A Study of the Effects of Motor Experience on Neuromuscular Control Strategies During Sprint Starts.

Much of the current research on sprint start has attempted to analyze the biomechanical characteristics of elite athletes to provide guidance on the training of sprint technique, with less attention paid to the effects of motor experience gained from long-term training on neuromuscular control characteristics. The present study attempted to investigate the effect of motor experience on the modular organization of the neuromuscular system during starting, based on he clarification of the characteristics of muscle synergies during starting. It was found that exercise experience did not promote an increase in the number of synergies but rather a more focused timing of the activation of each synergy, allowing athletes to quickly complete the postural transition from crouching to running during the starting.

EMPT: a sparsity Transformer for EEG-based motor imagery recognition.

Introduction: Transformer network is widely emphasized and studied relying on its excellent performance. The self-attention mechanism finds a good solution for feature coding among multiple channels of electroencephalography (EEG) signals. However, using the self-attention mechanism to construct models on EEG data suffers from the problem of the large amount of data required and the complexity of the algorithm. Methods: We propose a Transformer neural network combined with the addition of Mixture of Experts (MoE) layer and ProbSparse Self-attention mechanism for decoding the time-frequency-spatial domain features from motor imagery (MI) EEG of spinal cord injury patients. The model is named as EEG MoE-Prob-Transformer (EMPT). The common spatial pattern and the modified s-transform method are employed for achieving the time-frequency-spatial features, which are used as feature embeddings to input the improved transformer neural network for feature reconstruction, and then rely on the expert model in the MoE layer for sparsity mapping, and finally output the results through the fully connected layer. Results: EMPT achieves an accuracy of 95.24% on the MI EEG dataset for patients with spinal cord injury. EMPT has also achieved excellent results in comparative experiments with other state-of-the-art methods. Discussion: The MoE layer and ProbSparse Self-attention inside the EMPT are subjected to visualisation experiments. The experiments prove that sparsity can be introduced to the Transformer neural network by introducing MoE and kullback-leibler divergence attention pooling mechanism, thereby enhancing its applicability on EEG datasets. A novel deep learning approach is presented for decoding EEG data based on MI.

The anti-non-small cell lung cancer effect of Diosbulbin B: Targeting YY1 induced cell cycle arrest and apoptosis.

BACKGROUND: Toxic components frequently exhibit unique characteristics and activities, offering ample opportunities for the advancement of anti-cancer medications. As the main hepatotoxic component of Dioscorea bulbifera L. (DB), Diosbulbin B (DIOB) has been widely studied for its anti-tumor activity at nontoxic doses. However, the effectiveness and mechanism of DIOB against non-small cell lung cancer (NSCLC) remains unclear. PURPOSE: To evaluate the anti-NSCLC activity of DIOB and to elucidate the specific mechanism of action. METHOD: The effect of DIOB on NSCLCL in vitro was evaluated through CCK8, colony formation, and flow cytometry. The in vivo efficacy and safety of DIOB in treating NSCLC were assessed using various techniques, including HE staining, tunel staining, immunohistochemistry, and biochemical index detection. To understand the underlying mechanism, cell transfection, western blotting, molecular docking, cellular thermal shift assay (CESTA), and surface plasmon resonance (SPR) were employed for investigation. RESULTS: DIOB effectively hindered the progression of NSCLC both in vitro and in vivo settings at a no-observed-adverse-effect concentration (NOAEC) and a safe dosage. Specifically, DIOB induced significant G0/G1 phase arrest and apoptosis in A549, PC-9, and H1299 cells, while also notably inhibiting the growth of subcutaneous tumors in nude mice. Mechanistically, DIOB could directly interact with oncogene Yin Yang 1 (YY1) and inhibit its expression. The reduction in YY1 resulted in the triggering of the tumor suppressor P53, which induced cell cycle arrest and apoptosis in NSCLC cells by inhibiting the expression of Cyclin A2, B2, CDK1, CDK2, CDK4, BCL-2, and inducing the expression of BAX. In NSCLC cells, the induction of G0/G1 phase arrest and apoptosis by DIOB was effectively reversed when YY1 was overexpressed or P53 was knocked down. Importantly, we observed that DIOB exerted the same effect by directly influencing the expression of YY1-regulated c-Myc and BIM, particularly in the absence of P53. CONCLUSION: For the inaugural investigation, this research unveiled the anti-NSCLC impact of DIOB, alongside its fundamental mechanism. DIOB has demonstrated potential as a treatment agent for NSCLC due to its impressive efficacy in countering NSCLC.

