Dynamically adjustable SVEIR(MH) model of multiwave epidemics: Estimating the effects of public health measures against COVID-19.

The COVID-19 pandemic was characterized by multiple subsequent, overlapping outbreaks, as well as extremely rapid changes in viral genomes. The information about local epidemics spread and the epidemic control measures was shared on a daily basis (number of cases and deaths) via centralized repositories. The vaccines were developed within the first year of the pandemic. New modes of monitoring and sharing of epidemic data were implemented using Internet resources. We modified the basic SEIR compartmental model to include public health measures, multiwave scenarios, and the variation of viral infectivity and transmissibility reflected by the basic reproduction number R0 of emerging viral variants. SVEIR(MH) model considers the capacity of the medical system, lockdowns, vaccination, and changes in viral reproduction rate on the epidemic spread. The developed model uses daily infection reports for assessing the epidemic dynamics, and daily changes of mobility data from mobile phone networks to assess the lockdown effectiveness. This model was deployed to six European regions Baden-Württemberg (Germany), Belgium, Czechia, Lombardy (Italy), Sweden, and Switzerland for the first 2 years of the pandemic. The correlation coefficients between observed and reported infection data showed good concordance for both years of the pandemic (ρ = 0.84-0.94 for the raw data and ρ = 0.91-0.98 for smoothed 7-day averages). The results show stability across the regions and the different epidemic waves. Optimal control of epidemic waves can be achieved by dynamically adjusting epidemic control measures in real-time. SVEIR(MH) model can simulate different scenarios and inform adjustments to the public health policies to achieve the target outcomes. Because this model is highly representative of actual epidemic situations, it can be used to assess both the public health and socioeconomic effects of the public health measures within the first 7 days of the outbreak.

Molecular epidemiology analysis of symptomatic and asymptomatic norovirus infections in Chinese infants.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.

Revealing the characteristics of ZIKV infection through tissue-specific transcriptome sequencing analysis.

BACKGROUND: Recently, Zika virus (ZIKV) re-emerged in India and was potentially associated with microcephaly. However, the molecular mechanisms underlying ZIKV pathogenesis remain to be explored. RESULTS: Herein, we performed a comprehensive RNA-sequencing analysis on ZIKV-infected JEG-3, U-251 MG, and HK-2 cells versus corresponding uninfected controls. Combined with a series of functional analyses, including gene annotation, pathway enrichment, and protein-protein interaction (PPI) network analysis, we defined the molecular characteristics induced by ZIKV infection in different tissues and invasion time points. Data showed that ZIKV infection and replication in each susceptible organ commonly stimulated interferon production and down-regulated metabolic-related processes. Also, tissue-specific immune responses or biological processes (BPs) were induced after ZIKV infection, including GnRH signaling pathway in JEG-3 cells, MAPK signaling pathway in U-251 MG cells, and PPAR signaling pathway in HK-2 cells. Of note, ZIKV infection induced delayed antiviral interferon responses in the placenta-derived cell lines, which potentially explains the molecular mechanism by which ZIKV replicates rapidly in the placenta and subsequential vertical transmission occurs. CONCLUSIONS: Together, these data may provide a systemic insight into the pathogenesis of ZIKV infection in distinct human tissue-derived cell lines, which is likely to help develop prophylactic and therapeutic strategies against ZIKV infection.

Genetic characterization of two G8P[8] rotavirus strains isolated in Guangzhou, China, in 2020/21: evidence of genome reassortment.

BACKGROUND: The G8 rotavirus genotype has been detected frequently in children in many countries and even became the predominant strain in sub-Saharan African countries, while there are currently no reports from China. In this study we described the genetic characteristics and evolutionary relationship between rotavirus strains from Guangzhou in China and the epidemic rotavirus strains derived from GenBank, 2020-2021. METHODS: Virus isolation and subsequent next-generation sequencing were performed for confirmed G8P[8] specimens. The genetic characteristics and evolutionary relationship were analyzed in comparison with epidemic rotavirus sequences obtained from GenBank. RESULTS: The two Guangzhou G8 strains were DS-1-like with the closest genetic distance to strains circulating in Southeast Asia. The VP7 genes of the two strains were derived from a human, not an animal G8 rotavirus. Large genetic distances in several genes suggested that the Guangzhou strains may not have been transmitted directly from Southeast Asian countries, but have emerged following reassortment events. CONCLUSIONS: We report the whole genome sequence information of G8P[8] rotaviruses recently detected in China; their clinical and epidemiological significance remains to be explored further.

