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Abstract Background The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. Results We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes. m6A-sequencing shows that ablation of METTL16 causes upregulation of the m6A-enriched transcripts and downregulation of the m6A-depleted transcripts, similar to Meioc and/or Ythdc2 mutants. Further in vivo and in vitro experiments demonstrate that the methyltransferase activity site (PP185-186AA) of METTL16 is necessary for spermatogenesis. Conclusions Our findings support a molecular model wherein the m6A writer METTL16-mediated alternative splicing and translation efficiency regulation are required to control the mitosis-to-meiosis germ cell fate decision in mice, with implications for understanding meiosis-related male fertility disorders.

Summary: The importance of trained immunity in antitumor immunity has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis, is required for β-glucan-induced trained immunity in macrophages and ensuing antitumor activity. Unexpectedly, the shunt pathway, but not the classical cholesterol synthesis pathway, catalyzed by SQLE, is required for trained immunity induction. Specifically, 24(S),25-epoxycholesterol (24(S),25-EC), the shunt pathway metabolite, activates liver X receptor and increases chromatin accessibility to evoke innate immune memory. Meanwhile, SQLE-induced reactive oxygen species accumulation stabilizes hypoxia-inducible factor 1α protein for metabolic switching into glycolysis. Hence, our findings identify 24(S),25-EC as a key metabolite for trained immunity and provide important insights into how SQLE regulates trained-immunity-mediated antitumor activity.

IntroductionScalp electroencephalogram (EEG) analysis and interpretation are crucial for tracking and analyzing brain activity. The collected scalp EEG signals, however, are weak and frequently tainted with various sorts of artifacts. The models based on deep learning provide comparable performance with that of traditional techniques. However, current deep learning networks applied to scalp EEG noise reduction are large in scale and suffer from overfitting.MethodsHere, we propose a dual-pathway autoencoder modeling framework named DPAE for scalp EEG signal denoising and demonstrate the superiority of the model on multi-layer perceptron (MLP), convolutional neural network (CNN) and recurrent neural network (RNN), respectively. We validate the denoising performance on benchmark scalp EEG artifact datasets.ResultsThe experimental results show that our model architecture not only significantly reduces the computational effort but also outperforms existing deep learning denoising algorithms in root relative mean square error (RRMSE)metrics, both in the time and frequency domains.DiscussionThe DPAE architecture does not require a priori knowledge of the noise distribution nor is it limited by the network layer structure, which is a general network model oriented toward blind source separation.

For equivalent modeling of mixed wind farms (WFs), existing clustering indicators cannot consider the complex coupling characteristics between different types of wind turbines (WTs). In this paper, a refined equivalent modeling approach based on artificial intelligence technology is proposed. Firstly, the electromechanical transient performance of mixed WFs is analyzed. The WT type, wind speed and direction, and voltage dip are considered the dominant factors affecting the external dynamic response of mixed WFs. Secondly, the equivalent node model is established, including the selection of independent and dependent variables. Then, the multiple artificial neural networks (ANNs) are trained one by one based on small sample data, to fit the nonlinear relationship between the dependent variables and the independent variables. Finally, the dynamic response of the power systems with a mixed WF is simulated in the MATLAB platform. A comparison of the errors in electromechanical phenomena demonstrates that the proposed model can reflect the external characteristics of the test mixed WF in different wind conditions and voltage dips.

