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Abstract Background Numerous diseases-related acute lung injury (ALI) contributed to high mortality. Currently, the therapeutic effect of ALI was still poor. The detailed mechanism of ALI remained elusive and this study aimed to elucidate the mechanism of ALI. Method This study was performed to expose the molecular mechanisms of AMPK/Nrf2 pathway regulating oxidative stress in LPS-induced AMI mice. The mouse ALI model was established via intraperitoneal injection of LPS, then the lung tissue and blood samples were obtained, followed by injection with Dimethyl fumarate (DMF). Finally, Western blot, HE staining, injury score, lung wet/dry ratio, reactive oxygen species (ROS) and ELISA were used to elucidate the mechanism of AMPK/Nrf2 pathway in LPS -induced acute lung injury by mediating oxidative stress. Results The lung tissue injury score was evaluated, showing higher scores in the model group compared to the AMPK activator and control groups. DCFH-DA indicated that LPS increased ROS production, while AMPK activator DMF reduced it, with the model group exhibiting higher ROS levels than the control and AMPK activator groups. The lung wet/dry ratio was also higher in the model group. Western blot analysis revealed LPS reduced AMPK and Nrf2 protein levels, but DMF reversed this effect. ELISA results showed elevated IL-6 and IL-1β levels in the model group compared to the AMPK activator and control groups.Conclusion: Conclusion Activating the AMPK/Nrf2 pathway can improve LPS-induced acute lung injury by down-regulation of the oxidative stress and corresponding inflammatory factor level.

Abstract A new integration strategy of grid‐forming‐controlled wind farms connected to the bulk power systems through high‐voltage direct current transmission based on the modular multi‐level converter (MMC) is proposed to solve the problem of traditional uncontrollable DC overvoltage during the short circuit faults at the receiving end. However, a new DC overvoltage phenomenon appears after the fault is cleared, and the interaction between the wind farm and sending‐ and receiving‐end MMCs makes the DC overvoltage mechanism more complex; further exploration shows that DC overvoltage during the sending‐end fault recovery stage occurs under the new integration strategy. Therefore, the evolution process and mechanism of the new DC overvoltage are analysed. It is found that affected by the interaction between wind farms and MMCs, the alternate saturation of the integrators in the PI controller of MMCs is the main cause. Based on this understanding, additional controls are proposed to suppress this DC overvoltage during the fault recovery stage. Simulations are carried out on a test with MATLAB/Simulink, and the results verify the efficacy of the proposed methods in suppressing DC overvoltage.

ObjectiveDermatofibrosarcoma protuberans (DFSP) is a moderately malignant soft tissue sarcoma with localized infiltrative growth. The extensive surgical scope and high recurrence rate of DFSP brings dysfunctional, aesthetic, psychological and economic problems to patients. The aim of this study is to explore the global publication characteristics, research hotspots and future trends of DFSP over the past 32 years via an intuitive visualized way.MethodsThe Web of Science Core Collection (WoSCC) database was searched for papers related to DFSP published from 1990 to 2022. Then bibliometric analysis of these publications was performed, including collaborative networks, co-citation analysis of journals and references, and cluster analysis of keywords.ResultsA total of 1588 papers were retrieved between 1990-2022. The United States was the most prolific country, followed by China. The article Imatinib Mesylate in Advanced Dermatofibrosarcoma Protuberans: Pooled Analysis of Two Phase II Clinical Trials, received most citations. Research hotspots and future trends are mainly focused on disease diagnosis, COL1A1-PDGFB fusion gene, drug and surgical treatment, fibrosarcomatous transformation, and immunotherapy.ConclusionThe research on DFSP faces several clinical challenges. This study provides novel insights into future research directions and scientific decisions for DFSP.

Advanced metastatic cardia cancer is an intractable malignance with poor prognosis. It is often accompanied by upper digestive tract obstruction, which seriously affects the quality of patients. Therefore, effective relief of eating obstruction is an important goal in the treatment of cardia cancer. Immune checkpoint inhibitors (ICIs) have shown significant efficacy in cardia cancer, but only a small percentage of patients will benefit from them due to immune resistance. Oncolytic viruses have been shown to enhance the efficacy of ICIs by altering the immune microenvironment. This indicates that oncolytic virus has the potential value of overcoming the immune resistance of cardia cancer. Here, we present a case with local recurrent and multiple metastatic cardia cancer accompanied by eating obstruction. After 4 cycles of chemotherapy plus ICI therapy, the patient´s metastases were significant shrink, but the recurrent carida lesion were almost unchanged. Then we implemented exploratory local injection of recombinant human adenovirus type 5(H101) into recurrent cardia lesion by painless gastroscopy. Surprisingly, the cardia lesion shrank significantly, and the eating obstruction was greatly relieved. We also observed a significant increase of infiltrated CD4+T cells in biopsy tissues after H101 treatment. Our study not only conformed the value of oncolytic viruses to reverse ICI resistance in patients with gastric cancer, but also revealed its underlying impact on immune microenvironment.

Abstract Exploring effective antibacterial approaches for targeted treatment of pathogenic bacterial infections with reduced drug resistance is of great significance. Combinational treatment modality that leverages different therapeutic components can improve the overall effectiveness and minimize adverse effects, thus displaying considerable potential against bacterial infections. Herein, red blood cell membrane fuses with macrophage membrane to develop hybrid cell membrane shell, which further camouflages around drug‐loaded liposome to fabricate biomimetic liposome (AB@LRM) for precise antibacterial therapy. Specifically, photoactive agent black phosphorus quantum dots (BPQDs) and classical antibiotics amikacin (AM) are loaded in AB@LRM to accurately target the inflammatory sites through the guidance of macrophage membrane and long residence capability of red blood cell membrane, eventually exerting efficacious antibacterial activities. Besides, due to the excellent photothermal and photodynamic properties, BPQDs act as an efficient antibacterial agent when exposed to near‐infrared laser irradiation, dramatically increasing the sensitivity of bacteria to antibiotics. Consequently, the synergistic sterilizing effect produced by AB@LRM further restricts bacterial resistance. Upon laser irradiation, AB@LRM shows superior anti‐inflammatory and antibacterial properties in models of P. aeruginosa‐infected pneumonia and wounds. Hence, this light‐activatable antibacterial nanoplatform with good biocompatibility presents great potential to advance the clinical development in the treatment of bacterial infections.

Abstract Chiral functionalized piperidine and lactone heterocycles are widely spread in natural products and drug candidates with promising pharmacological properties. However, there remains no general asymmetric methodologies that enable rapid assemble both critical biologically important units into one three-dimensional chiral molecule. Herein, we describe a straightforward relay strategy for the construction of enantioenriched bridged piperidine-γ-butyrolactone skeletons incorporating three skipped stereocenters via asymmetric allylic alkylation and aza-Prins cyclization/lactonization sequences. The excellent enantioselectivity control in asymmetric allylation with the simplest allylic precursor is enabled by the synergistic Cu/Ir-catalyzed protocol; the success of aza-Prins cyclization/lactonization can be attributed to the pivotal role of the ester substituent, which acts as a preferential intramolecular nucleophile to terminate the aza-Prins intermediacy of piperid-4-yl cation species. The resulting chiral piperidine-γ-butyrolactone bridged-heterocyclic products show impressive preliminary biological activities against a panel of cancer cell lines.

