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

Objective:To investigate the different expression levels of programmed cell death 1 ligand 1 (PD-L1) in non-small cell carcinoma (NSCLC) of distribution characteristics of TCM constitutions and prognosis.Methods:The clinical data of 355 NSCLC patients who had been treated with immune checkpoint inhibitors (ICIs) from January 2019 to June 2023 in the Cancer Medical Center of the First Affiliated Hospital of Hunan University of Chinese Medicine were retrospectively analyzed, and their TCM constitutions were determined. According to the expression level of PD-L1, they were divided into three groups: low expression group (TPS≤1%), medium expression group (1% < TPS < 49%) and high expression group (TPS≥50%). Overall survival (OS) of patients was followed up, and the median OS were compared. Kaplan-Meier method was used to draw survival curves, and Log-rank test was used to compare the difference of survival curves. The independent risk factors of OS were analyzed by COX regression.Results:The distribution of different TCM constitutions showed statistical significance across the three groups ( P<0.05). The median OS for the medium and high expression groups were 21.082 months and 25.714 months, respectively, both significantly higher than the 14.437 months for the low expression group ( P<0.05). The survival curve of TCM constitutions showed that the constitutions significantly correlated with the prognosis of ICIs treatment were qi deficiency, phlegm dampness, and blood stasis ( P<0.05 or P<0.01). The median OS from high to low was 44.971 months for phlegm-dampness constitution, 23.297 months for qi-deficiency constitution, and 11.763 months for blood-stasis constitution. COX regression analysis indicated that medium PD-L1 expression ( HR=0.622, 95% CI=0.459,0.844, P=0.002), high PD-L1 expression ( HR=0.509, 95% CI=0.361,0.718, P<0.001), phlegm-dampness constitution ( HR=0.556, 95% CI=0.335,0.924, P=0.024), and blood-stasis constitution ( HR=2.952, 95% CI=1.929,4.518, P<0.001) were independent prognostic factors. Conclusions:The higher the expression level of PD-L1 in NSCLC patients, the better the prognosis of ICIs treatment. The prognosis of ICIs treatment is better for people with phlegm-dampness constitution and poor for those with blood stasis constitution.

Objective To observe the value of augmented reality(AR)navigation system for assisting CT-guided puncture of pulmonary nodules in dog models.Methods Five healthy dogs were selected,and 4 target lung rings were implanted in each dog to build pulmonary nodule models.Deferring to crossover design,CT-guided punctures were performed with or without AR navigation 2 and 4 weeks after successful modeling,respectively,while punctures with AR navigation were regarded as AR group and the others as conventional group,respectively.The time duration of puncturing,the times of CT scanning,of needle adjustment,and the deviation distance between needle pinpoint to the center of pulmonary nodule shown on three-dimensional reconstruction were compared between groups.Results The duration time of puncture in AR group and conventional group was(13.62±5.11)min and(20.16±4.76)min,respectively.In AR group,the times of CT scanning,of needle adjustment,and the deviation distance was 2.40±0.50,2.75±0.44 and(2.94±1.92)mm,respectively,while in conventional group was 3.10±0.64,3.70±0.57 and(4.90±3.38)mm,respectively.The introduction of AR navigation was helpful to shortening the duration of puncture,reducing times of CT scanning and needle adjustment,also decreasing positioning error of needle pinpoint(all P＜0.05).In contrast,the variance of puncture sequences and dogs had no obvious effect on the results(both P＞0.05).Conclusion AR navigation system could improve accuracy and efficiency in CT-guided puncture of pulmonary nodules in dog models.

Objective To investigate a novel stroke recurrence risk prediction model,which utilized radiomics machine learning methods and specifically combined carotid computed tomography angiography(CT A)with the Essen stroke risk score(ESRS).Methods A total of 136 patients who underwent carotid CT A were analyzed retrospectively.The features of carotid plaque were extrac-ted by machine learning to construct a radiomics feature model,as well as combined with ESRS.Based on clinical outcomes at one-year follow-up,the stroke recurrence risk prediction model was constructed using the logistic regression(LR)machine learning model.To construct an effective and robust model,the dataset was divided into a training set and a validation set in a ratio of 7∶3.The performance of this model was evaluated using area under the curve(AUC)of receiver operating characteristic(ROC)curve,sensi-tivity and specificity.Results The model had strong predictive value.In the training set,AUC,sensitivity and specificity of this model were 0.903,0.796 and 0.761,respectively.In the validation set,AUC,sensitivity and specificity of this model were 0.869,0.667 and 0.850,respectively.Conclusion The stroke recurrence risk prediction model constructed based on radiomics analysis of carotid plaque characteristics in carotid CTA,in combination with the ESRS,can provide reliable predictions for stroke prognosis.

