Two-dimensional Massless Dirac Fermions in Antiferromagnetic AFe2As2 (A = Ba, Sr)

We report infrared studies of AFe$_{2}$As$_{2}$ (A = Ba, Sr), two representative parent compounds of iron-arsenide superconductors, at magnetic fields (B) up to 17.5 T. Optical transitions between Landau levels (LLs) were observed in the antiferromagnetic states of these two parent compounds. Our observation of a $\sqrt{B}$ dependence of the LL transition energies, the zero-energy intercepts at B = 0 T under the linear extrapolations of the transition energies and the energy ratio ($\sim$ 2.4) between the observed LL transitions, combined with the linear band dispersions in two-dimensional (2D) momentum space obtained by theoretical calculations, demonstrates the existence of massless Dirac fermions in antiferromagnetic BaFe$_{2}$As$_{2}$. More importantly, the observed dominance of the zeroth-LL-related absorption features and the calculated bands with extremely weak dispersions along the momentum direction $k_{z}$ indicate that massless Dirac fermions in BaFe$_{2}$As$_{2}$ are 2D. Furthermore, we find that the total substitution of the barium atoms in BaFe$_{2}$As$_{2}$ by strontium atoms not only maintains 2D massless Dirac fermions in this system, but also enhances their Fermi velocity, which supports that the Dirac points in iron-arsenide parent compounds are topologically protected.Comment: Magneto-infrared study, Landau level spectroscopy, DFT+DMFT calculation

Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7

For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1

Antibacterial activity and mechanism of a scorpion venom peptide derivative in vitro and in vivo.

BmKn2 is an antimicrobial peptide (AMP) characterized from the venom of scorpion Mesobuthus martensii Karsch by our group. In this study, Kn2-7 was derived from BmKn2 to improve the antibacterial activity and decrease hemolytic activity. Kn2-7 showed increased inhibitory activity against both gram-positive bacteria and gram-negative bacteria. Moreover, Kn2-7 exhibited higher antibacterial activity against clinical antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). In addition, the topical use of Kn2-7 effectively protected the skin of mice from infection in an S. aureus mouse skin infection model. Kn2-7 exerted its antibacterial activity via a bactericidal mechanism. Kn2-7 killed S. aureus and E. coli rapidly by binding to the lipoteichoic acid (LTA) in the S. aureus cell wall and the lipopolysaccharides (LPS) in the E. coli cell wall, respectively. Finally, the hemolytic activity of Kn2-7 was significantly decreased, compared to the wild-type peptide BmKn2. Taken together, the Kn2-7 peptide can be developed as a topical therapeutic agent for treating bacterial infections

Improved deposition quality of calcium-phosphate coating on the surface of WE43 magnesium alloy via FCVA sputtering pretreatment

Calcium-phosphate (CaP) coatings have been widely used in the field of biodegradable magnesium alloys. This paper provides a novel pretreatment method before depositing CaP coatings on the surface of WE43 biomedical magnesium alloys. The surface morphology, phase composition, corrosion resistance and in vitro biological properties of coated samples were investigated. The results showed that a uniform and dense CaP coating formed on the surface of WE43 magnesium alloy pretreated by FCVA (Filtered Cathode Vacuum Arc Technology) possessed better corrosion resistance. Compared with WE43 substrate, Icorr of FCVA/CaP sample decreased by 85.56%. The ALP activity, OD value of COL secretion and mineralization of FCVA/CaP sample reached nearly 2 times higher than that of bare WE43

Lgr4 is crucial for skin carcinogenesis by regulating MEK/ERK and Wnt/β-catenin signaling pathways