Purpose: To investigate the potential of radiomics signatures (RSs) from intratumoral and peritumoral regions on multiparametric magnetic resonance imaging (MRI) to noninvasively evaluate HER2 status in breast cancer. Method: In this retrospective study, 992 patients with pathologically confirmed breast cancers who underwent preoperative MRI were enrolled. The breast cancer lesions were segmented manually, and the intratumor region of interest (ROIIntra) was dilated by 2, 4, 6 and 8 mm (ROIPeri2mm, ROIPeri4mm, ROIPeri6mm, and ROIPeri8mm, respectively). Quantitative radiomics features were extracted from dynamic contrast-enhanced T1-weighted imaging (DCE-T1), fat‐saturated T2‐weighted imaging (T2) and diffusion-weighted imaging (DWI). A three-step procedure was performed for feature selection, and RSs were constructed using a support vector machine (SVM) to predict HER2 status. Result: The best single-area RSs for predicting HER2 status were DCE_Peri4mm-RS, T2_Peri4mm-RS, and DWI_Peri4mm-RS, yielding areas under the curve (AUCs) of 0.716 (95% confidence interval (CI), 0.648–0.778), 0.706 (95% CI, 0.637–0.768), and 0.719 (95% CI, 0.651–0.780), respectively, in the test set. The optimal RSs combining intratumoral and peritumoral regions for evaluating HER2 status were DCE-T1_Intra + DCE_Peri4mm-RS, T2_Intra + T2_Peri6mm-RS and DWI_Intra + DWI_Peri4mm-RS, with AUCs of 0.752 (95% CI, 0.686–0.810), 0.754 (95% CI, 0.688–0.812) and 0.725 (95% CI, 0.657–0.786), respectively, in the test set. Combining three sequences in the ROIIntra, ROIPeri2mm, ROIPeri4mm, ROIPeri6mm and ROIPeri8mm areas, the optimal RS was DCE-T1_Peri4mm + T2_Peri4mm + DWI_Peri4mm-RS, achieving an AUC of 0.795 (95% CI, 0.733–0.849) in the test set. Conclusion: This study systematically explored the influence of the intratumoral region, different peritumoral sizes and their combination in radiomics analysis for predicting HER2 status in breast cancer based on multiparametric MRI and found the optimal RS.

Myeloid-derived suppressor cells (MDSCs) are important participants after acute myocardial infarction (AMI), but the role of their different subtypes in AMI remains controversial. The anti-inflammatory effect of ticagrelor in AMI has been discovered. However, the detailed anti-inflammatory mechanism has not been fully demonstrated. In this study, we aimed to determine whether ticagrelor can regulate the differentiation of MDSCs into anti-inflammatory subgroups to exert anti-inflammatory effects after AMI. In vitro experiments revealed no difference in the mRNA and protein expression of P2Y12 receptors on MDSCs and macrophages. Ticagrelor promotes the differentiation of in vitro cultured MDSCs to monocytic-MDSCs (M-MDSCs). A mouse AMI model was established to investigate the anti-inflammatory effects of ticagrelor in vivo after AMI by interfering with the differentiation of MDSCs. On the first day after AMI, spleen-derived polymorphonuclear-MDSCs (PMN-MDSCs) were predominant in the circulation and infarcted heart. Ticagrelor increased the percentage of M-MDSCs in the circulation and infarcted heart of AMI mice in a dose-dependent manner, attenuated cardiac inflammation and increased cardiac contractile function. M-MDSC injection significantly decreased cardiac inflammation levels and improved cardiac function in splenectomized AMI mice compared with PMN-MDSC injection. These data point to a novel anti-inflammatory role for ticagrelor after AMI by interfering with the differentiation of MDSCs.

Abstract The present study aims to explore the spatial and temporal changes and drivers of carbon emission patterns in China, with the aim of encouraging county-level carbon reduction policies in pursuit of sustainable development. To this end, we have studied the spatial disparities, spatio-temporal patterns, and evolution characteristics of carbon emissions using county-level carbon emissions data from China between 2002 and 2017. Additionally, we have comprehensively considered the dynamic impacts of both county-level and city-level environmental factors on carbon emissions based on an optimized hierarchical random forest model. The results show that the carbon emissions of China’s counties have generally followed an upward trend before stabilizing. Notable characteristics include elevated carbon emissions in the northern regions and reduced carbon emissions in the southern areas. Additionally, there are higher carbon emissions in the eastern regions compared to lower emissions in the western and inland areas, with discernible local clustering patterns. These findings underscore the importance of tailoring the government’s emission reduction strategy to address the phased variations in carbon emissions across different districts and counties. It is essential to emphasize the key role of major urban agglomerations and metropolitan areas in carbon emission reduction, while also addressing potential emission sources in the resource-rich, yet technologically disadvantaged, northwest region. Furthermore, improving energy efficiency through technological innovation should be the primary means of carbon emission reduction at the county level.

In order to construct a food-safe strain that could produce glycolate, the metabolic modification of Bacillus subtilis was carried out. In this study, the exogenous isocitrate lyase gene (aceA) was first integrated into the genome of Bacillus subtilis by homologous recombination, and the starting strain 164MCT-GA was constructed. Then the glycolate anabolism was optimized by means of metabolic engineering in the starting strain 164MCT-GA. The results showed that 164MCT-GA could synthesize glycolate with glycerol as substrate, and the yield of shaker fermentation was 0.114 g/L. To increase the supply of the key intermediate substrates, the citrate synthase gene (citA) and the glyoxylate reductase gene (yvcT) were overexpressed by replacing the native promoter with individual T7 promoter. The Bacillus strains were further engineered at multiple loci that included lactate dehydrogenase (ldh), phosphate acetyltransferase (pta) and acetyl-CoA transacetylase (mmgA, yhfs), in an attempt to modulate the carbon flux toward the formation of glycolate with a higher efficiency. The fermentation study revealed that the accumulated concentration of glycolate from the obtained B. subtilis strain GA3-52 reached 0.572 g/L, with a conversion rate of 0.175 g/g glycerol, the titer was more than five times as much as that achieved by 164MCT-GA. Thus, this study constructed a de novo synthesis pathway in B. subtilis, and laid the foundation for the fermentation production of high yield glycolic acid by food safety bacteria.

Abstract Background Autism spectrum disorder (ASD) is a serious developmental disorder of the brain. Recently, various deep learning methods based on functional magnetic resonance imaging (fMRI) data have been developed for the classification of ASD. Among them, graph neural networks, which generalize deep neural network models to graph structured data, have shown great advantages. However, in graph neural methods, because the graphs constructed are homogeneous, the phenotype information of the subjects cannot be fully utilized. This affects the improvement of the classification performance. Methods To fully utilize the phenotype information, this paper proposes a heterogeneous graph convolutional attention network (HCAN) model to classify ASD. By combining an attention mechanism and a heterogeneous graph convolutional network, important aggregated features can be extracted in the HCAN. The model consists of a multilayer HCAN feature extractor and a multilayer perceptron (MLP) classifier. First, a heterogeneous population graph was constructed based on the fMRI and phenotypic data. Then, a multilayer HCAN is used to mine graph-based features from the heterogeneous graph. Finally, the extracted features are fed into an MLP for the final classification. Results The proposed method is assessed on the autism brain imaging data exchange (ABIDE) repository. In total, 871 subjects in the ABIDE I dataset are used for the classification task. The best classification accuracy of 82.9% is achieved. Compared to the other methods using exactly the same subjects in the literature, the proposed method achieves superior performance to the best reported result. Conclusions The proposed method can effectively integrate heterogeneous graph convolutional networks with a semantic attention mechanism so that the phenotype features of the subjects can be fully utilized. Moreover, it shows great potential in the diagnosis of brain functional disorders with fMRI data.

Abstract IL-10+ regulatory B cells (Bregs) play a significant role in cancer immunotherapy and their presence is an indicator of negative outcome. We found that PPARδ is significantly upregulated in tumor-induced IL-10+ Bregs with a phenotype of CD19+CD24hiIgDlo/−CD38lo or CD19+CD24hiIgDlo/−CD38hi in both mice and humans, and the level of PPARδ expression was correlated with their potential to produce IL-10 and to inhibit T cell activation. Genetic inactivation of PPARδ in B cells impaired the development and function of IL-10+ B cells, and treatment with PPARδ inhibitor diminished the induction of IL-10+ Bregs by tumor and CD40 engagement. Importantly, immunotherapy with anti-CD40 or anti-PD1 antibody achieved a markedly improved outcome in tumor-bearing mice with PPARδ deficiency in B cells or treated with PPARδ inhibitor. This study shows that PPARδ is required for the development and function of IL-10+ Bregs, providing a new and effective target for selectively blocking Bregs and improving antitumor immunotherapy.

