The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.

2D PEG-ylated MoS2/Bi2 S3 composite nanosheets are successfully constructed by introducing bismuth ions to react with the two extra S atoms in a (NH4)2 MoS4 molecule precursor for solvothermal synthesis of MoS2. The MBP nanosheets can serve as a promising platform for computed tomography and photoacoustic-imaging-guided tumor diagnosis, as well as combined tumor photothermal therapy and sensitized radiotherapy.

Hepatitis B virus (HBV) causes chronic infection in about 350 million people worldwide. Given the important role of the most abundant liver-specific microRNA, miR-122, in hepatic function and liver pathology, here we investigated the potential role and mechanism of miR-122 in regulating HBV replication. We found that miR-122 expression in liver was significantly down-regulated in patients with HBV infection compared with healthy controls, and the miR-122 levels were negatively correlated with intrahepatic viral load and hepatic necroinflammation. The depletion of endogenous miR-122 by its antisense inhibitor led to enhanced HBV replication, whereas overexpression of miR-122 by transfection of mimic or its expression vector inhibited viral production. We next identified cyclin G 1 as an miR-122 target from multiple candidate target genes that are involved in the regulation of HBV replication. Overexpression and knockdown studies both showed that cyclin G 1 regulated viral replication in HBV transfected cells. We also observed that cyclin G 1 expression was up-regulated in HBV-infected patients, and cyclin G 1 levels were inversely associated with miR-122 expression in liver tissues. Using coimmunoprecipitation, a luciferase reporter system, and electrophoretic mobility shift assay, we further demonstrated that cyclin G 1 specifically interacted with p53, and this interaction blocked the specific binding of p53 to HBV enhancer elements and simultaneously abrogated p53-mediated inhibition of HBV transcription. Finally, we show that miR-122 suppressed HBV replication in p53 wildtype cells but not in null isogenic cells. Conclusion: miR-122 down-regulates its target cyclin G 1 , and thus interrupts the interaction between cyclin G 1 and p53 and abrogates p53-mediated inhibition of HBV replication. Our work shows that miR-122 down-regulation induced by HBV infection can impact HBV replication and possibly contribute to viral persistence and carcinogenesis. (HEPATOLOGY 2012;55:730-741)

The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

ObjectiveThe clinical features of rheumatic patients with coronavirus disease 2019 (COVID-19) have not been reported. This study aimed to describe the clinical features of COVID-19 in rheumatic patients and provide information for handling this situation in clinical practice.MethodsThis is a retrospective case series study. Deidentified data, including gender, age, laboratory and radiological results, symptoms, signs, and medication history, were collected from 2326 patients diagnosed with COVID-19, including 21 cases in combination with rheumatic disease, in Tongji Hospital between 13 January and 15 March 2020.ResultsLength of hospital stay and mortality rate were similar between rheumatic and non-rheumatic groups, while the presence of respiratory failure was more common in rheumatic cases (38% vs 10%, p<0.001). Symptoms of fever, fatigue and diarrhoea were seen in 76%, 43% and 23% of patients, respectively. There were four rheumatic patients who experienced a flare of rheumatic disease during hospital stay, with symptoms of muscle aches, back pain, joint pain or rash. While lymphocytopaenia was seen in 57% of rheumatic patients, only one patient (5%) presented with leucopenia in rheumatic cases. Rheumatic patients presented with similar radiological features of ground-glass opacity and consolidation. Patients with pre-existing interstitial lung disease showed massive fibrous stripes and crazy-paving signs at an early stage. Five rheumatic cases used hydroxychloroquine before the diagnosis of COVID-19 and none progressed to critically ill stage.ConclusionsRespiratory failure was more common in rheumatic patients infected with COVID-19. Differential diagnosis between COVID-19 and a flare of rheumatic disease should be considered.Trial registration numberChiCTR2000030795.

