Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.

Research on shock wave driving technology of methane explosion.

In order to improve the driving ability of the explosion wave simulation equipment, reduce the erosion effect of condensed explosives on the explosion wave simulation equipment, improve the safety of the test process, and make better use of the meteorological detonation driving method, it is necessary to optimize the source of the shock wave load in the driving section. Based on the finite volume method of FLACS, a methane detonation driving model corresponding to the test is established to explore the feasibility of using methane as an explosion source to test the structure against explosion shock wave. A methane detonation drive test was carried out to verify the accuracy of the numerical model. Finally, an engineering model for attenuation of shock wave overpressure peak value in pipeline is established by dimensional analysis, and the model coefficient is determined by numerical simulation and test data. The results show that the blast pressure is the highest when the methane volume ratio reaches 9.5 vol% in the methane-air mixture. Simply increasing oxygen content has little effect on the peak overpressure and positive pressure duration of shock wave. In the pure oxygen environment, the detonation effect can be achieved when the volume ratio of methane to oxygen is 1:2, and the incident pressure of the shock wave is proportional to the volume of the gas cloud. When the gas cloud volume is constant, a reasonable selection of methane-oxygen mixture ratio can achieve a better detonation effect, which can effectively increase the peak overpressure of the shock wave in the test section. The research results can provide technical reference for the development of new explosion wave simulation equipment.

Crystal structure of the iron-sulfur cluster transfer protein ApbC from Escherichia coli.

Iron-sulfur (Fe-S) clusters are ubiquitous and are necessary to sustain basic life processes. The intracellular Fe-S clusters do not form spontaneously and many proteins are required for their biosynthesis and delivery. The bacterial P-loop NTPase family protein ApbC participates in Fe-S cluster assembly and transfers the cluster into apoproteins, with the Walker A motif and CxxC motif being essential for functionality of ApbC in Fe-S protein biogenesis. However, the structural basis underlying the ApbC activity and the motifs' role remains unclear. Here, we report the crystal structure of Escherichia coli ApbC at 2.8 Å resolution. The dimeric structure is in a W shape and the active site is located in the 2-fold center. The function of the motifs can be annotated by structural analyses. ApbC has an additional N-terminal domain that differs from other P-loop NTPases, possibly conferring its inherent specificity in vivo.

Ultrasound-Based Deep Learning Radiomics Nomogram for the Assessment of Lymphovascular Invasion in Invasive Breast Cancer: A Multicenter Study.

RATIONALE AND OBJECTIVES: The aim of this study was to develop a deep learning radiomics nomogram (DLRN) based on B-mode ultrasound (BMUS) and color doppler flow imaging (CDFI) images for preoperative assessment of lymphovascular invasion (LVI) status in invasive breast cancer (IBC). MATERIALS AND METHODS: In this multicenter, retrospective study, 832 pathologically confirmed IBC patients were recruited from eight hospitals. The samples were divided into training, internal test, and external test sets. Deep learning and handcrafted radiomics features reflecting tumor phenotypes on BMUS and CDFI images were extracted. The BMUS score and CDFI score were calculated after radiomics feature selection. Subsequently, a DLRN was developed based on the scores and independent clinic-ultrasonic risk variables. The performance of the DLRN was evaluated for calibration, discrimination, and clinical usefulness. RESULTS: The DLRN predicted the LVI with accuracy, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI 0.90-0.95), 0.91 (95% CI 0.87-0.95), and 0.91 (95% CI 0.86-0.94) in the training, internal test, and external test sets, respectively, with good calibration. The DLRN demonstrated superior performance compared to the clinical model and single scores across all three sets (p < 0.05). Decision curve analysis and clinical impact curve confirmed the clinical utility of the model. Furthermore, significant enhancements in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indicated that the two scores could serve as highly valuable biomarkers for assessing LVI. CONCLUSION: The DLRN exhibited strong predictive value for LVI in IBC, providing valuable information for individualized treatment decisions.

[Evaluation of chemical constituents of Draconis Sanguis and its protective effect on renal tubular injury in diabetic kidney disease].

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.

Perioperative position management of 46 cases with simultaneous bilateral auricle reconstruction: A summary of experience.

