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1.
J Nanosci Nanotechnol ; 20(4): 2622-2627, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492286

RESUMO

Black TiO2-graphene oxide (GO) nanocomposites are synthesized via the pulsed laser ablating TiO2 powders and GO in deionized water. The simple process enables the preparation of black TiO2 nanoparticles and anchors them onto the GO sheet in one step. The TiO2-GO nanocomposites exhibit greatly enhancement for photocatalytic degradation of Rhodamine B (RB) dye in comparison with the pristine and the ablated black TiO2. The heterojunction structure plays an important role in efficient charge separation, which reduces the recombination of photogenerated electrons and holes. The unique two-dimensional structure of GO enables the composite to have a large specific surface area, and prevents the agglomeration of TiO2 nanoparticles, which are beneficial to the photocatalytic performance of the composite.

2.
Molecules ; 24(19)2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31590393

RESUMO

Coal-based porous materials for supercapacitors were successfully prepared using Taixi anthracite (TXA) by multi-stage activation. The characterization and electrochemical tests of activated carbons (ACs) prepared in different stages demonstrated that the AC from the third-stage activation (ACIII) shows good porous structures and excellent electrochemical performances. ACIII exhibited a fine specific capacitance of 199 F g-1 at a current density of 1 A g-1 in the three-electrode system, with 6 mol L-1 KOH as the electrolyte. The specific capacitance of ACIII remained 190 F g-1 even despite increasing the current density to 5 A g-1, indicating a good rate of electrochemical performance. Moreover, its specific capacitance remained at 98.1% of the initial value after 5000 galvanostatic charge-discharge (GCD) cycle tests at a current density of 1 A g-1, suggesting that the ACIII has excellent cycle performance as electrode materials for supercapacitors. This study provides a promising approach for fabricating high performance electrode materials from high-rank coals, which could facilitate efficient and clean utilization of high-rank coals.

3.
Sci Rep ; 9(1): 14571, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601950

RESUMO

Misfolding of translated proteins occurs in all domains of life. In most cells, misfolded proteins coalesce in discrete aggregates at distinct cellular locations. In many bacteria, including mycobacteria, protein aggregates are located at the cellular pole. Yet the mechanism by which aggregates are sorted to the mycobacterial pole is not known. Here, we show that in Mycobacterium smegmatis, the small heat shock protein HspX plays a critical role in the polar localization of aggregates of a model fluorescent misfolded protein, GLR103. HspX itself has a polar localization, which is dependent on its N-terminal domain. In a strain deleted for hspX, GLR103 is less liable to aggregation and no longer localizes to the pole, and redirecting HspX to the septum radically disrupts the normal polar localization of GLR103 aggregates. To further investigate the role of HspX in native protein aggregation, we performed semi-quantitative mass-spectrometry of mycobacterial protein aggregates in wild-type, hspX-deleted and hspX-overexpressing strains. We identified a subset of proteins that appeared to be HspX-dependent for aggregate formation. Furthermore, we demonstrate that for validated native protein aggregates, sorting to the cellular pole following proteotoxic stress required HspX. In summary, we have identified the cellular function of HspX in Mycobacterium smegmatis as both a pro-aggregase and polar sortase.

4.
Ecotoxicol Environ Saf ; 185: 109711, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31574369

RESUMO

There have been no controlled systematic studies on the dynamic variation of As in soil - soil porewater - root surface (Fe plaques) - rice plant system under alternate wetting and drying (AWD) irrigation. Therefore, effects of continuous flooding (CF) and AWD treatments (2F2D: 2-day flooding followed by 2-day drying; 7F2D: 7-day flooding followed by 2-day drying) on the migration of As from soil to brown rice were studied. Results indicated that As contents in brown rice of AWD treatments (0.03-0.17 mg/kg) were 43.3%-85.0% lower than CF (0.20-0.30 mg/kg). AWD irrigation promoted the transformation of Fe and associated As in rhizosphere soil from highly active forms (H2O and HCl-extracted Fe-bound As) to stable states (oxalate and DCB-extracted Fe-bound As), which decreased the release of As from rhizosphere soil. The dynamic variation of As contents in porewater was described by a dissolution factor (DF) which decreased significantly in AWD treatments and had a significant positive correlation (R2 = 0.83; P < 0.05) with As contents in brown rice. In addition, contents of Fe and associated As on the root surface were about 17.1% and 11.0% higher in AWD treatments than in CF treatment, respectively, and the transfer factor (TF) of As from root surface into root was 22.7% lower in AWD treatments than in CF. In summary, AWD irrigation reduced As contents in porewater through decreasing availability of As in rhizosphere soil; and AWD also reduced the transfer of As into rice roots through promoting As sequestration by Fe plaques on root surface.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31593426

