SEC61G assists EGFR-amplified glioblastoma to evade immune elimination.

Amplification of chromosome 7p11 (7p11) is the most common alteration in primary glioblastoma (GBM), resulting in gains of epidermal growth factor receptor (EGFR) copy number in 50 to 60% of GBM tumors. However, treatment strategies targeting EGFR have thus far failed in clinical trials, and the underlying mechanism remains largely unclear. We here demonstrate that EGFR amplification at the 7p11 locus frequently encompasses its neighboring genes and identifies SEC61G as a critical regulator facilitating GBM immune evasion and tumor growth. We found that SEC61G is always coamplified with EGFR and is highly expressed in GBM. As an essential subunit of the SEC61 translocon complex, SEC61G promotes translocation of newly translated immune checkpoint ligands (ICLs, including PD-L1, PVR, and PD-L2) into the endoplasmic reticulum and promotes their glycosylation, stabilization, and membrane presentation. Depletion of SEC61G promotes the infiltration and cytolytic activity of CD8+ T cells and thus inhibits GBM occurrence. Further, SEC61G inhibition augments the therapeutic efficiency of EGFR tyrosine kinase inhibitors in mice. Our study demonstrates a critical role of SEC61G in GBM immune evasion, which provides a compelling rationale for combination therapy of EGFR-amplified GBMs.

Recent Advances in DNA-Based Nanoprobes for In vivo MiRNA Imaging.

As a post transcriptional regulator of gene expression, microRNAs (miRNA) is closely related to many major human diseases, especially cancer. Therefore, its precise detection is very important for disease diagnosis and treatment. With the advancement of fluorescent dye and imaging technology, the focus has shifted from in vitro miRNA detection to in vivo miRNA imaging. This concept review summarizes signal amplification strategies including DNAzyme catalytic reaction, hybrid chain reaction (HCR), catalytic hairpin assembly (CHA) to enhance detection signal of lowly expressed miRNAs; external stimuli of ultraviolet (UV) light or near-infrared region (NIR) light, and internal stimuli such as adenosine triphosphate (ATP), glutathione (GSH), protease and cell membrane protein to prevent nonspecific activation for the avoidance of false positive signal; and the development of fluorescent probes with emission in NIR for in vivo miRNA imaging; as well as rare earth nanoparticle based the second near-infrared window (NIR-II) nanoprobes with excellent tissue penetration and depth for in vivo miRNA imaging. The concept review also indicated current challenges for in vivo miRNA imaging including the dynamic monitoring of miRNA expression change and simultaneous in vivo imaging of multiple miRNAs.

The LncRNA6524/miR-92a-2-5p/Dvl1/Wnt/ß-catenin axis promotes renal fibrosis in the UUO mouse model.

LncRNAs are reported to participate in multiple biological and pathological processes, including renal fibrosis due to obstructive nephropathy. However, the function and mechanisms of each lncRNA in this context differ. In this study, we created a fibrosis model in vitro using TGF-ß1 treatment and in vivo through unilateral ureteral obstruction. We demonstrated that lncRNA6524 expression increased in both models, as confirmed by qPCR. Additionally, we discovered that lncRNA6524 mediates the TGF-ß1-induced accumulation of extracellular matrix (ECM) proteins in BUMPT cells. We investigated the mechanism using dual luciferase reporter assays, immunofluorescence, and qPCR. Our results indicate that lncRNA6524 acts as a sponge for miR-92a-2-5p, promoting renal fibrosis by upregulating the Dvl1/Wnt/ß-catenin signaling pathway. In summary, our findings demonstrate a linear regulatory relationship among lncRNA6524, miR-92a-2-5p, and the Dvl1/Wnt/ß-catenin axis in renal epithelial cells during kidney obstruction. This highlights a new potential target for treating obstruction-related renal fibrosis.

The role of tRF-Val-CAC-010 in lung adenocarcinoma: implications for tumorigenesis and metastasis.