OBJECTIVES: The primary problem in simultaneous bilateral auricle reconstruction is the fragility of the reconstructed ear structure. Postoperative pressure is strictly prohibited to ensure the operation's effectiveness. The study aimed to summarize the experience of perioperative postural management in simultaneous bilateral auricular reconstruction. METHOD: This study summarizes the experience of perioperative postural management, providing preoperative sleeping posture adaptability training, neck movement training, standardization of the head position angles and the head suspension time in surgery, using protective headrests, paying attention to the transfer and handover procedures, and using specially designed pillows. RESULTS: The comprehensive nursing approach in simultaneous bilateral auricular reconstruction significantly reduced complications, improved patient comfort, and optimized postoperative adaptation. Preoperative posture training, standardized intraoperative head positions, and vigilant postoperative care played pivotal roles, demonstrating positive outcomes in 46 cases. DISCUSSION: Perioperative position management can reduce the risk of complications and pressure injuries, improving patients' postoperative comfort, emotional state, tolerance, and adaptability. CONCLUSION: All ears were viable and in good shape after long-term follow-up. The experiences discussed in this study can be broadly applied to technically mature ear reconstruction teams.

Research on interaction and trust theory model for cockpit human-machine fusion intelligence.

Based on Boyd's "Observation Orientation-Decision-Action (OODA)" aerial combat theory and the principles of operational success, an analysis of the operational division patterns for cross-generational human-machine collaboration was conducted. The research proposed three stages in the development of aerial combat human-machine fusion intelligence: "Human-Machine Separation, Functional Coordination," "Human-Machine Trust, Task Coordination," and "Human-Machine Integration, Deep Fusion." Currently, the transition from the first stage to the second stage is underway, posing challenges primarily related to the lack of effective methods guiding experimental research on human-machine fusion interaction and trust. Building upon the principles of decision neuroscience and the theory of supply and demand relationships, the study analyzed the decision-making patterns of human-machine fusion intelligence under different states. By investigating the correlations among aerial combat mission demands, dynamic operational limits of human-machine tasks, and aerial combat mission performance, a theoretical model of human-machine fusion interaction and trust was proposed. This model revealed the mechanistic coupling of human-machine interactions in aerial tasks, aiming to optimize the decision-making processes of human-machine systems to enhance mission performance. It provides methodological support for the design and application of intelligent collaborative interaction modes in aviation equipment.

Toxic effects of microplastics and nitrite exposure on intestinal histology, digestion, immunity, and microbial community of shrimp Litopenaeus vannamei.

Nitrite and microplastics (MPs) are environmental pollutants that threaten intestinal integrity and affect immune function of shrimp. In this study, the shrimp Litopenaeus vannamei were exposed to the individual and combined stress of nitrite and microplastics for 14 days, and the changes of intestinal histology and physiological functions were investigated. After single and combined stress, affectations occurred in intestinal tissue; the antioxidant enzyme activities (MDA, H2O2, CAT increased) and gene expression levels (CAT, SOD, GPx, HSP70 up-regulated) changed. The expression levels of detoxification genes (CYP450, UGT down-regulated, GST up-regulated), apoptosis genes (CASP-3 up-regulated) and endoplasmic reticulum stress genes (Bip, GRP94 down-regulated) changed. Furthermore, the stress also increased intestinal microbial diversity, causing bacterial composition variation, especially beneficial bacteria and pathogenic bacteria. These results suggested that nitrite and microplastics stress had adverse effects on the intestinal health of L. vannamei by affecting intestinal tissue morphology, immune response and microbial community.

Interrelationship between platelets and BUN in postmenopausal patients with coronary heart disease: findings of the NHANES from 2003 to 2016.

OBJECTIVE: During menopause, women are more likely to develop coronary heart disease (CHD) due to the significant changes in body metabolism brought on by the loss of estrogen. The purpose of this study was to investigate the independent association between platelet parameters and blood urea nitrogen (BUN) in postmenopausal patients with coronary artery disease in order to clarify the function performed by platelet parameters and BUN in thrombosis. PATIENTS AND METHODS: We took information from the NHANES between 2003 and 2016. Platelet count (PC), mean platelet volume (MPV), and PC/MPV were the independent variables, BUN was the dependent variable, and age, race, marital status, body mass index (BMI), inflammation indicators, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were the covariates. RESULTS: BUN decreased with increasing PC in postmenopausal heart disease patients after controlling for other factors. When PC/MPV was less than 30.5, there was a strong negative correlation with BUN. In addition, there was a strong positive correlation with BUN when MPV was less than 9.3 fL. CONCLUSIONS: The findings of this study will contribute to a better understanding of the mechanisms underlying thrombosis in postmenopausal women with CHD and offer fresh perspectives on how to create novel antithrombotic medications for an aging population.

Monaspin B, a Novel Cyclohexyl-furan from Cocultivation of Monascus purpureus and Aspergillus oryzae, Exhibits Potent Antileukemic Activity.

