Correlated states in twisted double bilayer graphene

Electron-electron interactions play an important role in graphene and related systems and can induce exotic quantum states, especially in a stacked bilayer with a small twist angle. For bilayer graphene where the two layers are twisted by a "magic angle", flat band and strong many-body effects lead to correlated insulating states and superconductivity. In contrast to monolayer graphene, the band structure of untwisted bilayer graphene can be further tuned by a displacement field, providing an extra degree of freedom to control the flat band that should appear when two bilayers are stacked on top of each other. Here, we report the discovery and characterization of such displacement-field tunable electronic phases in twisted double bilayer graphene. We observe insulating states at a half-filled conduction band in an intermediate range of displacement fields. Furthermore, the resistance gap in the correlated insulator increases with respect to the in-plane magnetic fields and we find that the g factor according to spin Zeeman effect is ~2, indicating spin polarization at half filling. These results establish the twisted double bilayer graphene as an easily tunable platform for exploring quantum many-body states

Identification and Functional Analysis of Variant Haplotypes in the 5′-Flanking Region of Protein Phosphatase 2A-Bδ Gene

Serine-threonine protein phosphatase 2A (PP2A) is a trimeric holoenzyme that plays an integral role in the regulation of cell growth, differentiation, and apoptosis. The substrate specificity and (sub)cellular localization of the PP2A holoenzymes are highly regulated by interaction with a family of regulatory B subunits (PP2A-Bs). The regulatory subunit PP2A-B/PR55δ (PP2A-Bδ) is involving in the dephosphorylation of PP2A substrates and is crucial for controlling entry into and exit from mitosis. The molecular mechanisms involved in the regulation of expression of PP2A-Bδ gene (PPP2R2D) remain largely unknown. To explore genetic variations in the 5′-flanking region of PPP2R2D gene as well as their frequent haplotypes in the Han Chinese population and determine whether such variations have an impact on transcriptional activity, DNA samples were collected from 70 healthy Chinese donors and sequenced for identifying genetic variants in the 5′-flanking region of PPP2R2D. Four genetic variants were identified in the 1836 bp 5′-flanking region of PPP2R2D. Linkage disequilibrium (LD) patterns and haplotype profiles were constructed for the genetic variants. Using serially truncated human PPP2R2D promoter luciferase constructs, we found that a 601 bp (−540 nt to +61 nt) fragment constitutes the core promoter region. The subcloning of individual 5′-flanking fragment revealed the existence of three haplotypes in the distal promoter of PPP2R2D. The luciferase reporter assay showed that different haplotypes exhibited distinct promoter activities. The EMSA revealed that the −462 G>A variant influences DNA-protein interactions involving the nuclear factor 1 (NF1). In vitro reporter gene assay indicated that cotransfection of NF1/B expression plasmid could positively regulate the activity of PPP2R2D proximal promoter. Introduction of exogenous NF1/B expression plasmid further confirmed that the NF1 involves in the regulation of PPP2R2D gene expression. Our findings suggest that functional genetic variants and their haplotypes in the 5′-flanking region of PPP2R2D are critical for transcriptional regulation of PP2A-Bδ

High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial

Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment

Celastrol Inhibits the Growth of Ovarian Cancer Cells in vitro and in vivo

Celastrol is a natural triterpene isolated from the Chinese plant Thunder God Vine with potent antitumor activity. However, the effect of celastrol on the growth of ovarian cancer cells in vitro and in vivo is still unclear. In this study, we found that celastrol induced cell growth inhibition, cell cycle arrest in G2/M phase and apoptosis with the increased intracellular reactive oxygen species (ROS) accumulation in ovarian cancer cells. Pretreatment with ROS scavenger N-acetyl-cysteine totally blocked the apoptosis induced by celastrol. Additionally, celastrol inhibited the growth of ovarian cancer xenografts in nude mice. Altogether, these findings suggest celastrol is a potential therapeutic agent for treating ovarian cancer

A comparative study of virus nucleic acid re-positive and non-re-positive patients infected with SARS-CoV-2 Delta variant strain in the Ningxia Hui Autonomous Region

