) rats were divided into sham, model, low-dose (5 g/kg, i.g.), high-dose (20 g/kg, i.g.), and nimodipine (20 mg/kg, i.g.) groups once daily for 7 days. The neurological scores, brain infarct volumes, lipid peroxidation, inflammatory cytokines, Nissl bodies, apoptotic neurons, and signalling pathways were all investigated and evaluated in vivo. RESULTS: Network pharmacology identified 117 HGWD targets related to IS and 36 candidate compounds. GO and KEGG analyses showed that HGWD anti-IS effects were mainly associated with PI3K-Akt and HIF-1 signalling pathways. HGWD effectively reduced the cerebral infarct volumes (19.19%), the number of apoptotic neurons (16.78%), and the release of inflammatory cytokines, etc. in MCAO rats. Furthermore, HGWD decreased the levels of HIF-1A, VEGFA, Bax, cleaved caspase-3, p-MAPK1, and p-c-Jun while increasing the expression of p-PI3K, p-AKT1, and Bcl-2. DISCUSSION AND CONCLUSION: This study initially elucidated the mechanism of HGWD anti-IS, which contributed to the further promotion and secondary development of HGWD in clinical practice.

Facile one-step fabrication of Cu-doped carbon dots as a dual-selective biosensor for detection of pyrophosphate ions and measurement of pH.

High-performance determination of pyrophosphate ions (PPi) and pH is an important goal in biological systems. In this work, Cu-doped carbon dots (Cu-CDs) were synthesized rapidly and simply via a one-pot hydrothermal method. The as-obtained Cu-CDs, with an average size of 2.55 nm, exhibit an excitation-independent fluorescence emission and possess desirable functional groups of carboxyl and amine, which can be served as fluorescence nanoprobes for detection of PPi based on surface passivation. Under the optimal condition, the linear range for detection of PPi was 0.05-20 µM, and the corresponding limit of detection (LOD) was 0.013 µM, indicative of a promising assay for the PPi. Moreover, the fluorescent intensity of the Cu-CDs is linear against pH value from 6 to 8.7 in buffer solution, suggesting the feasibility as a pH sensor. The synthesized Cu-CDs coated fluorescent paper indeed can monitor pH in urine with satisfaction by naked eyes through ultraviolet irradiation. The successful detection of PPi and the visual detection of pH value suggest a highly promising application of Cu-CDs in the field of biosensing.

One-step hydrothermal synthesis of nitrogen-doped carbon dots as a super selective and sensitive probe for sensing metronidazole in multiple samples.

A reliable, super selective and sensitive nitrogen-doped carbon dots (N-CDs) nanoprobe that can quantitatively and quickly detect the concentration of metronidazole (MTZ) in multiple samples was built. We first prepared the N-CDs using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC·HCl) as the precursor via a green, facile one-step hydrothermal method. The as-synthesized N-CDs were characterized by a variety of analytical and spectroscopic techniques, which revealed excitation-dependent fluorescence behavior with the maximum excitation and emission wavelengths being 335 and 370 nm, respectively. Significantly, the fluorescence emission of N-CDs underwent initial quenching upon the addition of MTZ via the inner filter effect (IFE), indicating a prospective detection method for MTZ. The linear range for MTZ detection was 0.1-250 µM, and the corresponding limit of detection (LOD) and limit of quantification (LOQ) were calculated to be only 70 nM and 233.33 nM, respectively. Moreover, due to the negligible cytotoxicity and superior biocompatibility, the fabricated N-CDs show a promising prospect for detecting MTZ in living cells. In general, our proposed N-CDs-based fluorescence sensing platform possesses super low LOD and LOQ values, wide linear range, and satisfactory selectivity, and can be applied to the detection of MTZ in multiple real samples.

Nitrogen and copper-doped carbon quantum dots with intrinsic peroxidase-like activity for double-signal detection of phenol.

