The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

OBJECTIVE: To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms. METHODS: Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting. RESULTS: Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05). CONCLUSION AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Diquat/poisoning* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Apoptosis ; Coumarins

Ochratoxin A (OTA) is ubiquitous in the food and feed fields. It has strong hepatotoxicity and nephrotoxicity, seriously threatening the health of humans and animals. Enzymatic degradation of mycotoxins is considered to be a promising method to control mycotoxin contaminations. In this study, a new ochratoxin A amidohydrolase from Microbulbifer thermotolerans (MiADH) was obtained. After heterologous expression in Escherichia coli and purification, the recombinant protein was studied regarding the hydrolysis activity, hydrolysis products, enzymatic properties, and substrate binding mode. MiADH can degrade OTA into ochratoxin α (OTα) and phenylalanine, demonstrating a detoxifying ability. It demonstrated the best performance at 70 ℃ and pH 8.0, and Cu²⁺ had the strongest inhibitory effect on the activity of MiADH. MiADH with good thermal stability exhibited huge potential for industrial application. Rational design guided by three-dimensional structural models and substrate docking analysis revealed the important amino acids affecting substrate binding and obtained multiple mutants with improved activity. Among these mutants, V324A had the highest activity, which was 4.2-fold that of the wild type. The identification of MiADH enriches the ochratoxin A degradation enzyme library and provides a new candidate enzyme for the biological detoxification of ochratoxin A in the food and feed industry.
Amidohydrolases/chemistry* ; Ochratoxins/metabolism* ; Substrate Specificity ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Actinomycetales/genetics*

To develop biocontrol agents for the control of kiwifruit bacterial canker, we isolated a strain CXG2-5 with inhibitory activity against Pseudomonas syringae pv. actinidiae (Psa), the pathogen of kiwifruit bacterial canker, from the rhizosphere soil of kiwifruit by the plate confrontation test. The strain was identified by morphological observation, physiological and biochemical tests, and molecular biological methods. The indoor control efficacy of the strain was determined by the inoculation of the strain into detached branches with wounds and into leaf discs by vacuum infiltration. The ability of the strain to expand and colonize leaf veins was determined by fluorescent labeling and scanning electron microscopy. Subsequently, the strain was prepared into microcapsules, the field control efficacy of which was evaluated. The strain CXG2-5 was identified as Pseudomonas benzenivorans. It demonstrated good antagonistic activity against Psa, with an inhibition zone diameter of 22 mm and an inhibition rate of 72.7%. The preventive effects of the strain on kiwifruit bacterial canker were better than the therapeutic effects on both detached branches and leaves, with the preventive effects reaching 65% and 92.4%, respectively. The control effect of microcapsules of this strain in the field reached 60.89%, which was slightly lower than that of 20% kasugamycin and higher than that of Bacillus subtilis wettable powder. In conclusion, strain CXG2-5 serves as a candidate for the control of kiwifruit bacterial canker, and the prepared microcapsules have good value for development and application.
Actinidia/microbiology* ; Plant Diseases/prevention & control* ; Pseudomonas syringae ; Pseudomonas/isolation & purification* ; Capsules ; Antibiosis ; Biological Control Agents ; Pest Control, Biological/methods*

This study aims to explore protective effects of Lycium barbarum polysaccharides(LBP)on intestinal damage caused by lipopolysaccharide(LPS)-induced inflammatory bowel disease(IBD)in chicks.Network pharmacology was initially employed to determine the target proteins of wolfberry in the prevention and treatment of IBD.Following this,protein-protein interaction analy-sis,GO and KEGG pathway enrichment analysis,and molecular docking studies were conducted.Subsequently,an animal study was conducted:a total of 100 one-day-old male Hy-line brown lay-ing hens were randomly divided into five groups:a blank control group(CON),an LPS treatment group(LPS),a low-dose LBP group(LPS+LBP 0.25 g/L,L-LBP),a medium-dose LBP group(LPS+LBP 0.5 g/L,M-LBP),and a high-dose LBP group(LPS+LBP 1 g/L,H-LBP).Upon reac-hing 21 days old,duodenal,jejunal,ileal,and cecal tissues were collected to determine SOD and GSH-Px levels.Furthermore,the mRNA expression levels of TNF-α,AKT1,IL-6,IL-1β and TP53 in the intestinal tissues were measured using quantitative real-time PCR.The results demonstrated that network pharmacology identified 45 active ingredients in wolfberry that target 116 key protein sites,including TNF,AKT1 and IL6.The primary objectives focus on signaling pathways including AGE-RAGE,IL-17,TNF,HIF-1,and NF-κB.Molecular docking showed excellent ligand-receptor docking scores,with stable binding facilitated by hydrogen bonds and hydrophobic interactions.Compared to the LPS group,the 0.5 g/L LBP exhibited notably higher levels of SOD and T-AOC.In comparison with the LPS group,the medium and high-dose LBP experimental groups showed notably decreased the mRNA expressions of TNF-α,AKT1,IL-6,and IL-1β,while TP53 mRNA expression was significantly upregulated(P＜0.01).In summary,wolfberry exerts preventive and therapeutic effects on IBD through a multi-component,multi-target,and multi-pathway mecha-nism.

