Fifty-year pollution history of microplastics and influencing factors in offshore sediments: A case study of Ningbo, China.

Sediment cores are optimal mediums for investigating the historical presence of offshore microplastics (MPs). In this study, two sediment cores were collected at varying water depths, i.e., XS2 (10 m) and XS3 (20 m), from the Xiangshan offshore (XSO) in Ningbo. We focused on the spatiotemporal distribution characteristics of MPs within two sediment cores and explored the response differences of MPs abundance to natural factors and human activities. The results showed that the MPs abundance in sediments has gradually increased since the late 1960s, but with interannual fluctuations. MPs abundance in XS2 and XS3 were 1133-8700 and 633-11433 items/kg dry weight, respectively. The predominant polymers were PA, PU, PET and ACR, with fragmented particles being the most prevalent shape of MPs. The MPs abundance in XS2 and XS3 had a similar response to natural factors, mainly including (i) MPs abundance significantly correlated with the sediment load of the Qiantang River (p < 0.01), indicating that sediment load might be an important factor affecting the MPs abundance and that MPs transported by rivers had characteristics of near-source sedimentation; (ii) typhoons had the effect of weakening the MPs abundance; and (iii) geological activities might be potential contributing factors to variations in MPs' abundance in deep sediments. Correlation analyses demonstrated that MPs in XSO was the result of multiple sources, stemming from plastic production, sewage discharge, marine fisheries and shipping activities. Notably, XS3 exhibited higher sensitivity to human activities compared to XS2, owing to differences in sampling locations. This study underscores the significance of employing two sediment cores, rather than a single core, as it provides a more comprehensive insight into the overarching trends and disparities in the historical pollution of MPs. Our findings contribute to a deeper understanding of the history of offshore MPs pollution, shedding new light on this critical environmental issue.

Molecular Epidemiology and Clinical Characteristics of an Outbreak on Respiratory Virus Coinfection in Gansu, China.

This study aims to analyze the epidemiological and pathogenic characteristics of an outbreak primarily caused by respiratory syncytial virus (RSV), human rhinovirus (HRV), and human metapneumovirus (HMPV) in a kindergarten and primary school. The outbreak was investigated by field epidemiological investigation, and the common respiratory pathogens were screened by RT-PCR detection technology. The attack rate of this outbreak was 63.95% (110/172). Main symptoms included cough (85.45%), sore throat (60.91%), and sneezing (60.00%). Multifactorial logistic regression analysis revealed that continuous handwashing and mouth and nose covering when sneezing were protective factors. All 15 collected throat swab specimens tested positive for viruses, with HMPV as the predominant pathogen (80.00%), followed by HRV (53.33%), and two cases of positive respiratory syncytial virus (13.33%). Among them, six samples showed coinfections of HMPV and HRV, and one had coinfections of HMPV and RSV, resulting in a coinfection rate of 46.67%. Genetic sequencing indicated that the HMPV genotype in this outbreak was A2c, and the HRV genotype was type A, resulting in a coinfection outbreak of HMPV, HRV, and RSV in schools and kindergartens, suggesting that multi-pathogen surveillance of respiratory tract infections should be strengthened.

Olgotrelvir, a dual inhibitor of SARS-CoV-2 Mpro and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19.

BACKGROUND: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance. METHODS: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (Mpro), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells. FINDINGS: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115. The dual mechanism of action of olgotrelvir and AC1115 was confirmed by enzyme activity inhibition assays and co-crystal structures of AC1115 with SARS-CoV-2 Mpro and human CTSL. AC1115 displayed antiviral activity by inhibiting replication of all tested SARS-CoV-2 variants in cell culture systems. Olgotrelvir also inhibited viral entry into cells using SARS-CoV-2 Spike-mediated pseudotypes by inhibition of host CTSL. In the K18-hACE2 transgenic mouse model of SARS-CoV-2-mediated disease, olgotrelvir significantly reduced the virus load in the lungs, prevented body weight loss, and reduced cytokine release and lung pathologies. Olgotrelvir demonstrated potent activity against the nirmatrelvir-resistant Mpro E166 mutants. Olgotrelvir showed enhanced oral bioavailability in animal models and in humans with significant plasma exposure without ritonavir. In phase I studies (ClinicalTrials.gov: NCT05364840 and NCT05523739), olgotrelvir demonstrated a favorable safety profile and antiviral activity. CONCLUSIONS: Olgotrelvir is an oral inhibitor targeting Mpro and CTSL with high antiviral activity and plasma exposure and is a standalone treatment candidate for COVID-19. FUNDING: Funded by Sorrento Therapeutics.