BackgroundGlobal positioning system (GPS)-based navigation apps are very useful in our lives. However, whether and how the usage of these apps affects spatial cognition and the sense of direction is still unclear.MethodsA total of 108 individuals were recruited and completed the GPS dependence, internet gaming behavior, and impulsivity test using scales. The eye-tracking-based general mental rotation (MR) task and target finding (TF; require individuals to find a target specified in a 3D street map in a rotated version of top 2D view map) task were used to assess their spatial cognition and the sense of direction. The correlation was used to relate GPS navigation usage, spatial cognition ability, and impulsivity. Subgroup analyses stratifying by gaming hours of individuals (< 2 h or ≥ 2 h) or maps (countryside or city) in TF task were performed. The moderating and mediating effect analyses were conducted to verify these relationships.ResultsThe GPS dependency score was nominal positively correlated with fixations in the TF task in the entire cohort (r = 0.202, unadjusted p = 0.036); it was significant in city (r = 0.254, p = 0.008) and gaming time of < 2 h (r = 0.459, p = 0.001) subgroups. The high-score (upper 30%) group of GPS dependency had more fixations on the original target building in the training area and indicative building in the test area than the low-score (lower 30%) group. GPS dependency was not associated with the correct rate and reaction time in the TF task or any of the indicators in the MR task (p > 0.05). The GPS dependency mediated the indirect effect of impulsivity on the fixations on TF. The internet gaming time moderated the association between GPS dependency and fixations on TF.ConclusionThe dependency on GPS-based navigation apps was associated with impaired spatial cognition but may not significantly affect the sense of direction.

Individuals with high risk of internet gaming disorder (HIGD) showed abnormal psychological performances in response inhibition, impulse control, and emotion regulation, and are considered the high-risk stage of internet gaming disorder (IGD). The identification of this population mainly relies on clinical scales, which are less accurate. This study aimed to explore whether these performances have highly accurate for discriminating HIGD from low-risk ones. Eye tracking based anti-saccade task, Barratt impulsiveness scale (BIS), and Wong and Law emotional intelligence scale (WLEIS) were used to evaluate psychological performances in 57 individuals with HIGD and 52 matched low risk of internet gaming disorder (LIGD). HIGD group showed significantly increased BIS total (t = −2.875, p = 0.005), attention (t = −2.139, p = 0.035), motor (t = −2.017, p = 0.046), and non-planning (t = −2.171, p = 0.032) scores, but significantly decreased WLEIS emotion regulation score (t = 2.636, p = 0.010) and correct rate of eye tracking anti-saccade task (t = 2.294, p = 0.024) compared with LIGD group. BIS total score was negatively correlated with the WLEIS total (r = −0.473, p < 0.001) and WLEIS emotion regulation (r = −0.366, p < 0.001) scores. A combination of the WLEIS emotion regulation score and the correct rate of anti-saccade task could discriminate HIGD from LIGD with 91.23% sensitivity, 82.69% specificity, and 87.16% accuracy. Participants with higher gaming hours daily were 40 times more likely to be high risk than their counterparts (p < 0.001). Hence, psychological performances were worse in HIGD. A combination of abnormal emotion regulation and response inhibition might be a potential marker to identify HIGD individuals.

Abstract Early embryos undergo extensive epigenetic reprogramming to achieve gamete‐to‐embryo transition, which involves the loading and removal of histone variant H2A.Z on chromatin. However, how does H2A.Z regulate gene expression and histone modifications during preimplantation development remains unrevealed. Here, by using ultra‐low‐input native chromatin immunoprecipitation and sequencing, the genome‐wide distribution of H2A.Z is delineated in mouse oocytes and early embryos. These landscapes indicate that paternal H2A.Z is removed upon fertilization, followed by unbiased accumulation on parental genomes during zygotic genome activation (ZGA). Remarkably, H2A.Z exhibits hierarchical accumulation as different peak types at promoters: promoters with double H2A.Z peaks are colocalized with H3K4me3 and indicate transcriptional activation; promoters with a single H2A.Z peak are more likely to occupy bivalent marks (H3K4me3+H3K27me3) and indicate development gene suppression; promoters with no H2A.Z accumulation exhibit persisting gene silencing in early embryos. Moreover, H2A.Z depletion changes the enrichment of histone modifications and RNA polymerase II binding at promoters, resulting in abnormal gene expression and developmental arrest during lineage commitment. Furthermore, similar transcription and accumulation patterns between mouse and porcine embryos indicate that a dual role of H2A.Z in regulating the epigenome required for proper gene expression is conserved during mammalian preimplantation development.