Abstract Background l‑Fucose is a rare sugar that has beneficial biological activities, and its industrial production is mainly achieved with brown algae through acidic/enzymatic fucoidan hydrolysis and a cumbersome purification process. Fucoidan is synthesized through the condensation of a key substance, guanosine 5′‑diphosphate (GDP)‑l‑fucose. Therefore, a more direct approach for biomanufacturing l‑fucose could be the enzymatic degradation of GDP‑l‑fucose. However, no native enzyme is known to efficiently catalyze this reaction. Therefore, it would be a feasible solution to engineering an enzyme with similar function to hydrolyze GDP‑l‑fucose. Results Herein, we constructed a de novo l‑fucose synthetic route in Bacillus subtilis by introducing heterologous GDP‑l‑fucose synthesis pathway and engineering GDP‑mannose mannosyl hydrolase (WcaH). WcaH displays a high binding affinity but low catalytic activity for GDP‑l‑fucose, therefore, a substrate simulation‑based structural analysis of the catalytic center was employed for the rational design and mutagenesis of selected positions on WcaH to enhance its GDP‑l‑fucose‑splitting efficiency. Enzyme mutants were evaluated in vivo by inserting them into an artificial metabolic pathway that enabled B. subtilis to yield l‑fucose. WcaHR36Y/N38R was found to produce 1.6 g/L l‑fucose during shake‑flask growth, which was 67.3% higher than that achieved by wild‑type WcaH. The accumulated l‑fucose concentration in a 5 L bioreactor reached 6.4 g/L. Conclusions In this study, we established a novel microbial engineering platform for the fermentation production of l‑fucose. Additionally, we found an efficient GDP‑mannose mannosyl hydrolase mutant for L‑fucose biosynthesis that directly hydrolyzes GDP‑l‑fucose. The engineered strain system established in this study is expected to provide new solutions for l‑fucose or its high value‑added derivatives production.

Sleep staging is the essential step in sleep quality assessment and sleep disorders diagnosis. However, most current automatic sleep staging approaches use recurrent neural networks (RNN), resulting in a relatively large training burden. Moreover, these methods only extract information of the whole epoch or adjacent epochs, ignoring the local signal variations within epoch. To address these issues, a novel deep learning architecture named segmented attention network (SAN) is proposed in this paper. The architecture can be divided into feature extraction (FE) and time sequence encoder (TSE). The FE module consists of multiple multiscale CNN (MMCNN) and residual squeeze and excitation block (SE block). The former extracts features from multiple equal-length EEG segments and the latter reinforced the features. The TSE module based on a multi-head attention mechanism could capture the temporal information in the features extracted by FE module. Noteworthy, in SAN, we replaced the RNN module with a TSE module for temporal learning and made the network faster. The evaluation of the model was performed on two widely used public datasets, Montreal Archive of Sleep Studies (MASS) and Sleep-EDFX, and one clinical dataset from Huashan Hospital of Fudan University, Shanghai, China (HSFU). The proposed model achieved the accuracy of 85.5%, 86.4%, 82.5% on Sleep-EDFX, MASS and HSFU, respectively. The experimental results exhibited favorable performance and consistent improvements of SAN on different datasets in comparison with the state-of-the-art studies. It also proved the necessity of sleep staging by integrating the local characteristics within epochs and adjacent informative features among epochs.

Background Myeloid-derived suppressor cell (MDSC) mobilisation is an important immune event in acute myocardial infarction (AMI). The A2B adenosine receptor (A2BAR) plays key role in regulating MDSC function, but its specific involvement in MDSC mobilisation in AMI remains unclear.Methods In AMI patients, the circulating MDSC ratio and A2BAR mRNA expression were measured. A mouse AMI model was established by left anterior descending coronary artery (LADCA) ligation. MDSCs were analysed by FACS and immunofluorescence staining (of heart tissue). A2BAR mRNA expression was assessed by qRT-PCR. Myocardial injury was detected by HE staining. Myocardial cell apoptosis was analysed by immunohistochemistry. Cardiac systolic function was evaluated by transthoracic echocardiography.Results In AMI patients, the circulating MDSC ratio was increased and positively correlated with A2BAR mRNA expression (r = 0.86, p

Background Chronic renal disease (CKD) is a common and irreversible loss of renal function. Renal fibrosis reflected the degree of renal dysfunction. However, the current biomarkers only characterize the renal function instead of indicating the fibrosis degree. The potential diagnostic value of urinary exosomes derived circRNAs for renal fibrosis needs to be further studied.Methods Urine exosomes from 3 chronic kidney disease (CKD) patients without renal fibrosis and 3 renal fibrotic patients were collected and human circRNAs microarray analysis were performed to detect the circRNAs expression profile. 110 biopsy-proven CKD patients and 54 healthy controls were enrolled and urine exosomes derived RNA was isolated. The expression of hsa_circ_0036649 was measured and the correlation with renal function parameter and pathological indicators was performed. The receiver operating characteristic (ROC) curve for the diagnosis of renal fibrosis was calculated.Results Human circRNAs microarray showed 365 circRNAs up expressed and 195 circRNAs down expressed in renal fibrotic patients compared to none fibrosis CKD patients. The expression of hsa_circ_0036649 was decreased in renal fibrotic patients according to RT-PCR and correlated with serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate and cystatin c. Further, the expression of hsa_circ_0036649 was correlated with the score of tubulointerstitial fibrosis (TIF) and the score of glomerular sclerosis. The ROC curve showed that hsa_circ_0036649 may predict renal fibrosis at a cut-off value of 0.597 with a sensitivity of 45.5% and specificity of 87.9%.Conclusion Expression of urinary exosomes derived hsa_circ_0036649 associated with the degree of renal fibrosis. Its potential role as a biomarker in CKD remained to be supported by further follow-up studies. Key MessagescircRNAs profile in urine exosomes in renal fibrosis patients was revealed.The expression of urine exosomes derived hsa_circ_0036649 was correlated to renal function and fibrosis degree.circRNAs derived from urinary exosomes may become a new research direction for biomarkers of renal fibrosis.

The oxidation of methane to formic acid or related oxygenates relies on efficient reaction with H2O2. Here, the authors report a TiO2-based catalyst to selectively form formic acid by using molecular O2 additives to avoid unwanted side reactions.

The marginal carbon emission factor can more accurately reflect the real-time carbon emission of the system. Based on the hourly output, load and external power data of Guangdong Province from 2017 to 2020, this paper uses the seemingly unrelated regressions (SUR) model to calculate the marginal carbon emission factor and carbon displacement coefficient of Guangdong’s power industry and compares them with the average carbon emission intensity, which can provide support for the formulation of emission reduction policies in the province. The study shows that the average carbon emission factor underestimates the actual carbon emission of the power system, and the marginal carbon emission factor is a more appropriate indicator to reflect the carbon emission of the system in policy regulation. In addition, this paper also analyzes the annual, quarterly and peak–valley heterogeneity of marginal carbon emissions. The results show that the marginal carbon emission factor at peak demand times increases significantly, featuring more gas turbines participating in power generation.

