Knockdown of LncRNA Lcn2-204 alleviates sepsis-induced myocardial injury by regulation of iron overload and ferroptosis.

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.

Experimental demonstration of wavefront reconstruction and correction techniques for variable targets based on distorted grating and deep learning.

This research presents a practical approach for wavefront reconstruction and correction adaptable to variable targets, with the aim of constructing a high-precision, general extended target adaptive optical system. Firstly, we delve into the detailed design of a crucial component, the distorted grating, simplifying the optical system implementation while circumventing potential issues in traditional phase difference-based collection methods. Subsequently, normalized fine features (NFFs) and structure focus features (SFFs) which both are independent of the imaging target but corresponded precisely to the wavefront aberration are proposed. The two features provide a more accurate and robust characterization of the wavefront aberrations. Then, a Noise-to-Denoised Generative Adversarial Network (N2D-GAN) is employed for denoising real images. And a lightweight network, Attention Mechanism-based Efficient Network (AM-EffNet), is applied to achieve efficient and high-precision mapping between features and wavefronts. A prototype of object-independent adaptive optics system is demonstrated by experimental setup, and the effectiveness of this method in wavefront reconstruction for different imaging targets has been verified. This research holds significant relevance for engineering applications of adaptive optics, providing robust support for addressing challenges within practical systems.

Multi-line-of-sight Hartmann-Shack wavefront sensing based on image segmentation and K-means sorting.

Multi-line-of-sight wavefront sensing, crucial for next-generation astronomy and laser applications, often increases system complexity by adding sensors. This research introduces, to the best of our knowledge, a novel method for multi-line-of-sight Hartmann-Shack wavefront sensing by using a single sensor, addressing challenges in centroid estimation and classification under atmospheric turbulence. This method contrasts with existing techniques that rely on multiple sensors, thereby reducing system complexity. Innovations include combining edge detection and peak extraction for precise centroid calculation, improved k-means clustering for robust centroid classification, and a centroid filling algorithm for subapertures with light loss. The method's effectiveness was confirmed through simulations for a five-line-of-sight system and experimental setup for two-line and three-line-of-sight systems, demonstrating its potential in real atmospheric aberration correction conditions. Experimental findings indicate that, when implemented in a closed-loop configuration, the method significantly reduces wavefront residuals from 1 λ to 0.1 λ under authentic atmospheric turbulence conditions. Correspondingly, the quality of the far-field spot is enhanced by a factor of 2 to 4. These outcomes collectively highlight the method's robust capability in enhancing optical system performance in environments characterized by genuine atmospheric turbulence.

Effect of NLRP3 gene knockdown on pyroptosis and ferroptosis in diabetic cardiomyopathy injury.

Diabetic cardiomyopathy (DCM) is a chronic disease caused by diabetes mellitus, which is recognized as a worldwide challenging disease. This study aimed to investigate the role and the potential mechanism of knocking down the NACHT-, LRR- and PYD domains-containing protein 3 (NLRP3), an inflammasome associated with onset and progression of various diseases, on high glucose or diabetes -induced cardiac cells pyroptosis and ferroptosis, two regulated non-necrosis cell death modalities discovered recent years. In the present study, both in vivo and in vitro studies were conducted simultaneously. Diabetic rats were induced by 55 mg/kg intraperitoneal injection of streptozotocin (STZ). Following the intraperitoneal injection of MCC950 (10 mg/kg), On the other hand, the DCM model in H9C2 cardiac cells was simulated with 35 mmol/L glucose and a short hairpin RNA vector of NLRP3 were transfected to cells. The results showed that in vivo study, myocardial fibers were loosely arranged and showed inflammatory cell infiltration, mitochondrial cristae were broken and the GSDMD-NT expression was found notably increased in the DM group, while the protein expressions of xCT and GPX4 was significantly decreased, both of which were reversed by MCC950. High glucose reduced the cell viability and ATP level in vitro, accompanied by an increase in LDH release. All of the above indicators were reversed after NLRP3 knockdown compared with the HG treated alone. Moreover, the protein expressions of pyroptosis- and ferroptosis-related fators were significantly decreased or increased, consistent with the results shown by immunofluorescence. Furthermore, the protective effects of NLRP3 knockdown against HG were reversed following the mtROS agonist rotenone (ROT) treatment. In conclusion, inhibition of NLRP3 suppressed DM-induced myocardial injury. Promotion of mitochondrial ROS abolished the protective effect of knockdown NLRP3, and induced the happening of pyroptosis and ferroptosis. These findings may present a novel therapeutic underlying mechanism for clinical diabetes-induced myocardial injury treatment.

