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Background As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing. Results We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel COCH + fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors, and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues. Conclusions The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.

The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8 + T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8 + T and immune-suppressive TNFRSF4 + Treg cells in tumours might derive from peripheral CX3CR1 + CD8 + T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3 + DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3 + DCs, Treg, exhausted CD8 + T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC. Nasopharyngeal carcinoma is a diverse cancer characterised by a heterogeneous microenvironment. Here, the authors use single cell sequencing to analyse the tumour microenvironment in 10 nasopharyngeal carcinoma tumours and identify different cell types including immune-suppressive T regulatory, tolerogenic dendritic, and exhausted CD8 T cells.

Super-enhancers (SEs) are expansive cis-regulatory elements known for amplifying oncogene expression across various cancers. However, their role in cervical cancer (CC), a remarkable global malignancy affecting women, remains underexplored. Here we applied integrated epigenomic and transcriptomic profiling to delineate the distinct SE landscape in CC by analyzing paired tumor and normal tissues. Our study identifies a tumor-specific SE at the EFNA1 locus that drives EFNA1 expression in CC. Mechanically, the EFNA1-SE region contains consensus sequences for the transcription factor FOSL2, whose knockdown markedly suppressed luciferase activity and diminished H3K27ac enrichment within the SE region. Functional analyses further underlined EFNA1's oncogenic role in CC, linking its overexpression to poor patient outcomes. EFNA1 knockdown strikingly reduced CC cell proliferation, migration, and tumor growth. Moreover, EFNA1 cis-interacted with its receptor EphA2, leading to decreased EphA2 tyrosine phosphorylation and subsequent activation of the Src/AKT/STAT3 forward signaling pathway. Inhibition of this pathway with specific inhibitors substantially attenuated the tumorigenic capacity of EFNA1-overexpressing CC cells in both in vitro and in vivo models. Collectively, our study unveils the critical role of SEs in promoting tumor progression through the FOSL2-EFNA1-EphA2-Src/AKT/STAT3 axis, providing new prognostic and therapeutic avenues for CC patients.

Extranodal natural killer/T‐cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein–Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single‐cell RNA sequencing (scRNA‐seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single‐cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV‐encoded genes and low infiltration of tumor‐associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single‐cell resolution, highlighting the crucial role of malignant NK cells with EBV‐encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL. Single‐cell RNA‐sequencing analysis and functional investigations uncover the pivotal role of EBV, particularly the viral gene LMP1, in the malignant transformation and progression of NKTCL. Malignant NK cells entertain with immune cells to jointly foster an immunosuppressive TME favorable for NKTCL development. Targeting TME components, including LMP1 and DPP4, emerges as a potential therapeutic strategy against NKTCL.

Ascorbate peroxidase (APX) is one of the important antioxidant enzymes in the active oxygen metabolism pathway of plants and animals, especially it is the key enzyme to clear H2O2 in chloroplast and the main enzyme of vitamin C metabolism. However, knowledge about APX gene family members and their evolutionary and functional characteristics in kiwifruit is limited. In this study, we identified 13 members of the APX gene family in the kiwifruit (cultivar: Hongyang) genome according the APX proteins conserved domain of Arabidopsis thaliana. Phylogenetic analysis by maximum likelihood split these 13 genes into four groups. The APX gene family members were distributed on nine chromosomes (Nos. 4, 5, 11, 13, 20, 21, 23, 25, 28). Most of the encoded hydrophilic and lipid-soluble enzymes were predicted to be located in the cytoplasm, nucleus and chloroplast. Among them, AcAPX4, AcAPX5, AcAPX8, AcAPX12 were transmembrane proteins, and AcAPX8 and AcAPX12 had the same transmembrane domain. The gene structure analysis showed that AcAPXs were composed of 4-22 introns, except that AcAPX10 was intron-free. Multiple expectation maximization for motif elicitation program (MEME) analyzed 13 APX protein sequences of Actinidia chinensis and identified 10 conserved motifs ranging in length from 15 to 50 amino acid residues. Additionally, the predicted secondary structures of the main motifs consisted of α-helix and random coils. The gene expression of fruits in different growth stages and bagging treatment were determined by qRT-PCR. The results showed that 8 AcAPXs had the highest expression levels during the color turning period and only the gene expression of AcAPX3 was consistent with the ascorbic acid content; five AcAPXs were consistent with the ascorbic acid content after bagging. Our data provided evolutionary and functional information of AcAPX gene family members and revealed the gene expression of different members in different growth stages and bagging treatments These results may be useful for future studies of the structures and functions of AcAPX family members.

Adenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from four AEG patients and performed integrated analysis with publicly available GAC single-cell datasets. Our study for the first time comprehensively deciphered the TME landscape of AEG, where heterogeneous AEG malignant cells were identified with diverse biological functions and intrinsic malignant nature. We also depicted transcriptional signatures and T cell receptor (TCR) repertoires for T cell subclusters, revealing enhanced exhaustion and reduced clone expansion along the developmental trajectory of tumor-infiltrating T cells within AEG. Notably, we observed prominent enrichment of tumorigenic cancer-associated fibroblasts (CAFs) in the AEG TME compared to GAC. These CAFs played a critical regulatory role in the intercellular communication network with other cell types in the AEG TME. Furthermore, we identified that the accumulation of CAFs in AEG might be induced by malignant cells through FGF-FGFR axes. Our findings provide a comprehensive depiction of the AEG TME, which underlies potential therapeutic targets for AEG patient treatment.