OBJECTIVE: Transfer RNA-derived fragments (tRFs) are short non-coding RNA (ncRNA) sequences, ranging from 14 to 30 nucleotides, produced through the precise cleavage of precursor and mature tRNAs. While tRFs have been implicated in various diseases, including cancer, their role in lung adenocarcinoma (LUAD) remains underexplored. This study aims to investigate the impact of tRF-Val-CAC-010, a specific tRF molecule, on the phenotype of LUAD cells and its role in tumorigenesis and progression in vivo. METHODS: The expression level of tRF-Val-CAC-010 was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Specific inhibitors and mimics of tRF-Val-CAC-010 were synthesized for transient transfection. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8), while cell invasion and migration were evaluated through Transwell invasion and scratch assays. Flow cytometry was utilized to analyze cell cycle and apoptosis. The in vivo effects of tRF-Val-CAC-010 on tumor growth and metastasis were determined through tumor formation and metastasis imaging experiments in nude mice. RESULTS: The expression level of tRF-Val-CAC-010 was upregulated in A549 and PC9 LUAD cells (P < 0.01). Suppression of tRF-Val-CAC-010 expression resulted in decreased proliferation of A549 and PC9 cells (P < 0.001), reduced invasion and migration of A549 (P < 0.05, P < 0.001) and PC9 cells (P < 0.05, P < 0.01), enhanced apoptosis in both A549 (P < 0.05) and PC9 cells (P < 0.05), and increased G2 phase cell cycle arrest in A549 cells (P < 0.05). In vivo, the tumor formation volume in the tRF-inhibitor group was significantly smaller than that in the model and tRF-NC groups (P < 0.05). The metastatic tumor flux value in the tRF-inhibitor group was also significantly lower than that in the model and tRF-NC groups (P < 0.05). CONCLUSION: This study demonstrates that tRF-Val-CAC-010 promotes proliferation, migration, and invasion of LUAD cells and induces apoptosis in vitro, however, its specific effects on the cell cycle require further elucidation. Additionally, tRF-Val-CAC-010 enhances tumor formation and metastasis in vivo. Therefore, tRF-Val-CAC-010 may serve as a novel diagnostic biomarker and potential therapeutic target for LUAD.

Polysaccharide Based Self-Driven Tubular Micro/Nanomotors as a Comprehensive Platform for Quercetin Loading and Anti-inflammatory Function.

Quercetin (QR) is a natural flavonoid with strong anti-inflammatory properties, but it suffers from poor water solubility and bioavailability. Micro/nanomotors (NMs) are tiny devices that convert external energy or chemical fuels into an autonomous motion. They are characterized by their small size, rapid movement, and self-assembly capabilities, which can enhance the delivery of bioactive ingredients. The study synthesized natural polysaccharide-based nanotubes (NTs) using a layer-by-layer self-assembly method and combined with urease (Ure), glucose oxidase (GOx), and Fe3O4 to create three types of NMs. These NMs were well-dispersed and biocompatible. In vitro experiments showed that NMs-Fe3O4 has excellent photothermal conversion properties and potential for use in photothermal therapy. Cellular inflammation model results demonstrated that QR-loaded NMs were not only structurally stable but also improved bioavailability and effectively inhibited the release of inflammatory mediators such as IL-1ß and IL-6, providing a safe and advanced carrier system for the effective use of bioactive components in food.

Methyl-ß-cyclodextrin asymmetrically extracts phospholipid from bilayers, granting tunable control over differential stress in lipid vesicles.

