Mass spectrometry-based proteomic landscape of rice reveals a post-transcriptional regulatory role of N6-methyladenosine.

Rice is one of the most important staple food and model species in plant biology, yet its quantitative proteomes are largely uncharacterized. Here we quantify the relative protein levels of over 15,000 genes across major rice tissues using a tandem mass tag strategy followed by intensive fractionation and mass spectrometry. We identify tissue-specific and tissue-enriched proteins that are linked to the functional specificity of individual tissues. Proteogenomic comparison of rice and Arabidopsis reveals conserved proteome expression, which differs from mammals in that there is a strong separation of species rather than tissues. Notably, profiling of N6-methyladenosine (m6A) across the rice major tissues shows that m6A at untranslated regions is negatively correlated with protein abundance and contributes to the discordance between RNA and protein levels. We also demonstrate that our data are valuable for identifying novel genes required for regulating m6A methylation. Taken together, this study provides a paradigm for further research into rice proteogenome.

Dynamics of endothelial cells migration in nature-mimicking blood vessels.

Endothelial cells (ECs) migration is a crucial early step in vascular repair and tissue neovascularization. While extensive research has elucidated the biochemical drivers of endothelial motility, the impact of biophysical cues, including vessel geometry and topography, remains unclear. Herein, we present a novel approach to reconstruct 3D self-assembly blood vessels-on-a-chip that accurately replicates real vessel geometry and topography, surpassing conventional 2D flat tube formation models. This vessels-on-a-chip system enables real-time monitoring of vasculogenesis and ECs migration at high spatiotemporal resolution. Our findings reveal that ECs exhibit increased migration speed and directionality in response to narrower vessel geometries, transitioning from a rounded to a polarized morphology. These observations underscore the critical influence of vessel size in regulating ECs migration and morphology. Overall, our study highlights the importance of biophysical factors in shaping ECs behavior, emphasizing the need to consider such factors in future studies of endothelial function and vessel biology.

Orbital Occupancy Modulation to Optimize Intermediate Absorption for Efficient Electrocatalysts in Water Electrolysis and Zinc-Ethanol-Air Battery.

Spin engineering is a promising way to modulate the interaction between the metal d-orbital and the intermediates and thus enhance the catalytic kinetics. Herein, an innovative strategy is reported to modulate the spin state of Co by regulating its coordinating environment. o-c-CoSe2-Ni is prepared as pre-catalyst, then in situ electrochemical impedance spectroscopy (EIS) and in situ Raman spectroscopy are employed to prove phase transition, and CoOOH/Co3O4 is formed on the surface as active sites. In hybrid water electrolysis, the voltage has a negative shift, and in zinc-ethanol-air battery, the charging voltage is lowered and the cycling stability is greatly increased. Coordinated atom substitution and crystalline symmetry change are combined to regulate the absorption ability of reaction intermediates with balanced optimal adsorption. Coordinated atom substitution weakens the adsorption while the crystalline symmetry change strengthens the adsorption. Importantly, the tetrahedral sites are introduced by Ni doping which enables the co-existence of four-coordinated sites and six-coordination sites in o-c-CoSe2-Ni. The dz2 + dx2-y2 orbital occupancy decreases after the atomic substitution, while increases after replacing the CoSe6-Oh field with CoSe6-Oh/CoSe4-Td. This work explores a new direction for the preparation of efficient catalysts for water electrolysis and innovative zinc-ethanol-air battery.

Research Progress of Group II Intron Splicing Factors in Land Plant Mitochondria.

Mitochondria are important organelles that provide energy for the life of cells. Group II introns are usually found in the mitochondrial genes of land plants. Correct splicing of group II introns is critical to mitochondrial gene expression, mitochondrial biological function, and plant growth and development. Ancestral group II introns are self-splicing ribozymes that can catalyze their own removal from pre-RNAs, while group II introns in land plant mitochondria went through degenerations in RNA structures, and thus they lost the ability to self-splice. Instead, splicing of these introns in the mitochondria of land plants is promoted by nuclear- and mitochondrial-encoded proteins. Many proteins involved in mitochondrial group II intron splicing have been characterized in land plants to date. Here, we present a summary of research progress on mitochondrial group II intron splicing in land plants, with a major focus on protein splicing factors and their probable functions on the splicing of mitochondrial group II introns.