Herein, a simple and facile one-step hydrothermal carbonization synthesis procedure for the fabrication of N, Cu-doped carbon quantum dots (N, Cu-CQDs) as a peroxidase-mimicking enzyme was reported. The peroxidase-like performance of N, Cu-CQDs was assessed based on the oxidative coupling reaction of phenol with 4-aminoantipyrine (4-AAP) in the presence of hydrogen peroxide (H2O2). The N, Cu-CQDs/4-AAP/H2O2 system was applied to sensing phenol based on double signals of absorption spectra (or colorimetric visualization) as well as fluorescence spectra. The obtained limits of detection (LODs) were as low as 0.12 µM and 0.02 µM, respectively. Moreover, the proposed method was successfully applied to the determination of phenol in sewage with satisfactory recovery. Our results demonstrate that the N, Cu-CQDs/4-AAP/H2O2/phenol sensing system has a great potential prospect for applications in environmental chemistry and biotechnology.

Yellow emission carbon dots for highly selective and sensitive OFF-ON sensing of ferric and pyrophosphate ions in living cells.

A simple "OFF-ON" fluorescent system was proposed for selective and sensitive detection of ferric ion (Fe3+) and pyrophosphate (PPi) in living cells. The method was constructed based on the bright yellow emission of carbon dots (y-CDs), which were prepared using o-phenylenediamine (OPD) as the precursor via a facile hydrothermal treatment. The as-obtained y-CDs, with an average size of 2.6 nm, exhibited an excitation-independent emission peak at 574 nm. The fluorescence of y-CDs can be remarkably quenched by Fe3+ with high selectivity and sensitivity. Interestingly, the quenched fluorescence can be recovered regularly upon addition of PPi, showing a promising detection for PPi. The linear ranges for Fe3+ and PPi detections were 0.05-80 and 0.5-120 µM, respectively, and the corresponding limit of detections (LODs) were 22.1 and 73.9 nM. As we proved the y-CDs have negligible cytotoxicity and excellent biocompatibility, further application to the fluorescence imaging of intracellular Fe3+ and PPi were conducted, suggesting the prepared y-CDs can be used to monitor Fe3+ and PPi variation in living cells. Overall, our developed y-CDs-based OFF-ON switch fluorescent probe has the advantages of simplicity, agility, high sensitivity and selectivity, which provides a promising platform for environmental and biology applications, and paves a new avenue for monitoring the hydrolysis process of adenosine triphosphate disodium salt (ATP) by detection of PPi in organisms.

Thermodynamic and Kinetic Influence of Oxygen Vacancies on the Solar Water Oxidation Reaction of α-Fe2O3 Photoanodes.

To reveal the role of oxygen vacancies in the solar water oxidation of α-Fe2O3 photoanodes, the kinetic and thermodynamic properties that are closely related to the water oxidation reaction of the α-Fe2O3 photoanode containing oxygen vacancies were investigated. Compared with the pristine α-Fe2O3 photoanode, the presence of surface oxygen vacancies can improve the water oxidation activity and stability of the α-Fe2O3 photoanode simultaneously, but the bulk oxygen vacancies have a negative effect on the water oxidation performance of the α-Fe2O3 photoanode. In thermodynamics, our investigations revealed that the presence of surface oxygen vacancies narrows the space charge region width of the α-Fe2O3 photoanode, which could boost the charge separation and transfer efficiency of the α-Fe2O3 photoanode during water oxidation. Because the surface property and hydrophilicity of α-Fe2O3 are modified owing to the presence of surface oxygen vacancies, the water oxidation kinetics of the α-Fe2O3 photoanode with surface oxygen vacancies is obviously boosted. Our findings in the present work provide comprehensive understanding of the thermodynamic and kinetic differences for α-Fe2O3 photoanodes with and without oxygen vacancies for solar water oxidation.

Fabrication of highly active phosphatase-like fluorescent cerium-doped carbon dots for in situ monitoring the hydrolysis of phosphate diesters.

