Spatial Filtering of Interlayer Exciton Ground State in WSe2/MoS2 Heterobilayer.

Long-life interlayer excitons (IXs) in transition metal dichalcogenide (TMD) heterostructure are promising for realizing excitonic condensates at high temperatures. Critical to this objective is to separate the IX ground state (the lowest energy of IX state) emission from other states' emissions. Filtering the IX ground state is also essential in uncovering the dynamics of correlated excitonic states, such as the excitonic Mott insulator. Here, we show that the IX ground state in the WSe2/MoS2 heterobilayer can be separated from other states by its spatial profile. The emissions from different moiré IX modes are identified by their different energies and spatial distributions, which fits well with the rate-diffusion model for cascading emission. Our results show spatial filtering of the ground state mode and enrich the toolbox to realize correlated states at elevated temperatures.

Layer-dependent correlated phases in WSe2/MoS2 moiré superlattice.

Electron correlation plays an essential role in the macroscopic quantum phenomena in the moiré heterostructure, such as antiferromagnetism and correlated insulating phases. Unlike the phenomena where the interaction involves only electrons in one layer, the interaction of distinct phases in two or more layers represents a new horizon forward, such as the one in the Kondo lattice model. Here, using interlayer excitons as a probe, we show that the interlayer interactions in heterobilayers of tungsten diselenide and molybdenum disulfide (WSe2/MoS2) can be electrically switched on and off, resulting in a layer-dependent correlated phase diagram, including single-layer, layer-selective, excitonic-insulator and layer-hybridized regions. We demonstrate that these correlated phases affect the interlayer exciton non-radiative decay pathways. These results reveal the role of strong correlation on interlayer exciton dynamics and pave the way for studying the layer-resolved strong correlation behaviour in moiré heterostructures.

Cuproptosis-related classification and personalized treatment in lower-grade gliomas to prompt precise oncology.

BACKGROUND: Cuproptosis is implicated in regulating tricarboxylic acid cycle and associated with tumor therapeutic sensitivity, patient outcomes and tumorigenesis. However, the classification and prognostic effect of cuproptosis-associated genes (CAGs), the relationship between cuproptosis and tumor microenvironment (TME) and the treatment of lower-grade glioma (LrGG) remain enigmatic. METHODS: The genetic and transcriptional alterations, prognostic value and classification related to cuproptosis were systematically analyzed. Subtypes of cuproptosis and cuproptosis score (Cuscore) were constructed and further confirmed by two external cohorts. The relationships between cuproptosis and TME, prognosis, and treatment response were also evaluated. RESULTS: Four clusters were identified based on cuproptosis-associated genes. The associations between cuproptosis-associated clusters and clinical features, prognosis, immune cell infiltration, and chemotherapy sensitivity were observed. The Cuscore is an independent prognostic indicator in LrGG patients. The nomogram is constructed according to Cuscore and clinical characteristics, and has good predictive ability and calibration. Patients with high Cuscore had a worse prognosis and advanced performance. A higher Cuscore also indicated a higher stromal score, abundant immune infiltration, and increased tumor mutation burden. A high Cuscore was remarkably related to immune checkpoint inhibitors, immunotherapy response and immune phenotype. CONCLUSIONS: This study demonstrates the clinical effect of CAGs, and suggests that cuproptosis could be a potential therapeutic target in LrGG.

LncRNA MIR4435-2HG suppression regulates macrophage M1/M2 polarization and reduces intestinal inflammation in mice with ulcerative colitis.