Object-independent wavefront sensing method based on an unsupervised learning model for overcoming aberrations in optical systems.

This Letter introduces the idea of unsupervised learning into object-independent wavefront sensing for the first time, to the best of our knowledge, which can achieve fast phase recovery of arbitrary objects without labels. First, a fine feature extraction method which only depends on the wavefront aberrations is proposed. Then, a lightweight neural network and an optical feature system are combined to form an unsupervised learning model, and the neural network is promoted to be well trained by reversely outputting fine features. Simulation results prove that the proposed method can effectively overcome the aberrations (static or variable) existing in the optical system and achieve wavefront sensing of different objects with high precision and efficiency.

Distortion correction for particle image velocimetry using multiple-input deep convolutional neural network and Hartmann-Shack sensing.

Aberrations degrade the accuracy of quantitative, imaging-based measurements, like particle image velocimetry (PIV). Adaptive optical elements can in principle correct the wavefront distortions, but are limited by their technical specifications. Here we propose an actuator-free correction based on a multiple-input deep convolutional neural network which uses an additional input from a wavefront sensor to correct time-varying distortions. It is applied for imaging flow velocimetry to conduct measurements through a fluctuating air-water phase boundary. Dataset for neural network is generated by an experimental setup with a deformable mirror. Correction performance of trained model is estimated in terms of image quality, which is improved significantly, and flow measurement results, where the errors induced by the distortion from fluctuating phase boundary can be corrected by 82 %. The technique has the potential to replace classical closed-loop adaptive optical systems where the performance of the actuators is not sufficient.

Anisodamine alleviates lipopolysaccharide-induced pancreatic acinar cell injury through NLRP3 inflammasome and NF-κB signaling pathway.

Purpose: Anisodamine (An) has anti-inflammatory effects, but its role in acute pancreatitis is still unknown. This study aimed to explore the action mechanism of An pretreatment in lipopolysaccharide (LPS)-induced pancreatic acinar cells, hoping to provide a research basis for the disease treatment.Materials and methods: Pancreatic acinar cells were pretreated with An at different concentrations and then induced by LPS. The viability and apoptosis of the treated cells were measured by Cell Counting Kit-8 and flow cytometry. The releases of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-18 were measured by enzyme-linked immunosorbent assay. The expressions of thioredoxin-interacting protein (TXNIP), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), NOD-like receptor protein 3 (NLRP3), Caspase-1, p65, and inhibitor of kappa B alpha (IκBα) in the treated cells were detected by Western blot and quantitative real-time polymerase chain reaction assay.Results: LPS promoted apoptosis of pancreatic acinar cells, suppressed cell viability, increased TNF-α, IL-1ß, and IL-18 releases and the expression levels of TXNIP, ASC, NLRP3, Caspase-1, p-p65, and p-IκBα, however, such effects of LPS could be alleviated by An pretreatment with the strongest effect when the concentration of An was set at 100 µg/mL. Moreover, overexpressed NLRP3 aggravated the effects of LPS in pancreatic acinar cells, which could be reversed by pretreatment of 100 µg/mL An.Conclusion: An pretreatment attenuated LPS-induced apoptosis and inflammatory response of pancreatic acinar cells through suppressing NLRP3 and inactivating NF-κB signaling pathway, thus, it could be explored as a potential therapy for treating acute pancreatitis.

