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.
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.
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.
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
O
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.
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.
Wave power results from converting wind energy into kinetic energy on the ocean's surface. Alterations in long-term ocean surface waves can have significant consequences for coastal regions, ...including erosion and an elevated risk of flooding. Our research has unveiled a discernible and escalating trend in several crucial oceanic parameters, encompassing sea-surface temperature (SST), 10-m wind speed (W10), and significant wave height (SWH), both on a global and regional scale. Importantly, we have established statistically substantial relationships between SST and W10 and W10 and SWH. Moreover, our analysis has revealed a temporal lag of one year in the cross-correlation between SST and W10, while no such temporal offset is evident between W10 and SWH. Significantly, our investigation has provided evidence that global wave power (WP) has exhibited an annual increase of 0.54% over the comprehensive 70-year period from 1951 to 2020. This upward trajectory can be primarily attributed to the phenomenon of upper-ocean warming, which serves to enhance W10. Specifically, when SST exceeds the 70-year average by 1 °C (1951–2020), a corresponding global increase of 0.8 m/s in W10 is observed. This elevation in W10, in turn, results in a 0.5 m increase in SWH, ultimately culminating in a substantial 32.8 kW/m boost in WP. Our comprehensive analysis of the 70-year dataset underscores the predominant role played by the oceanic region situated between latitudes 30°S and 60°S, contributing a substantial 52.3% share to global WP. Closely following is the South Pacific region, contributing 28.3% to the cumulative WP, followed by the South Atlantic (23.3%), the Indian Ocean (15.1%), and the North Atlantic and North Pacific regions, each contributing approximately 9.6% and 9.3%, respectively. The findings derived from our study cast a spotlight on the intensification of W10, the amplification of SWH, and the significant escalation in WP since the 1970s. These trends are intrinsically linked to the phenomenon of upper-ocean warming. Importantly, they portend a scenario in which the world's oceans will manifest even greater energy levels should current warming trends continue unabated.
•Global SST, W10, and SWH data covering 1951–2020 were analysed.•Statistical analysis reveals the cross-correlations of SST and W10 with a one-year lag, while there is no time lag for W10 and SWH.•Statistical analysis shows an upward trend for global SST, W10, SWH, and WP.•The most energetic ocean region is the S30o–S60o, which accounts for 52.3% of WP globally.•Upper-ocean warming induced stronger W10, consequently elevating SWH and significantly raising WP since the 1970s.
The out-of-time-ordered correlators (OTOC), a fundamental concept for quantifying quantum information scrambling, has recently been suggested to be an order parameter to dynamically detect both ...equilibrium quantum phase transitions (EQPTs) and dynamical quantum phase transitions (DQPTs). Here we report the first experimental observation of EQPTs and DQPTs in a quantum spin chain via quench dynamics of OTOC on a nuclear magnetic resonance quantum simulator. We observe that the quench dynamics of the OTOC can unambiguously detect the DQPTs and the equilibrium critical point, while conventional order parameters such as the longitudinal magnetization can not. Moreover, we investigate the two-body correlations throughout the quench dynamics, and find that OTOC can extract the equilibrium critical point with higher accuracy and is more robust to decoherence than that of two-body correlation. Our experiment paves a way for experimentally investigating DQPTs through OTOCs and for studying the EQPTs through the nonequilibrium quantum quench dynamics with quantum simulators.
This paper explores the relatively unexamined topic of interactions between corporeal and affective dimensions in male sexual labour, focusing on the role of intimacy in the bodywork of erotic gay ...massage in Taiwan. Feminist perspectives on bodywork and affective embodiment are used to analyse how intimacy is lived out during commodified same‐sex engagements. Drawing upon in‐depth interviews with 34 self‐identified gay masseurs, I examine two prominent servicing features of male‐for‐male massage: crafted intimacy and unscripted care. Whereas the former refers to the ‘boyfriend experience’ built up through tactile encounters, the latter regards erotic services as caring practices for the socially vulnerable, adding a moral dimension to the cultural significance of gay sexual commerce in Taiwan. This paper concludes that corporeal and affective dimensions are inseparable in understanding gay massage. Further research can benefit from more attention to somatic affection in the interplay between bodywork and intimacy in male sexual labour.
Electronic skin sensing devices are an emerging technology and have substantial demand in vast practical fields including wearable sensing, robotics, and user‐interactive interfaces. In order to ...imitate or even outperform the capabilities of natural skin, the keen exploration of materials, device structures, and new functions is desired. However, the very high resistance and the inadequate current switching and sensitivity of reported electronic skins hinder to further develop and explore the promising uses of the emerging sensing devices. Here, a novel resistive cloth‐based skin‐like sensor device is reported that possesses unprecedented features including ultrahigh current‐switching behavior of ≈107 and giant high sensitivity of 1.04 × 104–6.57 × 106 kPa−1 in a low‐pressure region of <3 kPa. Notably, both superior features can be achieved by a very low working voltage of 0.1 V. Taking these remarkable traits, the device not only exhibits excellent sensing abilities to various mechanical forces, meeting various applications required for skin‐like sensors, but also demonstrates a unique competence to facile integration with other functional devices for various purposes with ultrasensitive capabilities. Therefore, the new methodologies presented here enable to greatly enlarge and advance the development of versatile electronic skin applications.
A newly designed cloth‐based resistive electronic skin features ultrahigh current switching of ≈107 and extremely high sensitivity of 1.04 × 104–6.57 × 106 kPa–1 at pressures <3 kPa. And, notably, both features are achieved by a very low working voltage of 0.1 V. Taking these traits, our devices not only function as ultrasensitive sensors but can also be integrated with various functional components for multipurpose uses.
