Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species

Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu–Glu–Leu–Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu–Glu–Leu–Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species. © 2015, MDPI AG. All rights Reserved.published_or_final_versio

Omicron variant susceptibility to neutralizing antibodies induced in children by natural SARS-CoV-2 infection or COVID-19 vaccine

The novel SARS-CoV-2 Omicron variant may increase the risk of re-infection and vaccine breakthrough infections as it possesses key mutations in the spike protein that affect neutralizing antibody response. Most studies on neutralization susceptibility were conducted using specimens from adult COVID-19 patients or vaccine recipients. However, since the paediatric population has an antibody response to SARS-CoV-2 infection that is distinct from the adult population, it is critical to assess the neutralization susceptibility of pediatric serum specimens. This study compared the neutralization susceptibility of serum specimens collected from 49 individuals of <18 years old, including 34 adolescent BNT162b2 (Pfizer-BioNTech) vaccine recipients, and 15 recovered COVID-19 patients aged between 2 and 17. We demonstrated that only 38.2% of BNT162b2 vaccine recipients and 26.7% of recovered COVID-19 patients had their serum neutralization titre at or above the detection threshold in our live virus microneutralization assay. Furthermore, the neutralizing antibody titer against the Omicron variant was substantially lower than those against the ancestral virus or the Beta variant. Our results suggest that vaccine recipients and COVID-19 patients in the pediatric age group will likely be more susceptible to vaccine breakthrough infections or reinfections due to the Omicron variant than previous variants

Age-specific incidence rate in severe or symptomatic infection due to pandemic H1N1 2009 influenza virus

Poster Abstract Session - Influenza and H1N1 Diagnosis, Epidemiology, and Viral Outcome: abstract no. 1133BACKGROUND: Age-specific incidence of the 2009 pandemic influenza provides the scientific basis of public health policies and the basic science research on the age-related susceptibility to influenza. While previous epidemiological studies provided vital information for public health policies, most did not incorporate age-specific data of asymptomatic, symptomatic and severe infection in the analysis. In this study, we incorporated data from seroprevalence and microbiologically-confirmed infection to estimate the relative impact of the pandemic influenza on various age groups. METHODS: For the determination of pre-pandemic and post-pandemic seroprevalence, archived plasma samples randomly collected at the clinical biochemistry department of Queen Mary Hospital in the years 2007 and 2010 were used respectively. Microbiologically-confirmed cases and severe cases reported to the Centre for Health Protection (CHP) from May 1, 2009 to May 23, 2010 were included in our analysis. This study was approved by the institutional review board of the Hospital Authority of Hong Kong. RESULTS: 795 and 1000 plasma samples were collected in 2007 and 2010 respectively. In 2007, 8.7% and 14.2% of individuals had HI titers ≥40 and ≥10 respectively. The pre-existing cross-reactive antibodies were mainly found in patients aged >70 years old. In 2010, the overall proportion of individuals with HI titers ≥40 and ≥10 is 23.2% and 42.2%. The highest overall microbiologically-confirmed incidence rate was found in the 0-10 year age group, and decreased with increasing age (ρ=-1.0, p<0.01). A total of 282 severe cases were reported with a mean age was 47.6 years. The incidence rate of severe cases showed an apparent bimodal age distribution, with higher incidence rate in the age group 0-10 and those older than 50 years old, and the highest incidence rate being those between 51 and 60 years old. CONCLUSION: While the young adults were most commonly infected, the clinical consequence is most alarming in children and older adults aged over 50 years. Public policies should continue to target this high risk group.published_or_final_versionThe 49th Annual Meeting of the Infectious Diseases Society of America (IDSA 2011), Boston, MA., 20-23 October 2011

Assessment of SARS-CoV-2 Immunity in Convalescent Children and Adolescents

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for COVID-19 vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine Adverse Event Response and Evaluation Programme. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analysed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. 29 (87.88%) were males and 4 (12.12%) were females, with a median age of 15.25 years. 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management.The overall incidence of acute myocarditis/pericarditis was 18.52 (95% Confidence Interval [CI], 11.67-29.01) per 100,000 persons vaccinated. The incidence after the first and second doses were 3.37 (95%CI 1.12-9.51) and 21.22 (95%CI 13.78-32.28 per 100,000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI 2.38-12.53) and 37.32 (95% CI 26.98-51.25) per 100,000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose

Luminescent tricarbonylrhenium(I) polypyridine estradiol conjugates: Synthesis, crystal structure, and photophysical, electrochemical, and protein-binding properties

A series of luminescent tricarbonylrhenium(I) polypyridine estradiol complexes [Re(N-N)(CO)3(L)]-(CF3SO3) (N-N = 1,10-phenanthroline (phen), L = 4-(17α-ethynylestradiolyl)pyridine (py-est) (1a), 4-(N-(6-(4-(17α-ethynylestradiolyl)benzoylamino)hexanoyl) aminomethyl)pyridine (py-C6-est) (1b); N-N = 3,4,7,8-tetramethyl-1,10- phenanthroline (Me4-phen), L = py-est (2a), py-C6-est (2b); N-N = 4,7-diphenyl-1,10-phenanthroline (Ph2-phen), L = py-est (3a), py-C6-est (3b)) have been synthesized and characterized. The X-ray crystal structure of complex 1a has also been investigated. The photophysical and electrochemical properties of all the complexes have been studied. Upon irradiation, most of the complexes exhibited intense and long-lived triplet metal-to-ligand charge-transfer (3MLCT) (dπ(Re) → π*(N-N)) emission in fluid solutions at 298 K and in low-temperature glass. The excited states of the Me4-phen complexes possessed some triplet intraligand 3IL character. The lipophilicity of all the complexes has been determined by reversed-phase HPLC. In addition, the binding of these complexes to estrogen receptor α has been investigated by emission titrations. © 2006 American Chemical Society.link_to_subscribed_fulltex

Luminescent Tricarbonylrhenium(I) Dipyridoquinoxaline Iodine Complexes as Sensitive Probes for Indole-Binding Proteins

Luminescent tricarbonylrhenium(I) dipyridoquinoxaline indole complexes [Re(N−N)(CO)3(L)](CF3SO3) (N−N = dipyrido[3,2-f:2‘,3‘-h]quinoxaline (dpq), L = N-(3-pyridoyl)tryptamine (py-3-CONHC2H4-indole) (1a), N-(N-(3-pyridoyl)-6-aminohexanoyl)tryptamine (py-3-CONHC5H10CONHC2H4-indole) (1b); N−N = 2-(n-butylamido)dipyrido[3,2-f:2‘,3‘-h]quinoxaline (dpqa), L = py-3-CONHC2H4-indole (2a), py-3-CONHC5H10CONHC2H4-indole (2b)) and their indole-free counterparts [Re(N−N)(CO)3(py-3-CONH-Et)](CF3SO3) (py-3-CONH-Et = N-ethyl-(3-pyridyl)formamide; N−N = dpq (1c), dpqa (2c)) have been synthesized and characterized. The crystal structure of a related complex, [Re(dpqa)(CO)3(pyridine)](PF6), has also been studied. All the complexes exhibited triplet metal-to-ligand charge-transfer (3MLCT) (dπ(Re) → π*(N−N)) emission in fluid solutions at 298 K and in alcohol glass at 77 K. The emission quantum yields of the complexes were reduced upon changing from CH2Cl2 to aqueous buffer. The reduction was much more significant for the dpqa complexes than the dpq complexes due to the hydrogen-bonding interaction of the amide substituent of the dpqa ligand with water molecules. The interactions of these tricarbonylrhenium(I) complexes with indole-binding proteins including bovine serum albumin and tryptophanase have been studied by emission titrations and inhibition assays, respectively

Luminescent rhenium(I) diimine indole conjugates - Photophysical, electrochemical and protein-binding properties

Two novel luminescent rhenium(I) diimine indole complexes have been designed and their properties studied; these conjugates can be recognised by indole-binding proteins including bovine serum albumin, lysozyme and tryptophanase.link_to_subscribed_fulltex

Ebola virus disease: a highly fatal infectious disease reemerging in West Africa

Ebolavirus can cause a highly fatal and panic-generating human disease which may jump from bats to other mammals and human. High viral loads in body fluids allow efficient transmission by contact. Lack of effective antivirals, vaccines and public health infrastructures in parts of Africa make it difficult to health workers to contain the outbreak. © 2014 Institut Pasteur