Ultralow contact resistance between semimetal and monolayer semiconductors.

Advanced beyond-silicon electronic technology requires both channel materials and also ultralow-resistance contacts to be discovered1,2. Atomically thin two-dimensional semiconductors have great potential for realizing high-performance electronic devices1,3. However, owing to metal-induced gap states (MIGS)4-7, energy barriers at the metal-semiconductor interface-which fundamentally lead to high contact resistance and poor current-delivery capability-have constrained the improvement of two-dimensional semiconductor transistors so far2,8,9. Here we report ohmic contact between semimetallic bismuth and semiconducting monolayer transition metal dichalcogenides (TMDs) where the MIGS are sufficiently suppressed and degenerate states in the TMD are spontaneously formed in contact with bismuth. Through this approach, we achieve zero Schottky barrier height, a contact resistance of 123 ohm micrometres and an on-state current density of 1,135 microamps per micrometre on monolayer MoS2; these two values are, to the best of our knowledge, the lowest and highest yet recorded, respectively. We also demonstrate that excellent ohmic contacts can be formed on various monolayer semiconductors, including MoS2, WS2 and WSe2. Our reported contact resistances are a substantial improvement for two-dimensional semiconductors, and approach the quantum limit. This technology unveils the potential of high-performance monolayer transistors that are on par with state-of-the-art three-dimensional semiconductors, enabling further device downscaling and extending Moore's law.

Two-dimensional halide perovskite lateral epitaxial heterostructures.

Epitaxial heterostructures based on oxide perovskites and III-V, II-VI and transition metal dichalcogenide semiconductors form the foundation of modern electronics and optoelectronics1-7. Halide perovskites-an emerging family of tunable semiconductors with desirable properties-are attractive for applications such as solution-processed solar cells, light-emitting diodes, detectors and lasers8-15. Their inherently soft crystal lattice allows greater tolerance to lattice mismatch, making them promising for heterostructure formation and semiconductor integration16,17. Atomically sharp epitaxial interfaces are necessary to improve performance and for device miniaturization. However, epitaxial growth of atomically sharp heterostructures of halide perovskites has not yet been achieved, owing to their high intrinsic ion mobility, which leads to interdiffusion and large junction widths18-21, and owing to their poor chemical stability, which leads to decomposition of prior layers during the fabrication of subsequent layers. Therefore, understanding the origins of this instability and identifying effective approaches to suppress ion diffusion are of great importance22-26. Here we report an effective strategy to substantially inhibit in-plane ion diffusion in two-dimensional halide perovskites by incorporating rigid π-conjugated organic ligands. We demonstrate highly stable and tunable lateral epitaxial heterostructures, multiheterostructures and superlattices. Near-atomically sharp interfaces and epitaxial growth are revealed by low-dose aberration-corrected high-resolution transmission electron microscopy. Molecular dynamics simulations confirm the reduced heterostructure disorder and larger vacancy formation energies of the two-dimensional perovskites in the presence of conjugated ligands. These findings provide insights into the immobilization and stabilization of halide perovskite semiconductors and demonstrate a materials platform for complex and molecularly thin superlattices, devices and integrated circuits.

The role of body composition in left ventricular remodeling, reverse remodeling, and clinical outcomes for heart failure with mildly reduced ejection fraction: more knowledge to the "obesity paradox".

BACKGROUND: Although the "obesity paradox" is comprehensively elucidated in heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), the role of body composition in left ventricular (LV) remodeling, LV reverse remodeling (LVRR), and clinical outcomes is still unclear for HF with mildly reduced ejection fraction (HFmrEF). METHODS: Our study is a single-centre, prospective, and echocardiography-based study. Consecutive HFmrEF patients, defined as HF patients with a left ventricular ejection fraction (LVEF) between 40 and 49%, between January 2016 to December 2021 were included. Echocardiography was re-examined at 3-, 6-, and 12-month follow-up to assess the LVRR dynamically. Body mass index (BMI), fat mass, fat-free mass, percent body fat (PBF), CUN-BAE index, and lean mass index (LMI) were adopted as anthropometric parameters in our study to assess body composition. The primary outcome was LVRR, defined as: (1) a reduction higher than 10% in LV end-diastolic diameter index (LVEDDI), or a LVEDDI < 33 mm/m2, (2) an absolute increase of LVEF higher than 10 points compared with baseline echocardiogram, or a follow-up LVEF ≥50%. The secondary outcome was a composite of re-hospitalization for HF or cardiovascular death. RESULTS: A total of 240 HFmrEF patients were enrolled in our formal analysis. After 1-year follow-up based on echocardiography, 113 (47.1%) patients developed LVRR. Patients with LVRR had higher fat mass (21.7 kg vs. 19.3 kg, P = 0.034) and PBF (28.7% vs. 26.6%, P = 0.047) compared with those without. The negative correlation between anthropometric parameters and baseline LVEDDI was significant (all P < 0.05). HFmrEF patients with higher BMI, fat mass, PBF, CUN-BAE index, and LMI had more pronounced and persistent increase of LVEF and decline in LV mass index (LVMI). Univariable Cox regression analysis revealed that higher BMI (HR 1.042, 95% CI 1.002-1.083, P = 0.037) and fat mass (HR 1.019, 95% CI 1.002-1.036, P = 0.026) were each significantly associated with higher cumulative incidence of LVRR for HFmrEF patients, while this relationship vanished in the adjusted model. Mediation analysis indicated that the association between BMI and fat mass with LVRR was fully mediated by baseline LV dilation. Furthermore, higher fat mass (aHR 0.957, 95% CI 0.917-0.999, P = 0.049) and PBF (aHR 0.963, 95% CI 0.924-0.976, P = 0.043) was independently associated with lower risk of adverse clinical events. CONCLUSIONS: Body composition played an important role in the LVRR and clinical outcomes for HFmrEF. For HFmrEF patients, BMI and fat mass was positively associated with the cumulative incidence of LVRR, while higher fat mass and PBF predicted lower risk of adverse clinical events but not LMI.