Natural products are a rich resource for the discovery of innovative drugs. Microbial cocultivation enables discovery of novel natural products through tandem enzymatic catalysis between different fungi. In this study, Monascus purpureus, as a food fermentation strain capable of producing abundant natural products, was chosen as an example of a cocultivation pair strain. Cocultivation screening revealed that M. purpureus and Aspergillus oryzae led to the production of two novel cyclohexyl-furans, Monaspins A and B. Optimization of the cocultivation mode and media enhanced the production of Monaspins A and B to 1.2 and 0.8 mg/L, respectively. Monaspins A and B were structurally elucidated by HR-ESI-MS and NMR. Furthermore, Monaspin B displayed potent antiproliferative activity against the leukemic HL-60 cell line by inducing apoptosis, with a half-maximal inhibitory concentration (IC50) of 160 nM. Moreover, in a mouse leukemia model, Monaspin B exhibited a promising in vivo antileukemic effect by reducing white blood cell, lymphocyte, and neutrophil counts. Collectively, these results indicate that Monaspin B is a promising candidate agent for leukemia therapy.

Inhibition of astroglial hemichannels ameliorates infrasonic noise induced short-term learning and memory impairment.

As a kind of environmental noise, infrasonic noise has negative effects on various human organs. To date, research has shown that infrasound impairs cognitive function, especially the ability for learning and memory. Previously, we demonstrated that impaired learning and memory induced by infrasound was closely related with glia activation; however, the underlying mechanisms remain unclear. Connexin 43 hemichannels (Cx43 HCs), which are mainly expressed in hippocampal astrocytes, are activated under pathological conditions, lending support to the hypothesis that Cx43 HCs might function in the impaired learning and memory induced by infrasound. This study revealed that that blocking hippocampal Cx43 HCs or downregulating hippocampal Cx43 expression significantly alleviated impaired learning and memory induced by infrasound. We also observed that infrasound exposure led to the abundant release of glutamate and ATP through Cx43 HCs. In addition, the abundant release of glutamate and ATP depended on proinflammatory cytokines. Our finds suggested that the enhanced release of ATP and glutamate by astroglial Cx43 HCs may be involved in the learning and memory deficits caused by infrasound exposure.

Protein Z and Protein Z-dependent protease inhibitor in patients with acute ischemic stroke: A prospective mechanistic study.

OBJECTIVES: Protein Z (PZ) /Protein Z-dependent protease inhibitor (ZPI) (PZ/ZPI) system is a new anticoagulant system discovered in recent years, which plays an important role in many diseases. We aimed to compare the plasma PZ/ZPI levels of acute ischemic stroke (AIS) patients and non-stroke control participants and the role of PZ/ZPI in the development of stroke was preliminarily analyzed. MATERIALS AND METHODS: Enzyme linked immunosorbent assay (ELISA) was used to detect and compare plasma PZ levels of 86 patients with acute AIS and 85 non-stroke control patients. Multivariable Logistic regression was used to analyze whether PZ was an independent risk factor for AIS. RESULTS: In the present study, plasma PZ is closely related to inflammatory response, coagulation process and platelet activation, and may participate in the development of AIS by inducing inflammatory responses and interfering with the coagulation process. CONCLUSIONS: Our results suggested that plasma PZ level is one of the independent risk factors of AIS, and plasma ZPI was closely related to coagulation and platelet parameter and may play a role in the coagulation process during AIS.

An overview of ultrasound-derived radiomics and deep learning in liver.

Over the past few years, developments in artificial intelligence (AI), especially in radiomics and deep learning, have enabled the extraction of pathophysiology-related information from varied medical imaging and are progressively transforming medical practice. AI applications are extending into domains previously thought to be accessible only to human experts. Recent research has demonstrated that ultrasound-derived radiomics and deep learning represent an enticing opportunity to benefit preoperative evaluation and prognostic monitoring of diffuse and focal liver disease. This review summarizes the application of radiomics and deep learning in ultrasound liver imaging, including identifying focal liver lesions and staging of liver fibrosis, as well as the evaluation of pathobiological properties of malignant tumors and the assessment of recurrence and prognosis. Besides, we identify important hurdles that must be overcome while also discussing the challenges and opportunities of radiomics and deep learning in clinical applications.

6-Methyl flavone inhibits Nogo-B expression and improves high fructose diet-induced liver injury in mice.