Fluorescent and photoswitchable proteins are invaluable in life sciences and considered for applications in data storage. Of particular interest for in vivo studies are fluorescent proteins whose chromophores are generated autocatalytically from the amino acid chain; [1] some of them can also be switched between two states. [2,3] Alternatively, apoproteins can be used that spontaneously incorporate endogenous chromophores like retinal. [4,5] The open-chain tetrapyrrole chromophore of biliproteins is subject to remarkable excited-state control of the chromophore by the apoprotein. [6][7][8] Absorption and fluorescence of free bilins like the phycocyanobilin (PCB) is strongly increased in native biliproteins: the maximum can be shifted by over 100 nm, and a photochemical reaction path is opened in photochromic biliproteins like phytochromes [9] and cyano-(bacterio)chromes. [7] These natural variations and the possibility to modulate the photophysical properties render biliproteins, in principle, excellent biomarkers and photonic materials.Applications have been limited, however, because the bilin chromophores must be provided separately and then attached covalently to the apoproteins. Previously, genes of the apoprotein were co-expressed with genes whose products generate the bilin chromophore from endogenous heme and then attach it covalently to the apoprotein. [10][11][12] We now report an alternative approach that generates various biliproteins in situ from a single, multifunctional gene and endogenous heme. This approach is demonstrated by the synthesis of two persistently red-fluorescent biliproteins based on allophycocyanins, and by photochromic biliproteins derived from a novel cyanobacteriochrome that can be reversibly switched from a state absorbing and strongly fluorescing in the red, to a spectroscopically well-separated, less fluorescent state absorbing in the green spectral region.Gene slr1393 of the cyanobacterium Synechocystis sp. PCC6803 encodes a red-green photoreversible cyanobacteriochrome. The full-length protein contains three GAF domains, but GAF3 (aa 441-596) alone is capable of autocatalytically binding PCB to cysteine-528.[21] Addition of PCB to GA results in a reversibly photochromic chromoprotein, termed RGS (red-green switchable protein): state P r (l max = 650 nm) is strongly fluorescent (F F = 0.06); it is reversibly converted by irradiation with red light into state P g (l max = 539 nm), which has reduced and strongly blueshifted fluorescence (Table 1, Figure 1 a). Photoswitching can be repeated many times; it is stable over a wide pH range, and is retained after RGS is embedded into polyvinyl alcohol (PVA) film (see Figures S1 and S2 in the Supporting Information).Chromophorylated RGS can be produced in E. coli [11,13] that has been multiply transformed to produce the GAF3 apoprotein and two biosynthetic enzymes generating PCB from heme, that is, heme oxygenase (HO1) and the biliverdin reductase (PcyA). The cells show an intense red fluorescence that can be abolished by irradiation w...

Background and AimsPhosphorus deficiency is a major limiting factor for crop yield worldwide. Previous studies revealed that PHR1 and it homologues play a key role in regulating the phosphate starvation response in plants. However, the function of PHR homologues in common wheat (Triticum aestivum) is still not fully understood. The aim of the study was to characterize the function of PHR1 genes in regulating phosphate signalling and plant growth in wheat.MethodsWheat transgenic lines over-expressing a wheat PHR1 gene were generated and evaluated under phosphorus-deficient and -sufficient conditions in hydroponic culture, a soil pot trial and two field experiments.Key ResultsThree PHR1 homologous genes Ta-PHR1-A1, B1 and D1 were isolated from wheat, and the function of Ta-PHR1-A1 was analysed. The results showed that Ta-PHR1-A1 transcriptionally activated the expression of Ta-PHT1.2 in yeast cells. Over-expressing Ta-PHR1-A1 in wheat upregulated a subset of phosphate starvation response genes, stimulated lateral branching and improved phosphorus uptake when the plants were grown in soil and in nutrient solution. The data from two field trials demonstrated that over-expressing Ta-PHR1-A1 increased grain yield by increasing grain number per spike.ConclusionsTaPHR1 is involved in phosphate signalling in wheat, and was valuable in molecular breeding of crops, with improved phosphorus use efficiency and yield performance.

We exploited the oxide shell structure to explore the structure confinement effect on the nickel silicide growth in one-dimensional nanowire template. The oxide confinement structure is similar to the contact structure (via hole) in the thin film system or nanodevices passivated by oxide or nitride film. Silicon nanowires in direct contact with nickel pads transform into two phases of nickel silicides, Ni31Si12 and NiSi2, after one-step annealing at 550 °C. In a bare Si nanowire during the annealing process, NiSi2 grows initially through the nanowire, followed by the transformation of NiSi2 into the nickel-rich phase, Ni31Si12 starting from near the nickel pad. Ni31Si12 is also observed under the nickel pads. Although the same phase transformations of Si to nickel silicides are observed in nanowires with oxide confinement structure, the growth rate of nickel silicides, Ni31Si12 and NiSi2, is retarded dramatically. With increasing oxide thickness from 5 to 50 nm, the retarding effect of the Ni31Si12 growth and the annihilation of Ni2Si into the oxide confined-Si is clearly observed. Ni31Si12 and Ni2Si phases are limited to grow into the Si/SiOx core-shell nanowire as the shell thickness reaches 50 nm. It is experimental evidence that phase transformation is influenced by the stressed structure at nanoscale.