Gender differences in the relationship between serum uric acid and the long-term prognosis in heart failure: a nationwide study.

BACKGROUND: Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. METHODS: A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan-Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. RESULTS: Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120-134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p < 0.001, for male, Log-rank p = 0.150, for female), but not in all-cause mortality. Multivariate Cox regression analysis revealed that elevated SUA levels were associated with higher all-cause mortality and cardiovascular mortality in men (HR 1.11, 95% CI 1.05-1.18, p < 0.001, for all-cause death; HR 1.18, 95% CI 1.09-1.28, p < 0.001, for cardiovascular death), but not in women (HR 1.05, 95% CI 0.98-1.12, p = 0.186, for all-cause death; HR 1.01, 95% CI 0.91-1.12, p = 0.902, for cardiovascular death). Even using non-cardiovascular death as a competitive risk, adjusted Fine-Gray model also illustrated that SUA was an independent predictor of cardiovascular death in men (SHR 1.17, 95% CI 1.08-1.27, p < 0.001), but not in women (SHR 0.98, 95% CI 0.87 - 1.10, p = 0.690). CONCLUSIONS: Gender differences in the association between SUA and long-term prognosis of HF existed. SUA was an independent prognostic predictor for long-term outcomes of HF in men, but not in women.

Designing artificial two-dimensional landscapes via atomic-layer substitution.

Technology advancements in history have often been propelled by material innovations. In recent years, two-dimensional (2D) materials have attracted substantial interest as an ideal platform to construct atomic-level material architectures. In this work, we design a reaction pathway steered in a very different energy landscape, in contrast to typical thermal chemical vapor deposition method in high temperature, to enable room-temperature atomic-layer substitution (RT-ALS). First-principle calculations elucidate how the RT-ALS process is overall exothermic in energy and only has a small reaction barrier, facilitating the reaction to occur at room temperature. As a result, a variety of Janus monolayer transition metal dichalcogenides with vertical dipole could be universally realized. In particular, the RT-ALS strategy can be combined with lithography and flip-transfer to enable programmable in-plane multiheterostructures with different out-of-plane crystal symmetry and electric polarization. Various characterizations have confirmed the fidelity of the precise single atomic layer conversion. Our approach for designing an artificial 2D landscape at selective locations of a single layer of atoms can lead to unique electronic, photonic, and mechanical properties previously not found in nature. This opens a new paradigm for future material design, enabling structures and properties for unexplored territories.

A cancer-targeted glutathione-gated probe for self-sufficient ST/CDT combination therapy and FRET-based miRNA imaging.

A cancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy (ST) and chemodynamic therapy (CDT) was developed. The CGT probe is constructed using MnO2 nanosheet (MS) as carrier material to adsorb the elaborately designed functional DNAs. It can be internalized by cancer cells via specific recognition between the AS1411 aptamer and nucleolin. After CGT probe entering the cancer cells, the overexpressed GSH, as gate-control, can degrade MS to Mn2+ which can be used for CDT by Fenton-like reaction. Simultaneously, Mn2+-mediated CDT can further cascade with the enzyme-like activities (catalase-like activity and glucose oxidase-like activity) of CGT probe, achieving self-sufficient ST/CDT synergistic therapy. Meanwhile, the anchored DNAs are released, achieving in situ signal amplification via disubstituted-catalytic hairpin assembly (DCHA) and FRET (fluorescence resonance energy transfer) imaging of miR-21. The in vitro and in vivo experiments demonstrated that accurate and sensitive miRNA detection can be achieved using the CGT probe. Overall, the ingenious CGT probe opens a new avenue for the development of early clinical diagnosis and cancer therapy.

Corn-Based Fluorescent Light-Up Biosensors with Improved Signal-to-Background Ratio for Label-Free Detection of Long Noncoding RNAs.

