Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the ...potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
Aims/hypothesis
The unfolded protein response (UPR) in endoplasmic reticulum (ER) and autophagy are known to be related. We investigated the role of autophagy in UPR of pancreatic beta cells and the ...susceptibility of autophagy-deficient beta cells to the ER stress that is implicated in the development of diabetes.
Methods
Rat insulin promoter (RIP)-
Cre
+
;autophagy-related 7 (
Atg7
)
F/W
mice were bred with
ob/w
mice to derive RIP-
Cre
+
;
Atg7
F/F
-
ob/ob
mice and to induce ER stress in vivo.
GFP-LC3
+
-
ob/ob
mice were generated to examine in vivo autophagic activity. Real-time RT-PCR was performed to study the expression of the genes of the UPR machinery. Proteolysis was assessed by determining release of incorporated radioactive leucine.
Results
Production of UPR machinery was reduced in autophagy-deficient beta cells, which was associated with diminished production of p85α and p85β regulatory subunits of phosphoinositide 3-kinase. Because of compromised UPR machinery, autophagy-deficient beta cells were susceptible to ER stressors in vitro. When mice with beta cell-specific autophagy deficiency, which have mild hyperglycaemia, were bred with
ob/ob
mice to induce ER stress in vivo, severe diabetes developed, which was accompanied by an increase in beta cell death and accumulation of reactive oxygen species. The increased demand for UPR present in obesity was unmet in autophagy-deficient beta cells. Autophagy level and autophagic activity were enhanced by lipid, while proteolysis was reduced.
Conclusions/interpretation
These results suggest that autophagy is important for intact UPR machinery and appropriate UPR in response to lipid injury that increases demand for UPR. Autophagy deficiency in pancreatic beta cells may contribute to the progression from obesity to diabetes.
Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a ...reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.
To investigate the anti-obesity effect of Rubi Fructus (RF) extract using brown adipose tissue (BAT) and primary brown preadipocytes in vivo and in vitro.
Male C57BL/6 J mice (n=5 per group) were fed ...a high-fat diet (HFD) for 10 weeks with or without RF. Brown preadipocytes from the interscapular BAT of mice (age, post-natal days 1-3) were cultured with differentiation media (DM) including isobutylmethylxanthine, dexamethasone, T3, indomethacin and insulin with or without RF.
In HFD-induced obese C57BL/6 J mice, long-term RF treatment significantly reduced weight gain as well as the weights of the white adipose tissue, liver and spleen. Serum levels of total cholesterol and low-density lipoprotein cholesterol were also reduced in the HFD group which received RF treatment. Furthermore, RF induced thermogenic-, adipogenic- and mitochondria-related gene expressions in BAT. In primary brown adipocytes, RF effectively stimulated the expressions of thermogenic- and mitochondria-related genes. In addition, to examine whether LIPIN1, a regulator of adipocyte differentiation, is regulated by RF, Lipin1 small interfering RNA (siRNA) and RF were pretreated in primary brown adipocytes. Pretreatment with Lipin1 siRNA and RF downregulated the DM-induced expression levels of thermogenic- and mitochondria-related genes. Moreover, RF markedly upregulated AMP-activated protein kinase. Our study shows that RF is capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes.
This study demonstrates that RF prevents the development of obesity in mice fed with a HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes, which suggests that RF has potential as a therapeutic application for the treatment or prevention of obesity.
Abstract
We searched for shocked carbon chain chemistry (SCCC) sources with C
3
S abundances surpassing those of HC
5
N toward the dark cloud L1251, using the Effelsberg telescope at the
K
band ...(18–26 GHz). L1251-1 and L1251-3 are identified as the most promising SCCC sources. The two sources harbor young stellar objects. We conducted mapping observations toward L1251-A, the western tail of L1251, at
λ
∼ 3 mm with the Purple Mountain Observatory 13.7 m and the Nobeyama Radio Observatory 45 m telescopes in lines of C
2
H, N
2
H
+
, CS, HCO
+
, SO, HC
3
N, and C
18
O as well as in CO 3–2 using the James Clerk Maxwell Telescope (JCMT). The spectral data were combined with archival data including Spitzer and Herschel continuum maps for further analysis. Filamentary substructures labeled as F1–F6 were extracted in L1251, with F1 being associated with L1251-A hosting L1251-1. The peak positions of dense gas traced by HCO
+
are misaligned relative to those of the dust clumps. Episodic outflows are common in this region. The twisted morphology of F1 and velocity distribution along L1251-A may originate from stellar feedback. SCCC in L1251-1 may have been caused by outflow activities originated from the infrared source IRS1. The signposts of ongoing SCCC and the broadened line widths of C
3
S and C
4
H in L1251-1 as well as the distribution of HC
3
N are also related to outflow activities in this region. L1251-1 (IRS1) together with the previously identified SCCC source IRS3 demonstrate that L1251-A is an excellent region to study SCCC.
