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Nicotinamide adenine dinucleotide (NAD), a nucleotide-containing metabolite, can be incorporated into the RNA 5'-terminus to result in NAD-capped RNA (NAD-RNA). Since NAD has been heightened as one of the most essential metabolites in cells, its linkage to RNA represents a critical but poorly studied modification at the epitranscriptomic level. Here, we design a highly sensitive method, DO-seq, to capture NAD-RNAs. Using Drosophila , we identify thousands of previously unexplored NAD-RNAs and their dynamics in the fly life cycle, from embryo to adult. We show the evidence that chromosomal clustering might be the structural basis by which co-expression can couple with NAD capping on physically and functionally linked genes. Furthermore, we note that NAD capping of cuticle genes inversely correlates with their gene expression. Combined, we propose NAD-RNA epitranscriptome as a hidden layer of regulation that underlies biological processes. DO-seq empowers the identification of NAD-capped RNAs, facilitating functional investigation into this modification., Competing Interests: N.L. is an inventor on a pending patent arising from this work, filed by the Chinese Academy of Sciences. The other authors declare no competing interests., (© 2023 The Authors.)

Anticancer treatment regimens are effective but may lead to cardiac dysfunction. The meaning of this statement is that myocardial strain can be a good indicator of cancer treatment-related cardiac dysfunction. We used Bayesian network meta-analysis to compare and rank these regimens to comprehensively evaluate their influence on the heart. We searched multiple databases to identify relevant studies. Global longitudinal strain (GLS), global radial strain, global circumferential strain, and other parameters were collected at baseline (T0), from baseline to 3 months of follow-up (T3), from 3 months to 6 months of follow-up (T6), and from 6 months to 12 months or longer of follow-up (T12). The weight mean differences (WMD) with 95% confidence intervals (CI) were used to express continuous variables. Direct and indirect comparison and ranking of different regimens based on the forest plots and the surface under the cumulative ranking area. A total of 4613 subjects were included in 33 studies. Anthracycline-based chemotherapy (ANT), trastuzumab, paclitaxel plus carboplatin or clofarabine, and radiotherapy (RT) were more likely to reduce GLS and global circumferential strain at T3 and T12. In particular, ANT+RT resulted in a more significant decrease in GLS than ANT alone at T12 (WMD 1.15; 95% CI, 0.05-2.26). Interestingly, cardioprotective treatment regimens, such as anthracycline plus bisoprolol plus angiotensin-converting enzyme inhibitors (ANT+BB+ACEIs) (WMD -2.79; 95% CI, -5.06 to -0.52), and ANT plus rosuvastatin (STATINs) (WMD -2.92; 95% CI, -5.54 to -0.29), were more likely to improve GLS than ANT at T12. The included anticancer regimens, especially ANT+RT, reduced GLS at T12, but their combination with cardioprotective drugs improved them. These results will help clinicians choose the best therapy regimens., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Amphiphilicity is an excellent physicochemical property, which is yet to be explored from traditional surfactants to nanoparticles. This article shows that the amphiphilicity of copper nanoclusters (CuNCs) can be readily tuned by electrostatic interactions with cationic surfactants and cetyltrimethylammonium cations (CTA + ) with counterions Br - , Cl - , and C 7 H 8 O 3 S - . Due to the role of surface ligands, the complexes of glutathione-capped CuNCs (GSH-CuNCs) and the surfactants exhibit good amphiphilicity, which enables them to self-assemble like a molecular amphiphile. This could significantly increase the utility of metal nanoclusters in basic and applied research. As the concentration of the surfactant changes, the aggregates change from nanoparticles to network-like structures. After the formation of supramolecular self-assemblies by hydrophobic interactions, the enhancement of fluorescence intensity was observed, which can be ascribed to the suppression of intramolecular vibrations based on aggregation-induced emission (AIE) and combined with the compactness of GSH-CuNCs in self-assemblies. Our study provides a facile way to generate solid fluorescent materials with excellent fluorescence performance, which may find applications in light-emitting diodes (LEDs).