Ce-Doped carbon dots (CeCDs) were fabricated via a one-step hydrothermal carbonization using Ce(NO3)3·6H2O and EDTA·2H2O as precursors, and various experimental techniques were employed to characterize the morphology, structure and composition of the as-obtained CeCDs. Using the disodium salt of bis(4-nitrophenyl)phosphate (BNPP) as a DNA model substrate, mimetic phosphatase activity toward phosphate ester hydrolysis cleavage was investigated. It was found that similar to the catalytic character of the natural enzyme, CeCDs as a hydrolase mimic can exhibit a good catalytic activity for promoting BNPP hydrolysis, in which metal Ce(iii) acts as a center for binding and activation of the metal-bound hydroxide complex as well as a source of nucleophilic metal hydroxides. Additionally, based on the Inner Filter Effect (IFE), fluorescence spectra can be used to monitor the hydrolysis of BNPP using CeCDs, which mimic phosphatase. Thus, the unique properties of the CeCD mimetic phosphatases as well as the IFE sensing strategy would provide an ideal platform to monitor the catalytic phosphate ester hydrolysis processes. Finally, to validate the availability of the established catalytic systems, the CeCDs were further applied for degradation of organophosphorus pesticide chlorpyrifos. The degradation efficiency was estimated to be a satisfactory value of 74.50%, exhibiting a potential application prospect for treatment of the pollutants in the soil and water.

Preparation of palladium/carbon dot composites as efficient peroxidase mimics for H2O2 and glucose assay.

In this study, palladium/carbon dot composites (Pd-CDs) were fabricated via a facial hydrothermal route using ethanediamine and palladium chloride dihydrate as precursors. The obtained Pd-CDs showed an excellent intrinsic peroxidase-like activity, which could catalyze the oxidization of 3,3'5,5'-tetramethylbenzidine with the assistance of hydrogen peroxide (H2O2) and thus resulted in color change, accompanied by an absorption peak which appeared at 652 nm. Such response is H2O2 concentration-dependent and allows for the assay of H2O2 in the range of 0.1 to 30 µM with a limit of detection of 0.03 µM. Simultaneously, by combination of enzymatic oxidation of glucose with glucose oxidase and Pd-CD catalytic reaction, a colorimetric sensing platform was also constructed for glucose detection with high selectivity and sensitivity (limit of detection as low as 0.2 µM). Additionally, the proposed method exhibited capability for determination of glucose in real samples (fruit juice) with satisfactory recovery (98.5-103%), indicating potential application prospects in biochemical analysis.

Manganese(II)-doped carbon dots as effective oxidase mimics for sensitive colorimetric determination of ascorbic acid.

A colorimetric assay is presented for the determination of ascorbic acid (AA). Manganese(II) doped carbon dots (Mn-CDs) were prepared by a convenient hydrothermal route and are shown to possess oxidase-like catalytic ability. They catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by dissolved oxygen to form a blue colored product (oxTMB). AA can reduce blue oxTMB to colorless TMB. The fading of the blue color (measured at 652 nm) can be applied for quantifying AA in the 50 to 2500 nM concentration range and with a 9 nM detection limit. The method was successfully used for the quantitation of AA in real samples. Graphical abstract Schematic representation of a colorimetric assay platform for the sensitive detection of ascorbic acid (AA) in view of inhibitory effect of AA on the 3,3',5,5'-tetramethylbenzidine (TMB) oxidation, benefitting from excellent oxidase-like catalytic activity of manganese(II) doped carbon dots (Mn-CDs).

Insight into the Kinetic Influence of Oxygen Vacancies on the WO3 Photoanodes for Solar Water Oxidation.

Improvements to solar water oxidation performance for WO3 photoanodes due to oxygen vacancies have in general been ascribed to thermodynamic effects. Detailed insights into the water oxidation kinetics for WO3 photoanodes with oxygen vacancies are still lacking. Here, our experimental and computational investigations revealed that the water oxidation pathway on WO3 photoanodes with oxygen vacancies is more inclined to follow the four-hole pathway. This finding reasonably explained the common observations of higher faradaic efficiency for oxygen evolution, better stability, and faster kinetics for water oxidation usually achieved on the WO3 photoanodes with oxygen vacancies.

