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1.
Nano Lett ; 24(19): 5791-5798, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38695400

RESUMO

The second-order nonlinear transport illuminates a frequency-doubling response emerging in quantum materials with a broken inversion symmetry. The two principal driving mechanisms, the Berry curvature dipole and the skew scattering, reflect various information including ground-state symmetries, band dispersions, and topology of electronic wave functions. However, effective manipulation of them in a single system has been lacking, hindering the pursuit of strong responses. Here, we report on the effective manipulation of the two mechanisms in a single graphene moiré superlattice, AB-BA stacked twisted double bilayer graphene. Most saliently, by virtue of the high tunability of moiré band structures and scattering rates, a record-high second-order transverse conductivity ∼ 510 µm S V-1 is observed, which is orders of magnitude higher than any reported values in the literature. Our findings establish the potential of electrically tunable graphene moiré systems for nonlinear transport manipulations and applications.

2.
Nano Lett ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747346

RESUMO

Moiré superlattices have become a fertile playground for topological Chern insulators, where the displacement field can tune the quantum geometry and Chern number of the topological band. However, in experiments, displacement field engineering of spontaneous symmetry-breaking Chern bands has not been demonstrated. Here in a rhombohedral trilayer graphene moiré superlattice, we use a thermodynamic probe and transport measurement to monitor the Chern number evolution as a function of the displacement field. At a quarter filling of the moiré band, a novel Chern number of three is unveiled to compete with the well-established number of two upon turning on the electric field and survives when the displacement field is sufficiently strong. The transition can be reconciled by a nematic instability on the Fermi surface due to the pseudomagnetic vector field potentials associated with moiré strain patterns. Our work opens more opportunities to active control of Chern numbers in van der Waals moiré systems.

3.
World J Nucl Med ; 23(1): 33-42, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38595841

RESUMO

Objective The purpose of this study was to evaluate the prognostic significance of corrected baseline metabolic parameters in fluorodeoxyglucose positron emission tomography imaging ( 18 F-FDG PET/CT) for 3-year progression-free survival (PFS) in patients with primary diffuse large B cell lymphoma (DLBCL). Patients and Methods Retrospective clinical and pathological data were collected for 199 patients of DLBCL diagnosed between January 2018 and January 2021. All patients underwent 18 F-FDG PET/CT scans without any form of treatment. The corrected maximum standardized uptake value (corSUVmax), corrected mean standardized uptake value (corSUVmean), corrected whole-body tumor metabolic volume sum (corMTVsum), and corrected total lesion glycolysis of whole body (corTLGtotal) were corrected using the SUVmean in a 1-cm diameter mediastinal blood pool (MBP) from the descending thoracic aorta of patients. Kaplan-Meier survival curves and Cox regression were used to examine the predictive significance of corrected baseline metabolic parameters on 3-year PFS of patients. The incremental values of corrected baseline metabolic parameters were evaluated by using Harrell's C-indices, receiver operating characteristic, and Decision Curve Analysis. Results The multivariate analysis revealed that only the National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and corMTVsum had an effect on 3-year PFS of patients ( p < 0.05, respectively). The Kaplan-Meier survival analysis demonstrated significant differences in PFS between the risk groups classified by corSUVsum, corMTVsum, and corTLGtotal (log-rank test, p < 0.05). The predictive model composed of corMTVsum and corTLGtotal surpasses the predictive performance of the model incorporating MTVsum and TLGtotal. The optimal performance was observed when corMTVsum was combined with NCCN-IPI, resulting in a Harrell's C index of 0.785 and area under the curve values of 0.863, 0.891, and 0.947 for the 1-, 2-, and 3-year PFS rates, respectively. Conclusion The corMTVsum offers significant prognostic value for patients with DLBCL. Furthermore, the combination of corMTVsum with the NCCN-IPI can provide an accurate prediction of the prognosis.