To reduce the torque ripple in motors resulting from the use of conventional direct torque control (DTC), a model predictive control (MPC)-based DTC strategy for a direct matrix converter-fed induction motor is proposed in this paper. Two new look-up tables are proposed, these are derived on the basis of the control of the electromagnetic torque and stator flux using all the feasible voltage vectors and their associated switching states. Finite control set model predictive control (FCS-MPC) has then been adopted to select the optimal switching state that minimizes the cost function related to the electromagnetic torque. Finally, the experimental results are shown to verify the reduced torque ripple performance of the proposed MPC-based DTC method.

Abstract Smad4, a key mediator of the transforming growth factor‐β signaling, is mutated or deleted in 20% of pancreatic ductal adenocarcinoma (PDAC) cancers and significantly affects cancer development. However, the effect of Smad4 loss on the immunogenicity and tumor immune microenvironment of PDAC is still unclear. Here, a surprising function of Smad4 in suppressing mouse PDAC tumor immunogenicity is identified. Although Smad4 deletion in tumor cells enhances proliferation in vitro, the in vivo growth of Smad4‐deficient PDAC tumor is significantly inhibited on immunocompetent C57BL/6 (B6) mice, but not on immunodeficient mice or CD8+ cell‐depleted B6 mice. Mechanistically, Smad4 deficiency significantly increases tumor cell immunogenicity by promoting spontaneous DNA damage and stimulating STING‐mediated type I interferon signaling,which contributes to the activation of type 1 conventional dendritic cells (cDC1) and subsequent CD8+ T cells for tumor control. Furthermore, retarded tumor growth of Smad4‐deficient PDAC cells on B6 mice is largely reversed when Sting is codeleted, or when the cells are implanted into interferon‐alpha receptor‐deficientmice or cDC1‐deficientmice. Accordingly, Smad4 deficiency promotes PDAC immunogenicity by inducing tumor‐intrinsic DNA damage‐elicited type I interferon signaling.

BackgroundEscapism-based motivation (EBM) is considered as one of the diagnostic criteria for internet gaming disorder (IGD). However, how EBM affects the high risk of IGD (HIGD) population remains unclear.MethodsAn initial number of 789 college students participated in the general, internet gaming behavior, and motivation surveys. After multiple evaluations, 57 individuals were identified as HIGD (25 with EBM, H-EBM; 32 with non-EBM, H-nEBM). In addition, 51 no-gaming individuals were included as the control group (CONTR). The cohorts completed the psychological assessments and eye-tracking tests, and analyses of group differences, correlations, and influencing factors of the indicators were performed.ResultsThe Barratt impulsiveness score of H-nEBM and H-EBM was significantly higher than that of CONTR (MD = 3.605, P = 0.017; MD = 3.744, P = 0.022). In addition, emotional intelligence self-emotion management ability was significantly lower in the H-EBM than in CONTR (MD = –2.038, P = 0.004). Correct rates and reaction times in the anti-saccade task differed significantly between the three groups (F = 3.525, P = 0.033; F = 4.459, P = 0.014). However, no differences were found in the comparison of the digital span test (DST), trail making test (TMT), animal verbal fluency test, Stroop test, and mental rotation test results. The anti-saccade test indicators were positively correlated with the DST results but negatively correlated with the Stroop test results (P < 0.05). Correct rates in the mental rotation test were negatively correlated with the TMT results but positively correlated with the DST results (P < 0.05). The participants with high Stroop test scores and no lover experience and who were raised by their grandparents were likely to develop EBM to engage in high risk of internet gaming disorder (P < 0.05).ConclusionEBM has a significantly negative effect on impulsivity, self-emotion management ability, and response inhibition in the HIGD participants.

