IGSF8 is an innate immune checkpoint and cancer immunotherapy target.

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.

Induction of Siglec-G by RNA viruses inhibits the innate immune response by promoting RIG-I degradation.

RIG-I is a critical RNA virus sensor that serves to initiate antiviral innate immunity. However, posttranslational regulation of RIG-I signaling remains to be fully understood. We report here that RNA viruses, but not DNA viruses or bacteria, specifically upregulate lectin family member Siglecg expression in macrophages by RIG-I- or NF-κB-dependent mechanisms. Siglec-G-induced recruitment of SHP2 and the E3 ubiquitin ligase c-Cbl to RIG-I leads to RIG-I degradation via K48-linked ubiquitination at Lys813 by c-Cbl. By increasing type I interferon production, targeted inactivation of Siglecg protects mice against lethal RNA virus infection. Taken together, our data reveal a negative feedback loop of RIG-I signaling and identify a Siglec-G-mediated immune evasion pathway exploited by RNA viruses with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of Siglec-G, a known adaptive response regulator, in innate immunity.

Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO.

Excessive activation of dendritic cells (DCs) leads to the development of autoimmune and inflammatory diseases, which has prompted a search for regulators of DC activation. Here we report that Rhbdd3, a member of the rhomboid family of proteases, suppressed the activation of DCs and production of interleukin 6 (IL-6) triggered by Toll-like receptors (TLRs). Rhbdd3-deficient mice spontaneously developed autoimmune diseases characterized by an increased abundance of the TH17 subset of helper T cells and decreased number of regulatory T cells due to the increase in IL-6 from DCs. Rhbdd3 directly bound to Lys27 (K27)-linked polyubiquitin chains on Lys302 of the modulator NEMO (IKKγ) via the ubiquitin-binding-association (UBA) domain in endosomes. Rhbdd3 further recruited the deubiquitinase A20 via K27-linked polyubiquitin chains on Lys268 to inhibit K63-linked polyubiquitination of NEMO and thus suppressed activation of the transcription factor NF-κB in DCs. Our data identify Rhbdd3 as a critical regulator of DC activation and indicate K27-linked polyubiquitination is a potent ubiquitin-linked pattern involved in the control of autoimmunity.

Profiling of RNA editing events in plant organellar transcriptomes with high-throughput sequencing.

RNA editing is a crucial post-transcriptional modification process in plant organellar RNA metabolism. rRNA removal-based total RNA-seq is one of the most common methods to study this event. However, the lack of commercial kits to remove rRNAs limits the usage of this method, especially for non-model plant species. DSN-seq is a transcriptome sequencing method utilizing duplex-specific nuclease (DSN) to degrade highly abundant cDNA species especially those from rRNAs while keeping the robustness of transcript levels of the majority of other mRNAs, and has not been applied to study RNA editing in plants before. In this study, we evaluated the capability of DSN-seq to reduce rRNA content and profile organellar RNA editing events in plants, as well we used commercial Ribo-off-seq and standard mRNA-seq as comparisons. Our results demonstrated that DSN-seq efficiently reduced rRNA content and enriched organellar transcriptomes in rice. With high sensitivity to RNA editing events, DSN-seq and Ribo-off-seq provided a more complete and accurate RNA editing profile of rice, which was further validated by Sanger sequencing. Furthermore, DSN-seq also demonstrated efficient organellar transcriptome enrichment and high sensitivity for profiling RNA editing events in Arabidopsis thaliana. Our study highlights the capability of rRNA removal-based total RNA-seq for profiling RNA editing events in plant organellar transcriptomes and also suggests DSN-seq as a widely accessible RNA editing profiling method for various plant species.

Engineering the Interactions of Classical Cadherin Cell-Cell Adhesion Proteins.

Classical cadherins are calcium-dependent cell-cell adhesion proteins that play key roles in the formation and maintenance of tissues. Deficiencies in cadherin adhesion are hallmarks of numerous cancers. In this article, we review recent biophysical studies on the regulation of cadherin structure and adhesion. We begin by reviewing distinct cadherin binding conformations, their biophysical properties, and their response to mechanical stimuli. We then describe biophysical guidelines for engineering Abs that can regulate adhesion by either stabilizing or destabilizing cadherin interactions. Finally, we review molecular mechanisms by which cytoplasmic proteins regulate the conformation of cadherin extracellular regions from the inside out.

Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation.

Metazoan transcription is controlled through either coordinated recruitment of transcription machinery to the gene promoter or regulated pausing of RNA polymerase II (Pol II) in early elongation. We report that a striking difference between genes that use these distinct regulatory strategies lies in the "default" chromatin architecture specified by their DNA sequences. Pol II pausing is prominent at highly regulated genes whose sequences inherently disfavor nucleosome formation within the gene but favor occlusion of the promoter by nucleosomes. In contrast, housekeeping genes that lack pronounced Pol II pausing show higher nucleosome occupancy downstream, but their promoters are deprived of nucleosomes regardless of polymerase binding. Our results indicate that a key role of paused Pol II is to compete with nucleosomes for occupancy of highly regulated promoters, thereby preventing the formation of repressive chromatin architecture to facilitate further or future gene activation.

Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody.

E-cadherin (Ecad) is an essential cell-cell adhesion protein with tumor suppression properties. The adhesive state of Ecad can be modified by the monoclonal antibody 19A11, which has potential applications in reducing cancer metastasis. Using X-ray crystallography, we determine the structure of 19A11 Fab bound to Ecad and show that the antibody binds to the first extracellular domain of Ecad near its primary adhesive motif: the strand-swap dimer interface. Molecular dynamics simulations and single-molecule atomic force microscopy demonstrate that 19A11 interacts with Ecad in two distinct modes: one that strengthens the strand-swap dimer and one that does not alter adhesion. We show that adhesion is strengthened by the formation of a salt bridge between 19A11 and Ecad, which in turn stabilizes the swapped ß-strand and its complementary binding pocket. Our results identify mechanistic principles for engineering antibodies to enhance Ecad adhesion.

Retinoschisin Is Required for Pineal Gland Calcification and Cellular Communication in Pinealocytes of Rats and Mice.

Retinoschisin (RS1) is a secretory protein specifically localized to the extracellular domains in both the lateral retina and the pineal gland (PG). However, the functions of RS1 in the pineal body are poorly understood. To address this knowledge gap, in this study, we undertook histochemical, ultrastructural, and Western blotting analyses of the PG in rats and RS1-knock-in transgenic. We found that RS1 plays a key role in pineal gland calcification (PGC) in mice through both extracellular and intracellular pathways. RS1 was clustered around the cell membrane or intracellularly in pinealocytes, actively participating in the exchange of calcium and thereby mediating PGC. Additionally, RS1 deposition is essential for maintaining PGC architecture in the intercellular space of the adult PG. In RS1-knock-in mice with a nonsense mutation (p.Y65X) in the Rs1-domain of RS1, the Rs1-domain is chaotically dispersed in pinealocytes and the intercellular region of the PG. This prevents RS1 from binding calcified spots and forming calcified nodules, ultimately leading to the accumulation of calcareous lamellae in microvesicles. Additionally, RS1 was observed to colocalize with connexin-36, thereby modulating intercellular communication in the PG of both rats and mice. Our study revealed for the first time that RS1 is essential for maintaining PGC architecture and that it colocalizes with connexin 36 to modulate intercellular communication in the PG. These findings provide novel insights into the function of the RS1 gene in the PG.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early lung cancer.

