High-density switchable skyrmion-like polar nanodomains integrated on silicon.

Topological domains in ferroelectrics1-5 have received much attention recently owing to their novel functionalities and potential applications6,7 in electronic devices. So far, however, such topological polar structures have been observed only in superlattices grown on oxide substrates, which limits their applications in silicon-based electronics. Here we report the realization of room-temperature skyrmion-like polar nanodomains in lead titanate/strontium titanate bilayers transferred onto silicon. Moreover, an external electric field can reversibly switch these nanodomains into the other type of polar texture, which substantially modifies their resistive behaviours. The polar-configuration-modulated resistance is ascribed to the distinct band bending and charge carrier distribution in the core of the two types of polar texture. The integration of high-density (more than 200 gigabits per square inch) switchable skyrmion-like polar nanodomains on silicon may enable non-volatile memory applications using topological polar structures in oxides.

Freestanding crystalline oxide perovskites down to the monolayer limit.

Two-dimensional (2D) materials such as graphene and transition-metal dichalcogenides reveal the electronic phases that emerge when a bulk crystal is reduced to a monolayer1-4. Transition-metal oxide perovskites host a variety of correlated electronic phases5-12, so similar behaviour in monolayer materials based on transition-metal oxide perovskites would open the door to a rich spectrum of exotic 2D correlated phases that have not yet been explored. Here we report the fabrication of freestanding perovskite films with high crystalline quality almost down to a single unit cell. Using a recently developed method based on water-soluble Sr3Al2O6 as the sacrificial buffer layer13,14 we synthesize freestanding SrTiO3 and BiFeO3 ultrathin films by reactive molecular beam epitaxy and transfer them to diverse substrates, in particular crystalline silicon wafers and holey carbon films. We find that freestanding BiFeO3 films exhibit unexpected and giant tetragonality and polarization when approaching the 2D limit. Our results demonstrate the absence of a critical thickness for stabilizing the crystalline order in the freestanding ultrathin oxide films. The ability to synthesize and transfer crystalline freestanding perovskite films without any thickness limitation onto any desired substrate creates opportunities for research into 2D correlated phases and interfacial phenomena that have not previously been technically possible.

Comprehensive analysis reveals the prognostic and immunogenic characteristics of DNA methylation regulators in lung adenocarcinoma.

DNA methylation regulators (DMRs) play a key role in DNA methylation, thus mediating tumor occurrence, metastasis, and immunomodulation. However, the effects of DMRs on clinical outcomes and immunotherapy response remain unexplored in lung adenocarcinoma (LUAD). In this study, eight LUAD cohorts and one immunotherapeutic cohort of lung cancer were utilized. We constructed a DNA methylation regulators-related signature (DMRRS) using univariate and multivariate COX regression analysis. The DMRRS-defined low-risk group was preferentially associated with favorable prognosis, tumor-inhibiting microenvironment, more sensitivity to several targeted therapy drugs, and better immune response. Afterward, the prognostic value and predictive potential in immunotherapy response were validated. Collectively, our findings uncovered that the DMRRS was closely associated with the tumor immune microenvironment and could effectively predict the clinical outcome and immune response of LUAD patients.

Atomically Resolved Electrically Active Intragrain Interfaces in Perovskite Semiconductors.

Deciphering the atomic and electronic structures of interfaces is key to developing state-of-the-art perovskite semiconductors. However, conventional characterization techniques have limited previous studies mainly to grain-boundary interfaces, whereas the intragrain-interface microstructures and their electronic properties have been much less revealed. Herein using scanning transmission electron microscopy, we resolved the atomic-scale structural information on three prototypical intragrain interfaces, unraveling intriguing features clearly different from those from previous observations based on standalone films or nanomaterial samples. These intragrain interfaces include composition boundaries formed by heterogeneous ion distribution, stacking faults resulted from wrongly stacked crystal planes, and symmetrical twinning boundaries. The atomic-scale imaging of these intragrain interfaces enables us to build unequivocal models for the ab initio calculation of electronic properties. Our results suggest that these structure interfaces are generally electronically benign, whereas their dynamic interaction with point defects can still evoke detrimental effects. This work paves the way toward a more complete fundamental understanding of the microscopic structure-property-performance relationship in metal halide perovskites.