Oomycetes represent a unique group of plant pathogens that are destructive to a wide range of crops and natural ecosystems. Phytophthora species possess active small RNA (sRNA) silencing pathways, but little is known about the biological roles of sRNAs and associated factors in pathogenicity. Here we show that an AGO gene, PpAGO3, plays a major role in the regulation of effector genes hence the pathogenicity of Phytophthora parasitica. PpAGO3 was unique among five predicted AGO genes in P. parasitica, showing strong mycelium stage-specific expression. Using the CRISPR-Cas9 technology, we generated PpAGO3ΔRGG1-3 mutants that carried a deletion of 1, 2, or 3 copies of the N-terminal RGG motif (QRGGYD) but failed to obtain complete knockout mutants, which suggests its vital role in P. parasitica. These mutants showed increased pathogenicity on both Nicotiana benthamiana and Arabidopsis thaliana plants. Transcriptome and sRNA sequencing of PpAGO3ΔRGG1 and PpAGO3ΔRGG3 showed that these mutants were differentially accumulated with 25–26 nt sRNAs associated with 70 predicted cytoplasmic effector genes compared to the wild-type, of which 13 exhibited inverse correlation between gene expression and 25–26 nt sRNA accumulation. Transient overexpression of the upregulated RXLR effector genes, PPTG_01869 and PPTG_15425 identified in the mutants PpAGO3ΔRGG1 and PpAGO3ΔRGG3, strongly enhanced N. benthamiana susceptibility to P. parasitica. Our results suggest that PpAGO3 functions together with 25–26 nt sRNAs to confer dynamic expression regulation of effector genes in P. parasitica, thereby contributing to infection and pathogenicity of the pathogen.

Organic/polymer light-emitting diodes (OLEDs/PLEDs) have attracted a rising number of investigations due to their promising applications for high-resolution fullcolor displays and energy-saving solid-state lightings. Near-infrared (NIR) emitting dyes have gained increasing attention for their potential applications in electroluminescence and optical imaging in optical tele-communication platforms, sensing and medical diagnosis in recent decades. And a growing number of people focus on the “heavy metal-free” NIR electroluminescent materials to gain more design freedom with cost advantage. This review presents recent progresses in conjugated polymers and organic molecules for OLEDs/PLEDs according to their different luminous mechanism and constructing systems. The relationships between the organic fluorophores structures and electroluminescence properties are the main focus of this review. Finally, the approaches to enhance the performance of NIR OLEDs/PLEDs are described briefly. We hope that this review could provide a new perspective for NIR materials and inspire breakthroughs in fundamental research and applications.

Background Dendritic cells (DCs) play a critical role in antitumor immunity, but the therapeutic efficacy of DC-mediated cancer vaccine remains low, partly due to unsustainable DC function in tumor antigen presentation. Thus, identifying drugs that could enhance DC-based antitumor immunity and uncovering the underlying mechanism may provide new therapeutic options for cancer immunotherapy.Methods In vitro antigen presentation assay was used for DC-modulating drug screening. The function of DC and T cells was measured by flow cytometry, ELISA, or qPCR. B16, MC38, CT26 tumor models and C57BL/6, Balb/c, nude, and Batf3−/− mice were used to analyze the in vivo therapy efficacy and impact on tumor immune microenvironment by clotrimazole treatment.Results By screening a group of small molecule inhibitors and the US Food and Drug Administration (FDA)-approved drugs, we identified that clotrimazole, an antifungal drug, could promote DC-mediated antigen presentation and enhance T cell response. Mechanistically, clotrimazole acted on hexokinase 2 to regulate lactate metabolic production and enhanced the lysosome pathway and Chop expression in DCs subsequently induced DC maturation and T cell activation. Importantly, in vivo clotrimazole administration induced intratumor immune infiltration and inhibited tumor growth depending on both DCs and CD8+ T cells and potentiated the antitumor efficacy of anti-PD1 antibody.Conclusions Our findings showed that clotrimazole could trigger DC activation via the lactate-lysosome axis to promote antigen cross-presentation and could be used as a potential combination therapy approach to improving the therapeutic efficacy of anti-PD1 immunotherapy.

Due to no dc-link energy storage element in the matrix converter (MC), its input and output performances are highly sensitive to the unbalanced grid conditions. In order to mitigate the adverse effects of the unbalanced grid voltages, this paper proposes a simple and effective control strategy based on the finite-control set model predictive control (FCS-MPC). In this case, an extended instantaneous power theory is adapted to generate the source current references. As a result, both sinusoidal source currents and balanced output currents are ensured. Besides, complicated positive and negative sequence decomposition is avoided. Furthermore, an extended state observer (ESO) is designed to eliminate the grid voltages sensors, which not only estimates the grid voltages but also provides the delayed grid voltage information required for the source current reference calculation. The effectiveness of the proposed method is verified by the simulation and experimental results.