Crystal structure of conjugated molecules and polymers is fundamentally critical to understand their multilevel microstructures, carrier transport, and diverse functions. However, to determine the crystal structure of conjugated polymers is a significant challenge, mainly due to the poor crystallinity, weak diffraction, and instability under high‐energy radiation. Here, we build the possible crystal structures of eight typical conjugated polymers, covering several widely used molecular segments in organic optoelectronics. We model the packing structures of these seed polymers based on synchrotron X‐ray diffractions and molecular simulations. These crystal structures provide a new platform to predict the packing structures of more related polymer systems, extending the molecular scope. Based on this polymer crystal structure database, the multiscale microstructures and charge transport properties of conjugated polymers can be predicted before experiments. This study sets up a polymer crystal structure database to eliminate the current trial‐and‐error approaches and accelerating the design of high‐performance conjugated polymers. Combining X‐ray diffraction and molecular modeling, the atomic‐level crystal structures of eight typical conjugated polymers are built. These eight crystal structures compose a crystal structure database of conjugated polymers, covering widely used molecular segments in organic optoelectronics. The crystal structure database can be used to predict the packing structures and charge transport of other related polymers.

Traditional Chinese medicine has great advantages in improving symptoms of CHF such as chest tightness, shortness of breath, and fatigue. In addition, some traditional Chinese medicines can be used as both medicine and food, which have good effects on the prevention and treatment of CHF patients at home. A comprehensive search across China National Knowledge Infrastructure (CNKI), Wanfang, and Wei Pu (VIP) databases was conducted to retrieve pre-2022 literature related to CHF. After standardization, frequency analysis and Apriori algorithm were used to analyze these data. Among 626 effective medical records, Fuling, Huangqi, and Danshen are the most commonly used herbs; The medication for chest tightness is closely related to Tinglizi; The medication for palpitations is closely related to Guizhi, Fuzi, Zhigancao, and Wuweizi; The medication of fatigue and poor appetite is closely related to Huangqi and Baizhu; The medication for lower limb edema is closely related to Fuling and Tinglizi; The medication for coughing is closely related to the use of Tinglizi, Wuweizi, Kuxingren, and Sangbaipi; Insomnia is closely related to Suanzaoren and Dazao. The components in traditional Chinese medicine that have anti heart failure effects and reliable evidence can be potential candidates for drug discovery, while dietary therapeutic herbs such as Fuling, Huangqi, Danshen, and Zhigancao can be developed as health products.

Dysregulation of serine/arginine splicing factors (SRSFs) and abnormal alternative splicing (AS) have been widely implicated in various cancers but scarcely investigated in nasopharyngeal carcinoma (NPC). Here we examine the expression of 12 classical SRSFs between 87 NPC and 10 control samples, revealing a significant upregulation of SRSF3 and its association with worse prognosis in NPC. Functional assays demonstrate that SRSF3 exerts an oncogenic function in NPC progression. Transcriptome analysis reveals 1,934 SRSF3-regulated AS events in genes related to cell cycle and mRNA metabolism. Among these events, we verify the generation of a long isoform of AMOTL1 (AMOTL1-L) through a direct bond of the SRSF3 RRM domain with the exon 12 of AMOTL1 to promote exon inclusion. Functional studies also reveal that AMOTL1-L promotes the proliferation and migration of NPC cells, while AMOTL1-S does not. Furthermore, overexpression of AMOTL1-L, but not -S, significantly rescues the inhibitory effects of SRSF3 knockdown. Additionally, compared with AMOTL1-S, AMOTL1-L has a localization preference in the intracellular than the cell membrane, leading to a more robust interaction with YAP1 to promote nucleus translocation. Our findings identify SRSF3/AMOTL1 as a novel alternative splicing axis with pivotal roles in NPC development, which could serve as promising prognostic biomarkers and therapeutic targets for NPC.

Epstein-Barr virus (EBV) is a significant epigenetic driver in the development of epithelial-origin nasopharyngeal carcinoma (NPC) and gastric cancer (GC), which together represent 80% of EBV-associated malignancies. Despite its known association, the specific mechanisms, particularly those involving EBV-induced histone modifications, remain poorly understood. Through integrative analyses of single-cell and bulk transcriptome data from epithelial tumor tissues and EBV-infected cells, we identified KDM5B as a critical histone-modifying factor consistently upregulated following EBV infection. We demonstrated that EBV stimulates KDM5B expression via interactions of its latent gene EBNA1 with transcription factor CEBPB and through direct binding of its lytic gene BZLF1 to Zta-response elements on the KDM5B promoter. Functional assays revealed that KDM5B acts as an oncogene, correlating with poor survival outcomes in EBV-associated epithelial cancers. Mechanistically, KDM5B inhibited the tumor suppressor gene PLK2 through histone demethylation, thereby activating the PI3K/AKT/mTOR signaling pathway and promoting malignant progression. Furthermore, treatment with the KDM5B inhibitor AS-8351 markedly attenuated this signaling activity and exhibited strong anti-tumor effect in both in vitro and in vivo patient-derived xenograft models from EBV-associated tumors. Together, these findings provide novel insights into how EBV hijacks KDM5B to mediate histone demethylation of PLK2, facilitating tumor progression through the PI3K/AKT/mTOR pathway in epithelial cancers, highlighting promising therapeutic strategies targeting epigenetic alterations in EBV-associated cancers.