Introduction: The coil handle orientation plays a pivotal role in the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS). However, there is currently no consensus on the optimal individualized coil handle orientation, especially for non-motor areas. Case presentation: The present case reported a short-term effect of functional connectivity (FC)-guided rTMS with coil handle posterior-anterior 45° (PA45°) and posterior-anterior 135° (PA135°) on a patient with insomnia. Notably, in this case, the PA45° orientation was nearly perpendicular to the adjacent sulcus, while the PA135° orientation was almost parallel to it. Local brain activity and functional connectivity were assessed using resting-state functional magnetic resonance imaging (RS-fMRI). Additionally, motor evoked potentials (MEPs) were captured both pre and post-rTMS sessions. Findings: The coil handle orientation PA45° outperformed the PA135° in both RS-fMRI and MEP outcomes. Moreover, a 9-day rTMS treatment led to discernible improvements in symptoms of depression and anxiety, complemented by a modest enhancement in sleep quality.

Abstract Background Intermediate-risk acute pulmonary embolism (APE) patients are usually defined as hemodynamically stable, comprehending a great therapeutic dilemma. Although anticoagulation therapy is sufficient for most intermediate-risk APE patients, some patients can deteriorate and eventually require a systemic fibrinolytic agent or thrombectomy. Hence, this study aimed to evaluate the predictive value of differences in clinical data for the short-term prognosis of intermediate-risk APE patients. Methods A retrospective cohort of 74 intermediate-risk APE patients confirmed by computed tomography pulmonary angiography was analyzed in the present study. Adverse clinical event outcomes included PE-related in-hospital deaths, critical systolic blood pressure consistently under 90 mmHg, refractory to volume loading and vasopressor infusion requirements, mechanical ventilation, and cardiopulmonary resuscitation. The APE patients were stratified into two groups: adverse outcome (n = 25) and control (n = 49) groups. Then, the clinical data of the two groups were compared. Receiver operating characteristic (ROC) curves were used to explore the predictive value of white blood cell (WBC) counts and the right to left ventricular short-axis (RV/LV) ratio. Model calibration was assessed using the Hosmer–Lemeshow goodness-of-fit statistic. Results The brain natriuretic peptide, WBC count, and the RV/LV ratio were higher in patients with adverse outcomes compared to controls. The APE patients with adverse outcomes presented significantly higher rates of syncope, Negative T waves (NTW) in V1–V3, intermediate-high risk, thrombolytic therapy, and low arterial oxygen saturation (SaO2) compared to controls. In the multivariate logistic regression analysis, the SaO2 1.165 was predictive of adverse outcomes with sensitivity and specificity of 88.00 and 59.20%, respectively. The WBC counts were also able to predict adverse outcomes (AUC = 0.752, p 9.05 was predictive of adverse outcomes with sensitivity and specificity of 68.00 and 73.50%, respectively. Conclusion Overall, a SaO2

Lycopene is a very unstable fat-soluble pigment and is easily oxidized or isomerized during processing and storage. In recent years, microencapsulation has been used to improve the instability of lycopene. The microencapsulated lycopene can reduce the contact with the outside world, avoiding the adverse effects of the external environment, increasing the storage stability of lycopene, and improve its bioavailability in the intestine. The preparation, storage stability and bioavailability of lycopene microcapsules are reviewed in this paper, in order to provide a reference for the application of lycopene microcapsule technology.

BackgroundSince the end of 2019, Corona Virus Disease 2019, also known as COVID-19, has broken out in various countries. However, the change of China's COVID-19 prevention and control policy and the sharp increase in the number of infected people are making the teenagers have post-traumatic reactions. Negative post-traumatic reactions include: post-traumatic stress disorder (PTSD), depression, anxiety. Positive post-traumatic reaction mainly refers to post-traumatic growth (PTG). The purpose of this study is to explore the post-traumatic reaction, which refers to PTSD, depression, anxiety and the co-occurrence pattern of growth after trauma and to further explore the influence of family function on different categories of Post-traumatic Reactions.MethodsLatent profile analysis (LPA) was used to explore the co-occurrence of PTSD, depression, anxiety, and PTG. Multiple logistics regression was used to analyze the influence of family function on different categories of post-traumatic response.ResultsThere were three categories of post-traumatic reactions in adolescents infected with COVID-19 adolescents infected with COVID-19, namely: growth class, struggling class, and pain class. Multivariate Logistic regression showed that the growth class and struggling class were affected by problem solving and behavior control in family function, while the growth class and pain class were affected by problem solving, roles, behavior control, and general functioning. Multiple logistic regression showed that the growth class and struggling class were affected by problem solving and roles.ConclusionsThe findings of this study provide evidence for the identification of high-risk individuals and the provision of effective interventions in clinical practice, as well as the influence of family functioning on the different categories of PTSD among adolescents infected with COVID-19.

Elimination of intra-artifacts in EEG has been overlooked in most of the existing sleep staging systems, especially in deep learning-based approaches. Whether intra-artifacts, originated from the eye movement, chin muscle firing, or heart beating, etc., in EEG signals would lead to a positive or a negative masking effect on deep learning-based sleep staging systems was investigated in this paper. We systematically analyzed several traditional pre-processing methods involving fast Independent Component Analysis (FastICA), Information Maximization (Infomax), and Second-order Blind Source Separation (SOBI). On top of these methods, a SOBI-WT method based on the joint use of the SOBI and Wavelet Transform (WT) is proposed. It offered an effective solution for suppressing artifact components while retaining residual informative data. To provide a comprehensive comparative analysis, these pre-processing methods were applied to eliminate the intra-artifacts and the processed signals were fed to two ready-to-use deep learning models, namely two-step hierarchical neural network (THNN) and SimpleSleepNet for automatic sleep staging. The evaluation was performed on two widely used public datasets, Montreal Archive of Sleep Studies (MASS) and Sleep-EDF Expanded, and a clinical dataset that was collected in Huashan Hospital of Fudan University, Shanghai, China (HSFU). The proposed SOBI-WT method increased the accuracy from 79.0% to 81.3% on MASS, 83.3% to 85.7% on Sleep-EDF Expanded, and 75.5% to 77.1% on HSFU compared with the raw EEG signal, respectively. Experimental results demonstrate that the intra-artifacts bring out a masking negative impact on the deep learning-based sleep staging systems and the proposed SOBI-WT method has the best performance in diminishing this negative impact compared with other artifact elimination methods.

Deep sleep staging networks have reached top performance on large-scale datasets. However, these models perform poorer when training and testing on small sleep cohorts due to data inefficiency. Transferring well-trained models from large-scale datasets (source domain) to small sleep cohorts (target domain) is a promising solution but still remains challenging due to the domain-shift issue. In this work, an unsupervised domain adaptation approach, domain statistics alignment (DSA), is developed to bridge the gap between the data distribution of source and target domains. DSA adapts the source models on the target domain by modulating the domain-specific statistics of deep features stored in the Batch Normalization (BN) layers. Furthermore, we have extended DSA by introducing cross-domain statistics in each BN layer to perform DSA adaptively (AdaDSA). The proposed methods merely need the well-trained source model without access to the source data, which may be proprietary and inaccessible. DSA and AdaDSA are universally applicable to various deep sleep staging networks that have BN layers. We have validated the proposed methods by extensive experiments on two state-of-the-art deep sleep staging networks, DeepSleepNet+ and U-time. The performance was evaluated by conducting various transfer tasks on six sleep databases, including two large-scale databases, MASS and SHHS, as the source domain, four small sleep databases as the target domain. Thereinto, clinical sleep records acquired in Huashan Hospital, Shanghai, were used. The results show that both DSA and AdaDSA could significantly improve the performance of source models on target domains, providing novel insights into the domain generalization problem in sleep staging tasks.

The high incidence of heart failure secondary to myocardial infarction (MI) has been difficult to effectively address. MI causes strong aseptic inflammation, and infiltration of different immune cells and changes in the local inflammatory microenvironment play a key regulatory role in ventricular remodeling. Therefore, the possibility of improving the prognosis of MI through targeted immunity has been of interest and importance in MI. However, previously developed immune-targeted therapies have not achieved significant success in clinical trials. Here, we propose that the search for therapeutic targets from different immune cells may be more precise and lead to better clinical translation. Specifically, this review summarizes the role and potential therapeutic targets of various immune cells in ventricular remodeling after MI, especially monocytes/macrophages and neutrophils, as a way to demonstrate the importance and potential of immunomodulatory therapies for MI. In addition, we analyze the reasons for the failure of previous immunomodulatory therapies and the issues that need to be addressed, as well as the prospects and targeting strategies of using immune cells to drive novel immunomodulatory therapies, hoping to advance the development of immunomodulatory therapies by providing evidence and new ideas.