Lipid asymmetry - that is, a nonuniform lipid distribution between the leaflets of a bilayer - is a ubiquitous feature of biomembranes and is implicated in several cellular phenomena. Differential tension - that is, unequal lateral monolayer tensions comparing the leaflets of a bilayer- is closely associated with lipid asymmetry underlying these varied roles. Because differential tension is not directly measurable in combination with the fact that common methods to adjust this quantity grant only semi-quantitative control over it, a detailed understanding of lipid asymmetry and differential tension are impeded. To overcome these challenges, we leveraged reversible complexation of phospholipid by methyl-ß-cyclodextrin (mbCD) to tune the direction and magnitude of lipid asymmetry in synthetic vesicles. Lipid asymmetry generated in our study induced (i) vesicle shape changes and (ii) gel-liquid phase coexistence in 1-component vesicles. By applying mass-action considerations to interpret our findings, we discuss how this approach provides access to phospholipid thermodynamic potentials in bilayers containing lipid asymmetry (which are coupled to the differential tension of a bilayer). Because lipid asymmetry yielded by our approach is (i) tunable and (ii) maintained over minute to hour timescales, we anticipate that this approach will be a valuable addition to the experimental toolbox for systematic investigation into the biophysical role(s) of lipid asymmetry (and differential tension).

Genome-wide expression quantitative trait locus analysis reveals silk-preferential gene regulatory network in maize.

Silk of maize (Zea mays L.) contains diverse metabolites with complicated structures and functions, making it a great challenge to explore the mechanisms of metabolic regulation. Genome-wide identification of silk-preferential genes and investigation of their expression regulation provide an opportunity to reveal the regulatory networks of metabolism. Here, we applied the expression quantitative trait locus (eQTL) mapping on a maize natural population to explore the regulation of gene expression in unpollinated silk of maize. We obtained 3,985 silk-preferential genes that were specifically or preferentially expressed in silk using our population. Silk-preferential genes showed more obvious expression variations compared with broadly expressed genes that were ubiquitously expressed in most tissues. We found that trans-eQTL regulation played a more important role for silk-preferential genes compared to the broadly expressed genes. The relationship between 38 transcription factors and 85 target genes, including silk-preferential genes, were detected. Finally, we constructed a transcriptional regulatory network around the silk-preferential gene Bx10, which was proposed to be associated with response to abiotic stress and biotic stress. Taken together, this study deepened our understanding of transcriptome variation in maize silk and the expression regulation of silk-preferential genes, enhancing the investigation of regulatory networks on metabolic pathways.

Simultaneous Defect Passivation and Co-Catalyst Engineering Leads to Superior Photocatalytic Hydrogen Evolution on Metal Halide Perovskites.

Metal halide perovskites (MHPs) have emerged as attractive candidates for producing green hydrogen via photocatalytic pathway. However, the presence of abundant defects and absence of efficient hydrogen evolution reaction (HER) active sites on MHPs seriously limit the solar-to-chemical (STC) conversion efficiency. Herein, to address this issue, we present a bi-functionalization strategy through decorating MHPs with a molecular molybdenum-sulfur-containing co-catalyst precursor. By virtue of the strong chemical interaction between lead and sulfur and the good dispersion of the molecular co-catalyst precursor in the deposition solution, a uniform and intimate decoration of the MHPs surface with lead sulfide (PbS) and amorphous molybdenum sulfide (MoSx) co-catalysts is obtained simultaneously. We show that the PbS co-catalyst can effectively passivate the Pb-related defects on the MHPs surface, thus retarding the charge recombination and promoting the charge transfer efficiency significantly. The amorphous MoSx co-catalyst further promotes the extraction of photogenerated electrons from MHPs and facilitates the HER catalysis. Consequently, drastically enhanced photocatalytic HER activities are obtained on representative MHPs through the synergistic functionalization of PbS and MoSx co-catalysts. A solar-to-chemical (STC) conversion efficiency of ca. 4.63 % is achieved on the bi-functionalized FAPbBr3-xIx (FA=CH(NH2)2), which is among the highest values reported for MHPs.

cis-Regulatory variation affecting gene expression contributes to the improvement of maize kernel size.

cis-Regulatory variations contribute to trait evolution and adaptation during crop domestication and improvement. As the most important harvested organ in maize (Zea mays L.), kernel size has undergone intensive selection for size. However, the associations between maize kernel size and cis-regulatory variations remain unclear. We chose two independent association populations to dissect the genetic architecture of maize kernel size together with transcriptomic and genotypic data. The resulting phenotypes reflected a strong influence of population structure on kernel size. Compared with genome-wide association studies (GWASs), which accounted for population structure and relatedness, GWAS based on a naïve or simple linear model revealed additional associated single-nucleotide polymorphisms significantly involved in the conserved pathways controlling seed size in plants. Regulation analyses through expression quantitative trait locus mapping revealed that cis-regulatory variations likely control kernel size by fine-tuning the expression of proximal genes, among which ZmKL1 (GRMZM2G098305) was transgenically validated. We also proved that the pyramiding of the favorable cis-regulatory variations has contributed to the improvement of maize kernel size. Collectively, our results demonstrate that cis-regulatory variations, together with their regulatory genes, provide excellent targets for future maize improvement.

