Chemokines play a key role in orchestrating the recruitment and positioning of myeloid cells within the tumor microenvironment. However, the tropism regulation and functions of these cells in ...hepatocellular carcinoma (HCC) are not completely understood. Herein, by scrutinizing the expression of all chemokines in HCC cell lines and tissues, we found that CCL15 was the most abundantly expressed chemokine in human HCC. Further analyses showed that CCL15 expression was regulated by genetic, epigenetic, and microenvironmental factors, and negatively correlated with patient clinical outcome. In addition to promoting tumor invasion in an autocrine manner, CCL15 specifically recruited CCR1+ cells toward HCC invasive margin, approximately 80% of which were CD14+ monocytes. Clinically, a high density of marginal CCR1+CD14+ monocytes positively correlated with CCL15 expression and was an independent index for dismal survival. Functionally, these tumor‐educated monocytes directly accelerated tumor invasion and metastasis through bursting various pro‐tumor factors and activating signal transducer and activator of transcription 1/3, extracellular signal‐regulated kinase 1/2, and v‐akt murine thymoma viral oncogene homolog signaling in HCC cells. Meanwhile, tumor‐derived CCR1+CD14+ monocytes expressed significantly higher levels of programmed cell death‐ligand 1, B7‐H3, and T‐cell immunoglobulin domain and mucin domain‐3 that may lead to immune suppression. Transcriptome sequencing confirmed that tumor‐infiltrating CCR1+CD14+ monocytes were reprogrammed to upregulate immune checkpoints, immune tolerogenic metabolic enzymes (indoleamine and arginase), inflammatory/pro‐angiogenic cytokines, matrix remodeling proteases, and inflammatory chemokines. Orthotopic animal models confirmed that CCL15‐CCR1 axis forested an inflammatory microenvironment enriched with CCR1+ monocytes and led to increased metastatic potential of HCC cells. Conclusion: A complex tumor‐promoting inflammatory microenvironment was shaped by CCL15‐CCR1 axis in human HCC. Blockade of CCL15‐CCR1 axis in HCC could be an effective anticancer therapy.
Global soil carbon (C) stocks are expected to decline with warming, and changes in microbial processes are key to this projection. However, warming responses of critical microbial parameters such as ...carbon use efficiency (CUE) and biomass turnover (rB) are not well understood. Here, we determine these parameters using a probabilistic inversion approach that integrates a microbial‐enzyme model with 22 years of carbon cycling measurements at Harvard Forest. We find that increasing temperature reduces CUE but increases rB, and that two decades of soil warming increases the temperature sensitivities of CUE and rB. These temperature sensitivities, which are derived from decades‐long field observations, contrast with values obtained from short‐term laboratory experiments. We also show that long‐term soil C flux and pool changes in response to warming are more dependent on the temperature sensitivity of CUE than that of rB. Using the inversion‐derived parameters, we project that chronic soil warming at Harvard Forest over six decades will result in soil C gain of <1.0% on average (1st and 3rd quartiles: 3.0% loss and 10.5% gain) in the surface mineral horizon. Our results demonstrate that estimates of temperature sensitivity of microbial CUE and rB can be obtained and evaluated rigorously by integrating multidecadal datasets. This approach can potentially be applied in broader spatiotemporal scales to improve long‐term projections of soil C feedbacks to climate warming.
Model performance is substantially improved by integrating 22 years of data using a probabilistic inversion method. Warming reduces microbial carbon use efficiency (CUE) but increases microbial biomass turnover rate (rB). Two decades of soil warming increases the temperature sensitivities of CUE and rB suggesting no thermal adaptation of the microbial decomposer community.
Circular RNA in renal diseases Jin, Juan; Sun, Haolu; Shi, Chao ...
