Identification of metabolic biomarkers in idiopathic pulmonary arterial hypertension using targeted metabolomics and bioinformatics analysis.

Pulmonary arterial hypertension (PAH) is a life-threatening disease with a poor prognosis, and metabolic abnormalities play a critical role in its development. This study used metabolomics, machine learning algorithms and bioinformatics to screen for potential metabolic biomarkers associated with the diagnosis of PAH. In this study, plasma samples were collected from 17 patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and 20 healthy controls. Plasma metabolomic profiling was performed by high-performance liquid chromatography-mass spectrometry. Gene profiles of PAH patients were obtained from the GEO database. Key differentially expressed metabolites (DEMs) and metabolism-related genes were subsequently identified using machine learning algorithms. Twenty differential plasma metabolites associated with IPAH were identified (VIP score > 1 and p < 0 0.05), and enrichment analysis revealed the arginine biosynthesis pathway as the most altered pathway. Using machine learning models, including least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine (SVM), we extracted key metabolites that correlated with clinical phenotypes. Our results suggested that five metabolites, kynurenine, homoserine, tryptophan, AMP, and spermine, are potential biomarkers for IPAH. Bioinformatics analysis also identified 3 metabolism-related genes, MAPK6, SLC7A11 and CDC42BPA, that are strongly correlated with pulmonary hypertension, demonstrating strong predictive power and clinical relevance. Our findings revealed some key genes associated with metabolism in PH, and provided crucial information about complex metabolic reprogramming signals and may lead to the identification of useful metabolic biomarkers for the diagnosis of PAH.

Variational Transformer: A Framework Beyond the Tradeoff Between Accuracy and Diversity for Image Captioning.

Accuracy and diversity represent two critical quantifiable performance metrics in the generation of natural and semantically accurate captions. While efforts are made to enhance one of them, the other suffers due to the inherent conflicting and complex relationship between them. In this study, we demonstrate that the suboptimal accuracy levels derived from human annotations are unsuitable for machine-generated captions. To boost diversity while maintaining high accuracy, we propose an innovative variational transformer (VaT) framework. By integrating "invisible information prior (IIP)" and "auto-selectable Gaussian mixture model (AGMM)", we enable its encoder to learn precise linguistic information and object relationships in various scenes, thus ensuring high accuracy. By incorporating the "range-median reward (RMR)" baseline into it, we preserve a wider range of candidates with higher rewards during the reinforcement-learning-based training process, thereby guaranteeing outstanding diversity. Experimental results indicate that our method achieves simultaneous improvements in accuracy and diversity by up to 1.1% and 4.8%, respectively, over the state-of-the-art. Furthermore, our approach demonstrates its performance that is the closest to human annotations in semantic retrieval, with its score of 50.3 versus the human score of 50.6. Thus, the method can be readily put into industrial use.

Surgical complications after immediate implant-based breast reconstruction for breast cancer in women over 65 years.

BACKGROUND: While immediate breast reconstruction rates in breast cancer are increasing, they remain low in women over 65 years old. The aim was to investigate surgical outcomes in women older than 65 years receiving implant-based immediate breast reconstruction. METHOD: The population-based Stockholm Breast Reconstruction Database includes all adult women with breast cancer receiving an implant-based immediate breast reconstruction in Stockholm, Sweden, 2005-2015. Primary outcomes within 30 days from immediate breast reconstruction were: infection requiring antibiotics and reoperation on. Implant removal was a secondary outcome. Women more than 65 years were compared with younger age groups. Chi-square tests and multivariable logistic regression were applied for the primary outcomes, and Kaplan-Meier analysis for the secondary outcome. RESULTS: Among 1749 cases of immediate breast reconstruction, 140 (8.0%) were in women more than 65 years. Median follow-up was 74 months (1-198). Postoperative infection was not more common in women older than 65 years old (22 of 140, 15.7%) than in women under 65 years old (303 of 1609, 18.8%; P = 0.221). Reoperation on was more frequent in women older than 65 years than in other age groups (more than 65: 8.6%; 50-64: 6.5%; 40-49: 3.5%; less than 40: 1.6%; P < 0.001), however, age older than 65 years was not an independent risk factor in the multivariable analysis (OR 1.00, 95% c.i. 0.44 to 2.28). Overall, 6-year probability of implant removal was 11.4%, (8.1% due to complications and 3.3% due to patient preference). There was no statistically significant difference between age groups for either reason (P = 0.085 and P = 0.794 respectively). CONCLUSION: Older age alone was not associated with worse surgical outcomes after implant-based immediate breast reconstruction in highly selected patients older than 65 years when compared with their younger counterparts.