The analysis of HPV integration sites based on nanopore sequencing and the profiling changes along the course of photodynamic therapy.

OBJECTIVE: To detect the HPV genotype and integration sites in patients with high-risk HPV infection at different stages of photodynamic therapy using nanopore technology and to evaluate the treatment effect. METHODS: Four patients with HPV infection were selected and subjected to photodynamic therapy, and cervical exfoliated cell was sampled at before treatment, after three courses of treatment and six courses of treatment, their viral abundance and insertion sites were analyzed by nanopore technology, and pathological examinations were performed before and after treatment. In this study, we developed a novel assay that combined viral sequence enrichment and Nanopore sequencing for identification of HPV genotype and integration sites at once. The assay has obvious advantages over qPCR or NGS-based methods, as it has better sensitivity after viral sequences enrichment and can generate long-reads (kb to Mb) for better detection rate of structure variations, moreover, fast turn-around time for real-time viral sequencing and analysis. RESULTS: The pathological grade was reduced in all four patients after photodynamic therapy. Virus has been cleared in two cases after treatment, the virus amount reduced after treatment but not completely cleared in one case, and two type viruses were cleared and one type virus persisted after treatment in the last patient with multiple infection. Viral abundance and the number of integration sites were positively correlated. Gene enrichment analysis showed complete viral clearance in 1 patient and 3 patients required follow-up. CONCLUSION: Nanopore sequencing can effectively monitor the abundance of HPV viruses and integration sites to show the presence status of viruses, and combined with the results of gene enrichment analysis, the treatment effect can be dynamically assessed.

First principles study of structural and electron properties in scorodite: the bulk and surface.

Scorodite (FeAsO4·2H2O) is an ideal material for the fixation of arsenic that has attracted considerable research interest in recent decades. However, the position of the H atom in the scorodite crystal structure, water molecular configuration, surface morphology, and chemical state of the surface atoms have not been reported. In this work, density functional theory (DFT) is used to optimize the scorodite crystal structure, and the atomic bonding is analyzed. At the same time, a surface model is constructed to calculate the configuration and electronic structure of the surface atoms for different coordination groups. The results show that the tetrahedral [AsO4] and octahedral [FeO4(2H2O)] groups in the scorodite crystal structure have good stability(geometry configuration), and the covalent bond strength between the As atom and the bridged oxygen atom (Ob) is greater than that between the Ob atom and the Fe atom. The water molecules in the crystal structure do not seriously deform and ionize. The configuration of the water molecules remains stable through electrostatic interactions (Ow-Fe) and hydrogen bonding (H-Ob). The Fe atoms on the surface of scorodite can coordinate with OH and H2O, while the As atoms can only form a stable coordination with OH. When an Fe atom on the surface coordinates with two H2O atoms, the Fe atom will shrink to the inside of the bulk. With the increase in the hydroxylation number of the Fe atom, the bonding strength between the Fe atom and the Ob atom decreases. Different surface configurations do not affect the stability(geometry configuration) of the [AsO4] structure. In addition, the surface water molecular layer has a very weak effect on the surface coordination configuration. By contrast, in the surface configuration of the (W + OH) structure, the change in the surface atomic layer spacing is the smallest.

Study on Microstructure Evolution Mechanism of Gradient Structure Surface of AA7075 Aluminum Alloy by Ultrasonic Surface Rolling Treatment.

