[PreS1 Antigen of HBV Down-Regulates MHC-â on the Surface of Hepatocytes and Promotes Hepatocarcinogenesis].

Objective: To explore the internal mechanism of hepatocellular carcinoma (HCC) induced by chronic hepatitis B virus (HBV) infection. Methods: L02, HepG2 and Huh7 cells stably overexpressing HBV preS1 antigen were analyzed by flow cytometry, qRT-PCR and tumorigenesis in nude mice to evaluate the effect of preS1 antigen in HBV-related hepatocarcinogenesis. Results: Our results showed that the expression of cancer stem cell (CSCs) related factors and cell surface markers in preS1 overexpressing cells were up-regulated, and the tumorigenicity of these cells was enhanced in nude mice. In addition, preS1 overexpression could down-regulate the expression of major histocompatibility complex Ⅰ (MHC-Ⅰ). The expression of MHC-Ⅰ on the cell surface could be restored by adding interferon gamma (IFN-γ) in the process of cell culturing and the tumorigenicity of cells in nude mice could thus be reduced. Conclusion: Based on the above results, we believe that preS1 is a carcinogen of HBV and that it promotes the formation of liver cancer through down regulating MHC-Ⅰ on the surface of hepatocytes.

Allosteric mechanisms underlie GPCR signaling to SH3-domain proteins through arrestin.

Signals from 800 G-protein-coupled receptors (GPCRs) to many SH3 domain-containing proteins (SH3-CPs) regulate important physiological functions. These GPCRs may share a common pathway by signaling to SH3-CPs via agonist-dependent arrestin recruitment rather than through direct interactions. In the present study, 19F-NMR and cellular studies revealed that downstream of GPCR activation engagement of the receptor-phospho-tail with arrestin allosterically regulates the specific conformational states and functional outcomes of remote ß-arrestin 1 proline regions (PRs). The observed NMR chemical shifts of arrestin PRs were consistent with the intrinsic efficacy and specificity of SH3 domain recruitment, which was controlled by defined propagation pathways. Moreover, in vitro reconstitution experiments and biophysical results showed that the receptor-arrestin complex promoted SRC kinase activity through an allosteric mechanism. Thus, allosteric regulation of the conformational states of ß-arrestin 1 PRs by GPCRs and the allosteric activation of downstream effectors by arrestin are two important mechanisms underlying GPCR-to-SH3-CP signaling.

COLEC12 regulates apoptosis of osteosarcoma through Toll-like receptor 4-activated inflammation.

OBJECTIVE: To investigate the role of COLEC12 in osteosarcoma and observe the relationship between COLEC12 knockdown and the inflammation of osteosarcoma. Then, further explore whether the process is regulated by TLR4. METHOD: GEPIA and TCGA systems were used to predict the potential function of COLEC12. Western blot and RT-PCR were used to analyze the protein expression, or mRNA level, of COLEC12 in different tissue or cell lines. The occurrence and development of osteosarcoma were observed by using COLEC12 knockdown lentivirus. The inflammation indexes of osteosarcoma, in vitro and in vivo, were explored. TLR4 knockdown lentivirus was applied to the relationship between COLEC12 and TLR4. RESULTS: COLEC12 expression in SARC tumor tissue was higher than in normal, and a high expression of COLEC12 in SARC patients had a worse prognostic outcome. Pairwise gene correlation analysis revealed a potential relationship between COLEC12 and TLR4. The COLEC12 expression and mRNA level in the tumor or Saos-2 cells were increased. COLEC12 knockdown lentivirus could inhibit osteosarcoma development, in vivo and vitro, through reducing tumor volume and weight, weakening tumor proliferation, migration, and invasion, and enhancing apoptosis. Furthermore, COLEC12 knockdown could increase inflammation of osteosarcoma, in vivo and in vitro, through inducing myeloperoxidase (MPO), TLR4, NF-κB, and C3, and expression of related inflammatory factors. Finally, TLR4 knockdown lentivirus inhibits the progress of inflammation after COLEC12 regulation, in vivo and vitro. CONCLUSION: COLEC12 may be able to regulate apoptosis and inflammation of osteosarcoma, and TLR4 may be the downstream target factor of COLEC12 in inflammation.

Independent modulation of individual genomic component transcription and a cis-acting element related to high transcriptional activity in a multipartite DNA virus.

