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Abstract Biomarkers are not only of significant importance for cancer diagnosis and selection of treatment plans but also recently increasingly used for the evaluation of malignancy development and tumor heterogeneity. Large-size tumors from clinical patients can be unique and valuable sources for the study of cancer progression, particularly to the extent of intratumoral heterogeneity. In the present study, we obtained a series of post-surgery puncture samples from a breast cancer patient with a 4 × 3.5 × 2 cm tumor in its original size. Immunohistochemistry for Ki-67, COX-2, and CA IX was performed and the expression levels within the breast cancer tumor mass were evaluated in the reconstructed 3D models. To further evaluate the intratumoral heterogeneity, we performed high throughput whole transcriptome sequencing of 12 samples from different spatial positions within the tumor tissue. Comparing the reconstructed 3D distribution of biomarkers with projected tumor growth models, asymmetric and heterogeneous expansion of tumor mass was found to be possibly influenced by factors such as blood supply, inflammation and/or hypoxia stimulations, as suggested from the correlation between the results of Ki-67 and CA IX or COX-2 staining. Furthermore, high-throughput RNA sequencing data provided additional information for profiling the intratumoral heterogeneity and expanded the understanding of cancer progression. Digital technology for medical imaging once properly integrated with molecular pathology examinations will become particularly helpful in dissecting out in-depth information for precision medicine. We prospect that this approach, facilitated by rapidly advancing artificial intelligence, could provide new insights for clinical decision-making in the future. Strategies for the continuous development from the present study for better performance and application were discussed.

Previous neuroimaging studies based on electroencephalography (EEG) microstate analysis have identified abnormal neural electric activity in patients with psychiatric diseases. However, the microstate information in individuals with different degrees of fear of heights (FoH) remains unknown so far. The aim of the study was therefore to explore the changes of EEG microstate characteristics in different FoH individuals when exposed to high-altitude stimulated by virtual reality (VR). First, acrophobia questionnaire (AQ) before the experiment and 32-channel EEG signals under the virtual high-altitude exposure were collected from 69 subjects. Second, each subject was divided into one of three levels of FoH including no-FoH, mild or moderate FoH (m-FoH) and severe FoH (s-FoH) groups according to their AQ scores. Third, using microstate analysis, we transformed EEG data into sequences of characteristic topographic maps and computed EEG microstate features including microstate basic parameters, microstate sequences complexity and microstate energy. Finally, the extracted features as inputs were sent to train and test an support vector machine (SVM) for classifying different FoH groups. The results demonstrated that five types of microstates (labeled as A, B, C, D and F) were identified across all subjects, of which microstates A-D resembled the four typical microstate classes and microstate F was a non-canonical microstate. Significantly decreased occurrence, coverage and duration of microstate F and transition probabilities from other microstates to microstate F in m-FoH and s-FoH groups were observed compared to no-FoH group. It was also demonstrated that both m-FoH and s-FoH groups showed a notable reduction in sample entropy and Lempel-Ziv complexity. Moreover, energies of microstate D for m-FoH group and microstate B for s-FoH group in right parietal, parietooccipital and occipital regions exhibited prominent decreases as comparison to people without FoH. But, no significant differences were found between m-FoH and s-FoH groups. Additionally, the results indicated that AQ-anxiety scores were negatively correlated with microstate basic metrics as well as microstate energy. For classification, the performance of SVM reached a relatively high accuracy of 89 % for distinguishing no-FoH from m-FoH. In summary, the findings highlight the alterations of EEG microstates in people with fear of heights induced by virtual high-altitude, reflecting potentially underlying abnormalities in the allocation of neural assemblies. Therefore, the combination of EEG microstate analysis and VR may be a potential valuable approach for the diagnosis of fear of heights.

Abstract In this paper we revisit $$D_s \rightarrow f_0(980)$$ D s → f 0 ( 980 ) form factors from the light-cone sum rules based on the $${\bar{q}}q$$ q ¯ q picture of $$f_0(980)$$ f 0 ( 980 ) . The main motivation of this study is the decay width of $$D_s^+ \rightarrow \left[ \pi \pi \right] _{S}^{\textrm{I} = 0} e^+ \nu _e$$ D s + → π π S I = 0 e + ν e measured recently by BESIII collaboration and the $$D_s \rightarrow f_0(980)$$ D s → f 0 ( 980 ) form factor extracted under the resonant model, here the subscript S and superscript $$\textrm{I}=0$$ I = 0 indicate the S-wave isoscalar dipion system. Our result of the differential width of $$D_s^+ \rightarrow f_0(980) (\rightarrow \left[ \pi \pi \right] _{S}^{\textrm{I} = 0}) e^+ \nu _e$$ D s + → f 0 ( 980 ) ( → π π S I = 0 ) e + ν e decay obtained under the narrow width approximation is lower than the data, the result obtained under the resonant Flatté model is consistent with the data, indicating a sizable mixing $$\sim 20^{\circ }$$ ∼ 20 ∘ between $${\bar{s}}s$$ s ¯ s and $${\bar{u}}u+{\bar{d}}d$$ u ¯ u + d ¯ d of $$f_0$$ f 0 . In order to get a model independent prediction, we suggest to calculate $$D_s \rightarrow \left[ \pi \pi \right] ^{\textrm{I} = 0}$$ D s → π π I = 0 form factors with the isoscalar dipion light-cone distribution amplitudes. Our calculation of $$D_s \rightarrow \left[ \pi \pi \right] ^{\textrm{I} = 0}$$ D s → π π I = 0 form factors is carried out at leading twist level due to the finite knowledge of dipion system, the differential width shows a moderate evolution in contrast to that obtained from the narrow width approximation and the Flatté model. Since the $$D_s \rightarrow f_0(980)$$ D s → f 0 ( 980 ) form factors is dominated by the twist three contribution, further measurements on four-body semileptonic charm decays would help us to study the dimeson light-cone distribution amplitudes, especially for the subleading twist one.

Abstract Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma. Knock-down of HSL restrained proliferation, migration, and invasion of glioblastoma cells while adding to FAs could significantly rescue the inhibitory effect of si-HSL on tumor cells. Overexpression of HSL further promoted tumor cell proliferation and invasion. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the regulatory role of ncRNAs on HSL. Mechanistically, hsa_circ_0021205 regulated HSL expression by sponging miR-195-5p, which further promoted lipolysis and drove the malignant progression of glioblastoma. Besides, hsa_circ_0021205/miR-195-5p/HSL axis activated the epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggested that hsa_circ_0021205 promoted tumorigenesis of glioblastoma through regulation of HSL, and targeting hsa_circ_0021205/miR-195-5p/HSL axis can serve as a promising new strategy against glioblastoma.

This study investigated the impact of transcutaneous electrical acupoint stimulation (TEAS) at Neiguan acupoint (PC6) on the physiological and behavioral responses of participants exposed in virtual height. 40 participants were included in the study and were randomly assigned to either a control group or an intervention group. Participants had an immersive experience with a VR interactive platform that provided somatosensory interaction in height stimulation scenes. Psychological scores, behavioral and cognitive performance, and physiological responses were recorded and analyzed. The results indicated that the intervention group had significantly lower fear scores compared to the control group. Analysis of heart rate variability revealed that the intervention group exhibited improved heart rate variability, indicating enhanced cardiovascular function and emotion regulation. The behavioral and cognitive results demonstrated that the intervention group exhibited higher left eye openness, faster reaction times, and greater movement distance, suggesting enhanced attentional focus, cognitive processing, and reduced avoidance behaviors. These findings suggest that TEAS at PC6 can effectively reduce fear and improve the regulation of physiological and behavioral responses to negative emotional stimuli.