Journal of Cellular and Molecular Medicine,
June 2020, Volume:
24, Issue:
12
Journal Article
Peer reviewed
Open access
Circular RNA (circRNA) is a newly described type of non‐coding RNA. Active research is greatly enriching the current understanding of the expression and role of circRNA, and a large amount of ...evidence has implicated circRNA in the pathogenesis of certain renal diseases, such as renal cell carcinoma, acute kidney injury, diabetic nephropathy and lupus nephritis. Studies have found evidence that circRNAs regulate programmed cell death, invasion, and metastasis and serve as biomarkers in renal diseases. Recently, circRNAs were identified in exosomes secreted by the kidneys. Nevertheless, the function of circRNA in renal diseases remains ambiguous. Given that circRNAs are regulators of gene expression, they may be involved in the pathology of multiple renal diseases. Additionally, emerging evidence is showing that circulating circRNAs may serve as novel biomarkers for renal disease. In this review, we have summarized the identification, biogenesis, degradation, and functions of circRNA and have evaluated the roles of circRNA in renal diseases.
Optical imaging, especially fluorescence and photoacoustic imaging, is a non‐invasive imaging approach with high spatial and temporal resolution and high sensitivity, compared to positron emission ...tomography (PET) or magnetic resonance imaging (MRI). Due to the merits of imaging using the second near‐infrared (NIR‐II) window, like deeper penetration depth, high signal‐to‐noise ratio, high resolution, and low tissue damage, researchers have devoted great effort to developing contrast agents with NIR‐II absorption or emission. In this Review, we summarize recently developed organic luminescent and photoacoustic materials, ranging from small molecules to conjugated polymers. Then, we systematically introduce engineering strategies and describe the imaging performance classified by the skeleton cores. Finally, we elucidate the challenges and prospects of these NIR‐II organic dyes for potential clinical applications. We expect our summary can inspire researchers to expand the spectrum of NIR‐II contrast agents for diverse bioapplications.
Organic fluorophores in the second near‐infrared (NIR‐II) range have been validated as attractive imaging tools in biomedical research owing to their biocompatibility, flexible chemical structure, and tunable spectra. This Review systematically summarizes recent advances in the chemistry, design principles, and optical properties of NIR‐II organic contrast agents.
This study aimed to investigate the effects of the original thickness on the densification, microstructure, and nanoindentation hardness of silicon carbide (SiC) ceramics prepared by the spark plasma ...sintering (SPS) process. The densification of SiC ceramics with different initial thicknesses ranging from 50 to 2000 µm was investigated in combination with varying SPS sintering temperature at 1700–1900°C. The results indicated that the densification of SiC sample with the initial thickness of 50 µm was complete after sintering at 1700°C. On the contrary, when the initial thickness exceeded 50 µm, it resulted in a porous microstructure. When the initial thickness varied from 50 to 100 µm, dense SiC monolithic could be obtained after sintering at 1800°C. All the samples were fully densified after sintering at 1900°C. The predominant factors for the thickness effect were mainly derived from the unique characteristics of SPS. The hardness of SiC ceramics was measured using nanoindentation, and it was found to have a strong correlation with the initial thickness, mainly attributed to the densification status. The dense SiC product demonstrated nanoindentation hardness with high values of ∼28.0 GPa.
Nonlinear optical switches that reversibly convert between on/off states by thermal stimuli are promising for applications in the fields of photoelectronics and photonics. Currently one main drawback ...for practical application lies in the control of their switch temperature, especially for the temperature range near room temperature. By mixed melting treatment, here we describe an alloy-like nonlinear optical switch with tunable switch temperature via a dual solid solution approach within the coordination polymer system. We initially prepare a coordination polymer (i-PrNHMe
)Cd(SCN)
, which functions as a high-contrast thermoresponsive nonlinear optical switch originating from a phase transition at around 328 K. Furthermore, by taking advantage of a synergistic dual solid solution effect, the melt mixing of it with its analogue (MeNHEt
)Cd(SCN)
, which features an unequal anionic chain templated by an isomeric ammonium, can afford coordination polymer solid solutions with switch temperatures that are tunable in a range of 273-328 K merely by varying the component ratio.
Innate immunity is an indispensable arm of tumor immune surveillance, and the liver is an organ with a predominance of innate immunity, where mucosal-associated invariant T (MAIT) cells are enriched. ...However, little is known about the phenotype, functions, and immunomodulatory role of MAIT cells in hepatocellular carcinoma (HCC).
The distribution, phenotype, and function of MAIT cells in patients with HCC were evaluated by both flow cytometry (FCM) and
bioassays. Transcriptomic analysis of MAIT cells was also performed. Prognostic significance of tumor-infiltrating MAIT cells was validated in four independent cohorts of patients with HCC.