The materials with grain size gradient variation on the surface, which were prepared with mechanical-induced severe plastic deformation, always show high resistance to high and low cycle fatigue and frictional wear because of their good strength-ductility synergy. The ultrasonic surface rolling treatment (USRT) has the advantages of high processing efficiency, good surface quality, and large residual compressive stress introduced to the surface after treatment. The USRT was used to prepare aluminum alloy (AA7075) samples with a surface gradient structure; meanwhile, the microstructural evolution mechanism of the deformation layers on the gradient structure was studied with XRD, SEM, and TEM. The microstructure with gradient distribution of grain size and dislocation density formed on the surface of AA7075 aluminum alloy after USRT. The surface layer consists of nanocrystals with random orientation distribution, and high-density dislocation cells and subgrains formed in some grains in the subsurface layer, while the center of the material is an undeformed coarse-grained matrix. The results show that the dislocation slip dominates the grain refinement process, following the continuous cutting and refinement of dislocation cells, subgrains, and fragmentation of the second precipitates. This study systematically clarified the mechanism of grain refinement and nanocrystallization on the surface of high-strength aluminum alloys and laid a theoretical foundation for further research on mechanical behavior and surface friction and wear properties of high-strength non-ferrous materials with gradient structure.

Clinical Efficacy and Safety of AdV-tk Gene Therapy for Patients with Cervical Squamous Intraepithelial Lesion: A Prospective Study.

Cervical cancer is the fourth most common type of cancer for women in 2020, and many more women have cervical precancerous lesion-squamous intraepithelial lesion (SIL). Early treatment of cervical SIL to reverse or delay its progression is an important approach to reduce the incidence of cervical cancer. The efficacy and safety of adenovirus-based vectors expressing the thymidine kinase gene (AdV-tk) in the treatment of multiple types of cancers shows promise for its use in gynecology. We aim to provide relevant clinical efficacy and safety data after introducing AdV-tk for the treatment of cervical SIL for the first time through this prospective study. We conducted a maximum of 6 sessions to administer AdV-tk gene therapy to 23 patients (mean age: 35 years old) with cervical low-/high-grade SIL (LSIL/HSIL) who were enrolled from August 2015 to April 2018 and analyzed the clinical characteristics and follow-up outcomes (mean follow-up period: 7.3 months). The present study consisted of 17 patients (73.9%) with cervical HSIL and 6 patients with LSIL confirmed by colposcopy-directed biopsy. We observed an overall histological remission and regression rate of 87.0% (20/23, 95% confidence interval [95% CI]: 73.2-100, p < 0.001) after AdV-tk gene therapy. Eight patients (34.8%) were detected with human papillomavirus (HPV) 16/18 subtypes and 13 patients were found to be positive with at least one of the other 13 high-risk HPV (HR-HPV) subtypes, while 2 patients did not have any of the 15 HR-HPV subtypes. The overall clearance rate of HR-HPV was 76.2% (16/21, 95% CI: 58.0-94.4, p = 0.016) after AdV-tk gene therapy. For safety evaluation, no severe complications were reported in any of the 23 patients. The most commonly reported symptom was fever in 52.2% (12/23) of patients and all symptoms were fully resolved after symptomatic treatment. Our data indicate that AdV-tk gene therapy has high efficacy and safety in the treatment of cervical SIL among gynecological patients. Our findings provide clinical evidence on the potential promotion and application of AdV-tk in the treatment of cervical SIL, and potentially for cervical cancer, among gynecological patients.

Spatial-Temporal EEG Fusion Based on Neural Network for Major Depressive Disorder Detection.

In view of the major depressive disorder characteristics such as high mortality as well as high recurrence, it is important to explore an objective and effective detection method for major depressive disorder. Considering the advantages complementary of different machine learning algorithms in information mining process, as well as the fusion complementary of different information, in this study, the spatial-temporal electroencephalography fusion framework using neural network is proposed for major depressive disorder detection. Since electroencephalography is a typical time series signal, we introduce recurrent neural network embedded in long short-term memory unit for extract temporal domain features to solve the problem of long-distance information dependence. To reduce the volume conductor effect, the temporal electroencephalography data are mapping into a spatial brain functional network using phase lag index, then the spatial domain features were extracted from brain functional network using 2D convolutional neural networks. Considering the complementarity between different types of features, the spatial-temporal electroencephalography features are fused to achieve data diversity. The experimental results show that spatial-temporal features fusion can improve the detection accuracy of major depressive disorder with a highest of 96.33%. In addition, our research also found that theta, alpha, and full frequency band in brain regions of left frontal, left central, right temporal are closely related to MDD detection, especially theta frequency band in left frontal region. Only using single-dimension EEG data as decision basis, it is difficult to fully explore the valuable information hidden in the data, which affects the overall detection performance of MDD. Meanwhile, different algorithms have their own advantages for different application scenarios. Ideally, different algorithms should use their respective advantages to jointly address complex problems in engineering fields. To this end, we propose a computer-aided MDD detection framework based on spatial-temporal EEG fusion using neural network, as shown in Fig. 1. The simplified process is as follows: (1) Raw EEG data acquisition and preprocessing. (2) The time series EEG data of each channel are input as recurrent neural network (RNN), and RNN is used to process and extract temporal domain (TD) features. (3) The BFN among different EEG channels is constructed, and CNN is used to process and extract the spatial domain (SD) features of the BFN. (4) Based on the theory of information complementarity, the spatial-temporal information is fused to realize efficient MDD detection. Fig. 1 MDD detection framework based on spatial-temporal EEG fusion.

