Identification of novel porcine and bovine parvoviruses closely related to human parvovirus 4

Human parvovirus 4 (PARV4), a recently discovered parvovirus found exclusively in human plasma and liver tissue, was considered phylogenetically distinct from other parvoviruses. Here, we report the discovery of two novel parvoviruses closely related to PARV4, porcine hokovirus (PHoV) and bovine hokovirus (BHoV), from porcine and bovine samples in Hong Kong. Their nearly full-length sequences were also analysed. PARV4-like viruses were detected by PCR among 44.4% (148/333) of porcine samples (including lymph nodes, liver, serum, nasopharyngeal and faecal samples), 13% (4/32) of bovine spleen samples and 2% (7/362) of human serum samples that were sent for human immunodeficiency virus and hepatitis C virus antibody tests. Three distinct parvoviruses were identified, including two novel parvoviruses, PHoV and BHoV, from porcine and bovine samples and PARV4 from humans, respectively. Analysis of genome pequences from seven PHoV strains, from three BHoV strains and from one PARV4 strain showed that the two animal parvoviruses were most similar to PARV4 with 61.5-63% nt identities and, together with PARV4 (HHoV), formed a distinct cluster within the family Parvoviridae. The three parvoviruses also differed from other parvoviruses by their relatively large predicted VP1 protein and the presence of a small unique conserved putative protein. Based on these results, we propose a separate genus, Hokovirus, to describe these three parvoviruses. The co-detection of porcine reproductive and respiratory syndrome virus, the agent associated with the recent 'high fever' disease outbreaks in pigs in China, from our porcine samples warrants further investigation. © 2008 SGM.published_or_final_versio

Gasdermin D mutation protects against renal ischemia reperfusion injury

Pyroptosis, the most inflammatory form of cell death, is dependent on membrane pore formation governed by the assembly of cleaved Gasdermin D (GSDMD). We hypothesized that regulated necrosis pathways are crucial in the pathophysiology of acute kidney injury (AKI). Mice with an isoleucine‐to‐asparagine loss‐of‐function mutation in the Gasdermin D gene (GSDMDI105N/I105N) generated by ethylnitrosourea‐mutagenesis were subjected to bilateral renal ischemia–reperfusion injury (IRI) with bio‐molecular readouts performed at 24 h. IRI was also performed in mice pretreated with disulfiram. Whole‐body irradiation followed by syngeneic bone marrow transplantation generated chimeric mice prior to IRI. Mice homozygous for the GSDMD I105N mutation were protected from IRI, demonstrating lower serum creatinine and reduced histological injury, as well as decreased pro‐inflammatory cytokine expression and oxidative stress. Chimeric mice showed that this protection was predominantly governed by mutations in the parenchymal tissue, with a potential contribution from the hematopoietic compartment. Pharmacological inhibition of GSDMD pore formation using disulfiram protected against IRI. Manipulation of GSDMD is an attractive target to mitigate inflammation and cellular death following AKI

Mechanism of Protection Induced by Group A Streptococcus Vaccine Candidate J8-DT: Contribution of B and T-Cells Towards Protection

Vaccination with J8-DT, a leading GAS vaccine candidate, results in protective immunity in mice. Analysis of immunologic correlates of protection indicated a role of J8-specific antibodies that were induced post-immunization. In the present study, several independent experimental approaches were employed to investigate the protective immunological mechanisms involved in J8-DT-mediated immunity. These approaches included the passive transfer of mouse or rabbit immune serum/antibodies in addition to selective depletion of T-cell subsets prior to bacterial challenge. Passive transfer of J8-DT antiserum/antibodies from mice and rabbits conferred significant resistance against challenge to mice. To exclude the possibility of involvement of other host immune factors, the studies were repeated in SCID mice, which highlighted the need for an ongoing immune response for long-lived protection. Depletion of CD4+ and CD8+ T-cell subsets confirmed that an active de novo immune response, involving CD4+ T-helper cells, is required for continued synthesis of antibodies resulting in protection against GAS infection. Taken together these results indicate an involvement of CD4+ T-cells in J8-DT-mediated protection possibly via an ability to maintain antibody levels. These results have considerable relevance to the development of a broad spectrum passive immunotherapy for GAS disease

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society

ADAMTS13 mutational analysis in Chinese patients with chronic relapsing thrombotic thrombocytopenic purpura

Mutational analysis of ADAMTS13 gene was performed on three Chinese children with chronic relapsing thrombotic thrombocytopenic purpura, who all showed severe deficiency (<5% activity) of von Willebrand factor-cleaving protease (vWF-CP) and lack of inhibitors. In two patients, three new mutations, namely G194V, R349C and G1181R, were identified along with a fourth mutation A596V recently described in a French patient. No significant ADAMTS13 gene defect was detected in one patient, in whom the presence of low titer or non-neutralizing antibodies to vWF-CP was not excluded. The prevalence of G194V and G1181R mutations was 1.5% and 5.8% among normal Chinese subjects. They may constitute genetic susceptibility factors for thrombosis in the population.link_to_OA_fulltex

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB 2) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB 2 but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells. © 2009 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Non-covalent Binding of Luminescent Transition Metal Polypyridine Complexes to Avidin, Iodole-binding Proteins and Estrogen Receptors

A number of luminescent transition metal complexes possess rich photophysical and photochemical properties that allow them to serve as useful labels and probes for biological molecules. This article describes the current trend in this area of research, with emphasis on our recent work on luminescent rhenium(I), iridium(III) and ruthenium(II) polypyridine complexes as non-covalent probes for avidin, indole-binding proteins and estrogen receptors. We focus on the molecular design, photophysical properties and biomolecule-binding behaviour of these systems; different approaches to enhancing the detection sensitivity are also discussed

A simplified method of calculating cPRA for kidney allocation application in Hong Kong: a retrospective study

Calculated panel reactive antibody (cPRA) represents possibility of encountering an incompatible donor for organ transplant candidates and has gradually replaced traditional PRA as a measurement of sensitization level. We tested two cPRA calculation methods on a cohort of renal candidate (n = 613). HLA typing of 563 Chinese deceased renal donors was used to estimate allele and haplotype frequencies of Hong Kong donor pool. The OPTN formula was adopted to generate cPRA (cPRA (freq)). We also incorporated a computer script to compare unacceptable antigens of patients against HLA phenotype of donors. The cPRA based on historical donor filtering was the percentage of filter out count over total number of donors (cPRA (filter)). Values of cPRA (freq) and cPRA (filter) showed almost perfect agreement with Lin's correlation coefficient equal to 1.000. SD of bias was 0.6 cPRA point. Limit of agreement was 0.9 to -1.5 points difference. Furthermore, the poor agreement between our in-house cPRA and values from other online calculators indicated the necessity to use local population data for accurate cPRA calculation. Built-in donor filtering method was more practicable for Hong Kong due to factors such as cost and flexibility. An on-going donor pool can reflect population allele frequencies and permits efficient periodic update of cPRA

USMB-shMincle: a virus-free gene therapy for blocking M1/M2 polarization of tumor-associated macrophages

202303 bcwwVersion of RecordRGCOthersResearch Grants Council, University Grants Committee, 研究資助局: 14106518, 14111019, 14111720; Chinese University of Hong Kong, CUHK: 4054510, 4620528; Innovation and Technology Fund, ITF: ITS/068/18, InP/009/19, InP/159/19, PiH/009/19, PiH/010/19, PiH/394/19Publishe