Chemical doping of the SnSe monolayer: a first-principle calculation.

Using first-principles calculations, non-metallic doping at the Se site and metallic doping at the Sn site in a SnSe monolayer were systematically investigated. Our results showed that for non-metallic doping, the P atom acted as a highly promising p-type doping source due to its low formation energy and shallow acceptor level. However, n-type conductivity was predicted to be unfavorably realized with the substitution of F/Cl/Br atoms as they induced deep donor levels. For metallic doping, the Al atom introduced magnetism into the system and the optical absorption range was broadened due to dopant (Li, Mg, Al) modifications. These results were expected to provide a good reference for the realization of chemical doping in the SnSe monolayer.

Lineage-specific control of TFIIH by MITF determines transcriptional homeostasis and DNA repair.

The melanocytic lineage, which is prominently exposed to ultraviolet radiation (UVR) and radiation-independent oxidative damage, requires specific DNA-damage response mechanisms to maintain genomic and transcriptional homeostasis. The coordinate lineage-specific regulation of intricately intertwined DNA repair and transcription is incompletely understood. Here we demonstrate that the Microphthalmia-associated transcription factor (MITF) directly controls general transcription and UVR-induced nucleotide excision repair by transactivation of GTF2H1 as a core element of TFIIH. Thus, MITF ensures the rapid resumption of transcription after completion of strand repair and maintains transcriptional output, which is indispensable for survival of the melanocytic lineage including melanoma in vitro and in vivo. Moreover, MITF controls c-MYC implicated in general transcription by transactivation of far upstream binding protein 2 (FUBP2/KSHRP), which induces c-MYC pulse regulation through TFIIH, and experimental depletion of MITF results in consecutive loss of CDK7 in the TFIIH-CAK subcomplex. Targeted for proteasomal degradation, CDK7 is dependent on transactivation by MITF or c-MYC to maintain a steady state. The dependence of TFIIH-CAK on sequence-specific MITF and c-MYC constitutes a previously unrecognized mechanism feeding into super-enhancer-driven or other oncogenic transcriptional circuitries, which supports the concept of a transcription-directed therapeutic intervention in melanoma.

Facile fabrication of fluorescent Fe-doped carbon quantum dots for dopamine sensing and bioimaging application.

In this paper, we have presented a novel strategy to fabricate Fe-doped carbon quantum dots (Fe-CQDs) for dopamine sensing applications. The Fe-CQDs are obtained by one step hydrothermal carbonization, using ethylenediamine tetraacetic acid salts and ferric nitrate as the carbon and iron source, which simultaneously incorporates Fe (dopamine-bonding site) and luminescent carbon quantum dots (fluorophores). The added dopamine containing catechol groups might form complexes with Fe ions (doped in CQDs) due to coordination. Subsequently, dopamine was oxidized to generate dopamine-quinone (a known potent electron acceptor) species by ambient O2. Thus, the coordination induced dopamine in proximity to the CQDs, which provided favourable electron acceptors in close proximity to the CQDs and produced high quenching efficiencies. Such fluorescence responses can be used for well quantifying dopamine in the range of 0.01-50 µM with a detection limit of 5 nM (S/N = 3). The proposed sensing system has been successfully used for the assay of dopamine in human urine samples. Preliminary cell image study indicates that the obtained Fe-CQDs possess high photostability and low cytotoxicity, which make them promising for biological applications.

Dipole controlled Schottky barrier in the blue-phosphorene-phase of GeSe based van der Waals heterostructures.