Abstract Zinc finger protein 281 (ZNF281) has been shown to promote tumor progression. However, the underlying mechanism remains to be further elucidated. In this study, ZNF281 knockdown increased the expression of mitochondrial transcription factor A (TFAM) in hepatocellular carcinoma (HCC) cells, accompanied with increment of mitochondrial content, oxygen consumption rate (OCR) and levels of TCA cycle intermetabolites. Mechanistic investigation revealed that ZNF281 suppressed the transcription of TFAM, nuclear respiratory factor 1 (NRF1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Furthermore, ZNF281 interacted with NRF1 and PGC-1α, and was recruited onto the promoter regions of TFAM, TFB1M and TFB2M repressing their expression. Knockdown of TFAM reversed ZNF281 depletion induced up-regulation of mitochondrial biogenesis and function, as well as impaired epithelial mesenchymal transition, invasion and metastasis of HCC cells. Our research uncovered a novel suppressive function of ZNF281 on mitochondrial biogenesis through inhibition of the NRF1/PGC-1α-TFAM axis, which may hold therapeutic potentials for HCC.

Sewage sludge odorous gas release is a key barrier to resource utilization, and conditioners can mitigate the release of sulfur-containing gases. The gas release characteristics and sulfur compound distribution in pyrolysis products under both single and composite conditioning strategies of CaO, Fe2O3, and FeCl3 were investigated. This study focused on the inhibition mechanisms of these conditioners on sulfur-containing gas emissions and compared the theoretical and experimental sulfur content in the products to evaluate the potential synergistic effects of the composite conditioners. The findings indicated that at 650 °C, CaO, Fe2O3, and FeCl3 inhibited H2S release by 35.8%, 23.2%, and 9.1%, respectively. Notably, the composite of CaO with FeCl3 at temperatures ranging from 350 to 450 °C and the combination of Fe2O3 with FeCl3 at 650 °C were found to exert synergistic suppression on H2S emissions. The strongly alkaline CaO inhibited the metathesis reaction between HCl, a decomposition product of FeCl3, and the sulfur-containing compounds within the sewage sludge, thereby exerting a synergistic suppression on the emission of H2S. Conversely, at temperatures exceeding 550 °C, the formation of Ca-Fe compounds, such as FeCa2O4, appeared to diminish the sulfur-fixing capacity of the conditioners, resulting in increased H2S emissions. For instance, the combination of CaO and FeCl3 at 450 °C was found to synergistically reduce H2S emissions by 56.3%, while the combination of CaO and Fe2O3 at 650 °C synergistically enhances the release of H2S by 23.6%. The insights gained from this study are instrumental in optimizing the pyrolysis of sewage sludge, aiming to minimize its environmental footprint and enhance the efficiency of resource recovery.

To investigate the control mechanisms of NOx precursors and the synergistic effects of composite catalysts during proline pyrolysis, a systematic series of experiments was conducted utilizing composite catalysts with varying Fe-Ca ratios. Product distribution analysis was employed to elucidate the catalysts’ mechanisms in reducing NOx precursor emissions. The synergistic interactions between Fe and Ca were quantitatively assessed through comparative theoretical and experimental release calculations. The results indicate that an increase in the Fe content in the catalyst led to a rise in amine concentrations from 0.9% to 2.95%, implying that Fe facilitates the generation of amine-N through ring-opening and substitution reactions. When the Fe to Ca ratio was balanced at 1:1, nitrogen predominantly participated in the formation of purines via cyclization and substitution reactions. Additionally, all composite catalysts exhibited a suppressive effect on the release of NOx precursors, attributed to their significant enhancement of solid product retention. Fe-Ca composite catalyst synergistically inhibits the release of gaseous nitrogen. Notably, the strongest synergistic effect was observed with a 1:3 Fe to Ca ratio, which reduced the release of NH3 by 38.7% and HCN by 53.6% during proline pyrolysis. This study offers valuable insights into the control of NOx precursors and the optimization of nitrogen-rich biomass pyrolysis processes.

Abstract We study the pion electromagnetic form factor in the modulus squared dispersion relation, and do the model independent extraction of the chiral mass embedded in the sub-leading twist light-cone distribution amplitude. The motivation of this work is the recent measurement of timelike form factor in the resonant regions, which makes up the piece lacking solid QCD-based calculation. With the perturbative QCD calculation up to next-to-leading-order of strong coupling and twist four level of meson distribution amplitudes, we obtain the chiral mass of pion meson as $$m_0^\pi (1 \, \textrm{GeV}) = 1.31^{+0.27}_{-0.30} \, \textrm{GeV}$$ m 0 π ( 1 GeV ) = 1 . 31 - 0.30 + 0.27 GeV . Due to the chiral enhancement contribution from the sub-leading twist distribution amplitudes in the perturbative QCD calculation, we can not extract the lowest Gegenbauer moments of pion from the study of electromagnetic form factor. This problem could be settled down with the foresee Belle-II and BESIII measurement of the transition form factor especially in the large momentum transfers regions.

Backgrounds: The validity of heart rate variability (HRV) has been substantiated in mental workload assessments. However, cognitive tasks often coincide with physical exertion in practical mental work, but their synergic effects on HRV remains insufficiently established. The study aims were to investigate the combined effects of cognitive and physical load on autonomic nerve functions.Methods: Thirty-five healthy male subjects (aged 23.5 ± 3.3 years) were eligible and enrolled in the study. The subjects engaged in n-back cognitive tasks (1-back, 2-back, and 3-back) under three distinct physical conditions, involving isotonic contraction of the left upper limb with loads of 0 kg, 3 kg, and 5 kg. Electrocardiogram signals and cognitive task performance were recorded throughout the tasks, and post-task assessment of subjective experiences were conducted using the NASA-TLX scale.Results: The execution of n-back tasks resulted in enhanced perceptions of task-load feelings and increased reaction times among subjects, accompanied by a decline in the accuracy rate (p < 0.05). These effects were synchronously intensified by the imposition of physical load. Comparative analysis with a no-physical-load scenario revealed significant alterations in the HRV of the subjects during the cognitive task under moderate and high physical conditions. The main features were a decreased power of the high frequency component (p < 0.05) and an increased low frequency component (p < 0.05), signifying an elevation in sympathetic activity. This physiological response manifested similarly at both moderate and high physical levels. In addition, a discernible linear correlation was observed between HRV and task-load feelings, as well as task performance under the influence of physical load (p < 0.05).Conclusion: HRV can serve as a viable indicator for assessing mental workload in the context of physical activities, making it suitable for real-world mental work scenarios.

