Engineering the Band Topology in a Rhombohedral Trilayer Graphene Moiré Superlattice.

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.

Chemical Potential Characterization of Symmetry-Breaking Phases in a Rhombohedral Trilayer Graphene.

Rhombohedral trilayer graphene has recently emerged as a natural flat-band platform for studying interaction-driven symmetry-breaking phases. The displacement field (D) can further flatten the band to enhance the density of states, thereby controlling the electronic correlation that tips the energy balance between spin and valley degrees of freedom. To characterize the energy competition, chemical potential measurement─a direct thermodynamic probe of Fermi surfaces─is highly demanding to be conducted under a constant D. In this work, we characterize D-dependent isospin flavor polarization, where electronic states with isospin degeneracies of one and two can be identified. We also developed a method to measure the chemical potential at a fixed D, allowing for the extraction of energy variation during phase transitions. Furthermore, symmetry breaking could also be invoked in Landau levels, manifesting as quantum Hall ferromagnetism. Our work opens more opportunities for the thermodynamic characterization of displacement-field tuned van der Waals heterostructures.

The intervention effect of Aitongxiao prescription on primary liver cancer rats was evaluated based on high-throughput miRNA sequencing and bioinformatics analysis.

Liver cancer is a common malignant tumor known for its difficult treatment and poor prognosis. As a traditional Chinese medicine prescription, Aitongxiao prescription (ATXP) has been used in clinical treatment of primary liver cancer (PLC) for more than ten years, and its therapeutic effect is obvious and has been verified over time. However, the mechanism of ATXP in treating PLC has not been fully elucidated. This study aimed to detect the liver-protective effect of ATXP on a PLC rat model and explore its potential mechanism from the perspective of plasma extracellular vesicle miRNAs. Fifty SPF male SD rats were randomly selected, with six rats as the control group, and the remaining rats were injected with DEN to establish a primary liver cancer model. The model rats were randomly divided into the model group and the ATXP group. After 4 weeks of intervention, the liver-protective effect of ATXP was evaluated using plasma biochemical indicators and histopathological methods. Plasma extracellular vesicles were isolated and extracted, and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Significant differentially expressed miRNAs in extracellular vesicles were screened by Illumina sequencing to explore the therapeutic targets of ATXP and conduct functional analysis. The results showed that ATXP significantly reduced plasma liver function in PLC rats and alleviated liver pathological damage. In addition, plasma extracellular vesicles were isolated and identified. According to the results of GO and KEGG analysis, they were related to multiple biological processes and covered multiple signaling pathways (PI3K-Akt and MAPK signaling pathways, etc.). The interaction between miR-199a-3p and MAP3K4 was determined by bioinformatics methods and dual-luciferase reporter gene detection, confirming that MAP3K4 is the target gene of miR-199a-3p. In conclusion, ATXP protects the liver from DEN-induced PLC, which may be related to the regulation of plasma extracellular vesicle miR-199a-3p. This study further reveals the mechanism of ATXP in treating liver cancer and provides a theoretical basis for subsequent research.

Giant ferroelectric polarization in a bilayer graphene heterostructure.

At the interface of van der Waals heterostructures, the crystal symmetry and the electronic structure can be reconstructed, giving rise to physical properties superior to or absent in parent materials. Here by studying a Bernal bilayer graphene moiré superlattice encapsulated by 30°-twisted boron nitride flakes, we report an unprecedented ferroelectric polarization with the areal charge density up to 1013 cm-2, which is far beyond the capacity of a moiré band. The translated polarization ~5 pC m-1 is among the highest interfacial ferroelectrics engineered by artificially stacking van der Waals crystals. The gate-specific ferroelectricity and co-occurring anomalous screening are further visualized via Landau levels, and remain robust for Fermi surfaces outside moiré bands, confirming their independence on correlated electrons. We also find that the gate-specific resistance hysteresis loops could be turned off by the other gate, providing an additional control knob. Furthermore, the ferroelectric switching can be applied to intrinsic properties such as topological valley current. Overall, the gate-specific ferroelectricity with strongly enhanced charge polarization may encourage more explorations to optimize and enrich this novel class of ferroelectricity, and promote device applications for ferroelectric switching of various quantum phenomena.

Multivalley Superconductivity in Monolayer Transition Metal Dichalcogenides.

In transition metal dichalcogenides (TMDs), Ising superconductivity with an antisymmetric spin texture on the Fermi surface has attracted wide interest due to the exotic pairing and topological properties. However, it is not clear whether the Q valley with a giant spin splitting is involved in the superconductivity of heavily doped semiconducting 2H-TMDs. Here by taking advantage of a high-quality monolayer WS2 on hexagonal boron nitride flakes, we report an ionic-gating induced superconducting dome with a record high critical temperature of ∼6 K, accompanied by an emergent nonlinear Hall effect. The nonlinearity indicates the development of an additional high-mobility channel, which (corroborated by first principle calculations) can be ascribed to the population of Q valleys. Thus, multivalley population at K and Q is suggested to be a prerequisite for developing superconductivity. The involvement of Q valleys also provides insights to the spin textured Fermi surface of Ising superconductivity in the large family of transition metal dichalcogenides.

Integrated Plasma Metabolomics and Gut Microbiota Analysis: The Intervention Effect of Jiawei Xiaoyao San on Liver Depression and Spleen Deficiency Liver Cancer Rats.