Synthesis of C-N Axially Chiral N-Arylbenzo[g]indoles via a Central-to-Axial Chirality Conversion Strategy.

Gold-catalyzed cascade cyclization of diynes for the synthesis of previously unexplored C-N axially chiral N-arylbenzo[g]indoles was described. The transformation was achieved via a central-to-axial chirality conversion strategy. The chiral conversion exhibited high efficiency. Besides single C-N chiral axis, N-arylbenzo[g]indoles bearing both C-N and C-C chiral axes were also afforded. The title compound derived monophosphine ligand was prepared and was evaluated in Pd-catalyzed asymmetric allylic substitutions, showing excellent chiral induction ability.

Advance in Hippophae rhamnoides polysaccharides: Extraction, structural characteristics, pharmacological activity, structure-activity relationship and application.

Hippophae rhamnoides (Sea buckthorn) is an excellent medicinal and edible plant owing to its high nutritional and health-promoting properties. As an important bioactive component, H. rhamnoides polysaccharides (HRPs) have aroused wide attention due to their various pharmacological activities, including hepatoprotective, immuno-modulatory, anti-inflammatory, anti-oxidant, anti-tumor, hypoglycemic, anti-obesity, and so on. Nevertheless, the development and utilization of HRP-derived functional food and medicines are constrained to a lack of comprehensive understanding of the structure-activity relationship, application, and safety of HRPs. This review systematically summarizes the advancements on the extraction, purification, structural characteristics, pharmacological activities and mechanisms of HRPs. The structure-activity relationship, safety evaluation, application, as well as the shortcomings of current research and promising prospects are also highlighted. This article aims to offer a comprehensive understanding of HRPs and lay a groundwork for future research and utilization of HRPs as multifunctional biomaterials and therapeutic agents.

Wnt/ß-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target.

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and one of the leading causes of cancer-related deaths worldwide. The Wnt/ß-Catenin signaling pathway is a highly conserved pathway involved in several biological processes, including the improper regulation that leads to the tumorigenesis and progression of cancer. New studies have found that abnormal activation of the Wnt/ß-Catenin signaling pathway is a major cause of HCC tumorigenesis, progression, and resistance to therapy. New perspectives and approaches to treating HCC will arise from understanding this pathway. This article offers a thorough analysis of the Wnt/ß-Catenin signaling pathway's function and its therapeutic implications in HCC.

Preventive Effect of the Total Polyphenols from Nymphaea candida on Sepsis-Induced Acute Lung Injury in Mice via Gut Microbiota and NLRP3, TLR-4/NF-κB Pathway.

This study aimed to investigate the preventive effects of the total polyphenols from Nymphaea candida (NCTP) on LPS-induced septic acute lung injury (ALI) in mice and its mechanisms. NCTP could significantly ameliorate LPS-induced lung tissue pathological injury in mice as well as lung wet/dry ratio and MPO activities (p < 0.05). NCTP could significantly decrease the blood leukocyte, neutrophil, monocyte, basophil, and eosinophil amounts and LPS contents in ALI mice compared with the model group (p < 0.05), improving lymphocyte amounts (p < 0.05). Moreover, compared with the model group, NCTP could decrease lung tissue TNF-α, IL-6, and IL-1ß levels (p < 0.05) and downregulate the protein expression of TLR4, MyD88, TRAF6, IKKß, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB p65, NLRP3, ASC, and Caspase1 in lung tissues (p < 0.05). Furthermore, NCTP could inhibit ileum histopathological injuries, restoring the ileum tight junctions by increasing the expression of ZO-1 and occludin. Simultaneously, NCTP could reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Clostridiales and Lachnospiraceae, and enhance the content of SCFAs (acetic acid, propionic acid, and butyric acid) in feces. These results suggested that NCTP has preventive effects on septic ALI, and its mechanism is related to the regulation of gut microbiota, SCFA metabolism, and the TLR-4/NF-κB and NLRP3 pathways.

Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

Recent advances in drug delivery of celastrol for enhancing efficiency and reducing the toxicity.