INTRODUCTION: The study explored the effects of SHOX2 and RASSF1A DNA methylation in lung cancer (LC). METHOD: Bronchoalveolar lavage fluid (BALF) samples as well as LC and normal adjacent tissues were collected from 72 LC patients and 35 patients with benign pulmonary nodules. Quantitative analysis of SHOX2 and RASSF1A DNA methylation was performed in benign pulmonary nodules and different stages of LC. The diagnostic value of SHOX2 and RASSF1A DNA methylation in LC and benign pulmonary nodules was determined by receiver operating characteristics analysis. Gain/loss-of-function experiments were constructed in LC cells and mouse models of xenograft and pulmonary nodule metastasis. The levels of SHOX2 and transfer-associated genes were tested through qRT-PCR and Western blot. Malignant phenotype of LC cells were assessed by functional experiment. The tumor volume and weight of mice in xenograft models were measured. Pulmonary nodule metastasis was determined through HE staining assay. 5-Azacytidine appeared as a positive control drug. RESULT: SHOX2 DNA methylation or RASSF1A DNA methylation had a diagnostic efficiency in pulmonary nodules and early LC, with the two combined had better diagnostic value. SHOX2 expression was upregulated in LC. Similar to 5-Azacytidine, SHOX2 knockdown inhibited LC cell viability, migration and invasion in vitro as well as restrained LC tumorigenesis and pulmonary nodule metastasis in vivo, whereas overexpressed SHOX2 had the opposite effects. CONCLUSION: The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early LC. SHOX2 positively modulated the tumorigenesis and metastasis of LC by regulating DNA methylation processes.

Comparative molecular dynamics simulations provided insights into the mechanisms of cold-adaption of alginate lyases from the PL7 family.

Alginate is an important polysaccharide that is abundant in the marine environments, including the Polar Regions, and bacterial alginate lyases play key roles in its degradation. Many reported alginate lyases show characteristics of cold-adapted enzymes, including relatively low temperature optimum of activities (Topt) and low thermal stabilities. However, the cold-adaption mechanisms of alginate lyases remain unclear. Here, we studied the cold-adaptation mechanisms of alginate lyases by comparing four members of the PL7 family from different environments: AlyC3 from the Arctic ocean (Psychromonas sp. C-3), AlyA1 from the temperate ocean (Zobellia galactanivorans), PA1167 from the human pathogen (Pseudomonas aeruginosa PAO1), and AlyQ from the tropic ocean (Persicobacter sp. CCB-QB2). Sequence comparison and comparative molecular dynamics (MD) simulations revealed two main strategies of cold adaptation. First, the Arctic AlyC3 and temperate AlyA1 increased the flexibility of the loops close to the catalytic center by introducing insertions at these loops. Second, the Arctic AlyC3 increased the electrostatic attractions with the negatively charged substrate by introducing a high portion of positively charged lysine at three of the insertions mentioned above. Furthermore, our study also revealed that the root mean square fluctuation (RMSF) increased greatly when the temperature was increased to Topt or higher, suggesting the RMSF increase temperature as a potential indicator of the cold adaptation level of the PL7 family. This study provided new insights into the cold-adaptation mechanisms of bacterial alginate lyases and the marine carbon cycling at low temperatures.

Causal association between circulating blood cell traits and pulmonary embolism: a mendelian randomization study.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening thromboembolic disease for which there is limited evidence for effective prevention and treatment. Our goal was to determine whether genetically predicted circulating blood cell traits could influence the incidence of PE. METHODS: Using single variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) analyses, we identified genetic associations between circulating blood cell counts and lymphocyte subsets and PE. GWAS blood cell characterization summary statistics were compiled from the Blood Cell Consortium. The lymphocyte subpopulation counts were extracted from summary GWAS statistics for samples from 3757 individuals that had been analyzed by flow cytometry. GWAS data related to PE were obtained from the FinnGen study. RESULTS: According to the SVMR and reverse MR, increased levels of circulating white blood cells (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.81-0.95, p = 0.0079), lymphocytes (OR: 0.90, 95% CI: 0.84-0.97, p = 0.0115), and neutrophils (OR: 0.88, 95% CI: 0.81-0.96, p = 0.0108) were causally associated with PE susceptibility. MVMR analysis revealed that lower circulating lymphocyte counts (OR: 0.84, 95% CI: 0.75-0.94, p = 0.0139) were an independent predictor of PE. According to further MR results, this association may be primarily related to HLA-DR+ natural killer (NK) cells. CONCLUSIONS: Among European populations, there is a causal association between genetically predicted low circulating lymphocyte counts, particularly low HLA-DR+ NK cells, and an increased risk of PE. This finding supports observational studies that link peripheral blood cells to PE and provides recommendations for predicting and preventing this condition.