Frostbite injuries related to recreational nitrous oxide use: incidence, management, and complications in a Swedish case series.

Background: Nitrous oxide (N2O) use in recreational settings has been increasing in Sweden and Europe and consequently, the related injuries are also increasing. We aimed to investigate the incidence, management, and surgical outcomes of frostbite injury (FI) related to N2O use. Material and Method: All patients in a 22-month period from 2021 to 2022 presenting with FI related to N2O abuse from 2 plastic surgery clinics (1 national burn center) were identified. Data regarding patient comorbidity, mechanism of injury, initial management, treatment, and follow-up were investigated. Complications following surgery were categorized into minor (treated in outpatient setting) and major (requiring reoperation) complications. Results: In total, 9 patients were identified; among them, 5 patients provided consent and were included in the study. Direct contact with the gas canister was the most common injury mechanism (n = 4). All but 1 patient contracted full-thickness injuries, and these 4 patients later required surgery. The medial thigh was the most common area of injury. Outpatient clinic visits were common (mean 4.8 visits/patient). Surgical complications were common and all operated patients were diagnosed with minor complications and half of them with major complications (wound dehiscence and scar contracture). Conclusion: Frostbite injuries arising from recreational N2O use are complex and often require surgical intervention that may lead to complications. With the increasing incidence of N2O abuse in Sweden, further research is crucial to address this emerging public health concerns and optimize treatment strategies for these distinctive injuries.

Identification of TFRC as a biomarker for pulmonary arterial hypertension based on bioinformatics and experimental verification.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there is a paucity of studies that reflect the available biomarkers from separate gene expression profiles in PAH. METHODS: The GSE131793 and GSE113439 datasets were combined for subsequent analyses, and batch effects were removed. Bioinformatic analysis was then performed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and a protein-protein interaction (PPI) network analysis were then used to further filter the hub genes. Functional enrichment analysis of the intersection genes was performed using Gene Ontology (GO), Disease Ontology (DO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA). The expression level and diagnostic value of hub gene expression in pulmonary arterial hypertension (PAH) patients were also analyzed in the validation datasets GSE53408 and GSE22356. In addition, target gene expression was validated in the lungs of a monocrotaline (MCT)-induced pulmonary hypertension (PH) rat model and in the serum of PAH patients. RESULTS: A total of 914 differentially expressed genes (DEGs) were identified, with 722 upregulated and 192 downregulated genes. The key module relevant to PAH was selected using WGCNA. By combining the DEGs and the key module of WGCNA, 807 genes were selected. Furthermore, protein-protein interaction (PPI) network analysis identified HSP90AA1, CD8A, HIF1A, CXCL8, EPRS1, POLR2B, TFRC, and PTGS2 as hub genes. The GSE53408 and GSE22356 datasets were used to evaluate the expression of TFRC, which also showed robust diagnostic value. According to GSEA enrichment analysis, PAH-relevant biological functions and pathways were enriched in patients with high TFRC levels. Furthermore, TFRC expression was found to be upregulated in the lung tissues of our experimental PH rat model compared to those of the controls, and the same conclusion was reached in the serum of the PAH patients. CONCLUSIONS: According to our bioinformatics analysis, the observed increase of TFRC in the lung tissue of human PAH patients, as indicated by transcriptomic data, is consistent with the alterations observed in PAH patients and rodent models. These data suggest that TFRC may serve as a potential biomarker for PAH.

Catechol compounds as dual-targeting agents for fish protection against Ichthyophthirius multifiliis infections.

