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"Wei, Pan-Pan"
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Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution
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.
Journal Article
Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs
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.
Journal Article
LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner
Background
Long non-coding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, associated with chronic inflammation and damage to the biliary epithelium. The aim of the study is to identify if any lncRNA might associate with inflammation or oxidative stress in CCA and regulate the disease progression.
Methods
In this study, RNA-seqs datasets were used to identify aberrantly expressed lncRNAs. Small interfering RNA and overexpressed plasmids were used to modulate the expression of lncRNAs, and luciferase target assay RNA immunoprecipitation (RIP) was performed to explore the mechanism of miRNA-lncRNA sponging.
Results
We firstly analyzed five available RNA-seqs datasets to investigate aberrantly expressed lncRNAs which might associate with inflammation or oxidative stress. We identified that two lncRNAs, H19 and HULC, were differentially expressed among all the samples under the treatment of hypoxic or inflammatory factors, and they were shown to be stimulated by short-term oxidative stress responses to H
2
O
2
and glucose oxidase in CCA cell lines. Further studies revealed that these two lncRNAs promoted cholangiocyte migration and invasion via the inflammation pathway. H19 and HULC functioned as competing endogenous RNAs (ceRNAs) by sponging let-7a/let-7b and miR-372/miR-373, respectively, which activate pivotal inflammation cytokine IL-6 and chemokine receptor CXCR4.
Conclusions
Our study revealed that H19 and HULC, up-regulated by oxidative stress, regulate CCA cell migration and invasion by targeting IL-6 and CXCR4 via ceRNA patterns of sponging let-7a/let-7b and miR-372/miR-373, respectively. The results suggest that these lncRNAs might be the chief culprits of CCA pathogenesis and progression. The study provides new insight into the mechanism linking lncRNA function with CCA and may serve as novel targets for the development of new countermeasures of CCA.
Journal Article
Quantum-dot single-photon sources for the quantum internet
High-performance quantum light sources based on semiconductor quantum dots coupled to microcavities are showing their promise in long-distance solid-state quantum networks.
Journal Article
Combining the strengths of inverse-variance weighting and Egger regression in Mendelian randomization using a mixture of regressions model
With the increasing availability of large-scale GWAS summary data on various traits, Mendelian randomization (MR) has become commonly used to infer causality between a pair of traits, an exposure and an outcome. It depends on using genetic variants, typically SNPs, as instrumental variables (IVs). The inverse-variance weighted (IVW) method (with a fixed-effect meta-analysis model) is most powerful when all IVs are valid; however, when horizontal pleiotropy is present, it may lead to biased inference. On the other hand, Egger regression is one of the most widely used methods robust to (uncorrelated) pleiotropy, but it suffers from loss of power. We propose a two-component mixture of regressions to combine and thus take advantage of both IVW and Egger regression; it is often both more efficient (i.e. higher powered) and more robust to pleiotropy (i.e. controlling type I error) than either IVW or Egger regression alone by accounting for both valid and invalid IVs respectively. We propose a model averaging approach and a novel data perturbation scheme to account for uncertainties in model/IV selection, leading to more robust statistical inference for finite samples. Through extensive simulations and applications to the GWAS summary data of 48 risk factor-disease pairs and 63 genetically uncorrelated trait pairs, we showcase that our proposed methods could often control type I error better while achieving much higher power than IVW and Egger regression (and sometimes than several other new/popular MR methods). We expect that our proposed methods will be a useful addition to the toolbox of Mendelian randomization for causal inference.
Journal Article
High-Speed Measurement-Device-Independent Quantum Key Distribution with Integrated Silicon Photonics
Measurement-device-independent quantum key distribution (MDI QKD) removes all detector side channels and enables secure QKD with an untrusted relay. It is suitable for building a star-type quantum access network, where the complicated and expensive measurement devices are placed in the central untrusted relay and each user requires only a low-cost transmitter, such as an integrated photonic chip. Here, we experimentally demonstrate a 1.25-GHz silicon photonic chip-based MDI QKD system using polarization encoding. The photonic chip transmitters integrate the necessary encoding components for a standard QKD source. We implement random modulations of polarization states and decoy intensities, and demonstrate a finite-key secret rate of31bit/sover 36-dB channel loss (or 180-km standard fiber). This key rate is higher than state-of-the-art MDI QKD experiments. The results show that silicon photonic chip-based MDI QKD, benefiting from miniaturization, low-cost manufacture, and compatibility with CMOS microelectronics, is a promising solution for future quantum secure networks.