Multi-fidelity machine learning for predicting bandgaps of nonlinear optical crystals.

Nonlinear optical (NLO) materials are of great importance in modern optics and industry because of their intrinsic capability of wavelength conversion. Bandgap is a key property of NLO crystals. In recent years, machine learning (ML) has become a powerful tool to predict the bandgaps of compounds before synthesis. However, the shortage of available experimental data of NLO crystals poses a significant challenge for the exploration of new NLO materials using ML. In this work, we proposed a new multi-fidelity ML approach based on the multilevel descriptors developed by us (Z.-Y. Zhang, X. Liu, L. Shen, L. Chen and W.-H. Fang, J. Phys. Chem. C, 2021, 125, 25175-25188) and the gradient boosting regression tree algorithm. The calculated and experimental bandgaps of NLO crystals were collected as the low- and high-fidelity labels, respectively. The experimental values were predicted based on chemical compositions of crystals without prior knowledge about crystal structures. The multi-fidelity ML model overcame the performance of single-fidelity predictor. Furthermore, it was observed that less accurate predictions on the low-fidelity label may result in more accurate prediction on the high-fidelity label, at least in the present case. Using the multi-fidelity ML model with the best performance in this work, the mean absolute error on the test set of experimental bandgaps was 0.293 eV, which is smaller than that using the single-fidelity model (0.355 eV). It is far from perfect but accurate enough as an effective computational tool in the first step to discover novel NLO materials.

Construction of Highly Accurate Machine Learning Potential Energy Surfaces for Excited-State Dynamics Simulations Based on Low-Level Data Sets.

Machine learning is capable of effectively predicting the potential energies of molecules in the presence of high-quality data sets. Its application in the construction of ground- and excited-state potential energy surfaces is attractive to accelerate nonadiabatic molecular dynamics simulations of photochemical reactions. Because of the huge computational cost of excited-state electronic structure calculations, the construction of a high-quality data set becomes a bottleneck. In the present work, we first built two data sets. One was obtained from surface hopping dynamics simulations at the semiempirical OM2/MRCI level. Another was extracted from the dynamics trajectories at the CASSCF level, which was reported previously. The ground- and excited-state potential energy surfaces of ethylene-bridged azobenzene at the CASSCF computational level were constructed based on the former low-level data set. Although non-neural network machine learning methods can achieve good or modest performance during the training process, only neural network models provide reliable predictions on the latter external test data set. The BPNN and SchNet combined with the Δ-ML scheme and the force term in the loss functions are recommended for dynamics simulations. Then, we performed excited-state dynamics simulations of the photoisomerization of ethylene-bridged azobenzene on machine learning potential energy surfaces. Compared with the lifetimes of the first excited state (S1) estimated at different computational levels, our results on the E isomer are in good agreement with the high-level estimation. However, the overestimation of the Z isomer is unimproved. It suggests that smaller errors during the training process do not necessarily translate to more accurate predictions on high-level potential energies or better performance on nonadiabatic dynamics simulations, at least in the present case.

EP300 through upregulating the expression of vimentin to promote the progression of chordoma.

OBJECTIVE: There is a lack of effective drugs to treat the progression and recurrence of chordoma, which is widely resistant to treatment in chemotherapy. The authors investigated the functional and therapeutic relevance of the E1A-binding protein p300 (EP300) in chordoma. METHODS: The expression of EP300 and vimentin was examined in specimens from 9 patients with primary and recurrent chordoma with immunohistochemistry. The biological functions of EP300 were evaluated with Cell Counting Kit-8, clonogenic assays, and transwell assays. The effects of EP300 inhibitors (C646 and SGC-CBP30) on chordoma cell motility were assessed with these assays. The effect of the combination of EP300 inhibitors and cisplatin on chordoma cells was evaluated with clonogenic assays. Reverse transcription quantitative polymerase chain reaction and Western blot techniques were used to explore the potential mechanism of EP300 through upregulation of the expression of vimentin to promote the progression of chordoma. RESULTS: Immunohistochemistry analysis revealed a positive correlation between elevated EP300 expression levels and recurrence. The upregulation of EP300 stimulated the growth of and increased the migratory and invasive capabilities of chordoma cells, along with upregulating vimentin expression and consequently impacting their invasive properties. Conversely, EP300 inhibitors decreased cell proliferation and downregulated vimentin. Furthermore, the combination of EP300 inhibition and cisplatin exhibited an enhanced anticancer effect on chordoma cells, indicating that EP300 may influence chordoma sensitivity to chemotherapy. CONCLUSIONS: These findings indicate that EP300 functions as an oncogene in chordoma. Targeting EP300 offers a novel approach to the development and clinical treatment of chordoma.