Controlling the interface structure is of utmost importance to regulating the nanoscale Schottky barrier height (SBH). Herein, by using first-principles calculations, the electronic properties of the graphene (G) based blue-phosphorene-phase of GeSe van der Waals (vdW) heterostructures, including M/G and X/G interfaces (M = Ge; X = Se), are systematically investigated. When the layer spacing exceeds the vdW gap, n-type Schottky contacts are formed for both MX/G and XM/G heterojunctions. With the layer spacing decreasing to equilibrium distances, due to different charge transfer across the interface, MX/G and XM/G heterojunctions display n- and p-type Schottky contacts, respectively. Further decreasing the layer distance makes both heterojunctions transit into p-type ones. The layer-spacing-dependent SBHs can be rationalized by the increased charge transfer across the interface and the resulting interfacial dipole enhancement. Enlightened by the finding of dipole-controlled SBHs, using MX as building blocks, two different stacking patterns, i.e., nMX-MX-G and nXM-XM-G (n = 1 and 2), are designed to further modulate the SBH. Interestingly, due to the presence of the intrinsic dipole of MX, it is found that the magnitude and orientation of the interfacial dipole can be artificially engineered. With n increasing from 0 to 2, nMX-MX-G with an X/G interface changes from the n-type Schottky contact to Ohmic contact. The Fermi level meets the conduction band and G shows a p-type doping feature finally. Likewise, transition from p-type Schottky contact to Ohmic contact is observed for the nXM-XM-G with M/G interface, accompanied by the Fermi level touching the valence band and the feature of n-type doping for G. The role of nMX stacking seems like the role of applying an external electric field (E-field): applying positive E-field is equivalent to the increase of dipole moment while negative E-field corresponds to the offset of dipole moment. In brief, the SBHs of GeSe/G contact are found to be tunable which originates from the intrinsic dipole of MX. The predictable SBHs for these kinds of charming built-in dipole systems are expected to be highly desirable in electronic devices.

Chenodeoxycholic Acid from Bile Inhibits Influenza A Virus Replication via Blocking Nuclear Export of Viral Ribonucleoprotein Complexes.

Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous small molecules from host, such as estradiol and omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protection D1 (PD1), were demonstrated to be capable of inhibiting IAV infection. Chenodeoxycholic acid (CDCA), one of the main primary bile acids, is synthesized from cholesterol in the liver and classically functions in emulsification and absorption of dietary fats. Clinically, CDCA has been used in the treatment of patients with cholesterol gallstones for more than five decades. In this study, we showed that CDCA attenuated the replication of three subtypes of influenza A virus, including a highly pathogenic H5N1 strain, in A549 and MDCK cell cultures with IC50 ranging from 5.5 to 11.5 µM. Mechanistically, CDCA effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. In conclusion, as an endogenous physiological small molecule, CDCA can inhibit IAV replication in vitro, at least in part, by blocking vRNP nuclear export, and affords further studies for development as a potential antiviral agent against IAV infections.

Enhanced Photoelectrochemical Water Oxidation Performance on BiVO4 by Coupling of CoMoO4 as a Hole-Transfer and Conversion Cocatalyst.

Manipulation of interfacial charge separation and transfer is one of the primary breakthroughs to improve the water oxidation activity and stability of BiVO4 photoanode. In the present work, a CoMoO4-coupled BiVO4 (BiVO4/CoMoO4) film was designed and prepared as the photoanode for photoelectrochemical (PEC) water oxidation. Compared with the bare BiVO4 film, obviously improved PEC water oxidation performance was observed on the BiVO4/CoMoO4 film. Specifically, a higher water oxidation photocurrent density of 3.04 mA/cm2 at 1.23 V versus RHE was achieved on the BiVO4/CoMoO4 photoanode, which is of about 220% improvement over bare BiVO4 photoanode (1.34 mA/cm2 at 1.23 V vs RHE). In addition, the BiVO4/CoMoO4 film photoanode was of better stability and faster hole-to-oxygen kinetics for water oxidation, without significant activity attenuation for 6 h of reaction at 0.65 V versus RHE. The enhanced water oxidation performance on the BiVO4/CoMoO4 film photoanode can be ascribed to the synergistic effect of the following factors: (i) thermodynamically, the photogenerated holes of BiVO4 are directionally transferred to CoMoO4 through their physical coupling interface and valance band potential matching; and (ii) kinetically, the transferred holes induce the formation of Co3+-active sites on CoMoO4 that could synergistically oxidize H2O to molecular O2 with stable activity.