Metagenomic analysis reveals distinct changes in the gut microbiome of obese Chinese children.

BACKGROUND: The prevalence of obese children in China is increasing, which poses a great challenge to public health. Gut microbes play an important role in human gut health, and changes in gut status are closely related to obesity. However, how gut microbes contribute to obesity in children remains unclear. In our study, we performed shotgun metagenomic sequencing of feces from 23 obese children, 8 overweight children and 22 control children in Chengdu, Sichuan, China. RESULTS: We observed a distinct difference in the gut microbiome of obese children and that of controls. Compared with the controls, bacterial pathogen Campylobacter rectus was significantly more abundant in obese children. In addition, functional annotation of microbial genes revealed that there might be gut inflammation in obese children. The guts of overweight children might belong to the transition state between obese and control children due to a gradient in relative abundance of differentially abundant species. Finally, we compared the gut metagenomes of obese Chinese children and obese Mexican children and found that Trichuris trichiura was significantly more abundant in the guts of obese Mexican children. CONCLUSIONS: Our results contribute to understanding the changes in the species and function of intestinal microbes in obese Chinese children.

Virus-like Iron-Gold Heterogeneous Nanoparticles for Drug Target Screening.

Drug-target recognition has great impacts on revealing mechanisms of pharmacological activities, especially drug resistance and off-target effects. In recent years, chemoproteomics has been widely used for drug target screening and discovery due to its high-throughput, high accuracy, and sensitivity. However, there still remain challenges on how to efficiently and unambiguously track target proteins from complex biological matrices. Herein, we report a drug target screening method based on virus-like iron-gold heterogeneous nanoparticles (Au@Fe3O4 NPs). The unique structure of Au@Fe3O4 NPs not only maintains the magnetism of Fe3O4 NPs to facilitate protein enrichment and purification, but also increases drug modification by introducing more active sites on the surface of Au NPs. After coincubating the drug modified NPs with the cell lysate, the high loading of drug on the surface of Au@Fe3O4 NPs was beneficial for capturing target proteins with low abundance. This well-designed heterogeneous nanomaterial provides a novel strategy for improving the efficiency and accuracy of affinity-based proteomics.

MOF-Based Solid-State Proton Conductors Obtained by Intertwining Protic Ionic Liquid Polymers with MIL-101.

Solid-state proton conductors based on the use of metal-organic framework (MOF) materials as proton exchange membranes are being investigated as alternatives to the current state of the art. This study reports a new family of proton conductors based on MIL-101 and protic ionic liquid polymers (PILPs) containing different anions. By first installing protic ionic liquid (PIL) monomers inside the hierarchical pores of a highly stable MOF, MIL-101, then carrying out polymerization in situ, a series of PILP@MIL-101 composites was synthesized. The resulting PILP@MIL-101 composites not only maintain the nanoporous cavities and water stability of MIL-101, but the intertwined PILPs provide a number of opportunities for much-improved proton transport compared to MIL-101. The PILP@MIL-101 composite with HSO4 - anions shows superprotonic conductivity (6.3 × 10-2  S cm-1 ) at 85 °C and 98% relative humidity. The mechanism of proton conduction is proposed. In addition, the structures of the PIL monomers were determined by single crystal X-ray analysis, which reveals many strong hydrogen bonding interactions with O/NH···O distances below 2.6 Å.

Combined population transcriptomic and genomic analysis reveals cis-regulatory differentiation of non-coding RNAs in maize.