Objective To establish the method of infrared fingerprint,TLC identification and content determination of phenolic acid components of Yao medicine Calonyction muricatum(Linn)G.Methods The infrared fingerprint of 10 batches of Calonyction muricatum(Linn)G were established by infrared spectroscopy.The spectral datas were analyzed by similarity analysis,infrared spectroscopy(HCA),principal component analysis(PCA)and Partial-least-squares discriminant analysis(PLS-DA).Chlorogenic acid,heterochlorogenic acid A and caffeic acid of Calonyction muricatum(Linn)G were identified by TLC.The contents of neochlorogenic acid,chlorogenic acid,caffeic acid,cryptochlorogenic acid,isochlorogenic acid A and C were determined simultaneously by HPLC method.Results It could be suggested that organic acids,flavonoids and other compounds of Calonyction muricatum(Linn)G by infrared spectroscopy and nine common peaks were calibrated by infrared fingerprint;the similarity evaluation was above 0.999;the results of cluster analysis(CA)and principal component analysis(PCA)showed that it could be clustered into 2 categories,including S1,S2 and S3 were clustered into one categoriy and the rest were one.5 differential components(VIP>1)were selected by Partial-least-squares discriminant analysis;the test and control samples of TLC showed consistent locations the spots were clear,with good separation degree;the six components of Calonyction muricatum(Linn)G showed good linear relationship(r≥0.999 2),average sample recovery rate 97.77%-102.59%,and RSD less than 2.90% .Conclusion The TLC and infrared fingerprint were simple and stable,and the results of the six components were reliable,which can lay a scientific foundation for the quality control of the materials.

Purpose: This study was performed to analyze the rule of confluence of the caudate lobe bile duct (CLD) into the left hepatic duct (LHD) and to discuss the protective strategy during left hemihepatectomy. Methods: MRI of 400 patients and T-tube angiography images of 100 patients were collected, and the imaging rules of the confluence of the CLD into the LHD were summarized. The clinical data of 33 patients who underwent left hemihepatectomy using the protective strategy were analyzed. Results: MRI and T-tube angiography images showed that the length from the confluence point of the CLD into the LHD to the confluence of the left and right hepatic ducts was 1.19 ± 0.40 cm and 1.26 ± 0.39 cm, respectively. The average angle between the longitudinal axis of the 2 bile ducts was 68.27° ± 22.59° and 66.58 ± 22.88°, respectively. Coronal and cross-sectional images showed that inflow from the foot side to the cranial side was noted in 79.8% and 82.0% of patients, respectively, and inflow from the dorsal to the ventral side was observed in 84.5% and 88.0%, respectively. Based on these imaging rules, the safe transection length and plane were summarized, and the CLD was effectively protected in 33 cases of left hemihepatectomy. Conclusion In left hemihepatectomy, the LHD should be transected at least 1.5 cm away from the confluence of the left and right hepatic ducts, and the plane of transection should be oblique to the dorsal side at an angle of 45° with the LHD, these parameters represent an effective strategy to protect the CLD.

Objective:To explore the analgesic methods in ambulatory laparoscopic cholecystectomy (LC) patients.Methods:Three hundred patients were randomly divided into six groups receiving different analgesic regimen. VAS scores, postoperative blood pressure, CRP, IL-6, and the occurrence of postoperative adverse effects were recorded at 2, 4, 8, and 12 h postoperatively.Results:The success rate of ambulatory LC in this study was 66.22%. The dynamic VAS scores of patients in each group gradually decreased with time elapsing, with groups B and C being significantly lower than group A at 2 h and 4 h postoperatively ( P<0.05). Groups D, E and F were significantly different from group A at all postoperative time points ( P<0.05). There was a statistically significant difference at 8 h and 12 h postoperatively in group B vs. group D and group C vs. group E (all P<0.05). There was significant difference at the 12 h postoperatively between groups (B and C) compared to group F ( P<0.05). There was a significant difference in CRP and IL-6 between the groups (all P<0.05). Postoperative dizziness, nausea and delayed discharge were significantly higher in patients using analgesic pumps ( P<0.05). Conclusion:Local infiltration of ropivacaine combined with postoperative parecoxib sodium drip is a recommended analgesic regimen.