Prevalence and Evolution of Noroviruses between 1966 and 2019, Implications for Vaccine Design.

Noroviruses (NoVs), a group of single-stranded RNA viruses causing epidemic acute gastroenteritis in humans, are highly diverse, consisting of multiple genogroups with >30 genotypes. Their continual evolutions make NoV vaccine design and development difficult. Here, we report a study of NoV sequences obtained from a population-based diarrhea surveillance in Zhengding County of Hebei Province spanning from 2001 to 2019 and those available in the GenBank database from 1966 to 2019. NoV genotypes and/or variants that may evade immunity were screened and identified based on primary and conformational structures for vaccine design. We selected 366, 301, 139, 74 and 495 complete VP1-coding nucleotide sequences representing the predominant genotypes of GII.4, GII.2, GII.3, GII.6 and GII.17, respectively. A total of 16 distinct GII.4 variants were identified, showing a typical linear evolutionary pattern of variant replacement, while only 1-4 variants of the other genotypes were found to co-circulate over the 40-50-year period without typical variant replacement. The vaccine strain GII.4c is close to variant Sydney_2012 (0.053) in their primary structure, but they are distinct at epitopes A and E in conformations. Our data suggested GII.4 variant Sydney_2012, GII.2 variant A, a GII.3 strain, GII.6 variants B and C and GII.17 variant D are primary candidate strains for NoV vaccine development.

Four novel bisabolane-type sesquiterpenes from Curcuma longa.

Four novel bisabolane sesquiterpenes, turmerone A (1), turmerone B (2), turmerone C (3), and turmerone D (4), were isolated from the rhizomes of Curcuma longa. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS.

Systematic characterization of the metabolites of paeonol in rats using ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry with an integrative strategy.

Paeonol, an active constituent in the root bark of Paeonia suffruticosa Andrews, is used to treat inflammation, headache and other diseases in clinic. Though the data on pharmacological researches of paeonol abounds, its metabolic profile is not so clear. It is essential to systematically characterize the in vivo metabolites in order to better understand its mechanism of action. In this study, ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q/TOF-MS) with an integrative strategy was developed for analysis of paeonol metabolites. As a result, based on seven reference substances isolated or synthesized, twenty-five metabolites were detected and identified in urine, feces, bile and plasma of rats after oral administration of paeonol. To the best of our knowledge, 14 of these metabolites have not been reported previously. In addition, the dominating metabolic fates were oxidation, demethylation, hydrogenation, glucuronic acid and sulfate conjugations, and hydrogenation of paeonol was reported for the first time. This research provides scientific and reliable support for full understanding of the metabolic profiling of paeonol.

[Relationship among heart rate turbulence, QT dispersion and heart function in patients with dilated cardiomyopathy].

OBJECTIVE: To explore the relationship among heart rate turbulence (HRT), QT dispersion (QTd) and heart function in patients with dilated cardiomyopathy (DCM) and assess its clinical value. METHODS: A total of 81 DCM patients with ventricular premature contraction (VPC) were divided into two groups according to heart function: Group A (NYHA class I-II, n=34) and Group B (NYHA class III-IV, n=47). Thirty out-patient control cases were chosen from those undergoing regular physical examination. 24 hour holter was performed to monitor turbulence onset (TO) and turbulence slope (TS). Electrocardiogram (ECG) was used to assess QTd. Meanwhile left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), E and A-wave peak velocities, E/A were measured by echocardiogram. After a comparison of all indicators in each group, an investigation was conducted to discern the relationship among HRT, QTd and heart function. RESULTS: Compared with normal group, TO significantly increased in DCM A and B group: [0.38 (-0.99-1.85)% vs 1.82 (0.02-3.92)% vs (-4.03±3.48)%, P<0.01]. TS significantly decreased while QTd increased. The trend of QTd addition was apparent along with heart failure. TO was negatively correlated with LVEF (r=-0.701, P<0.05) but positively correlated with LVEDD (r=0.621, P<0.05). There was no correlation with E and A-wave peak velocities. TS and QTd also had an obvious correlation with LVEF and LVEDD (all P<0.05). CONCLUSIONS: HRT is dramatically blunted in DCM patients and has a certain correlation with cardiac dysfunction. A combined test of HRT and QTd is a sensitive and indirect index in assessing autonomic nerve functions. It has a high clinical value of predicting the prognosis.