Celastrol is a quinone methyl triterpenoid monomeric ingredient extracted from the root of Tripterygium wilfordii. Celastrol shows potential pharmacological activities in various diseases, which include inflammatory, obesity, cancer, and bacterial diseases. However, the application prospect of celastrol is largely limited by its low bioavailability, poor water solubility, and undesired off-target cytotoxicity. To address these problems, a number of drug delivery methods and technologies have been reported to enhance the efficiency and reduce the toxicity of celastrol. We classified the current drug delivery technologies into two parts. The direct chemical modification includes nucleic acid aptamer-celastrol conjugate, nucleic acid aptamer-dendrimer-celastrol conjugate, and glucolipid-celastrol conjugate. The indirect modification includes dendrimers, polymers, albumins, and vesicular carriers. The current technologies can covalently bond or encapsulate celastrol, which improves its selectivity. Here, we present a review that focalizes the recent advances of drug delivery strategies in enhancing the efficiency and reducing the toxicity of celastrol.

[Expression and diagnostic value of growth differentiation factor 15 in patients with septic cardiomyopathy].

OBJECTIVE: To explore the expression of growth differentiation factor 15 (GDF15) in patients with septic cardiomyopathy and its value in the diagnosis of septic cardiomyopathy. METHODS: A observational study was conducted. Fifty patients with septic cardiomyopathy admitted to Shanxi Bethune Hospital from May 2022 to March 2023 were selected as the experimental group. Forty-six patients with acute coronary syndrome (ACS) in the same period were selected as the case control group. Forty-nine healthy adults were selected as the healthy control group, who underwent physical examination in the physical examination center during the same period. The demographic data and clinical indicators of the subjects were recorded, and the serum GDF15 level was detected by double sandwich enzyme-linked immunosorbent assay (ELISA). And the 28-day outcome of patients with septic cardiomyopathy was followed up, and they were divided into survival group and death group. The serum GDF15 level of subjects in each group and its correlation with clinical indicators were analyzed and compared. Binary Logistic regression was used to analyze the risk factors of septic cardiomyopathy. Receiver operator characteristic curve (ROC curve) was used to evaluate the value of GDF15 in the diagnosis of septic cardiomyopathy. RESULTS: The serum GDF15 level of experimental group was significantly higher than that in the case control group and healthy control group [ng/L: 314.14 (221.96, 469.56) vs. 39.08 (26.27, 76.85), 6.39 (3.35, 14.42), both P < 0.01]. Correlation analysis showed that serum GDF15 level in patients with septic cardiomyopathy were correlated with cardiac troponin I (cTnI, r = 0.295, P = 0.038), brain natriuretic peptide (BNP, r = 0.464, P = 0.009), sequential organ failure assessment (SOFA, r = 0.363, P = 0.010) and acute physiology and chronic health evaluation II (APACHE II, r = 0.316, P = 0.025). However, there was no significant correlation with white blood cell count, neutrophil count, lymphocyte count, procalcitonin, C-reactive protein, lactic acid, albumin and other clinical indicators (r values were 0.086, 0.123, -0.051, 0.055, 0.119, 0.199, -0.234, all P > 0.05). Serum GDF15 level, SOFA score and APACHE II score in the death group (30 cases) were significantly higher than those in the survival group [20 cases; GDF15 (ng/L): 382.93±159.61 vs. 289.66±158.46, SOFA: 10.00 (7.00, 12.00) vs. 6.00 (5.00, 9.50), APACHE II: 21.70±6.07 vs. 14.85±7.57, all P < 0.05]. Binary Logistic regression analysis showed that serum GDF15 was an independent risk factor for the onset of septic cardiomyopathy [odds ratio (OR) = 1.062, 95% confidence interval (95%CI) was 1.011-1.115, P = 0.016]. ROC curve showed that the area under the curve (AUC) of GDF15 for predicting septic cardiomyopathy was 0.971, the specificity was 100%, and the sensitivity was 90.3%. CONCLUSIONS: The serum GDF15 level of patients with septic cardiomyopathy is significantly increased, and GDF15 may be used as an effective biomarker for the early diagnosis of septic cardiomyopathy.

Deep Learning Model for Prediction of Bronchopulmonary Dysplasia in Preterm Infants Using Chest Radiographs.