Background: Since the mid 80’ies, the western palliative care philosophy has influenced the development of palliative care in mainland China. However, it has caused several challenges. Objective: To explore the understanding of the ‘good death’ among authorities, professionals, patients, and their relatives in end-of-life care settings in mainland China. Design: Scoping review. The PRISMA-ScR checklist was used. The study is not registered. Settings: End-of-life care settings, Mainland China Participants: Authorities, healthcare professionals, adult patients, and general population in mainland China. Method: Literature searches were performed through Medline, CINAHL, PsycInfo, and Web of Sciences from 2001-2021, last search 21.4.2021. Inclusion criteria were: Empirical research studies investigating ‘good death’ or political documents about ‘good death’, perspectives from authorities, professionals, patients, and/or relatives, and studies following the Declaration of Helsinki. Exclusion criteria were: Literature reviews, languages other than English and Chinese, editorials, letters, comments, and children's death/dying.The analysis consisted of analysing the data including a descriptive numerical summary analysis and a qualitative thematic analysis. Results: Nineteen articles and two political documents were included. The 19 studies were carried out from 2003-2020, with data collected from 1999 to 2019. The political documents were written in 2012 and 2017, respectively. The thematic analysis resulted in three themes: ‘Medicalisation of death’, ‘Communication about death - a clash between two philosophies’, and ‘Dying and death were socially dependent’. The medicalisation of death meant the understanding of the ‘good death’ primarily focused on physical symptoms and treatments. The good death was understood as painless and symptom-free, where all symptoms could be measured and assessed. Dignity and shared decision-making were connected to the understanding of the ‘good death’. However, the contents of the ‘good death’ varied across the different actors. The understanding of the ‘good death’ in mainland China was a negotiation between Chinese traditional philosophy and contemporary western medicine practice. There was a tension between openness and silence about death, which reflected the importance of death education. The understanding of the ‘good death’ consisted partly of a timely and practical preparation for the death and afterlife, partly of a matter of social and financial issues. Conclusions: There seemed to be a clash between two different cultures in the understanding of a good death in Mainland China, where western philosophy seemed to rule the political medical actors while traditional Chinese philosophy seemed to rule parts of the population.

Background: The complex formed by disulfiram (DSF) and copper (Cu) is safe and effective for the prevention and treatment of triple-negative breast cancer (TNBC). Although previous studies have shown that DSF/Cu induces ferroptosis, the mechanism remains unclear. Methods: The mitochondrial morphology of TNBC treated with DSF/Cu was observed by transmission microscopy, and intracellular levels of iron, lipid reactive oxygen species (ROS), malondialdehyde, and glutathione were evaluated to detect the presence of ferroptosis. Target genes for the DSF/Cu-activated ferroptosis signaling pathway were examined by transcriptome sequencing analysis. Expression of the target gene, HOMX1, was detected by qRT-PCR, immunofluorescence and western blot. Results: The mitochondria of TNBC cells were significantly atrophied following treatment with DSF/Cu for 24 h. Addition of DSF/Cu supplement resulted in significant up-regulation of intracellular iron, lipid ROS and malondialdehyde levels, and significant down-regulation of glutathione levels, all of which are important markers of ferroptosis. Transcriptome analysis confirmed that DSF/Cu activated the ferroptosis signaling pathway and up-regulated several ferroptosis target genes associated with redox regulation, especially heme oxygenase-1 (HMOX-1). Inhibition of ferroptosis by addition of the ROS scavenger N-acetyl-L-cysteine (NAC) significantly increased the viability of DSF/Cu-treated TNBC cells. Conclusions: These results show that DSF/Cu increases lipid peroxidation and causes a sharp increase in HMOX1 activity, thereby inducing TNBC cell death through ferroptosis. DSF/Cu is a promising therapeutic drug for TNBC and could lead to ferroptosis-mediated therapeutic strategies for human cancer.

Purpose: Diabetic retinopathy (DR) is a serious complication of diabetes mellitus, which nearly happens to all the diabetic sufferers. This study aims to identify the preliminary molecular regulation involved in the therapeutic efficacy of astragaloside IV (AS- IV) for DR.Methods: Diabetic rat models were established and treated with AS-IV. Optical coherence tomography (OCT) and Hematoxylin-eosin (HE) staining was employed to demonstrate the histopathological changes. The main targets of AS-IV were identified by searching from public databases of traditional Chinese medicine (GeneCards, PharmMapper and Swiss Target Prediction). Besides, disease targets of DR were also obtained by integrated data from GEO datasets and predicted from public databases. Protein-protein interaction (PPI) network was constructed by Cytoscape with overlapping genes and 10 core targets were selected, on which Gene Ontology (GO) along with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted. The interaction between AS-IV and these crucial genes were analyzed using molecular docking. RT-qPCR and western blot were used to verify the expression variation of core targets.Results: OCT imaging and HE staining demonstrated that AS-IV administration significantly increased retinal thickness in diabetic rats, obviously alleviating DR induced histopathological changes as well as elevated blood glucose levels. 107 common targets of AS-IV and DR were determined after intersection. PPI network analysis filtered 10 hub genes potentially targeted by AS-IV, including VEGFA, CASP3, HIF1α, STAT3, CTNNB1, SRC, AKT1, EGFR, IL1β and IL6. Enrichment analysis indicated that these genes were mainly enriched in biological processes like T cell activation, epithelial cell proliferation and protein kinase B signaling, and involved in oxidative stress, apoptosis and inflammation-related pathways. The molecular docking prediction suggested that AS-IV exhibited stable binding to these core targets. In addition, mRNA levels of core targets in diabetic rats were differentially expressed before and after AS-IV treatment. Western blot further revealed that AS-IV treatment elevated DR-depressed protein levels of PI3K and AKT.Conclusion: Our study elucidated the effect of AS-IV in attenuating retinopathy induced by diabetes in rats and preliminarily unveiled the therapeutic efficacy of AS-IV in the treatment of DR might be attributed to activation of PI3K-AKT signaling pathway.

The influence of the coupled electroencephalography (EEG) signal in electrooculography (EOG) on EOG-based automatic sleep staging has been ignored. Since the EOG and prefrontal EEG are collected at close range, it is not clear whether EEG couples in EOG or not, and whether or not the EOG signal can achieve good sleep staging results due to its intrinsic characteristics. In this paper, the effect of a coupled EEG signal in an EOG signal on automatic sleep staging is explored. The blind source separation algorithm was used to extract a clean prefrontal EEG signal. Then the raw EOG signal and clean prefrontal EEG signal were processed to obtain EOG signals coupled with different EEG signal contents. Afterwards, the coupled EOG signals were fed into a hierarchical neural network, including a convolutional neural network and recurrent neural network for automatic sleep staging. Finally, an exploration was performed using two public datasets and one clinical dataset. The results showed that using a coupled EOG signal could achieve an accuracy of 80.4%, 81.1%, and 78.9% for the three datasets, slightly better than the accuracy of sleep staging using the EOG signal without coupled EEG. Thus, an appropriate content of coupled EEG signal in an EOG signal improved the sleep staging results. This paper provides an experimental basis for sleep staging with EOG signals.

