Abstract
Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and ...immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.
Using a prospective cohort for Hepatocellular Carcinoma (the PLANET study), this work revealed a dynamic landscape of phenotypic intra-tumor heterogeneity, providing several novel approaches for patient treatment and prognosis prediction.
Advanced exfoliation techniques are crucial for exploring the intrinsic properties and applications of 2D materials. Though the recently discovered Au-enhanced exfoliation technique provides an ...effective strategy for preparation of large-scale 2D crystals, the high cost of gold hinders this method from being widely adopted in industrial applications. In addition, direct Au contact could significantly quench photoluminescence (PL) emission in 2D semiconductors. It is therefore crucial to find alternative metals that can replace gold to achieve efficient exfoliation of 2D materials. Here, we present a one-step Ag-assisted method that can efficiently exfoliate many large-area 2D monolayers, where the yield ratio is comparable to Au-enhanced exfoliation method. Differing from Au film, however, the surface roughness of as-prepared Ag films on SiO2/Si substrate is much higher, which facilitates the generation of surface plasmons resulting from the nanostructures formed on the rough Ag surface. More interestingly, the strong coupling between 2D semiconductor crystals (e.g. MoS2, MoSe2) and Ag film leads to a unique PL enhancement that has not been observed in other mechanical exfoliation techniques, which can be mainly attributed to enhanced light-matter interaction as a result of extended propagation of surface plasmonic polariton (SPP). Our work provides a lower-cost and universal Ag-assisted exfoliation method, while at the same offering enhanced SPP-matter interactions.
Statins and therapeutic ultrasound (TUS) have been shown to ameliorate angiogenesis on ischemic hindlimb animals and promote human umbilical vein endothelial cells (HUVECs) tube formation and ...proliferation. Here, we evaluate the therapeutic effect of TUS in combination with atorvastatin (Ator) therapy on angiogenesis in hindlimb ischemia and HUVECs. After subjecting excision of the left femoral artery, all mice were randomly distributed to one of four groups: Control; Ator treated mice (Ator); TUS treated mice (TUS); and Ator plus TUS treated mice (Ator+TUS). At day 14 post-surgery, the Ator plus TUS treatment cohort had the greatest blood perfusion, accompanied by elevated capillary density. In vitro, Ator plus TUS augmented tube formation, migration and proliferative capacities of HUVECs. Additionally, the united administration upregulated expression of angiogenic factors phosphorylated Akt (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor (VEGF), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. Our data indicated that the united administration could significantly enhance ischemia-mediated angiogenesis and exert a protective effect against ischemic/hypoxia induced damage among HUVECs through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway.
Leflunomide (LEF) is a selective inhibitor of de novo pyrimidine synthesis, currently used in the treatment of rheumatoid arthritis. To evaluate the efficacy and safety of LEF in the treatment of ...proliferative lupus nephritis, a prospective multi-center controlled clinical trial was conducted.
Patients with biopsy-confirmed proliferative lupus nephritis were recruited. Patients of recent onset who had not used any immunosuppressive drug were given either oral LEF (group A) or IV cyclophosphamide (group B); relapsed patients who had received immunosuppressive therapy 3 months before were given LEF (group C). Efficacy and safety were evaluated at 6 months after treatment.
Total 51 patients were enrolled, 4 patients withdrew due to adverse events. For those initial treated patients, total response rate were 80% in group A and 75% in group B, complete remission rate were 40% and 25% respectively, not statistically different. Renal parameters (proteinuria, serum albumin and serum creatinine) and systemic lupus ery
These studies established a macaque model of early-phase endotoxic shock, and investigated the resuscitation effects of three different solutions. Twenty-four macaques were assigned to four groups. ...Nineteen animals were given an intravenous dose of 2.8 mg/kg lipopolysaccharide (LPS). At 60 min after LPS challenge, the animals were given (i) 5 mL/kg normal saline (Ns group, n = 6), (ii) 5% of 5 mL/kg sodium bicarbonate (Sb group, n = 6), (iii) hypertonic 3.5% sodium chloride of 5 mL/kg (Hs group, n = 7). The control group (Co group, n = 5) was first injected with 1 mL/kg Ns and with 5 mL/kg Ns 60 min later. Haemodynamic parameters and blood gases were measured during the experiment, and myocardial morphology was examined on termination of the experiment. Administration of LPS caused hypotension and decreases of the left ventricular work index (LVWI). In the Sb group, mean arterial pressure, cardiac index, systemic vascular resistance index, LVWI and right ventricular work index were significantly higher than those of the Ns group. Pathological changes of myocardium were identified in all of the LPS groups. The studies suggest that macaques are suitable models for studying endotoxic shock and potential fluid therapies.