Aquaculture is one of the fastest growing sectors in global food production, recognized as a significant contributor to poverty alleviation, food security, and income generation. However, the frequent occurrence of diseases caused by pathogen infections result in reduced yields and economic losses, posing a substantial constraint to the sustainable development of aquaculture. Here, our study identified that four catechol compounds, quercetin, luteolin, caffeic acid, and chlorogenic acid, exhibited potent antiparasitic effects against Ichthyophthirius multifiliis in both, in vitro and in vivo. The parasite is recognized as one of the most pathogenic to fish worldwide. Using a combination of in silico methods, the dipeptidyl peptidase (DPP) was identified as a critical target for catechol compounds. The two hydroxyl radicals of the catechol group were essential for its binding to and interacting with the DPP protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that catechol compounds disrupt pathways associated with the metabolism and growth of I. multifiliis, thereby exerting antiparasitic effects. Furthermore, these compounds attenuated the expression of proinflammatory cytokines in vivo in fish and promoted macrophage polarization toward M2 phenotype by inhibiting the STAT1 signaling pathway. The dual activity of catechol compounds, acting as both direct antiparasitic and anti-inflammatory agents in fish, offers a promising therapeutic approach for combating I. multifiliis infections in aquaculture.

Association of depression and sleep quality with frailty: a cross-sectional study in China.

Background: With the rapid growth of global aging, frailty has become a serious public health burden, affecting the life quality of older adults. Depressive symptoms (depression hereafter) and sleep quality are associated with frailty, but the pathways in which sleep quality and depression affect frailty remain unclear. Method: This cross-sectional study included 1866 community-dwelling older adults. Demographic characteristics and health-related data of them was collected, and we also assessed frailty, depression, and sleep quality. Descriptive statistics were carried out and ordinal logistic regression analysis was used to identify the factors correlated with frailty. Spearman correlation analysis and mediation analysis were employed to assess associations between sleep quality, depression and frailty. Two-sided p < 0.05 was considered as significant. Results: The results showed that 4.1% older adults were frail and 31.0% were pre-frail. Ordinal logistic regression showed that age, consumptions of vegetables, exercise, sleep quality, depression, number of chronic diseases, chronic pain, and self-rated health were correlated with frailty. Spearman correlation analysis revealed that frailty was associated with depression and sleep quality. There was a mediation effect that sleep quality was a significant and positive predictor of frailty (total effect = 0.0545, 95% boot CI = 0.0449-0.0641), and depression was a mediator between sleep quality and frailty (mediation effect = 60.4%). Conclusion: Depression and poor sleep quality may be early indicators of frailty in older adults. Improving the sleep quality and psychological state of older adults can improve frailty, which is beneficial for healthy aging.

Inclusion complex of quercetin with sulfobutylether ß-cyclodextrin: preparation, characterization, antioxidant and antibacterial activities and the inclusion mechanism.

Quercetin (QCT) has a variety of pharmacological effects, such as antioxidant, antibacterial, anticancer, anticardiovascular and antiaging effects. However, its poor water solubility, stability and bioavailability limit its applications. The special structure of cyclodextrins and their derivatives with a hydrophobic inner cavity and hydrophilic outer wall can load a variety of hydrophobic drugs of a suitable size and shape, thereby improving the stability and solubility of these molecules. In this study, an inclusion complex of quercetin and sulfobutylether-ß-cyclodextrin was prepared. It was characterized via FT-IR, UV, 1H NMR, XRD, DSC, and SEM analysis, which revealed the successful formation of the inclusion complex. In vitro biological activity estimations were carried out and the results indicated that the inclusion complex displayed higher antioxidative and antibacterial properties compared with free QCT. In addition, the mechanisms of inclusion were explored using 1H NMR analysis and docking calculations, thus providing a theoretical basis for obtaining an inclusion complex.

Sokotrasterol Sulfate Suppresses IFN-γ-Induced PD-L1 Expression by Inhibiting JAK Activity.

PD-1/PD-L1 monoclonal antibodies exhibit promising therapeutic effectiveness in multiple cancers. However, developing a simple and efficient non-antibody treatment strategy using the PD-1/PD-L1 signaling pathway still remains challenging. In this study, we developed a flow cytometry assay to screen bioactive compounds with PD-L1 inhibitory activity. A total of 409 marine natural products were screened, and sokotrasterol sulfate (SKS) was found to efficiently suppress the IFN-γ-induced PD-L1 expression. SKS sensitizes the tumor cells to antigen-specific T-cell killing in the T cell-tumor cell coculture system. Mechanistically, SKS directly targeted Janus kinase (JAK) to inhibit the downstream activation of signal transducer and activator of transcription (STAT) and the subsequent transcription of PDL1. Our findings highlight the immunological role of SKS that may act as a basis for a potential immunotherapeutic agent.