Excessive fructose consumption increases hepatic de novo lipogenesis, resulting in cellular stress, inflammation and liver injury. Nogo-B is a resident protein of the endoplasmic reticulum that regulates its structure and function. Hepatic Nogo-B is a key protein in glycolipid metabolism, and inhibition of Nogo-B has protective effects against metabolic syndrome, thus small molecules that inhibit Nogo-B have therapeutic benefits for glycolipid metabolism disorders. In this study we tested 14 flavones/isoflavones in hepatocytes using dual luciferase reporter system based on the Nogo-B transcriptional response system, and found that 6-methyl flavone (6-MF) exerted the strongest inhibition on Nogo-B expression in hepatocytes with an IC50 value of 15.85 µM. Administration of 6-MF (50 mg· kg-1 ·d-1, i.g. for 3 weeks) significantly improved insulin resistance along with ameliorated liver injury and hypertriglyceridemia in high fructose diet-fed mice. In HepG2 cells cultured in a media containing an FA-fructose mixture, 6-MF (15 µM) significantly inhibited lipid synthesis, oxidative stress and inflammatory responses. Furthermore, we revealed that 6-MF inhibited Nogo-B/ChREBP-mediated fatty acid synthesis and reduced lipid accumulation in hepatocytes by restoring cellular autophagy and promoting fatty acid oxidation via the AMPKα-mTOR pathway. Thus, 6-MF may serve as a potential Nogo-B inhibitor to treat metabolic syndrome caused by glycolipid metabolism dysregulation.

Novel flavonoid 1,3,4-oxadiazole derivatives ameliorate MPTP-induced Parkinson's disease via Nrf2/NF-κB signaling pathway.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a complex etiology. Neuroinflammation and oxidative stress are important factors driving the progression of PD. It has been reported that 1,3,4-oxadiazole and flavone derivatives have numerous biological functions, especially in the aspect of anti-inflammatory and antioxidant. Based on the strategy of pharmacodynamic combination, we introduced 1,3,4-oxadiazole moiety into the flavonoid backbone, designed and synthesized a series of novel flavonoid 1,3,4-oxadiazole derivatives. Further, we evaluated their toxicity, anti-inflammatory and antioxidant activities using BV2 microglia. Following a comprehensive analysis, compound F12 showed the best pharmacological activity. In vivo, we induced the classical PD animal model by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into C57/BL6J mice. Our results showed that compound F12 ameliorated MPTP-induced dysfunction in mice. Further, compound F12 reduced oxidative stress by promoting the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased the inflammatory response by inhibiting the nuclear translocation of nuclear factor-κB (NF-κB) in vivo and in vitro. Meanwhile, compound F12 inhibited the mitochondrial apoptotic pathway to rescue microglia inflammation-mediated loss of dopaminergic neurons. In conclusion, compound F12 reduced oxidative stress and inflammation and could be as a potential agent for PD treatment.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Fisetin treatment alleviates kidney injury in mice with diabetes-exacerbated atherosclerosis through inhibiting CD36/fibrosis pathway.

Diabetes-related vascular complications include diabetic cardiovascular diseases (CVD), diabetic nephropathy (DN) and diabetic retinopathy, etc. DN can promote the process of end-stage renal disease. On the other hand, atherosclerosis accelerates kidney damage. It is really an urge to explore the mechanisms of diabetes-exacerbated atherosclerosis as well as new agents for treatment of diabetes-exacerbated atherosclerosis and the complications. In this study we investigated the therapeutic effects of fisetin, a natural flavonoid from fruits and vegetables, on kidney injury caused by streptozotocin (STZ)-induced diabetic atherosclerosis in low density lipoprotein receptor deficient (LDLR-/-) mice. Diabetes was induced in LDLR-/- mice by injecting STZ, and the mice were fed high-fat diet (HFD) containing fisetin for 12 weeks. We found that fisetin treatment effectively attenuated diabetes-exacerbated atherosclerosis. Furthermore, we showed that fisetin treatment significantly ameliorated atherosclerosis-enhanced diabetic kidney injury, evidenced by regulating uric acid, urea and creatinine levels in urine and serum, and ameliorating morphological damages and fibrosis in the kidney. In addition, we found that the improvement of glomerular function by fisetin was mediated by reducing the production of reactive oxygen species (ROS), advanced glycosylation end products (AGEs) and inflammatory cytokines. Furthermore, fisetin treatment reduced accumulation of extracellular matrix (ECM) in the kidney by inhibiting the expression of vascular endothelial growth factor A (VEGFA), fibronectin and collagens, while enhancing matrix metalloproteinases 2 (MMP2) and MMP9, which was mainly mediated by inactivating transforming growth factor ß (TGFß)/SMAD family member 2/3 (Smad2/3) pathways. In both in vivo and in vitro experiments, we demonstrated that the therapeutic effects of fisetin on kidney fibrosis resulted from inhibiting CD36 expression. In conclusion, our results suggest that fisetin is a promising natural agent for the treatment of renal injury caused by diabetes and atherosclerosis. We reveal that fisetin is an inhibitor of CD36 for reducing the progression of kidney fibrosis, and fisetin-regulated CD36 may be a therapeutic target for the treatment of renal fibrosis.