4.
Phys Rev Lett ; 132(5): 056601, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38364175

RESUMO

In this Letter, we theoretically explore the physical properties of a new type of three-dimensional graphite moiré superlattice, the bulk alternating twisted graphite (ATG) system with homogeneous twist angle, which is grown by in situ chemical vapor decomposition method. Compared to twisted bilayer graphene (TBG), the bulk ATG system is bestowed with an additional wave vector degree of freedom due to the extra dimensionality. As a result, when the twist angle of bulk ATG is smaller than twice of the magic angle of TBG, there always exist "magic momenta" which host topological flat bands with vanishing in-plane Fermi velocities. Most saliently, when the twist angle is relatively large, a dispersionless three-dimensional zeroth Landau level would emerge in the bulk ATG, which may give rise to robust three-dimensional quantum Hall effects and unusual quantum-Hall physics over a large range of twist angles.

5.
Sci Rep ; 14(1): 1950, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38253674

RESUMO

Double core-holes (DCHs) show remarkable and sensitive effects for understanding electron correlations and coherence. With advanced modulation of x-ray free-electron laser (XFEL) facility, we propose the forthcoming all-attosecond XFEL pump-probe spectroscopy can decipher the hidden photon-initiated dynamics of DCHs. The benchmark case of neon is investigated, and norm-nonconserving Monte-Carlo wavefunction method simulates non-Hermitian dynamics among vast states, which shows superiority in efficiency and reliability. In our scheme, population transfer to DCHs is sequentially irradiated by pump and probe laser. By varying time delay, Stark shifts and quantum path interference of resonant lines sensitively emerge at specific interval of two pulses. These ubiquitous multi-channel effects are also observed in phase-fluctuating pulses, derived from extra phases of impulsive Raman processes by pump laser. Non-perturbation absorption/emission verifies the uniquely interchangeable role of two pules in higher intensity. Our results reveal sensitive and robust responses on pulse parameters, which show potential capacity for XFEL attosecond pulse diagnosis and further attosecond-timescale chemical analysis.

7.
Small ; 20(1): e2304502, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37649185

RESUMO

Reduced graphene oxide (rGO) has garnered extensive attention as electrodes, sensors, and membranes, necessitating the efficient reduction of graphene oxide (GO) for optimal performance. In this work, a swift reduction of GO that involves bringing GO foam in contact with semi-molten metals like tin (Sn) and lithium (Li) is presented. These findings reveal that the electrical resistance of GO foam is significantly diminished by its interaction with these metals, even in dry air. Taking inspiration from this technique, Sn foil is employed to encase the GO foam, followed by a calcination in 15 vol% H2 /Ar environment at 235 °C to fabricate the rGO, which demonstrates a remarkably lower electrical resistivity of 0.42 Ω cm when compared to the chemically reduced GO via hydrazine hydrate (650 Ω cm). The reduction mechanism entails the migration of Sn on GO and its subsequent reaction with oxygen functional groups. SnO/Sn(OH)2 formed from the reaction can be subsequently reversed through reduction by H2 to Sn. Utilizing this rGO as the host material for a sulfur cathode, a lithium-sulfur battery is constructed that displays a specific capacity of 1146 mAh g-1 and maintains a capacity retention of 68.4% after 300 cycles at a rate of 0.2 C.

8.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37925610

RESUMO

The increased production of high-quality oocytes lies at the heart of the search to accelerate the reproduction of high-quality breeding livestock using assisted reproductive technology. Follicle-stimulating hormone (FSH) maintains the arrest of oocyte meiosis during early follicular development in vivo and promotes the synchronous maturation of nucleus and cytoplasm to improve oocyte quality. However, the mechanism by which FSH maintains meiotic arrest in oocytes is still not fully understood. Oocytes spontaneously resume meiosis once released from the arrested state. In this study, we isolated goat antral follicles with a diameter of 2.0-4.0 mm, cultured them in vitro either with or without added FSH, and finally collected the oocytes to observe their meiotic state. The results showed that FSH effectively inhibited the meiotic recovery of oocytes in follicles [4 h: control (n = 84) vs. with FSH (n = 86), P = .0115; 6 h: control (n = 86) vs. FSH (n = 85), P = 0.0308; and 8 h: control (n = 95) vs. FSH (n = 101), P = 0.0039]. FSH significantly inhibited the downregulation of natriuretic peptide receptor 2 (NPR2) expression and cyclic guanosine monophosphate (cGMP) synthesis during follicular culture in vitro (P < 0.05). Further exploration found that FSH promoted the synthesis of 17ß-estradiol (E2) (P = .0249 at 4 h and P = .0039 at 8 h) and maintained the expression of the estrogen nuclear receptor ERß, but not the estrogen nuclear receptor ERα during follicle culture in vitro (P = .0190 at 2 h, and P = .0100 at 4 h). In addition, E2/ER (estrogen nuclear receptors ERα and ERß) mediated the inhibitory effect of FSH on the downregulation of NPR2 expression and cGMP synthesis, ultimately preventing the meiotic recovery of oocytes (P < .05). In summary, our study showed that FSH-induced estrogen production in goat follicles, and the E2/ER signaling pathway, both mediated meiotic arrest in FSH-induced goat oocytes.


