Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

OBJECTIVES: To analyze sex and age distribution of global disease burden of calcific aortic valve disease (CAVD) from 1990 to 2021. METHODS: CAVD data during 1990-2021 were obtained from the IHME website for Global Burden of Disease (GBD). The prevalence, mortality, years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed by gender and age groups. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC). RESULTS: In 2021, there were 13.32 million CAVD patients and 142 000 deaths caused by CAVD globally. Age-standardized prevalence was higher in males (193.2/10⁵) than that in females (128.9/10⁵). Patients in 65-<85 age group accounted for 64.0% of total cases, while those ≥85 years old accounted for 16.1%. From 1990 to 2021, prevalence increased in both sexes with an AAPC of 0.72% for males and 0.57% for females, respectively. Prevalence grew fastest from 2000 to 2010, slowed thereafter, and declined from 2015 to 2021. In <65 years old, the mortality of males was 2.4 times higher than that of females, while in ≥85 years old, mortality of females (117.3/10⁵) exceeded that of males (99.1/10⁵). YLD rates increased with age, and were higher in males for all age groups. DALY rates decreased overall but increased in ≥85 years old, with a greater increase in females. CONCLUSIONS There are significant gender and age disparities in global disease burden of CAVD, with the elderly, especially super-elderly females deserving particular attention. It is recommended to develop personalized intervention strategies for these populations.
Humans ; Male ; Female ; Aged ; Calcinosis/mortality* ; Prevalence ; Global Burden of Disease ; Aged, 80 and over ; Middle Aged ; Aortic Valve/pathology* ; Aortic Valve Stenosis/epidemiology* ; Age Distribution ; Adult ; Disability-Adjusted Life Years ; Sex Distribution ; Global Health ; Aortic Valve Disease/epidemiology* ; Sex Factors

Objective To investigate the protective effect of carvacrol(CAR)on high glucose(HG)-induced retinal ganglion cell(RGC)damage by regulating the protein kinase B(PKB,also known as Akt)/nuclear factor erythroid 2-relat-ed factor 2(Nrf2)signaling pathway.Methods The RGC-5 cells in the logarithmic growth phase were inoculated into 96-well cell culture plates with 4 × 104 cells/well and then treated with CAR(5.0 μmol·L-1,10.0 μmol·L-1,20.0 μmol·L-1,40.0 μmol·L-1,80.0 μmol·L-1,and 160.0 μmol·L-1)together with 30.0 mmol·L-1 glucose for 24 hours.Cell viability was detected by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay to screen the ex-perimental concentration of CAR.Then,these RGC-5 cells were inoculated into 6-well plates and randomly assigned into the Control group,30.0 mmol·L-1 glucose(HG)group,low-,medium-,and high-concentration CAR groups(CAR-L group,CAR-M group,and CAR-H group),and high-concentration CAR+Nrf2 pathway inhibitor(ML385)group(CAR-H+ML385 group).Flow cytometry was used to detect the apoptosis of RGC-5 cells.The fluorescent probe was used to de-tect the level of oxidative stress in RGC-5 cells.The enzyme-linked immunosorbent assay(ELISA)was employed to detect the level of superoxide dismutase(SOD),lactate dehydrogenase(LDH),malondialdehyde(MDA),glutathione peroxidase(GSH-PX),and reactive oxygen species(ROS)in the supernatant of RGC-5 cells.Western blot was used to detect the ex-pression of proteins related to the Akt/Nrf2 signaling pathway.Results Compared with the HG group,the survival rate of RGC-5 cells increased significantly when the concentration of CAR was above 20.0 μmol·L-1(all P＜0.05).Therefore,20.0 μmol·L-1,40.0 μmol·L-1,and 80.0 μmol·L-1 of CAR were used for subsequent experiments.Compared with the Control group,the apoptosis rate of RGC-5 cells in the HG group increased significantly,the protein expression of Bax and Caspase-3 was up-regulated significantly,the level of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),ROS,LDH,and MDA increased significantly,and the level of SOD and GSH-PX decreased significantly(all P＜0.05).Compared with the HG group,the apoptosis rate of RGC-5 cells in the CAR-L,CAR-M,and CAR-H groups de-creased significantly,the protein expression of Bax and Caspase-3 was down-regulated significantly,the level of IL-1β,IL-6,TNF-α,ROS,LDH,and MDA decreased significantly,and the level of SOD and GSH-PX increased significantly(all P＜0.05).Compared with the CAR-H group,the apoptosis rate of RGC-5 cells in the CAR-H+ML385 group increased signifi-cantly,the protein expression of Bax and Caspase-3 was up-regulated significantly,the level of IL-1β,IL-6,TNF-α,ROS,LDH,and MDA increased significantly,and the level of GSH-PX and SOD decreased significantly(all P＜0.05).Compared with the Control group,the p-Akt/Akt expression ratio and the relative expression level of Nrf2 in RGC-5 cells decreased significantly in the HG group(both P＜0.05).Compared with the HG group,the p-Akt/Akt expression ratio and the rela-tive expression level of Nrf2 in RGC-5 cells increased significantly in the CAR-L,CAR-M,and CAR-H groups(all P＜0.05).Compared with the CAR-H group,the p-Akt/Akt expression ratio and the relative expression level of Nrf2 decreased signifi-cantly in the CAR-H+ML385 group(both P＜0.05).Conclusion CAR may reduce the inflammatory response level in RGC-5 cells by activating the Akt/Nrf2 signaling pathway,thus inhibiting oxidative stress-related injury and apoptosis.

