SRSF2 plays an unexpected role as reader of m5C on mRNA, linking epitranscriptomics to cancer.

A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.

A conserved protein disulfide isomerase enhances plant resistance against herbivores.

Herbivore-associated molecular patterns (HAMPs) enable plants to recognize herbivores and may help plants adjust their defense responses. Here, we report on herbivore-induced changes in a protein disulfide isomerase (PDI) widely distributed across arthropods. PDI from the spider mite Tetranychus evansi (TePDI), a mesophyll-feeding agricultural pest worldwide, triggered immunity in multiple Solanaceae plants. TePDI-mediated cell death in Nicotiana benthamiana required the plant signaling proteins SGT1 (suppressor of the G2 allele of skp1) and HSP90 (heat shock protein 90), but was suppressed by spider mite effectors Te28 and Te84. Moreover, PDIs from phylogenetically distinct herbivorous and nonherbivorous arthropods triggered plant immunity. Finally, although PDI-induced plant defenses impaired the performance of spider mites on plants, RNAi experiments revealed that PDI genes are essential for the survival of mites and whiteflies. Our findings indicate that plants recognize evolutionarily conserved HAMPs to activate plant defense and resist pest damage, pointing to opportunities for broad-spectrum pest management.

Emerging Roles of RNA Methylation in Development.

More than 170 different types of chemical modifications have been identified on diverse types of RNA, collectively known as the epitranscriptome. Among them, N6-methyladenine (m6A), 5-methylcytosine (m5C), N1-methyladenine (m1A), and N7-methylguanosine (m7G) as the ubiquitous post-transcriptional modification are widely involved in regulating the metabolic processes such as RNA degradation, translation, stability, and export, mediating important physiological and pathological processes such as stress regulation, immune response, development, and tumorigenesis. Recently, the regulatory role of RNA modification during developmental processes is getting more attention. Therefore, the development of low-input even single-cell and high-resolution sequencing technologies is crucial for the exploration of the regulatory roles of RNA modifications in these important biological events of trace samples.This account focuses on the roles of RNA modifications in various developmental processes. We describe the distribution characteristics of various RNA modifications, catalytic enzymes, binding proteins, and the development of sequencing technologies. RNA modification is dynamically reversible, which can be catalyzed by methyltransferases and eliminated by demethylases. RNA m6A is the most abundant post-transcriptional modification on eukaryote mRNA, which is mainly concentrated near the stop codon, and involves in RNA metabolism regulation. RNA m5C, another most studied RNA modification, has been identified in a various of organisms and RNA species, mainly enriched in the regions downstream of translation initiation sites and broadly distributes across the whole coding sequence (CDS) in mammalian mRNAs. RNA m1A, with a lower abundance than m6A, is widely distributed in various RNA types, mainly locates in the 5' untranslated region (5'UTR) of mRNA and regulates translation. RNA m7G, one of the most common RNA modifications in eukaryotes, has been identified at cap regions and internal positions of RNAs and recently gained considerable attention.Thanks to the development of sequencing technology, m6A has been found to regulate the tumorigenic process, including tumor proliferation, invasion, and metastasis by modulating oncogenes and tumor suppressor genes, and affect oocyte maturation and embryonic development through regulating maternal and zygotic genes. m5C related proteins have been identified to participate in embryonic development, plant growth, and neural stem cell differentiation in a m5C dependent manner. m1A also has been revealed to be involved in these developmental processes. m7G dysregulation mainly involves in neurodevelopmental disorders and neurodegenerative diseases.Collectively, we summarized the gradually exhibited roles of RNA methylation during development, and discussed the possibility of RNA modifications as candidate biomarkers and potential therapeutic targets. The technological development is anticipated as the major driving force to expand our knowledge in this field.

Efficient Synthesis of Cyanohydrin Esters: P(NMe2)3 Mediated Direct Deoxygenation of Acyl Cyanides with Carboxylic Acids.