Emerging Two-Dimensional Tellurene and Tellurides for Broadband Photodetectors.

As with all stylish 2D functional materials, tellurene and tellurides possessing excellent physical and chemical properties such as high environmental stability, tunable narrow bandgap, and lower thermal conductivity, have aroused the great interest of the researchers. These properties of such materials also form the basis for relatively newfangled scholarly fields involving advanced topics, especially for broadband photodetectors. Integrating the excellent properties of many 2D materials, tellurene/telluride-based photodetectors show great flexibility, higher frequency response or faster time response, high signal-to-noise ratio, and so on, which make them leading the frontier of photodetector research. To fully understand the excellent properties of tellurene/tellurides and their optoelectronic applications, the recent advances in tellurene/telluride-based photodetectors are maximally summarized. Benefiting from the solid research in this field, the challenges and opportunities of tellurene/tellurides for future optoelectronic applications are also discussed in this review, which might provide possibilities for the realization of state-of-the-art high-performance tellurene/telluride-based devices.

Aumolertinib-based comprehensive treatment for an uncommon site of EGFR exon 20 insertion mutations with multiple metastases non-small cell lung cancer: a case report.

EGFR exon 20 insertion mutation is a rare mutation subtype of EGFR mutations, with no approved treatment in China so far. The clinical treatments of advanced EGFR exon 20 insertion mutations in non-small cell lung cancer (NSCLC) are mainly based on EGFR-TKI, chemotherapy, ICI, and other therapies. However, the efficacy is not satisfactory. Aumolertinib is the third-generation EGFR-TKI independently developed in China, which has shown excellent efficacy and safety in phase 2 and 3 clinical trials. This study aimed to share a case of applying aumolertinib as the core combined with other treatments for a patient with multiple metastases in NSCLC with an uncommon site of EGFR exon 20 insertion mutations. The comprehensive treatment benefited the patient in terms of 10 months of progression-free survival and a significant improvement in quality of life. We discussed whether we could further explore the potential of aumolertinib in treating EGFR exon 20 insertion mutations through this case report.

Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma.

Angiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated. In this study, we adopted differential expression analysis, Cox proportional hazards (PH) regression analysis and experimental validation to identify angiogenesis regulators correlated with a poor prognosis, immune infiltration and cancer progression in LUAD. These results showed that the diagnostic and prognostic models based on COL5A2 and EPHB2 served as independent biomarkers with superior predictive ability. The patients in the high-risk group exhibited a worse prognosis in the TCGA cohort (P < 0.001, HR = 1.72, 95% CI 1.28-2.30), GSE310210 cohort (P = 0.005, HR = 2.87, 95% CI 1.46-5.61), and GSE31019 cohort (P = 0.01, HR = 2.14, 95% CI 1.19-3.86) than patients in the low-risk group. The high prognostic risk patients had a higher TMB (P < 0.001); higher fractions of M0 macrophages, neutrophils, NK cells resting, and T cells CD4 memory activated (P < 0.05); and higher expression of immune checkpoints PD-1, PDL-1, PDL-2, and B7H3 (P < 0.001). Patients in the high-risk group were more sensitive to chemotherapeutic drugs and molecular targeted drugs such as cisplatin, doxorubicin, gefitinib, and bosutinib (P < 0.0001). In addition, inhibition of COL5A2 and EPHB2 effectively suppressed the proliferation and migration of LUAD cells. The current study identified angiogenesis regulators as potential biomarkers and therapeutic targets for LUAD and may help to further optimize cancer therapy.

Gate-Induced Interfacial Superconductivity in 1T-SnSe2.