Obtaining a greater number of high-quality oocytes to accelerate the reproduction of high-quality breeding livestock using artificial-assisted reproductive technology remains a pressing problem in animal husbandry and requires further research into the mechanism of oocyte maturation. We investigated the regulatory action of follicle-stimulating hormone (FSH) on the meiosis of oocytes during goat follicle culture in vitro. We found that FSH promoted 17ß-estradiol (E2) synthesis and that E2/ER (estrogen nuclear receptors ERα and ERß)-mediated FSH regulation of the CNP/NPR2 (C-type natriuretic peptide/natriuretic peptide receptor 2) signaling pathway and oocyte meiosis in goat follicles. This study provided an improved theoretical foundation for the increased production of high-quality oocytes using in vitro culture methods.


Assuntos
Receptor alfa de Estrogênio , Hormônio Foliculoestimulante , Animais , Hormônio Foliculoestimulante/farmacologia , Hormônio Foliculoestimulante/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptores de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Cabras , Oócitos , Transdução de Sinais , Estrogênios/metabolismo , Meiose
9.
Cancer Lett ; : 216514, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38036040

RESUMO

CD103+ DC is crucial for antitumor immune response. As a promising local therapy on cancers, nanosecond pulsed electric field (nsPEF) has been widely reported to stimulate anti-tumor immune response, but the underlying relationship between intratumoral CD103+ DC and nsPEF treatment remains enigmatic. Here, we focused on the behavior of CD103+ DC in response to nsPEF treatment and explored the underlying mechanism. We found that the nsPEF treatment led to the activation and accumulation of CD103+ DC in tumor. Depletion of CD103+ DC via Batf3-/- mice demonstrated CD103+ DC was necessary for intratumoral CD8+ T cell infiltration and activation in response to nsPEF treatment. Notably, NK cells recruited CD103+ DC into nsPEF-treated tumor through CCL5. Inflammatory array revealed CD103+ DC-derived IL-12 mediated the CCL5 secretion in NK cells. In addition, the boosted activation and infiltration of intratumoral CD103+ DC were abolished by cGAS-STING pathway inhibition, following IL-12 and CCL5 decreasing. Furthermore, nsPEF treatment promoting CD103+ DC-mediated antitumor response enhanced the effects of CD47 blockade strategy. Together, this study uncovers an unprecedented role for CD103+ DC in nsPEF treatment-elicited antitumor immune response and elucidates the underlying mechanisms.

10.
Nat Commun ; 14(1): 5550, 2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689704

RESUMO

Graphene has aroused great attention due to the intriguing properties associated with its low-energy Dirac Hamiltonian. When graphene is coupled with a correlated insulating substrate, electronic states that cannot be revealed in either individual layer may emerge in a synergistic manner. Here, we theoretically study the correlated and topological states in Coulomb-coupled and gate-tunable graphene-insulator heterostructures. By electrostatically aligning the electronic bands, charge carriers transferred between graphene and the insulator can yield a long-wavelength electronic crystal at the interface, exerting a superlattice Coulomb potential on graphene and generating topologically nontrivial subbands. This coupling can further boost electron-electron interaction effects in graphene, leading to a spontaneous bandgap formation at the Dirac point and interaction-enhanced Fermi velocity. Reciprocally, the electronic crystal at the interface is substantially stabilized with the help of cooperative interlayer Coulomb coupling. We propose a number of substrate candidates for graphene to experimentally demonstrate these effects.

