Cancer initiating cells (CICs) are responsible for the unrestrained cell growth and chemoresistance of malignant tumors. Histone demethylation has been shown to be crucial for ...self-renewal/differentiation of stem cells, but it remains elusive whether lysine-specific demethylase 1 (LSD1) regulates the stemness properties of CICs. Here we report that the abundant expression of leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is associated with the progression of hepatocellular carcinoma (HCC). Lgr5(+) HCC cells behave similarly to CICs and are highly tumorigenic and resistant to chemotherapeutic agents. Importantly, Lgr5(+) cells express higher levels of LSD1, which in turn regulates Lgr5 expression and promotes the self-renewal and drug resistance of Lgr5(+) CICs. Mechanistically, LSD1 promotes β-catenin activation by inhibiting the expression of several suppressors of β-catenin signaling, especially Prickle1 and APC in Lgr5(+) CICs, by directly regulating the levels of mono- and di-methylation of histone H3 lysine-4 at the promoters of these genes. Furthermore, LSD1-associated activation of the β-catenin signaling is essential for maintaining the activity of Lgr5(+) CICs. Together, our findings unravel the LSD1/Prickle1/APC/β-catenin signaling axis as a novel molecular circuit regulating the stemness and chemoresistance of hepatic Lgr5(+) CICs and provide potential targets to improve chemotherapeutic efficacies against HCC.
Dapsone is an important medication for the treatment of leprosy, but a life-threatening drug hypersensitivity syndrome develops in some patients. In this report from China, an
HLA-B
locus is ...identified as a strong genetic risk factor for the syndrome.
Dapsone (4-4′-sulfonyldianiline), which was first synthesized in 1908,
1
is both an antibiotic and an antiinflammatory agent. Dapsone alone or in combination with other drugs has been used for the prevention and treatment of infectious diseases (e.g., leprosy, malaria, and actinomycetoma, as well as
Pneumocystis jirovecii
pneumonia in persons with human immunodeficiency virus HIV infection) and chronic inflammatory diseases characterized by the infiltration of neutrophils or eosinophils (e.g., dermatitis herpetiformis, linear IgA dermatosis, subcorneal pustular dermatosis, and erythema elevatum diutinum).
2
,
3
About 0.5 to 3.6% of persons treated with dapsone have a drug hypersensitivity syndrome,
3
–
5
which was first described by . . .
AbstractBased on the theoretical solution for vibrations of simply supported bridges under moving train loads, resonance and cancellation conditions are derived. The results reveal two types of ...vibration cancellations for simply supported bridges under moving train loads: the first is related to a single moving load, which is independent of the number and the composition of the train, while the second is related to the interval between a pair of moving loads. When cancellation occurs, the free vibrations induced by the moving loads cancel to null, and the bridge response is determined by the loads still on it. A resonance disappearance effect occurs when train speed meets both the resonance and cancellation conditions, while the cancellation plays a predominant role. Bridge damping has an influence on the cancellation effect: the higher the damping and the longer the interval between the loads, the lower is the cancellation efficiency. In a case study, dynamic responses of a bridge under high-speed train loads are analyzed and the mechanisms of resonance and cancellation are explained to support the theoretical solution.
Aliment Pharmacol Ther 2011; 34: 344–352
Summary
Background Optimal duration of anti‐viral therapy in chronic hepatitis B virus (HBV) infection remains unclear.
Aim To investigate factors that ...could predict relapse after stopping anti‐viral agents.
Methods Chronic hepatitis B patients who were treated with anti‐viral agents (lamivudine, adefovir, entecavir) and have stopped the treatment were recruited. Anti‐viral agents were stopped according to the recommendations of the Asian Pacific Association for the Study of the Liver. Virological relapse was defined as an increase in serum HBV DNA to >1000 copies/mL after discontinuation of treatment.
Results Eighty‐four (69 treatment naïve and 15 lamivudine resistant) patients were eligible for this study. Thirty‐seven patients developed virological relapse at 4.3 ± 2.9 (range 1–11) months after discontinuation of therapy. The 1‐year cumulative probability of virological relapse was 42% and 47% in HBeAg (hepatitis B e antigen)‐positive (n = 41) and HBeAg (hepatitis B e antigen)‐negative (n = 43) patients, respectively. On multivariate analysis by Cox proportional hazard model, pre‐existing lamivudine resistance, delayed suppression of HBV DNA to undetectable level during anti‐viral therapy and to a higher HBsAg (hepatitis B surface antigen) level at the end of treatment were associated with virological relapse. Twelve of the 15 (80%) lamivudine resistant patients developed virological relapse. Among the 11 treatment naïve patients who had HBsAg ≤2 log IU/mL at the end of treatment, 1 (9%) of them had virological relapse.
Conclusions Treatment cessation among lamivudine resistant patients is associated with high risk of virological relapse. Serum HBsAg level at the end of treatment and rate of HBV DNA suppression can provide supplementary information to guide the timing of stopping anti‐viral drugs.
