miR-100 and miR-125b Contribute to Enhanced 3D Growth and Invasiveness and can be Functionally Transferred to Silence Target Genes in Recipient Cells.

Extracellular communication via the transfer of vesicles and nanoparticles is now recognized to play an important role in tumor microenvironment interactions. Cancer cells upregulate and secrete abundant levels of miR-100 and miR-125b that can alter gene expression by both cell- and non-cell-autonomous mechanisms. We previously showed that these miRNAs activate Wnt signaling in colorectal cancer (CRC) through noncanonical pairing with 5 negative regulators of Wnt signaling. To identify additional targets of miR-100 and miR-125b , we used bioinformatic approaches comparing multiple CRC cell lines, including knockout lines lacking one or both of these miRNAs. From an initial list of 96 potential mRNA targets, we tested 15 targets with 8 showing significant downregulation in the presence of miR-100 and miR-125b . Among these, Cingulin (CGN) and Protein tyrosine phosphatase receptor type-R (PTPRR) are downregulated in multiple cancers, consistent with regulation by increased levels of miR-100 and miR-125b. We also show that increased cellular levels of miR-100 and miR-125b enhance 3D growth and invasiveness in CRC and glioblastoma cell lines. Lastly, we demonstrate that extracellular transfer of miR-100 and miR-125b can silence both reporter and endogenous mRNA targets in recipient cells and also increase the invasiveness of recipient spheroid colonies when grown under 3D conditions in type I collagen.

Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis.

Co-inhibitory receptors (Co-IRs) are essential in controlling the progression of immunopathology in rheumatoid arthritis (RA) by limiting T cell activation. The objective of this investigation was to determine the phenotypic expression of Co-IR T cells and to assess the levels of serum soluble PD-1, PDL-2, and TIM3 in Taiwanese RA patients. METHODS: Co-IRs T cells were immunophenotyped employing multicolor flow cytometry, and ELISA was utilized for measuring soluble PD-1, PDL-2, and TIM3. Correlations have been detected across the percentage of T cells expressing Co-IRs (MFI) and different indicators in the blood, including ESR, high-sensitivity CRP (hsCRP), 28 joint disease activity scores (DAS28), and soluble PD-1/PDL-2/TIM3. RESULTS: In RA patients, we recognized elevated levels of PD-1 (CD279), CTLA-4, and TIGIT in CD4+ T cells; TIGIT, HLA-DR, TIM3, and LAG3 in CD8+ T cells; and CD8+CD279+TIM3+, CD8+HLA-DR+CD38+ T cells. The following tests were revealed to be correlated with hsCRP: CD4/CD279 MFI, CD4/CD279%, CD4/TIM3%, CD8/TIM3%, CD8/TIM3 MFI, CD8/LAG3%, and CD8+HLA-DR+CD38+%. CD8/LAG3 and CD8/TIM3 MFIs are linked to ESR. DAS28-ESR and DAS28-CRP exhibited relationships with CD4/CD127 MFI, CD8/CD279%, and CD8/CD127 MFI, respectively. CD4+CD279+TIM3+% was correlated with DAS28-ESR (p = 0.0084, N = 46), DAS28-CRP (p = 0.007, N = 47), and hsCRP (p = 0.002, N = 56), respectively. In the serum of patients with RA, levels of soluble PD-1, PDL-2, and Tim3 were extremely elevated. CD4+ TIM3+% (p = 0.0089, N = 46) and CD8+ TIM3+% (p = 0.0305, N = 46) were correlated with sTIM3 levels; sPD1 levels were correlated with CD4+CD279+% (p < 0.0001, N = 31) and CD3+CD279+% (p = 0.0084, N = 30). CONCLUSIONS: Co-IR expressions on CD4+ and CD8+ T cells, as well as soluble PD-1, PDL-2, and TIM3 levels, could function as indicators of disease activity and potentially play crucial roles in the pathogenesis of RA.

The role of alternative polyadenylation in epithelial-mesenchymal transition of non-small cell lung cancer.

