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In droplet-based single-cell and single-nucleus RNA-seq assays, systematic contamination of ambient RNA molecules biases the quantification of gene expression levels. Existing methods correct the contamination for all genes globally. However, there lacks specific evaluation of correction efficacy for varying contamination levels. Here, we show that DecontX and CellBender under-correct highly contaminating genes, while SoupX and scAR over-correct lowly/non-contaminating genes. Here, we develop scCDC as the first method to detect the contamination-causing genes and only correct expression levels of these genes, some of which are cell-type markers. Compared with existing decontamination methods, scCDC excels in decontaminating highly contaminating genes while avoiding over-correction of other genes.

Incorporating narrow-bandgap near-infrared absorbers as the third component in a donor/acceptor binary blend is a new strategy to improve the power conversion efficiency (PCE) of organic photovoltaics (OPV). However, there are two main restrictions: potential charge recombination in the narrow-gap material and miscompatibility between each component. The optimized design is to employ a third component (structurally similar to the donor or acceptor) with a lowest unoccupied molecular orbital (LUMO) energy level similar to the acceptor and a highest occupied molecular orbital (HOMO) energy level similar to the donor. In this design, enhanced absorption of the active layer and enhanced charge transfer can be realized without breaking the optimized morphology of the active layer. Herein, in order to realize this design, two new narrow-bandgap nonfullerene acceptors with suitable energy levels and chemical structures are designed, synthesized, and employed as the third component in the donor/acceptor binary blend, which boosts the PCE of OPV to 11.6%.

Enhancers act to regulate cell-type-specific gene expression by facilitating the transcription of target genes. In mammalian cells, active or primed enhancers are commonly marked by monomethylation of histone H3 at lysine 4 (H3K4me1) in a cell-type-specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals is unclear. In this study, we conducted SILAC mass spectrometry experiments with mononucleosomes and identified multiple H3K4me1-associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments association of the chromatin-remodeling complex BAF to enhancers in vivo and that, in vitro, H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of the BAF component BAF45C indicate that monomethylation, but not trimethylation, is accommodated by BAF45C's H3K4-binding site. Our results suggest that H3K4me1 has an active role at enhancers by facilitating binding of the BAF complex and possibly other chromatin regulators.

Pancreatic adenocarcinoma (PAAD) is an aggressive malignancy with high mortality and poor prognosis. Neutrophil extracellular traps (NETs) and the epithelial‐mesenchymal transition (EMT) significantly influence on the progression of various cancers. However, the underlying relevance of NETs‐ and EMT‐associated genes on the outcomes of patients with PAAD remains to be elucidated. Transcriptome RNA sequencing data, together with clinical information and single‐cell sequencing data of PAAD were collected from public databases. In the TCGA‐PAAD cohort, ssGSEA was used to calculate NET and EMT scores. WGCNA was used to determine the key gene modules. A risk model with eight NET‐ and EMT‐related genes (NERGs) was established using LASSO and multivariate Cox regression analysis. Patients in the reduced risk (RR) group showed better prognostic values compared with those in the elevated risk (ER) group. The prognostic model exhibited reliable and robust prediction when validated using an external database. The distributions of risk genes were explored in a single‐cell sequencing data set. Immune infiltration, immune cycle, and immune checkpoints were compared between the RR and ER groups. Moreover, potential chemotherapeutic drugs were examined. DCBLD2 was identified as a key gene in PAAD cell lines by qRT‐PCR, and was highly expressed in PAAD tissues. GSEA demonstrated that DCBLD2 induced the EMT. Transwell assays and western blotting showed that cell invasion and EMT induction were significantly reduced after DCBLD2 knockdown. Collectively, we constructed a prognosis model based on a NET and EMT gene signature, providing a valuable perspective for the prognostic evaluation and management of PAAD patient. [ABSTRACT FROM AUTHOR]

The electrochemical nitrate reduction reaction (NO3RR) is an environment‐friendly and promising alternative to the conventional Haber–Bosch ammonia synthesis process, which is a complex process of proton‐coupled electron transfer. Hereon, the amorphous CeOx support introduced to construct Cu/a‐CeOx heterostructure is prepared to provide sufficient *H and synergistically catalyze the NO3RR. Cu/a‐CeOx achieves a maximum ammonia yield of 1.52 mmol h−1 mgcat−1. In the flow cell, the NH3 yield reaches 17.93 mmol h−1 mgcat−1 at 1 A cm−2, which exceeds most of the state‐of‐the‐art catalysts. In situ X‐ray diffraction (XRD) and in situ Raman observe that the catalyst undergoes structural reconfiguration under operating conditions, thus confirming that Cu2O is not the true active center in the catalytic process. Furthermore, in situ characterizations and density functional theory (DFT) calculations demonstrate that the amorphous CeOx in Cu/a‐CeOx modulates the electronic structure of Cu and overcomes the higher potential barrier required for the decomposition of water on Cu, which greatly facilitates the hydrolysis process and provides a higher H‐coverage rate for the hydrogenation of NO3−, realizing a dynamic equilibrium between the production and consumption of active hydrogen. This component design strategy centered on the amorphous structure opens up a new pathway for the electrochemical NO3RR. [ABSTRACT FROM AUTHOR]

