A system-level mechanistic investigation of traditional Chinese medicine, Yinlai Decoction, for related diseases

Purpose: To systemically explore the pharmacological mechanisms of traditional Chinese medicine, Yinlai Decoction (YD), used in the clinical management of pediatric diseases such as pneumonia and recurrent respiratory tract infections.Methods: An ingredient-target-disease database of YD was constructed using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). First, the molecular targets related to lung and stomach diseases were searched and screened to avoid duplication. Second, the associations between these molecular targets were evaluated via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Gene Ontology (GO) and Pathway enrichment analysis in STRING.Results: A total of 627 chemical ingredients and 654 protein targets in YD were obtained. After further screening, 38 molecular targets linked to respiratory diseases, inflammatory responses and various infections were identified. Finally, 576 GO terms and 75 KEGG pathway terms were obtained by analyzing gene functional annotation clusters and abundance value of these targets. Most of these terms were closely related to the inflammatory response.Conclusion: Based on these in silico findings, the use of YD for treating respiratory diseases, inflammation and various infections, most probably via the suppression of inflammation, has been established. The approach adopted in this study can serve as a model methodology to develop an innovative TCM candidate drug at a network pharmacology level.Keywords: Yinlai Decoction, Network (System) pharmacology, Inflammation, Interacting genes/proteins, Gene ocntology, Pathway enrichment analysi

Experimental observation of magnetic bobbers for a new concept of magnetic solid-state memory

The use of chiral skyrmions, which are nanoscale vortex-like spin textures, as movable data bit carriers forms the basis of a recently proposed concept for magnetic solid-state memory. In this concept, skyrmions are considered to be unique localized spin textures, which are used to encode data through the quantization of different distances between identical skyrmions on a guiding nanostripe. However, the conservation of distances between highly mobile and interacting skyrmions is difficult to implement in practice. Here, we report the direct observation of another type of theoretically-predicted localized magnetic state, which is referred to as a chiral bobber (ChB), using quantitative off-axis electron holography. We show that ChBs can coexist together with skyrmions. Our results suggest a novel approach for data encoding, whereby a stream of binary data representing a sequence of ones and zeros can be encoded via a sequence of skyrmions and bobbers. The need to maintain defined distances between data bit carriers is then not required. The proposed concept of data encoding promises to expedite the realization of a new generation of magnetic solid-state memory

A feedback regulatory loop between methyltransferase PRMT1 and orphan receptor TR3

PRMT1, an arginine methyltransferase, plays an important role in numerous cellular processes. In this study, we demonstrate a feedback regulatory loop between PRMT1 and the orphan receptor TR3. Unlike another orphan receptor HNF4, TR3 is not methylated by PRMT1 although they physically interact with each other. By delaying the TR3 protein degradation, PRMT1 binding leads to the elevation of TR3 cellular protein level, thereby enhances the DNA binding and transactivation activity of TR3 in a non-methyltransferase manner. Another coactivator SRC-2 acts synergistically with PRMT1 to regulate TR3 functions. In turn, TR3 binding to the catalytic domain of PRMT1 causes an inhibition of the PRMT1 methyltransferase activity. This repression results in the functional changes in some of PRMT1 substrates, including STAT3 and Sam68. The negative regulation of PRMT1 by TR3 was further confirmed in both TR3-knockdown cells and TR3-knockout mice with the use of an agonist for TR3. Taken together, our study not only identifies a regulatory role of PRMT1, independent on methyltransferase activity, in TR3 transactivation, but also characterizes a novel function of TR3 in the repression of PRMT1 methyltransferase activity

Synchrotron Radiation Dominates the Extremely Bright GRB 221009A

The brightest Gamma-ray burst, GRB 221009A, has spurred numerous theoretical investigations, with particular attention paid to the origins of ultra-high energy TeV photons during the prompt phase. However, analyzing the mechanism of radiation of photons in the $\sim$MeV range has been difficult because the high flux causes pile-up and saturation effects in most GRB detectors. In this letter, we present systematic modeling of the time-resolved spectra of the GRB using unsaturated data obtained from Fermi/GBM (precursor) and SATech-01/GECAM-C (main emission and flare). Our approach incorporates the synchrotron radiation model, which assumes an expanding emission region with relativistic speed and a global magnetic field that decays with radius, and successfully fits such a model to the observational data. Our results indicate that the spectra of the burst are fully in accordance with a synchrotron origin from relativistic electrons accelerated at a large emission radius. The lack of thermal emission in the prompt emission spectra supports a Poynting-flux-dominated jet composition.Comment: 12 pages, 6 figures, 2 tables. Accepted for publication in ApJ

Functional building blocks for scalable multipartite entanglement in optical lattices