OBJECTIVE: To explore the effect and potential mechanism of LncRNA MIR4435-2HG on macrophage polarization and intestinal inflammation in ulcerative colitis (UC). Methods RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS) were co-cultured with Caco-2 cells to establish an inflammatory model of UC in vitro. Balb/c mice were orally administered dextran sulfate sodium (DSS) to establish an in vivo UC model. Flow cytometry and immunohistochemical (IHC) analyses were performed to assess the levels of surface phenotype markers. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were performed to measure the levels of inflammatory cytokines. Western blotting was used to analyze expression of the tight junction protein zona occludens 1 (ZO-1) and the key proteins of the JAK1/STAT1 signaling pathway (Janus kinase-1(JAK1), p-JAK1, signal transducer and activator of transcription 1 (STAT1), p-STAT1. Results In in vitro experiments, we found that inhibition of MIR4435-2HG was able to decrease the levels of CD68, iNOS, IL-6, and TEER, and increase the levels of CD206, Arg-1, IGF-1, and ZO-1. Meanwhile, inhibition of MIR4435-2HG significantly suppressed the levels of p- JAK1 and p- STAT1. In addition, we further demonstrated by in vivo experiments that inhibition of MIR4435-2HG significantly attenuated intestinal inflammation in mice, as evidenced by increased body weight, increased colon length and weight, decreased fecal scores, hemorrhagic scores, and DAI scores, and amelioration of colonic injury, and decreased inflammatory factors. Conclusions MIR4435-2HG suppression inhibits macrophage M1 polarization while promoting M2 polarization, thereby alleviating intestinal inflammation in mice with ulcerative colitis through JAK1/STAT1 signaling.

Clinical characteristics and risk factors for tigecycline-induced pancreatitis in a tertiary hospital: A retrospective study.

AIMS: To analyse the clinical characteristics and risk factors for tigecycline-induced pancreatitis (TIP) and evaluate the safety and efficiency of tigecycline use in non-TIP. METHODS: A retrospective case-control study was conducted on adult and juvenile patients administered tigecycline for >3 days. The adults were classified as TIP, non-TIP (pancreatitis with other causes) and non-pancreatitis. Univariate analyses were performed to compare TIP and non-pancreatitis, and multivariate analysis was used to identify risk factors for TIP. The clinical characteristics of TIP, and the safety and efficiency of tigecycline use in non-TIP were evaluated. RESULTS: A total of 3910 patients (3823 adults and 87 juveniles) were enrolled. The adult patients comprised 21 TIP, 82 non-TIP and 3720 non-pancreatitis. The TIP prevalence was 0.56% in adults and 1.15% in juveniles. The mean time from tigecycline use to symptom onset was 7.2 days, and all cases were mild pancreatitis. The mean time from tigecycline withdrawal to symptom relief was 3.6 days. The multivariate analysis identified comorbid renal insufficiency as an independent risk factor for TIP (odds ratio = 3.032). Among the 82 non-TIP patients, 81.7% had severe pancreatitis and 47.6% had necrotizing pancreatitis. The modified computed tomography severity score after tigecycline use was similar to that before tigecycline use, but the pancreatic enzymes and infection indices were significantly decreased. CONCLUSIONS: The prevalence of TIP was low. Comorbid renal insufficiency was as an independent risk factor for TIP. Tigecycline is safe and efficient for treatment of pancreatitis, especially necrotizing pancreatitis, with intra-abdominal infection.

Laser Cooling of a Lattice Vibration in van der Waals Semiconductor.

Laser cooling atoms and molecules to ultralow temperatures has produced plenty of opportunities in fundamental physics, precision metrology, and quantum science. Although theoretically proposed over 40 years, the laser cooling of certain lattice vibrations (i.e., phonon) remains a challenge owing to the complexity of solid structures. Here, we demonstrate Raman cooling of a longitudinal optical phonon in two-dimensional semiconductor WS2 by red-detuning excitation at the sideband of the exciton (bound electron-hole pair). Strong coupling between the phonon and exciton and appreciable optomechanical coupling rates provide access to cooling high-frequency phonons that are robust against thermal decoherence even at room temperature. Our experiment opens possibilities of laser cooling and control of individual optical phonon and, eventually, possible cooling of matter in van der Waals semiconductor.

Strain Quantum Sensing with Spin Defects in Hexagonal Boron Nitride.