RESUMO

Upconversion nanoparticles (UCNPs) have become competitive materials for bioanalysis, bioimaging, and early diagnosis of diseases, especially cancers. However, traditional upconversion luminescence (UCL) nanosensors are often challenged with complicated covalent modification and relatively poor stability. As efficient energy acceptors in the luminescence resonance energy-transfer (LRET) process, organic dyes exhibit unique advantages such as easy modification and stable property. Herein, a simple and universal bioplatform is constructed for in situ imaging and quantitation of intracellular microRNA-21 (miR-21) using dual-acceptor-based upconversion nanoprobes with enhanced quenching efficiency. In this assay, UCNPs with core-shell structures are synthesized, in which the emitting ions are confined in the shell to take the energy donors and acceptors in close proximity. The complementary DNA (cDNA) that can specifically recognize target miR-21 is labeled with organic dyes TAMRA and black hole quencher as dual acceptors and easily assembled on UCNPs via electrostatic adsorption. Compared with only one acceptor for LRET, two dyes quench more luminescence of UCNPs (>60%), which thus reduce the background and improve the sensitivity. With the enhanced quenching efficiency and simple assembly process, the proposed system is readily applied to in situ imaging of miR-21 in different cancer cells, which further achieves quantification of miR-21 in MCF-7 cells. Therefore, our proposed dual-acceptor-based upconversion nanoplatform opens up new opportunities for sensitive analysis of miRNA and provides potential applications in biomedical and clinical research.

6.
J Colloid Interface Sci ; 558: 21-31, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31580952

RESUMO

Three-dimensional graphitic carbon materials with controllable composition and hierarchically porous structure are promising electrode materials for supercapacitors. In this work, a modified phase inversion method combined with a calcination process was developed to prepare three-dimensional graphene networks embedded with nitrogen-doped carbon nanoparticles. When used as electrode for supercapacitors, the as-prepared material delivered a high capacitance of 431.9 F g-1 at 0.1 A g-1 and 156.8 F g-1 at 20 A g-1, as well as a stable cyclic behavior with no capacitance decay after 5000 cycles. Such a remakable capacitive performance was attributed to its hierarchically porous structure and proper nitrogen doping content (9.68 ±â€¯0.24 at%), which facilitated the migration of electrolyte ions and provided abundant redox active sites for the faradic reactions. The synthetic strategy may be exploited for the rational design and synthesis of new carbon materials with controlled doping level and three-dimensional porous structure.

7.
J Colloid Interface Sci ; 558: 211-219, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31586740

RESUMO

Porous interconnected carbon nanosheets (PICNs) with high electrochemical performance were prepared by doping urea and a co-hydrothermal precursor derived from soybean stalk (SS) and nickel nitrate. The specific surface area and average pore diameter of the as-synthesized PICNs are 2226.29 m2 g-1 and 1.89 nm, and their N and O contents are 5.08% and 9.4%, respectively, which is beneficial for increasing pseudocapacitance. Furthermore, the doping of the metal Ni increases the graphitization degree of the PICNs and promotes the conversion of pyridine-N to graphitized-N. Therefore, the PICNs possess a high specific capacitance of 407 F g-1 at a current density of 0.5 A g-1, a high capacitance retention of 78.62% even at 20 A g-1, and an outstanding cycling stability (over 93% retention rate after 10,000 charge/discharge cycles). Moreover, an energy density of 36.11 W h kg-1 is achieved at a power density of 517.8 W kg-1 during a two-electrode system test, and a retention rate of 87.5% is obtained after 10,000 cycles. This co-hydrothermal treatment as well as nitrogen-doping approach for preparing porous interconnected carbon from SS not only represents an alternative strategy for carbon-based supercapacitor materials but also provides a new option for the utilization of waste SS.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31570405

