Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.

Objective:To screen active antibacterial components from licorice extract using BamA and BamD, the core components of Escherichia coli ( E. coli) β-barrel assembly machinery (BAM), as targets in order to combat the increasingly serious problem of antibiotic resistance. Methods:Affinity ultrafiltration combined with high performance liquid chromatography-mass spectrometry (HPLC-MS) was used to screen the potential components interacting with BamA and BamD from licorice extract. Changes in the expression of bamA and bamD genes of E. coli after treatment with the compounds were detected by fluorescence quantitative PCR, and the effects of the compounds on the function of the BAM complex to integrate outer membrane proteins into the bacterial outer membrane were analyzed using an in vitro recombination system. The influence of the compounds on the integrity of bacterial membranes was evaluated through analyzing the accumulation of SDS within the bacterial cells. Results:Bioaffinity ultrafiltration combined with HPLC-MS screening revealed that 18β-glycyrrhetinic acid could interact with BamD. After 18β-glycyrrhetinic acid treatment, the expression of bamA gene increased by 1.5 times, and the expression of bamD gene increased by 2 times. However, the inhibitory effect of 18β-glycyrrhetinic acid on the membrane insertion function of the BAM complex was not observed in the in vitro recombinant system assay, and the cell membrane integrity assay experiments did not reveal any disruption of the E. coli cell membrane by 18β-glycyrrhetinic acid. Conclusions:Using BamA and BamD proteins as targets, a natural product screening method using affinity ultrafiltration combined with HPLC-MS is established. The screening result shows that 18β-glycyrrhetinic acid can interact with BamD and affect the expression of outer membrane proteins in E. coli. Therefore, the screening and experimental procedures established in this study are of good reference value for the screening of novel antimicrobial drugs from other sources targeting outer membrane proteins, and this study also suggests that the selection of the relevant target sites is crucial for the successful screening of the corresponding natural products.

Objective:To construct an in vitro reconstitution system for inverse autotransporters in order to further investigate their translocation mechanism. Methods:Intimin from Escherichi coli was used as a model substrate. Spheroplasts were prepared from Escherichi coli strains overexpressing Intimin to induce the expression of Intimin. Recombinant β-barrel assembly machinery (BAM) complex was obtained and purified, and then proteoliposomes containing BAM were prepared. Following the digestion with proteinase K, the translocation was detected by SDS-PAGE. Results:Spheroplasts were induced to express Intimin, and then BAM-containing proteoliposomes were added to the system. Compared with control and liposomes groups, the experimental group showed that Intimin was resistant to proteinase K treatment, indicating that Intimin was successfully translocated.Conclusions:The translocation of Intimin required the participation of BAM complex. An in vitro reconstitution system for inverse autotransporters was constructed in this study, providing a method to study the translocation mechanism of inverse autotransporters.

Objective:To construct a surface display system containing various lengths of the Ag43 passenger domain for an optimal bacterial surface display of foreign protein HPV16L1.Methods:(1) Ag43 gene sequences of different lengths were inserted into pET22b vector to construct four Ag43 surface display vectors (Ag43/138, Ag43/551, Ag43/552 and Ag43/700) using PCR and subcloning strategy. (2) The generation of four HPV16L1-Ag43 fusion constructs was completed by PCR and subcloning methods. (3) HPV16L1-Ag43 fusion proteins were expressed and analyzed by SDS-PAGE. (4) The surface exposure of HPV-16L1 was verified using trypsin digestion.Results:PCR analysis and sequencing results showed that Ag43 surface display vectors and HPV16L1-Ag43 fusions were constructed successfully. SDS-PAGE showed that the expression of HPV16L1-Ag43 fusion proteins could be induced with 0.2 mmol/L IPTG and the protein content was reduced after the cells were treated with trypsin, especially the content of Ag43/700-HPV16L1 that showed a drastic reduction.Conclusions:The Ag43 surface display system was successfully constructed and could be used for a successful display of HPV16L1. This study also showed that Ag43/700 comprising only the α-helix and the β-barrel of Ag43 provided an optimal surface display for HPV16L1.