Atherosclerotic cardio-cerebrovascular disease and death remain the leading cause of morbidity and mortality worldwide. Defective efferocytosis, the clearance of apoptotic cells by macrophages, is ...thought to lead to increased inflammation and necrotic core formation in atherosclerotic lesions. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here we show that lncRNA myocardial infarction associated transcript (MIAT) was markedly elevated in the serum of patients with symptoms of vulnerable atherosclerotic plaque and the macrophages of necrotic cores in an advanced atherosclerosis mouse model. MIAT knockdown attenuated atherosclerosis progression, reduced necrotic core size, and increased plaque stability in vivo. Furthermore, MIAT knockdown promoted clearance of apoptotic cells by macrophages in vivo and in vitro. Mechanistic studies revealed that MIAT acted as a micro RNA (miRNA) sponge to positively modulate the expression of anti-phagocytic molecule CD47 through sponging miR-149-5p. Together, these findings identified a macrophage MIAT/miR-149-5p /CD47 pathway as a key factor in the development of necrotic atherosclerotic plaques.
Inspired by the cubic Mn4CaO5 cluster of natural oxygen‐evolving complex in Photosystem II, tetrametallic molecular water oxidation catalysts, especially M4O4 cubane‐like clusters (M=transition ...metals), have aroused great interest in developing highly active and robust catalysts for water oxidation. Among these M4O4 clusters, however, copper‐based molecular catalysts are poorly understood. Now, bio‐inspired Cu4O4 cubanes are presented as effective molecular catalysts for electrocatalytic water oxidation in aqueous solution (pH 12). The exceptional catalytic activity is manifested with a turnover frequency (TOF) of 267 s−1 for (LGly‐Cu)4 at 1.70 V and 105 s−1 for (LGlu‐Cu)4 at 1.56 V. Electrochemical and spectroscopic study revealed a successive two‐electron transfer process in the Cu4O4 cubanes to form high‐valent CuIII and CuIIIO. intermediates during the catalysis.
Cu4O4 cubanes show exceptional activity for electrocatalytic water oxidation in aqueous solution, with a turnover frequency of 267 s−1 for (LGly‐Cu)4 at 1.70 V and 105 s−1 for (LGlu‐Cu)4 at 1.56 V, respectively. The unique cuboidal structure and high catalytic performance is reminiscent of the natural Mn4CaO5 clusters in PS II.
This study aimed to determine long non‐coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) expression in pancreatic cancer and to explore the potential molecular actions of SNHG14 in ...mediating pancreatic cancer progression. Gene expression was detected by quantitative real‐time PCR. Cell proliferation, growth and invasion were detected by respective CCK‐8, colony formation, and transwell invasion assays. Protein levels were measured by Western blotting. Cell apoptosis and caspase‐3 activity were detected by flow cytometry and caspase‐3 activity assay. The link between miR‐613 and its targets was evaluated by luciferase reporter assay. In vivo tumour growth was evaluated using a xenograft model of nude mice. SNHG14 expression was up‐regulated in cancerous tissues from pancreatic cancer patients. High expression of SNHG14 was associated with poor tumour differentiation, advanced TNM stage and nodal metastasis. SNHG14 overexpression enhanced cell proliferative, growth and invasive abilities, and suppressed apoptotic rates and caspase‐3 activity in pancreatic cancer cells, while SNHG14 knockdown exerted opposite effects. Mechanistic studies revealed that miR‐613 was targeted by SNHG14, and Annexin A2 (ANXA2) was targeted and inversely regulated by miR‐613 in pancreatic cancer cells. In vivo studies showed that SNHG14 knockdown attenuated tumour growth. MiR‐613 was down‐regulated and ANXA2 was up‐regulated in the pancreatic cancer tissues, and SNHG14 expression levels were inversely correlated with miR‐613 expression levels and positively correlated with the ANXA2 mRNA expression levels. Collectively, our results suggest that SNHG14 potentiates pancreatic cancer progression through modulation of annexin A2 expression via acting as a competing endogenous RNA for miR‐613.
Although chiral semiconductors have shown promising progress in direct circularly polarized light (CPL) detection and emission, they still face potential challenges. A chirality‐switching mechanism ...or approach integrating two enantiomers is needed to discriminate the handedness of a given CPL; additionally, a large material volume is required for sufficient chiroptical interaction. These two requirements pose significant obstacles to the simplification and miniaturization of the devices. Here, room‐temperature chiral polaritons fulfilling dual‐handedness functions and exhibiting a more‐than‐two‐order enhancement of the chiroptical signal are demonstrated, by embedding a 40 nm‐thick perovskite film with a 2D chiroptical effect into a Fabry–Pérot cavity. By mixing chiral perovskites with different crystal structures, a pronounced 2D chiroptical effect is accomplished in the perovskite film, featured by an inverted chiroptical response for counter‐propagating CPL. This inversion behavior matches the photonic handedness switch during CPL circulation in the Fabry–Pérot cavity, thus harvesting giant enhancement of the chiroptical response. Furthermore, affected by the unique quarter‐wave‐plate effects, the polariton emission achieves a chiral dissymmetry of ±4% (for the emission from the front and the back sides). The room‐temperature polaritons with the strong dissymmetric chiroptical interaction shall have implications on a fundamental level and future on‐chip applications for biomolecule analysis and quantum computing.
The light–matter interaction between a 2D chiroptical film and a Fabry–Pérot cavity is investigated. The chiroptical response inversion of the 2D chiroptical film shall be ideally suited to the circularly polarized light switching feature in the Fabry–Pérot cavity, resulting in the enhancement effect in the chiroptical signal.