BACKGROUND: The genome of Banana bunchy top virus (BBTV) consists of at least six circular, single-stranded DNA components of ~ 1 kb in length. Some BBTV isolates may also carry satellite DNA molecules that are not essential for BBTV infection. The relation between multipartite DNA virus replication and their transcriptional levels and the underlying mechanism remain unclear. RESULTS: To understand the coordinated replication and transcription of the multiple genomic components, the absolute amounts of each BBTV DNA component were measured by real-time PCR (qPCR), and their transcriptional levels were determined by RNAseq and reverse transcription-qPCR (qRT-PCR). Significant differences were found in the absolute amounts of individual BBTV genomic components. Transcriptional levels of each BBTV genomic component obtained from the RNAseq data matched closely to those obtained from qRT-PCR, but did not correspond to the absolute amount of each DNA component. The ratio of transcript over DNA copies ranged from 46.21 to 1059.44%, which was possibly regulated by the promoter region in the intergenic region of each component. To further determine this speculation, the promoter region of the DNA-S, -M or -N was constructed to the upstream of green fluorescent protein (GFP) gene for transient expression by agrobacterium-mediated transformation method. The qRT-PCR showed the highest transcriptional activity was promoted by DNA-N promoter, about 386.58% activity comparing with CaMV 35S promoter. Confocal microscopy observation showed that the intensity of green fluorescence was corresponding to that of qRT-PCR. CONCLUSIONS: Our data clearly showed that BBTV was able to control the transcriptional level of each DNA component independently by through the promoter sequences in the intergenic region. Moreover, a cis-acting element from DNA-N component had a high transcriptional activity.

Protective immunity induced by DNA vaccine encoding viral membrane protein against SGIV infection in grouper.

Singapore grouper iridovirus (SGIV) is the main grouper-infecting virus in southern China that causes serious economic losses. However, there is no effective way to control this viral disease. In this study, SGIV ORF19R (SGIV-19R) encoding a viral membrane protein was constructed into pcDNA3.1-HA and then was used to evaluate the immune protective effects in grouper Epinephelus coioides. Subcellular localization showed that SGIV-19R distributed in the cytoplasm and co-localization analysis indicated the protein partially co-localized with the endoplasmic reticulum (ER). RT-PCR and Western blot analyses confirmed the expression of the vaccine plasmids in grouper muscle tissues. Moreover, the transcription levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), myxovirus resistance 1 (Mx1) and immunoglobulin M (IgM) genes were significantly up-regulated in the spleen, liver and kidney of vaccinated groupers. SGIV challenge experiments showed the relative percent survival (RPS) was significantly enhanced in fish with 49.9% at the DNA dose of 45 µg pcDNA3.1-19R, while 75.0% RPS when using 90 µg pcDNA3.1-19R. Meanwhile, vaccination with pcDNA3.1-19R significantly reduced the virus replication, evidenced by a low viral load in the spleen of survivals groupers after SGIV challenge. These results imply that pcDNA3.1-19R could induce protective immunity in grouper, and might be a potential vaccine candidate for controlling SGIV disease.

Gene deletion strategy to examine the involvement of the two chondroitin lyases in Flavobacterium columnare virulence.

Flavobacterium columnare is an important bacterial pathogen of freshwater fish that causes high mortality of infected fish and heavy economic losses in aquaculture. The pathogenesis of this bacterium is poorly understood, in part due to the lack of efficient methods for genetic manipulation. In this study, a gene deletion strategy was developed and used to determine the relationship between the production of chondroitin lyases and virulence. The F. johnsoniae ompA promoter (PompA) was fused to sacB to construct a counterselectable marker for F. columnare. F. columnare carrying PompA-sacB failed to grow on media containing 10% sucrose. A suicide vector carrying PompA-sacB was constructed, and a gene deletion strategy was developed. Using this approach, the chondroitin lyase-encoding genes, cslA and cslB, were deleted. The ΔcslA and ΔcslB mutants were both partially deficient in digestion of chondroitin sulfate A, whereas a double mutant (ΔcslA ΔcslB) was completely deficient in chondroitin lyase activity. Cells of F. columnare wild-type strain G4 and of the chondroitin lyase-deficient ΔcslA ΔcslB mutant exhibited similar levels of virulence toward grass carp in single-strain infections. Coinfections, however, revealed a competitive advantage for the wild type over the chondroitin lyase mutant. The results indicate that chondroitin lyases are not essential virulence factors of F. columnare but may contribute to the ability of the pathogen to compete and cause disease in natural infections. The gene deletion method developed in this study may be employed to investigate the virulence factors of this bacterium and may have wide application in many other members of the phylum Bacteroidetes.