Atomic reconstruction and oxygen adsorption behavior of the pyrite (100) surface: a DFT study.

The analysis of the surface chemical behavior of pyrite is highly crucial in the fields of environmental conservation, metal extraction, and flotation separation. In this paper, the mechanism of atomic reconstruction on the pyrite surface and the adsorption behavior of O2 on a reconstructed surface are calculated by density functional theory (DFT). Different reconstruction surfaces were constructed by deleting S and Fe atoms on the (100) surface of pyrite. In addition, the geometric configuration, formation energy, binding energy, cohesion energy, and surface electronic properties of the reconstruction surface were calculated. The adsorption energies and geometric configurations of O2 on different reconstructed surfaces were also determined. The results show that under Fe-poor conditions, the charge of Fe atoms increases, and S atoms form Sn on the reconstructed surface. The binding energy between the Sn and the substrate (ideal surface) is lower, which is similar to the Sn adsorption on the substrate surface with the Fe atom as the site. Sn has high cohesive energy and is resistant to being attacked by oxidants, which leads to structural collapse, and a low affinity for O2. Under S-poor conditions, the -[Fe-S]n- plane structure formed on the reconstructed surface. The -[Fe-S]n- structure stably bonds to the substrate by an Fe-S bond, and exhibits strong binding energy. However, the -[Fe-S]n- structure has low cohesive energy and exhibits thermodynamic instability. In contrast, O2 shows a strong affinity for the -[Fe-S]n- structure, indicating that the deficiency of the S atom promotes the surface oxidation reaction. The mechanism of atomic reconstruction on the surface of pyrite is of utmost importance for understanding its surface chemical behavior.

Peroxymonosulfate activation by Fe-N-S co-doped tremella-like carbocatalyst for degradation of bisphenol A: Synergistic effect of pyridine N, Fe-Nx, thiophene S.

Bisphenol A (BPA) has received increasing attention due to its long-term industrial application and persistence in environmental pollution. Iron-based carbon catalyst activation of peroxymonosulfate (PMS) shows a good prospect for effective elimination of recalcitrant contaminants in water. Herein, considering the problem about the leaching of iron ions and the optimization of heteroatoms doping, the iron, nitrogen and sulfur co-doped tremella-like carbon catalyst (Fe-NS@C) was rationally designed using very little iron, S-C3N4 and low-cost chitosan (CS) via the impregnation-calcination method. The as-prepared Fe-NS@C exhibited excellent performance for complete removal of BPA (20 mg/L) by activating PMS with the high kinetic constant (1.492 min-1) in 15 min. Besides, the Fe-NS@C/PMS system not only possessed wide pH adaptation and high resistance to environmental interference, but also maintained an excellent degradation efficiency on different pollutants. Impressively, increased S-C3N4 doping amount modulated the contents of different N species in Fe-NS@C, and the catalytic activity of Fe-NS@C-1-x was visibly enhanced with increasing S-C3N4 contents, verifying pyridine N and Fe-Nx as main active sites in the system. Meanwhile, thiophene sulfur (C-S-C) as active sites played an auxiliary role. Furthermore, quenching experiment, EPR analysis and electrochemical test proved that surface-bound radicals (·OH and SO4⋅-) and non-radical pathways worked in the BPA degradation (the former played a dominant role). Finally, possible BPA degradation route were proposed. This work provided a promising way to synthesize the novel Fe, N and S co-doping carbon catalyst for degrading organic pollutants with low metal leaching and high catalytic ability.