The metastatic non-small cell lung cancer (NSCLC) is one of the cancers with high incidence, poor survival, and limited treatment. Epithelial-mesenchymal transition (EMT) is the first step by which an early tumor converts to an invasive one. Studying the underlying mechanisms of EMT can help the understanding of cancer metastasis and improve the treatment. In this study, 1013 NSCLC patients and 123 NSCLC cell lines are deeply analyzed for the potential roles of alternative polyadenylation (APA) in the EMT process. A trend of shorter 3'-UTRs (three prime untranslated region) is discovered in the mesenchymal samples. The identification of EMT-related APA events highlights the proximal poly(A) selection of CARM1. It is a pathological biomarker of mesenchymal tumor and cancer metastasis through losing miRNA binding to upregulate the EMT inducer of CARM1 and releasing miRNAs to downregulate the EMT inhibitor of RBM47. The crucial role of this APA event in EMT also guides its effect on drug responses. The patients with shorter 3'-UTR of CARM1 are more benefit from chemotherapy drugs, especially cisplatin. A stratification of NSCLC patients based on this APA event is useful for chemotherapy design in future clinics.

PdeERF114 recruits PdeWRKY75 to regulate callus formation in poplar by modulating the accumulation of H2 O2 and the relaxation of cell walls.

Callus formation is important for numerous biological processes in plants. Previously, we revealed that the PdeWRKY75-PdeRBOHB module positively regulates hydrogen peroxide (H2 O2 ) accumulation, thereby affecting callus formation in poplar. In this study, we identified and confirmed a transcription factor, PdeERF114, that interacts with PdeWRKY75 both in vitro and in vivo. Gene expression analysis identified both PdeRBOHB and PdeEXPB2 as downstream genes of PdeERF114 and PdeWRKY75. Overexpression (OE) and reduced-expression (RE) transgenic poplar lines for these four genes were generated, and the observation of callus formation was also performed in all plant materials. We demonstrated that PdeERF114 and PdeWRKY75 formed a protein complex and that this complex could bind W-Box motifs in the promoters of PdeRBOHB and PdeEXPB2, thereby positively regulating the expression of PdeRBOHB and PdeEXPB2. The OE/RE transgenic lines for these four genes also showed enhanced/reduced callus formation. Overall, we revealed a novel gene regulatory network for the regulation of callus formation in plants that involves four genes and regulates callus formation through two pathways: the accumulation of H2 O2 in explants and the relaxation of cell walls. In the future, the four genes could be used to enhance transformation effectiveness in genetic engineering.

AgeAnnoMO: a knowledgebase of multi-omics annotation for animal aging.

Aging entails gradual functional decline influenced by interconnected factors. Multiple hallmarks proposed as common and conserved underlying denominators of aging on the molecular, cellular and systemic levels across multiple species. Thus, understanding the function of aging hallmarks and their relationships across species can facilitate the translation of anti-aging drug development from model organisms to humans. Here, we built AgeAnnoMO (https://relab.xidian.edu.cn/AgeAnnoMO/#/), a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8596 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes multiple aging regulators across species via multi-omics data, comprehensively annotating aging-related genes, proteins, metabolites, mitochondrial genes, microbiotas and age-specific TCR and BCR sequences tied to aging hallmarks for these species and tissues. AgeAnnoMO not only facilitates a deeper and more generalizable understanding of aging mechanisms, but also provides potential insights of the specificity across tissues and species in aging process, which is important to develop the effective anti-aging interventions for diverse populations. We anticipate that AgeAnnoMO will provide a valuable resource for comprehending and integrating the conserved driving hallmarks in aging biology and identifying the targetable biomarkers for aging research.

Systematic Investigation of Novel, Controlled Low-Temperature Sintering Processes for Inkjet Printed Silver Nanoparticle Ink.

Functional inks enable manufacturing of flexible electronic devices by means of printing technology. Silver nanoparticle (Ag NP) ink is widely used for printing conductive components. A sintering process is required to obtain sufficient conductivity. Thermal sintering is the most commonly used method, but the heat must be carefully applied to avoid damaging low-temperature substrates such as polymer films. In this work, two alternative sintering methods, damp heat sintering and water sintering are systematically investigated for inkjet-printed Ag tracks on polymer substrates. Both methods allow sintering polyvinyl pyrrolidone (PVP) capped Ag NPs at 85°C. In this way, the resistance is significantly reduced to only 1.7 times that of the samples on polyimide sintered in an oven at 250°C. The microstructure of sintered Ag NPs is analyzed. Taking the states of the capping layer under different conditions into account, the explanation of the sintering mechanism of Ag NPs at low temperatures is presented. Overall, both damp heat sintering and water sintering are viable options for achieving high conductivity of printed Ag tracks. They can broaden the range of substrates available for flexible electronic device fabrication while mitigating substrate damage risks. The choice between them depends on the specific application and the substrate used.

