Differential pathogenic and molecular features in neurological infection of SARS-CoV-2 Omicron BA.5.2 and BA.2.75 and Delta.

The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global threat, exacerbated by the emergence of viral variants. Two variants of SARS-CoV-2, Omicron BA.2.75 and BA.5, led to global infection peaks between May 2022 and May 2023, yet their precise characteristics in pathogenesis are not well understood. In this study, we compared these two Omicron sublineages with the previously dominant Delta variant using a human angiotensin-converting enzyme 2 knock-in mouse model. As expected, Delta exhibited higher viral replication in the lung and brain than both Omicron sublineages which induced less severe lung damage and immune activation. In contrast, the Omicron variants especially BA.5.2 showed a propensity for cellular proliferation and developmental pathways. Both Delta and BA.5.2 variants, but not BA.2.75, led to decreased pulmonary lymphocytes, indicating differential adaptive immune response. Neuroinvasiveness was shared with all strains, accompanied by vascular abnormalities, synaptic injury, and loss of astrocytes. However, Immunostaining assays and transcriptomic analysis showed that BA.5.2 displayed stronger immune suppression and neurodegeneration, while BA.2.75 exhibited more similar characteristics to Delta in the cortex. Such differentially infectious features could be partially attributed to the weakened interaction between Omicron Spike protein and host proteomes decoded via co-immunoprecipitation followed by mass spectrometry in neuronal cells. Our present study supports attenuated replication and pathogenicity of Omicron variants but also highlights their newly infectious characteristics in the lung and brain, especially with BA.5.2 demonstrating enhanced immune evasion and neural damage that could exacerbate neurological sequelae.

Nomogram for predicting coronary artery lesions in patients with Kawasaki disease.

BACKGROUND: Coronary artery lesions are the most important complications of Kawasaki disease. Approximately 25-30% of untreated patients develop coronary artery disease, which can lead to long-term cardiovascular sequelae. AIM: The aim of this study is to evaluate the risk factors for coronary artery lesions in Kawasaki disease and to construct a nomogram for predicting the likelihood of developing such lesions. METHODS: Data from 599 patients between January 2012 and June 2020 were reviewed retrospectively. Patients were randomly assigned to the training set (n = 450) and the validation set (n = 149). A comparison of clinical features and laboratory data was performed, followed by multivariate logistic regression analysis to identify independent risk factors and develop the nomogram. The predictive efficiency of the nomogram was evaluated using the calibration curve, area under the receiver operating characteristic curve (AUC), C-index, and decision curve analysis (DCA). RESULTS: Intravenous immunoglobulin (IVIG) resistance, delayed IVIG treatment, C-reactive protein, and neutrophil/lymphocyte ratio were identified as independent risk factors for the development of coronary artery lesions. The nomogram was constructed based on these four variables. The calibration curve of the nomogram showed a high degree of agreement between the predicted probability and the actual probability. The AUC of the nomogram in the training and validation set was 0.790 and 0.711, respectively. In addition, DCA revealed that the nomogram provided a significant net benefit, further supporting its clinical utility. CONCLUSIONS: The constructed nomogram demonstrates a strong and reliable performance in predicting coronary artery lesions, which enables clinicians to make timely and tailored clinical decisions.

Characteristics of replication and pathogenicity of SARS-CoV-2 Alpha and Delta isolates.

The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally, from B.1.17 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) to B.1.1.529 (Omicron). The emerging or re-emerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics, pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 â€‹cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 â€‹cells. We utilized both animal models of human ACE2 (hACE2) transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.

Oseltamivir Treatment for Influenza During the Flu Season of 2018-2019: A Longitudinal Study.

Background: Oseltamivir resistance in influenza virus (IFV) has been of widespread concern. An increase in the frequency of viruses with reduced inhibition was observed. Whether oseltamivir is effective is uncertain. We conducted this study to understand the real-world situation in northern China and the clinical efficacy for patients with IFV infection after the use of oseltamivir. Methods: The longitudinal study was performed on influenza-like illness (ILI) cases in a tertiary general hospital in Beijing, China during the flu season of 2018-2019. All ILI cases (≥18 years) were recruited into the study. We analyzed the effect of the oseltamivir therapy on the number of clinic visits, hospitalization frequency, and the duration of fever and cough. Results: A total of 689 ILI patients were recruited in this study with 355 in the oseltamivir therapy group and 334 in the supportive therapy group. Among the ILI patients, 388 patients were detected for IFV infection (364 IFV-A and 24 IFV-B) and divided into two groups with or without the oseltamivir therapy (302 vs. 86). There were no significant differences in the basic characteristics between the oseltamivir and supportive therapy groups in the ILI patients or in the IFV positive patients (all p < 0.05). After adjusting for the potential confounders, oseltamivir therapy reduced the times of clinic visits in the ILI and IFV positive patients (p = 0.043 and p = 0.011). No effectiveness with oseltamivir therapy was observed in the outcomes of hospitalization frequency, and the duration of fever and cough. Conclusion: Oseltamivir use may reduce the times of clinic visits. However, we did not observe the differences in the duration of fever, cough, and the frequency of hospitalization between oseltamivir therapy and supportive therapy.