Layered metal chalcogenide materials provide a versatile platform to investigate emergent phenomena and two-dimensional (2D) superconductivity at/near the atomically thin limit. In particular, gate-induced interfacial superconductivity realized by the use of an electric-double-layer transistor (EDLT) has greatly extended the capability to electrically induce superconductivity in oxides, nitrides, and transition metal chalcogenides and enable one to explore new physics, such as the Ising pairing mechanism. Exploiting gate-induced superconductivity in various materials can provide us with additional platforms to understand emergent interfacial superconductivity. Here, we report the discovery of gate-induced 2D superconductivity in layered 1T-SnSe2, a typical member of the main-group metal dichalcogenide (MDC) family, using an EDLT gating geometry. A superconducting transition temperature Tc ≈ 3.9 K was demonstrated at the EDL interface. The 2D nature of the superconductivity therein was further confirmed based on (1) a 2D Tinkham description of the angle-dependent upper critical field Bc2, (2) the existence of a quantum creep state as well as a large ratio of the coherence length to the thickness of superconductivity. Interestingly, the in-plane Bc2 approaching zero temperature was found to be 2-3 times higher than the Pauli limit, which might be related to an electric field-modulated spin-orbit interaction. Such results provide a new perspective to expand the material matrix available for gate-induced 2D superconductivity and the fundamental understanding of interfacial superconductivity.

Improved charge separation efficiency of hematite photoanodes by coating an ultrathin p-type LaFeO3 overlayer.

Many metal-oxide candidates for photoelectrochemical water splitting exhibit localized small polaron carrier conduction. Especially hematite (α-Fe2O3) photoanodes often suffer from low carrier mobility, which causes the serious bulk electron-hole recombination and greatly limits their PEC performances. In this study, the charge separation efficiency of hematite was enhanced greatly by coating an ultrathin p-type LaFeO3 overlayer. Compared to the hematite photoanodes, the solar water splitting photocurrent of the Fe2O3/LaFeO3 n-p junction exhibits a 90% increase at 1.23 V versus the reversible hydrogen electrode, due to enlarging the band bending and expanding the depletion layer.

Atomic-level imaging of beam-sensitive COFs and MOFs by low-dose electron microscopy.

Electron microscopy, an important technique that allows for the precise determination of structural information with high spatiotemporal resolution, has become indispensable in unravelling the complex relationships between material structure and properties ranging from mesoscale morphology to atomic arrangement. However, beam-sensitive materials, particularly those comprising organic components such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), would suffer catastrophic damage from the high energy electrons, hindering the determination of atomic structures. A low-dose approach has arisen as a possible solution to this problem based on the integration of advancements in several aspects: electron optical system, detector, image processing, and specimen preservation. This article summarizes the transmission electron microscopy characterization of MOFs and COFs, including local structures, host-guest interactions, and interfaces at the atomic level. Revolutions in advanced direct electron detectors, algorithms in image acquisition and processing, and emerging methodology for high quality low-dose imaging are also reviewed. Finally, perspectives on the future development of electron microscopy methodology with the support of computer science are presented.

Intragrain impurity annihilation for highly efficient and stable perovskite solar cells.

Intragrain impurities can impart detrimental effects on the efficiency and stability of perovskite solar cells, but they are indiscernible to conventional characterizations and thus remain unexplored. Using in situ scanning transmission electron microscopy, we reveal that intragrain impurity nano-clusters inherited from either the solution synthesis or post-synthesis storage can revert to perovskites upon irradiation stimuli, leading to the counterintuitive amendment of crystalline grains. In conjunction with computational modelling, we atomically resolve crystallographic transformation modes for the annihilation of intragrain impurity nano-clusters and probe their impacts on optoelectronic properties. Such critical fundamental findings are translated for the device advancement. Adopting a scanning laser stimulus proven to heal intragrain impurity nano-clusters, we simultaneously boost the efficiency and stability of formamidinium-cesium perovskite solar cells, by virtual of improved optoelectronic properties and relaxed intra-crystal strain, respectively. This device engineering, inspired and guided by atomic-scale in situ microscopic imaging, presents a new prototype for solar cell advancement.