Bronchopulmonary dysplasia (BPD) is common in preterm infants and may result in pulmonary vascular disease, compromising lung function. This study aimed to employ artificial intelligence (AI) techniques to help physicians accurately diagnose BPD in preterm infants in a timely and efficient manner. This retrospective study involves two datasets: a lung region segmentation dataset comprising 1491 chest radiographs of infants, and a BPD prediction dataset comprising 1021 chest radiographs of preterm infants. Transfer learning of a pre-trained machine learning model was employed for lung region segmentation and image fusion for BPD prediction to enhance the performance of the AI model. The lung segmentation model uses transfer learning to achieve a dice score of 0.960 for preterm infants with ≤ 168 h postnatal age. The BPD prediction model exhibited superior diagnostic performance compared to that of experts and demonstrated consistent performance for chest radiographs obtained at ≤ 24 h postnatal age, and those obtained at 25 to 168 h postnatal age. This study is the first to use deep learning on preterm chest radiographs for lung segmentation to develop a BPD prediction model with an early detection time of less than 24 h. Additionally, this study compared the model's performance according to both NICHD and Jensen criteria for BPD. Results demonstrate that the AI model surpasses the diagnostic accuracy of experts in predicting lung development in preterm infants.

tert-Butyl Nitrite-Induced Radical Nitrile Oxidation Cycloaddition: Synthesis of Isoxazole/Isoxazoline-Fused Benzo 6/7/8-membered Oxacyclic Ketones.

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3-H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N-O fragment donor.

Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia.

In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KITmut ) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KITmut transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KITmut (D816V/H/Y or N822K) were tested for KITmut transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KITmut were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KITmut -high (KIT_H) group and the KITmut -low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (p = 0.0040 and 0.021, respectively) and Course 2 consolidation (p = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KITmut and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patient with KIT mutation.

The African swine fever virus MGF300-4L protein is associated with viral pathogenicity by promoting the autophagic degradation of IKKß and increasing the stability of IκBα.

African swine fever (ASF) is a highly contagious, often fatal viral disease caused by African swine fever virus (ASFV), which imposes a substantial economic burden on the global pig industry. When screening for the virus replication-regulating genes in the left variable region of the ASFV genome, we observed a notable reduction in ASFV replication following the deletion of the MGF300-4L gene. However, the role of MGF300-4L in ASFV infection remains unexplored. In this study, we found that MGF300-4L could effectively inhibit the production of proinflammatory cytokines IL-1ß and TNF-α, which are regulated by the NF-κB signaling pathway. Mechanistically, we demonstrated that MGF300-4L interacts with IKKß and promotes its lysosomal degradation via the chaperone-mediated autophagy. Meanwhile, the interaction between MGF300-4L and IκBα competitively inhibits the binding of the E3 ligase ß-TrCP to IκBα, thereby inhibiting the ubiquitination-dependent degradation of IκBα. Remarkably, although ASFV encodes other inhibitors of NF-κB, the MGF300-4L gene-deleted ASFV (Del4L) showed reduced virulence in pigs, indicating that MGF300-4L plays a critical role in ASFV pathogenicity. Importantly, the attenuation of Del4L was associated with a significant increase in the production of IL-1ß and TNF-α early in the infection of pigs. Our findings provide insights into the functions of MGF300-4L in ASFV pathogenicity, suggesting that MGF300-4L could be a promising target for developing novel strategies and live attenuated vaccines against ASF.

Deep Learning-Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease.

Alzheimer's disease (AD) is a pressing concern in neurodegenerative research. To address the challenges in AD drug development, especially those targeting Aß, this study uses deep learning and a pharmacological approach to elucidate the potential of pyrroloquinoline quinone (PQQ) as a neuroprotective agent for AD. Using deep learning for a comprehensive molecular dataset, blood-brain barrier (BBB) permeability is predicted and the anti-inflammatory and antioxidative properties of compounds are evaluated. PQQ, identified in the Mediterranean-DASH intervention for a diet that delays neurodegeneration, shows notable BBB permeability and low toxicity. In vivo tests conducted on an Aß1₋42-induced AD mouse model verify the effectiveness of PQQ in reducing cognitive deficits. PQQ modulates genes vital for synapse and anti-neuronal death, reduces reactive oxygen species production, and influences the SIRT1 and CREB pathways, suggesting key molecular mechanisms underlying its neuroprotective effects. This study can serve as a basis for future studies on integrating deep learning with pharmacological research and drug discovery.