Electronic Structure Modulation of Nickel Sites by Cationic Heterostructures to Optimize Ethanol Electrooxidation Activity in Alkaline Solution.

It is a good idea for efficient production of hydrogen to use ethanol oxidation reaction (EOR) in place of oxygen evolution reaction (OER) in water electrolysis process. Ni-based non-precious electrocatalysts are widely used in the conversion of ethanol to acetic acid. Here, different selenide heterostructures (NiCoSe, NiFeSe, and NiCuSe) are prepared in which Ni sites are regulated by transition metal. The valence state of Ni is NiCuSe < NiCoSe < NiFeSe in the three heterojunctions. NiCoSe shows the optimized charge distribution of Ni sites and outstanding catalytic activity. The effective modulations lead to optimized d-band center and facilitates both adsorption and desorption of reaction intermediates, which improves the kinetics of EOR. The results of this work prove that with appropriate designed catalyst it is possible to replace kinetically slow OER with faster EOR in water electrolysis to produce hydrogen.

hsa-mir-133a-2 promotes the proliferation and invasion of cervical cancer cells by targeting the LAMB3-mediated PI3K/ATK pathway.

OBJECTIVE: Cervical cancer, one of the common types of malignant tumors progressed in women, is on the rise in developing countries. Numerous previous studies have demonstrated that hsa-mir-133a-2 miRNA is abnormally expressed in cervical cancer cells. However, its fundamental mechanism in cervical cancer needs to be further clarified. Our study set out to investigate the effect of hsa-mir-133a-2 on the phenotypes of cervical cancer cells as well as any potential molecular processes involved in the proliferation and invasion of cervical cancer cells. METHODS: The Cancer Genome Atlas-cervical squamous cell carcinoma and endocervical adenocarcinoma(TCGA-CESC) was adopted in order to verify the expression of hsa-mir-133a-2 in cervical cancer tissues and to identify its potential targets. The interaction between Laminin subunit beta-3(LAMB3) and hsa-mir-133a-2 was verified by TargetScan database as well as Luciferase reporter assay. The Cell Counting Kit-8 (CCK8) and transwell methods were utilized to assess the influence of hsa-mir-133a-2 on the proliferation and invasion characteristics of cervical cancer cells. We studied the role that hsa-mir-133a-2 plays in cervical cancer progression through Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis as well as Western Blot (WB) experiment. RESULTS: Down-regulation of hsa-mir-133a-2 was detected in cervical cancer tissues. It directly targeted LAMB3 and negatively regulated LAMB3 expression. The overexpression of hsa-mir-133a-2 has a significant inhibiting effect on cervical cancer cell proliferation and invasion. The overexpression of hsa-mir-133a-2 significantly inhibits the proliferation and invasion of cervical cancer cells. Moreover, the LAMB3 was able to up-regulate the phosphorylation levels of AKT and phosphatidylinositol 3-kinase (PI3K) protein in cervical cancer cells. hsa-mir-133a-2 could also modulate the PI3K/AKT signaling pathway by targeting LAMB3. CONCLUSION: hsa-mir-133a-2 inhibits cervical cancer cell proliferation and invasion by indirectly regulating the PI3K/AKT signaling pathway, providing us with a new clinical treatment strategy for cervical cancer.

Genome-edited ATP BINDING CASSETTE B1 transporter SD8 knockouts show optimized rice architecture without yield penalty.

This study reports the identification of the rice open reading frame Semi-Dwarf in chr8 (SD8) that encodes a putative ortholog of Arabidopsis thaliana ABCB1. Genome editing of SD8 leads to optimized rice architecture by reducing plant height and flag-leaf angle without yield penalty. Rice SD8 knockouts may also have the potential for increased yield under high density planting.