Multi-Dopant Engineering in Perovskite Cs2SnCl6: White Light Emitter and Spatially Luminescent Heterostructure.

Bi3+/Te4+ co-doped Cs2SnCl6 with dual emission spectrum (i.e., 450 and 575 nm) was achieved by a modified solution method, which can overcome the phase separation in the previous method for Cs2SnCl6 crystal growth. The two emission peaks arising from the two dopants Bi3+ and Te4+ have distinct photoluminescence (PL) lifetimes. Thus, the control of dopant ratio or PL delay time will regulate the PL intensity ratio between 450 and 575 nm peaks leading to adjustable emission color. The energy transfer between the two emission centers, which is confirmed by the optical spectra and PL lifetime, has a critical distance around 7.8 nm with a maximum of 50% transfer efficiency. The Bi3+/Te4+ co-doped Cs2SnCl6 with superior stability in water and aqua regia was fabricated into a single-phase white light-emitting diode. In the meantime, various luminescent heterostructures were obtained by epitaxial Cs2SnCl6 crystal growth with different dopants, which can broaden the study of composition engineering in halide perovskites.

Air pollutants and outpatient visits for influenza-like illness in Beijing, China.

BACKGROUND: Air pollution leads to many adverse health conditions, mainly manifested by respiratory or cardiac symptoms. Previous studies are limited as to whether air pollutants were associated to influenza-like illness (ILI). This study aimed to explore the association between air pollutants and outpatient visits for ILI, especially during an outbreak of influenza. METHODS: Daily counts of hospital visits for ILI were obtained from Peking University Third Hospital between January 1, 2015, and March 31, 2018. A generalized additive Poisson model was applied to examine the associations between air pollutants concentrations and daily outpatient visits for ILI when adjusted for the meteorological parameters. RESULTS: There were 35862 outpatient visits at the fever clinic for ILI cases. Air quality index (AQI), PM2.5, PM10, CO and O3 on lag0 days, as well as nitrogen dioxide (NO2) and sulfur dioxide (SO2) on lag1 days, were significantly associated with an increased risk of outpatient visits for ILI from January 2015 to November 2017. From December 2017 to March 2018, on lag0 days, air pollutants PM2.5 [risk ratio (RR) = 0.971, 95% CI: 0.963-0.979], SO2 (RR = 0.892, 95% CI: 0.840-0.948) and CO (RR = 0.306, 95% CI: 0.153-0.612) were significantly associated with a decreased risk of outpatient visits for ILI. Interestingly, on the lag2 days, all the pollutants were significantly associated with a reduced risk of outpatient visits for ILI except for O3. We did not observe the linear correlations between the outpatient visits for ILI and any of air pollutants, which were instead associated via a curvilinear relationship. CONCLUSIONS: We found that the air pollutants may be associated with an increased risk of outpatient visits for ILI during the non-outbreak period and with a decreased risk during the outbreak period, which may be linked with the use of disposable face masks and the change of outdoor activities. These findings expand the current knowledge of ILI outpatient visits correlated with air pollutants during an influenza pandemic.

Dual-Emission Luminescence of Magnesium Coordination Polymers Based on Mixed Organic Ligands.

Presented herein are two luminescent magnesium coordination polymers (Mg-CPs), namely [Mg2 (H2O)2 (2-NDC)4 (1,10-phen)2] (1) and [Mg2 (H2O)(1,4-NDC)2 (1,10-phen)] (2), in which 2-NDCH=2-naphthalenecarboxylic acid, 1,4-NDCH2 =1,4-naphthalene dicarboxylic acid, and 1,10-phen=1,10-phenanthroline. Based on the mixed ligands, the title compounds exhibit linker-based photoluminescence (PL) properties thanks to the unique configuration of the Mg(2+) ions. The two compounds show interesting dual emission on excitation of the different luminophores of the mixed linkers. In particular, the emissions of compound 2 could be tuned from green to yellow simply by varying the excitation energies. Furthermore, 2 could be excited by using a commercial λ=450 nm blue LED chip to generate white-light emission, which allows the fabrication of a white-light-emitting diode (WLED) with 20 lm W(-1) luminous efficacy. This work may provide a new method for designing tunable PL CPs by using the low-cost and abundant magnesium ion.

Tunable photoluminescence and direct white-light emission in Mg-based coordination networks.

The bpy, dpe and dppe were introduced as auxiliary ligands, respectively, to construct three magnesium-1,4-NDC coordination polymers (Mg-CPs) that exhibited tunable photoluminescence (PL) and direct white-light emission upon varying the excitation light.

