Objective To establish a rapid analysis method for cyanide based on a ratiometric fluores-cent probe,providing a quantitative strategy for on-site visual and rapid detection of cyanide.Methods A dual-emission ratiometric fluorescent probe(AuNCs-FL)was constructed by using bovine serum al-bumin(BSA)-stabilized gold nanoclusters(AuNCs,fluorescence emission at 660 nm)as the responsive signal unit and fluorescein(FL,emission at 515 nm)as the internal reference.Results The etching effect of cyanide on AuNCs resulted in fluorescence quenching at 660 nm,while the fluorescence inten-sity of FL at 515 nm remained unchanged,enabling a rapid response analysis of cyanide shift from red to green fluorescence.The developed probe enabled rapid analysis of cyanide within 3 min,with a limit of detection(LOD)of 3.4 mg/L and a visual detection range of 10-100 mg/L.Conclusion The AuNCs-FL fluorescent probe is structurally simple,low-cost,and easy to operate,delivering rapid and accurate results.It also avoids the interference from sulfides encountered in commercial cyanide test kits,making it suitable for the on-site rapid detection of suspected powder samples in cyanide poisoning cases.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective To compare the differences between swept-source optical coherence tomography angiography(SS-OCTA)and ultra-wide-field fluorescein angiography(UWFA)in detecting non-perfusion areas(NPs)in patients with diabetic retinopathy(DR),to evaluate the accuracy of SS-OCTA in predicting NPs outside its visible range,and to explore the distribution patterns of NPs.Methods A retrospective analysis was made on 69 DR patients(88 eyes)who under-went both UWFA and SS-OCTA examinations at the Ophthalmology Department of Sichuan Provincial People's Hospital from December 2022 to September 2024.Manual NP labeling was conducted to compare the detection rate of NPs between the two imaging techniques.The distribution patterns of NPs and the accuracy of SS-OCTA for predicting NPs outside its visible range were also analyzed.Results In a scanning area of 20 mm x 24 mm,the overall NP detection rate by SS-OCTA was 47.40％,with UWFA taken as the standard.The NP detection rate by SS-OCTA was 51.56％in the superotemporal quad-rant,58.35％in the inferotemporal quadrant,45.50％in the superonasal quadrant,and 43.17％in the inferonasal quad-rant.Most NPs occurred in the inferonasal quadrant,accounting for 41.71％of the total NP.The accuracy of SS-OCTA in predicting NPs was 75.00％in the superonasal quadrant and 78.41％in the inferonasal quadrant.The ischemic indices(ISI)of the two imaging techniques were highly positively correlated(r2=0.74).Conclusion Although SS-OCTA can-not yet fully replace UWFA for NP detection in DR patients due to a small visible range,it is still an effective tool to assess retinal ischemia.SS-OCTA has the ability to predict NPs outside its visible range in its scanning range.The inferonasal quadrant is the region where NPs occur most frequently in DR patients,so it is suggested that special attention should be paid to this region in early diagnosis and follow-up periods.