Adolescent's explicit and implicit cigarette cognitions predict experimentation with both cigarettes and e-cigarettes.

Background: Past year, month, and lifetime adolescent e-cigarette use rates remain persistently high, despite falling cigarette use rates. Previous investigations have noted a strong relationship between an individual's positive and negative cognitions related to a behavior, and subsequent initiation of that behavior.Objective: This investigation was conducted to determine the impact positive and negative explicit and implicit cigarette-related cognitions may have on the use of cigarettes and e-cigarettes among at-risk, cigarette-naive adolescents.Methods: A three-year longitudinal investigation evaluated the relationship between cigarette-related cognitions and subsequent cigarette and e-cigarette use among 586 alternative high school students (female: 50.8%; mean age: 17.4 years; Hispanic/Latino: 75.0%) who had never smoked cigarettes at the baseline assessment. Multilevel logistic regression models were used to generate demographics-adjusted odds ratios (OR) and 95% confidence intervals (95% CI).Results: Students with higher positive explicit cigarette cognitions at the baseline had greater odds of subsequent cigarette use (OR = 1.72, 95% CI 1.11-2.68). If students also reported an increase over time in positive (OR = 3.45, 95% CI 2.10-5.68) or negative (OR = 1.93, 95% CI 1.03-3.61) explicit cigarette cognitions, the odds of cigarette use increased. The odds of dual use of cigarettes and e-cigarettes were greater among students who had higher negative implicit cigarette cognitions at the baseline (OR = 2.07, 95% CI 1.03-4.17) compared to those with lower levels of negative implicit cognitions.Conclusion: Prevention programming that focuses on decreasing positive cognitions related to nicotine and tobacco use may have greater overall effect on decreasing use compared to programs that only focus on increasing negative cognitions individuals form surrounding cigarette or e-cigarettes.

Autophagy-Inducing MoO3-x Nanowires Boost Photothermal-Triggered Cancer Immunotherapy.

Autophagy could play suppressing role in cancer therapy by facilitating release of tumor antigens from dying cells and inducing immunogenic cell death (ICD). Therefore, discovery and rational design of more effective inducers of cytotoxic autophagy is expected to develop new strategies for finding innovative drugs for precise and successful cancer treatment. Herein, we develop MoO3-x nanowires (MoO3-x NWs) with high oxygen vacancy and strong photothermal responsivity to ablate tumors through hyperthermia, thus promote the induction of cytotoxic autophagy and severe ICD. As expected, the combination of MoO3-x NWs and photothermal therapy (PTT) effectively induces autophagy to promote the release of tumor antigens from the ablated cells, and induces the maturation and antigen presentation of dendritic cells (DCs), subsequently activates cytotoxic T lymphocytes (CTLs)-mediated adaptive immunity. Furthermore, the combination treatment of MoO3-x NWs with immune checkpoint blockade of PD-1 could promote the tumor-associated macrophages (TAMs) polarization into tumor-killing M1 macrophages, inhibit infiltration of Treg cells at tumor sites, and alleviate immunosuppression in the tumor microenvironment, finally intensify the anti-tumor activity in vivo. This study provides a strategy and preliminary elucidation of the mechanism of using MoO3-x nanowires with high oxygen vacancy to induce autophagy and thus enhance photothermal immunotherapy.

Interphase Regulation by Multifunctional Additive Empowering High Energy Lithium-Ion Batteries with Enhanced Cycle Life and Thermal Safety.