Objective
To analyze the relevant literature regarding the effect of tuina on postpartum milk secretion and thus summarize the clinical rules on tuina for lactation disorder.
Method
Investigate the ...relationship between tuina and postpartum milk secretion for four aspects, including the initial time of lactation, level of serum prolactin, volume of lactation, and Chinese medicine’s understanding of tuina on milk secretion.
Result and Conclusion
Tuina on breasts after childbirth can speed and promote lactation. This has been proved by clinical practice over the past hundreds of years, along with modern laboratory and scientific research. This method, therefore, is of great significance in obstetrical nursing.
To rapidly and sensitively detect the four virulence-associated factors of Streptococcus suis, a multiplex PCR was developed.
In the process of this reaction, four distinct DNA targets were ...amplified. One target was based on the serotype 2 (and 1/2) specific cps gene and the others were based on Streptococcus suis mrp, epf (epf*) and sly gene, encoding the MRP, EF(EF*) and Sly proteins of Streptococcus suis. 72 isolates, which including 48 strains of Streptococcus suis and 24 strains of negative control, and 49 clinical specimens were detected by the multiplex PCR assay.
All PCR products were detected by electrophoresis on 1.2% agarose gels. With the 48 Streptococcus suis strains, the positive detection rates of cps2+, mrp+, epf+, epf*+ and sly+ were 16/48, 14/48, 12/48, 3/48 and 26/48,respectively. The results were confirmed by bacteriological examination. There were no specific amplification products including 49 clinical specimens and 24 negative control strains.
The results demonstrated that multiplex PCR
In the QCD factorization (QCDF) approach we study the direct CP violation in bar.B.sup.0 → ρ.sup.0(ω)ρ.sup.0(ω) → π.sup.+ π.sup.- π.sup.+ π.sup.- via the ρ-ω mixing mechanism. We find that the CP ...violation can be enhanced by double ρ-ω mixing when the masses of the π.sup.+π.sup.- pairs are in the vicinity of the ω resonance, and the maximum CP violation can reach 28%. We also compare the results from the naive factorization and the QCD factorization.
The Cover Feature illustrates a slurry coated solid‐state sulfur/sulfide cathode capable of the large‐scale fabrication for all‐solid‐state lithium–sulfur batteries. After the screening of solvents, ...the compatibility of sulfide electrolytes with elemental sulfur is achieved in organic solvents, and a practical lithium–sulfur pouch cell with considerable discharge areal capacity is also demonstrated. This work constitutes a great success in improving the development of practical sulfide‐based all‐solid‐state batteries. More information can be found in the Article by Q. Zhang and co‐workers.
Aim:Cinnamon extracts rich in procyanidin oligomers have shown to improve pancreatic β-cell function in diabetic db/db mice. The aim of this study was to identify the active compounds in extracts ...from two species of cinnamon responsible for the pancreatic β-cell protection in vitro.Methods:Cinnamon extracts were prepared from Cinnamomum tamala (CT-E) and Cinnamomum cassia (CC-E). Six compounds procyanidin B2 (cpd1), (-)-epicatechin (cpd2), cinnamtannin B1 (cpd3), procyanidin C1 (cpd4), parameritannin A1 (cpd5) and cinnamtannin D1 (cpd6) were isolated from the extracts. INS-1 pancreatic β-cells were exposed to palmitic acid (PA) or H2 O2 to induce lipotoxicity and oxidative stress. Cell viability and apoptosis as well as ROS levels were assessed. Glucose-stimulated insulin secretion was examined in PA-treated β-cells and murine islets.Results:CT-E, CC-E as well as the compounds, except cpd5, did not cause cytotoxicity in the β-cells up to the maximum dosage using in this experiment. CT-E and CC-E (12.5-50 μg/mL) dose-dependently increased cell viability in both PA- and H2 O2 -treated β-cells, and decreased ROS accumulation in H2 O2 -treated β-cells. CT-E caused more prominent β-cell protection than CC-E. Furthermore, CT-E (25 and 50 μg/mL) dose-dependently increased glucose-stimulated insulin secretion in PA-treated β-cells and murine islets, but CC-E had little effect. Among the 6 compounds, trimer procyanidins cpd3, cpd4 and cpd6 (12.5-50 μmol/L) dose-dependently increased the cell viability and decreased ROS accumulation in H2 O2 -treated β-cells. The trimer procyanidins also increased glucose-stimulated insulin secretion in PA-treated β-cells.Conclusion:Trimer procyanidins in the cinnamon extracts contribute to the pancreatic β-cell protection, thus to the anti-diabetic activity.
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![CP Violation for [B.sup.0] ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1687-7357/small "CP Violation for [B.sup.0] ← ρ.sup.0] → [π.sup.+] [π.sup.-] [π.sup.+] [π.sup.-] in QCD factorization")
