Histone acetylation regulates ORMDL3 expression-mediated NLRP3 inflammasome overexpression during RSV-allergic exacerbation mice.

Whether respiratory syncytial virus (RSV) infection in early life may induce orosomucoid 1-like protein 3 (ORMDL3) and lead to NOD-like receptor protein 3 (NLRP3) inflammasome overexpression in asthma, which could be alleviated by the inhibition of HAT p300. First, we explored the relationship between RSV, ORMDL3, and recurrent wheezing in the future through clinical data of infants with RSV-induced bronchiolitis. Then, we used bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) and an asthmatic mouse model of repeated RSV infection and OVA sensitization and challenge (rRSV + OVA) in early life to assess the effects of ORMDL3 on NLRP3 inflammasome and that of histone acetylation on ORMDL3 regulation. ORMDL3 overexpression is the independent risk factor of recurrent wheezing in RSV-bronchiolitis follow-up. In BEAS-2B, ORMDL3-induced NLRP3 inflammasome expression. BEAS-2B infected by RSV resulted in overexpression of ORMDL3 and NLRP3 inflammasome and histone hyperacetylation, while ORMDL3-small interfering RNA and C646 interfered could decrease NLRP3 inflammasome. ORMDL3 overexpression in mouse lung increased NLRP3 inflammasome. The expression of ORMDL3 and NLRP3 inflammasome significantly increased, with histone hyperacetylation in the lung in rRSV + OVA mice. p300 and acetylH3 bound to ORMDL3 promoter. In C646 + rRSV + OVA mice, C646 alleviated lung inflammation and overexpression of ORMDL3 and NLRP3 inflammasome. RSV activated ORMDL3 overexpression through histone hyperacetylation and induced NLRP3 inflammasome expression.

Refractory Mycoplasma Pneumonia in Children: A Systematic Review and Meta-analysis of Laboratory Features and Predictors.

Background: Mycoplasma pneumoniae is a common pathogen of community-acquired pneumonia (CAP) in children. M. pneumoniae infection is usually regarded as a self-limiting disease, but in some special cases, it can also develop into refractory Mycoplasma pneumoniae pneumonia (RMPP). The aim of this study is to analyze the clinical characteristics of CRP (C-reactive protein), LDH (lactate dehydrogenase), ESR (erythrocyte sedimentation rate), D-dimer, neutrophils (%), lymphocytes (%), and lung consolidation in RMPP and explore their prediction results in the early stage of RMPP, which is important for early treatment. Methods: This systematic search was conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wangfang, and Cqvip, and the date was set until February 23, 2021. For the continuous variables, mean difference (MD) with 95% CI was adopted to evaluate CRP, LDH, ESR, D-dimer, neutrophils (%), lymphocytes (%), and the correlation between lung consolidation and RMPP. Results: 20 studies including 5289 patients were included in the analysis, and the results showed that the CRP of the RMPP group (MD (95% CI): 22.29 (12.20, 32.38), P < 0.001), LDH (MD (95% CI): 145.13 (78.62, 211.64), P < 0.001), neutrophils (%) (MD (95% CI): 7.27 (0.31, 14.23), P = 0.04), and D-dimer (MD (95% CI): 1.79 (-1.17, 4.74), P = 0.24) was higher than that of the NRMPP group; the risk of lung consolidation in the RMPP group (OR (95% CI): 14.29 (4.52, 45.12), P < 0.001) was higher than that in the NRMPP group, and there was no difference in ESR (MD (95% CI): 8.11 (-1.34, 17.56), P = 0.09) and lymphocytes (%) (MD (95% CI): -6.27 (-12.81, 0.27), P = 0.06) between the two groups. Conclusion: So, the available evidence indicates that CRP, LDH, neutrophils (%), D-dimer, and lung consolidation are predictive factors for RMPP.

Chemoselective Perfluoromethylation of Thio- and Selenoamides.

A chemo- and regioselective perfluoromethylation using thioamides/selenoamides (prepared one step from corresponding lactams) as starting materials has been discovered. The reaction demonstrated complementary chemoselectivity to the C-H trifluoromethylation of (hetero)arenes as well as remarkable functional group compatibility especially toward radical sensitive olefin-, alkyne-, and arylhalide-bearing substrates. The examples of perfluorothio-/selenolated drug molecules indicated application potential of this strategy in drug modification and drug-analogue preparation.

Recent Advances in the Catalytic Enantioselective Reactions of para-Quinone Methides.

In recent years, the catalytic enantioselective reactions of p-QMs have drawn much attention, because of their distinctive reactivities. As such, a variety of chiral catalytic systems have been developed. This Focus Review describes the reactions of p-QMs according to the chiral catalyst system used, with the aim of provide the first complete picture of the exciting developments in this field. Special emphasis is placed on recent work regarding their reaction mechanisms.

Direct access to spirobiisoxazoline via the double 1,3-dipolar cycloaddition of nitrile oxide with allenoate.

The double [3 + 2]-cycloadditions between nitrile oxides and allenoates have been achieved. In the presence of DABCO combined with Et3N, 2-substituted buta-2,3-dienoates reacted with oxime chlorides to afford spirobiisoxazolines in 55-90% yields via the double 1,3-dipolar cycloaddition. Notably, the construction of double isoxazoline moieties and two chiral centers including a spiro carbon center was achieved.

Enantioselective Organocatalytic 1,6-Addition of Azlactones to para-Quinone Methides: An Access to α,α-Disubstituted and ß,ß-Diaryl-α-amino acid Esters.

This work describes the first enantioselective 1,6-additions of azlactones to para-quinone methides. In the presence of a chiral phosphoric acid, 1,6-adducts were obtained in high yields (up to 96%) with excellent diastereoselectivities and enantioselectivities (all >20:1 diastereoselectivity ratio (dr), up to 99% enantiomeric excess (ee)). Importantly, the method offers a facile synthetic approach, not only to enantiopure α,α-disubstituted α-amino acid esters, but also to unnatural enantioenriched ß,ß-diaryl-α-amino acid esters bearing adjacent tertiary and quaternary stereogenic centers.

[Quantitative study of meridian topology model based on acupoint-symptom relationship].

Meridian theory plays an important role in the guidance of clinical practice of acupuncture and moxibustion. Since the publication of Zhenjiu Jiayi Jing (A-B Classic of Acupuncture and Moxibustion), the meridian theory has been developed. In the paper, in view of complex science, the topological properties of acupoint-symptom network were analyzed quantitatively by taking acupoint as node and indication as the connection, such as high clustering coefficient and the small world effect. It was the first time to give the abstraction for the topological proof of the high efficiency information transmission property of acupoint-symptom network meridian system at different times. Its quantitative and digitalized significance was analyzed on the development of meridian theory under the complex scientific background so as to provide a new thought and method for the study of meridian theory and acupuncture modernization.

Enolate-mediated 1,3-dipolar cycloaddition reaction of ß-functionalized ketones with nitrile oxides: direct access to 3,4,5-trisubstituted isoxazoles.

TMG-catalyzed [3 + 2] organocatalytic 1,3-dipolar cycloaddition reactions of ß-functionalized ketones with nitrile oxides have been developed. This strategy could generate 3,4,5-trisubstituted isoxazoles in high yields and regioselectivities.