High energy density lithium-ion batteries (LIBs) adopting high-nickel layered oxide cathodes and silicon-based composite anodes always suffer from unsatisfied cycle life and poor safety performance, especially at elevated temperatures. Electrode /electrolyte interphase regulation by functional additives is one of the most economic and efficacious strategies to overcome this shortcoming. Herein, cyano-groups (-CN) are introduced into lithium fluorinated phosphate to synthesize a novel multifunctional additive of lithium tetrafluoro (1,2-dihydroxyethane-1,1,2,2-tetracarbonitrile) phosphate (LiTFTCP), which endows high nickel LiNi0.8 Co0.1 Mn0.1 O2 /SiOx -graphite composite full cell with an ultrahigh cycle life and superior safety characteristics, by adding only 0.5 wt % LiTFTCP into a LiPF6 -carbonate baseline electrolyte. It is revealed that LiTFTCP additive effectively suppresses the HF generation and facilitates the formation of a robust and heat-resistant cyano-enriched CEI layer as well as a stable LiF-enriched SEI layer. The favorable SEI/CEI layers greatly lessen the electrode degradation, electrolyte consumption, thermal-induced gassing and total heat-releasing. This work illuminates the importance of additive molecular engineering and interphase regulation in simultaneously promoting the cycling and thermal safety of LIBs with high-nickel NCMxyz cathode and silicon-based composite anode.

Evolutionary Implications of the RNA N6-Methyladenosine Methylome in Plants.

Epigenetic modifications play important roles in genome evolution and innovation. However, most analyses have focused on the evolutionary role of DNA modifications, and little is understood about the influence of posttranscriptional RNA modifications on genome evolution. To explore the evolutionary significance of RNA modifications, we generated transcriptome-wide profiles of N6-methyladenosine (m6A), the most prevalent internal modification of mRNA, for 13 representative plant species spanning over half a billion years of evolution. These data reveal the evolutionary conservation and divergence of m6A methylomes in plants, uncover the preference of m6A modifications on ancient orthologous genes, and demonstrate less m6A divergence between orthologous gene pairs with earlier evolutionary origins. Further investigation revealed that the evolutionary divergence of m6A modifications is related to sequence variation between homologs from whole-genome duplication and gene family expansion from local-genome duplication. Unexpectedly, a significant negative correlation was found between the retention ratio of m6A modifications and the number of family members. Moreover, the divergence of m6A modifications is accompanied by variation in the expression level and translation efficiency of duplicated genes from whole- and local-genome duplication. Our work reveals new insights into evolutionary patterns of m6A methylomes in plant species and their implications, and provides a resource of plant m6A profiles for further studies of m6A regulation and function in an evolutionary context.

Phosphorus-Mediated Local Charge Distribution of N-Configuration Adsorption Sites with Enhanced Zincophilicity and Hydrophilicity for High-Energy-Density Zn-Ion Hybrid Supercapacitors.

Tailor-made carbonaceous-based cathodes with zincophilicity and hydrophilicity are highly desirable for Zn-ion storage applications, but it remains a great challenge to achieve both advantages in the synthesis. In this work, a template electrospinning strategy is developed to synthesize nitrogen and phosphorous co-doped hollow porous carbon nanofibers (N, P-HPCNFs), which deliver a high capacity of 230.7 mAh g-1 at 0.2 A g-1 , superior rate capability of 131.0 mAh g-1 at 20 A g-1 , and a maximum energy density of 196.10 Wh kg-1 at the power density of 155.53 W kg-1 . Density functional theory calculations (DFT) reveal that the introduced P dopants regulate the distribution of local charge density of carbon materials and therefore facilitate the adsorption of Zn ions due to the increased electronegativity of pyridinic-N. Ab initio molecular dynamics (AIMD) simulations indicate that the doped P species induce a series of polar sites and create a hydrophilic microenvironment, which decreases the impedance between the electrode and the electrolyte and therefore accelerates the reaction kinetics. The marriage of ex situ/in situ experimental analyses and theoretical simulations uncovers the origin of the enhanced zincophilicity and hydrophilicity of N, P-HPCNFs for energy storage, which accounts for the faster ion migration and electrochemical processes.