[Iron store status of children aged 6 to 17 years in Beijing in 2016-2017].

OBJECTIVE: To quantitatively assess the concentration and distribution of body iron(BI) in children aged 6 to 17 years in Beijing. METHODS: A total of 1392 children aged 6 to 17 years in Beijing were randomly selected for questionnaire survey and physical examination in 2016-2017. Fasting venous blood was collected, serum ferritin(SF) and serum soluble transferrin receptor(sTfR) were measured by immunoturbidimetric assay. BI were calculated, and the concentration and distribution of BI in children aged 6 to 17 years was assessed. RESULTS: The average BI level of children aged 6 to 17 in Beijing was(5.49±2.94) mg/kg. The average BI level of boys was higher than that of girls, and the average BI level of children with abdominal obesity was higher than that of children without abdominal obesity, and the differences were statistically significant(P<0.05). The concentration of BI in children aged 6 to 17 years in Beijing was 4-7.99 mg/kg, accounting for the highest proportion(57.3%). The concentration of BI<0 mg/kg accounted for the lowest proportion(4.3%). There were significant differences in the distribution of BI concentration in different gender, age and abdominal obesity(P<0.05). The anemia rate of children aged 6 to 17 in Beijing was 2.7%(95%CI 1.9-3.6), the low ferritin rate(SF<25 µg/L) was 22.5%(95%CI 20.0-24.8), and the iron deficiency rate(SF<15 µg/L) was 7.8%(95%CI 6.4-9.3), the negative iron stores(BI<0 mg/kg) rate was 4.3%(95%CI 3.2-5.3). The anemia rate, low ferritin rate, iron deficiency rate and negative iron stores rate were higher in girls than boys, and higher in children aged 12 to 17 years than in children aged 6 to 11 years, and the differences were statistically significant(P<0.01). CONCLUSION: Iron deficiency was still present in children aged 6 to 17 in Beijing from 2016 to 2017. The proportion of low BI level in girls and children aged 12 to 17 is higher, respectively.

Plant-derived nanovesicles: harnessing nature's power for tissue protection and repair.

Tissue damage and aging lead to dysfunction, disfigurement, and trauma, posing significant global challenges. Creating a regenerative microenvironment to resist external stimuli and induce stem cell differentiation is essential. Plant-derived nanovesicles (PDNVs) are naturally bioactive lipid bilayer nanovesicles that contain proteins, lipids, ribonucleic acid, and metabolites. They have shown potential in promoting cell growth, migration, and differentiation into various types of tissues. With immunomodulatory, microbiota regulatory, antioxidant, and anti-aging bioactivities, PDNVs are valuable in resisting external stimuli and facilitating tissue repair. The unique structure of PDNVs provides an optimal platform for drug encapsulation, and surface modifications enhance their stability and specificity. Moreover, by employing synergistic administration strategies, PDNVs can maximize their therapeutic potential. This review summarized the progress and prospects of PDNVs as regenerative tools, provided insights into their selection for repair activities based on existing studies, considered the key challenge for clinical application, and anticipated their continued prominent role in the field of biomedicine.

Predicting drug-drug interactions based on multi-view and multichannel attention deep learning.

Predicting drug-drug interactions (DDIs) has become a major concern in the drug research field because it helps explore the pharmacological function of drugs and enables the development of new therapeutic drugs. Existing prediction methods simply integrate multiple drug attributes or perform tasks on a biomedical knowledge graph (KG). Though effective, few methods can fully utilize multi-source drug data information. In this paper, a multi-view and multichannel attention deep learning (MMADL) model is proposed, which not only extracts rich drug features containing both drug attributes and drug-related entity information from multi-source databases, but also considers the consistency and complementarity of different drug feature representation learning approaches to improve the effectiveness and accuracy of DDI prediction. A single-layer perceptron encoder is applied to encode multi-source drug information to obtain multi-view drug representation vectors in the same linear space. Then, the multichannel attention mechanism is introduced to obtain the attention weight by adaptively learning the importance of drug features according to their contributions to DDI prediction. Further, the representation vectors of multi-view drug pairs with attention weights are used as inputs of the deep neural network to predict potential DDI. The accuracy and precision-recall curves of MMADL are 93.05 and 95.94, respectively. The results indicate that the proposed method outperforms other state-of-the-art methods.