For decades, researchers have been concerned with house price modeling, and recognition has grown for the necessity of considering environmental and contextual variables in the process. This research examines the association between neighborhood characteristics and all individual house sale prices in Lucas County, Ohio, from 2012 to 2016, through a multilevel modeling (MLM) approach. Although there are various ways to define neighborhoods, census tracts and school districts are used in this study. Neighborhood characteristics include a foreclosure score, race heterogeneity, median household income, and built environment variables, such as walkability indexes. School district characteristics include student performance, tuition expenditures per pupil, and percent of expenditures spent on classroom instruction. The advantage of the multilevel model, is that it allows us to derive reliable estimates of place differences, representing a considerable improvement over the single-level model. Significant correlations were identified between house prices and foreclosure score, student performance, and tuition expenditures per pupil. The MLM results indicate that house prices not only lay in house characteristics themselves but also in neighborhood features, thus MLM offers good prediction accuracy and high explanatory power.

AbstractBackground The non-invasive identification of novel renal fibrosis biomarkers needs to be further studied.Methods We collected urine samples from 77 biopsy-proven CKD patients and 15 healthy controls. The expression of urinary TREM-1 and TREM-2 was measured and the correlation with renal function parameter and pathological indicators was performed. The receiver operating characteristic (ROC) curve for the diagnosis of renal fibrosis was calculated. The protein expression of TREM-1 and TREM-2 in kidney tissues was measured.Results The TREM-1/TREM-2 ratio was decreased in CKD patients and correlated with serum creatinine, estimated glomerular filtration rate and cystatin c. Further, the TREM-1/TREM-2 ratio was significantly decreased in moderate-severe fibrosis patients compared with none-mild renal fibrosis. TREM-1/TREM-2 ratio was correlated with the score of tubulointerstitial fibrosis (TIF) and the score of glomerular sclerosis. The ROC curve showed that the urinary TREM-1/TREM-2 ratio can diagnosemoderate-severe renal fibrosis at a cut-off value of 1.338 with a sensitivity of 86.4% and specificity of 81.8%. In human moderate-severe fibrosis kidney tissue, the protein expression of TREM-1 was lower and the TREM-2 was higher than none-mild fibrosis kidney tissue.Conclusion Urinary TREM-1/TREM-2 ratio was a potential biomarker for the diagnosis of renal fibrosis in CKD patients.

BackgroundNew-onset atrial fibrillation (NOAF) is associated with worse prognostic outcomes in cases diagnosed with ST-segment elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, as a credible and convenient marker of insulin resistance, has been shown to be predictive of outcomes for STEMI patients following revascularization. The association between TyG index and NOAF among STEMI patients following PCI, however, has not been established to date.ObjectiveTo assess the utility of the TyG index as a predictor of NOAF incidence in STEMI patients following PCI, and to assess the relationship between NOAF and long-term all-cause mortality.MethodsThis retrospective cohort research enrolled 549 STEMI patients that had undergone PCI, with these patients being clustered into the NOAF group and sinus rhythm (SR) group. The predictive relevance of TyG index was evaluated through logistic regression analyses and the receiver operating characteristic (ROC) curve. Kaplan-Meier curve was employed to explore differences in the long-term all-cause mortality between the NOAF and SR group.ResultsNOAF occurred in 7.7% of the enrolled STEMI patients after PCI. After multivariate logistic regression analysis, the TyG index was found to be an independent predictor of NOAF [odds ratio (OR): 8.884, 95% confidence interval (CI): 1.570–50.265, P = 0.014], with ROC curve analyses further supporting the predictive value of this parameter, which exhibited an area under ROC curve of 0.758 (95% CI: 0.720–0.793, P < 0.001). All-cause mortality rates were greater for patients in the NOAF group in comparison with the SR group over a median 35-month follow-up period (log-rank P = 0.002).ConclusionsThe TyG index exhibits values as an independent predictor of NOAF during hospitalization, which indicated a poorer prognosis after a relatively long-term follow-up.

Infantile hemangiomas (IHs) are the most frequent vascular tumors that occur during infancy. Microribonucleic acids (miRNAs) have been demonstrated as critical regulators of gene expression in various diseases. However, the function of miRNAs in IH still remains largely unknown. In the present study, we performed a miRNA microarray analysis of IH and identified 68 differentially expressed miRNAs (DEMs). In addition, miRNA-gene networks and protein-protein interactions were constructed, and the hub miRNAs and genes of IH were screened out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used for biological analysis of DEMs and differentially expressed genes (DEGs). The pathway enrichment analysis of DEMs revealed several tumor-related pathways, including proteoglycans in cancer, signaling pathway regulating pluripotency of stem cells and TGF-beta signaling pathway. DEGs were mainly enriched in biological processes, including intracellular signal transduction, cell adhesion, and cell death. KEGG pathway analysis indicated that DEGs were enriched in tumorigenesis- and angiogenesis-related pathways such as proteoglycans in cancer, MAPK signaling pathway and Rap1 signaling pathway. Collectively, this study first established a comprehensive miRNA-gene network in IH, which should provide novel insights into IH pathogenesis and be beneficial to the understanding of neovascularization-related disorders.

Objective: To investigate maternal plasma concentrations of tissue kallikrein (TK) in normal and preeclamptic pregnancies. Methods: 96 women with singleton pregnancies were categorized into normal, mild preeclampsia and preeclampsia with severe features. Plasma levels of TK were quantified by ELISA and left lateralrecumbencyposition BP measured. Results: Maternal plasma TK concentrations were significantly lower in preeclampsia with severe features compared with mild preeclampsia and normal pregnant. Plasma TK concentrations were negatively correlated with systolic and diastolic blood pressure, and 24-hour urine protein. Conclusion: Lower maternal plasma TK may be a risk marker that reflects the severity of preeclampsia.

Feature extraction (FE) plays an important role in machine learning. In order to handle the “dimensionality disaster”problem, the usual approach is to transform the original sample into a low-dimensional target space, in which the FE task is performed. However, the data in reality will always be corrupted by various noises or interfered by outliers, making the task of feature extraction extremely challenging. Thence, we propose a novel image FE method via approximate orthogonal low-rank embedding (AOLRE), which adopts an orthogonal matrix to reserve the major energy of the samples, and the introduction of the ℓ2,1-norm makes the features more compact, differentiated and interpretable. In addition, the weighted Schatten p-norm is adopted in this model for fully exploring the effects of different ranks while approaching the original hypothesis of low rank. Meanwhile, as a robust measure, the correntropy is applied in AOLRE. This can effectively suppress the adverse influences of contaminated data and enhance the robustness of the algorithm. Finally, the introduction of the classification loss item allows our model to effectively fit the supervised scene. Five common datasets are used to evaluate the performance of AOLRE. The results show that the recognition accuracy and robustness of AOLRE are significantly better than those of several advanced FE algorithms, and the improvement rate ranges from 2% to 15%.

Vertebrate erythropoiesis involves nuclear and chromatin condensation at the early stages of terminal differentiation, which is a unique process to distinguish mature erythrocytes from erythroblasts. However, the underlying mechanisms of chromatin condensation during erythrocyte maturation remain elusive. Here, we reported a novel zebrafish mutantcas7 with erythroid maturation deficiency. Positional cloning showed that a single base mutation in tprb gene, which encodes nucleoporin translocated promoter region (Tpr), is responsible for the disrupted erythroid maturation and upregulation of erythroid genes, including ae1-globin and be1-globin. Further investigation revealed that deficient erythropoiesis in tprbcas7 mutant was independent on HIF signaling pathway. The proportion of euchromatin was significantly increased, whereas the percentage of heterochromatin was markedly decreased in tprbcas7 mutant. In addition, TPR knockdown in human K562 cells also disrupted erythroid differentiation and dramatically elevated the expression of globin genes, which suggests that the functions of TPR in erythropoiesis are highly conserved in vertebrates. Taken together, this study revealed that Tpr played vital roles in chromatin condensation and gene regulation during erythroid maturation in vertebrates.