An efficient synthesis of cyanohydrin esters via a P(NMe2)3 mediated direct deoxygenation process has been exploited, circumventing the release or transformation of the CN─ anion during the reaction. This approach possesses a broad scope and acts as a powerful supplement for the construction of diverse cyanohydrin esters. It offers advantages such as mild conditions, straightforward operations, and excellent scalability, affirming the feasibility and versatility of this approach and highlighting its potential in practical synthesis.

P(NMe2)3-Mediated Regioselective N-Alkylation of 2-Pyridones via Direct Deoxygenation of α-Keto Esters.

A practical and regioselective direct N-alkylation of 2-pyridones is enabled by use of α-keto esters in the P(NMe2)3-mediated deoxygenation process. The reaction proceeds under mild conditions to produce N-alkylated 2-pyridones with high selectivity and generality, and the protocol is shown to be applicable for the scale-up synthesis, which makes it promising for practical applications.

Correlation Between Insulin Resistance and Urinary Incontinence in Female Patients with Type 2 Diabetes Mellitus.

INTRODUCTION AND HYPOTHESIS: Patients with type 2 diabetes mellitus (T2DM) are at a high risk of developing urinary incontinence; however, its pathogenesis is unclear. The purpose of this study is to explore the relationship between insulin resistance and urinary incontinence and its severity in female patients with T2DM. METHODS: A total of 366 women with T2DM aged ≥18 years were enrolled in this study. Insulin resistance was evaluated by the homeostasis model insulin resistance (HOMA-IR) index and urinary incontinence was assessed by the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF). All subjects were divided into four groups according to HOMA-IR quartiles. Logistic regression analysis was performed to investigate the relationship between insulin resistance and urinary incontinence and its severity. RESULTS: Among the 366 patients, 186 (50.8%) had urinary incontinence. The prevalence of urinary incontinence increased significantly with HOMA-IR quartiles (p < 0.001). Adjusted logistic regression analysis showed that compared with HOMA-IR ≤ 1.76, 2.81 ≤ HOMA-IR ≤ 4.27 was associated with a significantly increased risk of moderate incontinence (OR = 2.197, 95% CI 1.031-4.683, p = 0.041), and HOMA-IR ≥ 4.28 was associated with a significantly increased risk of severe incontinence (OR = 5.699, 95% CI 1.685-19.276, p = 0.005). Binary logistic regression analysis showed that HOMA-IR was the independent risk factor for urinary incontinence (p < 0.001). CONCLUSIONS: Higher levels of insulin resistance are associated with urinary incontinence and its severity in female patients with type 2 diabetes mellitus.

Inhibitory activity and antioomycete mechanism of citral against Phytophthora capsici.

The natural terpenoid citral has antifungal activity against multiple fungi, but its bioactivity against oomycetes is unclear. Therefore, this study investigated the antioomycete activity and mechanism of citral against Phytophthora capsici, a highly destructive invasive oomycete. Results showed that citral not only had a great inhibition on the mycelial growth of P. capsici (EC50 = 94.15 mg/L), but also had a significant inhibition on multiple spores, such as sporangia formation, zoospore discharge and zoospore germination. Citral at 4000 mg/L exhibited favorable protective (73.33%) and curative efficacy (55.11%) against pepper Phytophthora blight. Citral significantly damaged the hyphal morphology, disrupted the cell membrane integrity, increased the permeability of cell membrane, and increased the glycerol content in P. capsici. A total of 250 upregulated and 288 downregulated proteins were identified in iTRAQ-based quantitative proteomic analysis. Downregulated proteins were mostly enriched in pathways of ABC transporters, cyanoamino acid metabolism and starch and sucrose metabolism, suggesting an inhibition of citral on transmembrane transporter (e.g., ABC transporters) and pathogenicity (e.g., ß-glucosidases) proteins. Upregulated proteins were enriched in biosynthesis of unsaturated fatty acids, pyruvate metabolism and glycolysis/gluconeogenesis, suggesting an activation of citral on energy generation proteins, including acyl-CoA oxidase, D-lactate dehydrogenase, pyruvate kinase, acetyl-CoA synthetase and phosphoenolpyruvate carboxykinase. Biochemical and iTRAQ analysis suggested that cell membrane may be the target of citral in P. capsici.