This paper attempts to establish a psychophysical basis for both stationary (tension in chord sonorities) and transitional (resolution in chord progressions) harmony. Harmony studies the phenomenon of combining notes in music to produce a pleasing effect greater than the sum of its parts. Being both aesthetic and mathematical in nature, it has baffled some of the brightest minds in physics and mathematics for centuries. With stationary harmony acoustics, traditional theories explaining consonances and dissonances that have been widely accepted are centred around two schools: rational relationships (commonly credited to Pythagoras) and Helmholtz's beating frequencies. The first is more of an attribution than a psychoacoustic explanation while electrophysiological (amongst other) discrepancies with the second still remain disputed. Transitional harmony, on the other hand, is a more complex problem that has remained largely elusive to acoustic science even today. In order to address both stationary and transitional harmony, we first propose the notion of interharmonic and subharmonic modulations to address the summation of adjacent and distant sinusoids in a chord. Based on this, earlier parts of this paper then bridges the two schools and shows how they stem from a single equation. Later parts of the paper focuses on subharmonic modulations to explain aspects of harmony that interharmonic modulations cannot. Introducing the concept of stationary and transitional subharmonic tensions, we show how it can explain perceptual concepts such as tension in stationary harmony and resolution in transitional harmony, by which we also address the five fundamental questions of psychoacoustic harmony such as why the pleasing effect of harmony is greater than that of the sum of its parts. Finally, strong correlations with traditional music theory and perception statistics affirm our theory with stationary and transitional harmony., Competing Interests: The authors declare no conflicts of financial interest., (Copyright © 2019 Paul Yaozhu Chan et al.)

A method for the rapid determination of 18 polychlorinated biphenyls (PCBs) in tea by gas chromatography-mass spectrometry (GC-MS) coupled with dispersive solid-phase extraction (dSPE) was developed and evaluated. Carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) and primary secondary amine (PSA) were used as sorbents in pretreatment process. PCBs were ultrasonically extracted from tea samples with hexane-acetone (1:1, v/v), and purified with the mixed sorbents of MWCNTs-COOH and PSA after replacing hexane-acetone by toluene. The PCBs were determined by an electron impact ionization source and selected ion monitoring mode. The analytes were qualitatively confirmed from the retention time and relative abundance ratio of characteristic ions, and quantified by a matrix-matched standard solution. The chromatographic and MS parameters influencing separation and sensitivity were optimized, and major factors affecting the extraction and cleanup efficiency including type and volume of extraction solvent, extraction time, type and amount of cleanup sorbent, and clean-up time were investigated. The performance of the method was evaluated. Under optimum conditions, satisfactory linear relationship was observed with the content of PCBs ranging from 5 to 500 μg/kg, with correlation coefficients ( r ) no less than 0.9998. The 18 PCBs in three kinds of tea matrices including Biluochun tea, Tieguanyin tea and Pu'er tea were spiked at 5, 10 and 100 μg/kg to evaluate recoveries, which ranged from 90.7% to 115.2% with relative standard deviations ( n =5) between 0.3% and 10.9%. The limits of detection and the limits of quantification were 0.3-1.7 μg/kg and 5 μg/kg for each PCB, respectively. The method is simple, rapid, accurate, sensitive and effective, and is suitable for the determination of the 18 PCBs in different kinds of tea.

In this study, we used next-generation sequencing methods to screen 300 individuals for BRCA1 and BRCA2 . A novel mutation (c.849dupT) in BRCA2 was identified in a female patient and her unaffected brothers. This mutation leads to the truncation of BRCA2 functional domains. Moreover, BRCA2 mRNA expression levels in mutation carriers are significantly reduced compared to noncarriers. Immunofluorescence and western blot assays showed that this mutation resulted in reduced BRCA2 protein expression. Thus, we identified a novel mutation that damaged the function and expression of BRCA2 in a family with breast cancer history. The pedigree analysis suggested that this mutation is strongly associated with familial breast cancer. Genetic counsellors suggest that mutation carriers in this family undergo routine screening for breast cancer, as well as other malignancies, such as prostate and ovarian cancer. The effects of this BRCA2 mutation on drug resistance should be taken into consideration during treatment., Competing Interests: CONFLICT OF INTEREST: The authors declare that they have no competing interests.

A valid and encyclopaedic evaluation method for assessing the quality of Sanhuang Gypsum Soup (SGS) has been set up based on analysis of high-performance liquid chromatography (HPLC) fingerprint combined with the quantitative analysis of multicomponents by single marker (QAMS) method, hierarchical cluster analysis (HCA), and similarity analysis. 20 peaks of the common model were obtained and used for the similarity analysis and HCA analysis. Berberine was selected as an internal reference, and the relative correction factors of mangiferin, geniposide, liquiritin, epiberberine, coptisine, baicalin, palmatine, harpagosid, wogonoside, cinnamic acid, cinnamic aldehyde, baicalein, glycyrrhizic acid, and wogonin were established. The accuracy of quantitative analysis of multicomponents by the single-marker method was verified by comparing the contents of the fourteen components calculated by the external standard method with those of the quantitative analysis of multicomponents by the single-marker method. No significant difference was found in the quantitative results of the established quantitative analysis of multicomponents by a single-marker method and an external standard method. In summary, these methods were applied to evaluate the quality of SGS successfully. As a result, these evaluation methods have great potential to be widely used in the quality control of traditional Chinese medicines (TCM).

Cancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer 1-3 , but efficacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes 4-6 . To depict the baseline landscape of the composition, lineage and functional states of tumor infiltrating lymphocytes, here we performed deep single-cell RNA sequencing for 12,346 T cells from 14 treatment-naïve non-small-cell lung cancer patients. Combined expression and T cell antigen receptor based lineage tracking revealed a significant proportion of inter-tissue effector T cells with a highly migratory nature. As well as tumor-infiltrating CD8 + T cells undergoing exhaustion, we observed two clusters of cells exhibiting states preceding exhaustion, and a high ratio of "pre-exhausted" to exhausted T cells was associated with better prognosis of lung adenocarcinoma. Additionally, we observed further heterogeneity within the tumor regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of those activated tumor Tregs, which included IL1R2, correlated with poor prognosis in lung adenocarcinoma. Our study provides a new approach for patient stratification and will help further understand the functional states and dynamics of T cells in lung cancer.

c-MET is a receptor tyrosine kinase and potential oncological target for cancer therapy. The activities of 1,2,3-triazolo[4,5-b]pyrazine series of c-MET inhibitors were analyzed according to the three-dimensional quantitative structure-activity relationship and molecular docking methods. The results indicated that the hydrophobic and electrostatic fields play key roles in activity and QSAR model was reliable enough for activity prediction. Moreover, the docking results do validate the predicted 3D-QSAR scores, vital residues Asp1222, Asp1231, Met1160, Tyr1259 and Tyr1230 found in binding site. Four new c-MET inhibitor analogs designed in this Letter which are being currently synthesized by our laboratories., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The biological functions of the differentially abundant proteins between superior and inferior spikelet grains were investigated based on the isobaric tags for relative and absolute quantification to further clarify the mechanism of rice grain filling at the proteomic level, as well as the response of inferior spikelets to drought dress (-20kPa or -40kPa). Compared with superior spikelets, inferior ones had lower sink strength due to the lower sink activities (lower abundances of ADP-glucose pyrophosphorylase, granule-bound starch synthase, starch branching enzyme and pullulanase) and smaller sink sizes (lower abundances of structural proteins). The slower and later grain filling resulted from the weaker decomposition and conversion of photoassimilate and the slower cell division. Moderate drought stress (-20kPa) promoted the grain filling of inferior spikelets through regulating the proteins associated with photoassimilate supply and conversion. These proteins may be important targets for rice breeding programs that raise the rice yield under drought condition. The findings offer new insights into rice grain-filling and provide theoretical evidences for better quality control and scientific improvement of super rice in practice., Biological Significance: Rice cultivars with large panicles do not always guarantee high yield and grain quality probably due to the slow grain filling and many unfilled grains of inferior spikelets. In general, earlier-flowering superior spikelets, which are usually located on apical primary branches, fill faster and produce larger and heavier grains. In contrast, later-flowering inferior spikelets located on proximal secondary branches are either sterile or fill slowly and poorly, and the differences are more significant in large panicle rice or super rice. The increase of rice yield has been limited by the unsatisfactory grain filling of inferior spikelets, and the inferior spikelets are more prone to environmental factors during grain filling. Thus, we herein investigated the biological functions of differently abundant proteins between superior and inferior spikelet grains by using iTRAQ to unravel the mechanism of rice grain filling and the response of inferior spikelets to drought stress at proteomic level. This study offers new insights into rice grain-filling and provides valuable evidences for better quality control and scientific improvement of super rice in practice., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We provide the raw data for protein and peptide identification and quantization of superior and inferior spikelets in hybrid rice during grain filling. The mass spectrometry proteomics data have been deposited to the Proteome Xchange Consortium via the PRIDE partner repository with the dataset identifier PXD001046. Our data presented here is also related to the article "Comparative proteomics analysis of superior and inferior spikelets in hybrid rice during grain filling and response of inferior spikelets to drought stress using isobaric tags for relative and absolute quantification "in the Journal of Proteomics [1].