EMP80 mediates the C-to-U editing of nad7 and atp4 and interacts with ZmDYW2 in maize mitochondria.

RNA C-to-U editing is important to the expression and function of organellar genes in plants. Although several families of proteins have been identified to participate in this process, the underlying mechanism is not fully understood. Here we report the function of EMP80 in the C-to-U editing at the nad7-769 and atp4-118 sites, and the potential recruitment of ZmDYW2 as a trans deaminase in maize (Zea mays) mitochondria. Loss of EMP80 function arrests embryogenesis and endosperm development in maize. EMP80 is a PPR-E+ protein localised to mitochondria. An absence of EMP80 abolishes the C-to-U RNA editing at nad7-769 and atp4-118 sites, resulting in a cysteine-to-arginine (Cys→Arg) change in Nad7 and Atp4 in the emp80 mutant. The amino acid change consequently reduces the assembly of complexes I and V, leading to an accumulation of the F1 subcomplex of complex V. EMP80 was found to interact with atypical DYW-type PPR protein ZmDYW2, which interacts with ZmNUWA. Co-expression of ZmNUWA enhances the interaction between EMP80 and ZmDYW2, suggesting that EMP80 potentially recruits ZmDYW2 as a trans deaminase through protein-protein interaction, and ZmNUWA may function as an enhancer of this interaction.

Microstructure and Phase Evolution Characteristics of the In Situ Synthesis of TiC-Reinforced AZ91D Magnesium Matrix Composites.

TiC-reinforced AZ91D magnesium alloy composites were synthesized through the in situ reaction between an AZ91D melt and Ti-C-Al preforms. The microstructural evolution characteristics and phase transformation were investigated at different melt reaction temperatures (1013, 1033, and 1053 K), with the aim of understanding the in situ formation mechanism of TiC particles from thermodynamic and kinetic perspectives. The results showed that the temperature played a critical role in determining the formation and morphology of TiC. Initially, only the Al3Ti phase was formed through the reaction between Ti and Al when the temperature was 1013 K. With the increase in the melt temperature, the A13Ti's thermodynamic stability decreased, and dissolution and precipitation reactions occurred at higher temperatures (1033 and 1053 K, respectively), contributing to the formation of TiC particles. The formation of the TiC phase was attributed to two factors: Firstly, A13Ti as an intermediate product reacted with carbon and formed TiC with increasing temperature. Secondly, the in situ TiC reaction was promoted due to the increased reaction-driving force provided by the increasing temperature.

Functions of PPR Proteins in Plant Growth and Development.

Pentatricopeptide repeat (PPR) proteins form a large protein family in land plants, with hundreds of different members in angiosperms. In the last decade, a number of studies have shown that PPR proteins are sequence-specific RNA-binding proteins involved in multiple aspects of plant organellar RNA processing, and perform numerous functions in plants throughout their life cycle. Recently, computational and structural studies have provided new insights into the working mechanisms of PPR proteins in RNA recognition and cytidine deamination. In this review, we summarized the research progress on the functions of PPR proteins in plant growth and development, with a particular focus on their effects on cytoplasmic male sterility, stress responses, and seed development. We also documented the molecular mechanisms of PPR proteins in mediating RNA processing in plant mitochondria and chloroplasts.

Cross-neutralization of RBD mutant strains of SARS-CoV-2 by convalescent patient derived antibodies.

BACKGROUND: The emergence of COVID-19 pandemic resulted in an urgent need for the development of therapeutic interventions. Of which, neutralizing antibodies play a crucial role in the prevention and resolution of viral infection. METHODS: We generated antibody libraries from 18 different COVID-19 recovered patients and screened neutralizing antibodies to SARS-CoV-2 and its mutants. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Clones were then reconstituted into whole human IgG for epitope binning assay and all 19 IgG were classified into 6 different epitope groups or Bins. RESULTS: Although all antibodies were found to bind RBD, the antibodies in Bin2 had superior inhibitory ability of the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 showed stronger binding affinity or ability to mutant RBDs (N501Y, W463R, R408I, N354D, V367F, and N354D/D364Y) derived from different SARS-CoV-2 strains as well, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 and its mutations. Furthermore, such neutralizing antibodies strongly restricted the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized wildtype and more transmissible mutant pseudovirus entry into hACE2 overexpressed 293T cells. In Vero-E6 cells, one of these antibodies can even block the entry of live SARS-CoV-2 into cells at 12.5 nM. CONCLUSIONS: These results indicate that the neutralizing human antibodies from the patient-derived antibody libraries have the potential to fight SARS-CoV-2 and its mutants in this global pandemic.