We present a hydrodynamic theory for systems of dipolar active Brownian particles which, in the regime of weak dipolar coupling, predicts the onset of motility-induced phase separation (MIPS), ...consistent with Brownian dynamics (BD) simulations. The hydrodynamic equations are derived by explicitly coarse-graining the microscopic Langevin dynamics, thus allowing for a mapping of the coarse-grained model and particle-resolved simulations. Performing BD simulations at fixed density, we find that dipolar interactions tend to hinder MIPS, as first reported in Liao
et al.
,
Soft Matter
, 2020,
16
, 2208. Here we demonstrate that the theoretical approach indeed captures the suppression of MIPS. Moreover, the analysis of the numerically obtained, angle-dependent correlation functions sheds light into the underlying microscopic mechanisms leading to the destabilization of the homogeneous phase.
We present a hydrodynamic theory for systems of dipolar active Brownian particles which, in the regime of weak dipolar coupling, predicts the onset of motility-induced phase separation (MIPS), consistent with Brownian dynamics (BD) simulations.
Sedum plumbizincicola X.H. Guo et S.B. Zhou ex L.H. Wu (Crassulaceae), a new species restricted to lead–zinc mining areas in Zhejiang Province, China, is described and illustrated. This taxon belongs ...to sect. Sedum (H. Ohba) S.H. Fu based on the adaxially gibbous carpels and follicles. It superficially resembles S. alfredii Hance and three other Sedum species found in the same area, but differs from these other taxa in bearing 4-merous flowers. Differences in geographical distribution, growth habit, phenology, macromorphology, leaf and stem anatomy, as well as seed micromorphology among S. plumbizincicola, S. alfredii and other related taxa in the genus Sedum are also reported. nrDNA internal transcribed spacers (ITS) sequences from seven populations of S. plumbizincicola support the recognition of this as a taxonomic entity distinct from S. alfredii.
Potassium‐ion batteries based on conversion/alloying reactions have high potential applications in new‐generation large‐scale energy storage. However, their applications are hindered by inherent ...large‐volume variations and sluggish kinetics of the conversion/alloying‐type electrode materials during the repeated insertion and extraction of bulky K+ ions. Although some efforts have been focused on this issue, the reported potassium‐ion batteries still suffer from poor cycling lifespans. Here, a superior stable antimony selenide (Sb2Se3) anode is reported for high‐performance potassium‐ion batteries through a combined strategy of conductive encapsulation and 2D confinement. The Sb2Se3 nanorods are uniformly coated with a conductive N‐doped carbon layer and then confined between graphene nanosheets. The synergistic effects between conductive coating and confinement effectively buffer the large volumetric variation of the conversion/alloying anodes, which can maintain structural stability for superior cyclability. The as‐prepared anodes exhibit a high reversible specific capacity of ≈590 mA h g−1 and outstanding cycling stability over 350 cycles. In situ and ex situ characterizations reveal a high structural integration of the large‐volume‐change Sb2Se3 anodes during a reversible K storage mechanism of two‐step conversion and multistep alloying processes. This work can open up a new possibility for the design of stable conversion/alloying‐based anodes for high‐performance potassium‐ion batteries.
A combined strategy of conductive encapsulation and 2D confinement is developed to design stable conversion/alloying‐type electrode materials for potassium‐ion batteries (PIBs). When applied as anodes for PIBs, the Sb2Se3‐based composite exhibits high specific capacities and excellent cycling performance. The high structural stability and reversible conversion and alloying mechanism of the composite anode are demonstrated by in situ and ex situ characterizations.
The recent advances in 60-GHz radios have called for the parallel development of compact and efficient millimeter-wave antennas. This brief addresses for the first time the design, fabrication, and ...characterization of on-chip inverted-F and quasi-Yagi antennas for 60-GHz radios. The design was made using the Zeland IE3D software package. The fabrication was realized with the back-end-of-line process of silicon substrates of low resistivity 10 /spl Omega//spl middot/cm. The characterization was conducted on wafer with Cascade Microtech coplanar probes and an HP8510XF network analyzer. The results show that the inverted-F antenna achieved a minimum return loss of 32 dB and a gain of -19 dBi at 61 GHz; while the quasi-Yagi antenna achieved a minimum return loss of 6.75 dB and a gain of -12.5 dBi at 65 GHz. Good agreement has been observed between the measured and simulated results.
In order to address the present difficulty in experimentally generating the relativistic Laguerre-Gaussian laser, primarily due to damage caused to optical modulators, a high-reflectivity phase ...mirror is applied in the femtosecond petawatt laser system to generate a relativistic hollow laser at the highest intensity of 6.3 × 1019 W / cm2 for the first time. A simple optical model is used to verify that the vortex laser may be generated in this new scheme; using such a relativistic vortex laser, the hollow plasma drill and acceleration are achieved experimentally and proven by particle-in-cell simulations. With the development of the petawatt laser, this scheme opens up possibilities for the convenient production of the relativistic hollow laser at high repetition and possible hollow plasma acceleration, which is important for a wide range of applications such as the generation of radiation sources with orbital angular momentum, fast ignition for inertial confinement fusion, and jet research in the astrophysical environment.
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