EEG spectral slope: A reliable indicator for continuous evaluation of consciousness levels during propofol anesthesia.

The level of consciousness undergoes continuous alterations during anesthesia. Prior to the onset of propofol-induced complete unconsciousness, degraded levels of behavioral responsiveness can be observed. However, a reliable index to monitor altered consciousness levels during anesthesia has not been sufficiently investigated. In this study, we obtained 60-channel EEG data from 24 healthy participants during an ultra-slow propofol infusion protocol starting with an initial concentration of 1 µg/ml and a stepwise increase of 0.2 µg/ml in concentration. Consecutive auditory stimuli were delivered every 5 to 6 s, and the response time to the stimuli was used to assess the responsiveness levels. We calculated the spectral slope in a time-resolved manner by extracting 5-second EEG segments at each auditory stimulus and estimated their correlation with the corresponding response time. Our results demonstrated that during slow propofol infusion, the response time to external stimuli increased, while the EEG spectral slope, fitted at 15-45 Hz, became steeper, and a significant negative correlation was observed between them. Moreover, the spectral slope further steepened at deeper anesthetic levels and became flatter during anesthesia recovery. We verified these findings using an external dataset. Additionally, we found that the spectral slope of frontal electrodes over the prefrontal lobe had the best performance in predicting the response time. Overall, this study used a time-resolved analysis to suggest that the EEG spectral slope could reliably track continuously altered consciousness levels during propofol anesthesia. Furthermore, the frontal spectral slope may be a promising index for clinical monitoring of anesthesia depth.

Cell-type-specific alternative polyadenylation promotes oncogenic gene expression in non-small cell lung cancer progression.

Disrupted alternative polyadenylation (APA) is frequently involved in tumorigenesis and cancer progression by regulating the gene expression of oncogenes and tumor suppressors. However, limited knowledge of tumor-type- and cell-type-specific APA events may lead to novel APA events and their functions being overlooked. Here, we compared APA events across different cell types in non-small cell lung cancer (NSCLC) and normal tissues and identified functionally related APA events in NSCLC. We found several cell-specific 3'-UTR alterations that regulate gene expression changes showed prognostic value in NSCLC. We further investigated the function of APA-mediated 3'-UTR shortening through loss of microRNA (miRNA)-binding sites, and we identified and experimentally validated several oncogene-miRNA-tumor suppressor axes. According to our analyses, we found SPARC as an APA-regulated oncogene in cancer-associated fibroblasts in NSCLC. Knockdown of SPARC attenuates lung cancer cell invasion and metastasis. Moreover, we found high SPARC expression associated with resistance to several drugs except cisplatin. NSCLC patients with high SPARC expression could benefit more compared to low-SPARC-expression patients with cisplatin treatment. Overall, our comprehensive analysis of cell-specific APA events shed light on the regulatory mechanism of cell-specific oncogenes and provided opportunities for combination of APA-regulated therapeutic target and cell-specific therapy development.

Cooperation between IRTKS and deubiquitinase OTUD4 enhances the SETDB1-mediated H3K9 trimethylation that promotes tumor metastasis via suppressing E-cadherin expression.

Elevated expression and genetic aberration of IRTKS, also named as BAIAP2L1, have been observed in many tumors, especially in tumor progression. however, the molecular and cellular mechanisms involved in the IRTKS-enhanced tumor progression are obscure. Here we show that higher IRTKS level specifically increases histone H3 lysine 9 trimethylation (H3K9me3) by promoting accumulation of the histone methyltransferase SETDB1. Furthermore, we reveal that IRTKS recruits the deubiquitinase OTUD4 to remove Lys48-linked polyubiquitination at K182/K1050 sites of SETDB1, thus blocking SETDB1 degradation via the ubiquitin-proteasome pathway. Interestingly, the enhanced IRTKS-OTUD4-SETDB1-H3K9me3 axis leads to a general decrease in chromatin accessibility, which inhibits transcription of CDH1 encoding E-cadherin, a key molecule essential for maintaining epithelial cell phenotype, and therefore results in epithelial-mesenchymal transition (EMT) and malignant cell metastasis. Clinically, the elevated IRTKS levels in tumor specimens correlate with SETDB1 levels, but negatively associate with survival time. Our data reveal a novel mechanism for the IRTKS-enhanced tumor progression, where IRTKS cooperates with OTUD4 to enhance SETDB1-mediated H3K9 trimethylation that promotes tumor metastasis via suppressing E-cadherin expression. This study also provides a potential approach to reduce the activity and stability of the known therapeutic target SETDB1 possibly through regulating IRTKS or deubiquitinase OTUD4.