Featuring excellent coherence and operated parallelly, ultracold atoms in optical lattices form a competitive candidate for quantum computation. For this, a massive number of parallel entangled atom pairs have been realized in superlattices. However, the more formidable challenge is to scale-up and detect multipartite entanglement due to the lack of manipulations over local atomic spins in retro-reflected bichromatic superlattices. Here we developed a new architecture based on a cross-angle spin-dependent superlattice for implementing layers of quantum gates over moderately-separated atoms incorporated with a quantum gas microscope for single-atom manipulation. We created and verified functional building blocks for scalable multipartite entanglement by connecting Bell pairs to one-dimensional 10-atom chains and two-dimensional plaquettes of $2\times4$ atoms. This offers a new platform towards scalable quantum computation and simulation

Pairing symmetry and properties of iron-based high temperature superconductors

Pairing symmetry is important to indentify the pairing mechanism. The analysis becomes particularly timely and important for the newly discovered iron-based multi-orbital superconductors. From group theory point of view we classified all pairing matrices (in the orbital space) that carry irreducible representations of the system. The quasiparticle gap falls into three categories: full, nodal and gapless. The nodal-gap states show conventional Volovik effect even for on-site pairing. The gapless states are odd in orbital space, have a negative superfluid density and are therefore unstable. In connection to experiments we proposed possible pairing states and implications for the pairing mechanism.Comment: 4 pages, 1 table, 2 figures, polished versio

The combination of hand grip strength and modified Glasgow prognostic score predicts clinical outcomes in patients with liver cancer

PurposePrevious studies have shown that both hand grip strength (HGS) and the modified Glasgow Prognostic Score (mGPS) are associated with poor clinical outcomes in patients with liver cancer. In spite of this, no relevant studies have been conducted to determine whether the combination of HGS and mGPS can predict the prognosis of patients with liver cancer. Accordingly, this study sought to explore this possibility.MethodsThis was a multicenter study of patients with liver cancer. Based on the optimal HGS cutoff value for each sex, we determined the HGS cutoff values. The patients were divided into high and low HGS groups based on their HGS scores. An mGPS of 0 was defined as low mGPS, whereas scores higher than 0 were defined as high mGPS. The patients were combined into HGS-mGPS groups for the prediction of survival. Survival analysis was performed using Kaplan–Meier curves. A Cox regression model was designed and adjusted for confounders. To evaluate the nomogram model, receiver operating characteristic curves and calibration curves were used.ResultsA total of 504 patients were enrolled in this study. Of these, 386 (76.6%) were men (mean [SD] age, 56.63 [12.06] years). Multivariate analysis revealed that patients with low HGS and high mGPS had a higher risk of death than those with neither low HGS nor high mGPS (hazard ratio [HR],1.50; 95% confidence interval [CI],1.14–1.98; p = 0.001 and HR, 1.55; 95% CI, 1.14–2.12, p = 0.001 respectively). Patients with both low HGS and high mGPS had 2.35-fold increased risk of death (HR, 2.35; 95% CI, 1.52–3.63; p < 0.001). The area under the curve of HGS-mGPS was 0.623. The calibration curve demonstrated the validity of the HGS-mGPS nomogram model for predicting the survival of patients with liver cancer.ConclusionA combination of low HGS and high mGPS is associated with poor prognosis in patients with liver cancer. The combination of HGS and mGPS can predict the prognosis of liver cancer more accurately than HGS or mGPS alone. The nomogram model developed in this study can effectively predict the survival outcomes of liver cancer

Rhinosinusitis derived Staphylococcal enterotoxin B possibly associates with pathogenesis of ulcerative colitis

BACKGROUND: During clinical practice, we noticed that some patients with both ulcerative colitis (UC) and chronic rhinosinusitis (CRS) showed amelioration of UC after treatment of CRS. This study was designed to identify a possible association between CRS and UC. METHODS: Thirty-two patients with both CRS and UC received treatment with functional endoscopic sinus surgery (FESS) for CRS. Clinical symptom scores for CRS and UC, as well as serum levels of anti-Staphylococcal enterotoxin B (SEB) were evaluated at week 0 and week 12. Sinus wash fluid SEB content was measured with enzyme-linked immunosorbent assay (ELISA). The surgically removed tissues were cultured to identify growth of Staphylococcus. aureus (S. aureus). Immunohistochemistry was employed to identify anti-SEB positive cells in the colonic mucosa. Colonic biopsies were obtained and incubated with SEB. Mast cell activation in the colonic mucosa in response to incubation with SEB was observed with electron microscopy and immunoassay. RESULTS: The clinical symptom scores of CRS and UC severe scores (UCSS) were significantly reduced in the UC-CRS patients after FESS. The number of cultured S. aureus colonies from the surgically removed sinus mucosa significantly correlated with the decrease in UCSS. High levels of SEB were detected in the sinus wash fluids of the patients with UC-CRS. Histamine and tryptase release was significantly higher in the culture supernate in the patients with UC-CRS than the patients with UC-only and normal controls. Anti-SEB positive cells were located in the colonic mucosa. CONCLUSION: The pathogenesis of UC in some patients may be associated with their pre-existing CRS by a mechanism of swallowing sinusitis-derived SEB. We speculate that SEB initiates inappropriate immune reactions and inflammation in the colonic mucosa that further progresses to UC