OBJECTIVE: This study aims to investigate the mechanism of K (lysine) acetyltransferase 2A (KAT2A) regulation and control on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). METHODS: The expression levels of KAT2A in PDLSCs were compared from each generation of the normal (H-PDLSCs) and periodontitis tissues (P-PDLSCs). The influences of KAT2A gene interference on the osteogenic differentiation of PDLSCs were also detected. In addition, the influences of the KAT2A gene interference to the canonical Wnt pathway and ligands were detected. The upstream and down-stream relationships between KAT2A and canonical Wnt pathway were also determined. RESULTS: The decreased expression of KAT2A in PDLSCs from the inflammatory tissue in each generation was compared with that in PDLSCs from the healthy tissue, and the difference was statistically significant (P<0.05). When the KAT2A gene was disrupted, the osteogenesis ability of PDLSC was declined, and the difference was statistically significant (P<0.05). The canonical Wnt pathway was activated, and the antagonist Dickkopf-1 (DKK-1) was reduced. After the DKK-1 addition, the osteogenic differentiation of the disturbed PDLSCs was recovered, and KAT2A was unaffected. CONCLUSIONS The KAT2A expression in PDLSCs was decreased because of perio-dontitis. The classical Wnt pathway was activated to inhibit the osteogenic differentiation of the cells.
Acetyltransferases ; Cell Differentiation ; Cells, Cultured ; Histone Acetyltransferases ; metabolism ; Humans ; Lysine ; Osteogenesis ; Periodontal Ligament ; metabolism ; Periodontitis ; metabolism ; Stem Cells ; Wnt Signaling Pathway

Objective:To investigate the trait of exosomes serected by mesenchymal stem cells derived form orofacial bone(OMMSCs-Exo) and the communication between the exosomes and macrophages.Methods:OMMSCs were isolated from orthognathic surgical sites and cultured by limited dilution.Their cell surface markers were characterized by flow cytometry.the rate of colony formation and the differentiation potential of OMMSCs were evaluated.Exosomes were prepaired from the culture supernatants of OMMSCs(P4-P6).Transmission electron microscopy(TEM) and western blot were used to identify the exosomes.The expression of miRNAs associated with immunity such as miR-223 and miR-let-7c were determined by Real-time RT-PCR.Human peripheral blood mononuclear cells(PBMCs) were isolated from health donor and co-cultured with OMMSCs-Exo.After co-cultured for 24 h,the communication between exosomes and macrophages was tested using a confocal microscope.Results:Human OMMSCs were proved to have the characteristics of mesenchymal stem cells.The diameter of OMMSCs-Exo ranged from 40 to 160 nm.The OMMSCs-Exo expressed CD63 and CD81 and contained miRNAs associated with immune regulation such as miR223 and miR-let-7c.OMMSCs-Exo could be uptaken by macrophages.After co-culture of OMMSCs-Exo with marcrophages for 72 h,miR223 expression in macrophages increased.Conclusion:OMMSCs-Exo has the potential of immune regulation.

Objective:To compare acetyltransferase MORF level in periodontal ligament stem cells( PDLSCs) derived from healthy individuals ( H-PDLSCs) with those derived from the individuals with periodontitis ( P-PDLSCs ) . And to determine the effect of MORF on the osteogenic differentiation potential of PDLSCs. Methods: Human H-PDLSCs and P-PDLSCs were cultured and cloned with limited dilution method. H-PDLSCs were stimulated by LPS, TNF-α, IL-β and the mix of the 3 inflammatory factors to imitate inflammatory environment ( IP-PDLSCs ) . Quantitative RT-PCR and Western Blot were applied to examine different expression of MORF in H-PDLSCs and P-PDLSCs. Western Blot was applied to detect expression of MORF in IP-PDLSCs. Quantitative RT-PCR, Western Blot and alizarin red staining were applied to determine osteogenic differentiation potential of H-PDLSCs with MORF knock-down. Results:Quantitative RT-PCR and Western Blot showed lower expression of MORF in P-PDLSCs compared with H-PDLSCs( P<0. 05). Western Blot revealed lower expression of MORF in IP-PDLSCs. Quantitative RT-PCR, Western Blot and alizarin red stai-ning indicated osteogenic differentiation potential was inhibited in H-PDLSCs with MORF knockdown(P<0. 05). Conclusion: Peri-odontitis can suppress the expression of MORF in PDLSCs and inhibite the osteogenic differentiation potential of PDLSCs.