Evaluation of Treatment Patterns and Maintenance Dose Titration Among Patients With Crohn's Disease Initiating Biologics With 3 Years of Follow-Up.

Background: There is limited real-world evidence on treatment patterns of patients with Crohn's disease (CD) initiating biologics with an extensive follow-up period. This study describes persistence and dose titration among CD patients with 3 years of follow-up. Methods: This retrospective observational study was conducted using the STATinMED RWD Insights all-payer medical and pharmacy data. Adult patients with at least 1 CD medical claim and at least 1 medical/pharmacy claim for a biologic (adalimumab [ADA], certolizumab pegol (CZP), infliximab [IFX] and its biosimilar products [IFX-BS], ustekinumab [UST], and vedolizumab [VDZ]) between September 2016 and October 2018 were identified. Commercially insured patients with continuous capture for at least 12 months before and at least 36 months after biologics initiation were selected. Confirmed CD patients were included in the final cohort. Baseline patient characteristics and treatment patterns over the 3-year follow-up period were evaluated. Results were summarized using means and SD or counts and percentages. Results: A total of 2309 confirmed patients with CD were identified (847 [36.7%] IFX, 534 [23.1%] ADA, 486 [21.1%] VDZ, 394 [17.1%] UST, 85 [3.7%] CZP, and 72 [3.1%] IFX-BS). CZP and IFX-BS were excluded due to small sample sizes. Approximately half of CD patients were between ages 35 and 54. Patients on UST had a higher Charlson Comorbidity Index score. Common comorbidities (>10%) included anemia, anxiety, depression, and hypertension. Persistence over 3 years' follow-up was highest for UST (61.4%) patients, followed by VDZ (58.0% ), ADA (52.1% , and IFX (48.1%). The discontinuation rate without switch or restart was highest for ADA (37.3%), followed by UST (30.7%), IFX (28.1%), and VDZ (25.3%). Over the 3 years of follow-up, the dose titration rate was highest for IFX (76.5%) and lowest for UST (50.8%). In particular, UST had the lowest dose escalation rate (35.5%) and highest dose-reduction rate (16.5%). Conclusions: Patients with CD on UST had the highest persistence and lowest dose escalation across different biologic users over the 3-year follow-up period, possibly suggesting a better clinical response of UST. Future studies with longer follow-up adjusting for confounders are needed to better understand treatment patterns among biologics users.

Integrated control of braking-yaw-roll stability under steering-braking conditions.

Sharp steering-braking at a high speed exposes sport utility vehicles with high gravity centers and narrow wheel tracks to the risks of tire locking, sideslip and rollover. To avoid these risks and ensure braking safety, yaw stability and roll stability upon steering-braking, a braking-yaw-roll stability integrated control strategy was proposed, which consists of a supervisor, an upper and a lower controller for the front and rear axle independent drive electric vehicle. In the supervisor, a nonlinear vehicle predictive model was constructed and four control modes were proposed according to the vehicle status and rollover indexes. The weight coefficients between braking force, yaw stability and roll stability are determined dynamically by the control mode and output to the upper controller. The upper controller used a nonlinear model predictive control to determine the longitudinal braking force distribution of the four wheels. And in the lower controller, the regenerative braking torque and friction braking torque of each wheel were distributed. Finally, simulation verifications were carried out on the high and low adhesion roads. The results show that the control strategy proposed in this study can effectively prevent the vehicle from rollover while ensuring braking safety and yaw stability.

Improved antioxidant activity of rutin via lipase-mediated esterification with oleic acid.