KEY MESSAGE: Long intergenic non-coding RNA (lincRNA), cis-acting expression quantitative trait locus (cis-eQTL), maize, regulatory evolution. The law of genetic variation during domestication explains the evolutionary mechanism and provides a theoretical basis for improving existing varieties of maize. Previous studies focused on exploiting regulatory variations controlling the expression of protein-coding genes rather than of non-protein-coding genes. Here, we examined the genetic and evolutionary features of long non-coding RNAs from intergenic regions (long intergenic non-coding RNAs, lincRNAs) using population-scale transcriptome data and identified 1168 lincRNAs with cis-acting expression quantitative trait loci (cis-eQTLs). We found that lincRNAs are more likely to be regulated by cis-eQTLs, which exert stronger effects than the protein-coding genes. During maize domestication and improvement, upregulated alleles of lincRNAs, which originated from both standing variation and new mutation, accumulate more frequently and show larger effect sizes than the coding genes. A stronger signature of genetic differentiation was observed in their regulatory regions compared to those of randomly sampled lincRNAs. In addition, we found that cis-regulatory differentiation of lincRNAs is related to the sequence conservation of lincRNA transcripts. Non-conserved lincRNAs more tend to gain upregulated alleles and show a stronger relationship with selected traits than conserved lincRNAs between maize and its wild relatives. Our findings in maize improve the understanding of cis-regulatory variation in lincRNA genes during domestication and improvement and provide an effective approach for prioritizing candidates for further investigation.

Mechanistic Insights Into the Rhodium-Catalyzed C-H Alkenylation/Directing Group Migration and [3+2] Annulation: A DFT Study.

The mechanism of the rhodium-catalyzed C-H alkenylation/directing group migration and [3+2] annulation of N-aminocarbonylindoles with 1,3-diynes has been investigated with DFT calculations. On the basis of mechanistic studies, we mainly focus on the regioselectivity of 1,3-diyne inserting into the Rh-C bond and the N-aminocarbonyl directing group migration involved in the reactions. Our theoretical study uncovers that the directing group migration undergoes a stepwise ß-N elimination and isocyanate reinsertion process. As studied in this work, this finding is also applicable to other relevant reactions. Additionally, the role of Na+ versus Cs+ involved in the [3+2] cyclization reaction is also probed.

Theoretical Insights into the Generation Mechanism of the Tyr122 Radical Catalyzed by Intermediate X in Class Ia Ribonucleotide Reductase.

Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to deoxyribonucleotides in all organisms. There is an ∼35 Å long-range electron-hole transfer pathway during the catalytic process of class Ia RNR, which can be described as Tyr122ß â†” [Trp48ß]? ↔ Tyr356ß â†” Tyr731α ↔ Tyr730α ↔ Cys439α. The formation of the Y122• radical initiates this long-range radical transfer process. However, the generation mechanism of Y122• is not yet clear due to confusion over the intermediate X structures. Based on the two reported X structures, we examined the possible mechanisms of Y122• generation by density functional theory (DFT) calculations. Our examinations revealed that the generation of the Y122• radical from the two different core structures of X was via a similar two-step reaction, with the first step of proton transfer for the formation of the proton receptor of Y122 and the second step of a proton-coupled long-range electron transfer reaction with the proton transfer from the Y122 hydroxyl group to the terminal hydroxide ligand of Fe1III and simultaneously electron transfer from the side chain of Y122 to Fe2IV. These findings provide an insight into the formation mechanism of Y122• catalyzed by the double-iron center of the ß subunit of class Ia RNR.

The relationship between the local environment, N-type, spin state and catalytic functionality of carbon-hosted FeII/III-N4 for the conversion of CO2 to CO.