The radiation-free and unmarked body surface monitoring technology is developed for reducing the additional radiation dose generated by positioning error verification during radiotherapy positioning,and further reducing the positioning error and monitoring the displacement deviation of patients during radiotherapy in real time.At present,the widely used optical surface guided radiotherapy technology is also a type of radiotherapy guided by body surface monitoring.The system mainly uses optical imaging equipment as a tool to complete body surface scanning,three-dimensional reconstruction,real-time monitoring,etc.,thereby assisting doctors to carry out radiotherapy more accurately.Herein the study elaborates on the methods,technologies and research results of guided radiotherapy from the aspects of body surface markers,three-dimensional surface imaging systems and mobile devices,and provides prospects for future researches.

Objective:To investigate the influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.Methods:A case-control study was conducted in January 2024 to select adult fluorosis patients (case group) and healthy individuals (control group) from the drinking water-borne endemic fluorosis areas in Helinger County, Hohhot City, Inner Mongolia Autonomous Region as the survey subjects. Urine samples were collected to determine urinary fluoride concentration. A questionnaire survey was conducted. SPSS 25.0 software was used for χ 2 test and multivariate logistic regression analysis. Restricted cubic spline (RCS) was used to analyze the association between urinary fluoride concentration and the risk of dental fluorosis in adults. Results:A total of 161 individuals were included in the survey, including 100 in the case group and 61 in the control group. The results of univariate analysis showed that there were statistically significant differences in the distribution of gender, smoking, and urinary fluoride concentration between the case group and the control group (χ 2 = 7.54, 5.02, 9.69, P < 0.05). The results of multivariate logistic regression analysis indicated that gender ( OR = 0.36, 95% CI: 0.18 - 0.73, P = 0.005) and urinary fluoride concentration ( OR = 3.08, 95% CI: 1.46 - 6.67, P = 0.003) were the influencing factors of adult fluorosis. RCS analysis showed a significant linear dose-response relationship between the risk of dental fluorosis and urinary fluoride concentration ( Poverall trend = 0.001, Pnonlinear = 0.071). When the urinary fluoride concentration was greater than 1.57 mg/L, the risk of dental fluorosis increased with the increase of urinary fluoride concentration. Conclusion:Gender and urinary fluoride concentration are the risk factors of dental fluorosis in adults in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.

Pulpitis is a prevalent inflammatory disease in dentistry, and root canal therapy remains the primary clinical treatment for it. However, pulp removal leads to reduced tooth fracture resistance and complications such as secondary infection and tooth fracture. As a potential alternative, vital pulp therapy (VPT) relies on precise assessment of pulp status; yet current clinical diagnostic methods lack specificity. The establishment of appropriate animal models for pulpitis is crucial for investigating its pathogenesis, developing specific diagnostic biomarkers, and optimizing VPT strategies. This review systematically summarizes experimental animals selection based on anatomical compatibility and pathological similarity, as well as model construction methods and multimodal evaluation systems for pulpitis animal models, aiming to provide insights for related researches.

Objective:To investigate the influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.Methods:A case-control study was conducted in January 2024 to select adult fluorosis patients (case group) and healthy individuals (control group) from the drinking water-borne endemic fluorosis areas in Helinger County, Hohhot City, Inner Mongolia Autonomous Region as the survey subjects. Urine samples were collected to determine urinary fluoride concentration. A questionnaire survey was conducted. SPSS 25.0 software was used for χ 2 test and multivariate logistic regression analysis. Restricted cubic spline (RCS) was used to analyze the association between urinary fluoride concentration and the risk of dental fluorosis in adults. Results:A total of 161 individuals were included in the survey, including 100 in the case group and 61 in the control group. The results of univariate analysis showed that there were statistically significant differences in the distribution of gender, smoking, and urinary fluoride concentration between the case group and the control group (χ 2 = 7.54, 5.02, 9.69, P < 0.05). The results of multivariate logistic regression analysis indicated that gender ( OR = 0.36, 95% CI: 0.18 - 0.73, P = 0.005) and urinary fluoride concentration ( OR = 3.08, 95% CI: 1.46 - 6.67, P = 0.003) were the influencing factors of adult fluorosis. RCS analysis showed a significant linear dose-response relationship between the risk of dental fluorosis and urinary fluoride concentration ( Poverall trend = 0.001, Pnonlinear = 0.071). When the urinary fluoride concentration was greater than 1.57 mg/L, the risk of dental fluorosis increased with the increase of urinary fluoride concentration. Conclusion:Gender and urinary fluoride concentration are the risk factors of dental fluorosis in adults in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.