Objectives The study aimed to explore the association of coping styles and social support with psychological distress among patients with end-stage renal disease (ESRD) as well as gender differences in these associations. Methods A cross-sectional study of 769 ESRD patients was conducted at 25 hospitals in Qiqihar City, China. All information was collected using structured questionnaires that were self-administered by the patients. Patients’ psychological health status, coping styles and perceived social support were measured using the 12-item General Health Questionnaire, the Medical Coping Modes Questionnaire and the Multidimensional Scale of Perceived Social Support. Student’s t test, analysis of variance (ANOVA) and binary logistic regression analysis were used for data analysis. Results A total of 72.3% of participants reported psychological distress, and the prevalence of distress was higher in females (77.0%) than in males (68.8%). The usage of the acceptance-resignation coping style was positively related to psychological distress (B = 0.459, P

Abstract Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unknown. Here, we found that glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide production and autophagy in mycobacteria-challenged macrophages. Meanwhile, maturation and acidification of mycobacterial phagosomes were attenuated in RAW264.7 cells after glucocorticoids treatment. Consequently, we observed a glucocorticoid-induced increase in the survival of intracellular mycobacteria in both primary macrophages and cell lines. Glucocorticoids treatment decreased the activation of TBK1 kinase, which promotes the maturation of autophagosomes. Inhibition of TBK1 also decreased the production of nitric oxide. Furthermore, several autophagy-related genes were down-regulated, while activation of the Akt/mTOR signaling pathway was increased after glucocorticoids treatment, which may account for autophagy inhibition during mycobacterial infection. Restoration of autophagy with the agonist rapamycin abolished glucocorticoid-mediated enhancement of mycobacterial survival, suggesting that glucocorticoids blocked anti-mycobacterial defense via autophagy inhibition. Collectively, this study demonstrates that glucocorticoids impair innate antimicrobial autophagy and promote mycobacterial survival in macrophages, which is a novel mechanism for glucocorticoid-mediated immunosuppression. Our findings may provide important clues for tuberculosis prevention.

ObjectivesThe main objective of this study was to explore the associations of family relationships and negative life events with depressive symptoms among Chinese adolescents.MethodsA cross-sectional study of 3081 middle school students was conducted in Ganzhou City, Jiangxi Province, China. Students were asked to complete questionnaires regarding family relationships, negative life events, and depressive symptoms. A mediation analysis was carried out using a multiple regression analysis and the PROCESS macro method.ResultsOf all participants, 19.9% reported experiencing depressive symptoms. The prevalence of depressive symptoms was 13.0% and 29.2% in participants with good and poor parental relationships, and the prevalence of depressive symptoms was 11.4% and 30.9% in participants with closed and alienated parental-child relationships, respectively. Parental relationships, parental-child relationships, and negative life events were positively correlated with depressive symptoms. The effect of parental relationships on depressive symptoms was fully mediated by negative life events (Effect = 0.052, 95% CI = [0.023, 0.082]), while the effect of parent-child relationships on adolescent depressive symptoms was partially mediated by negative life events (Effect = 0.075, 95% CI = [0.048, 0.104]).ConclusionsOur results showed a high prevalence of depressive symptoms in Chinese adolescents. Poor family relationships may have the potential to increase the risk of depressive symptoms, and they could affect depressive symptoms through negative life events.