Iron and nitrogen codoped carbon (Fe-N-C) materials are promising alternatives to precious metal catalysts for the carbon dioxide electrochemical reduction reaction (CO2RR); however, the influence of the oxidation state, spin state, N-type and local environment of Fe-N on its catalytic activity remains poorly understood. In this study, we employed density functional theory (DFT) calculations to evaluate the catalytic activity of the pyridine-type FeIII/IIN4 motifs at the armchair and zigzag edges, the activity of the pyrrole-type FeIII/IIN4 sites in the bulk plane of carbon-based materials for the two-electron CO2RR by analyzing the stability of initial reactants, free-energy evolutions and energy barriers for the possible elementary reactions in the different spin states. The Fe ions in the armchair-edge pyridine-type FeN4 are mainly in the +2 oxidation state, and use the high spin state in the spin uncoupling manner to achieve the most efficient CO2-COOH-CO conversion. In contrast, the zigzag-edge pyridine-type FeIIN4 employs the medium spin state in the spin uncoupling manner to achieve the highest catalytic activity in the two-electron CO2RR. However, the Fe ions in the pyrrole-type bulk-hosted FeN4 mainly remain in the +3 valence state during the conversion process of CO2 to CO and utilize the medium spin state with spin coupling to obtain the highest catalytic activity. The corresponding kinetic analyses show that the armchair-edge pyridine-type FeIIN4 catalyst exhibited the best catalytic performance among the three cases. Consequently, these findings present significant insights into the design of Fe single-atom catalysts for enhancing CO2RR catalytic activity by producing more armchair-edge pyridine-type FeN4 sites, which may be constructed by introducing micropores in the carbon materials.

mmu-lncRNA 121686/hsa-lncRNA 520657 induced by METTL3 drive the progression of AKI by targeting miR-328-5p/HtrA3 signaling axis.

The pathogenesis of acute kidney injury (AKI) is still not fully understood, and effective interventions are lacking. Here, we explored whether methyltransferase 3 (METTL3) was involved in the progression of AKI via regulation of cell death. We reported that PT（proximal tubule）-METTL3-knockout (KO) noticeably suppressed ischemic-induced AKI via inhibition of renal cell apoptosis. Furthermore, we also found that the expression of mmu-long non-coding RNA (lncRNA) 121686 was upregulated in antimycin-treated Boston University mouse proximal tubule (BUMPT) cells and a mouse ischemia-reperfusion (I/R)-induced AKI model. Functionally, mmu-lncRNA 121686 could promote I/R-induced mouse renal cell apoptosis. Mechanistically, mmu-lncRNA 121686 acted as a competing endogenous RNA (ceRNA) to prevent microRNA miR-328-5p-mediated downregulation of high-temperature requirement factor A 3 (Htra3). PT-mmu-lncRNA 121686-KO mice significantly ameliorated the ischemic-induced AKI via the miR-328-5p/HtrA3 axis. In addition, hsa-lncRNA 520657, homologous with lncRNA 121686, sponged miR-328-5p and upregulated Htra3 to promote I/R-induced human renal cell apoptosis. Interestingly, we found that mmu-lncRNA 121686/hsa-lncRNA 520657 upregulation were dependent on METTL3 via N6-methyladenosine (m6A) modification. The mmu-lncRNA 121686/miR-328-5p or hsa-lncRNA 520657/miR-328-5p /HtrA3 axis was induced in vitro by METTL3 overexpression; in contrast, this effect was attenuated by METTL3 small interfering RNA (siRNA). Furthermore, we found that PT-METTL3-KO or METTL3 siRNA significantly suppressed ischemic, septic, and vancomycin-induced AKI via downregulation of the mmu-lncRNA 121686/miR-328-5p/HtrA3 axis. Taken together, our data indicate that the METTL3/mmu-lncRNA 121686/hsa-lncRNA 520657/miR-328-5p/HtrA3 axis potentially acts as a therapeutic target for AKI.

Sequenced treatment alternatives to relieve adolescent depression (STAR-AD): a multicentre open-label randomized controlled trial protocol.