Endophytic bacterial communities in wild rice (Oryza officinalis) and their plant growth-promoting effects on perennial rice.

Endophytic bacterial microbiomes of plants contribute to the physiological health of the host and its adaptive evolution and stress tolerance. Wild rice possesses enriched endophytic bacteria diversity, which is a potential resource for sustainable agriculture. Oryza officinalis is a unique perennial wild rice species in China with rich genetic resources. However, endophytic bacterial communities of this species and their plant growth-promoting (PGP) traits remain largely unknown. In this study, endophytic bacteria in the root, stem, and leaf tissues of O. officinalis were characterized using 16S rRNA gene Illumina sequencing. Culturable bacterial endophytes were also isolated from O. officinalis tissues and characterized for their PGP traits. The microbiome analysis showed a more complex structure and powerful function of the endophytic bacterial community in roots compared with those in other tissue compartments. Each compartment had its specific endophytic bacterial biomarkers, including Desulfomonile and Ruminiclostridium for roots; Lactobacillus, Acinetobacter, Cutibacterium and Dechloromonas for stems; and Stenotrophomonas, Chryseobacterium, Achromobacter and Methylobacterium for leaves. A total of 96 endophytic bacterial strains with PGP traits of phosphate solubilization, potassium release, nitrogen fixation, 1-aminocyclopropane-1-carboxylate (ACC) deaminase secretion, and siderophore or indole-3-acetic acid (IAA) production were isolated from O. officinalis. Among them, 11 strains identified as Enterobacter mori, E. ludwigii, E. cloacae, Bacillus amyloliquefaciens, B. siamensis, Pseudomonas rhodesiae and Kosakonia oryzae were selected for inoculation of perennial rice based on their IAA production traits. These strains showed promising PGP effects on perennial rice seedlings. They promoted plants to form a strong root system, stimulate biomass accumulation, and increase chlorophyll content and nitrogen uptake, which could fulfil the ecologically sustainable cultivation model of perennial rice. These results provide insights into the bacterial endosphere of O. officinalis and its application potential in perennial rice. There is the prospect of mining beneficial endophytic bacteria from wild rice species, which could rewild the microbiome of cultivated rice varieties and promote their growth.

A Shared Hippocampal Network in Retrieving Science-related Semantic Memories.

In responding to the calls for revisiting the role that hippocampus (HIP) plays in semantic memory retrieval, this study used functional neuroimaging-based connectivity technique to elucidate the functional brain network involved in retrieving the correct and incorrect science-related semantic memories. Unlike episodic memory retrieval, the 40 scientific concepts learned during middle and high school were selected to assess 46 science majors' semantic memory retrieval and correctness monitoring, which requires neither the support of spatial information nor events to retrieve the memory. Our results demonstrated that HIP was significantly and robustly engaged in the semantic memory retrieval of correct scientific concepts than incorrect ones. Importantly, the Granger causality analysis indicated that effective connectivity of [Formula: see text] and [Formula: see text] was shared by the semantic memory retrieval of both correct and incorrect scientific concepts. On the other hand, the strengths of connectivity in the [Formula: see text] and [Formula: see text] brain networks appeared more pronounced during the processing of correct scientific concepts than of incorrect ones. The shared hippocampal networks highlight the role of the HIP as a hub to coordinate the INS, ACC, and MTG, in turn, support the semantic memory retrieval of scientific concepts.

A vacuolar transporter plays important roles in zinc and cadmium accumulation in rice grain.

