A pyrene-phenol-based fluorescent probe PyP which showed typical intramolecular charge transfer(ICT)and monomer-excimer activities was synthesized by using pyrene carboxaldehyde hydrazone and 4-tert-butyl-2,6-diformylphenol as the raw materials.The effects of solvents on PyP were studied,and the results showed that the color of protic polar solvents(Ethanol,N,N-dimethylformamide,methanol and H2O)were successfully identified.Based on the solvent polarity-regulated PyP monomer-excimer switching,the rapid and highly sensitive ratiometric probe,"Turn-off"and"Turn-on"multimodal probes were established for detection of trace water content in organic solvents(Dimethyl sulfoxide,N,N-dimethylformamide,ethanol and methanol),with detection limits(3σ/k)of 0.0021％,0.046％,0.062％and 0.024％.The method was successfully used to detect water content in dimethyl sulfoxide,N,N-dimethy lformamide,ethanol and methanol commercial organic solvents,with recoveries ranging from 97.2％to 108.0％.The developed method showed good accuracy and stability,and had good application prospect.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective To analyze the application value of assisted compressed sensing(ACS)combined with deep reconstruction(DR)(ACS+DR)algorithm in MR abdominal T2WI.Methods A total of 60 patients were prospectively selected to undergo three types of respiratory-triggered transverse T2 sequence scans:fast spin echo(FSE),propeller scanning(ARMS),and ACS+DR.Two radiologists independently evaluated the images for respiratory motion artifacts,gastrointestinal peristalsis artifacts,sharpness of intrahepatic vessel and bile duct,lesion clarity,and overall image quality.Additionally,the signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),and contrast ratio(CR)between lesions and liver parenchyma signal intensity were calculated.Wilcoxon and independent sample Mann-Whitney U tests were used to compare objective scores and subjective evaluations among different groups.Results The scan time for the ACS+DR sequence was 35 s,for the ARMS sequence 180 s,and for the FSE sequence 210 s.The ACS+DR sequence showed superior performance over the other sequences in terms of scan time,respiratory motion artifacts,intrahepatic vessel and bile duct sharpness,lesion clarity,and overall image quality(P＜0.05).Compared with FSE sequence,the ARMS and ACS+DR sequences exhibited higher SNR,CNR,and CR(P＜0.05).The ACS+DR sequence showed better SNR and CNR than the ARMS sequence(P＜0.05);however,there was no significant difference between the two sequences in CR(P＞0.05).No significant difference was found among the three sequences in the number of detected lesions(P＞0.05).Conclusion The ACS+DR reconstruction algorithm for upper abdominal imaging not only ensures high image quality but also significantly improves scan speed,making it valuable for clinical application.

Objective:To investigate the effects and underlying mechanism of ionizing radiation on the adipogenic of mesenchymal stem cells(MSCs).Methods:Mouse MSCs were cultured in vitro and treated with 2 Gy and 6 Gy radiation with 60Co,and the radiation dose rate was 0.98 Gy/min.Bulk RNA-seq was performed on control and irradiated MSCs.The changes of adipogenic differentiation and oxidative stress pathways of MSC were revealed by bioinformatics analysis.Oil Red O staining was used to detect the adipogenic differentiation ability of MSCs in vitro,and real-time fluorescence quantitative PCR(qPCR)was used to detect the expression differences of key regulatory factors Cebpa,Lpl and Pparg after radiation treatment.At the same time,qPCR and Western blot were used to detect the effect of inhibition of Nrf2,a key factor of antioxidant stress pathway,on the expression of key regulatory factors of adipogenesis.Moreover,the species conservation of the irradiation response of human bone marrow MSCs and mouse MSC was determined by qPCR.Results:Bulk RNA-seq suggested that ionizing radiation promotes adipogenic differentiation of MSCs and up-regulation of oxidative stress-related genes and pathways.The results of Oil Red O staining and qPCR showed that ionizing radiation promoted the adipogenesis of MSCs,with high expression of Cebpa,Lpl and Pparg,as well as oxidative stress-related gene Nrf2.Nrf2 pathway inhibitors could further enhance the adipogenesis of MSCs in bone marrow after radiation.Notably,the similar regulation of oxidative pathways and enhanced adipogenesis post irradiation were observed in human bone marrow MSCs.In addition,irradiation exposure led to up-regulated mRNA expression of interleukin-6 and down-regulated mRNA expression of colony stimulating factor 2 in human bone marrow MSCs.Conclusion:Ionizing radiation promotes adipogenesis of MSCs in mice,and oxidative stress pathway participates in this effect,blocking Nrf2 further promotes the adipogenesis of MSCs.Additionally,irradiation activates oxidative pathways and promotes adipogenic differentiation of human bone marrow MSCs.

Objective:To establish an in vitro cell model simulating acute graft-versus-host disease(aGVHD)bone marrow microenvironment injury with the advantage of mouse serum of aGVHD model and explore the effect of serum of aGVHD mouse on the adipogenic differentiation ability of mesenchymal stem cells(MSCs).Methods:The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model,respectively.Bone marrow transplantation(BMT)mouse model(n=20)was established by being injected with bone marrow cells(1 × 10'per mouse)from donor mice within 4-6 hours after receiving a lethal dose(8.0 Gy,72.76 cGy/min)of y ray general irradiation.A mouse model of aGVHD(n=20)was established by infusing a total of 0.4 ml of a mixture of donor mouse-derived bone marrow cells(1 × 107 per mouse)and spleen lymphocytes(2 × 106 per mouse).The blood was removed from the eyeballs and the mouse serum was aspirated on the 7th day after modeling.Bone marrow-derived MSCs were isolated from 1-week-old C57BL/6N male mice and incubated with 2％,5％and 10％BMT mouse serum and aGVHD mouse serum in the medium,respectively.The effect of serum in the two groups on the in vitro adipogenic differentiation ability of mouse MSCs was detected by Oil Red O staining.The expression levels of related proteins PPARy and CEBPα were detected by Western blot.The expression differences of key adipogenic transcription factors including PPARy,CEBPα,FABP4 and LPL were determined by real-time quantitative PCR(RT-qPCR).Results:An in vitro cell model simulating the damage of bone marrow microenvironment in mice with aGVHD was successfully established.Oil Red O staining showed that the number of orange-red fatty droplets was significantly reduced and the adipogenic differentiation ability of MSC was impaired at aGVHD serum concentration of 10％compared with BMT serum.Western blot experiments showed that adipogenesis-related proteins PPARy and CEBPα expressed in MSCs were down-regulated.Further RT-qPCR assay showed that the production of PPARy,CEBPα,FABP4 and LPL,the key transcription factors for adipogenic differentiation of MSC,were significantly reduced.Conclusion:The adipogenic differentiation capacity of MSCs is inhibited by aGVHD mouse serum.