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Vibrio cholerae causes a severe disease that kills thousands of people annually. The outer membrane protein OmpU is the most abundant outer membrane protein in V. cholerae, and has been identified as an important virulence factor that is involved in host‐cell interaction and recognition, as well as being critical for the survival of the pathogenic V. cholerae in the host body and in harsh environments. The mechanism of these processes is not well understood owing to a lack of the structure of V. cholerae OmpU. Here, the crystal structure of the V. cholerae OmpU trimer is reported to a resolution of 2.2 Å. The protomer forms a 16‐β‐stranded barrel with a noncanonical N‐terminal coil located in the lumen of the barrel that consists of residues Gly32–Ser42 and is observed to participate in forming the second gate in the pore. By mapping the published functional data onto the OmpU structure, the OmpU structure reinforces the notion that the long extracellular loop L4 with a β‐hairpin‐like motif may be critical for host‐cell binding and invasion, while L3, L4 and L8 are crucially implicated in phage recognition by V. cholerae. [ABSTRACT FROM AUTHOR]

Aims: To investigate the roles of neurotrophic factors on cognition in patients with Alzheimer's disease (AD) carrying Apolipoprotein E (APOE) ε4. Methods: Totals of 173 patients with AD were divided into APOE ε4 carrier and non‐carrier groups, and their demographics, cognition, and neurotrophic factors in cerebrospinal fluid (CSF) were compared. Multiple linear regression analyses were performed to assess correlations among APOE ε4, neurotrophic factors and cognition. Mediation analyses were conducted to assess the sequential associations among APOE ε4, nerve growth factor (NGF), and cognition. Results: Global cognition and multiple domains were impaired in the APOE ε4 carrier group (all p < 0.05). NGF level in the APOE ε4 carrier group was lower than that in the non‐carrier group (p = 0.016). NGF level showed significant correlations with both global and multiple domains cognitions. Specifically, NGF mediated the association between APOE ε4 and Animal Fluency Test score (β, −0.45; 95% CI [−0.96, −0.07]; p < 0.001) and Trail Making Test‐A (time) (β, 0.15; 95% CI [0.01, 0.33]; p < 0.001). Conclusion: APOE ε4 is associated with cognitive impairment, and those carrying APOE ε4 have decreased NGF level in CSF. Declined NGF level is correlated with compromised cognition. NGF mediates APOE ε4‐associated cognitive impairment. [ABSTRACT FROM AUTHOR]

Aims: To explore the roles of apolipoprotein E (APOE) ε4 on the neuropathology and neuroinflammation in Alzheimer's disease (AD) patients. Methods: AD patients were divided into the APOE ε4 carrier and the APOE ε4 non‐carrier groups according to APOE genotype. Demographic information, cognitive function, the levels of neuropathological proteins and neuroinflammatory factors in cerebrospinal fluid (CSF) were compared between the two groups, and their correlations were subsequently analyzed. Results: β amyloid protein (Aβ)1–42 level from the APOE ε4 carrier group was significantly lower than that from the non‐carrier group (p = 0.023), which was associated with worse cognitive function. The nitric oxide (NO) level was significantly elevated in the APOE ε4 carrier group compared to the non‐carrier group (p = 0.016), which was significantly and positively correlated with the Trail Making Test (TMT)‐A‐time (r = 0.21, p = 0.026) and TMT‐B‐time (r = 0.38, p < 0.01). Conclusion: APOE ε4 is associated with poorer cognition, particularly the early symptoms of memory, language, and attention. APOE ε4 is associated with lower Aβ1–42 level, and the more numbers of APOE ε4 are carried, the lower level of Aβ1–42 is measured. APOE ε4 is associated with elevated NO level, which is linked to the impaired attention and executive function. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) and SARS‐CoV‐2 (COVID‐19) cause pandemic infections where cytokine storm syndrome and lung inflammation lead to high mortality. Given the high social and economic cost of respiratory viruses, there is an urgent need to understand how the airways defend against virus infection. Here we use mice lacking the WD and linker domains of ATG16L1 to demonstrate that ATG16L1‐dependent targeting of LC3 to single‐membrane, non‐autophagosome compartments – referred to as non‐canonical autophagy – protects mice from lethal IAV infection. Mice with systemic loss of non‐canonical autophagy are exquisitely sensitive to low‐pathogenicity IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high mortality. IAV was controlled within epithelial barriers where non‐canonical autophagy reduced IAV fusion with endosomes and activation of interferon signalling. Conditional mouse models and ex vivo analysis showed that protection against IAV infection of lung was independent of phagocytes and other leucocytes. This establishes non‐canonical autophagy in airway epithelial cells as a novel innate defence that restricts IAV infection and lethal inflammation at respiratory surfaces. SYNOPSIS: Non‐canonical functions of the autophagy protein ATG16L1 are mediated by its C‐terminal WD domain. Here, mice expressing WD domain‐lacking ATG16L1 are found to be highly sensitive to influenza virus infection, resulting in cytokine storm and lethal pneumonia. The WD domain of ATG16L1 prevents lethal infection by influenza A virus.Infection is controlled by epithelial cells and is independent of phagocytic cells.Non‐canonical ATG16L1 function reduces interferon signalling by slowing virus endocytosis and fusion with endosomal membranes. [ABSTRACT FROM AUTHOR]