An inverted AluYb8 insertion in the MUTYH intron 15 (AluYb8MUTYH variant) has been reported to be associated with reduced MUTYH1 expression and mitochondrial dysfunction with age. However, the underlying mechanism remains unknown. In this study, we identified a novel transcript associated with the AluYb8MUTYH variant, which revealed that this transcript is about 780 nucleotides in length with a poly-A tail, lacks protein-coding potential, referred to as lncMUTYH. The results from the reporter gene system confirmed that the lncMUTYH down-regulates MUTYH1 expression at the translational level. Site-directed mutagenesis on the 5′-terminal exon sequences of α-MUTYH and lncMUTYH constructs revealed that lncMUTYH can act as a trans-regulator that depends on the partial base pairing between its exonized AluYb8 sequence and the 5′UTR of α-MUTYH to impede MUTYH 1 expression. Furthermore, we have demonstrated a correlation between decreased mitochondrion-localized MUTYH1 caused by lncMUTYH and lowered levels of mitochondrial biological function indicators, such as mtDNA content, mitochondrial regulatory gene expression, oxygen consumption rate, ATP product, and mitochondrial respiratory capacity. Notably, we found that lncMUTYH inhibited the M2-like polarization of macrophages, and CD68/CD206-positive cell fractions were significantly lower in lncMUTYH ectopically expressing cells. The results confirmed that the AluYb8MUTYH-associated lncMUTYH, derived from an AluYb8 insertion mutation, acts as a trans-regulatory factor that inhibits the MUTYH1 protein expression, leading to a progressive mitochondrial dysfunction that may disrupt macrophage differentiation. In summary, lncMUTYH can contribute to AluYb8MUTYH-associated mitochondrial dysfunction with age and hamper the macrophage polarization process, potentially increasing the risk of developing age-related diseases. A novel non-coding RNA was identified derived from the AluYb8 insertion in the MUTYH gene, namely lncMUTYH. LncMUTYH selectively decreased the MUTYH1 protein localized in mitochondrial, which is dependent on the sequence and orientation derived from AluYb8 insertion. Overexpression of lncMUTYH dampens the mitochondrial function and M2-like polarization of macrophages, partly due to the suppression of the MUTYH1 protein. [ABSTRACT FROM AUTHOR]

Jumonji D3 (JMJD3) histone demethylase epigenetically regulates development and differentiation, immunity, and tumorigenesis by demethylating a gene repression histone mark, H3K27-me3, but a role for JMJD3 in metabolic regulation has not been described. SIRT1 deacetylase maintains energy balance during fasting by directly activating both hepatic gluconeogenic and mitochondrial fatty acid [beta]-oxidation genes, but the underlying epigenetic and gene-specific mechanisms remain unclear. In this study, JMJD3 was identified unexpectedly as a gene-specific transcriptional partner of SIRT1 and epigenetically activated mitochondrial [beta]-oxidation, but not gluconeogenic, genes during fasting. Mechanistically, JMJD3, together with SIRT1 and the nuclear receptor PPAR[alpha], formed a positive autoregulatory loop upon fasting-activated PKA signaling and epigenetically activated [beta]-oxidation-promoting genes, including Fgf21, Cptla, and Mcad. Liver-specific downregulation of JMJD3 resulted in intrinsic defects in [beta]-oxidation, which contributed to hepatosteatosis as well as glucose and insulin intolerance. Remarkably, the lipid-lowering effects by JMJD3 or SIRT1 in diet-induced obese mice were mutually interdependent. JMJD3 histone demethylase may serve as an epigenetic drug target for obesity, hepatosteatosis, and type 2 diabetes that allows selective lowering of lipid levels without increasing glucose levels., Introduction In mammals, the liver plays a central role in maintaining energy balance in response to nutrient deprivation by activating lipid and glucose metabolic pathways. During early fasting, the liver [...]