BACKGROUND: Adolescent major depressive disorder (MDD) is a prevalent mental health problem with low treatment success rates. Whether fluoxetine or fluoxetine combined with cognitive-behavioural therapy (CBT) is the more effective initial treatment for adolescent MDD remains controversial, and few studies have investigated whether treatment switching or augmentation is preferred when the initial treatment is not working well. METHODS: We developed a multicentre open-label Sequential Multiple Assignment Randomized Trial (SMART) design, consisting of two phases lasting 8 weeks each. In phase 1 (at baseline), patients will be recruited and grouped in fluoxetine group or fluoxetine combined with CBT group by patient self-selection. In phase 2 (after 8 weeks of treatment), the nonresponders will be randomly assigned to six groups, in which participants will switch to sertraline, vortioxetine, or duloxetine or added aripiprazole, olanzapine, or lithium carbonate to fluoxetine. After the full 16 weeks of treatment, we will assess the long-term sustainability of the treatment effects by evaluating participants during their subsequent naturalistic treatment. The primary outcome will be the response rate, determined by the Children's Depression Rating Scale-Revised (CDRS-R). Secondary outcomes include the change in scores on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment. DISCUSSION: The results from this study will aid clinicians in making informed treatment selection decisions for adolescents with MDD. TRIAL REGISTRATION: This protocol was registered at ClinicalTrials.gov with Identifier: NCT05814640.

Integrated Multi-Omics Reveals Significant Roles of Non-Additively Expressed Small RNAs in Heterosis for Maize Plant Height.

Heterosis is a complex biological phenomenon regulated by genetic variations and epigenetic changes. However, the roles of small RNAs (sRNAs), an important epigenetic regulatory element, on plant heterosis are still poorly understood. Here, an integrative analysis was performed with sequencing data from multi-omics layers of maize hybrids and their two homologous parental lines to explore the potential underlying mechanisms of sRNAs in plant height (PH) heterosis. sRNAome analysis revealed that 59 (18.61%) microRNAs (miRNAs) and 64,534 (54.00%) 24-nt small interfering RNAs (siRNAs) clusters were non-additively expressed in hybrids. Transcriptome profiles showed that these non-additively expressed miRNAs regulated PH heterosis through activating genes involved in vegetative growth-related pathways while suppressing those related to reproductive and stress response pathways. DNA methylome profiles showed that non-additive methylation events were more likely to be induced by non-additively expressed siRNA clusters. Genes associated with low-parental expression (LPE) siRNAs and trans-chromosomal demethylation (TCdM) events were enriched in developmental processes as well as nutrients and energy metabolism, whereas genes associated with high-parental expression (HPE) siRNAs and trans-chromosomal methylation (TCM) events were gathered in stress response and organelle organization pathways. Our results provide insights into the expression and regulation patterns of sRNAs in hybrids and help to elucidate their potential targeting pathways contributing to PH heterosis.

A NIR Programmable In Vivo miRNA Magnifier for NIR-II Imaging of Early Stage Cancer.

Aberrant expressions of biomolecules occur much earlier than tumor visualized size and morphology change, but their common measurement strategies such as biopsy suffer from invasive sampling process. In vivo imaging of slight biomolecule expression difference is urgently needed for early cancer detection. Fluorescence of rare earth nanoparticles (RENPs) in second near-infrared (NIR-II) region makes them appropriate tool for in vivo imaging. However, the incapacity to couple with signal amplification strategies, especially programmable signal amplification strategies, limited their application in lowly expressed biomarkers imaging. Here we develop a 980/808 nm NIR programmed in vivo microRNAs (miRNAs) magnifier by conjugating activatable DNAzyme walker set to RENPs, which achieves more effective NIR-II imaging of early stage tumor than size monitoring imaging technique. Dye FD1080 (FD1080) modified substrate DNA quenches NIR-II downconversion emission of RENPs under 808 nm excitation. The miRNA recognition region in DNAzyme walker is sealed by a photo-cleavable strand to avoid "false positive" signal in systemic circulation. Upconversion emission of RENPs under 980 nm irradiation activates DNAzyme walker for miRNA recognition and amplifies NIR-II fluorescence recovery of RENPs via DNAzyme catalytic reaction to achieve in vivo miRNA imaging. This strategy demonstrates good application potential in the field of early cancer detection.