Multilocus sequences confirm the close genetic relationship of four phytoplasmas of peanut witches'-broom group 16SrII-A.

Four witches'-broom diseases associated with Arachis hypogaea (peanut), Crotalaria pallida, Tephrosia purpurea, and Cleome viscosa were observed in Hainan Province, China during field surveys in 2004, 2005, and 2007. In previously reported studies, we identified these four phytoplasmas as members of subgroup 16SrII-A, and discovered that their 16S rRNA gene sequences were 99.9-100% identical to one another. In this study, we performed extensive phylogenetic analyses to elucidate relationships among them. We analyzed sequences of the 16S rRNA gene and rplV-rpsC, rpoB, gyrB, dnaK, dnaJ, recA, and secY combined sequence data from two strains each of the four phytoplasmas from Hainan province, as well as strains of peanut witches'-broom from Taiwan (PnWB-TW), "Candidatus Phytoplasma australiense", "Ca. Phytoplasma mali AT", aster yellows witches'-broom phytoplasma AYWB, and onion yellows phytoplasma OY-M. In the 16S rRNA phylogenetic tree, the eight Hainan strains form a clade with PnWB-TW. Analysis of the seven concatenated gene regions indicated that the four phytoplasmas collected from Hainan province cluster most closely with one another, but are closely related to PnWB-TW. The results of field survey and phylogenetic analysis indicated that Cr. pallida, T. purpurea, and Cl. viscosa may be natural plant hosts of peanut witches'-broom phytoplasma.

Caffeine supplementation improves the cognitive abilities and shooting performance of elite e-sports players: a crossover trial.

We explored the effect of 3 mg/kg of caffeine supplementation on the cognitive ability and shooting performance of elite e-sports players. Nine e-sports players who had received professional training in e-sports and had won at least eighth place in national-level e-sports shooting competitions. After performing three to five familiarization tests, we employed a single blind, randomized crossover design to divide participants into caffeine trial (CAF) and placebo trial (PL). The CAF trial took capsules with 3 mg/kg of caffeine, whereas the PL trial took a placebo capsule. After a one-hour rest, the Stroop task, the visual search ability test, and the shooting ability test were conducted. The CAF trial's performance in the Stroop task in terms of congruent condition (P = 0.023) and visual search reaction time with 20 items (P = 0.004) was significantly superior to those of the PL trial. In the shooting test, the CAF trial's kill ratio (P = 0.020) and hit accuracy (P = 0.008) were significantly higher, and the average time to target (P = 0.001) was significantly shorter than those of the PL trial. Caffeine supplementation significantly improves e-sports players' reaction times and shooting performance.

Using protein granularity to extract the protein sequence features.

The feature extraction of protein sequences is a challenging problem. It might need a lot of theoretical and practical knowledge from many fields. The difficulty would increase when investigators extract the features solely from protein sequences. In this paper, we present a method of protein granularity. The concepts of protein granularity, granularity order, granularity bound, granularity limit, and granularity increment are given respectively. The protein granularity can dig out the useful information solely from protein sequences. We provide an approach to construct the feature vectors. The feature vectors include the amino acid composition information, the sequence-order information, the same amino acid 'neighbor' information, and the sequence length information. Hence, the feature vectors can better represent protein sequences. Our feature extraction method does obviously consider the protein sequence length effects. An experiment of the protein structure class prediction was carried out. The prediction achieved 96.6% overall accuracy, and the success rate for each subset is all-α 92.3%, all-ß 100%, α/ß 100%, α+ß 93.5%, respectively. The last three success rates for subsets are equal to the best success rates in the published literatures. The overall accuracy of PG-SVM prediction is the second best result only having one protein prediction error difference with the first best result. The theoretical and experimental results demonstrate the application of protein granularity succeeds in the feature extraction of protein sequences.

Study on Impact Mechanical Properties of Reentrant Bionic Automotive Energy Absorbing Box.