LncRNA TUG1 reverses LPS-induced cell apoptosis and inflammation of macrophage via targeting MiR-221-3p/SPRED2 axis.

This study aimed to identify the role of lncRNA TUG1 with miR-221-3p on mice with lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Animal model was established, and lung tissue histopathologic status and permeability were detected by hematoxylin-eosin (HE) or Evans blue dye assay respectively. Levels of inflammation cytokines, lncRNA TUG1, miR-221-3p, sprouty related EVH1 domain-containing 2 (SPRED2), and phosphorylated (p)-ERK1/2 were determined by ELISA, qRT-PCR or Western blot. Pulmonary impairment and apoptosis were examined by flow cytometry. We observed that LPS up-regulated levels of tumor necrosis factor-α (TNF-α), Interleukin-1ß (1L-1ß), and ERK1/2 phosphorylation, and reduced SPRED2 levels, which were rescued by overexpressed lncRNA TUG1. StarBase and dual-luciferase reporter assay verified that miR-221-3p was targeted by lncRNA TUG1. MiR-221-3p could reverse the effect of lncRNA TUG1 on cell apoptosis, levels of TNF-α, IL-1ß, SPRED2, and p-ERK1/2. Therefore, overexpressed lncRNA TUG1 attenuated LPS-induced pulmonary impairment in ARDS mice via regulating miR-221-3p/SPRED2 axis.

CAROTID ARTERY ULTRASOUND FOR ASSESSING FLUID RESPONSIVENESS IN PATIENTS UNDERGOING MECHANICAL VENTILATION WITH LOW TIDAL VOLUME AND PRESERVED SPONTANEOUS BREATHING.

ABSTRACT: Objective : This study aimed to investigate whether changes in carotid artery corrected flow time (ΔFTc bolus ) and carotid artery peak flow velocity respiratory variation (Δ V peak bolus ) induced by the fluid challenge could reliably predict fluid responsiveness in mechanically ventilated patients with a tidal volume < 8 mL/kg Predicted Body Weight while preserving spontaneous breathing. Methods : Carotid artery corrected flow time, Δ V peak, and hemodynamic data were measured before and after administration of 250 mL crystalloids. Fluid responsiveness was defined as a 10% or more increase in stroke volume index as assessed by noninvasive cardiac output monitoring after the fluid challenge. Results : A total of 43 patients with acute circulatory failure were enrolled in this study. Forty-three patients underwent a total of 60 fluid challenges. The ΔFTc bolus and Δ V peak bolus showed a significant difference between the fluid responsiveness positive group (n = 35) and the fluid responsiveness negative group (n = 25). Spearman correlation test showed that ΔFTc bolus and Δ V peak bolus with the relative increase in stroke volume index after fluid expansion ( r = 0.5296, P < 0.0001; r = 0.3175, P = 0.0135). Multiple logistic regression analysis demonstrated that ΔFTc bolus and Δ V peak bolus were significantly correlated with fluid responsiveness in patients with acute circulatory failure. The areas under the receiver operating characteristic curves of ΔFTc bolus and Δ V peak bolus for predicting fluid responsiveness were 0.935 and 0.750, respectively. The optimal cutoff values of ΔFTc bolus and Δ V peak bolus were 0.725 (sensitivity = 97.1%, specificity = 84%) and 4.21% (sensitivity = 65.7%, specificity = 80%), respectively. Conclusion : In mechanically ventilated patients with a tidal volume < 8 mL/kg while preserving spontaneous breathing, ΔFTc bolus and Δ V peak bolus could predict fluid responsiveness. The predictive performance of ΔFTc bolus was superior to Δ V peak bolus .

Sodium butyrate administration improves intestinal development of suckling lambs.