Design, synthesis, and SAR study of novel flavone 1,2,4-oxadiazole derivatives with anti-inflammatory activities for the treatment of Parkinson's disease.

Inflammation is one of a major feature of Parkinson's disease (PD) which poses a threat to people's health in the world. It has been reported that antioxidation and anti-inflammation have significant effects on the treatment of PD. 1,2,4-oxadiazole and flavone derivatives have remarkable antioxidant and anti-inflammatory activities. In order to find highly effective drugs for PD treatment, based on the remarkable anti-inflammatory and antioxidant activities of the 1,2,4-oxadiazole pharmacophore and the flavonoid pharmacophore, we designed and synthesized a novel series of 3-methyl-8-(3-methyl-1,2,4-oxadiazol-5-yl)-2-phenyl-4H-chromen-4-one derivatives by pharmacophore combination, and evaluated their anti-inflammatory and antioxidation activities for PD treatment. Preliminary structure-activity relationship (SAR) analysis was conducted by their inhibitory activities against reactive oxygen species (ROS) and NO release in LPS-induced BV2 Microglia cells, and the optimal compound Flo8 exhibited the most potent anti-inflammatory and antioxidant activities. Both in vivo and in vitro results showed that Flo8 inhibited neuronal apoptosis by inhibiting inflammatory and apoptotic signaling pathways. In vivo studies also showed that the compound Flo8 ameliorated motor and behavioral deficits and increased serum dopamine levels in MPTP-induced PD model mice. Taken together, this study demonstrated the compound Flo8 could be a promising agent for the treatment of PD.

Four new diastereoisomeric neolignan glycosides from the root bark of Lycium chinense Miller. and their α-glucosidase inhibitory activity.

Four new diastereoisomeric neolignan glycosides (1-4) along with nine known lignan glycosides (5-13) were isolated from the root bark of Lycium chinense Mill. Their structures with absolute configurations were elucidated on the basis of NMR spectroscopy, ECD, Mo2(OAc)4-induced ECD spectra, enzymatic hydrolysis and acid hydrolysis. The isolated compounds were evaluated for their α-glucosidase inhibitory activity. Compounds 8 and 13 exhibited moderate inhibitory activities against α-glucosidase with IC50 values of 26.82 ± 2.71 and 43.14 ± 2.81 µg/mL.

Three-Dimensional Hounsfield Units Measurement of Pedicle Screw Trajectory for Predicating Screw Loosening in Lumbar Fusion Surgery.

Purpose: Dual-energy X-ray absorptiometry (DXA) is commonly used for evaluation of bone mineral density before spinal surgery, but frequently leads to overestimation in degenerative spinal diseases due to osteoproliferation factors. We introduce a novel method to compare the predictive ability of Hounsfield Units (HU) and DXA methods to predict screw loosening after lumbar interbody fusion surgery in degenerative spinal diseases by measuring HU of pedicle screw trajectory on computed tomography (CT) images preoperatively. Patients and Methods: This retrospective study was conducted on patients who underwent posterior lumbar fusion surgery for degenerative diseases. CT HUs measurement was performed using medical imaging software, including the cancellous region on cross-sections of the vertebral body and three-dimensional pedicle screw trajectory. Receiver operating characteristic (ROC) curve analyses were performed for the risk of pedicle screw loosening in association with the Hounsfield scale and preoperative BMD, and the area under the curve (AUC) and the cutoff values were calculated. Results: A total of 90 patients were enrolled and were divided into loosening (n = 33, 36.7%) and non-loosening groups (n = 57, 63.3%). No significant differences in age, gender, length of fixation and preoperative BMD were found between both groups. The loosening group showed lower CT HU values in the vertebral body and screw trajectory than the non-loosening group. Screw trajectory HU (ST-HU) exhibited a higher AUC value than vertebral body HU (B-HU). The cutoff values of B-HU and ST-HU were 160 and 110 HUs, respectively. Conclusion: Three-dimensional pedicle screw trajectory HU values yields a stronger predictive value than vertebral body HU values and BMD and may provide more guidance for surgery. The risk of screw loosening is significantly increased at ST-HU <110 or B-HU <160 at L5 segment.