In order to impprove the protective effect of the automotive energy absorption (EA) box, the design of the reentrant bioinspired EA box is proposed, that is, novel bioinspired structures are inserted into the original EA box to improve the EA effect of the box. The improved bionic structures with curvature are designed according to the spider web: honeycomb structure (HS), arc-honeycomb structure (AHS), negative Poisson structure (PS), and arc negative Poisson structure (APS). A new bionic automobile energy absorbing box is constructed by combining with automobile energy absorbing box. Experiments and simulations further verify excellent mechanical properties of bionic structures. The results show that EA of AHS and APS is 117.2% and 105.8% of HS and PS. Their specific energy absorption is 112.2% and 102.7% of HS and PS. HS EA box structure, AHS energy absorption box structure, PS energy absorption box structure, and APS energy absorption box structure are 114.2%, 117%, 109.2%, and 116.2% higher than traditional EA box structures, respectively. The excellent characteristics of biological structures can provide ideas for structural design objectives of engineering applications and greatly simplify the process of optimal design.

Cloning and sequence analysis of two banana bunchy top virus genomes in Hainan.

The genome of Banana bunchy top virus (BBTV) consists of six segments of single-stranded DNA of approximately 1 kb in length. We identified and sequenced the complete genomes of two BBTV isolates, one with and one without satellite DNA, from Haikou, Hainan, China. The Haikou-2 isolate contains six genomic segments and an additional satellite DNA while the Haikou-4 isolate contains only six genomic segments. Typical of other babuviruses, each genomic segment encodes a single open reading frame and contains the highly conserved stem-loop and major common regions. Phylogenetic analysis of the two Haikou isolates together with existing sequence records in GenBank confirmed the grouping of BBTV into two large groups and further refined the geographical distribution of each group. To accommodate the changes in the BBTV geographical distribution, the two groups are proposed as the Southeast Asian group and the Pacific-Indian Oceans group. Both the Haikou-2 and Haikou-4 isolates belong to the newly proposed Southeast Asian group.

Silencing of molt-regulating transcription factor gene, CiHR3, affects growth and development of sugarcane stem borer, Chilo infuscatellus.

RNA interference (RNAi) is a technology for conducting functional genomic studies and a potential tool for crop protection against insect pests. Development of reliable methods for production and delivery of double-stranded RNA (dsRNA) is the major challenge for efficient pest control. In this study, Chilo infuscatellus Snellen (Crambidae: Lepidoptera) was fed with CiHR3 dsRNA expressed in bacteria or synthesized in vitro. The dsRNA ingested by C. infuscatellus successfully triggered silencing of the molt-regulating transcription factor CiHR3, an important gene for insect growth and development, and caused significant abnormalities and weight loss in insects within seven days of treatment. This study is an ideal example of feeding-based RNAi mediated by dsRNA expressed in bacteria or synthesized in vitro. The results also suggested that feeding-based RNA interference is a potential method for the management of C. infuscatellus.

Comparison of posterior decompression techniques and conventional laminectomy for lumbar spinal stenosis.

Objectives: To compare the efficacy of posterior decompression techniques with conventional laminectomy for lumbar spinal stenosis. Methods: The Embase, PubMed, and Cochrane Library databases were searched with no language limitations from inception to January 13, 2022. The main outcomes were functional disability, perceived recovery, leg and back pain, complications. A random effects model was used to pooled data. Risk ratio (RR), mean difference (MD) and 95% confidence interval (CI) were used to report results. The study protocol was published in PROSPERO (CRD42022302218). Results: 14 trials including 1,106 participants were included in the final analysis. Bilateral laminotomy was significantly more efficacious in improve functionality than laminectomy [MD: -2.94; (95% CI, -4.12 to -1.76)]. Low incidence of iatrogenic instability due to bilateral laminectomy compared with laminectomy [RR: 0.11; (95% CI, 0.02 to 0.59)]. In addition, between those who received bilateral laminotomy and those undergoing laminectomy, the result showed significant difference regarding recovery [RR: 1.31; (95% CI, 1.03 to 1.67)]. Conclusions: This study provides evidence that bilateral laminotomy has advantages in functional recovery, postoperative stability, and postoperative rehabilitation outcomes. Further research is needed to determine whether posterior techniques provide a safe and effective option for conventional laminectomy.

Genomic sequencing and analysis of Chilli ringspot virus, a novel potyvirus.