This study was conducted to investigate the effects of sodium butyrate (SB) supplementation on growth performance, intestinal barrier functions, and intestinal bacterial communities in sucking lambs. Forty lambs of 7 d old, with an average body weight (BW) of 4.46 ±â€…0.45 kg, were allocated into the control (CON) or SB group, with each group having five replicate pens (n = 5). Lambs were orally administered SB at 1.8 mL/kg BW in the SB group or the same volume of saline in the CON group. Treatments were administered from 7 to 35 d of age, when one lamb from each replicate was slaughtered to obtain intestinal tissues and contents. The results showed that supplementation with SB tended to increase the BW (P = 0.079) and the starter intake (P = 0.089) of lambs at 35 d of age. The average daily gain of lambs in the SB group was significantly greater than that in the CON group (P < 0.05). The villus height of jejunum in the SB group was markedly higher (P < 0.05) than that in the CON group. In ileum, lambs in the SB group had lower (P < 0.05) crypt depth and greater (P < 0.05) villus-to-crypt ratio than those in the CON group. Compared with the CON group, the mRNA and protein expressions of Claudin-1 and Occludin were increased (P < 0.05) in the SB group. Supplementation with SB decreased the relative abundances of pathogenic bacteria, including Clostridia_UCG-014 (P = 0.094) and Romboutsia (P < 0.05), which were negatively associated with the intestinal barrier function genes (P < 0.05). The relative abundance of Succiniclasticum (P < 0.05) was higher in the SB group, and it was positively correlated with the ratio of villi height to crypt depth in the jejunum (P < 0.05). Compared with the CON group, the function "Metabolism of Cofactors and Vitamins" was increased in the SB group lambs (P < 0.05). In conclusion, SB orally administration during suckling period could improve the small intestine development and growth performance of lambs by inhibiting the harmful bacteria (Clostridia_UCG-014, Romboutsia) colonization, and enhancing intestinal barrier functions.

It is well known that butyrate and its derivatives have various benefits for the rumen development of ruminants, whereas its effects on the small intestine in preweaned lambs have received little attention. Therefore, the present study investigated the effects of sodium butyrate (SB) supplementation on growth performance, intestinal barrier functions, and intestinal bacterial communities in sucking lambs. The results indicated that SB dietary treatment has beneficial effects on the small intestine development and growth performance of suckling lambs.

Revealing quality chemicals of Tetrastigma hemsleyanum roots in different geographical origins using untargeted metabolomics and random-forest based spectrum-effect analysis.

Tetrastigma hemsleyanum root is a popular functional food in China, and the price varies based on the origin of the product. The link between the origin, metabolic profile, and bioactivity of T. hemsleyanum must be investigated. This study compares the metabolic profiles of 254 samples collected from eight different areas with 49 potential key chemical markers using plant metabolomics. The metabolic pathways of the five critical flavonoid metabolites were annotated and enriched using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Moreover, a random forest model aiding the spectrum-effect relationship analysis was developed for the first time indicating catechin and darendoside B as potential quality markers of antioxidant activity. The findings of this study provide a comprehensive understanding of the chemical composition and bioactive compounds of T. hemsleyanum as well as valuable information on the evaluation of the quality of various samples and products in the market.

Calcium activated potassium channel and protein kinase C participate in the cardiac protection of remote post conditioning.

The present study was designed to investigate the roles of Ca(2+) activated K(+) channel (KCa) and protein kinase C (PKC) in the protective mechanisms of remote ischemic post conditioning (RPostC) when rat heart was subjected to ischemia/reperfusion (I/R) injury in vivo. Rat heart was subjected to regional ischemia for 45 min and reperfusion for 180 min in vivo to mimic I/R injury. RPostC was induced by 5 min right femoral artery occlusion followed by 5 min reperfusion for 3 cycles (totally 30 min) after 15 min of cardiac ischemia. Delayed remote ischemic post conditioning (delayed RPostC) was induced after 10 min of cardiac reperfusion. The hemodynamic parameters including mean arterial blood pressure and heart rate (HR) were recorded, and lactate dehydrogenase (LDH) release in plasma and infarct size were determined, and arrhythmia scores were calculated. In contrast to I/R, RPostC reduced infarct size and LDH release during reperfusion, the occurrence of arrhythmia was decreased, but no changes in delayed RPostC. The specific inhibitor of KCa iberiotoxin and PKC inhibitor chelerythrine both attenuated the role of RPostC. The findings indicated that RPostC had a protective effect on myocardial ischemia/reperfusion injury. Opening of KCa and activating of PKC may be involved in the mechanisms of RPostC.