Localization Performance Analysis and Algorithm Design of Reconfigurable Intelligent Surface-Assisted D2D Systems.

The research on high-precision and all-scenario localization using the millimeter-wave (mmWave) band is of great urgency. Due to the characteristics of mmWave, blockages make the localization task more complex. This paper proposes a cooperative localization system among user equipment (UEs) assisted by reconfigurable intelligent surfaces (RISs), which considers device-to-device (D2D) communication. RISs are used as anchor points, and position estimation is achieved through signal exchanges between UEs. Firstly, we establish a localization model based on this system and derive the UEs' positioning error bound (PEB) as a performance metric. Then, a UE-RIS joint beamforming design is proposed to optimize channel state information (CSI) with the objective of achieving the minimum PEB. Finally, simulation analysis demonstrates the advantages of the proposed scheme over RIS-assisted base station positioning, achieving centimeter-level accuracy with a 10 dBm lower transmission power.

Infrared Bilateral Polarity Ship Detection in Complex Maritime Scenarios.

In complex maritime scenarios where the grayscale polarity of ships is unknown, existing infrared ship detection methods may struggle to accurately detect ships among significant interference. To address this issue, this paper first proposes an infrared image smoothing method composed of Grayscale Morphological Reconstruction (GMR) and a Relative Total Variation (RTV). Additionally, a detection method considering the grayscale uniformity of ships and integrating shape and spatiotemporal features is established for detecting bright and dark ships in complex maritime scenarios. Initially, the input infrared images undergo opening (closing)-based GMR to preserve dark (bright) blobs with the opposite suppressed, followed by smoothing the image with the relative total variation model to reduce clutter and enhance the contrast of the ship. Subsequently, Maximally Stable Extremal Regions (MSER) are extracted from the smoothed image as candidate targets, and the results from the bright and dark channels are merged. Shape features are then utilized to eliminate clutter interference, yielding single-frame detection results. Finally, leveraging the stability of ships and the fluctuation of clutter, true targets are preserved through a multi-frame matching strategy. Experimental results demonstrate that the proposed method outperforms ITDBE, MRMF, and TFMSER in seven image sequences, achieving accurate and effective detection of both bright and dark polarity ship targets.

Recent Progress in Interface Engineering of Nanostructures for Photoelectrochemical Energy Harvesting Applications.

With rapid and continuous consumption of nonrenewable energy, solar energy can be utilized to meet the energy requirement and mitigate environmental issues in the future. To attain a sustainable society with an energy mix predominately dependent on solar energy, photoelectrochemical (PEC) device, in which semiconductor nanostructure-based photocatalysts play important roles, is considered to be one of the most promising candidates to realize the sufficient utilization of solar energy in a low-cost, green, and environmentally friendly manner. Interface engineering of semiconductor nanostructures has been qualified in the efficient improvement of PEC performances including three basic steps, i.e., light absorption, charge transfer/separation, and surface catalytic reaction. In this review, recently developed interface engineering of semiconductor nanostructures for direct and high-efficiency conversion of sunlight into available forms (e.g., chemical fuels and electric power) are summarized in terms of their atomic constitution and morphology, electronic structure and promising potential for PEC applications. Extensive efforts toward the development of high-performance PEC applications (e.g., PEC water splitting, PEC photodetection, PEC catalysis, PEC degradation and PEC biosensors) are also presented and appraised. Last but not least, a brief summary and personal insights on the challenges and future directions in the community of next-generation PEC devices are also provided.

A TiSe monolayer as a superior anode for applications of Li/Na/K-ion batteries.