Objective:To analyze the grassroots diseases category policy of DIP,explore the influencing mechanism on patient flow,and provide references for other DIP reform pilot regions.Methods:It conducts game theory analysis on the service supply behaviors of different medical institutions under the grassroots diseases category policy,and reveals the reasons affecting the role of grassroots diseases category.Results:Research has found that grassroots diseases can weaken the siphonage of tertiary institutions,but the prerequisite is to establish reasonable disease payment standards;there is a competitive relationship among secondary medical institutions,and secondary medical institutions will still exacerbate grassroots siphonage;the supervision and assessment mechanism for grassroots diseases is not sound,making it difficult to avoid the unreasonable medical service behavior of medical institutions under grassroots diseases.Conclusion:It is needed to further optimize the formulation of payment standards for grassroots diseases in medical insurance departments,consider adding grassroots diseases to primary medical institutions and resolving competitive conflicts between primary and secondary medical institutions,improve the supervision and assessment mechanism for grassroots diseases to prevent unreasonable medical service behavior.

Objective To fabricate wall-less vascular tissue mimicking materials(TMM)with different tube diameters that match the hemodynamic parameters of human carotid arteries,and to investigate their hemodynamic characteristics.Methods TMM with different diameters and blood mimicking fluids containing scattering particles were fabricated.The variation laws of hemodynamic parameters under different flow velocities and TMM phantom diameters were verified.Key hemodynamic parameters including peak systolic velocity(PSV),end-diastolic velocity(EDV),and resistance index were measured using Doppler ultrasound,and their clinical application value in carotid artery diseases was evaluated.Results The fabricated samples exhibited a sound velocity of(1506.2±0.1)m/s and an attenuation of(0.76±0.01)dB/cm,and the vascular diameters were 4.0 and 6.0 mm,which corresponded to the normal clinical range of the external and internal carotid arteries,respectively.For the 4.0 mm TMM,both PSV and EDV were linearly correlated with flow velocity(R2=0.77,P<0.001;R2=0.74,P=0.001),and Pearson correlation analysis confirmed strong positive correlations(r=0.89,95%CI:0.82-0.93;r=0.94,95%CI:0.90-0.97,all P<0.001).For the 6.0 mm TMM,PSV and EDV also demonstrated significant linear correlations with flow velocity(R2=0.70,P=0.001;R2=0.61,P=0.005),with Pearson correlation analysis revealing strong positive correlations(r=0.86,95%CI:0.78-0.91;r=0.79,95%CI:0.68-0.87).All the data were consistent with hemodynamic parameters and followed the variation law of hemodynamic parameters.Conclusion The fabricated TMM and blood mimicking fluids meet the requirements for clinical ultrasound research on hemodynamics,and their material ratios can be used as a reference for the subsequent researches with diverse objectives.

Objective:To study the relationship between urinary arsenic methylation metabolism patterns and skin keratinization and pigmentation abnormalities in population exposed to arsenic through drinking water.Methods:Using a cross-sectional study method, a survey on endemic arsenic poisoning was conducted among permanent residents of drinking water endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region in 2004 (before water improvement). In 2017 (after water improvement), 71 arsenic exposed individuals were followed up as survey subjects. According to the "Diagnosis of Endemic Arsenism" (WS/T 211-2015), the clinical grading of skin injuries (skin keratinization, pigmentation abnormalities) in the survey subjects was evaluated. Urine samples were collected for detection of arsenic methylation metabolite levels by high-performance liquid chromatography inductively coupled plasma mass spectrometry and calibrated with urinary creatinine. The changes and amplitudes of urinary arsenic methylation indicators before and after water improvement were calculated and analyzed according to the outcome of skin keratinization and pigmentation abnormalities which were divided into reduced, unchanged, and added groups.Results:(1) The changes in urinary total arsenic (TAs), inorganic arsenic (iAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) levels in different outcome groups of skin keratinization were compared, and the differences were statistically significant ( H = 9.08, 8.77, 9.28, 8.57, P < 0.05). The changes in urinary TAs, iAs, MMA, DMA levels, iAs percentage (iAs%), DMA percentage (DMA%), and primary methylation index (PMI) in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 8.04, 10.67, 8.29, 9.14, 6.30, 9.10, 7.20, P < 0.05). (2) The comparison of amplitudes in urinary TAs, iAs, MMA, and DMA levels in different outcome groups of skin keratinization showed statistically significant differences ( H = 6.92, 7.34, 6.66, 6.16, P < 0.05). The amplitudes in urinary iAs level, iAs%, DMA%, and PMI in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 7.94, 7.61, 9.95, 7.22, P < 0.05). Conclusion:The changes pattern of urinary TAs, iAs, MMA, DMA, iAs%, DMA%, and PMI in population exposed to arsenic through drinking water is related to the transformation of skin keratinization and pigmentation abnormalities.