Chilli ringspot virus (ChiRSV), a novel potyvirus, was recently found in Hainan, China with high prevalence. The genomic sequence of the ChiRSV-HN/14 isolate was determined by sequencing overlapping cDNA segments generated by reverse transcription polymerase chain reaction with degenerate and/or specific primers. ChiRSV genome (GenBank Acc. no. JN008909) comprised of 9,571 nucleotides (nt) excluding the 3'-terminal poly (A) tail and contained a large open reading frame of 9,240 nt encoding a large polyprotein of 3,079 amino acids with predicted Mr of 349.1 kDa. A small, overlapping PIPO coding region was also found to span from nt 2,913 to 3,095, with a capacity to encode a peptide of 60 amino acids. ChiRSV shares sequence identities of only 48.5-65.4 and 42.9-68.7% with closely related potyviruses at the nucleotide and the amino acid levels, respectively. Phylogenetic analysis of the genomic sequences provided further evidence that ChiRSV is a distinct species of the Potyvirus genus. ChiRSV-HN/14 is most closely related to Tobacco vein banding mosaic virus and two other pepper-infecting potyviruses.

Identification, characterization, and expression of a novel P450 gene encoding CYP6AE25 from the Asian corn borer, Ostrinia furnacalis.

An allele of the cytochrome P450 gene, CYP6AE14, named CYP6AE25 (GenBank accession no. EU807990) was isolated from the Asian com borer, Ostrinia fumacalis (Guenée) (Lepidoptera: Pyralidae) by RT-PCR. The cDNA sequence of CYP6AE25 is 2315 bp in length and contains a 1569 nucleotides open reading frame encoding a putative protein with 523 amino acid residues and a predicted molecular weight of 59.95 kDa and a theoretical pI of 8.31. The putative protein contains the classic heme-binding sequence motif F××G×××C×G (residues 451-460) conserved among all P450 enzymes as well as other characteristic motifs of all cytochrome P450s. It shares 52% identity with the previously published sequence of CYP6AE14 (GenBank accession no. DQ986461) from Helicoverpa armigera. Phylogenetic analysis of amino acid sequences from members of various P450 families indicated that CYP6AE25 has a closer phylogenetic relationship with CYP6AE14 and CYP6B1 that are related to metabolism of plant allelochemicals, CYP6D1 which is related to pyrethroid resistance and has a more distant relationship to CYP302A1 and CYP307A1 which are related to synthesis of the insect molting hormones. The expression level of the gene in the adults and immature stages of O. furnacalis by quantitative real-time PCR revealed that CYP6AE25 was expressed in all life stages investigated. The mRNA expression level in 3(rd) instar larvae was 12.8- and 2.97-fold higher than those in pupae and adults, respectively. The tissue specific expression level of CYP6AE25 was in the order of midgut, malpighian tube and fatty body from high to low but was absent in ovary and brain. The analysis of the CYP6AB25 gene using bioinformatic software is discussed.

A New Method to Obtain the Complete Genome Sequence of Multiple-Component Circular ssDNA Viruses by Transcriptome Analysis.

Circular single-stranded DNA (ssDNA) viruses are widely distributed globally, infecting diverse hosts ranging from bacteria, archaea, and eukaryotes. Among these, the genome of Banana bunchy top virus (BBTV) comprises at least six circular, ssDNA components that are ∼1 kb in length. Its genome is usually amplified and obtained at the DNA level. However, RNA-based techniques to obtain the genome sequence of such multi-component viruses have not been reported. In this study, transcriptome sequencing analysis showed that the full-length of BBTV each genomic component was transcribed into viral mRNA (vmRNA). Accordingly, the near-complete genome of BBTV B2 isolate was assembled using transcriptome sequencing data from virus-infected banana leaves. Assembly analysis of BBTV-derived reads indicated that the full-length sequences were obtained for DNA-R, DNA-U3, DNA-S, DNA-M, DNA-N, NewS2, and Sat4 components, while two gaps (73 and 25 nt) missing in the DNA-C component which was further filled by reverse transcription-PCR (RT-PCR). The RT-qPCR analysis indicated that the vmRNA levels of coding regions were 3.19-103.53 folds higher than those of non-coding regions, implying that the integrity of genome assembly depended on the transcription level of non-coding region. In conclusion, this study proposes a new approach to obtain the genome of nanovirids, and provides insights for studying the transcriptional mechanism of the family Nanoviridae, Genomoviridae, and Geminiviridae.

The complete genome of Banana streak GF virus Yunnan isolate infecting Cavendish Musa AAA group in China.