Construction of a ceRNA network of regulated ferroptosis in doxorubicin-induced myocardial injury.

Background: Ferroptosis and long-noncoding RNAs (lncRNAs) play crucial roles in doxorubicin (DOX)-induced myocardial injury (DIMI). Nevertheless, there is no research to construct competing endogenous RNAs (ceRNAs) network between lncRNAs and ferroptosis-related key gene. So our research was designed to screen ferroptosis-related genes from differentially expressed mRNAs in DIMI and construct lncRNAs regulated ferroptosis-related key gene ceRNAs network. Methods: The male mice were injected with DOX intraperitoneally to induce myocardial injury, myocardial injury was evaluated by hematoxylin and eosin (HE) staining, and ferroptosis-related protein-glutathione peroxidase 4 (GPx4) protein expression was detected. The differentially expressed lncRNAs and mRNAs were detected by microarray, and the ferroptosis-related genes were screened to construct a protein-protein associations (PPA) network, the highest maximal clique centrality (MCC) score gene were identified by Cytoscape software, miRNAs bound to key genes and lncRNAs bound to miRNAs were predicted; then, the obtained lncRNAs were intersected with differentially expressed lncRNAs detected by microarray. Finally, the lncRNA/miRNA/mRNA ceRNA network of the highest MCC score gene regulating ferroptosis in DIMI was constructed. The expressions of the key components in ceRNA network were detected by qRT-PCR. Results: Compared with the control group, in the DOX group, myocardial enzymes and HE staining showed that myocardium structure was changed, and GPx4 protein expression was decreased. The differentially expressed 10,265 lncRNAs and 6,610 mRNAs in the DOX group were detected via microarray. Among them, 114 ferroptosis-related genes were obtained to construct PPA networks, and Becn1 was identified as the key gene. Finally, the ceRNA network including Becn1, three miRNAs and four lncRNAs was constructed by predicting data of the Starbase database. The relative expressions of these components in ceRNA net were up-regulated and consistent with microarray results. Conclusions: Based on the microarray detection results and bioinformatics analysis, we screened ferroptosis-related gene Becn1 and constructed the lncRNA/miRNA/mRNA ceRNA network of regulated ferroptosis in DIMI.

[Mitochondrial aldehyde dehydrogenase 2 alleviates septic liver injury by inhibiting ferroptosis in mouse model].