RESUMO

Colistin is a drug of last resort for the treatment of many multidrug resistant Gram-negative bacteria, including Klebsiella pneumoniae However, bacteria readily acquire resistance to this antibiotic via lipopolysaccharide modifications caused by spontaneous mutations or from enzymes acquired by lateral gene transfer. The fitness cost associated with these modifications remains poorly understood. In this study, we show that colistin-resistant K. pneumoniae are more susceptible to killing by a newly isolated lytic phage than the colistin sensitive parent strain. We observe this behavior for colistin-resistance conferred by a horizontally transferred mcr-1 containing plasmid and also from the inactivation of the chromosomal gene mgrB By measuring zeta potentials, we found that the phage particles were negatively charged at neutral pH and that colistin-resistant bacteria had less negative zeta potentials than did wildtype. These results suggest that the decreased negative surface charge of colistin-resistant cells lowers the electrostatic repulsion between the phage and bacteria, thereby promoting phage adherence and subsequent infection. To further explore this, we tested the effect of phage treatment on K. pneumoniae growing in several different environments. We found that colistin-resistant cells were more susceptible to phage than were the wildtype cells when growing in biofilms or infected moth larvae and when colonizing the mammalian gut. A better understanding of these fitness costs may lead to new treatment approaches that minimize the emergence and spread of colistin-resistant pathogens in human and environmental reservoirs.

9.
Adv Mater ; : e1903796, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573709

RESUMO

Electrocatalytic CO2 reduction (ECR) is a promising technology to simultaneously alleviate CO2 -caused climate hazards and ever-increasing energy demands, as it can utilize CO2 in the atmosphere to provide the required feedstocks for industrial production and daily life. In recent years, substantial progress in ECR systems has been achieved by the exploitation of various novel electrode materials. The anodic materials and cathodic catalysts that have, respectively, led to high-efficiency energy input and effective heterogenous catalytic conversion in ECR systems are comprehensively reviewed. Based on the differences in the nature of energy sources and the role of materials used at the anode, the fundamentals of ECR systems, including photo-anode-assisted ECR systems and bio-anode-assisted ECR systems, are explained in detail. Additionally, the cathodic reaction mechanisms and pathways of ECR are described along with a discussion of different design strategies for cathode catalysts to enhance conversion efficiency and selectivity. The emerging challenges and some perspective on both anode materials and cathodic catalysts are also outlined for better development of ECR systems.

10.
Biometrics ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489979

RESUMO

Mapping of disease incidence has long been of importance to epidemiology and public health. In this paper, we consider identification of clusters of spatial units with elevated disease rates and develop a new approach that estimates the relative disease risk in association with potential risk factors and simultaneously identifies clusters corresponding to elevated risks. A heterogeneity measure is proposed to enable the comparison of a candidate cluster and its complement under a pair of complementary models. A quasi-likelihood procedure is developed for estimating the model parameters and identifying the clusters. An advantage of our approach over traditional spatial clustering methods is the identification of clusters that can have arbitrary shapes due to abrupt or non-contiguous changes while accounting for risk factors and spatial correlation. Asymptotic properties of the proposed methodology are established and a simulation study shows empirically sound finite-sample properties. The mapping and clustering of enterovirus 71 infection in Taiwan are carried out for illustration. This article is protected by copyright. All rights reserved.

11.
J Synchrotron Radiat ; 26(Pt 5): 1448-1461, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31490132

RESUMO

The Karabo distributed control system has been developed to address the challenging requirements of the European X-ray Free Electron Laser facility, including complex and custom-made hardware, high data rates and volumes, and close integration of data analysis for distributed processing and rapid feedback. Karabo is a pluggable, distributed application management system forming a supervisory control and data acquisition environment as part of a distributed control system. Karabo provides integrated control of hardware, monitoring, data acquisition and data analysis on distributed hardware, allowing rapid control feedback based on complex algorithms. Services exist for access control, data logging, configuration management and situational awareness through alarm indicators. The flexible framework enables quick response to the changing requirements in control and analysis, and provides an efficient environment for development, and a single interface to make all changes immediately available to operators and experimentalists.