A core feature of drug-resistant epilepsy is hyperexcitability in the motor cortex, and low-frequency repetitive transcranial magnetic stimulation (rTMS) is a suitable treatment for seizures. However, the antiepileptic effect causing network reorganization has rarely been studied. Here, we assessed the impact of rTMS on functional network connectivity (FNC) in resting functional networks (RSNs) and their relation to treatment response. Fourteen patients with medically intractable epilepsy received inhibitive rTMS with a figure-of-eight coil over the vertex for 10 days spread across two weeks. We designed a 6-week follow-up phase divided into four time points to investigate FNC and rTMS-induced timing-dependent plasticity, such as seizure frequency and abnormal interictal discharges on electroencephalography (EEG). For psychiatric comorbidities, the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A) were applied to measure depression and anxiety before and after rTMS. FNC was also compared to that of a cohort of 17 healthy control subjects. The after-effects of rTMS included all subjects that achieved the significant decrease rate of more than 50% in interictal epileptiform discharges and seizure frequency, 12 (14) patients with the reduction rate above 50% compared to the baseline, as well as emotional improvements in depression and anxiety (p < 0.05). In the analysis of RSNs, we found a higher synchronization between the sensorimotor network (SMN) and posterior default-mode network (pDMN) in epileptic patients than in healthy controls. In contrast to pre-rTMS, the results demonstrated a weaker FNC between the anterior DMN (aDMN) and SMN after rTMS, while the FNC between the aDMN and dorsal attention network (DAN) was greater (p < 0.05, FDR corrected). Importantly, the depressive score was anticorrelated with the FNC of the aDMN-SMN (r = −0.67, p = 0.0022), which was markedly different in the good and bad response groups treated with rTMS (p = 0.0115). Based on the vertex suppression by rTMS, it is possible to achieve temporary clinical efficacy by modulating network reorganization in the DMN and SMN for patients with refractory epilepsy.

The stark discrepancy in the prognosis of epilepsy is closely related to brain damage features and underlying mechanisms, which have not yet been unraveled. In this study, differences in the epileptic brain functional connectivity states were explored through a network-based connectivity analysis between intractable mesial temporal lobe epilepsy (MTLE) patients and benign epilepsy with centrotemporal spikes (BECT). Resting state fMRI imaging data were collected for 14 MTLE patients, 12 BECT patients and 16 healthy controls (HCs). Independent component analysis (ICA) was performed to identify the cortical functional networks. Subcortical nuclei of interest were extracted from the Harvard-Oxford probability atlas. Network-based statistics were used to detect functional connectivity (FC) alterations across intranetworks and internetworks, including the connectivity between cortical networks and subcortical nuclei. Compared with HCs, MTLE patients showed significant lower activity between the connectivity of cortical networks and subcortical nuclei (especially hippocampus) and lower internetwork FC involving the lateral temporal lobe; BECT patients showed normal cortical-subcortical FC with hyperconnectivity between cortical networks. Together, cortical-subcortical hypoconnectivity in MTLE suggested a low efficiency and collaborative network pattern, and this might be relevant to the final decompensatory state and the intractable prognosis. Conversely, cortical-subcortical region with normal connectivity remained well in global cooperativity, and compensatory internetwork hyperconnectivity caused by widespread cortical abnormal discharge, which might account for the self-limited clinical outcome in BECT. Based on the fMRI functional network study, different brain network patterns might provide a better explanation of mechanisms in different types of epilepsy.

Fate determination and expansion of Hematopoietic Stem and Progenitor Cells (HSPCs) is tightly regulated on both transcriptional and post-transcriptional level. Although transcriptional regulation of HSPCs have achieved a lot of advances, its post-transcriptional regulation remains largely underexplored. The small size and high fecundity of zebrafish makes it extraordinarily suitable to explore novel genes playing key roles in definitive hematopoiesis by large-scale forward genetics screening. Here, we reported a novel zebrafish mutant line gemin5cas008 with a point mutation in gemin5 gene obtained by ENU mutagenesis and genetic screening, causing an earlier stop codon next to the fifth WD repeat. Gemin5 is an RNA-binding protein with multifunction in post-transcriptional regulation, such as regulating the biogenesis of snRNPs, alternative splicing, stress response, and translation control. The mutants displayed specific deficiency in definitive hematopoiesis without obvious defects during primitive hematopoiesis. Further analysis showed the impaired definitive hematopoiesis was due to defective proliferation of HSPCs. Overall, our results indicate that Gemin5 performs an essential role in regulating HSPCs proliferation.

Pseudomonas chlororaphis P3 has been well-engineered as a platform organism for biologicals production due to enhanced shikimate pathway and excellent physiological and genetic characteristics. Gentisate displays high antiradical and antioxidant activities and is an important intermediate that can be used as a precursor for drugs. Herein, a plasmid-free biosynthetic pathway of gentisate was constructed by connecting the endogenous degradation pathway from 3-hydroxybenzoate in Pseudomonas for the first time. As a result, the production of gentisate reached 365 mg/L from 3-HBA via blocking gentisate conversion and enhancing the gentisate precursors supply through the overexpression of the rate-limiting step. With a close-up at the future perspectives, a series of bioactive compounds could be achieved by constructing synthetic pathways in conventional Pseudomonas to establish a cell factory.

Head and neck squamous cell carcinomas (HNSCC) are well suited for cancer vaccination strategies. In addition to tumor-associated antigens (TAAs) and endogenous retrovirus (ERV) encoded proteins, HNSCCs have a relatively high tumor mutational burden encoding potential neoepitopes. Peptide vaccine candidates are prioritized by predicted high-affinity to major histocompatibility complex (MHC) class I with MHC-II affinity largely not being considered. Herein, we extend previous studies to evaluate therapeutic vaccination in the mouse oral cancer (MOC) 22 model. Two distinct MOC22 derived SLPs were tested – a TSA-oriented mutant intercellular adhesion molecule 1 (mICAM1) and p15E, an ERV encoded antigen. In silico prediction revealed mICAM1 SLP bore strong MHC-I and MHC-II epitopes sharing a mutant residue with vaccination significantly increasing both antigen-specific IFN-γ producing CD4+ and CD8+ T cells. By contrast, p15E SLP had a predicted high-affinity MHC-I epitope but lacked an MHC-II epitope and vaccination induced antigen-specific CD8+ but not CD4+ T cell responses. Therapeutic mICAM1 vaccination attenuated tumor growth effectively with mICAM1-specific T cells displaying durable IFN-γ production compared with p15E SLP. Furthermore, mICAM1 SLPs carrying weakened MHC-II binding epitopes were unable to control tumor growth. These data underscore the potential value of therapeutic targeting of HNSCC epitopes and highlight the importance of studying distinct antigen classes in this setting. Moreover, they raise the possibility that, at least in part, CD4+ T cell help is critical for cancer vaccination in this preclinical HNSCC model and suggest in silico prediction approaches prioritize overlapping MHC-I and MHC-II epitopes to generate potent cancer vaccines.

