Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc . The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.

Background and aims Liver injury is found in some of patients with COVID-19. Liver injury of COVID-19 patients based on severity grading and abdominal radiological signs have not been reported until now. The aim of our study is to determine clinical profiles of the patients based on severity grading, describe abdominal radiological signs, and investigate the correlations of the severity with clinical profiles and radiological signs. Methods This retrospective cohort study included 115 patients with COVID-19 from Jan 2020 to Feb 2020. Medical records of the patients were collected and CT images were reviewed. Results Common clinical manifestations of patients with COVID-19 were fever (68.70%), cough (56.52%), fatigue (31.30%); some of them had gastrointestinal symptoms (diarrhea, 12.17%; nausea or vomiting 7.83%; inappetence, 7.83%). Abnormal liver function was observed in some of patients with COVID-19. Significant differences in the levels of AST, albumin,CRP were observed among different groups classified by the severity. Common findings of upper abdominal CT scan were liver hypodensity (26.09%) and pericholecystic fat stranding (21.27%); liver hypodensity was more frequently found in critical cases (58.82%). The severity of COVID-19 correlated with semi-quantitative CT score of pulmonary lesions, CT-quantified liver/spleen attenuation ratio in patients with COVID-19. Conclusions Some of the patients with COVID-19 displayed liver damage revealed by liver functional tests and upper abdominal CT imaging, and the severity of COVID-19 patients correlated with some of liver functional tests and CT signs; thus, it will allow an earlier identification of high-risk patients for early effective intervention. Keywords COVID-19 • Liver • Clinical profiles • Tomography • X-ray computed Abbreviations CT Computed tomography COVID-19 Coronavirus disease 2019 SARS-CoV-2 The severe acute respiratory syndrome coronavirus 2 2019-nCoV 2019 Novel coronavirus ARDS Acute respiratory distress syndrome MOF Multiple organ failure DILI Drug-induced liver injury ROI Regions of interest ICC Intraclass correlation efficient Ping Lei and Lan Zhang contributed equally to this study.

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. Since PAs exposure is obscure and clinical presentation of HSOS is unspecific, it is challenge to establish the diagnosis of PAs-induced HSOS. Gynura segetum is one of the most wide-use herbals containing PAs. The aim of our study is to describe the features of contrast-enhanced computed tomography (CT) in gynura segetum-induced HSOS, and then determine diagnostic performance of radiological signs. We retrospectively analyzed medical records and CT images of HSOS patients (71 cases) and the controls (222 cases) enrolled from January 1, 2008, to Oct 31, 2015. The common findings of contrast CT in PAs-induced HSOS included: ascites (100%), hepatomegaly (78.87%), gallbladder wall thickening (86.96%), pleural effusion (70.42%), hepatic vein narrowing (87.32%), patchy liver enhancement (92.96%), and heterogeneous hypoattenuation (100%); of these signs, patchy enhancement and heterogeneous hypoattenuation were valuable features. Then, the result of diagnostic performance demonstrated that contrast CT possessed better performance in diagnosing PAs-induced HSOS compared with various parameters of Seattle criteria. In conclusion, the patients with PAs-induced HSOS display distinct radiologic features at CT-scan, which reveals that contrast-enhanced CT provides an effective noninvasive method for diagnosing PAs-induced HSOS.

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Cystic fibrosis is characterized by deficiency of the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-) transporter. The packaging constraints of adeno-associated viral (AAV) vectors preclude delivery of both an active promoter and CFTR cDNA to target cells. We hypothesized that segmental trans-splicing, in which two AAV vectors deliver the 5' and 3' halves of the CFTR cDNA, could mediate splicing of two pre-mRNAs into a full-length, functional CFTR mRNA. Using a segmental trans-splicing 5' donor-3' acceptor pair that split the CFTR cDNA between exons 14a and 14b, cotransfection of donor and acceptor plasmids into CFTR(-) cells resulted in full-length CFTR message and protein. Microinjection of plasmids into CFTR(-) cells produced cAMP-activated Cl(-) conductance. Vectors created with an engineered human serotype, AAV6.2, were used to deliver CFTR donor and acceptor constructs, resulting in full-length CFTR mRNA and protein as well as cAMP-activated Cl(-) conductance in CFTR(-) cells, including human CF airway epithelial IB3-1 cells. Thus, segmental trans-splicing can be used with AAV vectors to mediate expression of CFTR, a strategy potentially applicable to individuals with CF.

Zinc homeostasis was investigated in Nostoc punctiforme. Cell tolerance to Zn 2؉ over 14 days showed that ZnCl 2 levels above 22 M significantly reduced cell viability. After 3 days in 22 M ZnCl 2 , ca. 12% of the Zn 2؉ was in an EDTA-resistant component, suggesting an intracellular localization. Zinquin fluorescence was detected within cells exposed to concentrations up to 37 M relative to 0 M treatment. Radiolabeled 65 Zn showed Zn 2؉ uptake increased over a 3-day period, while efflux occurred more rapidly within a 3-h time period. Four putative genes involved in Zn 2؉ uptake and efflux in N. punctiforme were identified: (i) the predicted Co/Zn/Cd cation transporter, putative CDF; (ii) the predicted divalent heavy-metal cation transporter, putative Zip; (iii) the ATPase component and Fe/Zn uptake regulation protein, putative Fur; and (iv) an ABC-type Mn/Zn transport system, putative zinc ZnuC, ZnuABC system component. Quantitative real-time PCR indicated the responsiveness of all four genes to 22 M ZnCl 2 within 3 h, followed by a reduction to below basal levels after 24 h by putative ZIP, ZnuC, and Fur and a reduction to below basal level after 72 h by putative CDF efflux gene. These results demonstrate differential regulation of zinc transporters over time, indicating a role for them in zinc homeostasis in N. punctiforme.Cyanobacteria are photosynthetic prokaryotes, many of which accumulate heavy metals. Consequently, they have attracted interest as a tool for the removal of metals from wastewater. Cyanobacteria, including Anabaena nodosum (10), Nostoc linkia (12), Microcystis aeruginosa (39), and Synechococcus sp. strain PCC7942 (16), are able to accumulate the heavy metals cadmium, zinc, copper, and chromium, respectively. Heavy metal accumulation involves an initial rapid, passive adsorption of the metal to components of the cell wall over seconds or minutes, followed by a slower process that results in the sequestration of the metal to an EDTA-resistant compartment, such as the cytoplasm, within hours (for reviews, see references 7 and 29). Cell wall components that have a high affinity for metals account for the bulk of the adsorbed metals (17). In M. aeruginosa, metal accumulation was only marginally decreased in cells treated with metabolic inhibitors and in heat-killed cells compared to the total metal uptake (34). Substantial data exist showing sorption of metals in cyanobacteria; however, the capacity of live cells to tolerate or accumulate metals and the molecular mechanisms underlying these processes are relatively unknown. In contrast to many bacterial species, cyanobacteria possess a metallothionein, SmtA, which may store Zn 2ϩ and prevent intracellular Zn 2ϩ toxicity (8). Polyphosphate granules may sequester intracellular metal ions, including zinc ions (4). These cellular characteristics make cyanobacteria unique organisms in regard to their ability to accumulate metals.Genomic analysis indicated that Nostoc punctiforme, a filamentous cyanobacterium, contains transporters that may function in...