OBJECTIVE: To observe the ferroptosis triggered by in different pathways during cecal ligation and puncture (CLP)-induced liver injury in septic mice, and to investigate whether mitochondrial aldehyde dehydrogenase 2 (ALDH2) can alleviate sepsis-induced liver injury by inhibiting ferroptosis. METHODS: Sixty 8-week-old male C57BL/6J mice were randomly divided into sham operation group (Sham group), CLP group, ferroptosis inhibitor ferrostain-1 (Fer-1) group, ALDH2-specific agonist Alda-1 group, iron chelator deferasirox Fe3+ chelate (DXZ) group and dimethyl sulfoxide (DMSO) group, with 10 mice in each group. The septic liver injury was induced by CLP in mice model. In the Sham group, only laparotomy was performed without ligation and puncture of the cecum. 10 mL/kg 5% DMSO, 5 mg/kg Fer-1, 50 mg/kg DXZ and 10 mg/kg Alda-1 were injected intraperitoneally 1 hour before CLP in the DMSO, Fer-1, DXZ and Alda-1 groups respectively. At 24 hours after operation, eyeball blood and liver tissue were collected from anesthetized mice. The hepatic structure and inflammatory infiltration were observed by hematoxylin-eosin (HE) staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum, the levels of hepatic malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected. Western blotting was used to detect the protein expressions of ALDH2, ferroptosis-related proteins glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1) and transferrin receptor 1 (TFR1) in liver tissue. RESULTS: Compared with Sham group, the mice in CLP group showed varying degrees of congestion, disorganized hepatocyte arrangement, inflammatory cell infiltration at 24 hours after operation. Compared with the CLP group, the mice in the Fer-1 group, DXZ group and Alda-1 group liver morphology, liver injury and inflammatory cell infiltration was improved. Compared with Sham group, the serum levels of ALT and AST, the contents of MDA and ROS, and the expression of TFR1 protein in CLP group were significantly increased, while the activity of SOD and the expressions of ALDH2, GPX4 and FSP1 protein in CLP group were significantly decreased. Compared with CLP group, serum ALT and AST levels in Fer-1, DXZ and Alda-1 groups were significantly decreased [ALT (U/L): 45.76±10.81, 37.30±2.98, 36.40±12.75 vs. 73.06±12.20, AST (U/L): 61.57±2.69, 52.41±6.92, 56.05±8.29 vs. 81.59±5.46, all P < 0.05], and the contents of MDA, ROS and TFR1 protein expression in liver tissue were significantly decreased [MDA (µmol/L): 0.60±0.10, 0.57±0.18, 0.83±0.39 vs. 1.61±0.30, ROS (fluorescence intensity): 270.34±9.64, 276.02±62.33, 262.05±18.55 vs. 455.38±36.07, TFR1/GAPDH: 0.90±0.04, 1.01±0.09, 0.55±0.08 vs. 1.18±0.06, all P < 0.05], and the SOD activity and ALDH2, GPX4 and FSP1 protein expressions in liver tissue were significantly increased [SOD (kU/g): 88.77±8.20, 88.37±4.47, 93.43±7.24 vs. 50.27±3.57, ALDH2/GAPDH: 1.10±0.15, 1.02±0.07, 1.14±0.07 vs. 0.70±0.04, GPX4/GAPDH: 1.02±0.12, 0.99±0.08, 1.05±0.19 vs. 0.71±0.10, FSP1/GAPDH: 1.06±0.24, 1.02±0.08, 0.93±0.09 vs. 0.66±0.03, all P < 0.05]. There was no significant difference in the parameters between DMSO group and CLP group. CONCLUSIONS: Both GPX4 and FSP1 mediated ferroptosis are involved in liver injury in septic mice. Activation of ALDH2 and inhibition of ferroptosis can alleviatehepatic injury. ALDH2 may play a protective role by regulating FSP1 and GPX4 mediated ferroptosis.

A new efficient multi-stage strategy based on the complementarity of ultrafiltration and high resolution biochromatogram for the screening of skin-whitening candidates from the fibrous root of Bletilla striata.

Ultrafiltration-high performance liquid chromatography (UF-HPLC) and high resolution biochromatogram (HR-biochromatogram), have been proven to be effective methods for the rapid discovery of enzyme inhibitors in natural medicines. In attempt to conquer false-positive and false- negative screening results, a new multi-stage strategy based on the complementarity of UF-HPLC and HR-biochromatogram has been proposed for the fast screening of tyrosinase inhibitory components using the fibrous root of Bletilla striata as a case study. For the first two stages, UF- HPLC and HR-biochromatogram, were applied individually for the screening of high-affinity tyrosinase ligands and tyrosinase inhibitors. After that, the inconsistent results, which yielded two potential active fractions, indicated a third stage screening. Thus, a "strengthen" biochromatogram was established to microfractionate the concentrated extract and further evaluate the tyrosinase inhibitors. The complementarity nature of two different screening methods was firstly explored to distinguish tyrosinase inhibitors from the fibrous root of Bletilla striata. As a result, four compounds were screened, isolated and characterized as new potent tyrosinase inhibitors. The screening results were verified by tyrosinase inhibition assays, melanin inhibitory in zebrafish and molecular docking. All compounds possessed much higher tyrosinase inhibition than α-arbutin, especially, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol demonstrated stronger tyrosinase inhibition than kojic acid. This study presented a new screening strategy which had a great potential in rapidly and efficiently exploring tyrosinase inhibitors in complex mixtures. Moreover, it is the first time to reveal the skin-whitening nature of the fibrous root of B. striata, which indicating the promising prospect in the full utilization of B. striata plant.