Lgr4 is a member of the leucine-rich, G protein-coupled receptor family of proteins, and has recently been shown to augment Wnt/β-catenin signaling via binding to Wnt agonists R-spondins. It plays an important role in skin development, but its involvement in skin tumorigenesis is unclear. Here, we report that mice deficient for Lgr4 are resistant to 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced keratinocyte proliferation and papilloma formation. We show that TPA treatment activates MEK1, ERK1/2 and downstream effector AP-1 in wild-type (WT) epidermal cells and mice, but not in cells or mice where Lgr4 is depleted. Wnt/β-catenin signaling is also dramatically activated by TPA treatment, and this activation is abolished when Lgr4 is deleted. We provide evidences that blocking both MEK1/ERK1/2 and Wnt/β-catenin pathways prevents TPA-induced increase in the expression of Ccnd1 (cyclin D1), a known Wnt/β-catenin target gene, and that the activation of MEK1/ERK1/2 pathway lies upstream of Wnt/β-catenin signal pathway. Collectively, our findings identify Lgr4 as a critical positive factor for skin tumorigenesis by mediating the activation of MEK1/ERK1/2 and Wnt/β-catenin pathways

Re-stratification of patients with copy-number low endometrial cancer by clinicopathological characteristics

Abstract Objective To stratify patients with copy-number low (CNL) endometrial cancer (EC) by clinicopathological characteristics. Methods EC patients who underwent surgery between June 2018 and June 2022 at Peking University People’s Hospital were included and further classified according to TCGA molecular subtyping: POLE ultramutated, microsatellite instability high (MSI-H), CNL, and copy-number high (CNH). Clinicopathological characteristics and prognosis of CNL patients were retrospectively reviewed. The Cox proportional hazards regression model was applied to perform univariate and multivariate analysis, and independent risk factors were identified. Differentially expressed genes (DEGs) according to overall survival (OS) were screened based on the transcriptome of CNL cases from the TCGA program. Finally, a nomogram was established, with an accuracy analysis performed. Results (1) A total of 279 EC patients were included, of whom 168 (60.2%) were in the CNL group. A total of 21 patients had recurrence and 6 patients deceased, and no significant difference in recurrence-free survival (RFS) was exhibited among the four molecular subtypes (P = 0.104), but that in overall survival (OS) was statistically significant (P = 0.036). (2) CNL patients were divided into recurrence and non-recurrence groups, and significant differences (P < 0.05) were found between the two groups in terms of pathological subtype, FIGO stage, ER, PR, glycated hemoglobin (HbA1c), and high-density lipoprotein cholesterol (HDL-C). All the above factors were included in univariate and multivariate Cox regression models, among which pathological subtype, PR, and HDL-C were statistically different (P < 0.05), resulting in three independent risk factors for the prognosis of patients in the CNL group. (3) By comparing the transcriptome of tumor tissues between living and deceased CNL patients from the TCGA database, 903 (4.4%) DEGs were screened, with four lipid metabolism pathways significantly enriched. Finally, a nomogram was established, and internal cross-validation was performed, showing good discrimination accuracy with an AUC of 0.831 and a C-index of 0.748 (95% CI 0.444–1.052). (4) According to the established nomogram and the median total score (85.89), patients were divided into the high score group (n = 85) and low score group (n = 83), and the 8 patients with recurrence were all in the high score group. Survival analysis was performed between the two groups, and the difference in RFS was statistically significant (P = 0.010). Conclusion In the CNL group of EC patients, pathological subtype, PR, and HDL-C were independent prognostic risk factors, the nomogram established based upon which had a good predictive ability for the recurrence risk of patients with CNL EC

Secondary structure and enzyme release assay of Kn2-7.

<p>(A) and (B) Secondary structure analysis of the Kn2-7 and BmKn2 peptides. (A) Circular dichroism spectra of 0.1 mg/mL of Kn2-7 in water, 30% TFE/H₂O or 70% TFE/H₂O. (B) Circular dichroism spectra of 0.1 mg/mL of BmKn2 in water, 30% TFE/H₂O or 70% TFE/H₂O. (C) and (D) Enzyme release assay. (C) <i>S. aureus</i> AB94004 treated with Kn2-7 or BmKn2 was harvested, and the catalase activities of the supernatants were measured; 0.9% saline was used as the negative control, and ampicillin sodium was used as the antibiotic control. (D) <i>E. coli</i> AB94012 treated with Kn2-7 or BmKn2 was harvested, and the catalase activities in the supernatants were measured; 0.9% saline was used as the negative control, and kanamycin was used as the antibiotic control.</p