BACKGROUND: Oxidation is a major problem for oils and fats, which can be mitigated by antioxidants. Rutin has excellent antioxidant activity, but its poor lipid solubility greatly limits its practical application. In this study, an efficient enzymatic synthesis route of lipophilic rutin ester was established using oleic acid as an acyl donor, and the antioxidant potential of rutin oleate was evaluated for the first time by proton (1 H) nuclear magnetic resonance (NMR) spectroscopy. RESULTS: The synthesized product was finally identified as rutin oleate by Fourier transform infrared, high-performance liquid chromatography-mass spectrometry, and 1 H, carbon-13, and DEPT-135 NMR analyses, and the acylation site was the 4‴-OH of the rhamnose group in the rutin molecule. The maximum conversion was over 93% after 48 h of reaction using Novozym 435 as catalyst under the best conditions among these tests. The conversion of rutin ester decreased with the increase of carbon chain length and the number of carbon-carbon double bonds of the fatty acid molecule. Most importantly, rutin oleate exhibited antioxidant capacity comparable to butylated hydroxytoluene and its counterparts (rutin and oleic acid) at low temperatures (60° C), but had a significant advantage at high temperatures (120° C). CONCLUSION: The antioxidant activity of rutin was significantly enhanced by lipase-mediated esterification with oleic acid. Therefore, rutin oleate could be further developed as a novel antioxidant for use in oil- and fat-based foods. © 2023 Society of Chemical Industry.

Constructing Sub 10 nm Scale Interfused TiO2/SiOx Bicontinuous Hybrid with Mutual-Stabilizing Effect for Lithium Storage.

TiO2 has been considered as a promising intercalation lithium-ion-battery (LIB) anode material owing to its robust cyclability. However, it suffers from low capacity. Herein, we construct a sub 10 nm scale interfused TiO2/SiOx hybrid with a bicontinuous structure, in which bridged TiO2 nanoparticles (over 80 wt %) are densely packed within a wormlike SiOx network, through the simple oxidation of MAX Ti3SiC2 ceramic. State-of-the-art in situ microscopy characterization unravels a "mutual-stabilizing" effect from the interfused TiO2/SiOx hybrid upon lithiation. That is to say, the two interpenetrated active components restrain the volume expansion of each other with the stress being relieved through abundant interfaces. Meanwhile, the stress generated from one phase functioned as the compressive force on the other phase and vice versa, offsetting the overall volume effect and synergistically reinforcing the structure integrity. Benefiting from the "mutual-stabilizing" effect, the TiO2/SiOx composite manifests a high and stable specific capacity (∼671 mAh g-1 after 580 cycles at 0.1 A g-1) with a low volume expansion of ∼14% even in an extended potential window of 0.01-3.0 V (vs Li+/Li). The concept of mutual-stabilizing effect, in principle, applies to a wide class of interfused bicontinuous hybrids, providing insight into the design of LIB anode materials with high capacity and longevity.

Long-term outcomes of implant-based immediate breast reconstruction with and without radiotherapy: a population-based study.

BACKGROUND: Radiotherapy (RT) is a risk factor for impaired outcomes after implant-based immediate breast reconstruction (IBR). Large studies including long-term follow-up are relatively scarce. The purpose of this analysis was to assess long-term effects of RT in implant-based IBR, distinguishing between implant removal because of postoperative complications versus patient preference. METHODS: This population-based cohort study included all patients with breast cancer who underwent implant-based IBR in Stockholm between 2005 and 2015. Data were collected through national registers and medical charts. The main endpoint was implant removal owing to postoperative complications (wound breakdown, infection, bleeding) or patient preference (dissatisfaction, pain, capsular contracture), with or without conversion to autologous reconstruction. RESULTS: Some 1749 implant-based IBRs in 1687 women were included. Median follow-up was 72 (range 1-198) months. Reconstructions were divided according to receipt of RT: No RT (n = 856, 48.9 per cent), adjuvant RT (n = 749, 42.8 per cent), and previous RT (n = 144, 8.2 per cent). Implant removal occurred after 266 reconstructions (15.2 per cent); 68 (7.9 per cent) in the no RT, 158 (21.1 per cent) in the adjuvant RT, and 40 (27.8 per cent) in the previous RT group. Implant removal was because of postoperative complications in 152 instances (57.1 per cent) and was most common in the first 3 years. This was especially observed in the previous RT group, where 15 of 23 implant removals occurred during the first 6 months. Implant removal owing to patient preference (114 of 266, 42.9 per cent) became more common with increasing follow-up. CONCLUSION: Implant removal after implant-based IBR is significantly associated with RT. The reason for implant removal shifts over time from postoperative complications to patient preference.