Improved low-dose positron emission tomography image reconstruction using deep learned prior.

Positron emission tomography (PET) is a promising medical imaging technology that provides non-invasive and quantitative measurement of biochemical process in the human bodies. PET image reconstruction is challenging due to the ill-poseness of the inverse problem. With lower statistics caused by the limited detected photons, low-dose PET imaging leads to noisy reconstructed images with much quality degradation. Recently, deep neural networks (DNN) have been widely used in computer vision tasks and attracted growing interests in medical imaging. In this paper, we proposed a maximuma posteriori(MAP) reconstruction algorithm incorporating a convolutional neural network (CNN) representation in the formation of the prior. Rather than using the CNN in post-processing, we embedded the neural network in the reconstruction framework for image representation. Using the simulated data, we first quantitatively evaluated our proposed method in terms of the noise-bias tradeoff, and compared with the filtered maximum likelihood (ML), the conventional MAP, and the CNN post-processing methods. In addition to the simulation experiments, the proposed method was further quantitatively validated on the acquired patient brain and body data with the tradeoff between noise and contrast. The results demonstrated that the proposed CNN-MAP method improved noise-bias tradeoff compared with the filtered ML, the conventional MAP, and the CNN post-processing methods in the simulation study. For the patient study, the CNN-MAP method achieved better noise-contrast tradeoff over the other three methods. The quantitative enhancements indicate the potential value of the proposed CNN-MAP method in low-dose PET imaging.

Heat shock protein 70 expression protects against sepsis-associated cardiomyopathy by inhibiting autophagy.

OBJECTIVES: Increasing evidence suggests that heat shock protein 70 (Hsp70) has a protective effect in sepsis-induced cardiomyopathy; however, the protective mechanism remains unclear. METHODS: Previous studies have also implicated autophagy in sepsis-induced cardiomyopathy. The aim of the current study was to reveal the protective mechanisms of Hsp70 in sepsis-induced cardiomyopathy using a cecal ligation and puncture (CLP) rat sepsis model. The roles of Hsp70 and autophagy in sepsis-induced cardiomyopathy were investigated by pretreating rats with the Hsp70 inhibitor quercetin or the autophagy inhibitor 3-methyladenine (3-Ma) before CLP. We also investigated the protective mechanisms of Hsp70 and the relationship between Hsp70 and autophagy in vitro by stimulating H9c2 cells with lipopolysaccharide (LPS) to simulate sepsis. RESULTS: The result show that inhibition of Hsp70 promoted sepsis-induced death in rats, while inhibition of autophagy inhibited sepsis-induced death. These results suggested that both Hsp70 and autophagy were involved in sepsis-induced cardiomyopathy. Overexpression of Hsp70 in H9c2 myocardial cells in vitro suppressed LPS-induced apoptosis, while inhibition of autophagy with 3-Ma also decreased LPS-induced H9c2 cell apoptosis, suggesting that the protective effect of Hsp70 in sepsis-induced cardiomyopathy was related to autophagy regulation. CONCLUSION: Overall, these results suggested that Hsp70 protected against sepsis-induced cardiac impairment by attenuating sepsis-induced autophagy.