The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Objective In order to provide a better reference and basis for the selection of reasonable hypoglycemic drugs for clinical treatment,the study conducted a comprehensive clinical evaluation of the innovator sodium-glucose transporters 2(SGLT-2)inhibitors,based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition).Methods The real-world studies,randomized controlled trials,Meta-analysis/systematic review,drug clinical use guidelines,expert consensus and drug description evaluation evidence were collected,and the included drugs were assigned and evaluated from five dimensions:pharmaceutical characteristics,efficacy,safety,economy and other attributes.Results All SGLT-2 inhibitors had evaluation scores above 75,with dagaglifloztin tablets having the highest score of 84.6,and canaglifloztin having the lowest score of 75.1.Conclusions All five original SGLT-2 inhibitors showed good clinical utility,the difference is that the participating original drugs have different advantageous intervals in clinical use.The results show that dagliflozin has the most ideal clinical utility,and its clinical use should be safer and more effective.Due to the short time on the market and insufficient evidence-based reasons,the advantages of clinical use of proline hemegliflozin are not obvious compared with other evaluated drugs.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective In order to provide a better reference and basis for the selection of reasonable hypoglycemic drugs for clinical treatment,the study conducted a comprehensive clinical evaluation of the innovator sodium-glucose transporters 2(SGLT-2)inhibitors,based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition).Methods The real-world studies,randomized controlled trials,Meta-analysis/systematic review,drug clinical use guidelines,expert consensus and drug description evaluation evidence were collected,and the included drugs were assigned and evaluated from five dimensions:pharmaceutical characteristics,efficacy,safety,economy and other attributes.Results All SGLT-2 inhibitors had evaluation scores above 75,with dagaglifloztin tablets having the highest score of 84.6,and canaglifloztin having the lowest score of 75.1.Conclusions All five original SGLT-2 inhibitors showed good clinical utility,the difference is that the participating original drugs have different advantageous intervals in clinical use.The results show that dagliflozin has the most ideal clinical utility,and its clinical use should be safer and more effective.Due to the short time on the market and insufficient evidence-based reasons,the advantages of clinical use of proline hemegliflozin are not obvious compared with other evaluated drugs.

Objective To quantify the intraretinal fluid(IRF)volume in patients with diabetic macular edema(DME)using a deep learning-based three-dimensional segmentation model and to investigate the relationship of IRF volume with visual function and retinal biomarkers based on optical coherence tomography(OCT).Methods A total of 37 pa-tients(42 eyes)with DME who received treatment in the Ophthalmology Department of Sichuan Provincial People's Hospi-tal from July 2022 to September 2024 were prospectively included in this study.A three-dimensional segmentation model was used to automatically quantify the IRF volume within a 6 mm × 6 mm OCT scan at baseline and at the last follow-up.The correlation of visual acuity with IRF volume,central subfield thickness(CST),disorganization of the retinal inner lay-ers(DRIL),hyperreflective foci(HRF),external limiting membrane(ELM),ellipsoid zone(EZ),and vitreomacular in-terface abnormality(VMIA)was analyzed at baseline and the last follow-up.Additionally,the correlation of IRF volume with CST,DRIL,HRF,ELM,EZ,and VMIA was analyzed at both time points.Furthermore,the correlation of the visual acuity at the last follow-up with the IRF volume,CST,DRIL,HRF,ELM,EZ,and VMIA at baseline was analyzed.Results Compared with the baseline value,patients exhibited a significant increase in the best corrected visual acuity(BCVA)(logMAR),a significant decrease in the IRF volume and CST,a significant reduction in the HRF,a significant re-covery in the DRIL,ELM,and EZ(all P＜0.05),and no significant changes in the VMIA(P=1.000)at the last follow-up.At baseline,the BCVA was negatively correlated with the IRF volume,CST,DRIL,and HRF,but positively correlated with the ELM and EZ(all P＜0.05);there was no correlation between the BCVA and VMIA(P=0.069).At the last follow-up,the BCVA was negatively correlated with the DRIL,HRF,and VMIA,but positively correlated with the ELM and EZ(all P＜0.01);the BCVA did not correlate with the IRF volume and CST(P=0.419 and 0.994).At baseline,the IRF volume was positively correlated with the CST(P＜0.001)but negatively correlated with the ELM and EZ(P＜0.01);the IRF vol-ume did not correlate with the DRIL,HRF,and VMIA(all P＞0.05).At the last follow-up,the IRF volume was positively correlated with the CST and HRF(all P＜0.01);however,it was not correlated with the DRIL,ELM,EZ,and VMIA(all P＞0.05).The BCVA at the last follow-up was positively correlated with the BCVA,ELM,and EZ at baseline,but negative-ly correlated with the IRF volume,CST,DRIL,HRF,and VMIA at baseline(all P＜0.05).Conclusion The baseline IRF volume in DME patients is an important influencing factor of visual acuity at baseline and the last follow-up.Hence,the IRF volume may serve as a potential biomarker in the management of DME.