12.
Eur J Surg Oncol ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31481274

RESUMO

OBJECTIVE: We seek to explore the clinical significance of serum squamous cell carcinoma antigen (SCC-Ag) and the optimal cut-off value for predicting tumor recurrence and survival in operable cervical squamous cell carcinoma patients. METHODS: A total of 3471 patients with cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The cut-off value of serum SCC-Ag for tumor recurrence was calculated using the receiver operating characteristic (ROC) curve. The progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed. RESULTS: The optimal cut-off value of serum SCC-Ag level for predicting tumor recurrence was calculated and set at 2.75 ng/mL. Compared to the value of 1.5 ng/mL used in clinical practice, our results showed that serum SCC-Ag level >2.75 ng/mL was closely related to extrapelvic metastases in relapsed patients (P = 0.035). Multivariate analysis showed that neither serum SCC-Ag level >1.5 ng/mL nor serum SCC-Ag level >2.75 ng/mL was independent risk factors for PFS and OS in all patients. However, among 964 patients with at least one high-risk factor (parametrial invasion, vaginal margin invasion and lymph node metastasis), serum SCC-Ag level > 2.75 ng/mL, instead of serum SCC-Ag level > 1.5 ng/mL, could be used as an independent factor affecting PFS (P = 0.018). CONCLUSION: Preoperative serum SCC-Ag level > 2.75 ng/mL is closely related to extrapelvic recurrence, and is an independent factor for tumor recurrence and survival in cervical squamous cell carcinoma patients with high-risk factors.

13.
Chin J Nat Med ; 17(7): 506-516, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514982

RESUMO

MSC transplantation has been explored as a new clinical approach to stem cell-based therapies for bone diseases in regenerative medicine due to their osteogenic capability. However, only a small population of implanted MSC could successfully reach the injured areas. Therefore, enhancing MSC migration could be a beneficial strategy to improve the therapeutic potential of cell transplantation. Catharmus tinctorius volatile oil (CTVO) was found to facilitate MSC migration. Further exploration of the underlying molecular mechanism participating in the pro-migratory ability may provide a novel strategy to improve MSC transplantation efficacy. This study indicated that CTVO promotes MSC migration through enhancing ROCK2 mRNA and protein expressions. MSC migration induced by CTVO was blunted by ROCK2 inhibitor, which also decreased myosin light chain (MLC) phosphorylation. Meanwhile, the siRNA for ROCK2 inhibited the effect of CTVO on MSC migration ability and attenuated MLC phosphorylation, suggesting that CTVO may promote BMSC migration via the ROCK2/MLC signaling. Taken together, this study indicates that C. tinctorius volatile oil could enhance MSC migration via ROCK2/MLC signaling in vitro. C. tinctorius volatile oil-targeted therapy could be a beneficial strategy to improve the therapeutic potential of cell transplantation for bone diseases in regenerative medicine.

14.
Lancet ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31492501

RESUMO

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

15.
Org Lett ; 21(18): 7630-7634, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31503499

RESUMO

We present a novel Cu-catalyzed aromatic metamorphosis of 3-aminoindazoles via oxidative cleavage of two C-N bonds of 3-aminoindazoles. This unprecedented reactivity of 3-aminoindazoles allows one to forge diverse nitrile-containing triphenylenes in decent yields via generation of the cyano group in situ. The current study reveals that 3-aminoindazoles could be harnessed as radical precursors via oxidative denitrogenation, the reaction mechanism of which was supported by density functional theory calculations.

16.
Chemistry ; 2019 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-31544271

RESUMO

A visible light-driven radical silylative cyclization of aza-1,6-dienes featuring an acrylonitrile or acrylate moiety and an electron-neutral olefin was developed, which allows for stereoselective synthesis of densely functionalized piperidines in a highly atom-economical manner. Depending on the substitution pattern of the electron-neutral olefin, poor to excellent diastereoselectivity was observed. It was suggested that the 6-exo-trig cyclization was initiated by a chemoselective addition of silyl radical toward electron-deficient olefin and the geometry of the remaining olefin is closely associated with the cis-stereoselectivity. DFT calculations supported that a transition state with a cyano group locating at the axial position of the forming piperidine ring might be involved, in which either the increase of 1,3-diaxial repulsion or the lack of hydrogen bonding interaction will diminish diastereoselectivity.