Analysis of Single-Cell RNA-Seq Identifies Cell-Cell Communication Associated with Tumor Characteristics.

Tumor ecosystems are composed of multiple cell types that communicate by ligand-receptor interactions. Targeting ligand-receptor interactions (for instance, with immune checkpoint inhibitors) can provide significant benefits for patients. However, our knowledge of which interactions occur in a tumor and how these interactions affect outcome is still limited. We present an approach to characterize communication by ligand-receptor interactions across all cell types in a microenvironment using single-cell RNA sequencing. We apply this approach to identify and compare the ligand-receptor interactions present in six syngeneic mouse tumor models. To identify interactions potentially associated with outcome, we regress interactions against phenotypic measurements of tumor growth rate. In addition, we quantify ligand-receptor interactions between T cell subsets and their relation to immune infiltration using a publicly available human melanoma dataset. Overall, this approach provides a tool for studying cell-cell interactions, their variability across tumors, and their relationship to outcome.

First-Principles Study on the Stabilities, Electronic and Optical Properties of GexSn1-xSe Alloys.

We systematically study, by using first-principles calculations, stabilities, electronic properties, and optical properties of GexSn1-xSe alloy made of SnSe and GeSe monolayers with different Ge concentrations x = 0.0, 0.25, 0.5, 0.75, and 1.0. Our results show that the critical solubility temperature of the alloy is around 580 K. With the increase of Ge concentration, band gap of the alloy increases nonlinearly and ranges from 0.92 to 1.13 eV at the PBE level and 1.39 to 1.59 eV at the HSE06 level. When the Ge concentration x is more than 0.5, the alloy changes into a direct bandgap semiconductor; the band gap ranges from 1.06 to 1.13 eV at the PBE level and 1.50 to 1.59 eV at the HSE06 level, which falls within the range of the optimum band gap for solar cells. Further optical calculations verify that, through alloying, the optical properties can be improved by subtle controlling the compositions. Since GexSn1-xSe alloys with different compositions have been successfully fabricated in experiments, we hope these insights will contribute to the future application in optoelectronics.

Autophosphorylation of the carboxyl-terminal domain is not required for oncogenic transformation by lung-cancer derived EGFR mutants.

Aberrant activation of cancer-derived mutants of the epidermal growth factor receptor (EGFR) is closely associated with cancer pathogenesis and is thought to be mediated through multiple tyrosine phosphorylations within the C-terminal domain. Here, we examined the consequences of the loss of these C-terminal phosphorylation sites on cellular transformation in the context of lung-cancer-derived L858R, exon 19 deletion and exon 20 insertion mutant EGFR. Oncogenic EGFR mutants with substitution of the 10 potential C-terminal tyrosine autophosphorylation sites for phenylalanine (CYF10) were still able to promote anchorage-independent growth in soft agar at levels comparable to the parental L858R or exon19 deletion or exon 20 insertion mutants with intact autophosphorylation sites. Furthermore, these CYF10 mutants retained the ability to transform Ba/F3 cells in the absence of IL-3. Bead-based phosphorylation and immunoprecipitation analyses demonstrated that key EGFR-associated proteins-including Grb2 and PLC-γ-are neither phosphorylated nor bound to CYF10 mutants in transformed cells. Taken together, we conclude that tyrosine phosphorylation is not required for oncogenic activity of lung-cancer-derived mutant EGFR, suggesting these mutants can lead to cellular transformation by an alternative mechanism independent of EGFR phosphorylation.