Objective: To assess the effectiveness and safety of electroacupuncture for the treatment of diabetic peripheral neuropathy (DPN). Clinical studies in China have shown the beneficial effect of electroacupuncture compared with conventional medicine. However, the effectiveness of electroacupuncture has not been well acknowledged internationally. Methods: We searched the following databases from their inception through February 2016: MEDLINE, the Cochrane Central Register of Controlled Trials (April, 2015), SinoMed, China National Knowledge Infrastructure, VIP, Wanfang Database, Chinese Important Conference Papers Database, and the Chinese Dissertation Database. Randomized controlled trials (RCTs) were included if they compared electroacupuncture to conventional medicine, placebo, or no treatment on DPN patients. RevMan 5.3 software was used for data analysis, with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). Results: Eleven RCTs involving 837 participants were included. The methodological quality of included RCTs was generally poor in terms of sequence generation, allocation concealment, blinding, incomplete outcome data, and selective outcome reporting. Meta-analysis showed that electroacupuncture had a better effect on global symptom improvement than methylcobalamin (RR = 1.29; 95% CI: 1.14–1.46) and vitamin B (RR = 1.60; 95% CI: 1.33–1.94). Only two RCTs reported adverse events. Conclusions: Because of the high risk of bias of included trials, we cannot make a conclusion on the effectiveness of electroacupuncture for DPN. More rigorously designed and conducted multicenter double-blind RCTs are needed to support the use of electroacupuncture for DPN.

The metal–organic frameworks material functionalized by grafting amino group of tetraethylenepentamine on the coordinative unsaturated Cr (III) centers is described. The obtained tetraethylenepentamine-functionalized adsorbents with different mass ratios of tetraethylenepentamine have been characterized by scanning electron microscopy, Fourier-transform infrared, X-ray powder diffraction, and N 2 adsorption and desorption isotherms. Significantly, MIL-101-tetraethylenepentamine 60% exhibited high adsorption capacity (350 mg/g) for removal of uranium (VI) from water at pH 4.5. At uranium concentration 30 mg/L, the isotherm was best described by Langmuir model.

NLRC3, a member of the NLR family, has been reported as a negative regulator of inflammatory signaling pathways in innate immune cells. However, the direct role of NLRC3 in modulation of CD4+ T-cell responses in infectious diseases has not been studied. In the present study, we showed that NLRC3 plays an intrinsic role by suppressing the CD4+ T cell phenotype in lung and spleen, including differentiation, activation, and proliferation. NLRC3 deficiency in CD4+ T cells enhanced the protective immune response against Mycobacterium tuberculosis infection. Finally, we demonstrated that NLRC3 deficiency promoted the activation, proliferation, and cytokine production of CD4+ T cells via negatively regulating the NF-κB and MEK-ERK signaling pathways. This study reveals a critical role of NLRC3 as a direct regulator of the adaptive immune response and its protective effects on immunity during M. tuberculosis infection. Our findings also suggested that NLRC3 serves as a potential target for therapeutic intervention against tuberculosis.

The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with Mycobacterium tuberculosis (MTB) strain H37Rv and the therapeutic potential of VB5 in vivo with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38), the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6) and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages. We further treated the H37Rv-infected mice with VB5 to explore VB5’s promotion of the clearance of H37Rv in the lungs and the effect of VB5 on regulating the percentage of inflammatory cells. Our data showed that VB5 enhanced the phagocytosis and inflammatory response in macrophages infected with H37Rv. Oral administration of VB5 decreased the number of colony-forming units of H37Rv in lungs of mice at 1, 2, and 4 weeks after infection. In addition, VB5 regulated the percentage of macrophages and promoted CD4+ T cells to express interferon-γ and interleukin-17; however, it had no effect on the percentage of polymorphonuclear neutrophils, CD4+ and CD8+ T cells. In conclusion, VB5 significantly inhibits the growth of MTB by regulating innate immunity and adaptive immunity.