Previous neuroimaging studies have revealed abnormal brain networks in patients with major depressive disorder (MDD) in emotional processing. While any cognitive task consists of a series of stages, little is yet known about the topology of functional brain networks in MDD for these stages during emotional face recognition. To address this problem, electroencephalography (EEG)-based functional brain networks of MDD patients at different stages of facial information processing were investigated in this study. First, EEG signals were collected from 16 patients with MDD and 18 age-, gender-, and education-matched normal subjects when performing an emotional face recognition task. Second, the global field power (GFP) method was employed to divide group-averaged event-related potentials into different stages. Third, using the phase transfer entropy (PTE) approach, the brain networks of MDD patients and normal individuals were constructed for each stage in negative and positive face processing, respectively. Finally, we compared the topological properties of brain networks of each stage between the two groups using graph theory approaches. The results showed that the analyzed three stages of emotional face processing corresponded to specific neurophysiological phases, namely, visual perception, face recognition, and emotional decision-making. It was also demonstrated that depressed patients showed abnormally decreased characteristic path length at the visual perception stage of negative face recognition and normalized characteristic path length in the stage of emotional decision-making during positive face processing compared to healthy subjects. Furthermore, while both the MDD and normal groups’ brain networks were found to exhibit small-world network characteristics, the brain network of patients with depression tended to be randomized. Moreover, for patients with MDD, the centro-parietal region may lose its status as a hub in the process of facial expression identification. Together, our findings suggested that altered emotional function in MDD patients might be associated with disruptions in the topological organization of functional brain networks during emotional face recognition, which further deepened our understanding of the emotion processing dysfunction underlying MDD.

Abstract Chemo-resistance hinders the therapeutic efficacy of temozolomide (TMZ) in treating glioblastoma multiforme (GBM). Recurrence of GBM even after combination of maximal tumor resection, concurrent radio-chemotherapy, and systemic TMZ applocation is inevitable and attributed to the high therapeutic resistance of glioma stem cells (GSCs), which can survive, evolve, and initiate tumor tissue remodeling, the underlying mechanisms of GSCs chemo-resistance, have not been fully elucidated up-to-now. Emerging evidence showed that METTL3-mediated N6-methyladenosine (m6A) modification contributed to the self-renew and radio-resistance in GSCs, however, its role on maintenance of TMZ resistance of GSCs has not been clarified and need further investigations. We found that the cell viability and half-maximal inhibitory concentration (IC50) of GSCs against TMZ significantly decreased after GSCs underwent serum-induced differentiation to adherent growth of tumor cells. Besides, METTL3 expression and total m6A modification declined dramatically in consistence with GSCs differentiation. Knockdown of METTL3 weakened self-renew, proliferation and TMZ IC50 of GSCs, whereas enhanced TMZ induced γH2AX level, indicating upregulation of double-strand DNA damage. We also found that mRNA stability of two critical DNA repair genes (MGMT and APNG) was regulated by METTL3-mediated m6A modification. In conclusion, we speculated that METTL3-mediated m6A modification of MGMT and APNG mRNAs played crucial roles on suppression of TMZ sensitivity of GSCs, which suggest a potential new therapeutic target of METTL3 against GBM.

Abstract Ferroptosis induced by detrimental accumulation of lipid peroxides has been recently linked to a variety of pathological conditions ranging from acute tissue injuries to chronic degenerative diseases and suppression of ferroptosis by small chemical inhibitors is beneficial to the prevention and treatment of these diseases. However, in vivo applicable small chemical ferroptosis inhibitors are limited currently. In this study, we screened an alkaloid natural compound library for compounds that can inhibit RSL3-induced ferroptosis in HT1080 cells and identified a group of bisbenzylisoquinoline (BBIQ) compounds as novel ferroptosis-specific inhibitors. These BBIQ compounds are structurally different from known ferroptosis inhibitors and they do not appear to regulate iron homeostasis or lipid ROS generation pathways, while they are able to scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH) in cell-free reactions and prevent accumulation of lipid peroxides in living cells. These BBIQ compounds demonstrate good in vivo activities as they effectively protect mice from folic acid-induced renal tubular ferroptosis and acute kidney injury. Several BBIQ compounds are approved drugs in Japan and China for traditional uses and cepharanthine is currently in clinical trials against SARS-CoV-2, our discovery of BBIQs as in vivo applicable ferroptosis inhibitors will expand their usage to prevent ferroptotic tissue damages under various pathological conditions.

Abstract The decay width of the $$D_s^{*}$$ D s ∗ meson is dominated by the electromagnetic mode $$D_s^*\rightarrow D_s \gamma $$ D s ∗ → D s γ , and it is thus the longest-lived charged vector meson. In light of this point, we perform the first QCD LCSRs calculation of $$D_s^{*}\rightarrow \phi $$ D s ∗ → ϕ helicity form factors and discuss the experiment potential of discovering exclusive $$D_s^{*}$$ D s ∗ weak decays. The main result is the partial decay widths, which read as $$\varGamma _{D_s^*\rightarrow l \nu } = 2.44 \times 10^{-12} \, \textrm{GeV}$$ Γ D s ∗ → l ν = 2.44 × 10 - 12 GeV , $$\varGamma _{D_s^*\rightarrow \phi l \nu } = (3.28^{+0.82}_{-0.71}) \times 10^{-14} \, \textrm{GeV}$$ Γ D s ∗ → ϕ l ν = ( 3 . 28 - 0.71 + 0.82 ) × 10 - 14 GeV , $$\varGamma _{D_s^{*} \rightarrow \phi \pi } = ( 3.81^{+1.52}_{-1.33} ) \times 10^{-14} \, \textrm{GeV}$$ Γ D s ∗ → ϕ π = ( 3 . 81 - 1.33 + 1.52 ) × 10 - 14 GeV and $$\varGamma _{D_s^{*}\rightarrow \phi \rho } = ( 1.16^{+0.42}_{-0.39} ) \times 10^{-13} \, \textrm{GeV}$$ Γ D s ∗ → ϕ ρ = ( 1 . 16 - 0.39 + 0.42 ) × 10 - 13 GeV . We show that these channels are promising in the near future, serving as the first experimental observation of weak decays of a vector meson, and would open up a new playground for precision test of the standard model.

Abstract In order to accurately evaluate power system stability in a timely manner after faults, and further improve the feature extraction ability of the model, this paper presents an improved transient stability assessment (TSA) method of CNN + GRU. This comprises a convolutional neural network (CNN) and gated recurrent unit (GRU). CNN has the feature extraction capability for a micro short-term time sequence, while GRU can extract characteristics contained in a macro long-term time sequence. The two are integrated to comprehensively extract the high-order features that are contained in a transient process. To overcome the difficulty of sample misclassification, a multiple parallel (MP) CNN + GRU, with multiple CNN + GRU connected in parallel, is created. Additionally, an improved focal loss (FL) function which can implement self-adaptive adjustment according to the neural network training is introduced to guide model training. Finally, the proposed methods are verified on the IEEE 39 and 145-bus systems. The simulation results indicate that the proposed methods have better TSA performance than other existing methods.

Metabolism remodelling of macrophages in the glioblastoma microenvironment contributes to immunotherapeutic resistance. However, glioma stem cell (GSC)-initiated lipid metabolism remodelling of transformed macrophages (tMΦs) and its effect on the glioblastoma microenvironment have not been fully elucidated. Total cholesterol (TC) levels and lipid metabolism enzyme expression in macrophages in the GSC microenvironment were evaluated and found that the TC levels of tMΦs were increased, and the expression of the lipid metabolism enzymes calmodulin (CaM), apolipoprotein E (ApoE), and liver X receptor (LXR) was upregulated. Knockdown of HOXC-AS3 led to a decrease in the proliferation, colony formation, invasiveness, and tumorigenicity of tMΦs. Downregulation of CaM resulted in a decline in TC levels. HOXC-AS3 overexpression led to increases in both CaM expression levels and TC levels in tMΦs. RNA pull down and mass spectrometry experiments were conducted and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was screened as the HOXC-AS3 binding proteins related to lipid metabolism. RIP and RNA pull down assays verified that HOXC-AS3 can form a complex with hnRNPA1. Knockdown of hnRNPA1 downregulated CaM expression; however, downregulation of HOXC-AS3 did not affect hnRNPA1 expression.TMΦs underwent lipid metabolism remodelling induced by GSC via the HOXC-AS3/hnRNPA1/CaM pathway, which enhanced the protumor activities of tMΦs, and may serve as a potential metabolic intervening target to improve glioblastoma immunotherapy.