ObjectiveThis study aimed to provide a basis for epidemic prevention and control measures as well as the management of re-positive personnel by analyzing and summarizing the characteristics of re-positive patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infections discharged from a hospital in the Ningxia Hui Autonomous Region in 2021.MethodsThis case-control study included a total of 45 patients with Delta variant infections diagnosed in the Fourth People's Hospital of the Ningxia Hui Autonomous Region between October 17 and November 28, 2021. Based on the nucleic acid test results post-discharge, the patients were dichotomized into re-positive and non-re-positive groups. Based on the time of the first re-positive test, the re-positive group was further divided into <7 and ≥7 days groups to compare their clinical characteristics and explore the possible influencing factors of this re-positivity.ResultsOf the 45 total patients, 16 were re-positive (re-positivity rate: 35.6%), including four patients who were re-positive after 2 weeks (re-positivity rate: 8.8%). The median time of the first re-positive after discharge was 7 days (IQR: 14-3). The re-positive group was younger than the non-re-positive group (35 vs. 53, P < 0.05), had a higher proportion of patients who were not receiving antiviral therapy (56.2 vs. 17.2%, P < 0.05). The median CT value of nucleic acid in the re-positive group was considerably greater than that at admission (36.7 vs. 22.6 P < 0.05). The findings demonstrated that neutralizing antibody treatment significantly raised the average IgG antibody level in patients, particularly in those who had not received COVID-19 vaccine (P < 0.05). The median lowest nucleic acid CT value of the ≥7 days group during the re-positive period and the immunoglobulin G (IgG) antibody level at discharge were lower than those in the <7 days group (P < 0.05). When compared to the non-positive group, patients in the ≥7 days group had a higher median virus nucleic acid CT value (27.1 vs. 19.2, P < 0.05) and absolute number of lymphocytes at admission (1,360 vs. 952, P < 0.05), and a lower IgG antibody level at discharge (P < 0.05).ConclusionsIn conclusion, this study found that: (1) The re-positivity rate of SARS-CoV-2 Delta variant infection in this group was 35.6%, while the re-positivity rate was the same as that of the original strain 2 weeks after discharge (8.0%). (2) Young people, patients who did not use antiviral therapy or had low IgG antibody levels at discharge were more likely to have re-positive. And the CT value of nucleic acid at the time of initial infection was higher in re-positive group. We speculated that the higher the CT value of nucleic acid at the time of initial infection, the longer the intermittent shedding time of the virus. (3) Re-positive patients were asymptomatic. The median CT value of nucleic acid was > 35 at the re-positive time, and the close contacts were not detected as positive. The overall transmission risk of re-positive patients is low

Layer-by-Layer Epitaxy of Multilayer MoS2 Wafers

Two-dimensional (2D) semiconductor of MoS2 has great potential for advanced electronics technologies beyond silicon1-9. So far, high-quality monolayer MoS2 wafers10-12 are already available and various demonstrations from individual transistors to integrated circuits have also been shown13-15. In addition to the monolayer, multilayers have narrower band gaps but improved carrier mobilities and current capacities over the monolayer5,16-18. However, achieving high-quality multilayer MoS2 wafers remains a challenge. Here we report the growth of high quality multilayer MoS2 4-inch wafers via the layer-by-layer epitaxy process. The epitaxy leads to well-defined stacking orders between adjacent epitaxial layers and offers a delicate control of layer numbers up to 6. Systematic evaluations on the atomic structures and electronic properties were carried out for achieved wafers with different layer numbers. Significant improvements on device performances were found in thicker-layer field effect transistors (FETs), as expected. For example, the average field-effect mobility ({\mu}FE) at room temperature (RT) can increase from ~80 cm2V-1s-1 for monolayer to ~110/145 cm2V-1s-1 for bilayer/trilayer devices. The highest RT {\mu}FE=234.7 cm2V-1s-1 and a record-high on-current densities of 1.704 mA{\mu}m-1 at Vds=2 V were also achieved in trilayer MoS2 FETs with a high on/off ratio exceeding 107. Our work hence moves a step closer to practical applications of 2D MoS2 in electronics.Comment: 13 pages,4 Figure