Background. Circulating endothelial progenitor cells (EPCs) play important roles in vascular repair. However, the mechanisms of high-glucose- (HG-) induced cord blood EPC senescence and the role of B2 receptor (B2R) remain unknown. Methods. Cord blood samples from 26 patients with gestational diabetes mellitus (GDM) and samples from 26 healthy controls were collected. B2R expression on circulating CD34+ cells of cord blood mononuclear cells (CBMCs) was detected using flow cytometry. The plasma concentrations of 8-isoprostaglandin F2α (8-iso-PGF2α) and nitric oxide (NO) were measured. EPCs were treated with HG (40 mM) alone or with bradykinin (BK) (1 nM). The B2R and eNOS small interfering RNAs (siRNAs) and the PI3K antagonist LY294002 were added to block B2R, eNOS, and PI3K separately. To determine the number of senescent cells, senescence-associated β-galactosidase (SA-β-gal) staining was performed. The level of mitochondrial reactive oxygen species (ROS) in EPCs was assessed by Mito-Sox staining. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assays. Mitochondrial DNA (mtDNA) copy number and the relative length of telomeres were detected by real time-PCR. The distribution of human telomerase reverse transcriptase (hTERT) in the nucleus, cytosol, and mitochondria of EPCs was detected by immunofluorescence. The expression of B2R, p16, p21, p53, P-Ser473AKT, T-AKT, eNOS, and hTERT was demonstrated by Western blot. Results. B2R expression on circulating CD34+ cells of CBMCs was significantly reduced in patients with GDM compared to healthy controls. Furthermore, B2R expression on circulating CD34+ cells of CBMCs was inversely correlated with plasma 8-iso-PGF2α concentrations and positively correlated with plasma NO levels. BK treatment decreased EPC senescence and ROS generation. Furthermore, BK treatment of HG-exposed cells led to elevated P-Ser473AKT and eNOS protein expression compared with HG treatment alone. BK reduced hTERT translocation in HG-induced senescent EPCs. B2R siRNA, eNOS siRNA, and antagonist of the PI3K signalling pathway blocked the protective effects of BK. Conclusion. BK, acting through PI3K-AKT-eNOS signalling pathways, reduced hTERT translocation, increased the relative length of telomeres while reducing mtDNA copy number, and finally protected against EPC senescence induced by HG.

The effects of Lysinibacillus sp. LF-N1 and Penicillium oxalicum DH-1 inoculants (LFPO group) on compost succession and the microbial dynamic structure of co-composting wheat straw and cow manure composting were investigated. The inoculants contributed to longer thermophilic stages, higher temperatures (62.8 °C) and lower microbial diversity in the LFPO treatment compared to the control group (CK). Moreover, LFPO inoculation increased the germination index and accelerated organic matter and lignocellulose degradation in the compost. Microbial analysis confirmed that the inoculants effectively altered the microbial communities. The predominant biomarkers for bacteria and fungi in inoculated compost were members of Lysinibacillus and Penicillium, respectively. Functional prediction showed greater lignocellulose degradation and less pathogen accumulation in the LFPO group. The cooccurrence network analysis showed that the network structure in LFPO compost was greatly simplified compared to that in CK. Bacterial cluster A was dominated by Lysinibacillus, and fungal cluster B was represented by Penicillium, which were significantly correlated with temperature and lignocellulose degradation, respectively (p < 0.05). These results demonstrated that the LF-N1 and DH-1 inoculants drove the bacterial and fungal assemblies to induce physicochemical property changes during cocomposting.

IntroductionInsomnia with short sleep duration has a more serious negative impact on patient health. The existing literature suggests that medication therapy is more effective for this phenotype of insomnia compared with cognitive–behavioural therapy. However, the potential side effects of hypnotic medications hinder their clinical application. Acupuncture has been widely used in the treatment of insomnia, but it remains unclear whether it has therapeutic efficacy for insomnia with short sleep duration. The purpose of this trial is to evaluate the efficacy and safety of acupuncture for insomnia with short sleep duration.Methods and analysisThis study is designed as a randomised, single-centre, single-blinded, placebo acupuncture controlled trial involving 152 participants. Eligible patients will be divided into two groups according to the objective total sleep time: insomnia with normal sleep duration group and insomnia with short sleep duration group. Then, patients in each group will be randomly assigned to two subgroups, the treatment group (acupuncture) and the control group (placebo acupuncture), in a 1:1 ratio with 38 subjects in each subgroup. The primary outcome is the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. Secondary outcomes are actigraphy, the Beck Anxiety Inventory, the Beck Depression Inventory and the Fatigue Severity Scale. All adverse effects will be assessed by the Treatment Emergent Symptom Scale. Outcomes will be evaluated at baseline, post treatment, as well as at 1-week and 1-month follow-up.Ethics and disseminationThis protocol has been approved by the ethics committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine (no. 2019-17). Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed journals for publications.Trial registration numberChiCTR1900023473; Pre-results.

Improved street lighting can provide better use of public space and helps to promote safety while driving or walking. In terms of balancing benefits and impacts, on the basis of cost saving, this research adopts two prominent mathematical models, the maximal coverage location problem and the location set covering problem, to optimize street light locations. By comparing with the currently installed lights following the rule of thumb, the mathematical models in this research achieve the effect of saving electric energy while meeting residents’ traffic safety needs and living conditions. Furthermore, the models can provide greater coverage of illumination using the same amount of energy.

Abstract Background Arbutin is a plant-derived glycoside with potential antioxidant, antibacterial and anti-inflammatory activities. Currently, it is mainly produced by plant extraction or enzymatic processes, which suffers from expensive processing cost and low product yield. Metabolic engineering of microbes is an increasingly powerful method for the high-level production of valuable biologicals. Since Pseudomonas chlororaphis has been widely engineered as a phenazine-producing platform organism due to its well-characterized genetics and physiology, and faster growth rate using glycerol as a renewable carbon source, it can also be engineered as the cell factory using strong shikimate pathway on the basis of synthetic biology. Results In this work, a plasmid-free biosynthetic pathway was constructed in P. chlororaphis P3 for elevated biosynthesis of arbutin from sustainable carbon sources. The arbutin biosynthetic pathway was expressed under the native promoter P phz using chromosomal integration. Instead of being plasmid and inducer dependent, the metabolic engineering approach used to fine-tune the biosynthetic pathway significantly enhanced the arbutin production with a 22.4-fold increase. On the basis of medium factor optimization and mixed fed-batch fermentation of glucose and 4-hydroxybenzoic acid, the engineered P. chlororaphis P3-Ar5 strain led to the highest arbutin production of 6.79 g/L with the productivity of 0.094 g/L/h, with a 54-fold improvement over the initial strain. Conclusions The results suggested that the construction of plasmid-free synthetic pathway displays a high potential for improved biosynthesis of arbutin and other shikimate pathway derived biologicals in P. chlororaphis.

Objective: The aim of this study was to summarize the evidence of health literacy and health outcomes in hypertensive patients. Methods: Articles published in English were searched from six databases: MEDLINE, CINAHL, Embase, ERIC, psycINFO, and SCOPUS. The articles published up to September 2017 were included. Results: Nineteen publications were included in the review. There was quality and consistent evidence that hypertensive patients with lower literacy had poorer knowledge. There was inconsistent evidence to show the relationship between health literacy and clinical outcomes, of systolic and diastolic blood pressure, and blood pressure control; behavioral outcomes, of self-care, self-efficacy, adherence; patient-physician interactions outcomes, of patient-physician communication, patient trust, involvement in decision making and other outcomes. Conclusion: The person with low health literacy is likely to have poor knowledge of hypertension. However, there is insufficient evidence to suggest that health literacy is associated with outcomes of hypertension independently. Keywords: Health literacy, Hypertension, Outcomes, Integrative review

Objective: The purpose of this study is to assess the awareness on cardiac rehabilitation (CR) in patients with coronary heart disease (CHD). Methods: Inpatients diagnosed with coronary heart disease were recruited from 3 hospitals in this study. The study employed a cardiac structured questionnaire to assess respondents' level of awareness, and bivariate to analyze the sociodemographic factors that influence the awareness on CR. Results: Of all 500 participants, 66.40% were male and the mean age was 62.51 ± 9.96 years. The mean score of knowledge was 44.00 ± 17.00 (score range: 0–93), and the mean level of awareness was 47.31% (awareness range: 0–100%). The highest mean level of awareness was in the reexamination subscale (98%) and the lower were in the basic information about CR program, SP optimized medication and heart rate subscale. Bivariate analysis showed that higher age was associated with less knowledge. Patients with higher education level and better income status had better knowledge. And patients who lived in rural and had no jobs had less knowledge. Conclusions: This study showed low levels of awareness on CR program in CHD patients in Baoding. Therefore, the need for health education is indicated in this study to improve the awareness on CR among CHD patients. Keywords: Coronary heart disease, Cardiac rehabilitation, Awareness, Influencing factors