Through whole-genome bisulfite sequencing and RNA-seq, we determined the potential impact of autophagy in regulating DNA methylation in Arabidopsis, providing a solid foundation for further understanding the molecular mechanism of autophagy and how plants cope with nitrogen deficiency. A total of 335 notable differentially expressed genes (DEGs) were discovered in wild-type Arabidopsis (Col-0-N) and an autophagic mutant cultivated under nitrogen starvation (atg5-1-N). Among these, 142 DEGs were associated with hypomethylated regions (hypo-DMRs) and were upregulated. This suggests a correlation between DNA demethylation and the ability of Arabidopsis to cope with nitrogen deficiency. Examination of the hypo-DMR-linked upregulated DEGs indicated that the expression of MYB101, an ABA pathway regulator, may be regulated by DNA demethylation and the recruitment of transcription factors (TFs; ERF57, ERF105, ERF48, and ERF111), which may contribute to the growth arrest induced by abscisic acid (ABA). Additionally, we found that DNA methylation might impact the biosynthesis of salicylic acid (SA). The promoter region of ATGH3.12 (PBS3), a key enzyme in SA synthesis, was hypomethylated, combined with overexpression of PBS3 and its potential TF AT3G46070, suggesting that autophagy defects may lead to SA-activated senescence, depending on DNA demethylation. These findings suggest that DNA hypomethylation may impact the mechanism by which Arabidopsis autophagy mutants (atg5-1) respond to nitrogen deficiency, specifically in relation to ABA and SA regulation. Our evaluation of hormone levels verified that these two hormones are significantly enriched under nitrogen deficiency in atg5-1-N compared to Col-0-N.

Abstract Resistance to 5-fluorouracil (5-FU) in chemotherapy and recurrence of colorectal tumors is a serious concern that impedes improvements to clinical outcomes. In the present study, we found that conditioned medium (CM) derived from 5-FU-resistant HCT-8/FU cells reduced 5-FU chemosensitivity in HCT-8 colon cancer cells, with corresponding changes to number and morphology of Cajal bodies (CBs) as observable nuclear structures. We found that U2AF homology motif kinase 1 (UHMK1) altered CB disassembly and reassembly and regulated the phosphorylation of coilin, a major component of CBs. This subsequently resulted in a large number of variations in RNA alternative splicing that affected cell survival following 5-FU treatment, induced changes in intracellular phenotype, and transmitted preadaptive signals to adjacent cells in the tumor microenvironment (TME). Our findings suggest that CBs may be useful for indicating drug sensitivity or resistance in tumor cells in response to stress signals. The results also suggest that UHMK1 may be an important factor for maintaining CB structure and morphology by regulating splicing events, especially following cellular exposure to cytotoxic drugs. Graphical Abstract Video Abstract

A prolonged period of vigilance task will lead to vigilance decrement and a drop in cognitive efficiency. Although transcranial direct current stimulation (tDCS) can be used to improve cognitive performance following vigilance decrement, the findings in this area of study are inconsistent. This study aims to identify the neuroelectrophysiological and behavioral effects of tDCS over the left dorsolateral prefrontal cortex (DLPFC) on executive vigilance under a continuous monotonous condition. We recruited 29 participants who randomly received 30 min active or sham tDCS before the vigilance task (anode electrode at the left DLPFC, cathode electrode at the right supraorbital area). Participants completed four sessions of vigilance task and five sessions of self-report sleepiness, Oddball task, and Go/Nogo task, for a total of about 5 h. EEG was acquired in real-time throughout the experiment. Repeated measures of ANOVA were utilized to analyze the evolution of each metric with task-on-time. The results demonstrated that subjective arousal state, vigilance performance, event-related potentials (ERPs), and EEG power were significantly affected by time on task. Brain stimulation did not significantly affect the evolution of subjective and objective executive vigilance performance, but significantly modulated spontaneous activity in the alpha and beta bands across the entire brain. The continuous enhancement of the prefrontal cortex increased P2 amplitude for the Oddball task, which was associated with the enhancement of the early stage of information processing. P3 amplitude had a temporary enhancement effect, which significantly decreased following a cognitive fatigue. tDCS had a continuous enhancement effect on N2 amplitude for the Go/Nogo task, which was associated with the enhanced inhibition of distracting stimuli. Together, the current data suggest that anodal tDCS over left DLPFC possibly enhances the early stage of relevant information processing and the inhibitory control of distracting stimuli during a continuous and monotonous vigilance task.

Abstract Background Tumor microenvironment (TME) critically contributed to the malignant progression of transformed cells and the chemical responses to chemotherapy reagents. Osteopontin (OPN) is a secretory onco-protein with several splicing isoforms, all of which were known to regulate tumor growth and able to alter cell-cell or cell-TME communication, however, the exact role and regulation of the OPN splicing isoforms was not well understood. Methods In this study, the effects of conditioned medium from the culture of OPN splicing isoforms overexpressing cells on cell functions were evaluated. The methods of nuclear calcium reporter assays and subcellular distribution of nuclear factor of activated T cells c2 (NFATc2) assays were used to investigate the molecular mechanism underlining the roles of OPN splicing isoforms. Results We found that the survival of NSCLC cells treated with cisplatin was increased by secretory OPNc in the condition medium, where reduction of apoptosis by OPNc was associated with the activation of cellular calcium signals and subsequent nuclear translocation of NFATc2. Conclusions The results revealed a mechanism of OPN and downstream signal for tumor cells to survive in chemo-stressed TME, which emphasized the importance of secretory proteins in alternative splicing isoforms. Our study not only demonstrated the importance of OPN neutralization for anti-tumor effects, but also implied that modulation in calcium/NFATc2/ROS axis could be a novel approach for improving the long-term outcome of NSCLC treatment.

Abstract Many studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.

Abstract Background TCAB1, a.k.a. WRAP53β or WDR79, is an important molecule for the maintenance of Cajal bodies and critically involved in telomere elongation and DNA repair. Upregulation of TCAB1 were discovered in a variety types of cancers. However, the function of TCAB1 in tumor cell senescence remains absent. Methods The TCAB1 knockdown cell lines were constructed. The expression levels of TCAB1, p21, p16 and p53 were detected by qRT-PCR and western blotting. Staining of senescence-associated β-galactosidase was used to detect senescent cells. The ubiquitination of the p21 was analysed by immunoprecipitation and in vivo ubiquitination assay. TCGA databases were employed to perform in silico analyses for the mRNA expression of TCAB1, p21, p16 and p53. Results Here, we discovered that knockdown of TCAB1 induced rapid progression of cellular senescence in A549, H1299 and HeLa cells. In exploiting the mechanism underlining the role of TCAB1 on senescence, we found a significant increase of p21 at the protein levels upon TCAB1 depletion, whereas the p21 mRNA expression was not altered. We verified that TCAB1 knockdown was able to shunt p21 from proteasomal degradation by regulating the ubiquitination of p21. In rescue assays, it was demonstrated that decreasing the expression of p21 or increasing the expression of TCAB1 were able to attenuate the cellular senescence process induced by TCAB1 silencing. Conclusions This study revealed the importance of TCAB1 for its biological functions in the regulation of cell senescence. Our results will be helpful to understand the mechanisms of senescence in cancer cells, which could provide clues for designing novel strategies for developing effective treatment regimens.