Objective:To investigate the correlation between the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), and cardiovascular calcification in patients on maintenance hemodialysis (MHD), and to evaluate their predictive value for cardiovascular calcification.Methods:This retrospective case-control analysis was conducted on the clinical data of 362 patients with chronic kidney disease who underwent regular hemodialysis for >3 months at the Hemodialysis Center of the Second People′s Hospital of Hefei from December 2018 to December 2023. Patients were divided into a cardiovascular calcification group (216 cases) and a cardiovascular non-calcification group (146 cases). The cardiovascular calcification group was further categorized according to different calcification sites, with 69 cases in the vascular calcification group, 79 in the valve calcification group, and 68 in the vascular and valve calcification group. Spearman correlation analysis was used to assess the correlation between cardiovascular calcification and various indicators. Risk factors for cardiovascular calcification in patients with MHD were analyzed using binary logistic regression analysis. The predictive value of the NLR and MHR for cardiovascular calcification was analyzed using the receiver operating characteristic (ROC) curve.Results:This study enrolled 362 cases, including 233 males and 129 females aged 29-89 years. Age, the NLR, and the MHR were positively correlated with cardiovascular calcification in patients on MHD ( r=0.338, 0.383, and 0.391, respectively, all P<0.05). In contrast, serum magnesium was negatively correlated with cardiovascular calcification ( r=-0.169, P<0.05). Age ( OR=1.063, 95% CI 1.036-1.092, P<0.001), male sex ( OR=2.017, 95% CI 1.104-3.685, P=0.023), neutrophil count ( OR=1.737, 95% CI 1.326-2.276, P<0.001), the NLR ( OR=1.722, 95% CI 1.310-2.263, P<0.001), and the MHR ( OR=1.352, 95% CI 1.153-1.586, P<0.001) were identified as independent risk factors for cardiovascular calcification in patients on MHD. Serum magnesium ( OR=0.034, 95% CI 0.001-0.797, P=0.036) was a protective factor. The combined area under the curve (AUC) of the NLR and MHR was the largest (AUC=0.804, 95% CI 0.759-0.850); the AUC for the NLR and MHR used alone was 0.725 (95% CI 0.672-0.779) and 0.730 (95% CI 0.677-0.783), respectively. Conclusions:The MHR, and the NLR are independent risk factors for cardiovascular calcification in patients with MHD. The combination of the MHR and NLR has a greater clinical predictive value for cardiovascular calcification.

Objective To explore the perioperative trend of heart rate variability(HRV)in patients undergoing aortic valve replacement(AVR)under cardiopulmonary bypass and investigate the influence of age and/or postoperative atrial fibrillation(POAF)on this trend.Methods Baseline and clinical data of 134 patients undergoing AVR due to aortic valve disease in Department of Car-diovascular Surgery of Northern Theater General Hospital of PLA from January 2021 to January 2023 were collected and retrospectively studied.According to the age and/or POAF,they were divided into group A(aged＜60 years,no POAF,49 cases),group B(aged＜60 years,complicated with POAF,21 cases),group C(aged≥60 years,no POAF,30 cases)and group D(aged≥60 years,with POAF,34 cases).The dynamic electrocardiogram indicators were collected in 7 d be-fore and 7 d after operation.The changes in perioperative HRV were also observed.Results After operation,the standard deviation of sinus heart beat RR intervals,average of the standard devia-tions of NN intervals for each 5 min segment of a 24 h HRV recording(SDNNidx),root mean square of successive RR interval differences,and percentage of successive RR intervals that differ by more than 50 ms were significantly lower than those in 7 d before operation[61.172±17.449 ms vs 804.567±230.518 ms,20.284±9.432 ms vs 42.933±12.876 ms,1.307±0.196 ms vs 1.412±0.148 ms,3.00(1.30,7.23)ms vs 5.30(3.00,10.40)ms,P＜0.01].The group D had obvi-ously lower SDNNidx than the group A in 7 d after surgery(42.568±14.749 ms vs 46.467±11.754 ms,P＜0.05).Conclusion Autonomic dysfunction is observed in the early stage after AVR.For the patients aged≥60 years with POAF,the HRV indicators are significantly decreased,the dys-function of the vagus nerve is aggravated,and the disorder is exacerbated because of their syner-gistic effect.

Objective To investigate the effect of programmed cell death-ligand 1(PD-L1)monoclonal antibody and paclitaxel(PTX)combined with lentinan(LNT)on human breast cancer MDA-MB-231 cells in vitro.Methods MDA-MB-231 cells,human peripheral blood mononuclear cells(PBMCs),and MDA-MB-231+PBMCs co-culture were randomly divided into control group,PTX group,LNT group,MPDL3280A(PD-L1 monoclonal antibody)group,PTX+LNT group,and PTX+LNT+MPDL3280A group.The cell activity was detected by CCK8.The expressions of MHC-I and PD-L1 were detected by flow cytometry.The levels of IFN-γ and TNF-α were detected by ELISA kits.Results Compared with control group,the activity of MDA-MB-231 cells was significant inhibited in PTX group,MPDL3280A group,PTX+LNT group,and PTX+LNT+MPDL3280A group(P＜0.01).LNT group and PTX+LNT+MPDL3280A group significantly promoted the immune effect of PBMCs(P＜0.05,P＜0.01).PTX+LNT+MPDL3280A group significantly inhibited the activity of MDA-MB-231cells co-cultured with PBMCs(0.56±0.16 vs.0.39±0.13,P＜0.05).Compared with the negative control,LNT significantly promoted the expression of PD-L1 in MDA-MB-231 and the secretion of IFN-γ by PBMCs(P＜0.05).Conclusion By blocking the effect between PD-L1 and PD-1,PD-L1 monoclonal antibody can improve immunity and promote the antitumor effect of PTX combined with LNT in vitro.