11.
BMJ Open ; 13(8): e072632, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37550031

RESUMO

OBJECTIVES: The prognosis of invasive micropapillary carcinoma (IMPC) of the breast is determined by many clinicopathological factors. This study aims to identify prognostic factors and develop reliable nomogram to predict the overall survival (OS) in patients with IMPC. DESIGN: Log-rank test and Cox proportional hazards analysis were used to identify variables and construct a nomogram based on the training cohort. C-index and calibration curves were performed to evaluate the performance of the model in the training cohort and validation cohorts. SETTING: We collected the patient data from the Surveillance, Epidemiology and End Results (SEER) database. This database holds data related to the cancer incidence from 18 population-based cancer registries in the USA. PARTICIPANTS: The SEER database was used to screen 754 eligible patients as the study cohort. The whole cohort was randomly divided into a training cohort (n=377) and a validation cohort (n=377). RESULTS: Age at diagnosis, hormone receptors, number of positive regional lymph nodes and clinical stage were independent prognostic factors for patients with IMPC. The calibration curves presented excellent consistency between the actual and nomogram-predict survival probabilities in the training and validation cohorts. The C-index values of the nomogram were 0.794 and 0.774 for OS in the training and validation cohorts, respectively. CONCLUSIONS: The novel nomogram provides new insights of the risk of each prognostic factor and can assist doctors in predicting the 1-year, 3-year and 5-year OS in patients with IMPC.


Assuntos
Carcinoma , Nomogramas , Humanos , Prognóstico , Fatores de Risco
12.
Nat Commun ; 14(1): 4892, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37580381

RESUMO

A representative class of kagome materials, AV3Sb5 (A = K, Rb, Cs), hosts several unconventional phases such as superconductivity, [Formula: see text] non-trivial topological states, and electronic nematic states. These can often coexist with intertwined charge-density wave states. Recently, the discovery of the isostructural titanium-based single-crystals, ATi3Bi5 (A = K, Rb, Cs), which exhibit similar multiple exotic states but without the concomitant charge-density wave, has opened an opportunity to disentangle these complex states in kagome lattices. Here, we combine high-resolution angle-resolved photoemission spectroscopy and first-principles calculations to investigate the low-lying electronic structure of RbTi3Bi5. We demonstrate the coexistence of flat bands and several non-trivial states, including type-II Dirac nodal lines and [Formula: see text] non-trivial topological surface states. Our findings also provide evidence for rotational symmetry breaking in RbTi3Bi5, suggesting a directionality to the electronic structure and the possible emergence of pure electronic nematicity in this family of kagome compounds.

13.
Nano Lett ; 23(15): 7008-7013, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37466311

RESUMO

The recent discovery of strongly correlated phases in twisted transition-metal dichalcogenides (TMDs) highlights the significant impact of twist-induced modifications on electronic structures. In this study, we employed angle-resolved photoemission spectroscopy with submicrometer spatial resolution (µ-ARPES) to investigate these modifications by comparing valence band structures of twisted (5.3°) and nontwisted (AB-stacked) bilayer regions within the same WSe2 device. Relative to the nontwisted region, the twisted area exhibits pronounced moiré bands and ∼90 meV renormalization at the Γ-valley, substantial momentum separation between different layers, and an absence of flat bands at the K-valley. We further simulated the effects of lattice relaxation, which can flatten the Γ-valley edge but not the K-valley edge. Our results provide a direct visualization of twist-induced modifications in the electronic structures of twisted TMDs and elucidate their valley-dependent responses to lattice relaxation.

14.
Nano Lett ; 23(12): 5625-5633, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37310876

RESUMO

Kagome superconductors AV3Sb5 (A = K, Rb, Cs) provide a fertile playground for studying intriguing phenomena, including nontrivial band topology, superconductivity, giant anomalous Hall effect, and charge density wave (CDW). Recently, a C2 symmetric nematic phase prior to the superconducting state in AV3Sb5 drew enormous attention due to its potential inheritance of the symmetry of the unusual superconductivity. However, direct evidence of the rotation symmetry breaking of the electronic structure in the CDW state from the reciprocal space is still rare, and the underlying mechanism remains ambiguous. The observation shows unconventional unidirectionality, indicative of rotation symmetry breaking from six-fold to two-fold. The interlayer coupling between adjacent planes with π-phase offset in the 2 × 2 × 2 CDW phase leads to the preferred two-fold symmetric electronic structure. These rarely observed unidirectional back-folded bands in KV3Sb5 may provide important insights into its peculiar charge order and superconductivity.