Hexagonal boron nitride is not only a promising functional material for the development of two-dimensional optoelectronic devices but also a good candidate for quantum sensing thanks to the presence of quantum emitters in the form of atom-like defects. Their exploitation in quantum technologies necessitates understanding their coherence properties as well as their sensitivity to external stimuli. In this work, we probe the strain configuration of boron vacancy centers (VB-) created by ion implantation in h-BN flakes thanks to wide-field spatially resolved optically detected magnetic resonance and submicro Raman spectroscopy. Our experiments demonstrate the ability of VB- for quantum sensing of strain and, given the omnipresence of h-BN in 2D-based devices, open the door for in situ imaging of strain under working conditions.

Donor-Acceptor Pair Quantum Emitters in Hexagonal Boron Nitride.

Quantum emitters are needed for a myriad of applications ranging from quantum sensing to quantum computing. Hexagonal boron nitride (hBN) quantum emitters are one of the most promising solid-state platforms to date due to their high brightness and stability and the possibility of a spin-photon interface. However, the understanding of the physical origins of the single-photon emitters (SPEs) is still limited. Here we report dense SPEs in hBN across the entire visible spectrum and present evidence that most of these SPEs can be well explained by donor-acceptor pairs (DAPs). On the basis of the DAP transition generation mechanism, we calculated their wavelength fingerprint, matching well with the experimentally observed photoluminescence spectrum. Our work serves as a step forward for the physical understanding of SPEs in hBN and their applications in quantum technologies.

Magnetic Phase Transitions and Magnetoelastic Coupling in a Two-Dimensional Stripy Antiferromagnet.

Materials with a quasi-one-dimensional stripy magnetic order often exhibit low crystal and magnetic symmetries, thus allowing the presence of various energy coupling terms and giving rise to macroscopic interplay between spin, charge, and phonon. In this work, we performed optical, electrical and magnetic characterizations combined with first-principles calculations on a van der Waals antiferromagnetic insulator chromium oxychloride (CrOCl). We detected the subtle phase transition behaviors of exfoliated CrOCl under varying temperature and magnetic field and clarified its controversial spin structures. We found that the antiferromagnetism and its air stability persist down to few-layer samples, making it a promising candidate for future 2D spintronic devices. Additionally, we verified the magnetoelastic coupling effect in CrOCl, allowing for the potential manipulation of the magnetic states via electric field or strain. These virtues of CrOCl provide us with an ideal platform for fundamental research on spin-charge, spin-phonon coupling, and spin-interactions.

Signature of Cascade Transitions between Interlayer Excitons in a Moiré Superlattice.

A moiré superlattice in transition metal dichalcogenides heterostructure provides an exciting platform for studying strongly correlated electronics and excitonic physics, such as multiple interlayer exciton (IX) energy bands. However, the correlations between these IXs remain elusive. Here, we demonstrate the cascade transitions between IXs in a moiré superlattice by performing energy- and time-resolved photoluminescence measurements in the MoS_{2}/WSe_{2} heterostructure. Furthermore, we show that the lower-energy IX can be excited to higher-energy ones, facilitating IX population inversion. Our finding of cascade transitions between IXs contributes to the fundamental understanding of the IX dynamics in moiré superlattices and may have important applications, such as in exciton condensate, quantum information protocols, and quantum cascade lasers.

Robust Room Temperature Valley Hall Effect of Interlayer Excitons.

The Berry curvature in the band structure of transition metal dichalcogenides (TMDs) introduces a valley-dependent effective magnetic field, which induces the valley Hall effect (VHE). Similar to the ordinary Hall effect, the VHE spatially separates carriers or excitons, depending on their valley index, and accumulates them at opposite sample edges. The VHE can play a key role in valleytronic devices, but previous observations of the VHE have been limited to cryogenic temperatures. Here, we report a demonstration of the VHE of interlayer excitons in a MoS2/WSe2 heterostructure at room temperature. We monitored the in-plane propagation of interlayer excitons through photoluminescence mapping and observed their spatial separation into two opposite transverse directions that depended on the valley index of the excitons. Our theoretical simulations reproduced the salient features of these observations. Our demonstration of the robust interlayer exciton VHE at room temperature, enabled by their intrinsically long lifetimes, will open up realistic possibilities for the development of opto-valleytronic devices based on TMD heterostructures.