A deep learning approach to automate whole-genome prediction of diverse epigenomic modifications in plants.

Epigenetic modifications function in gene transcription, RNA metabolism, and other biological processes. However, multiple factors currently limit the scientific utility of epigenomic datasets generated for plants. Here, using deep-learning approaches, we developed a Smart Model for Epigenetics in Plants (SMEP) to predict six types of epigenomic modifications: DNA 5-methylcytosine (5mC) and N6-methyladenosine (6mA) methylation, RNA N6-methyladenosine (m6 A) methylation, and three types of histone modification. Using the datasets from the japonica rice Nipponbare, SMEP achieved 95% prediction accuracy for 6mA, and also achieved around 80% for 5mC, m6 A, and the three types of histone modification based on the 10-fold cross-validation. Additionally, > 95% of the 6mA peaks detected after a heat-shock treatment were predicted. We also successfully applied the SMEP for examining epigenomic modifications in indica rice 93-11 and even the B73 maize line. Taken together, we show that the deep-learning-enabled SMEP can reliably mine epigenomic datasets from diverse plants to yield actionable insights about epigenomic sites. Thus, our work opens new avenues for the application of predictive tools to facilitate functional research, and will almost certainly increase the efficiency of genome engineering efforts.

Assessment of HCMV-encoded microRNAs in plasma as potential biomarkers in pregnant women with adverse pregnancy outcomes.

BACKGROUND: Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections and can lead to adverse pregnancy outcomes (APOs). HCMV encodes multiple microRNAs (miRNAs) that have been reported to be partially related to host immune responses, cell cycle regulation, viral replication, and viral latency, and can be detected in human plasma. However, the relevance for HCMV-encoded miRNAs in maternal plasma as an indicator for APOs has never been evaluated. METHODS: Expression profiles of 22 HCMV-encoded miRNAs were first measured in plasma samples from 20 pregnant women with APOs and 28 normal controls using quantitative reverse-transcription polymerase chain reaction. Next, markedly changed miRNAs were validated in another independent validation set consisting of 20 pregnant women with APOs and 27 control subjects. Markedly changed miRNAs were further assessed in the placenta tissues. HCMV DNA in peripheral blood leukocytes (PBLs) and anti-HCMV immunoglobulin M (IgM) and anti-HCMV immunoglobulin G (IgG) in plasma were also examined in both training and validation sets. Diagnostic value and risk factors were compared between APO cohorts and normal controls. RESULTS: Analysis of the training and validation data sets revealed that plasma concentrations of hcmv-miR-UL148D, hcmv-miR-US25-1-5p and hcmv-miR-US5-1 were significantly increased in pregnant women with APOs compared with normal controls. Hcmv-miR-US25-1-5p presented the largest area under the receiver-operating characteristic (ROC) curve (AUC) (0.735; 95% CI, 0.635-0.836), with a sensitivity of 68% and specificity of 71%. Furthermore, plasma levels of hcmv-miR-US25-1-5p and hcmv-miR-US5-1 correlated positively with APOs (P=0.029 and 0.035, respectively). Hcmv-miR-US25-1-5p in the placenta tissues were dramatically increased in APOs, and correlated with plasma hcmv-miR-US25-1-5p. Nevertheless, neither the concentration of HCMV DNA in PBLs nor the positivity rates of anti-HCMV IgM and anti-HCMV IgG in plasma showed a statistically significant correlation with APOs. CONCLUSIONS: We identified a unique signature of HCMV-encoded miRNAs in pregnant women with APOs that may be useful as a potential noninvasive biomarker for predicting and monitoring APOs during HCMV infection.