BackgroundThe aims of our study were (1) to assess the right ventricular (RV) myocardial mechanics by two-dimensional (2D) and three-dimensional (3D) speckle-tracking echocardiography (STE) in patients with an ischemic or non-ischemic etiology of end-stage heart failure (HF) and (2) to explore which RV index evaluated by 2D- and 3D-STE was the most powerful indicator for identifying the ischemic and non-ischemic etiologies of end-stage HF.MethodsA total of 96 patients with left ventricular ejection fraction (LVEF) < 30% were enrolled in our study: 42 patients (mean age, 52 ± 10 years; 9.5% female) with ischemic cardiomyopathy and 54 patients (mean age, 46 ± 14 years; 16.7% female) with non-ischemic cardiomyopathy. A total of 45 healthy subjects (mean age, 46 ± 13 years; 24.4% female) served as controls. The longitudinal strain of the RV free wall (RVFWLS) was determined by both 2D- and 3D-STE.ResultsCompared to controls, patients with an ischemic or non-ischemic etiology of end-stage HF had lower 2D-RVFWLS, 3D-RVFWLS and RV ejection fraction (RVEF) values (P < 0.05). Patients with non-ischemic cardiomyopathies (NICMs) had significantly lower 3D-RVFWLS and RVEF values than in those with ischemic cardiomyopathies (ICMs), whereas 2D-RVFWLS and conventional RV function parameters did not differ between the two subgroups. RVEF was highly related to 3D-RVFWLS (r = 0.72, P < 0.001), modestly related to 2D-RVFWLS (r = 0.51, P < 0.001), and weakly related to conventional RV function indices (r = –0.26 to 0.46, P < 0.05). Receiver operating characteristic curve analysis revealed that the optimal 3D-RVFWLS cut-off value to distinguish NICM from ICM patients was –14.78% (area under the curve: 0.73, P < 0.001), while 2D-RVFWLS and conventional RV echocardiographic parameters did not.ConclusionOur study demonstrated the superiority of 3D-RVFWLS over 2D-RVFWLS and conventional RV function indices in identifying the ischemic and non-ischemic etiologies of end-stage HF. These findings support the idea that 3D-RVFWLS may be a promising non-invasive imaging marker for distinguishing NICM from ICM.

Abstract Background Drug resistance to 5-fluorouracil (5-FU) and recurrence after chemotherapy in colorectal cancer remain a challenge to be resolved for the improvement of patient outcomes. It is recognized that a variety of secretory proteins released from the tumor cells exposed to chemo-drugs into the tumor microenvironment (TME) contributed to the cell-to-cell communication, and altered the drug sensitivity. One of these important factors is osteopontin (OPN), which exists in several functional forms from alternative splicing and post-translational processing. In colon cancer cells, increased total OPN expression was observed during the progression of tumors, however, the exact role and regulation of the OPN splicing isoforms was not well understood. Methods We assayed precisely the abundance of major OPN splicing isoforms under 5-FU treatments in colon cancer cell lines with different sensitivities to 5-FU, and also evaluated the effects of the condition medium from OPN splicing isoforms overexpressed cells on cell functions. The methods of nuclear calcium reporter assays and ChIP (chromatin immunoprecipitation) assays were used to investigate the molecular mechanism underlining the production of OPN isoforms. Results We discovered that OPNc was a most increased splicing isoform to a significant abundance following 5-FU treatment of colon cancer cells. OPNc as a secretory protein in the conditioned medium exerted a more potent effect to promote cell survival in 5-FU than other OPN isoforms. The kinetic response of nuclear calcium signals could be used to indicate an immediate effect of the conditioned medium containing OPNc and other isoforms. Methyl-CpG binding protein 2 (MeCP2) was identified to regulate the splicing of opn gene, where the phosphorylation of MeCP2 at S421 site, possibly by calmodulin dependent protein kinase II (CaMKII) was required. Conclusions The results demonstrated that the production of OPNc was highly controlled under epigenetic regulations, where MeCP2 and the activation of nuclear calcium signaling were involved. It was also suggested that OPNc could transmit the stress signal of cells upon chemotherapy in TME and promoted the survival of adjacent colon cancer cells.

Abstract In this paper we calculate the $$\bar{B}_s \rightarrow f_0(980)$$ B¯s→f0(980) form factors from light-cone sum rules with B meson DAs. With adopting the quark–antiquark configuration of light scalar mesons, the high twist two-particle and the three-particle contributions are found to be $$\sim 25\%$$ ∼25% individual, and totally they give about $$50\%$$ 50% correction to certain form factors in the considered energy regions. We further explore the light-cone sum rules approach to study the $$S-$$ S- wave $$\bar{B}_s \rightarrow KK$$ B¯s→KK form factors, the $$f_0+f'_0+f''_0$$ f0+f0′+f0′′ resonance model is proposed and the result shows that the background effect from $$f'_0+f''_0$$ f0′+f0′′ accounts $$\sim 5\%$$ ∼5% . As a by-product, we extract the strong coupling $$|g_{f_0 KK }| = 1.08^{+0.05}_{-0.14}$$ |gf0KK|=1.08-0.14+0.05 GeV with taking the $$\bar{B}_s \rightarrow f_0(980)$$ B¯s→f0(980) form factors calculated previous under the narrow width approximation.

Abstract Background Na+/H+ exchanger regulatory factor 1 (NHERF1) is an important scaffold protein participates in the modulation of a variety of intracellular signal pathways. NHERF1 was able to enhance the effects of chemo-drugs in breast and cervical cancer cells. Anaplastic lymphoma kinase (ALK) fusion mutations are validated molecules targeted therapy in lung cancers, where crizotinib can be used as the specific inhibitor to suppress tumor progression. However, due to the less frequent occurrence of ALK mutations and the complexity for factors to determine drug responses, the genes that could alter crizotinib sensitivity are unclear. Methods Both ALK-translocated and ALK-negative lung adenocarcinoma specimens in tissue sections were collected for immunohistochemistry. The possible mechanisms of NHERF1 and its role in the cell sensitivity to crizotinib were investigated using an ALK-positive and crizotinib-sensitive lung adenocarcinoma cell line H3122. Either a NHERF1 overexpression vector or agents for NHERF1 knockdown was used for crizotinib sensitivity measures, in association with cell viability and apoptosis assays. Results The expression level of NHERF1 in ALK-translocated NSCLC was significantly higher than that in other lung cancer tissues. NHERF1 expression in ALK positive lung cancer cells was regulated by ALK activities, and was in return able to alter the sensitivity to crizotinib. The function of NHERF1 to influence crizotinib sensitivity was depending on its subcellular distribution in cytosol instead of its nucleus localized form. Conclusion Ectopically overexpressed NHERF1 could be a functional protein for consideration to suppress lung cancers. The determination of NHERF1 levels in ALK positive NSCLC tissues might be useful to predict crizotinib resistance, especially by distinguishing cytosolic or nuclear localized NHERF1 for the overexpressed molecules.