Primary liver cancer is the third most common malignancy, and hepatocellular carcinoma is its main subtype, with a high recurrence rate and high mortality. Intestinal microflora and metabolic disorders are present in most HCC patients. Traditional Chinese medicine (TCM) plays an important role in the composition of intestinal microorganisms and the transformation of active metabolites. Many scholars are trying to develop related drugs to assist in the treatment of liver cancer. In the preliminary study of the research group, it was found that the Jiawei Xiaoyao San has a certain therapeutic effect on liver cancer, but the specific mechanism is still unclear. Therefore, this study constructed a liver cancer rat model with liver stagnation and spleen deficiency, to explore the regulatory effect of Jiawei Xiaoyao San on plasma metabolites and intestinal microflora and to find the potential mechanism of Jiawei Xiaoyao San in the treatment of liver cancer. Plasma samples and fecal samples were collected from liver cancer rats with liver depression and spleen deficiency for microbiome 16S rDNA sequencing and metabolic ESI-QTRAP-MS/MS analysis. Various bioinformatics methods were used to analyze the dataset individually and in combination. The analysis and identification of plasma metabolomics showed that the intervention effect of Jiawei Xiaoyao San on liver cancer rats with liver depression and spleen deficiency was related to 11 differential metabolites and signal pathways such as primary bile acid biosynthesis, phenylalanine metabolism, pantothenate and COA biosynthesis, metabolic pathways, cholesterol metabolism, and bile secretion. Combined with fecal microbiological analysis, it was found that Jiawei Xiaoyao San could significantly change the composition of intestinal flora in liver cancer rates, increase beneficial bacteria, and reduce the composition of harmful bacteria. This study provides some experimental basis for the traditional Chinese medicine theory and clinical application of Jiawei Xiaoyao San in the adjuvant treatment of liver cancer. The potential mechanism may be to regulate metabolism and intestinal flora to play the role of regulating liver depression, activating blood, and detoxifying, to achieve the purpose of adjuvant treatment of liver cancer.

Weighing patient attributes in antibiotic prescribing for upper respiratory tract infections: A discrete choice experiment on primary care physicians in Hubei Province, China.

Objectives: This study aimed to determine how primary care physicians weigh intervenable patient attributes in their decisions of antibiotic prescribing for upper respiratory tract infections (URTIs). Methods: A discrete choice experiment (DCE) was conducted on 386 primary care physicians selected through a stratified cluster sampling strategy in Hubei province, China. The patient attributes tested in the DCE were identified through semi-structured interviews with 13 primary care physicians, while the choice scenarios were determined by a D-efficient design with a zero prior parameter value. Conditional logit models (CL) and mixed logit models (MXL) were established to determine the preference of the study participants in antibiotic prescribing for URTI patients with various attributes. Relative importance (RI) was calculated to reflect the influence of each attribute. Results: In addition to age and duration of symptoms, the interventionable patient attributes were also considered by the primary care physicians in their antibiotic prescribing decisions. They preferred to prescribe antibiotics for URTI patients with difficulties to schedule a follow-up appointment (p < 0.001) and for those without a clear indication of refusal to antibiotics (p < 0.001). Patient request for antibiotics had an RI ranging from 15.2 to 16.3%, compared with 5.1-5.4% for easiness of follow-up appointment. The influence of these two interventionable patient attributes was most profound in the antibiotic prescribing decisions for patients aged between 60 and 75 years as indicated by their interaction effects with age (ß = 0.69 for request for antibiotics, p < 0.01; ß = -1.2 for easiness of follow-up, p < 0.001). Conclusion: Reducing patient pressure and improving accessibility and continuity of care may help primary care physicians make rational antibiotic prescribing decisions for URTIs.

Effects of Volume-Price Contracts on Pharmaceutical Prices: A Retrospective Comparative Study of Public Hospitals in Hubei of China.

Background: Pharmaceutical expenditure has been increasing worldwide. Many countries have attempted to contain the increase through collective bargaining, including in China. In 2015, the Chinese government introduced a new policy to empower regional governments to reduce pharmaceutical prices through its existing tendering system which enables a lower price for products with higher procurement volumes. Xiangyang municipality in Hubei province took a lead in piloting this initiative. Objectives: This study aimed to evaluate the effects of the volume-price contract initiative on pharmaceutical price procured by the public hospitals in Xiangyang. Methods: A retrospective comparative design was adopted. The price of cardiovascular medicines (349 products under 164 International Nonproprietary Names) procured by the public hospitals in Xiangyang was compared with those procured in Yichang municipality in Hubei. A total of 15,921 procurement records over the period from January 2017 to December 2018 were examined (Xiangyang started the volume-price contract initiative in January 2018). Generalized linear regression models with a difference-in-differences approach which could reflect the differences between the two cities between January 2018 and December 2018 were established to test the effects of the volume-price contract initiative on pharmaceutical prices. Results: On average, the procurement price for cardiovascular medicines adjusted by defined daily dosage in Xiangyang dropped by 41.51%, compared with a 0.22% decrease in Yichang. The difference-in-differences results showed that the volume-price contract initiative resulted in a 36.24% drop (p = 0.006) in the price (30.23% for the original brands, p = 0.008), in addition to the therapeutic competition effect (31.61% reduction in the price, p = 0.002). The top 100 domestic suppliers were highly responsive to the initiative (82.80% drop in the price, p = 0.001). Conclusion: The volume-price contract initiative has the potential to bring down the price of pharmaceutical supplies. Higher responses from the domestic suppliers are evident.