Overexpression of KLF14 protects against immune-mediated hepatic injury in mice.

The underlying immunopathogenic mechanisms of autoimmune hepatitis (AIH) have not yet been well elucidated. An impairment in regulatory T cells (Tregs) is key to the development of AIH. Krüppel-like factors (KLFs) regulate a broad of cellular processes including immunocyte maturation. KLF14 may regulate Treg differentiation, but the biological functions remain far from elucidated. In this study, we identified the hepatic expression of KLF14 in human and murine liver diseases. Immune-mediated hepatitis was induced by concanavalin A (Con A). A KLF14 recombinant adenoviruses plasmid (Ad-KLF14) was constructed and injected into mice. Tregs were assessed by flow cytometry analysis; inflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), were tested by enzyme-linked immunosorbent assay (ELISA). The expression of KLF14 was suppressed in a time-and dose-dependent manner. Changes in cytokine levels were consistent with the degree of hepatic injury. Overexpression of KLF14 protected the liver from immune-mediated damage in vivo. Ad-KLF14 transfection before Con A challenge increased the frequency of Tregs in liver mononuclear cells (MNCs), and suppressed the expression of cytokines. All of these improvements were completely abrogated after Treg deletion in vivo by intraperitoneal injection of a CD25 antibody. In conclusion, these data suggest that KLF14 plays an as-yet unrecognized role in immune-mediated hepatitis mainly via induced Treg differentiation. Our findings extend the knowledge of the biological function of KLF14 to the autoimmune disease field, and indicate the possibility of KLF14 as a therapeutic target in AIH patients.

Determining layer number of two-dimensional flakes of transition-metal dichalcogenides by the Raman intensity from substrates.

Transition-metal dichalcogenide (TMD) semiconductors have been widely studied due to their distinctive electronic and optical properties. The property of TMD flakes is a function of their thickness, or layer number (N). How to determine the N of ultrathin TMD materials is of primary importance for fundamental study and practical applications. Raman mode intensity from substrates has been used to identify the N of intrinsic and defective multilayer graphenes up to N = 100. However, such analysis is not applicable to ultrathin TMD flakes due to the lack of a unified complex refractive index (ñ) from monolayer to bulk TMDs. Here, we discuss the N identification of TMD flakes on the SiO2/Si substrate by the intensity ratio between the Si peak from 100 nm (or 89 nm) SiO2/Si substrates underneath TMD flakes and that from bare SiO2/Si substrates. We assume the real part of ñ of TMD flakes as that of monolayer TMD and treat the imaginary part of ñ as a fitting parameter to fit the experimental intensity ratio. An empirical ñ, namely, ñ(eff), of ultrathin MoS2, WS2 and WSe2 flakes from monolayer to multilayer is obtained for typical laser excitations (2.54 eV, 2.34 eV or 2.09 eV). The fitted ñ(eff) of MoS2 has been used to identify the N of MoS2 flakes deposited on 302 nm SiO2/Si substrate, which agrees well with that determined from their shear and layer-breathing modes. This technique of measuring Raman intensity from the substrate can be extended to identify the N of ultrathin 2D flakes with N-dependent ñ. For application purposes, the intensity ratio excited by specific laser excitations has been provided for MoS2, WS2 and WSe2 flakes and multilayer graphene flakes deposited on Si substrates covered by a 80-110 nm or 280-310 nm SiO2 layer.

Application of the steady-state intestinal perfusion system in measuring intestinal fluid absorption and bicarbonate secretion in vivo.

