The PB2 I714S mutation influenced mammalian adaptation of the H3N2 canine influenza virus by interfering with nuclear import efficiency and RNP complex assembly.

Avian influenza viruses (AIVs) are the origin of multiple mammal influenza viruses. The genetic determinants of AIVs adapted to humans have been widely elucidated, however, the molecular mechanism of cross-species transmission and adaptation of AIVs to canines are still poorly understood. In this study, two H3N2 influenza viruses isolated from a live poultry market (A/environment/Guangxi/13431/2018, GX13431) and a swab sample from a canine (A/canine/Guangdong/0601/2019, GD0601) were used to investigate the possible molecular basis that determined H3N2 AIV adapting to canine. We found that GD0601 exhibited more robust polymerase activity in cells and higher pathogenicity in mice compared with its evolution ancestor H3N2 AIV GX13431. A series of reassortments of the ribonucleoprotein (RNP) complex showed that the PB2 subunit was the crucial factor that conferred high polymerase activity of GD0601, and the substitution of I714S in the PB2 subunit of GD0601 attenuated the replication and pathogenicity in mammal cells and the mouse model. Mechanistically, the reverse mutation of I714S in the PB2 polymerase subunit which was identified in AIV GX13431 reduced the nuclear import efficiency of PB2 protein and interfered with the interactions of PB2-PA/NP that affected the assembly of the viral RNP complex. Our study reveals amino acid mutation at the position of 714 in the nuclear localization signal (NLS) area in PB2 plays an important role in overcoming the barrier from poultry to mammals of the H3N2 canine influenza virus and provides clues for further study of mammalian adaptation mechanism of AIVs.

Deoxycholic acid inducing chronic atrophic gastritis with colonic mucosal lesion correlated to mucosal immune dysfunction in rats.

The present study aimed to explore the underlying mechanism of bile reflux-inducing chronic atrophic gastritis (CAG) with colonic mucosal lesion. The rat model of CAG with colonic mucosal lesion was induced by free-drinking 20 mmol/L sodium deoxycholate to simulate bile reflux and 2% cold sodium salicylate for 12 weeks. In comparison to the control group, the model rats had increased abundances of Bacteroidetes and Firmicutes but had decreased abundances of Proteobacteria and Fusobacterium. Several gut bacteria with bile acids transformation ability were enriched in the model group, such as Blautia, Phascolarctobacter, and Enterococcus. The cytotoxic deoxycholic acid and lithocholic acid were significantly increased in the model group. Transcriptome analysis of colonic tissues presented that the down-regulated genes enriched in T cell receptor signaling pathway, antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and intestinal immune network for IgA production in the model group. These results suggest that bile reflux-inducing CAG with colonic mucosal lesion accompanied by gut dysbacteriosis, mucosal immunocompromise, and increased gene expressions related to repair of intestinal mucosal injury.

Understanding secondary particles in a regional site of Yangtze River Delta: Insights from mass spectrometric measurement.

Submicron particulate matter (PM1) poses significant risks to health risks and global climate. In this study, secondary organic aerosols (SOA) and inorganic compositions were examined for their physicochemical characteristics and evolution using high-resolution aerosol instruments in Changzhou over one-month period. The results showed that transport accompanied by regional static conditions leaded to the occurrence of heavy pollution. In addition, regional generation and local emissions also leaded to the occurrence of light and moderate pollution during the observation period in Changzhou. Organic aerosols (OA) and nitrate (NO3-) accounted for 45 % and 23 % of PM1, respectively. The increase in PM1 was dominated by the contribution of NO3- and OA. SOA was dominance in OA (63 % with 40 % MO-OOA), which was higher than primary organic aerosols (POA). Besides, photochemical reactions and the high oxidizing nature of the urban atmosphere promoted the production of OA, especially MO-OOA in Changzhou. Our results highlight that secondary particles contribute significantly to PM pollution in Changzhou, underlining the importance of controlling emissions of gaseous precursors, especially under high oxidation conditions.

Rapid adaptive substitution of L226Q in HA protein increases the pathogenicity of H9N2 viruses in mice.