To realize the win-win benefits and resource coordination of the multilevel operating entities of a “microgrid cluster (MGC), microgrid (MG) and user” and improve the self-consumption of new energy in the MGC, this paper proposes an energy trading model and solution algorithm of an “MGC, MG and user” based on a multi-agent-system, incentive demand response, and hierarchical Stackelberg game theory. By analyzing the game objectives and strategies of these participants, the unique Stackelberg equilibrium (SE) of the hierarchical Stackelberg game is proved theoretically. The game optimization process is divided into two levels. In the upper-level game, the MGC as a leader stimulates the MG to participate in intracluster dispatching by establishing an internal price incentive mechanism. As the follower, the MG determines the number of electricity transactions based on the realized internal price to maximize its own profits. In the lower-level game, the MG leads the game by deciding electricity selling prices based on the load demands of users, and the user as follower adjust electricity consumption using strategies to balance expenditure and experience of electricity usage. Simulation results verified the effectiveness and good convergence of the proposed method and demonstrated that the proposed hierarchical game strategy can improve the economic benefits of each participant, which is conducive to the establishment of friendly grid-connected MGC.

Integration of large-scale cluster electric vehicles (EVs) and their spatial-temporal transfer randomness are likely to affect the safety and economic operation of the distribution network. This paper investigates the spatial-temporal distribution prediction of EVs’ charging load and then evaluates the reliability of the distribution network penetrated with large-scale cluster EVs. To effectively predict the charging load, trip chain technology, Monte Carlo method and Markov decision process (MDP) theory are employed. Moreover, a spatial-temporal transfer model of EVs is established, and based on which, an EV energy consumption model and a charging load prediction model are constructed with consideration of temperature, traffic condition and EV owner’s subjective willingness in different scenarios. With the application of sequential Monte Carlo method, the paper further evaluates distribution network reliability in various charging scenarios. In the evaluation, indices including per unit value (PUV), fast voltage stability index (FVSI), loss of load probability (LOLP), system average interruption frequency index (SAIFI), system average interruption duration index (SAIDI), and expected energy not supplied (EENS) are incorporated. To validate the proposed prediction model and evaluation method, a series of numerical simulations are conducted on the basis of taking the traffic-distribution system of a typical city as an example. The result demonstrates that the proposed spatial-temporal transfer model is more practical in charging load prediction than the popularly used Dijkstra’s shortest path algorithm. Moreover, high temperature, congestion and the increment of EV penetration rate will further weaken distribution network reliability.

Background and ObjectiveThere is a paucity of research that has explored “False Alarm” mechanisms. In order to remedy this deficiency in knowledge, the present study used event-related potential (ERP) technology to reveal the mechanisms underlying False Alarm in response to fear stimuli.MethodsThis study selected snakes as experimental materials and the “oddball paradigm” was used to simulate the conditions of False Alarm. The mechanism underlying False Alarm was revealed by comparing cognitive processing similarities and differences between real snakes and toy snakes.ResultsEvent-related potential findings demonstrated that there was no significant difference between N1 and P2 components induced by real and toy snakes in the early processing stage. Compared with toy snakes, real snakes induced smaller N2 amplitude, larger P3 amplitude, and a shorter P3 latency at the late processing stage. The results of brain topographic mapping analysis showed that the brain regions activated by a real or toy snake were basically the same within the time windows of 110–150 and 220–270 ms, respectively. In the time window of 300–360 and 400–500 ms, the degree of brain regions activation with a real snake was significantly greater than that induced by a toy snake.ConclusionFalse Alarm is caused by the brain’s inability to distinguish, in the early stage of cognitive processing, stimulus objects with similar appearances. When the brain is able to distinguish the differences between different stimulus objects in the late stage of cognitive processing, False Alarm disappears.

Glioma is the most common primary intracranial malignant tumour in adults. It has a high incidence and poses a serious threat to human health. Circular RNA is a hotspot of cancer research. In this study, we aimed to explore the role of circ_0001367 in gliomagenesis and the underlying mechanism. First, qRT-PCR was conducted, which showed that circ_0001367 level was downregulated in glioma tissues and cells. Next, gain-of-function and loss-of-function assays were performed, which indicated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells. Subsequent bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation assays and cell function assays demonstrated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells by absorbing miR-545-3p and thereby regulating the expression of leucine zipper protein (LUZP1). Finally, an in vivo experiment was conducted, which demonstrated that circ_0001367 inhibited glioma growth in vivo by modulating miR-545-3p and LUZP1. Taken together, the results of this study demonstrate that the circ_0001367/miR-545-3p/LUZP1 axis may be a novel target for glioma therapy.

Tyrosine kinase inhibitors (TKIs) to BCR-ABL1 have been successfully used to treat chronic myeloid leukemia (CML), however, multiple TKI-associated adverse events have been reported and become an emerging problem in patients. The mechanisms of TKI-induced toxicity are not fully understood and it remains challenging to predict potential cardiovascular toxicity of a compound. In this study, we established a zebrafish model to evaluate potential in vivo cardiovascular toxicity of TKIs. We treated the endothelium labeled Tg(kdrl:EGFP) transgenic zebrafish embryos with TKIs then performed confocal imaging to evaluate their vascular structure and function. We found that among FDA approved CML TKIs, ponatinib (the only approved TKI that is efficacious to T315I mutation) is the most toxic one. We then evaluated safety profiles of several clinical stage kinase inhibitors that can target T315I and found that HQP1351 treatment leads to vasculopathies similar to those induced by ponatinib while the allosteric ABL inhibitor asciminib does not induce noticeable cardiovascular defects, indicating it could be a promising therapeutic reagent for patients with T315I mutation. We then performed proof-of-principle study to rescue those TKI-induced cardiovascular toxicities and found that, among commonly used anti-hypertensive drugs, angiotensin receptor blockers such as azilsartan and valsartan are able to reduce ponatinib or HQP1351 induced cardiovascular toxicities. Together, this study establishes a zebrafish model that can be useful to evaluate cardiovascular toxicity of TKIs as well as to develop strategies to minimize TKI-induced adverse events.

Acquired chemoresistance is a major limiting factor in the clinical treatment of glioblastoma (GBM). However, the mechanism by which GBM acquires therapeutic resistance remains unclear. Here, we aimed to investigate whether METTL3-mediated N6-methyladenosine (m6A) modification contributes to the temozolomide (TMZ) resistance in GBM. We demonstrated that METTL3 METTL3-mediated m6A modification were significantly elevated in TMZ-resistant GBM cells. Functionally, METTL3 overexpression impaired the TMZ-sensitivity of GBM cells. In contrast, METTL3 silencing or DAA-mediated total methylation inhibition improved the sensitivity of TMZ-resistant GBM cells to TMZ in vitro and in vivo. Furthermore, we found that two critical DNA repair genes (MGMT and APNG) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved TMZ resistance in GBM cells. Collectively, METTL3 acts as a critical promoter of TMZ resistance in glioma and extends the current understanding of m6A related signaling, thereby providing new insights into the field of glioma treatment.