17.
Mol Med Rep ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31545441

RESUMO

p53 and mouse double minute 2 homolog (MDM2) serve key regulatory roles in the apoptosis of synovial cells. The present study aimed to investigate the effects of electroacupuncture (EA) at the 'Zusanli' (ST36) and 'Xuanzhong' (GB39) acupoints on apoptosis in an adjuvant arthritis (AA) rat model. A total of 40 male Sprague­Dawley rats were randomly divided into Control, AA, AA + EA and AA + sham EA groups (n=10 rats in each group). Rats in all the groups, with the exception of the control group, were injected with Complete™ Freund's adjuvant into the bilateral hindlimb footpad to establish the AA model. Rats in the AA + EA group were treated with EA at the ST36 and GB39 acupoints. Rats in the AA + sham EA group were treated with percutaneous electrical stimulation at a position of 5 mm away from the ST36 and GB39 acupoints. The arthritis index scores and hindlimb paw volumes of the rats in each group were recorded. Subsequently, pathological changes in the synovial tissue were evaluated by hematoxylin and eosin (H&E) staining, and the apoptotic rate of the synovial cells was detected by TUNEL staining. In addition, the expression levels of the apoptosis­associated proteins, Bax, phorbol­12­myristate­13­acetate­induced protein 1 (Noxa) and p53 upregulated modulator of apoptosis (PUMA), were determined by western blot analysis. The expression of both the gene and protein of p53 and MDM2 in synovial tissue was detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analysis, respectively. The results indicated that the arthritis index scores and hindlimb paw volumes upon EA stimulation were significantly decreased compared with those of the AA group (P<0.05). H&E staining revealed that the synovial inflammation of EA stimulation was significantly decreased compared with the AA group (P<0.05). The TUNEL assay results indicated that the apoptotic rate of synovial cells in the AA + EA group was significantly increased compared with that in the AA group (P<0.05). Furthermore, an increased expression of proapoptotic proteins was confirmed by the increased expression levels of Bax, Noxa and PUMA in the AA + EA group. The results of RT­qPCR and western blot analysis demonstrated that, compared with the AA group, EA stimulation led to a marked increase in p53 (P<0.05) and a significant decrease in MDM2 (P<0.05) gene and protein expression. Taken together, these results demonstrated that EA performed on the ST36 and GB39 acupoints led to a significant amelioration in AA injury of model rats, by regulating the p53 signaling pathway and inducing apoptosis.

19.
iScience ; 19: 1214-1224, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31551198

RESUMO

Pincer complexes are a remarkably versatile family benefited from their stability, diversity, and tunability. Many of them contain aromatic organic rings at the periphery, and aromaticity plays an important role in their stability and properties, whereas their metallacyclic cores are not aromatic. Herein, we report rhodapentalenes, which can be viewed as pincer complexes in which the metallacyclic cores exhibit considerable aromatic character. Rhodapentalenes show good thermal stability, although the rhodium-carbon bonds in such compounds are fragile. Experimental and computational studies suggest that the stabilization of rigid CCC pincer architectures together with an intrinsic aromaticity is vital for these metallacyclic rhodium species. Dearomatization-aromatization reactions, corresponding to metal-ligand cooperation of classical aromatic pincer complexes, were observed in this system. These findings suggest a new concept for pincer chemistry, the internal aromaticity involving metal d-orbitals, which would be useful for exploiting the nature of construction motif and inspire further applications.

20.
Cancer Res ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551362

RESUMO

Molecular characterization of lung squamous cell carcinoma (LUSC), one of the major subtypes of lung cancer, has not sufficiently improved its non-stratified treatment strategies over decades. Accumulating evidence suggests that lineage-specific transcriptional regulators control differentiation states during cancer evolution, and underlie their distinct biological behaviors. In this study, by investigating the super-enhancer landscape of LUSC, we identified a previously undescribed 'neural' subtype defined by Sox2 and a neural lineage factor Brn2, as well as the classical LUSC subtype defined by Sox2 and its classical squamous partner p63. Robust protein-protein interaction and genomic co-occupancy of Sox2 and Brn2, in place for p63 in the classical LUSC, indicated their transcriptional cooperation imparting this unique lineage state in the 'neural' LUSC. Forced expression of p63 downregulated Brn2 in the 'neural' LUSC cells and invoked the classical LUSC lineage with more squamous/epithelial features, which were accompanied by increased activities of ErbB/Akt and MAPK-ERK pathways suggesting differential dependency. Collectively, our data demonstrate heterogeneous cell lineage states of LUSC featured by Sox2 cooperation with Brn2 or p63, for which distinct therapeutic approaches may be warranted.

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