Using density functional theory (DFT), we investigated the energy-storage capabilities of a two-dimensional TiSe monolayer for applications of the anode material of Li/Na/K-ion batteries. The TiSe monolayer showed high thermodynamic stability at 800 K according to ab initio molecular dynamics (AIMD) simulation. The ion-diffusion barrier was estimated to be 0.29/0.36/0.33 eV for Li/Na/K, respectively, indicating the high-rate capacity of this material. The theoretical specific capacity was 422.63 mA h g-1 for Li/Na/K, with an energy density of 1000.19, 802.30, and 802.41 mW h g-1, respectively. Fully charged TiSe was mechanically stable according to the calculated elastic constants. Our results show that the TiSe monolayer could be used as an excellent anode material for Li/Na/K-ion batteries.

Selection and Validation of Reference Genes for Reverse-Transcription Quantitative PCR Analysis in Sclerotium rolfsii.

Reference genes are important for the accuracy of gene expression profiles using reverse-transcription quantitative PCR (RT-qPCR). However, there are no available reference genes reported for Sclerotium rolfsii; it actually has a pretty diverse and wide host range. In this study, seven candidate reference genes (UBC, ß-TUB, 28S, 18S, PGK, EF1α and GAPDH) were validated for their expression stability in S. rolfsii under conditions of different developmental stages, populations, fungicide treatments, photoperiods and pHs. Four algorithm programs (geNorm, Normfinder, Bestkeeper and ΔCt) were used to evaluate the gene expression stability, and RefFinder was used to integrate the ranking results of four programs. Two reference genes were recommended by RefFinder for RT-qPCR normalization in S. rolfsii. The suitable reference genes were GAPDH and UBC across developmental stages, PGK and UBC across populations, GAPDH and PGK across fungicide treatments, EF1α and PGK across photoperiods, ß-TUB and EF1α across pHs and PGK and GAPDH across all samples. Four target genes (atrB, PacC, WC1 and CAT) were selected for the validation of the suitability of selected reference genes. However, using one or two reference genes in combination to normalize the expression of target genes showed no significant difference in S. rolfsii. In short, this study provided reliable reference genes for studying the expression and function of genes in S. rolfsii.

RNA methylations in human cancers.

RNA methylations, as the prevalent post-transcriptional modifications, are critical in regulating various biological processes, such as RNA transcription, splicing, structure, stability, and translation. Its dysregulation is closely related to the occurrence of human malignancies. The advance of high-throughput sequencing technology facilitates the investigations about how methylation of coding and non-coding RNAs regulates cancer progression through reshaping the transcriptomics. Here, we review the current progress about the regulatory role of several representative RNA modifications in cancers, including N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A) and 2'-O-methylation (Nm). Meanwhile, we also discuss the potential clinical value of RNA methylation in diagnostic and therapeutic implications of human cancers.

Self-referenced electro-optic response measurement of dual-parallel Mach-Zehnder modulators employing single-tone level control and low-frequency bias swing.

A self-referenced method is proposed to characterize the electro-optic frequency response of dual-parallel Mach-Zehnder modulators (DPMZMs) based on single-tone level control and low-frequency bias swing. The single-tone driving signal and the low-frequency bias signal of the DPMZM mix with each other after photodetection, and a low-frequency beat note is generated in the electrical domain. The functional relationship between the desired low-frequency amplitude and the single-tone driving level is investigated and established, from which the modulation depth and half-wave voltage are extracted with the help of regression analysis. We experimentally demonstrate the feasibility of the proposed method and compare it with the conventional ones to check the consistency. The self-referenced method features single-tone modulation and low-frequency detection for measuring high-speed DPMZMs, which avoids the use of a broadband photodetector (PD) and the influence of the uneven response of the PD.

Thin-film lithium-niobate modulator with a combined passive bias and thermo-optic bias.