Long noncoding RNAs (lncRNAs) play pivotal roles in multifarious physiological and pathological processes, and their aberrant expression may disturb the normal regulatory network of gene expression to induce diverse human diseases. Herein, we construct a fluorescent light-up biosensor with a low background for label-free detection of lncRNAs by coupling duplex-specific nuclease (DSN)-assisted target recycling amplification with transcription-driven synthesis of fluorogenic RNA aptamer-Corns. We design two linear probes, including a capture probe for initiating a cyclic cleavage reaction and a linear template for transcribing RNA aptamer-Corn. Target lncRNA is recognized by capture probes assembled on magnetic bead (MB) surfaces to trigger a DSN-assisted cyclic cleavage reaction, releasing abundant T7 promoter sequences. After magnetic separation, free T7 promoter hybridizes with a linear template to induce efficient transcription amplification with the assistance of T7 RNA polymerase, producing numerous fluorogenic RNA aptamer-Corns that can light up small-molecule fluorogens 3,5-difluoro-4-hydroxybenzylidene-imidazolinone-2-oxime (DFHO). Notably, the introduction of MBs facilitates both the separation of cleaved capture probes and the enrichment/isolation of target lncRNAs from the complex biological matrix. Benefiting from the high efficiency of DSN/T7 RNA polymerase-mediated cascade amplification and high signal-to-background ratio of the Corn-DFHO complex, this biosensor is capable of sensitively quantifying lncRNA with a detection limit of 31.98 aM. Moreover, it can precisely quantify lncRNA at the single-cell level and even in complex biological samples, and it can differentiate tumor cells from normal cells. Importantly, this Corn-based biosensor is readily extended to detect other lncRNAs by altering capture probe sequences, opening a new avenue for molecular diagnosis.

Construction of a Quantum-Dot-Based FRET Nanosensor through Direct Encoding of Streptavidin-Binding RNA Aptamers for N6-Methyladenosine Demethylase Detection.

N6-Methyladenosine (m6A) demethylases can catalyze the removal of the methyl modification on m6A, and it is closely associated with the occurrence, proliferation, differentiation, and metastasis of malignancies. The m6A demethylases (e.g., fat mass and obesity-associated protein (FTO)) may act as a cancer biomarker and are crucial for anticancer drug screening and early clinical diagnosis. Herein, we demonstrate the construction of a quantum-dot-based Förster resonance energy-transfer (FRET) nanosensor through direct encoding of streptavidin-binding RNA aptamers (SA aptamers) for m6A demethylase detection. This nanosensor employs multiple Cy5-molecule-labeled SA aptamers as the building materials to construct the 605QD-RNA-Cy5 nanoassembly, and it exploits the hinder effect of m6A upon elongation and ligation reactions to distinguish m6A-containing RNA probes from demethylated RNA probes. When m6A demethylase is present, the m6A-containing RNA probes are demethylated to generate the demethylated RNA probes, initiating strand extension and ligation reactions to yield a complete transcription template for SA aptamers. Subsequently, a T7-assisted cascade transcription amplification reaction is activated to transcribe abundant SA aptamers with the incorporation of multiple Cy5 fluorophores. The Cy5-incorporated SA aptamers can self-assembly onto the streptavidin-coated 605QD surface to obtain the 605QD-SA aptamer-Cy5 nanoassemblies, resulting in the generation of distinct FRET signals. This nanosensor exhibits ultrahigh sensitivity and excellent specificity, and it can detect endogenous FTO at the single-cell level. Furthermore, this nanosensor can precisely measure enzyme kinetic parameters, screen m6A demethylase inhibitors, and differentiate the FTO expression between breast cancer patients and healthy individual tissues, offering a versatile platform for clinical diagnostic and drug discovery.

Tuning colour centres at a twisted hexagonal boron nitride interface.

The colour centre platform holds promise for quantum technologies, and hexagonal boron nitride has attracted attention due to the high brightness and stability, optically addressable spin states and wide wavelength coverage discovered in its emitters. However, its application is hindered by the typically random defect distribution and complex mesoscopic environment. Here, employing cathodoluminescence, we demonstrate on-demand activation and control of colour centre emission at the twisted interface of two hexagonal boron nitride flakes. Further, we show that colour centre emission brightness can be enhanced by two orders of magnitude by tuning the twist angle. Additionally, by applying an external voltage, nearly 100% brightness modulation is achieved. Our ab initio GW and GW plus Bethe-Salpeter equation calculations suggest that the emission is correlated to nitrogen vacancies and that a twist-induced moiré potential facilitates electron-hole recombination. This mechanism is further exploited to draw nanoscale colour centre patterns using electron beams.

Deep-Learning Electron Diffractive Imaging.

We report the development of deep-learning coherent electron diffractive imaging at subangstrom resolution using convolutional neural networks (CNNs) trained with only simulated data. We experimentally demonstrate this method by applying the trained CNNs to recover the phase images from electron diffraction patterns of twisted hexagonal boron nitride, monolayer graphene, and a gold nanoparticle with comparable quality to those reconstructed by a conventional ptychographic algorithm. Fourier ring correlation between the CNN and ptychographic images indicates the achievement of a resolution in the range of 0.70 and 0.55 Å. We further develop CNNs to recover the probe function from the experimental data. The ability to replace iterative algorithms with CNNs and perform real-time atomic imaging from coherent diffraction patterns is expected to find applications in the physical and biological sciences.