We present the results of a Hubble Space Telescope ACS/HRC FUV, ACS/WFC optical study into the cluster populations of a sample of 22 Luminous Infrared Galaxies in the Great Observatories All-Sky LIRG ...Survey. Through integrated broadband photometry, we have derived ages and masses for a total of 484 star clusters contained within these systems. This allows us to examine the properties of star clusters found in the extreme environments of LIRGs relative to lower luminosity star-forming galaxies in the local universe. We find that by adopting a Bruzual & Charlot simple stellar population model and Salpeter initial mass function, the age distribution of the clusters declines as , consistent with the age distribution derived for the Antennae Galaxies, and interpreted as evidence for rapid cluster disruption occurring in the strong tidal fields of merging galaxies. The large number of young clusters identified in the sample also suggests that LIRGs are capable of producing more high-mass clusters than what is observed to date in any lower luminosity star-forming galaxy in the local universe. The observed cluster mass distribution of is consistent with the canonical −2 power law used to describe the underlying initial cluster mass function (ICMF) for a wide range of galactic environments. We interpret this as evidence against mass-dependent cluster disruption, which would flatten the observed CMF relative to the underlying ICMF distribution.
Current immunotherapy paradigms aim to reinvigorate CD8
T cells, but the contribution of humoral immunity to antitumor immunity remains understudied. Here, we demonstrate that in head and neck ...squamous cell carcinoma (HNSCC) caused by human papillomavirus infection (HPV
), patients have transcriptional signatures of germinal center (GC) tumor infiltrating B cells (TIL-Bs) and spatial organization of immune cells consistent with tertiary lymphoid structures (TLS) with GCs, both of which correlate with favorable outcome. GC TIL-Bs in HPV
HNSCC are characterized by distinct waves of gene expression consistent with dark zone, light zone and a transitional state of GC B cells. Semaphorin 4a expression is enhanced on GC TIL-Bs present in TLS of HPV
HNSCC and during the differentiation of TIL-Bs. Our study suggests that therapeutics to enhance TIL-B responses in HNSCC should be prioritized in future studies to determine if they can complement current T cell mediated immunotherapies.
Alkylanilines are a group of chemicals whose ubiquitous presence in the environment is a result of the multitude of sources from which they originate. Exposure assessments indicate that most ...individuals experience lifelong exposure to these compounds. Many alkylanilines have biological activity similar to that of the carcinogenic multi-ring aromatic amines. This review provides an overview of human exposure and biological effects. It also describes recent investigations into the biochemical mechanisms of action that lead to the assessment that they are most probably more complex than those of the more extensively investigated multi-ring aromatic amines. Not only is nitrenium ion chemistry implicated in DNA damage by alkylanilines but also reactions involving quinone imines and perhaps reactive oxygen species. Recent results described here indicate that alkylanilines can be potent genotoxins for cultured mammalian cells when activated by exogenous or endogenous phase I and phase II xenobiotic-metabolizing enzymes. The nature of specific DNA damage products responsible for mutagenicity remains to be identified but evidence to date supports mechanisms of activation through obligatory N-hydroxylation as well as subsequent conjugation by sulfation and/or acetylation. A fuller understanding of the mechanisms of alkylaniline genotoxicity is expected to provide important insights into the environmental and genetic origins of one or more human cancers and may reveal a substantial role for this group of compounds as potential human chemical carcinogens.
Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). To enable the development of ...more efficacious therapies, we aim to study the heterogeneity, signatures of unique cell populations, and cell-cell interactions of non-immune and immune cell populations in 6 human papillomavirus (HPV)
and 12 HPV
HNSCC patient tumor and matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset of 134,606 cells, we show cell type-specific signatures associated with inflammation and HPV status, describe the negative prognostic value of fibroblasts with elastic differentiation specifically in the HPV
TME, predict therapeutically targetable checkpoint receptor-ligand interactions, and show that tumor-associated macrophages are dominant contributors of PD-L1 and other immune checkpoint ligands in the TME. We present a comprehensive single-cell view of cell-intrinsic mechanisms and cell-cell communication shaping the HNSCC microenvironment.
Large Area Light Detectors With MMC Readouts Kim, M. B.; Chung, J. S.; Jeon, J. A. ...
IEEE transactions on applied superconductivity,
08/2023, Volume:
33, Issue:
5
Journal Article
Peer reviewed
We present the development of the light detectors with magnetic microcalorimeter (MMC) readouts designed for the AMoRE neutrinoless double beta decay experiment. The detectors are composed of Ge or ...Si wafer as an absorber for scintillation light and an MMC detector to monitor the temperature of the wafer. Five measurements were carried out with one Ge wafer and four Si wafers prepared under various conditions. Different details of the light detector assembly have been tested to find the optimal configuration for the future AMoRE-II experiment. Direct comparisons in signal size were performed with the different wafers while considering favorable conditions for the future AMoRE setup. Moreover, a baseline resolution of 34.3 eV FWHM was obtained in a detector setup with a 2-inch Si wafer.
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