The aim of this study was to establish plasma cytokine/chemokine profiles in patients with 3 different presentations of active tuberculosis (TB), compared to the profiles observed in bacillus Calmette-Guérin (BCG)-vaccinated healthy individuals and patients with other pulmonary diseases (non-TB patients). To this end, plasma samples were collected from 151 TB patients including 68 pulmonary TB (PTB), 43 endobronchial TB, and 40 tuberculosis pleurisy (TP) patients, as well as 107 no-TB cases including 26 non-TB patients and 81 BCG-vaccinated healthy controls. A liquid array-based multiplexed immunoassay was used to screen plasma samples for 20 distinct cytokines and chemokines. Multinomial logistic regression was used to analyze associations between cytokines/chemokines and TB/non-TB patients. Compared to our findings with the no-TB donors, the median plasma levels of the proinflammatory cytokines/chemokines TNF-α, IL-6, IP-10, IFN-γ, and MIP-1β were significantly elevated in TB patients, suggesting their potential use as biomarkers for diagnosing TB patients. Further comparisons with healthy donors showed that only the median TNF-α plasma level was highly produced in the plasma of all 3 types of TB patients. Plasma IL-6 production was higher only in TP patients, while the plasma levels of IP-10, IFN-γ, and MIP-1β were markedly enhanced in both PTB and TP patients. Unexpectedly, among the above cytokines/chemokines, MIP-1β was also highly expressed in non-TB patients, compared with healthy donors. Our results suggested that TNF-α may be an ideal biomarker for diagnosing the 3 forms of TB presentation, while the other factors (IL-6, IP-10, MCP-1, and IFN-γ) can potentially facilitate differential diagnosis for the 3 TB presentation types. Further characterization of immune responses associated with different types of TB diseases will provide a basis for developing novel TB diagnostics.

The purpose of this paper is to commemorate the late scholar Loet Leydesdorff for his great academic contribution on the basis of data from Web of Science. In the span of more than 40 years, he had 526 publications, with the years 2004-2021 being the most productive (394 publications). His international collaborations spread widely across 36 countries, with Germany, the USA, the UK, China, Russia, and South Korea being the most significant. His most frequent collaboration partners included Lutz Bornmann (Germany), Staša Milojević (USA), Caroline Wagner (USA), Henry Etzkowitz (USA), Jonathan Adams (UK), Ronald Rousseau (Belgium), and Ping Zhou (China). With a broad and deep knowledge background, Leydesdorff's research extended across multiple disciplines and fields, but he was most active in library and information science and computer science. He made profound contributions to the study of bibliometrics, innovation systems (the Triple Helix model), and communications. Leydesdorff had a remarkable and extensive citation impact, with citations in 221 WoS subject categories from 120 countries. His publications in 1996, 1998, 2000, 2005, 2006, and 2012 are highly cited, and those on university-industry-government relations (the Triple Helix model) are the most cited. [ABSTRACT FROM AUTHOR]

To retrieve the right collection of publications in interdisciplinary research, we have developed a search strategy with four progressive steps and take the area of public affairs (PA) as a case study. A set of seed publications in PA is first identified, followed by the construction of a pool set of publications with wider coverage for refinement in the next step, which is critical and in which an expanded set of publications is established on the basis of the references and text semantic information, thus generating two respective subsets. One of these subsets is obtained on the basis of the number of references shared between each publication pair between the seed set and the pool set. To optimize the results, we construct two models, viz. a support vector machine (SVM) and a fully connected neural network (FCNN), and find that the FCNN model outperforms the SVM model. The second subset of publications are collected by selecting the publications with high topic similarity to the seed publications collected in the first step. The final step is to integrate the seed publications with the expanded publications collected in steps 1 and 3. The results show that PA research involves an extremely wide range of disciplines (n = 45), among which public administration, environmental sciences, economics, management, and health policy and services, among others, play the most significant roles. [ABSTRACT FROM AUTHOR]

For single-phase current source converter (SCSC), at least one upper device and one lower device have to be gated on and maintained at any time. Otherwise, an open-circuit of the DC-link current would occur and destroy the devices. In addition, a bulky DC-link inductor is usually required to obtain a smooth DC-link current. To address these issues, this study proposes a novel SCSC with high reliability and high-power density. In the proposed circuit, even all the switches are turned on or turned off simultaneously, neither short-circuit nor open-circuit will happen. The inductance in DC-side is reduced significantly byadopting the active power decoupling technique. First, the operation principle of the proposed converter is introduced in detail. Then, a closed-loop control method is presented to regulate the DC-link current, maintain the DC component of the decoupling capacitor voltage, and achieve sinusoidal grid current. Besides, the parameter design of the circuit and controller is investigated. Moreover, the efficiency comparison between the proposed and other SCSCs is carried out. Finally, the effectiveness of the proposed topology is verified by the experimental results. [ABSTRACT FROM AUTHOR]