A subregion-based positron emission tomography/computed tomography (PET/CT) radiomics model for the classification of non-small cell lung cancer histopathological subtypes.

BACKGROUND: This study classifies lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) using subregion-based radiomics features extracted from positron emission tomography/computed tomography (PET/CT) images. METHODS: In this study, the standard 18F-fluorodeoxyglucose (FDG) PET/CT images of 150 patients with lung ADC and 100 patients with SCC were retrospectively collected from the PET Center of the First Affiliated Hospital, College of Medicine, Zhejiang University. First, the 3D feature vector of each tumor voxel (whose basis is PET value, CT value, and CT local dominant orientation) was extracted. Using K-means individual clustering and population clustering, each tumor was divided into 4 subregions that reflect intratumoral regional heterogeneity. Next, based on each subregion, 385 radiomics features were extracted. Clinical features including age, gender, and smoking history were included. Thus, there were a total of 1,543 features extracted from PET/CT images and clinical reports. Statistical tests were then used to eliminate irrelevant and redundant features, and the recursive feature elimination (RFE) algorithm was used to select the best feature subset to classify SCC and ADC. Finally, 7 types of classifiers were tested to achieve the optimized model for the classification: support vector machine (SVM) with linear kernel, SVM with radial basis function kernel (SVM-RBF), random forest, logistic regression, Gaussian process classifier, linear discriminant analysis, and the AdaBoost classifier. Furthermore, 5-fold cross-validation was applied to obtain the sensitivity, specificity, accuracy, and area under the curve (AUC) for performance evaluation. RESULTS: Our model exhibited the best performance with the subregion radiomics features and SVM-RBF classifier, with a 5-fold cross-validation sensitivity, specificity, accuracy, and AUC of 0.8538, 0.8758, 0.8623, and 0.9155, respectively. The interquartile range feature from subregion 2 of CT and the gender feature from the clinical reports are the 2 optimized features that achieved the highest comprehensive score. CONCLUSIONS: Our proposed model showed that SCC and ADC could be classified successfully using PET/CT images, which could be a promising tool to assist radiologists or medical physicists during diagnosis. The subregion-based method illustrated that non-small cell lung cancer (NSCLC) depicts intratumoral regional heterogeneity on both CT and PET images. By defining these heterogeneities through a subregion-based method, the diagnostic performance was improved. The 3D feature vector (whose basis is PET value, CT value, and CT local dominant orientation) showed superiority in reflecting NSCLC intratumoral regional heterogeneity.

Corrigendum to "ALDH2 Overexpression Alleviates High Glucose-Induced Cardiotoxicity by Inhibiting NLRP3 Inflammasome Activation".

[This corrects the article DOI: 10.1155/2019/4857921.].

Inhibitory effect of acetyl-11-keto-ß-boswellic acid on titanium particle-induced bone loss by abrogating osteoclast formation and downregulating the ERK signaling pathway.

Wear debris-induced osteoclast accumulation around implants plays a crucial role during the progression of periprosthetic osteolysis (PPO). We have confirmed that acetyl-11-keto-ß-boswellic acid (AKBA) promotes bone formation and protects against particle-induced bone destruction in vivo. However, the effect of AKBA on titanium-induced bone resorption is unknown. In this study, we detected the inhibitory effect of AKBA on titanium-induced bone erosion in vivo and used RAW264.7 cells and bone marrow macrophages (BMMs) to investigate the effect and underlying mechanism of AKBA on the differentiation and resorptive function of osteoclasts. Our findings revealed that AKBA inhibited particle-induced bone loss and osteoclast formation in vivo. Furthermore, AKBA exerted inhibitory effects on RANKL-induced osteoclastogenesis, osteoclastic ring-dependent resorption and the expression of osteoclast marker genes via the ERK signaling pathway in vitro. Our data further established the protective effect of AKBA on titanium particle-induced bone erosion from a new perspective of bone erosion prevention, strongly confirming that AKBA is an appropriate agent for protection against PPO.