Rice grain is a poor dietary source of zinc (Zn) but the primary source of cadmium (Cd) for humans; however, the molecular mechanisms for their accumulation in rice grain remain incompletely understood. This study functionally characterized a tonoplast-localized transporter, OsMTP1. OsMTP1 was preferentially expressed in the roots, aleurone layer, and embryo of seeds. OsMTP1 knockout decreased Zn concentration in the root cell sap, roots, aleurone layer and embryo, and subsequently increased Zn concentration in shoots and polished rice (endosperm) without yield penalty. OsMTP1 haplotype analysis revealed elite alleles associated with increased Zn level in polished rice, mostly because of the decreased OsMTP1 transcripts. OsMTP1 expression in yeast enhanced Zn tolerance but did not affect that of Cd. While OsMTP1 knockout resulted in decreased uptake, translocation and accumulation of Cd in plant and rice grain, which could be attributed to the indirect effects of altered Zn accumulation. Our results suggest that rice OsMTP1 primarily functions as a tonoplast-localized transporter for sequestrating Zn into vacuole. OsMTP1 knockout elevated Zn concentration but prevented Cd deposition in polished rice without yield penalty. Thus, OsMTP1 is a candidate gene for enhancing Zn level and reducing Cd level in rice grains.

Relaxation spectral analysis in multi-contrast vascular magnetic particle imaging.

BACKGROUND: Magnetic nanoparticles (MNPs) are used as tracers without ionizing radiation in vascular imaging, molecular imaging, and neuroimaging. The relaxation mechanisms of magnetization in response to excitation magnetic fields are important features of MNPs. The basic relaxation mechanisms include internal rotation (Néel relaxation) and external physical rotation (Brownian relaxation). Accurate measurement of these relaxation times may provide high sensitivity for predicting MNP types and viscosity-based hydrodynamic states. It is challenging to separately measure the Néel and Brownian relaxation components using sinusoidal excitation in conventional MPI. PURPOSE: We developed a multi-exponential relaxation spectral analysis method to separately measure the Néel and Brownian relaxation times in the magnetization recovery process in pulsed vascular MPI. METHODS: Synomag-D samples with different viscosities were excited using pulsed excitation in a trapezoidal-waveform relaxometer. The samples were excited at different field amplitudes ranging from 0.5 to 10 mT at intervals of 0.5 mT. The inverse Laplace transform-based spectral analysis of the relaxation-induced decay signal in the field-flat phase was performed by using PDCO, a primal-dual interior method for convex objectives. Néel and Brownian relaxation peaks were elucidated and measured on samples with various glycerol and gelatin concentrations. The sensitivity of viscosity prediction of the decoupled relaxation times was evaluated. A digital vascular phantom was designed to mimic a plaque with viscous MNPs and a catheter with immobilized MNPs. Spectral imaging of the digital vascular phantom was simulated by combining a field-free point with homogeneous pulsed excitation. The relationship between the Brownian relaxation time from different tissues and the number of periods for signal averages was evaluated for a scan time estimation in the simulation. RESULTS: The relaxation spectra of synomag-D samples with different viscosity levels exhibited two relaxation time peaks. The Brownian relaxation time had a positive linear relationship with the viscosity in the range 0.9 to 3.2 mPa · s. When the viscosity was >3.2 mPa · s, the Brownian relaxation time saturated and did not change with increasing viscosity. The Néel relaxation time decreased slightly with an increase in the viscosity. The Néel relaxation time exhibited a similar saturation effect when the viscosity level was >3.2 mPa · s for all field amplitudes. The sensitivity of the Brownian relaxation time increased with the field amplitude and was maximized at approximately 4.5 mT. The plaque and catheter regions were differentiated from the vessel region in the simulated Brownian relaxation time map. The simulation results show that the Néel relaxation time was 8.33±0.09 µs in the plaque region, 8.30±0.08 µs in the catheter region, and 8.46±0.11 µs in the vessel region. The Brownian relaxation time was 36.60±2.31 µs in the plaque region, 30.17±1.24 µs in the catheter region, and 31.21±1.53 µs in the vessel region. If we used 20 excitation periods for image acquisition in the simulation, the total scan time of the digital phantom was approximately 100 s. CONCLUSION: Quantitative assessment of the Néel and Brownian relaxation times through inverse Laplace transform-based spectral analysis in pulsed excitation, highlighting their potential for use in multi-contrast vascular MPI.