The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy.

Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPRmt) take part in various aging-related diseases. Our research intents to explore the role and underlying mechanism of UPRmt in IVDD. Nucleus pulposus (NP) cells were exposed to IL-1ß and nicotinamide riboside (NR) served as UPRmt inducer to treat NP cells. Detection of ATP, NAD + and NADH were used to determine the function of mitochondria. MRI, Safranin O-fast green and Immunohistochemical examination were used to determine the degree of IVDD in vivo. In this study, we discovered that UPRmt was increased markedly in the NP cells of human IVDD tissues than in healthy controls. In vitro, UPRmt and mitophagy levels were promoted in NP cells treated with IL-1ß. Upregulation of UPRmt by NR and Atf5 overexpression inhibited NP cell apoptosis and further improved mitophagy. Silencing of Pink1 reversed the protective effects of NR and inhibited mitophagy induced by the UPRmt. In vivo, NR might attenuate the degree of IDD by activating the UPRmt in rats. In summary, the UPRmt was involved in IVDD by regulating Pink1-induced mitophagy. Mitophagy induced by the UPRmt might be a latent treated target for IVDD.

Fabrication of a novel HKUST-1/CoFe2O4/g-C3N4 electrode for the electrochemical detection of ciprofloxacin in physiological samples.

In this work, a novel HKUST-1/CoFe2O4/g-C3N4 electrode was successfully prepared via the hydrothermal method and the high-temperature calcination method, which can be applied as an electrochemical sensor for the precise detection of ciprofloxacin (CIP) in physiological samples. The novel electrode was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR), and its electrochemical performance was further evaluated via the cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. The results demonstrated that the HKUST-1/CoFe2O4/g-C3N4 electrode exhibited an optimal linear range of 0.05-180 µmol L-1 for the CIP detection, which demonstrated a low limit of detection (LOD) of 0.0026 µmol L-1 and a low limit of quantitation (LOQ) of 0.0087 µmol L-1, respectively. Additionally, the novel semiconductor sensors exhibited exceptional selectivity, stability and repeatability in the determination of CIP. The recovery rate of CIP was found to range from 98.00% to 104.00% in serum, with the relative standard deviations (RSD) below 2.62% (n = 5), while the recovery rate of CIP was found to range from 96.00% to 105.00%, with the RSD less than 3.23% (n = 5) in urine. The current study extends to the application of the semiconductor-based electrochemical sensors and offers a new approach for the clinical pharmaceutical analysis to ensure medication safety, which could provide valuable insights into the potential of semiconductor sensors for future clinical applications.

Extraction, purification, structural characteristics, bioactivity and potential applications of polysaccharides from Avena sativa L.: A review.

Avena sativa L. (A. sativa L.), commonly known as oat, is a significant cereal grain crop with excellent edible and medicinal value. Oat polysaccharides (OPs), the major bioactive components of A. sativa L., have received considerable attention due to their beneficial bioactivities. However, the isolation and purification methods of OPs lack innovation, and the structure-activity relationship remains unexplored. This review emphatically summarized recent progress in the extraction and purification methods, structural characteristics, biological activities, structure-to-function associations and the potential application status of OPs. Different materials and isolation methods can result in the differences in the structure and bioactivity of OPs. OPs are mainly composed of various monosaccharide constituents, including glucose, arabinose and mannose, along with galactose, xylose and rhamnose in different molar ratios and types of glycosidic bonds. OPs exhibited a broad molecular weight distribution, ranging from 1.34 × 105 Da to 4.1 × 106 Da. Moreover, structure-activity relationships demonstrated that the monosaccharide composition, molecular weight, linkage types, and chemical modifications are closely related to their multiple bioactivities, including immunomodulatory activity, antioxidant effect, anti-inflammatory activity, antitumor effects etc. This work can provide comprehensive knowledge, update information and promising directions for future exploitation and application of OPs as therapeutic agents and multifunctional food additives.

Myocardin reverses insulin resistance and ameliorates cardiomyopathy by increasing IRS-1 expression in a murine model of lipodystrophy caused by adipose deficiency of vacuolar H+-ATPase V0d1 subunit.