Irradiation of the chest wall after breast removal and implant placement (reconstruction) increases the risk of complications. These may lead to removal of the implant. Some women then choose a new breast reconstruction without an implant. The aim of this project was to find out how much irradiation affects complications after breast reconstruction using implants. This work used information on women who had a breast reconstruction with implants in Stockholm, Sweden, from 2005 to 2015. The main focus was on removal of the implant. This could be due to complications or patient preference. Implant removal could be with or without a new breast reconstruction. Of 1749 reconstructed breasts in 1687 women, 266 implants were removed. This was most often because of a complication, especially in the first years after surgery, but nearly as often due to patient wish. Implant removal owing to patient wish occurred later. Irradiation was a major factor increasing the risk of implant removal, together with, for example, smoking and obesity.

Phenolic composition and neuroprotective effects of the ethyl-acetate fraction from Inonotus sanghuang against H2O2-induced apoptotic cell death of primary cortical neuronal cells.

The study aimed to characterize phenolic compounds of the Inonotus sanghuang's ethyl-acetate fraction (EAF) and assess the neuroprotective effect of EAF using the H2O2-treated primary cortical neuronal cells (PCNC) model. Using HPLC-ECD, 5 phenolics were identified and quantified from EAF. H2O2-treated PCNC experiments in vitro showed that pretreatment with EAF increased the GSH-PX and SOD activities and reduced the NO, MDA, and Aß contents. Furthermore, EAF suppressed the production of IL-1ß, IFN-γ, IL-6, and TNF-α in H2O2-treated PCNC. Other mechanisms found that EAF reduced Bax, caspase 9, and caspase 3 expressions at the mRNA and protein levels while increasing Bcl-2 expression at the mRNA and protein levels. These results showed that EAF could serve as potential agents for anti-NDD. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01107-x.

A novel oppositional binary crow search algorithm with optimal machine learning based postpartum hemorrhage prediction model.

Postpartum hemorrhage (PPH) is an obstetric emergency instigated by excessive blood loss which occurs frequently after the delivery. The PPH can result in volume depletion, hypovolemic shock, and anemia. This is particular condition is considered a major cause of maternal deaths around the globe. Presently, physicians utilize visual examination for calculating blood and fluid loss during delivery. Since the classical methods depend on expert knowledge and are inaccurate, automated machine learning based PPH diagnosis models are essential. In regard to this aspect, this study introduces an efficient oppositional binary crow search algorithm (OBCSA) with an optimal stacked auto encoder (OSAE) model, called OBCSA-OSAE for PPH prediction. The goal of the proposed OBCSA-OSAE technique is to detect and classify the presence or absence of PPH. The OBCSA-OSAE technique involves the design of OBCSA based feature selection (FS) methods to elect an optimum feature subset. Additionally, the OSAE based classification model is developed to include an effective parameter adjustment process utilizing Equilibrium Optimizer (EO). The performance validation of the OBCSA-OSAE technique is performed using the benchmark dataset. The experimental values pointed out the benefits of the OBCSA-OSAE approach in recent methods.

Long noncoding RNA TDRG1 aggravates doxorubicin-induced cardiomyopathy by binding with miR-873-5p to upregulate PRKAR2.

Doxorubicin-induced cardiomyopathy (DCM) is a life-threatening event. The long noncoding RNAs (lncRNAs) have been reported with close associations with DCM, which may provide novel insight into pathophysiological mechanisms of DCM. DCM rat model and cell models were established using doxorubicin. Echocardiography analyses were performed to assess cardiac function. We found that testis developmental-related gene 1 (TDRG1) expression was upregulated in DCM rats and in doxorubicin-treated human umbilical vein endothelial cells (HUVECs). TDRG1 knockdown enhanced cell viability, promoted tube formation, and inhibited apoptosis of doxorubicin-treated HUVECs. Additionally, knockdown of TDRG1 alleviated cardiac injury in DCM rats. Mechanistically, miR-873-5p was identified to bind with TDRG1. In addition, protein kinase cAMP-dependent type II regulatory subunit alpha (PRKAR2) was confirmed to bind with miR-873-5p as a target mRNA. MiR-873-5p negatively regulated PRKAR2 mRNA and protein levels. At last, rescue assays indicated that the overexpression of PRKAR2 restored the effect of TDRG1 knockdown on doxorubicin-treated HUVEC angiogenesis and apoptosis. To conclude, TDRG1 aggravates DCM progression by binding with miR-873-5p to upregulate PRKAR2. This work suggested the potential of TDRG1 as a target for DCM treatment.