15.
Small ; 19(36): e2300286, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37162459

RESUMO

Lithium-sulfur (Li-S) battery has been considered as a strong contender for commercial aerospace battery, but the commercialization requires Ah-level pouch cells with both efficient discharge at high rates and ultra-high energy density. In this paper, the application of lithium-sulfur batteries for powering drones by using the cathode of highly dispersed sulfur nanoparticles with well-controlled particle sizes have been realized. The sulfur nanoparticles are prepared by a precipitation method in an eco-friendly and efficient way, and loaded on graphene oxide-cetyltrimethylammonium bromide by molecular grafting to realize a large-scale fabrication of sulfur-based cathodes with superior electrochemical performance. A button cell based on the cathode exhibits an excellent discharge capacity of 62.8 mAh cm-2 at a high sulfur loading of 60 mg cm-2 (i.e., 1046.7 mAh g-1 ). The assembled miniature pouch cell (PCmini) shows a discharge capacity of 130 mAh g-1 , while the formed Ah-level pouch cell (PCAh) achieves energy density of 307 Wh kg-1 at 0.3C and 92 Wh kg-1 at 4C. Especially, a four-axis propeller drone powered by the PC has successfully completed a long flight (>3 min) at high altitudes, demonstrating the practical applicability as aviation batteries.

16.
Sci Bull (Beijing) ; 68(11): 1127-1133, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37210331

RESUMO

We report an observation of quantum oscillations (QOs) in the correlated insulators with valley anisotropy of twisted double bilayer graphene (TDBG). The anomalous QOs are best captured in the magneto resistivity oscillations of the insulators at v = -2, with a period of 1/B and an oscillation amplitude as high as 150 kΩ. The QOs can survive up to ∼10 K, and above 12 K, the insulating behaviors are dominant. The QOs of the insulator are strongly D dependent: the carrier density extracted from the 1/B periodicity decreases almost linearly with D from -0.7 to -1.1 V/nm, suggesting a reduced Fermi surface; the effective mass from Lifshitz-Kosevich analysis depends nonlinearly on D, reaching a minimal value of 0.1 me at D = ∼ -1.0 V/nm. Similar observations of QOs are also found at v = 2, as well as in other devices without graphite gate. We interpret the D sensitive QOs of the correlated insulators in the picture of band inversion. By reconstructing an inverted band model with the measured effective mass and Fermi surface, the density of state at the gap, calculated from thermal broadened Landau levels, agrees qualitatively with the observed QOs in the insulators. While more theoretical understandings are needed in the future to fully account for the anomalous QOs in this moiré system, our study suggests that TDBG is an excellent platform to discover exotic phases where correlation and topology are at play.


Assuntos
Excipientes , Grafite , Humanos , Anisotropia , Inversão Cromossômica , Meio Ambiente
17.
Comput Methods Programs Biomed ; 234: 107506, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37003041

RESUMO

OBJECTIVE: Multimodal medical fusion images have been widely used in clinical medicine, computer-aided diagnosis and other fields. However, the existing multimodal medical image fusion algorithms generally have shortcomings such as complex calculations, blurred details and poor adaptability. To solve this problem, we propose a cascaded dense residual network and use it for grayscale and pseudocolor medical image fusion. METHODS: The cascaded dense residual network uses a multiscale dense network and a residual network as the basic network architecture, and a multilevel converged network is obtained through cascade. The cascaded dense residual network contains 3 networks, the first-level network inputs two images with different modalities to obtain a fused Image 1, the second-level network uses fused Image 1 as the input image to obtain fused Image 2 and the third-level network uses fused Image 2 as the input image to obtain fused Image 3. The multimodal medical image is trained through each level of the network, and the output fusion image is enhanced step-by-step. RESULTS: As the number of networks increases, the fusion image becomes increasingly clearer. Through numerous fusion experiments, the fused images of the proposed algorithm have higher edge strength, richer details, and better performance in the objective indicators than the reference algorithms. CONCLUSION: Compared with the reference algorithms, the proposed algorithm has better original information, higher edge strength, richer details and an improvement of the four objective SF, AG, MZ and EN indicator metrics.


