1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex

Ulcerative colitis(UC)is characterized by chronic relapsing intestinal inflammation.Currently,there is no effective treatment for the disease.According to our preliminary data,1,8-cineole,which is the main active compound of Amomum compactum Sol.ex Maton volatile oil and an effective drug for the treatment of pneumonia,showed remarkable anti-inflammatory effects on colitis pathogenesis.However,its mechanism of action and direct targets remain unclear.This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate sodium salt-induced colitis mouse model.The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells.In addition,1,8-cineole targets were revealed by drug affinity responsive target stability,thermal shift assay,cellular thermal shift assay,and heat shock protein 90(HSP90)adenosine triphosphatases(ATPase)activity assays.The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function.Mechanistically,1,8-cineole directly interacted with HSP90 and decreased its ATPase activity,also inhibited nucleotide-binding and oligomerization domain-,leucine rich repeat-,and pyrin domain-containing 3(NLRP3)binding to HSP90 and suppressor of G-two allele of SKP1(SGT1)and suppressed NLRP3 inflammasome activation in macrophages.These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.

New sights into new-onset and relapsed minimal change disease post COVID-19 vaccination:A systemic review of the clinical characteristics and underlying pathogenesis

Background::Minimal change disease(MCD)following coronavirus disease 2019(COVID-19)vaccination has been increasingly reported;however,the clinical characteristics and pathogenesis of patients with MCD have not been thoroughly discussed.Methods::A systematic literature search of published data up until May 10,2023,was conducted using the PubMed,Embase,Cochrane Library,Web of Science,and SinoMed databases.MCD patients diagnosed by renal biopsy following COVID-19 vaccination were analyzed with the largest sample size to date.Results::A total of 85 patients were included in the present statistical analysis,including 50 new-onset and 35 relapsed MCD subjects following COVID-19 vaccination.Compared with new-onset MCD patients,the relapsed patients had previously suffered from one or two other diseases(12/50 vs.34/35,p<0.001).The laboratory results indicated that new-onset MCD was more serious than MCD relapse,as evidenced by higher serum creatinine(p=0.036)and urinary protein levels(p<0.001),along with lower levels of serum albumin(p<0.001).The new-onset subjects responded to corticosteroids alone,while the relapsed patients acquired combined therapies involving immunosuppressants and steroids(p<0.001).Compared with MCD onset after two vaccine doses,those who immediately flared after the first vaccination had more comorbidities(p=0.011).Comparatively,the first dose-onset patients showed a higher response rate to treatments than the second dose-onset patients(44/50 vs.22/35,p=0.017).Conclusions::New-onset MCD was more severe than relapsed MCD in terms of laboratory results and clinical manifestations after COVID-19 vaccination.Overall,combining both corticosteroid therapy and immunosuppressive treatment yields an effective approach to managing the condition.

Improvement of signal processing in Coriolis mass flowmeters for gas-liquid two-phase flow

As an increasingly popular flow metering technology,Coriolis mass flowmeter exhibits high measurement accuracy under single-phase flow condition and is widely used in the industry.However,under complex flow conditions,such as two-phase flow,the measurement accuracy is greatly decreased due to various factors including improper signal processing methods.In this study,three digital signal processing methods—the quadrature demodulation(QD)method,Hilbert method,and sliding discrete time Fourier transform method—are analyzed for their applications in processing sensor signals and providing measurement results under gas-liquid two-phase flow condition.Based on the analysis,specific improvements are applied to each method to deal with the signals under two-phase flow condition.For simulation,sensor signals under single-and two-phase flow conditions are established using a random walk model.The phase difference tracking performances of these three methods are evaluated in the simulation.Based on the digital signal processor,a converter program is implemented on its evaluation board.The converter program is tested under single-and two-phase flow conditions.The improved signal processing methods are evaluated in terms of the measurement accuracy and complexity.The QD algorithm has the best performance under the single-phase flow condition.Under the two-phase flow condition,the QD algorithm performs a little better in terms of the indication error and repeatability than the improved Hilbert algorithm at 160,250,and 420 kg/h flow points,whereas the Hilbert algorithm outperforms the QD algorithm at the 600 kg/h flow point.