Objective To analyze the epidemiological characteristics of aggregative vomiting and diarrhea outbreak in Jing'an District of Shanghai in 2017 and 2018，and provide data support for further development of effective prevention and control measures. Methods A descriptive epidemiological method was used to analyze aggregative vomiting and diarrhea outbreak data in Jing'an District in 2017 and 2018. Results A total of 49 outbreaks were reported in Jing'an District in 2017 and 2018，involving 565 cases，with the overall attack rate of 1.89%. The median duration of the outbreak was 5 days and outbreaks mainly occurred in spring and autumn. The attack rate in kindergartens was higher than that in primary and secondary schools, while the total number of outbreak cases in kindergartens was less. The main clinical symptoms of the cases were vomiting, with a higher proportion than that of diarrhea and fever. The vomiting proportion was higher in kindergartens and elementary schools, while the diarrhea proportion was higher in middle schools. Conclusion There were some differences in the epidemic characteristics between kindergartens and primary and secondary schools, therefore different control measures should be adopted according to the characteristics of different institutions. The outbreaks were mainly spread through human-to-human transmission. Early detection and early reporting of epidemics in collective institutions had a positive impact on the control of the spread of the epidemic.

Data of patients underwent bronchoscopic treatment of tracheal stenosis from May 2011 to April 2016 were collected.Patients were questioned about the medical history before operation, and the airway was fully evaluated.The laryngeal mask was used for the patients with upper 1/3 tracheal stenosis and subglottic stenosis, and endotracheal intubation was applied for the other patients.Patients with severe tracheal stenosis received extracorporeal membrane oxygenation (ECMO)-assisted ventilation.The tracheal tube or laryngeal mask was removed immediately when patients were awake and spontaneous breathing and swallowing reflex recovered after operation, and oxygen was inhaled by mask.A total of 189 patients were included in this study, 93 patients received endotracheal intubation, and 91 patients were ventilated via the laryngeal mask, and 5 patients underwent ECMO-assisted ventilation.Forty-four patients adopted the method of preserving spontaneous breathing, and the other 145 patients did not.There were 165 patients in whom the endotracheal tube or laryngeal mask was removed immediately after they were awake, and the remaining 24 cases were sent to the intensive care unit with the endotracheal tube.For the patients with tracheal stenosis, preoperative interview and airway assessment are especially important, and appropriate airway management strategies should be developed; vital signs should be closely observed during operation, and the proper ventilation mode is selected, and ECMO-assisted ventilation could be considered for the patients with severe tracheal stenosis; the timing of removal of the endotracheal tube or laryngeal mask should be seized after operation.

Objective To explore whether there is a visual spatial attention span deficit in children with Chi-nese language learning disability and the characteristics of brain electrophysiological dynamic change. Methods Adop-ting event-related potentials ( ERP ) technology and levels of visual spatial attention span with fixed location cuing pa-radigm were used to explore the characteristics of brain electrophysiological dynamic change. Results Based on the behavioral data,the repeated findings of analysis of variance on reaction time showed that both the main effect of the type of subjects[F(1,35)=4. 34,P<0. 05,η2=0. 11],and the main effect of attention span[F(1,35)=138. 75,P<0. 001,η2=0. 79] had statistical significance. The repeated analysis of variance on accuracy showed that the main effect of subjects type[F(1,35)= 4. 99,P<0. 05,η2=0. 13],and the main effect of attention span[F(1,35)=101. 83,P<0. 01,η2=0. 74] were significantly different. Under large and small attention span conditions,the children with Chinese language learning disability showed a longer time of reaction and a lower accuracy rate than the children in the control group. With the electroencephalograph( EEG) data and under large and small attention span conditions,the Chinese learning disability children showed enhanced P1 amplitude and reduced N1 amplitude. Conclusions There is a visual spatial attention span deficit in children with Chinese learning disability which may be caused by a weak prima-ry sensory processing ability and divided attention deficit.