Abstract Background Increased cell mobility is a signature when tumor cells undergo epithelial-to-mesenchymal transition. TGF-β is a key stimulating factor to promote the transcription of a variety of downstream genes to accelerate cancer progression and metastasis, including osteopontin (OPN) which exists in several functional forms as different splicing variants. In non-small cell lung cancer cells, although increased total OPN expression was observed under various EMT conditions, the exact constitution and the underlining mechanism towards the generation of such OPN splicing isoforms was poorly understood. Methods We investigated the possible mechanisms of osteopontin splicing variant and its role in EMT and cancer metastasis using NSCLC cell line and cell and molecular biology techniques. Results In this study, we determined that OPNc, an exon 4 excluded shorter form of Opn gene products, appeared to be more potent to promote cell invasion. The expression of OPNc was selectively increased to higher abundance during EMT following TGF-β induction. The switching from OPNa to OPNc could be enhanced by RUNX2 (a transcription factor that recognizes the Opn gene promoter) overexpression, but appeared to be strictly in a HDAC dependent manner in A549 cells. The results suggested the increase of minor splicing variant of OPNc required both (1) the enhanced transcription from its coding gene driven by specific transcription factors; and (2) the simultaneous modulation or fluctuation of the coupled splicing process that depends to selective classed of epigenetic regulators, predominately HDAC family members. Conclusion Our study not only emphasized the importance of splicing variant for its role in EMT and cancer metastasis, but also helped to understand the possible mechanisms of the epigenetic controls for defining the levels and kinetic of gene splicing isoforms and their generations.

Abstract Background Bacillus subtilis is developed to be an attractive expression host to produce both secreted and cytoplasmic proteins owing to its prominent biological characteristics. Chromosomal integration is a stable expression strategy while the expression level is not ideal compared with plasmid expression. Thus, to meet the requirement of protein overexpression, promoter, as one of the key elements, is important. It is necessary to obtain an ideal promoter for overproduction of foreign proteins from a single copy expression cassette. Results The activity of promoter P ylb was further enhanced by optimizing the − 35, − 10 core region and upstream sequence (UP) by substituting both sequences with consensus sequences. The final engineered promoter exhibited almost 26-fold in β-galactosidase (BgaB) activity and 195-fold in super-folded green fluorescent protein (sfGFP) intensity than that of WT. The two proteins account for 43% and 30% of intracellular proteins, respectively. The promoter was eventually tested by successful extracellular overproduction of Methyl Parathion Hydrolase (MPH) and Chlorothalonil hydrolytic dehalogenase (Chd) to a level of 0.3 g/L (144 U/mL) and 0.27 g/L (4.4 U/mL) on shake-flask culture condition. Conclusions A strong promoter was engineered for efficient chromosomally integrated expression of heterologous proteins.

Autophagy is a highly conserved cell degradation process that widely exists in eukaryotic cells. In plants, autophagy helps maintain cellular homeostasis by degrading and recovering intracellular substances through strict regulatory pathways, thus helping plants respond to a variety of developmental and environmental signals. Autophagy is involved in plant growth and development, including leaf starch degradation, senescence, anthers development, regulation of lipid metabolism, and maintenance of peroxisome mass. More and more studies have shown that autophagy plays a role in stress response and contributes to maintain plant survival. The meristem is the basis for the formation and development of new tissues and organs during the post-embryonic development of plants. The differentiation process of meristems is an extremely complex process, involving a large number of morphological and structural changes, environmental factors, endogenous hormones, and molecular regulatory mechanisms. Recent studies have demonstrated that autophagy relates to meristem development, affecting plant growth and development under stress conditions, especially in shoot and root apical meristem. Here, we provide an overview of the current knowledge about how autophagy regulates different meristems under different stress conditions and possibly provide new insights for future research.

Recent studies have reported that cancer associated fibroblasts (CAFs) and glioma stem-like cells (GSCs) played active roles in glioma progression in tumor microenvironment (TME). Long non-coding RNAs (lncRNAs) have been found to be closely associated with glioma development in recent years, however, their molecular regulatory mechanisms on CAFs in GSCs remodeled TME kept largely unelucidated. Our study found that GSCs could induce malignant transformation of fibroblasts (t-FBs) based on dual-color fluorescence tracing orthotopic model. Associated with poor prognosis, Lnc HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1) was highly expressed in high-grade gliomas and t-FBs. Depleting HOTAIRM1 inhibited the proliferation, invasion, migration, and even tumorigenicity of t-FB. Conversely, overexpression of HOTAIRM1 promoted malignancy phenotype of t-FB. Mechanistically, HOTAIRM1 directly bound with miR-133b-3p, and negatively regulated the latter. MiR-133b-3p partly decreased the promotion effect of HOTAIRM1 on t-FBs. Furthermore, transforming growth factor-β (TGFβ) was verified to be a direct target of miR-133b-3p. HOTAIRM1 can modulate TGFβ via competing with miR-133b-3p. Collectively, HOTAIRM1/miR-133b-3p/TGFβ axis was involved in modulating t-FBs malignancy in TME remodeled by GSCs, which had the potential to serve as a target against gliomas.

This paper aims to investigate the evolution of the chemical structure of coal char during pyrolysis. Two bituminous coals (coals A and B) and one lignite (coal C) were pyrolyzed in a fixed bed in N2 from 600 °C to 1100 °C. The chemical structure of coal char was characterized by Raman spectroscopy and X-ray diffraction (XRD). The carbon and oxygen functionalities of coal char were analyzed by X-ray photoelectron spectroscopy (XPS). The Raman spectroscopic parameters AD/AG (AD1/AG, AD2/AG, and AD3/AG) increased from 600 °C to 900 °C and then decreased after 900 °C, indicating that the degree of order of coal char first decreased and then increased with increasing pyrolysis temperatures (600–1100 °C). The content of graphite-like microcrystalline carbon decreased and then increased with an increase in temperature. Prominent diffraction peaks of microcrystalline carbon for coal chars A and B were observed, but only minerals were shown in diffraction patterns of coal char C since the ash content of coal chars A and B is much lower that that of coal char C. The lateral size of the crystallite plane (La) generally increased between 600 °C and 1100 °C. The relative content of C=O and COOH in coal chars A and B generally decreased as the temperature increased, suggesting an increase in the degree of order at higher temperatures. The oxygen functionalities of coal char were composed of organic oxygen and oxygen-containing bonds of minerals.

Solid polymer electrolytes (SPEs) are promising for the next-generation all-solid-state lithium metal battery (LMB) applications. The effect of semicrystalline structure on ion transport is two-fold: the crystalline domains provide a tortuous diffusion pathway (structural effect) while the tethered chains can cause sluggish ion diffusion (dynamic effect). These two effects are intertwining in a bulk semicrystalline SPE system. In this work, we fabricate a series of polymer single crystal (PSC)-based SPEs by infiltrating lithium bis(trifluoromethylsulfonyl) imide (LiTFSI) into poly(ethylene oxide) (PEO) PSC films. The obtained SPE films show anisotropic conducting behavior with the in-plane conductivity being one to three orders of magnitudes greater than the through-plane conductivity, which can be attributed to the PSC-guided ion transport. The room temperature in-plane conductivity of the PSC SPE can be comparable to its amorphous counterpart, indicating that the tortuosity effect plays a major role in the reduced ionic conductivity of semicrystalline SPEs. PSC-LiTFSI superstructure is observed in the PSC SPEs due to selective perforation of the crystalline PEO lamellae by LiTFSI salts. This work demonstrates the importance of the crystalline morphology on the ion transport in semicrystalline SPEs.