Assuntos
Processamento de Imagem Assistida por Computador , Imagem Multimodal , Processamento de Imagem Assistida por Computador/métodos , Imagem Multimodal/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Diagnóstico por Computador
18.
Nat Commun ; 14(1): 2136, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37059725

RESUMO

The realization of graphene gapped states with large on/off ratios over wide doping ranges remains challenging. Here, we investigate heterostructures based on Bernal-stacked bilayer graphene (BLG) atop few-layered CrOCl, exhibiting an over-1-GΩ-resistance insulating state in a widely accessible gate voltage range. The insulating state could be switched into a metallic state with an on/off ratio up to 107 by applying an in-plane electric field, heating, or gating. We tentatively associate the observed behavior to the formation of a surface state in CrOCl under vertical electric fields, promoting electron-electron (e-e) interactions in BLG via long-range Coulomb coupling. Consequently, at the charge neutrality point, a crossover from single particle insulating behavior to an unconventional correlated insulator is enabled, below an onset temperature. We demonstrate the application of the insulating state for the realization of a logic inverter operating at low temperatures. Our findings pave the way for future engineering of quantum electronic states based on interfacial charge coupling.

19.
RSC Adv ; 13(12): 7972-7979, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36909774

RESUMO

Motivated by the successful synthesis of Janus monolayers of transition metal dichalcogenides (i.e., MoSSe), we computationally investigated the structural, electronic, optical, and transport properties of functionalized Janus MXenes, namely MM'CT2 (M, M' = Zr, Ti, Hf, M ≠ M', T = -O, -F, -OH). The results of the calculations demonstrate that five stable O-terminated Janus MXenes (ZrTiCO2-I, ZrHfCO2-I, ZrHfCO2-III, HfTiCO2-I, and HfTiCO2-III), exhibit modest bandgaps of 1.37-1.94 eV, visible-light absorption (except for ZrHfCO2-I), high carrier mobility, and promising oxidization capability of photoinduced holes. Additionally, their indirect-gap, spatially separated electron-hole pairs, and the dramatic difference between the mobilities of electrons and holes could significantly limit the recombination of photoinduced electron-hole pairs. Our results indicate that the functionalized Janus MXene monolayers are ideal and promising materials for application in visible light-driven photocatalysis.

20.
NPJ Precis Oncol ; 7(1): 28, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36922568

RESUMO

Genomic studies have demonstrated a high frequency of genetic alterations in components of the SWI/SNF complex including the core subunit SMARCA4. However, the mechanisms of tumorigenesis driven by SMARCA4 mutations, particularly in colorectal cancer (CRC), remain largely unknown. In this study, we identified a specific, hotspot mutation in SMARCA4 (c. 3721C>T) which results in a conversion from arginine to tryptophan at residue 1157 (R1157W) in human CRC tissues associated with higher-grade tumors and controls CRC progression. Mechanistically, we found that the SMARCA4R1157W mutation facilitated its recruitment to PRMT1-mediated H4R3me2a (asymmetric dimethylation of Arg 3 in histone H4) and enhanced the ATPase activity of SWI/SNF complex to remodel chromatin in CRC cells. We further showed that the SMARCA4R1157W mutant reinforced the transcriptional expression of EGFR and TNS4 to promote the proliferation of CRC cells and patient-derived tumor organoids. Importantly, we demonstrated that SMARCA4R1157W CRC cells and mutant cell-derived xenografts were more sensitive to the combined inhibition of PRMT1 and SMARCA4 which act synergistically to suppress cell proliferation. Together, our findings show that SMARCA4-R1157W is a critical activating mutation, which accelerates CRC progression through facilitating chromatin recruitment and remodeling. Our results suggest a potential precision therapeutic strategy for the treatment of CRC patients carrying the SMARCA4R1157W mutation.

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