Spatial engineering of single-atom Fe adjacent to Cu-assisted nanozymes for biomimetic O2 activation.

The precise design of single-atom nanozymes (SAzymes) and understanding of their biocatalytic mechanisms hold great promise for developing ideal bio-enzyme substitutes. While considerable efforts have been directed towards mimicking partial bio-inspired structures, the integration of heterogeneous SAzymes configurations and homogeneous enzyme-like mechanism remains an enormous challenge. Here, we show a spatial engineering strategy to fabricate dual-sites SAzymes with atomic Fe active center and adjacent Cu sites. Compared to planar Fe-Cu dual-atomic sites, vertically stacked Fe-Cu geometry in FePc@2D-Cu-N-C possesses highly optimized scaffolds, favorable substrate affinity, and fast electron transfer. These characteristics of FePc@2D-Cu-N-C SAzyme induces biomimetic O2 activation through homogenous enzymatic pathway, resembling functional and mechanistic similarity to natural cytochrome c oxidase. Furthermore, it presents an appealing alternative of cytochrome P450 3A4 for drug metabolism and drug-drug interaction. These findings are expected to deepen the fundamental understanding of atomic-level design in next-generation bio-inspired nanozymes.

Extendable piezo/ferroelectricity in nonstoichiometric 2D transition metal dichalcogenides.

Engineering piezo/ferroelectricity in two-dimensional materials holds significant implications for advancing the manufacture of state-of-the-art multifunctional materials. The inborn nonstoichiometric propensity of two-dimensional transition metal dichalcogenides provides a spiffy ready-available solution for breaking inversion centrosymmetry, thereby conducing to circumvent size effect challenges in conventional perovskite oxide ferroelectrics. Here, we show the extendable and ubiquitous piezo/ferroelectricity within nonstoichiometric two-dimensional transition metal dichalcogenides that are predominantly centrosymmetric during standard stoichiometric cases. The emerged piezo/ferroelectric traits are aroused from the sliding of van der Waals layers and displacement of interlayer metal atoms triggered by the Frankel defects of heterogeneous interlayer native metal atom intercalation. We demonstrate two-dimensional chromium selenides nanogenerator and iron tellurides ferroelectric multilevel memristors as two representative applications. This innovative approach to engineering piezo/ferroelectricity in ultrathin transition metal dichalcogenides may provide a potential avenue to consolidate piezo/ferroelectricity with featured two-dimensional materials to fabricate multifunctional materials and distinguished multiferroic.

Macrophage xCT deficiency drives immune activation and boosts responses to immune checkpoint blockade in lung cancer.

Tumor-associated macrophages (TAMs) play an important role in remodeling the tumor microenvironment (TME), which promotes tumor growth, immunosuppression and angiogenesis. Because of the high plasticity of macrophages and the extremely complex tumor microenvironment, the mechanism of TAMs in cancer progression is still largely unknown. In this study, we found that xCT (SLC7A11) was overexpressed in lung cancer-associated macrophages. Higher xCT in TAMs was associated with poor prognosis and was an independent predictive factor in lung cancer. In addition, lung cancer growth and progression was inhibited in xCT knockout mice, especially macrophage-specific xCT knockout mice. We also found that the deletion of macrophage xCT inhibited AKT/STAT6 signaling activation and reduced M2-type polarization of TAMs. Macrophage xCT deletion recruited more CD8+ T cells and activated the lung cancer cell-mediated and IFN-γ-induced JAK/STAT1 axis and increased the expression of its target genes, including CXCL10 and CD274. The combination of macrophage xCT deletion and anti-PDL1 antibody achieved better tumor inhibition. Finally, combining the xCT inhibitor erastin with an anti-PDL1 antibody was more potent in inhibiting lung cancer progression. Therefore, suppression of xCT may overcome resistance to cancer immunotherapy.