In Mycobacterium tuberculosis-infected macrophages, cyclooxygenase-2 (COX-2) expression considerably increases to defend the body against mycobacteria by regulating adaptive immunity and restoring the mitochondrial inner membrane. Moreover, in cancer cells, COX-2 enhances the autophagy machinery, an important bactericidal mechanism. However, the association between M. tuberculosis-induced COX-2 and autophagy-mediated antimycobacterial response has not been explored. Here, COX-2 expression silencing reduced the autophagy and bactericidal activity against intracellular M. tuberculosis, while COX-2 overexpression reversed the above effects. In addition, enhancement of bactericidal activity was suppressed by inhibiting autophagy in COX-2-overexpressing cells, indicating that COX-2 accelerated mycobacterial elimination by promoting autophagy. Furthermore, the regulatory effects of COX-2 on autophagy were mediated by its catalytic products, which functioned through inhibiting the protein kinase B/mammalian target of rapamycin pathway. Thus, COX-2 contributes to host defense against mycobacterial infection by promoting autophagy, establishing the basis for development of novel therapeutic agents against tuberculosis by targeting COX-2. [ABSTRACT FROM AUTHOR]

Background: Potent antitumor responses can be induced through cytokine immunotherapy. Interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are among the most effective cytokines to induce tumor-specific systemic immune responses and can act synergistically. To overcome the limitations of combined use of these two cytokines, we have constructed an IL2-GMCSF fusion protein and characterized its antitumor effects in this study.Methods: The expression of IL-2 receptor and GM-CSF receptor of cell lines were detected with quantitative real-time PCR. On this basis, the bioactivities of IL2-GMCSF, especially effects on DC2.4 cells were assayed. Another function of IL2-GMCSF-bridge two types of cells-was assessed by cell contact counting and cytotoxicity assays. The anti-tumor activity in vivo of IL2-GMCSF was evaluated in the melanoma model. The statistical significance among treatment groups were determined by One-Way ANOVA.Results: The fusion protein IL2-GMCSF maintained the activities of IL-2 and GM-CSF, and could significantly promote DC2.4 cell activities, including phagocytosis, proliferation and cytokine secretion. In addition to the inherent cytokine activity, IL2-GMCSF bridges direct cell-cell interactions and enhances splenocyte killing efficacy against multiple tumor cell lines in vitro. Co-injection of IL2-GMCSF and inactivated B16F10 mouse melanoma cells induced complete immunoprotective responses in about 30 % of mice.Conclusion: These results suggested that IL2-GMCSF can efficiently regulate immune responses against tumors. Furthermore, as the bridging effect relies on both IL-2R and GM-CSFR and promotes interactions between immune and tumor cells, IL2-GMCSF may be utilized as a useful tool for dissecting specific immune responses for future clinical applications. [ABSTRACT FROM AUTHOR]

To improve the input and output waveform quality in terms of total harmonic distortion (THD) for the three-level diode-clamped matrix converter topology, the phase disposition carrier-based modulation method is a good option. However, it is difficult to implement because of the loss of zero-current commutations. Aiming at addressing the problem above, a hybrid switching sequence for the phase disposition method is presented to realise the safe commutation, and a prediction-based method is used to alternate the switching sequences. The current direction information of the switches in cascaded rectifier for commutations is obtained by a current reconstruction method. As demonstrated by experimental results, the phase disposition method contributes to lower input and output waveforms THD values compared with the phase opposition disposition method. [ABSTRACT FROM AUTHOR]

This study proposes a new power decoupling circuit applied to the single-phase current source converter (SCSC). Differing from the existing power decoupling technologies, the proposed power decoupling circuit could be viewed as a controlled voltage source in series with the DC inductor, and work with SCSC independently. That facilitates the separate design of the modulation schemes and the control algorithms for the power decoupling circuit and SCSC, and reduces the operation restrictions imposed by requirements. The fundamental principle of the proposed converter is analysed, and the voltage reference requirement for the buffer capacitor is investigated. To guarantee high input current quality of SCSC, a control method, where the input current is treated as a virtual control input, is proposed. Finally the effectiveness of this topology is verified by the simulations and experimental results. [ABSTRACT FROM AUTHOR]