Aim: Adipose tissue (AT) dysfunction that occurs in both obesity and lipodystrophy is associated with the development of cardiomyopathy. However, it is unclear how dysfunctional AT induces cardiomyopathy due to limited animal models available. We have identified vacuolar H+-ATPase subunit Vod1, encoded by Atp6v0d1, as a master regulator of adipogenesis, and adipose-specific deletion of Atp6v0d1 (Atp6v0d1AKO) in mice caused generalized lipodystrophy and spontaneous cardiomyopathy. Using this unique animal model, we explore the mechanism(s) underlying lipodystrophy-related cardiomyopathy. Methods and Results: Atp6v0d1AKO mice developed cardiac hypertrophy at 12 weeks, and progressed to heart failure at 28 weeks. The Atp6v0d1AKO mouse hearts exhibited excessive lipid accumulation and altered lipid and glucose metabolism, which are typical for obesity- and diabetes-related cardiomyopathy. The Atp6v0d1AKO mice developed cardiac insulin resistance evidenced by decreased IRS-1/2 expression in hearts. Meanwhile, the expression of forkhead box O1 (FoxO1), a transcription factor which plays critical roles in regulating cardiac lipid and glucose metabolism, was increased. RNA-seq data and molecular biological assays demonstrated reduced expression of myocardin, a transcription coactivator, in Atp6v0d1AKO mouse hearts. RNA interference (RNAi), luciferase reporter and ChIP-qPCR assays revealed the critical role of myocardin in regulating IRS-1 transcription through the CArG-like element in IRS-1 promoter. Reducing IRS-1 expression with RNAi increased FoxO1 expression, while increasing IRS-1 expression reversed myocardin downregulation-induced FoxO1 upregulation in cardiomyocytes. In vivo, restoring myocardin expression specifically in Atp6v0d1AKO cardiomyocytes increased IRS-1, but decreased FoxO1 expression. As a result, the abnormal expressions of metabolic genes in Atp6v0d1AKO hearts were reversed, and cardiac dysfunctions were ameliorated. Myocardin expression was also reduced in high fat diet-induced diabetic cardiomyopathy and palmitic acid-treated cardiomyocytes. Moreover, increasing systemic insulin resistance with rosiglitazone restored cardiac myocardin expression and improved cardiac functions in Atp6v0d1AKO mice. Conclusion: Atp6v0d1AKO mice are a novel animal model for studying lipodystrophy- or metabolic dysfunction-related cardiomyopathy. Moreover, myocardin serves as a key regulator of cardiac insulin sensitivity and metabolic homeostasis, highlighting myocardin as a potential therapeutic target for treating lipodystrophy- and diabetes-related cardiomyopathy.

Serum proteomics identifies novel diagnostic biomarkers for asthma in preschool children.

Background: Asthma is characterized by airway hyperresponsiveness, reversible airway obstruction, and chronic airway inflammation. It is the most common chronic disease in childhood. However, the diagnosis of childhood asthma remains challenging, and there is an urgent need to develop new diagnostic methods. Methods: To identify biomarkers of asthma in children, we adopted the Orbitrap-based data-independent acquisition (DIA) mass spectrometry proteomics method to analyze the serum proteomic signatures of children with acute asthma and convalescent children. Results: We identified 747 proteins in 46 serum samples and 50 differentially expressed proteins (DEPs) that distinguished between asthmatic and healthy children. Next, functional enrichment analysis of the DEPs was conducted, it was indicated that the DEPs were significantly enriched in immune-related and function terms and pathways. Furthermore, we performed statistical analysis and identified MMP14, ABHD12B, PCYOX1, LTBP1, CFHR4, APOA1, IGHG4, ANG and IGFALS proteins as the diagnostic biomarker candidates. Ultimately, a promising asthma diagnostic model for preschool children based on IGFALS was built and evaluated. The area under the curve (AUC) of the IGFALS model was 0.959. Conclusions: In this study, the DIA proteome strategy was used and the largest number of proteins of asthmatic children serum proteomics was identified. The proteomics results showed that the DEPs play the central role of the inflammation-immune mechanism in asthma pathogenesis, suggesting that these proteins may be used in asthma diagnosis, prognosis, or therapy, and suggested biomarkers for asthma of preschool children. In conclusion, our results provide insight into the pathophysiology of asthma. We believe that the diagnostic model will facilitate clinical decision-making regarding asthma in preschool children.