Despite their fewer densities in HCC tumor than normal liver, MAIT cells were significantly enriched in the HCC microenvironment compared with other mucosa-associated organs. Tumor-derived MAIT cells displayed a typical CCR7
CD45RA
CD45RO
CD95
effector memory phenotype with lower costimulatory and effector capabilities. Tumor-educated MAIT cells significantly upregulated inhibitory molecules like PD-1, CTLA-4, TIM-3, secreted significantly less IFNγ and IL17, and produced minimal granzyme B and perforin while shifting to produce tumor-promoting cytokines like IL8. Transcriptome sequencing confirmed that tumor-derived MAIT cells were reprogrammed toward a tumor-promoting direction by downregulating genes enriched in pathways of cytokine secretion and cytolysis effector function like
and
and by upregulating genes like
, and
(
). High infiltration of MAIT cells in HCC significantly correlated with an unfavorable clinical outcome, revealed by FCM, qRT-PCR, and multiplex IHC analyses, respectively.
HCC-infiltrating MAIT cells were functionally impaired and even reprogrammed to shift away from antitumor immunity and toward a tumor-promoting direction.
.
Abstract
Synergistic photoredox and copper catalysis confers new synthetic possibilities in the pharmaceutical field, but is seriously affected by the consumptive fluorescence quenching of Cu(II). By ...decorating bulky auxiliaries into a photoreductive triphenylamine-based ligand to twist the conjugation between the triphenylamine-based ligand and the polar Cu(II)–carboxylate node in the coordination polymer, we report a heterogeneous approach to directly confront this inherent problem. The twisted and polar Cu(II)–dye conjunction endows the coordination polymer with diode-like photoelectronic behaviours, which hampers the inter- and intramolecular photoinduced electron transfer from the triphenylamine
-
moiety to the Cu(II) site and permits reversed-directional ground-state electronic conductivity, rectifying the productive loop circuit for synergising photoredox and copper catalysis in pharmaceutically valuable decarboxylative C(sp
3
)–heteroatom couplings. The well-retained Cu(II) sites during photoirradiation exhibit unique inner-spheric modulation effects, which endow the couplings with adaptability to different types of nucleophiles and radical precursors under concise reaction conditions, and distinguish the multi-olefinic moieties of biointeresting steride derivatives in their late-stage trifluoromethylation-chloration difunctionalisation.
Permafrost degradation may induce soil carbon (C) loss, critical for global C cycling, and be mediated by microbes. Despite larger C stored within the active layer of permafrost regions, which are ...more affected by warming, and the critical roles of Qinghai-Tibet Plateau in C cycling, most previous studies focused on the permafrost layer and in high-latitude areas. We demonstrate in situ that permafrost degradation alters the diversity and potentially decreases the stability of active layer microbial communities. These changes are associated with soil C loss and potentially a positive C feedback. This study provides insights into microbial-mediated mechanisms responsible for C loss within the active layer in degraded permafrost, aiding in the modeling of C emission under future scenarios.
Dielectric switches that can be converted between high and low dielectric states by thermal stimuli have attracted much interest owing to their many potential applications. Currently one main ...drawback for practical application lies in the non‐tunability of their switch temperatures (TS). We report here an ionic co‐crystal (Me3NH)4Ni(NCS)6 that contains a multiply rotatable Me3NH+ ion and a solely rotatable one due to a more spacious supramolecular cage for the former one. This compound undergoes an isostructural order–disorder phase transition and it can function as a frequency‐tuned dielectric switch with highly adjustable TS, which is further revealed by the variable‐temperature structure analyses and molecular dynamics simulations. In addition, the distinct arrangements and molecular dynamics of two coexisting Me3NH+ ions confined in different lattice spaces as well as the notable offset effect on the promoting/hindering of dipolar reorientation after dielectric transition provide a rarely observed but fairly good model for understanding and modulating the dipole motion in crystalline environment.
Dipole motion in a crystal: The ionic co‐crystal (Me3NH)4Ni(NCS)6 undergoes an order–disorder phase transition and functions as a frequency‐tuned dielectric switch with a highly adjustable switching temperature. The distinct arrangements and molecular dynamics of two coexisting Me3NH+ ions provide a model for understanding/modulating the dipole motion in a crystalline environment.
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