Inferring evolutionary trajectories from cross-sectional transcriptomic data to mirror lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is a deadly tumor with dynamic evolutionary process. Although much endeavors have been made in identifying the temporal patterns of cancer progression, it remains challenging to infer and interpret the molecular alterations associated with cancer development and progression. To this end, we developed a computational approach to infer the progression trajectory based on cross-sectional transcriptomic data. Analysis of the LUAD data using our approach revealed a linear trajectory with three different branches for malignant progression, and the results showed consistency in three independent cohorts. We used the progression model to elucidate the potential molecular events in LUAD progression. Further analysis showed that overexpression of BUB1B, BUB1 and BUB3 promoted tumor cell proliferation and metastases by disturbing the spindle assembly checkpoint (SAC) in the mitosis. Aberrant mitotic spindle checkpoint signaling appeared to be one of the key factors promoting LUAD progression. We found the inferred cancer trajectory allows to identify LUAD susceptibility genetic variations using genome-wide association analysis. This result shows the opportunity for combining analysis of candidate genetic factors with disease progression. Furthermore, the trajectory showed clear evident mutation accumulation and clonal expansion along with the LUAD progression. Understanding how tumors evolve and identifying mutated genes will help guide cancer management. We investigated the clonal architectures and identified distinct clones and subclones in different LUAD branches. Validation of the model in multiple independent data sets and correlation analysis with clinical results demonstrate that our method is effective and unbiased.

Causal relationship between Gut Microbiota and Obstructive sleep apnea.

OBJECTIVE: Although observational studies have identified relations between gut microbiota and obstructive sleep apnea (OSA), their causal links remain elusive. Hence, we aimed to investigate this causal relation using the Mendelian randomization (MR) approach. METHODS: Summary-level gut microbiota data were acquired using the maximum available genome-wide association study (GWAS) from the MiBioGen consortium while obtaining summary-level OSA data using publicly available GWAS from the FinnGen Consortium. A two-sample MR analysis was used for assessing gut microbiota and OSA causal effect, using the inverse variance-weighted (IVW) approach as the primary analysis method. The results were further examined for pleiotropy and heterogeneity. Moreover, the reverse MR analysis did not find a causal relationship. RESULTS: Four gut microbiota were found to have nominally significant association to OSA according to the IVW method. Among them, the family Peptostreptococcaceae (OR = 1.171, 95% CI: 1.027-1.334) and genus Coprococcus3 (OR = 1.163, 95% CI: 1.007-1.343), these two florae that may increase the risk of OSA. Family Acidaminococcaceae (OR = 0.843, 95% CI: 0.729-0.975) and genus Blautia (OR = 0.830, 95% CI: 0.708-0.972) may have an ameliorative effect on OSA. No evidence of pleiotropy or heterogeneity was found. CONCLUSIONS: MR analysis indicated that a causal relation is existed between specific gut microbiota and OSA at the genetic prediction level, offering innovative perspectives into the mechanisms underlying gut microbiota-mediated OSA development.

Uncovering the Role of PdePrx12 Peroxidase in Enhancing Disease Resistance in Poplar Trees.

Peroxidase (Prx)-related genes are reported to be involved in the metabolism of hydrogen peroxide (H2O2) in plants. Here, we found that the expression of the PdePrx12 gene was upregulated in wild-type (WT) poplar line NL895 infected with the pathogens Botryosphaeria dothidea strain 3C and Alternaria alternata strain 3E. The PdePrx12 gene was cloned in the poplar line NL895 and its overexpression (OE) and reduced-expression (RE) vectors were constructed. OE and RE transgenic lines were then generated. The H2O2 content in the leaves was measured by DAB staining and spectrophotometric analysis, and the data revealed that the OE line had a reduced H2O2 content, whereas the RE line had an increased H2O2 content. These transgenic and WT plants were also inoculated with the 3C/3E pathogens. The leaf area infected by pathogen 3C/3E was determined and the OE line was found to have a larger area of infection, whereas the RE line was found to have a smaller area of infection. This result suggested PdePRX12 is involved in disease resistance in poplar. Given these results, this study demonstrated that when poplar is infected by pathogens, the expression of PdePrx12 is inhibited, leading to an increase in H2O2 content, thereby enhancing disease resistance.