Solution-grown BiI/BiI3 van der Waals heterostructures for sensitive X-ray detection.

X-ray detectors must be operated at minimal doses to reduce radiation health risks during X-ray security examination or medical inspection, therefore requiring high sensitivity and low detection limits. Although organolead trihalide perovskites have rapidly emerged as promising candidates for X-ray detection due to their low cost and remarkable performance, these materials threaten the safety of the human body and environment due to the presence of lead. Here we present the realization of highly sensitive X-ray detectors based on an environmentally friendly solution-grown thick BiI/BiI3/BiI (BixIy) van der Waals heterostructure. The devices exhibit anisotropic X-ray detection response with a sensitivity up to 4.3 × 104 µC Gy-1 cm-2 and a detection limit as low as 34 nGy s-1. At the same time, our BixIy detectors demonstrate high environmental and hard radiation stabilities. Our work motivates the search for new van der Waals heterostructure classes to realize high-performance X-ray detectors and other optoelectronic devices without employing toxic elements.

CTRP6 protects against ferroptosis to drive lung cancer progression and metastasis by destabilizing SOCS2 and augmenting the xCT/GPX4 pathway.

Lung cancer is a highly heterogeneous malignancy, and despite the rapid development of chemotherapy and radiotherapy, acquired drug resistance and tumor progression still occur. Thus, it is urgent to identify novel therapeutic targets. Our research aims to screen novel biomarkers associated with the prognosis of lung carcinoma patients and explore the potential regulatory mechanisms. We obtained RNA sequencing (RNA-seq) data of lung cancer patients from public databases. Clinical signature analysis, weighted gene coexpression network analysis (WGCNA) and the random forest algorithm showed that C1q/tumor necrosis factor-related protein-6 (CTRP6) is a core gene related to lung cancer prognosis, and it was determined to promote tumor proliferation and metastasis both in vivo and in vitro. Mechanistically, silencing CTRP6 was determined to promote xCT/GPX4-involved ferroptosis through functional assays related to lipid peroxidation, Fe2+ concentration and mitochondrial ultrastructure. By performing interactive proteomics analyses in lung tumor cells, we identified the interaction between CTRP6 and suppressor of cytokine signaling 2 (SOCS2) leading to SOCS2 ubiquitination degradation, subsequently enhancing the downstream xCT/GPX4 signaling pathway. Moreover, significant correlations between CTRP6-mediated SOCS2 and ferroptosis were revealed in mouse models and clinical specimens of lung cancer. As inducing ferroptosis has been gradually regarded as an alternative strategy to treat tumors, targeting CTRP6-mediated ferroptosis could be a potential strategy for lung cancer therapy.

Alternating BiI3-BiI van der Waals Photodetector with Low Dark Current and High-Performance Photodetection.

The emerging two-dimensional (2D) van der Waals (vdW) materials and their heterostructures hold great promise for optoelectronics and photonic applications beyond strictly lattice-matching constraints and grade interfaces. However, previous photodetectors and optoelectronic devices rely on relatively simple vdW heterostructures with one or two blocks. The realization of high-order heterostructures has been exponentially challenging due to conventional layer-by-layer arduous restacking or sequential synthesis. In this study, we present an approach involving the direct exfoliation of high-quality BiI3-BiI heterostructure nanosheets with alternating blocks, derived from solution-grown binary heterocrystals. These heterostructure-based photodetectors offer several notable advantages. Leveraging the "active layer energetics" of BiI layers and the establishment of a significant depletion region, our photodetector demonstrates a significant reduction in dark current compared with pure BiI3 devices. Specifically, the photodetector achieves an extraordinarily low dark current (<9.2 × 10-14 A at 5 V bias voltage), an impressive detectivity of 8.8 × 1012 Jones at 638 nm, and a rapid response time of 3.82 µs. These characteristics surpass the performance of other metal-semiconductor-metal (MSM) photodetectors based on various 2D materials and structures at visible wavelengths. Moreover, our heterostructure exhibits a broad-band photoresponse, covering the visible, near-infrared (NIR)-I, and NIR-II regions. In addition to these promising results, our heterostructure also demonstrated the potential for flexible and imaging applications. Overall, our study highlights the potential of alternating vdW heterostructures for future optoelectronics with low power consumption, fast response, and flexible requirements.