This study focused on the faint interface bonding between carbon fiber (CF) and poly(phthalazinone ether ketone) (PPEK) thermoplastic, a multistage hybrid interface layer was constructed via the condensation reaction of N-[3-(Trimethoxysilyl)propyl]-N,N,N-trimethylammonium chloride (KHN+) and the electrostatic adsorption of graphene oxide (GO). The influence of the contents of GO (0.2 wt%, 0.4 wt%, 0.6 wt%) on the interfacial properties of composites was explored. FTIR, Raman spectra, XPS tests indicated the successful preparation of CF-KHN+-GO reinforcements. The multistage hybrid interface layer significantly increased fiber surface roughness without surface microstructure destruction. Simultaneously, polarity and wettability are remarkably improved as evidenced by the dynamic contact angle experiment. The interlaminar shear strength (ILSS) and flexural strength of the CF/PPEK composites with 0.4 wt% GO (CF-KHN+-4GO) were 74.57 and 1508 MPa, which was 25.2% and 23.5% higher than that of untreated CF/PPEK composite, respectively. Dynamic mechanical analysis proved that CF/GO/PPEK composites have excellent high-temperature mechanical properties. This study furnishes an unsophisticated and valid strategy to build an interface transition layer with a strong binding force, which would offer a new train of thought in preparing high-performing structural composites.

Abstract We study B → ππ form factors using QCD light-cone sum rules with B-meson distribution amplitudes. These form factors describe the semileptonic decay B → π π ℓ ν ¯ ℓ $$ B\to \pi \pi \ell {\overline{\nu}}_{\ell } $$ , and constitute an essential input in B → ππℓ + ℓ − and B → πππ decays. We employ the correlation functions where a dipion isospin-one state is interpolated by the vector light-quark current. We obtain sum rules where convolutions of the P -wave B ¯ 0 → π + π 0 $$ {\overline{B}}^0\to {\pi}^{+}{\pi}^0 $$ form factors with the timelike pion vector form factor are related to universal B-meson distribution amplitudes. These sum rules are valid in the kinematic regime where the dipion state has a large energy and a low invariant mass, and reproduce analytically the known light-cone sum rules for B → ρ form factors in the limit of ρ-dominance and zero width, thus providing a systematics for so far unaccounted corrections to B → ρ transitions. Using data for the pion vector form factor, we estimate finite-width effects and the contribution of excited ρ-resonances to the B → ππ form factors. We find that these contributions amount up to ∼ 20% in the small dipion mass region where they can be effectively regarded as a nonresonant (P -wave) background to the B → ρ transition.

OBJECTIVE:To investigate the potential for static upright balance function and brain-blood oxygen parameters to evaluate pilot workload. METHODS:Phase 1: The NASA Task Load Index (NASA-TLX) was used to compare the workloads of real flights with flight simulator simulated flight tasks in 15 pilots (Cohort 1). Phase 2: To determine the effects of workload, 50 cadets were divided equally into simulated flight task load (experimental) and control groups (Cohort 2). The experimental group underwent 2 h of simulated flight tasks, while the control group rested for 2 h. Their static upright balance function was evaluated using balance index-1 (BI-1), before and after the tasks, with balance system posturography equipment and cerebral blood oxygen parameters monitored with near infrared spectroscopy (NIRS) in real time. Sternberg dual-task and reaction time tests were performed in the experimental and control groups before and after the simulated flight tasks. RESULTS:(Phase1) There was a significant correlation between the workload caused by real flight and simulated flight tasks (P

We calculate the time-like pion electromagnetic form factor in the kT factorization formalism with the inclusion of the next-to-leading-order (NLO) corrections of the leading-twist and sub-leading-twist contributions. It's found that the total NLO correction can enhance (reduce) the magnitude (strong phase) of the leading order form factor by 20%–30% (5 GeV2, and the NLO twist-3 correction plays the key role to narrow the gap between the pQCD predictions and the measured values for the time-like pion electromagnetic form factor.

In this paper, by employing the kT factorization theorem, we made the first calculation for the space-like scalar pion form factor Q2F(Q2) at the leading order (LO) and the next-to-leading order (NLO) level, and then found the time-like scalar pion form factor Fa,I′(1) by analytic continuation from the space-like one. From the analytical evaluations and the numerical results, we found the following points: (a) the NLO correction to the space-like scalar pion form factor has an opposite sign with the LO one but is very small in magnitude, can produce at most 10% decrease to the LO result in the considered Q2 region; (b) the NLO time-like scalar pion form factor Fa,I′(1) describes the O(αs2) contribution to the factorizable annihilation diagrams of the considered B→ππ decays, i.e. the NLO annihilation correction; (c) the NLO part of the form factor Fa,I′(1) is very small in size, and is almost independent of the variation of cutoff scale μ0, but this form factor has a large strong phase around −55° and may play an important role in producing large CP violation for B→ππ decays; and (d) for B0→π+π− and π0π0 decays, the newly known NLO annihilation correction can produce only a very small enhancement to their branching ratios, less than 3% in magnitude, and therefore we could not interpret the well-known ππ-puzzle by the inclusion of this NLO correction to the factorizable annihilation diagrams.

Adeno-Associated Viruses (AAV) are widely used gene-therapy vectors for both clinical applications and laboratory investigations. The titering of different AAV preparations is important for quality control purposes, as well as in comparative studies. However, currently available methods are limited in their ability to detect various serotypes with sensitivity and convenience. Here, we took advantage of a newly discovered AAV receptor protein with high affinity to multiple AAV serotypes, and developed an ELISA-like method named “VIRELISA” (virus receptor-linked immunosorbent assay) by adopting fusion with a streptavidin-binding peptide (SBP). It was demonstrated that optimized VIRELISA assays exhibited satisfactory performance for the titering of AAV2. The linear range of AAV2 was 1 × 105 v.g. to 5 × 109 v.g., with an LOD (limit of detection) of 5 × 104 v.g. Testing of VIRELISA for the quantification of AAV1 was also successful. Our study indicated that a generic protocol for the quantification of different serotypes of AAVs was feasible, reliable and cost-efficient. The applications of VIRELISA will not only be of benefit to laboratory research due to its simplicity, but could also potentially be used for monitoring the circulation AAV loads both in clinical trials and in wild type infection of a given AAV serotype.

Centriolar satellites are non-membrane cytoplasmic granules that deliver proteins to centrosome during centrosome biogenesis and ciliogenesis. Centriolar satellites are highly dynamic during cell cycle or ciliogenesis and how they are regulated remains largely unknown. We report here that sorting nexin 17 (SNX17) regulates the homeostasis of a subset of centriolar satellite proteins including PCM1, CEP131, and OFD1 during serum-starvation-induced ciliogenesis. Mechanistically, SNX17 recruits the deubiquitinating enzyme USP9X to antagonize the mindbomb 1 (MIB1)-induced ubiquitination and degradation of PCM1. SNX17 deficiency leads to enhanced degradation of USP9X as well as PCM1 and disrupts ciliogenesis upon serum starvation. On the other hand, SNX17 is dispensable for the homeostasis of PCM1 and USP9X in serum-containing media. These findings reveal a SNX17/USP9X mediated pathway essential for the homeostasis of centriolar satellites under serum starvation, and provide insight into the mechanism of USP9X in ciliogenesis, which may lead to a better understating of USP9X-deficiency-related human diseases such as X-linked mental retardation and neurodegenerative diseases.

In order to solve problems of low efficiency of locomotive transportation and indefinite materials route caused by shortage of efficient monitoring and control methods of track locomotive transportation system of Chengzhuang Coal Mine, the paper pointed out necessity of designing management system of underground materials transportation. It analyzed advantages and disadvantages of active RFID technology and passive RFID technology with high-frequency, and proposed a management system of underground materials transportation based on UHF RFID. The system is composed of passive RFID label of anti-metal, fixed-mode UHF FRID reader-writer, handed-mode FRID reader-writer and management software of material transportation, and can realize functions of distinguishing, location and remote monitoring for underground locomotives and materials. The actual application showed that the system can improve efficiency of mine auxiliary haulage system effectively.