Background: The steady-state intestinal perfusion system represents a tool used in measuring intestinal fluid absorption and bicarbonate secretion in vivo; however, detailed procedures and parameters were not elucidated fully. Aim: We focused on the methods of the steady-state intestinal perfusion system comprehensively including the blood pressure, hematocrit, blood gas, and heart rate of mouse. Methods: Anesthetized, tracheally intubated, and artificially ventilated mice were used for this system. The blood pressure, hematocrit, blood gas, heart rate, and rate of fluid absorption and HCO3 - secretion of the small intestine and colon at different time points were evaluated. Results: Blood pressure, hematocrit, blood gas, and heart rate became stable at the 30 min time point after completion of surgery and could be maintained for 2 h. Rates of fluid absorption and bicarbonate secretion were also kept stable during the period of steady state of mice. Rates of fluid absorption and bicarbonate secretion were different among the jejunum, ileum, proximal, and mid-distal colon. Conclusion: The steady-state intestinal perfusion system is a reliable system for measuring intestinal fluid absorption and bicarbonate secretion in vivo.

Quantum interference between dark-excitons and zone-edged acoustic phonons in few-layer WS2.

Fano resonance which describes a quantum interference between continuum and discrete states, provides a unique method for studying strongly interacting physics. Here, we report a Fano resonance between dark excitons and zone-edged acoustic phonons in few-layer WS2 by using the resonant Raman technique. The discrete phonons with large momentum at the M-point of the Brillouin zone and the continuum dark exciton states related to the optically forbidden transition at K and Q valleys are coupled by the exciton-phonon interactions. We observe rich Fano resonance behaviors across layers and modes defined by an asymmetry-parameter q: including constructive interference with two mirrored asymmetry Fano peaks (weak coupling, q > 1 and q < - 1), and destructive interference with Fano dip (strong coupling, ∣q∣ < < 1). Our results provide new insight into the exciton-phonon quantum interference in two-dimensional semiconductors, where such interferences play a key role in their transport, optical, and thermodynamic properties.

Interlayer donor-acceptor pair excitons in MoSe2/WSe2 moiré heterobilayer.

Localized interlayer excitons (LIXs) in two-dimensional moiré superlattices exhibit sharp and dense emission peaks, making them promising as highly tunable single-photon sources. However, the fundamental nature of these LIXs is still elusive. Here, we show the donor-acceptor pair (DAP) mechanism as one of the origins of these excitonic peaks. Numerical simulation results of the DAP model agree with the experimental photoluminescence spectra of LIX in the moiré MoSe2/WSe2 heterobilayer. In particular, we find that the emission energy-lifetime correlation and the nonmonotonic power dependence of the lifetime agree well with the DAP IX model. Our results provide insight into the physical mechanism of LIX formation in moiré heterostructures and pave new directions for engineering interlayer exciton properties in moiré superlattices.

Development of a Deep Learning System to Detect Esophageal Cancer by Barium Esophagram.

Background: Implementation of deep learning systems (DLSs) for analysis of barium esophagram, a cost-effective diagnostic test for esophageal cancer detection, is expected to reduce the burden to radiologists while ensuring the accuracy of diagnosis. Objective: To develop an automated DLS to detect esophageal cancer on barium esophagram. Methods: This was a retrospective study using deep learning for esophageal cancer detection. A two-stage DLS (including a Selection network and a Classification network) was developed. Five datasets based on barium esophagram were used for stepwise training, validation, and testing of the DLS. Datasets 1 and 2 were used to respectively train and test the Selection network, while Datasets 3, 4, and 5 were respectively used to train, validate, and test the Classification network. Finally, a positioning box with a probability value was outputted by the DLS. A region of interest delineated by experienced radiologists was selected as the ground truth to evaluate the detection and classification efficiency of the DLS. Standard machine learning metrics (accuracy, recall, precision, sensitivity, and specificity) were calculated. A comparison with the conventional visual inspection approach was also conducted. Results: The accuracy, sensitivity, and specificity of our DLS in detecting esophageal cancer were 90.3%, 92.5%, and 88.7%, respectively. With the aid of DLS, the radiologists' interpretation time was significantly shortened (Reader1, 45.7 s vs. 72.2 s without DLS aid; Reader2, 54.1 s vs. 108.7 s without DLS aid). Respective diagnostic efficiencies for Reader1 with and without DLS aid were 96.8% vs. 89.3% for accuracy, 97.5% vs. 87.5% for sensitivity, 96.2% vs. 90.6% for specificity, and 0.969 vs. 0.890 for AUC. Respective diagnostic efficiencies for Reader2 with and without DLS aid were 95.7% vs. 88.2% for accuracy, 92.5% vs. 77.5% for sensitivity, 98.1% vs. 96.2% for specificity, and 0.953 vs. 0.869 for AUC. Of note, the positioning boxes outputted by the DLS almost overlapped with those manually labeled by the radiologists on Dataset 5. Conclusions: The proposed two-stage DLS for detecting esophageal cancer on barium esophagram could effectively shorten the interpretation time with an excellent diagnostic performance. It may well assist radiologists in clinical practice to reduce their burden.