It is essential to bias a thin-film lithium-niobate Mach-Zehnder electro-optic (EO) modulator at the desired operation condition to ensure optimal performance of the modulator. While thermo-optic (TO) control can solve the problem of bias drift, it consumes significant electric power. In this paper, we propose a technique to largely reduce bias power consumption by combining passive bias and TO bias. In our design, waveguide sections with different widths are introduced in the two arms of the MZ modulator to produce a desired phase difference of π/2 rad (the desired operation condition), and local heating with electrode heaters placed on the waveguides is employed to provide compensation for any phase drift caused by fabrication errors and other effects. As the TO control only serves to compensate for small errors, the electric power required is low and the response is fast. To demonstrate our technique experimentally, we fabricate several modulators of the same design on the same chip. Our experimental modulators can operate up to ∼40 GHz with a half-wave voltage of ∼2.0 V over a wide optical bandwidth, and the performances are insensitive to ambient temperature variations. The TO bias powers required range from 1 mW to 15 mW, and the thermal rise and fall times are 47 µs and 14 µs, respectively. Our technique can facilitate the development of practical high-speed EO modulators on the lithium-niobate-on-insulator platform.

Self-reference frequency response characterization of photodiode chips based on photonic sampling and microwave de-embedding.

In this work, we propose and demonstrate a self-reference on-chip testing method to obtain the frequency response characteristics of photodiode chips based on photonic sampling and microwave de-embedding. The half-frequency photonic sampling enables self-reference extraction of the combined response of the photodiode chip, the adapter network and the receiver network. The microwave de-embedding under short-open-load-device (SOLD) termination is used to realize on-chip de-embedding of the adapter network and the receiver network in terms of the transmission loss and the impedance mismatch. The proposed on-chip testing method is free of any extra electro-optical transducer standard, which is favorable for performance monitoring in chip evaluation.

A ratiometric fluorescence strategy based on polyethyleneimine surface-modified carbon dots and Eosin Y for the ultrasensitive determination of protamine and trypsin.

In this work, we report a novel and ultrasensitive dual-signal fluorescence emission detection system for protamine and trypsin based on the electrostatic interaction between polyethyleneimine (PEI) surface-modified positively charged carbon quantum dots (CDs-PEI) and the anionic fluorescent dye Eosin Y. The fluorescence system exhibited yellow-green fluorescence from Eosin Y and blue fluorescence from CDs-PEI. As a cationic peptide, protamine quenched the yellow-green fluorescence of Eosin Y at 542 nm through electrostatic interaction. In the presence of trypsin, protamine was specifically hydrolyzed by trypsin, which led to the subsequent recovery of the fluorescence of Eosin Y. Simultaneously, the blue fluorescence emission of CDs-PEI at 452 nm remained constant during the whole process. Hence, a ratiometric fluorescent nanoprobe for protamine and trypsin detection with high sensitivity was successfully constructed based on CDs-PEI and Eosin Y. For protamine detection, the ratiometric fluorescence intensity (I542/I452) exhibited an excellent linear relationship in the range of 0.1-5.2 µg mL-1 with a limit of detection (LOD) of 0.03 µg mL-1. And the linear relationship between I542/I452 and trypsin concentration ranged from 0.4 to 56 ng mL-1 with an LOD of 0.21 ng mL-1. Upon evaluating the performance of this method for the detection of trypsin in actual human urine samples, satisfactory results were finally obtained.

Size-tunable bismuth quantum dots for self-powered photodetectors under ambient conditions.

Although black phosphorus analogue, bismuthene, has been extensively investigated in recent years, yet the investigation into the photoelectronic devices is still in its infancy. In this contribution, uniform zero-dimensional (0D) bismuth (Bi) quantum dots (QDs) with different sizes were successfully synthesized by a simple solvothermal method. The as-synthesized 0D Bi QDs serve as working electrode materials by a direct deposition for photoelectrochemical (PEC)-type photodetection. The PEC results demonstrate that the as-fabricated 0D Bi QD-based electrode not only possess suitable self-powered broadband photoresponse, but also displays excellent photodetection performance. Under simulated light, the photocurrent density and photoresponsivity of the as-fabricated 0D Bi QD-based electrode can reach 2690 nA cm-2, and 22.0µA W-1, respectively. In addition, the as-prepared Bi QDs with the average diameter of 17 nm exhibit the best PEC photoresponse behavior in the studied size range of Bi QDs, mainly ascribed to the synergistic effect of suitable band gap and accessible active sites. It is anticipated that the uniform Bi QDs can be served as building blocks for a variety of photoelectronic devices, further expanding the application prospects of bismuthene, and can provide in-depth acknowledge on the performance optimization of monoelement Bi-based optical devices.

Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the development of non-alcoholic fatty liver disease: a cross-sectional study.

BACKGROUND: This study aimed to investigate the correlation of circulating total bilirubin (TB) and UGT1A1 with NAFLD in Chinese Han population. METHODS: 172 adults were enrolled from the Qingdao Municipal Hospital from May 2019 to October 2020. All individuals were examined with MRI-PDFF and divided into no steatosis, mild steatosis, moderate steatosis, and severe steatosis groups according to the MRI-PDFF values. The biochemical indexes and UGT1A1 were measured. RESULTS: There was no significant difference of circulating TB and UGT1A1 levels between NAFLD group and controls. In the moderate steatosis and severe steatosis groups, the circulating TB levels were higher than that in control group (all P < 0.05). In addition, circulating TB levels were weak positively associated with liver fat fraction in NAFLD patients (ρ = 0.205, P = 0.001). There was no significant correlation between circulating UGT1A1 levels with liver fat fraction in patients with NAFLD (ρ = 0.080, P = 0.179), but positively correlation was found in patients with severe steatosis (ρ = 0.305, P = 0.026). CONCLUSIONS: The circulating TB levels were significant high in patients with moderate and severe steatosis. Circulating TB levels were weakly associated with liver fat fraction in patients with NAFLD, and the circulating UGT1A1 levels were positively correlated with liver fat fraction in NAFLD patients with severe steatosis. TRIAL REGISTRATION: ChiCTR, ChiCTR1900022744. Registered 24 April 2019 - Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=38304&htm=4 .

MiR-146a-5p, targeting ErbB4, promotes 3T3-L1 preadipocyte differentiation through the ERK1/2/PPAR-γ signaling pathway.

BACKGROUND: MicroRNAs (MiRNAs) are known to participate in preadipocyte differentiation, but the manner in which miR-146a-5p participates in this process remains unclear. This study was performed to examine the participation of miR-146a-5p in 3T3-L1 cell differentiation. MATERIAL AND METHODS: miR-146a-5p expression was upregulated and down-regulated to examine effects on 3T3-L1 cell differentiation. Bioinformatics analysis was performed to predict its target genes, and the signaling pathway it regulates was identified by qRT-PCR and Western blotting. The expression of miR-146a-5p in epididymal adipose tissue from obese mice and in an obese mouse adipose cell model was examined by qRT-PCR. RESULTS: 3T3-L1 cells differentiated into mature adipocytes successfully, as verified by increased areas of intracellular lipid droplets and elevated expression of mature adipocyte markers, and these cells had elevated miR-146a-5p expression. The intracellular lipid droplet and triglyceride contents and the expression of mature adipocyte markers were significantly increased in miR-146a-5p-overexpressing 3T3-L1 cells and markedly decreased in miR-146a-5p-inhibited 3T3-L1 cells. ErbB4 was a predicted target gene of miR-146a-5p. In miR-146a-5p-overexpressing 3T3-L1 cells, ErbB4 expression and ERK1/2 phosphorylation were decreased and the expression of PPAR-γ was increased; the opposite was observed in miR-146a-5p-inhibited 3T3-L1 cells. In addition, miR-146a-5p expression was significantly increased in the mouse epididymal adipose tissue and adipose cell model. CONCLUSIONS: Upregulated miR-146a-5p expression was related to 3T3-L1 cell differentiation. MiR-146a-5p promoted 3T3-L1 cell differentiation by targeting ErbB4 and via the ERK1/2/PPAR-γ signaling pathway.