Identification of Skp1 as a target of mercury sulfide for neuroprotection.

Mercury sulfide (HgS) exerts extensive biological effects on neuronal function. To investigate the direct target of HgS in neuronal cells, we developed a biotin-tagged HgS probe (bio-HgS) and employed an affinity purification technique to capture its target proteins. Then, we identified S-phase kinase-associated protein 1 (Skp1) as a potential target of HgS. Unexpectedly, we discovered that HgS covalently binds to Skp1 through a "Cys62-HgS-Cys120" mode. Moreover, our findings revealed that HgS inhibits the ubiquitin-protease system through Skp1 to up-regulate SNAP-25 expression, thereby triggering synaptic vesicle exocytosis to regulate locomotion ability in C. elegans. Collectively, our findings may promote a comprehensive interpretation of the pharmacological mechanism of mercury sulfide on neuroprotective function.

Clinical analysis of 114 cases of bronchiolitis in infants.

BACKGROUND: Bronchiolitis is a common lower respiratory tract infection in infants and young children. Severe cases may be accompanied by obvious dyspnea and oxygen saturation decline. AIM: To summarize the clinical features, standard diagnosis, and treatment of bronchiolitis. METHODS: This is a retrospective analysis of 114 pediatric patients (74 males, 40 females) who were first diagnosed as having bronchioles at the Department of Pediatrics of Tongling Maternal and Child Health Hospital from January 2019 to December 2019. The clinical features, imaging features, treatment, and other clinical data were recorded and analyzed. RESULTS: The age of onset of the disease was mainly from 1 mo to 6 mo (75.4%), and the time to hospital visit was mostly from the 2nd day to the 4th day of the course of the disease (75.4%). Lung imaging examination showed increase in lung texture, fuzzy (93.8%). The main treatment was atomization therapy: Budesonide combined with terbutaline (45.6%) and budesonide combined with salbutamol (38.5%). The average hospitalization time was 7.1 ± 2.4 d, and the overall cure rate was 94.7%. In patients without bacterial infection, the use of antibiotics significantly prolonged the length of hospital stay (7.8 ± 2.5 d vs 5.7 ± 1.8 d) and improved the cure rate (98.3% vs 87.9%, P < 0.05). CONCLUSION: Infants with bronchiolitis are mainly male and tend to have a good prognosis. However, the unneeded use of antibiotics may prolong the length of hospital stay significantly, which imposes the burden both on the patients and hospital system.

Neuroinflammation inhibition by small-molecule targeting USP7 noncatalytic domain for neurodegenerative disease therapy.

Neuroinflammation is a fundamental contributor to progressive neuronal damage, which arouses a heightened interest in neurodegenerative disease therapy. Ubiquitin-specific protease 7 (USP7) has a crucial role in regulating protein stability in multiple biological processes; however, the potential role of USP7 in neurodegenerative progression is poorly understood. Here, we discover the natural small molecule eupalinolide B (EB), which targets USP7 to inhibit microglia activation. Cocrystal structure reveals a previously undisclosed covalent allosteric site, Cys576, in a unique noncatalytic HUBL domain. By selectively modifying Cys576, EB allosterically inhibits USP7 to cause a ubiquitination-dependent degradation of Keap1. Keap1 function loss further results in an Nrf2-dependent transcription activation of anti-neuroinflammation genes in microglia. In vivo, pharmacological USP7 inhibition attenuates microglia activation and resultant neuron injury, thereby notably improving behavioral deficits in dementia and Parkinson's disease mouse models. Collectively, our findings provide an attractive future direction for neurodegenerative disease therapy by inhibiting microglia-mediated neuroinflammation by targeting USP7.

[Stability characteristics of soil organic carbon pool following development of sand-fixing forest in Mu Us sandy land, China]. / æ¯›ä¹Œç´ æ²™åœ°å›ºæ²™æž—å‘è‚²è¿‡ç¨‹ä¸­åœŸå£¤æœ‰æœºç¢³åº“ç¨³å®šæ€§ç‰¹å¾.

The study aimed to reveal the cumulative effects and stability characteristics of soil organic carbon (SOC) during forest development at the Mu Us sandy land, China. Using space for time substitution, surface soil samples were collected from semi-fixed sandy lands and restored arbor and shrub lands with the ages of 22, 32 and 53 years in the Yulin sand control region in Northern Shaanxi Province. The content of total organic carbon (TOC), oxidizable labile organic carbon, and resistant carbon and the characteristics of mineralized carbon emission and decomposition ratio were analyzed. The results showed that the increment of TOC for 22 to 53 years shrub and arbor lands from resistant carbon were 3.5-6.2 g·kg-1 and 3.2-7.7 g·kg-1, and from oxidized labile carbon were 2.8-3.4 g·kg-1 and 1.3-2.8 g·kg-1, respectively, compared with semi-fixed sand land. The ratio of soil oxidizable labile carbon in shrub land and arbor land were stable and maintained at 37.0% and 26.8%, respectively. However, the ratio decreased to 25.7% and 17.4% after incubated at a constant temperature for 60 days. The mineralization rate of shrub and arbor lands with 22-53 years was not significant at the ending of soil incubation. Carbon losses from oxidized liable carbon were 76.9%-98.7%, and only 1.3%-23.5% from resistant carbon in all sand-fixing forest plots. Compared with the maximum carbon emission rate, the soil cumulative carbon release exhibited a higher correlation with soil enzyme activities of ß-glucosidase and dehydrogenase, but the enzyme activities did not change from 32-53 years. In conclusion, SOC pool showed stable characteristics of lower emission and higher sequestration with the increases of sand-fixing forest stand age. The carbon fixation effect of arbor sand-fixing forest was better than that of shrub sand-fixing forest.