Layer-engineered interlayer excitons.

Photoluminescence (PL) from excitons serves as a powerful tool to characterize the optoelectronic property and band structure of semiconductors, especially for atomically thin two-dimensional transition metal dichalcogenide (TMD) materials. However, PL quenches quickly when the thickness of TMD materials increases from monolayer to a few layers, due to the change from direct to indirect band transition. Here, we show that PL can be recovered by engineering multilayer heterostructures, with the band transition reserved to be a direct type. We report emission from layer-engineered interlayer excitons from these multilayer heterostructures. Moreover, as desired for valleytronics devices, the lifetime, valley polarization, and valley lifetime of the generated interlayer excitons can all be substantially improved as compared with that in the monolayer-monolayer heterostructure. Our results pave the way for controlling the properties of interlayer excitons by layer engineering.

Inhibition of Na+ /H+ exchanger isoform 3 improves gut fluidity and alkalinity in cystic fibrosis transmembrane conductance regulator-deficient and F508del mutant mice.

BACKGROUND AND PURPOSE: Constipation and intestinal obstructive episodes are major health problems in cystic fibrosis (CF) patients. Three FDA-approved drugs against constipation-prone irritable bowel syndrome were tested for their ability to increase luminal fluidity and alkalinity in cystic fibrosis transmembrane conductance regulator (CFTR) null (cftr-/- ) and F508del mutant (F508delmut/mut ) murine intestine. EXPERIMENTAL APPROACH: Guanylate cyclase C agonist linaclotide, PGE1 analogue lubiprostone and intestine-specific NHE3 inhibitor tenapanor were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anaesthetized cftr-/- , F508delmut/mut and WT mice. Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration. KEY RESULTS: Basal jejunal fluid absorptive rates were significantly higher and basal HCO3- output was significantly lower in cftr-/- and F508delmut/mut compared to WT mice. In cftr-/- and F508delmut/mut mice, all three drugs significantly inhibited the fluid absorptive rate and increased alkaline output in the jejunum and tenapanor and lubiprostone, but not linaclotide, in the colon. After tenapanor pre-incubation, linaclotide elicited a robust fluid secretory response in WT jejunum, while no further change in absorptive rates was observed in cftr-/- and F508delmut/mut jejunum, suggesting that the increase in gut fluidity and alkalinity by linaclotide in CF gut is mediated via NHE3 inhibition. Lubiprostone also inhibited fluid absorption in cftr-/- and F508delmut/mut jejunum via NHE3 inhibition but had a residual NHE3-independent effect. CONCLUSION AND IMPLICATIONS: Linaclotide, lubiprostone and tenapanor reduced fluid absorption and increased alkaline output in the CF gut. Their application may ameliorate constipation and reduce obstructive episodes in CF patients.

Electrically controllable router of interlayer excitons.

Optoelectronic devices that allow rerouting, modulation, and detection of the optical signals would be extremely beneficial for telecommunication technology. One of the most promising platforms for these devices is excitonic devices, as they offer very efficient coupling to light. Of especial importance are those based on indirect excitons because of their long lifetime. Here, we demonstrate excitonic transistor and router based on bilayer WSe2 Because of their strong dipole moment, excitons in bilayer WSe2 can be controlled by transverse electric field. At the same time, unlike indirect excitons in artificially stacked heterostructures based on transition metal dichalcogenides, naturally stacked bilayers are much simpler in fabrication.