Immunogenicity of recombinant human bocavirus-1,2 VP2 gene virus-like particles in mice.

Human bocavirus (HBoV), a recently identified pathogen with a worldwide distribution is closely related to paediatric acute respiratory infection and gastroenteritis. The present study was performed to evaluate the immunogenicity of HBoV1 and HBoV2 virus-like particles (VLPs) as vaccine candidates in mice. Both HBoV1 and HBoV2 VLPs were expressed in the bacmid virus­SF9 cell system. Mice were inoculated three times at 3-week intervals with HBoV VLPs at one dose intramuscular (i.m.) or intradermal (i.d.) with or without the addition of the alum adjuvant. ELISA was used to detected antibody, and ELISPOT was used to test cellular immune responses. HBoV-specific IgG antibodies were induced and alum adjuvant improved the antibody titres and avidity, while the inoculation pathway had no influence. T helper type 1/ type 2 immune responses were balanced induced by HBoV1 VLPs but not HBoV2 VLPs. Serum IgG antibody cross-reactivity rates of the two subtypes were similar, but cross-reactions of HBoV1 immunization groups were higher. The single i.m. group had more interferon-γ-secreting splenocytes. These data indicate that HBoV VP2 VLPs have good immunogenicity with induction of strong humoral and cellular immune responses, and they may be potential candidate vaccines for HBoV infection.

[Virus detection in bronchoalveolar lavage fluid of 122 children with severe pneumonia].

OBJECTIVE: To investigate the prevalence of viral pathogen in children with severe pneumonia in Hunan. METHOD: Bronchoalveolar lavage fluid [BALF] were collected from 122 hospitalized children with severe pneumonia in People's Hospital of Hunan province from January 2011 to December 2011. Nested- or reverse transcription Polymerase chain reaction (PCR or RT-PCR) was used to screen Adenovirus (ADV), Human Bocavirus (HBoV), Parainfluenzaviruses1-4 (PIV1-4), Human Respiratory Syneytial virus (RSV), Influenza virus A (IFVA), Influenza virus B (IFVB), Human Rhinovirus(HRV), Human Metapneumovirus (HMPV), human coronaviruses NL63 and HKU1 (HCoV-NL63, HCoV- HKU1). RESULTS: Among the 122 bronchoalveolar lavage fluid, viral agents were detected in 60 samples(49.1%), among which ADV (40.98%) was the most common virus, followed by RSV (7.37%) and HBoV (7.37%). Two viruses were detected in 21 individual (35%) samples, of which 20 were dual positive for ADV (40%). CONCLUSION: ADV is the most frequently detected viral etiology of severe pneumonia in children in Hunan during this year. And its Coinfection with other respiratory viruses was common.

[Enzyme-linked immunospot test detected specific cellular immune response induced by human bocavirus VP2 virus-like particles].

OBJECTIVE: To discuss the enzyme linked immune spot test (ELISPOT) detected the cellular immune response induced by human Bocavirus (HBoV) VP2 virus-like particles (VLPs). METHODS: After immunized by HBoV VP2 VLPs, the specific cellular immune response in mice were detected by ELISPOT assay, observe the ELISPOT results at the conditions of different polypeptide stimulate, different cell culture time, different cell concentration and different specific stimulus peptide concentration, then screening the right ELISPOT experimental conditions and establish the ELISPOT method. RESULTS: The spots induced by HBoV1 VLPs immunized mice spleen lymphocytes stimulate with polypeptide P3 (GYIPIENEL) and P5 (LYQMPFFLL)were 233 spots/10(6) cells and 157 spots/10(6) cells,spots induced by HBoV2 VLPs immunized mice spleen lymphocytes stimulate with polypeptide P8 (GYIPVIHEL) were 113 spots/10(6) cells; 24 hours is the best time for culture, at this time HBoV1 and HBoV2 groups specificity secretion IFN-gamma ratio were 232 spots/10(6) cells and 119/10(6) cells; Best concentration of mice spleen lymphocyte is 5 x 10(5), right now HBoV1 and HBoV2 group specificity secretion IFN-gamma ratio were 232 spots/10(6) cells and 108/10(6) cells; Best concentration of polypeptides is 10 microg/ml, HBoV1 and HBoV2 group specificity secretion IFN -gamma ratio were 233 spots/10(6) cells and 96/10(6) cells. CONCLUSIONS: HBoV1 and HBoV2 specificT-cell epitope in BABL/c mice were P3, P5 (HBoV1) and P8 (HBoV2). The best experiment condition were: cell cultivated for 24 h, cells concentration for 5 x 10(5) cells/well, stimulating polyperides concentration for 10 microg/ml, it can use to study the cellular immune induced by HBoV in mice.