Background: Since the first human infection with H9N2 virus was reported in 1998, the number of cases of H9N2 infection has exceeded one hundred by 2021. However, there is no systematic description of the biological characteristics of H9N2 viruses isolated from humans. Methods: Therefore, this study analyzed the pathogenicity in mice of all available H9N2 viruses isolated from human cases in China from 2013 to 2021. Results: Although most of the H9N2 viruses analyzed showed low or no pathogenicity in mice, the leucine to glutamine substitution at residue 226 (L226Q) in the hemagglutinin (HA) protein rapidly emerged during the adaptation of H9N2 viruses, and was responsible for severe infections and even fatalities. HA amino acid 226Q conferred a remarkable competitive advantage on H9N2 viruses in mice relative to viruses containing 226L, increasing their virulence, infectivity, and replication. Conclusion: Thus, our study demonstrates that the adaptive substitution HA L226Q rapidly acquired by H9N2 viruses during the course of infection in mice contributed to their high pathogenicity.

The impact of backpack load on adolescent's stair descent gait.

This study investigates the impact of increasing backpack load on the gait of adolescents during stair descent. Sixteen healthy male students (age = 12.9 ± 0.6 years) were required to descend the stairs in 4 loaded conditions. The kinematic, kinetic, and EMG data were collected synchronously and gait parameters, especially indicators of balance control, were analyzed. The posterior tilt angles (COM-COP IA in the sagittal plane) (0 %-42 %, 48 %-53 %, 58 %-91 %, p < 0.01), trunk anterior tilt angles (9-33 %, 51-65 %, p < 0.01), and CV of stride length (p < 0.01) increased with the backpack load. The COM-Step edge separation decreased with the increased backload (p < 0.01). In addition, the hip flexion torque (25-40 %, 45-51 %, p < 0.01), the rectus femoris activation, and the hip stiffness increased significantly as the load up to 15 % Body Weight (BW)and 20 % BW. The increasing backpack load may affect adolescent's stair descent gait. Especially as the load was up to 15 % BW, the adolescents' bodies tended to tilt backwards relative to the support foot during the single stance phase. They may activate the hip flexors and tilt forward the trunk to recover from the balance perturbation, which was associated with increased hip flexion torques. This adjustment was more pronounced with the increasing backpack load. However, excessive forward flexion may increase the risk of forward falls. The boundaries of adjustment need further research in the future. Findings from this study provide baseline information on the intrinsic mechanisms of balance control during stair descent.

Cross-Species Transmission Potential of H4 Avian Influenza Viruses in China: Epidemiological and Evolutionary Study.

H4 avian influenza viruses (AIVs) have been widely detected in live poultry markets in China. However, the potential public health impact of H4 AIVs remains largely uncertain. Here, we fully analyzed the distribution and phylogenetic relationship of H4 AIVs in China. We obtained 31 isolates of H4 viruses in China during 2009-2022 through surveillance in poultry-associated environments, such as live poultry markets and poultry farms. Genomic sequence analysis together with publicly available data revealed that frequent reassortment and introduction of H4 AIV from wild birds to poultry may have occurred. We identified 62 genotypes among 127 whole genome sequences of H4 viruses in China, indicating that H4 AIVs had great genetic diversity in China. We also investigated molecular markers and found that drug resistance mutations frequently occurred in the M2 protein and a few mutations related to receptor binding and the host signature in H4 AIVs. Our study demonstrates the cross-species transmission potential of H4 AIVs in China and provides some reference significance for its risk assessment.

Changes in Adiposity and Cognitive Function in Older Adults: The REGARDS Study.

OBJECTIVES: Adiposity may have a role in the risk of dementia. Fewer studies have focused on the relationship between change in adiposity and cognitive decline. Our study aimed to explore the association between the change in adiposity and cognitive function in Black and White older adults. METHODS: The participants were 12,204 older adults without cognitive impairment (62.8 ±â€…8.0 years) in the United States. The percent body mass index change (%BMI change) and percent waist circumference change (%WC change) were measured at 2 in-home visits (first: 2003-2007, second: 2013-2016). Cognitive status was assessed by the Six-Item Screener annually. Memory and executive function were measured by word list learning, MOCA recall and orientation, and letter and animal fluency every 2 years. Logistic regression or linear regression models were used to estimate the relationship between percent change in adiposity and cognitive function. RESULTS: After 12.7 ±â€…1.7 years, a greater decrease in %BMI change or %WC change was significantly associated with a higher risk of cognitive impairment. Compared to older adults with -5% ≤ change ≤ 5% from baseline, a significantly higher risk of cognitive impairment and greater loss in memory and executive function were found among those who experienced more than a 10% decline in %BMI change or %WC change. Older adults who experienced a 5%-10% decrease in %BMI change had a higher risk of cognitive impairment and greater loss of memory compared to those with -5% ≤ change ≤ 5%. DISCUSSION: A greater decrease in %BMI (>5%) and %WC (>10%) change was associated with greater cognitive loss observed over time.