Development and clinical validation of a microfluidic-based platform for CTC enrichment and downstream molecular analysis.

Background: Although many CTC isolation and detection methods can provide information on cancer cell counts, downstream gene and protein analysis remain incomplete. Therefore, it is crucial to develop a technology that can provide comprehensive information on both the number and profile of CTC. Methods: In this study, we developed a novel microfluidics-based CTC separation and enrichment platform that provided detailed information about CTC. Results: This platform exhibits exceptional functionality, achieving high rates of CTC recovery (87.1%) and purification (∼4 log depletion of WBCs), as well as accurate detection (95.10%), providing intact and viable CTCs for downstream analysis. This platform enables successful separation and enrichment of CTCs from a 4 mL whole-blood sample within 15 minutes. Additionally, CTC subtypes, selected protein expression levels on the CTC surface, and target mutations in selected genes can be directly analyzed for clinical utility using immunofluorescence and real-time polymerase chain reaction, and the detected PD-L1 expression in CTCs is consistent with immunohistochemical assay results. Conclusion: The microfluidic-based CTC enrichment platform and downstream molecular analysis together provide a possible alternative to tissue biopsy for precision cancer management, especially for patients whose tissue biopsies are unavailable.

LINC01426 Triggers Growth and Metastasis of Lung Adenocarcinoma as a Prognostic Indicator.

The vital regulation of abnormally expressed lncRNAs in human cancers has been identified. This study is aimed at illustrating the role of LINC01426 in influencing malignant behaviors of lung adenocarcinoma (LUAD) and the possible mechanism. Differential expressions of LINC01426 in a downloaded profile containing LUAD and normal tissues were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) database and were reconfirmed in clinical samples collected in our hospital. In addition, LINC01426 level in lung carcinoma cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR) as well. The relationship between LINC01426 expression and the age, tumor node metastasis (TNM) staging, lymphatic metastasis, tumor differentiation, and overall survival of LUAD was analyzed. After intervening LINC01426 level in H1299 and PC9 cells, proliferative and metastatic changes were assessed by functional experiments. LINC01426 was upregulated in LUAD tissues and cell lines. Its level was closely linked to TNM staging, lymphatic metastasis, tumor differentiation, and overall survival of LUAD. Knockdown of LINC01426 suppressed proliferative and metastatic abilities in H1299 and PC9 cells. LINC01246 is upregulated in LUAD samples and predicts a poor prognosis. It drives malignant process of LUAD via stimulating proliferative and metastatic abilities.

Ferroelectricity in untwisted heterobilayers of transition metal dichalcogenides.

Two-dimensional materials with out-of-plane (OOP) ferroelectric and piezoelectric properties are highly desirable for the realization of ultrathin ferro- and piezoelectronic devices. We demonstrate unexpected OOP ferroelectricity and piezoelectricity in untwisted, commensurate, and epitaxial MoS2/WS2 heterobilayers synthesized by scalable one-step chemical vapor deposition. We show d33 piezoelectric constants of 1.95 to 2.09 picometers per volt that are larger than the natural OOP piezoelectric constant of monolayer In2Se3 by a factor of ~6. We demonstrate the modulation of tunneling current by about three orders of magnitude in ferroelectric tunnel junction devices by changing the polarization state of MoS2/WS2 heterobilayers. Our results are consistent with density functional theory, which shows that both symmetry breaking and interlayer sliding give rise to the unexpected properties without the need for invoking twist angles or moiré domains.