Banana streak virus (BSV) belongs to the members of the genus Badnavirus, family Caulimoviridae. At present, BSV contains nine species in the International Committee on Taxonomy of Viruses (ICTV) classification report (2018b release). Previous study indicated that the viral particles of Banana streak virus Acuminata Yunnan (BSV-Acum) were purified from banana (Cavendish Musa AAA group) leaves in Yunnan Province, China, and its complete genome was obtained. To further determine whether this sample infecting with Banana streak GF virus (BSGFV), the polymerase chain reaction (PCR) cloning and complete genome analysis of the Banana streak GF virus Yunnan isolate (BSGFV-YN) isolate were carried out in this study. The result showed that BSGFV-YN infecting Cavendish Musa AAA group was co-infecting this sample. Its genome contains a total of 7,325 bp in length with 42% GC content. This complete genome sequence was deposited in GenBank under accession number MN296502. Sequence analysis showed that the complete genome of BSGFV-YN was 98.14% sequence similarity to BSGFV Goldfinger, while it was 49.10-57.09% to other BSV species. Two phylogenetic trees based on the complete genome and ORFIII polyprotein indicated that BSGFV-YN and other BSV species clustered into a group, while it was the highest homology with BSGFV Goldfinger. Although BSGFV-YN and BSGFV Goldfinger were highly homologous, their cultivating bananas are different. The former cultivating banana was from Cavendish Musa AAA group, while the latter cultivating banana was from Goldfinger Musa AAAB group. Compared with BSGFV Goldfinger, the genome of BSGFV-YN has an extra multiple repetitive sequences in the intergenetic region between ORFIII and ORFI, suggesting that this region might be related to host selection. In summary, a BSGFV-YN distant from BSV-Acum was identified from the same sample, and its complete genome sequence was determined and analyzed. The study extends the polymorphism of BSVs in China and provides scientific clue for the evolutionary relationship with host selection of badnaviruses.

Banana bunchy top virus (BBTV) nuclear shuttle protein interacts and re-distributes BBTV coat protein in Nicotiana benthamiana.

Banana bunchy top virus (BBTV) is a circular single-stranded DNA virus with multi-components. The knowledge about interaction between viral proteins and pathogenesis mechanism of BBTV remains unclear. In this study, the coat protein gene (CP, ORF 516 bp) and nuclear shuttle protein gene (NSP, ORF 465 bp) from BBTV B2 isolate of the Southeast-Asia group were cloned. The intracellular localization analysis showed the CP locates in the cell nucleus of tobacco cells, while the NSP distributes in the cell nucleus and cytoplasm. Co-localization analysis indicated the NSP itself does not change distribution, but CP re-distributes to the cell nucleus and cytoplasm, suggesting that NSP interacts with CP and re-locates the CP in the cell. The interaction between CP and NSP was further verified by co-immunoprecipitation (Co-IP) in tobacco protoplasts. The study will help us to understand the interaction between viral proteins and pathogenesis mechanism of BBTV in host plants.

Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling.

Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by ß-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a ß-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-ß-arrestin-1 signalling complex. Replacing the C-terminal region of ß-arrestin-1 with its counterpart on ß-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between ß-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes.

Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis.

OBJECTIVE: Midodrine has been reported to improve systemic and renal hemodynamics in patients with cirrhotic ascites. However, the results of clinical trials are conflicting. The aim of this study is to evaluate the effects of midodrine on cirrhotic ascites through a meta-analysis and systematic review. METHODS: We searched PubMed (January 1966-December 2014), EMBASE (January 1966-December 2014), the Cochrane Library (Issue 11, 2014), ScienceDirect (January 1966-December 2014), and the China National Knowledge Infrastructure (January 1979-December 2014) databases using the terms 'midodrine' AND 'cirrhosis' AND 'ascites' AND 'paracentesis' for all relevant randomized controlled trials using midodrine for treatment of cirrhotic ascites. RESULTS: In all, 10 trials with a total of 462 patients were included. As a novel therapy for cirrhotic ascites, midodrine was not found to improve survival [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.23-2.91]; although it might improve response rates (OR 3.36, 95% CI 1.47-7.69) and reduce plasma renin activity (MD -3.10, 95% CI -5.37 to -0.84). When midodrine was used as an alternative to albumin in large-volume paracentesis, the mortality was higher for midodrine than for albumin (OR 10.76, 95% CI 1.35-85.97). However, there was no statistically significant difference in the development of paracentesis-induced circulatory dysfunction between midodrine group and albumin group (OR 1.69, 95% CI 0.43-6.72). CONCLUSIONS: Midodrine may have treatment effects on cirrhotic ascites. Better powered and well-designed trials are required to assess the extent of the efficacy of midodrine in specifically targeted patients.