Journal Article
Realization of two-dimensional spin-orbit coupling for Bose-Einstein condensates
Cold atoms with laser-induced spin-orbit (SO) interactions provide a platform to explore quantum physics beyond natural conditions of solids. Here we propose and experimentally realize two-dimensional (2D) SO coupling and topological bands for a rubidium-87 degenerate gas through an optical Raman lattice, without phase-locking or fine-tuning of optical potentials. A controllable crossover between 2D and 1D SO couplings is studied, and the SO effects and nontrivial band topology are observed by measuring the atomic cloud distribution and spin texture in momentum space. Our realization of 2D SO coupling with advantages of small heating and topological stability opens a broad avenue in cold atoms to study exotic quantum phases, including topological superfluids.
Journal Article
Efficacy and safety of TACE combined with lenvatinib and PD‐1 inhibitors for unresectable recurrent HCC: A multicenter, retrospective study
Background There is no consensus on the optimal regimen for unresectable recurrent hepatocellular carcinoma (HCC), so this retrospective study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and PD‐1 inhibitors (T‐L‐P) versus TACE combined with lenvatinib (T‐L) or TACE alone. Method Data were collected from 204 patients with unresectable recurrent HCC who received T‐L‐P, T‐L, or TACE alone at three medical centers from January, 2019 to December, 2020 for analysis. The survival outcomes, tumor response, and adverse events were compared between three groups, and risk factors were further investigated. Results The median overall survival in the T‐L‐P, T‐L, and TACE alone groups were not reached, 25.6, and 15.7 months, respectively (p < 0.001). The median progression‐free survival in the T‐L‐P, T‐L, and TACE alone groups were 24.1, 17.3, and 13.7 months, respectively (p < 0.001). The best objective response rate in the T‐L‐P, T‐L, and TACE alone groups were 70.4%, 48.9%, and 42.5%, respectively. The best disease control rate in the T‐L‐P, T‐L, and TACE alone groups were 100.0%, 97.8%, and 87.5%, respectively. There was no significant difference between the T‐L‐P and T‐L groups for Grade 3/4 adverse events. Conclusion T‐L‐P regimen was safe and superior to T‐L or TACE alone in improving survival for unresectable recurrent HCC patients. Transarterial chemoembolization (TACE) combined with Lenvatinib and PD‐1 inhibitors may have a better survival benefit and a manageable safety profile in patients with unresectable recurrent HCC compared with TACE plus Lenvatinib and TACE alone. This strategy has brought light to patients with unresectable recurrent HCC.
Journal Article
Cell type-dependent function of LATS1/2 in cancer cell growth
The Hippo pathway controls organ size and tissue homeostasis, and its dysregulation often contributes to tumorigenesis. Extensive studies have shown that the Hippo pathway inhibits cell proliferation, and survival in a cell-autonomous manner. We examined the function of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in cancer cells. As expected, loss of LATS1/2 promotes cancer cell growth in most cell lines. Surprisingly, however, LATS1/2 deletion inhibits the growth of murine MC38 colon cancer cells, especially under detachment conditions. This growth inhibitory effect caused by LATS1/2 deletion is due to uncontrolled activation of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), the key downstream transcriptional coactivators inhibited by LATS1/2. We identified Wnt inducible signaling pathway protein 2 (
Wisp2
) and coiled-coil domain containing 80 (
Ccdc80
) as direct targets of YAP/TAZ. Their expression is selectively induced by LATS1/2 deletion in MC38 cells. Furthermore, deletion of WISP2 and CCDC80 prevents the growth inhibitory effect of LATS1/2 loss in MC38 cells. Our study demonstrates that the function of LATS1/2 in cell growth is cell context dependent, suggesting that LATS1/2 inhibition can be a therapeutic approach for some cancer types.
Journal Article