Effect of Lactobacillus rhamnosus GG fermentation on the structural and functional properties of dietary fiber in bamboo shoot and its application in bread.

The purpose of this study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) fermentation on the composition, structure, and functional properties of dietary fiber (DF) in bamboo shoot. Then, we added it to bread to evaluate the texture properties, digestive properties, and functionality of bread. After LGG fermentation, the DF was decomposed into pieces, which had stronger water-swelling capacity and nitrite adsorption capacity. The ability of producing short-chain fatty acids was significantly improved and the digestive resistance was remarkable enhanced as well. Except the bread hardness was increased, there was no significant difference in other texture properties when adding 3% FTDF-LGG to bread. It had good adsorption capacity of cholesterol and more than 25% reduced the release of reducing sugar. Overall, the technic of LGG fermentation had improved functional properties of DF in bamboo shoot, which could be applied to bread production for exerting its effects in the future. PRACTICAL APPLICATIONS: Bamboo shoots are immature and tender stems of bamboo, rich in nutritional value, and rich in DF. Bamboo shoot DF has been proven to have a variety of biological activities, and is the main material for bamboo shoot to exert functional activities. In this study, bamboo shoot DF was modified by LGG fermentation, which showed stronger functional activity, and was successfully applied to bread. This study lays the foundation for the fermented modified bamboo shoot DF and its application in food.

Extracellular vesicles from bone marrow stromal cells reduce the impact of stroke on glial cell activation and blood brain-barrier permeability via a putative miR-124/PRX1 signalling pathway.

Ischaemic stroke (IS) is a cerebrovascular disease caused by cerebral infarction and cerebral artery occlusion. In this study, we proposed that EVs from bone marrow stromal cells (BMSCs) could reduce the impact of stroke by reducing the resultant glial cell activation and blood-brain barrier (BBB) leak. We furthermore investigated some of the signalling mechanisms. The transient middle cerebral artery occlusion (t-MCAO) mouse model was established. The behavioural deficits and neuronal damage were verified using Bederson's scale and the 28-point neurological score. The area of cerebral infarction was detected. The expressions of astrocytes/microglia markers and BBB permeability were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The internalization of EVs by astrocytes/microglia in the peripheral area was detected by fluorescence labelling. The expressions of astrocyte/microglia markers were measured by RT-qPCR. Levels of TNF-α and IL-1ß in microglia were detected by ELISA. BBB permeability was evaluated. The downstream target genes and pathway of miR-124 were analysed. Microglia/astrocytes were treated by oxygen-glucose deprivation reoxygenation (OGD/R). OGD/R microglia/astrocyte conditioned medium was used to culture bEnd.3 cells. The transendothelial electric resistance (TEER) of bEnd.3 cells was measured, and BBB permeability was characterized. Our results suggested that EVs from BMSCs can indeed reduce the extent of stroke-mediated damage and evidenced that these effects are mediated via expression of the non-coding RNA, miR-124 that may act via the peroxiredoxin 1 (PRX1). Our results provided further motivation to pursue the use of modified EVs as a treatment option for neurological diseases.

Optimal recycle price game theory model for second-hand mobile phone recycling.

Human societies develop rapidly through the advancement of technology; however, with these advancements, many problems are emerging. The topic chosen for this study surrounds the e-waste, which has become a major problem around the world. Second-hand and unused mobile phones are a big part of globally generated e-waste. If these devices are properly recycled, they can generate substantial economic and resource value. Yet if they are indiscriminately discarded, they cause a profound environmental impact. Given the current low recovery rate of mobile phones, an increase in recovery rates becomes critical in lessening economic and environmental impacts. Based on the status quo of second-hand mobile phone recycling processes in China, this article analyzes the behavior of individuals and recyclers through a comprehensive static information game theory and finds ways to increase the recycling rate of second-hand mobile phones. The study helps the customers, to clearly identify the recycle price. In case of market, the government policy can be introduced with a reward and punishment mechanism. Furthermore, under the ideological guidance of game theory, this paper also establishes a corresponding price model of second-hand mobile phone recycling based on best response dynamics like search, variable neighborhood search, and hybrid meta-heuristic method. This model shows that the recovery time differences have a significant impact on the recovery price. Moreover, to an extent, this model can promote the possibility and initiative of customers choosing cell phone recycling.