Recently, attention has been focused on the central role of TREM2 in diverse pathologies. However, the role of TREM2 signaling in the tumor microenvironment of hepatocellular carcinoma (HCC) remains ...poorly understood. Herein, we systematically investigated the single-cell transcriptomes of human HCC tissues and found that
was predominantly expressed by a macrophage subpopulation enriched in tumor tissues that resemble lipid-associated macrophages (LAMs). The accumulation of TREM2
LAM-like cells in HCC was confirmed in two additional cohorts using scRNA-seq analysis and immunohistochemistry. High expression of TREM2 correlated with high infiltrating macrophage abundance and poor prognosis. Based on systematic interrogations of transcriptional profiles and cellular interactions,
LAM-like cells were identified to mainly originate from
monocytes and represented an immunosuppressive state. TREM2
LAM-like cells recruited suppressive Treg cells, facilitating microenvironment remodeling. Furthermore, gene regulatory analysis and
functional assays indicated that activation of LXR signaling could promote the reprogramming of
LAM-like cells. Correlation analysis of bulk RNA-sequencing data demonstrated that the enrichment of
LAM-like cells was an independent indicator of adverse clinical outcomes in HCC patients. Our comprehensive analyses provide deeper insights into the immunosuppressive role of TREM2
LAM-like cells in HCC.
The α2δ subunit is a high-voltage activated (HVA) calcium channel (Cav1 and Cav2) auxiliary subunit that increases the density and function of HVA calcium channels in the plasma membrane of mammals. ...However, its function in plant parasitic nematodes remains unknown. In this study, we cloned the full-length cDNA sequence of the voltage-gated calcium channel (VGCC) α2δ subunit (named DdCavα2δ) in Ditylenchus destructor. We found that DdCavα2δ tends to be expressed in the egg stage, followed by the J3 stage. RNA-DIG in situ hybridization experiments showed that the DdCavα2δ subunit was expressed in the body wall, esophageal gland, uterus, post uterine, and spicules of D. destructor. The in vitro application of RNA interference (RNAi) affected the motility, reproduction, chemotaxis, stylet thrusting, and protein secretion of D. destructor to different degrees by targeting DdCα1D, DdCα1A, and DdCavα2δ in J3 stages, respectively. Based on the results of RNAi experiments, it was hypothesized that L-type VGCC may affect the motility, chemotaxis, and stylet thrusting of D. destructor. Non-L-type VGCC may affect the protein secretion and reproduction of D. destructor. The DdCavα2δ subunit gene also affected the motility, chemotaxis, and reproduction of D. destructor. These findings reveal the independent function of the VGCC α2δ subunit in D. destructor as well as give a theoretical foundation for future research on plant parasitic nematode VGCC.
Circular RNAs (circRNAs), which are involved in various human malignancies, have emerged as promising biomarkers. The present study aimed to investigate unique expression profiles of circRNAs in ...hepatocellular carcinoma (HCC) and identify novel biomarkers associated with HCC development and progression.
CircRNA expression profiles of HCC tissues were jointly analyzed to identify differentially expressed circRNAs. Overexpression plasmid and siRNA targeting candidate circRNAs were used in functional assays in vitro. CircRNA-miRNA interactions were predicted using miRNAs expressed in the miRNA-seq dataset GSE76903. To further screen downstream genes targeted by the miRNAs, survival analysis and qRT-PCR were conducted to evaluate their prognostic role in HCC and construct a ceRNA regulatory network.
Three significantly upregulated circRNAs, hsa_circ_0002003, hsa_circ_0002454, and hsa_circ_0001394, and one significantly downregulated circRNA, hsa_circ_0003239, were identified and validated by qRT-PCR. Our in vitro data indicated that upregulation of hsa_circ_0002003 accelerated cell growth and metastasis. Mechanistically, DTYMK, DAP3, and STMN1, which were targeted by hsa-miR-1343-3p, were significantly downregulated in HCC cells when hsa_circ_0002003 was silenced and were significantly correlated with poor prognosis in patients with HCC.
Hsa_circ_0002003 may play critical roles in HCC pathogenesis and serve as a potential prognostic biomarker for HCC. Targeting the hsa_circ_0002003/hsa-miR-1343-3p/STMN1 regulatory axis could be an effective therapeutic strategy in patients with HCC.
With the ability to activate certain signaling pathways, chemokines and their receptors may facilitate tumor progression at key steps, including proliferation, immunomodulation, and metastasis. ...Nevertheless, their prognostic value and regulatory mechanism warrant thorough studies in liver cancer. Here, by screening the expression profiles of all known chemokines in independent liver cancer cohorts, we found that CCL23 was frequently downregulated at mRNA and protein levels in liver cancer. Decreased CCL23 correlated with shortened patient survival, enrichment of signatures related to cancer stem cell property, and metastatic potential. In addition to serving as a tumor suppressor through recruiting CD8+ T cell infiltration in liver cancer, CCL23 could repress cancer cell proliferation, stemness, and mobility. Mechanistically, the expression of CCL23 was transcriptionally regulated by ESR1. On the other hand, CCL23 could suppress the activation of AKT signaling and thus promote the expression of ESR1, forming a feedback loop in liver cancer cells. Collectively, these findings reveal that loss of CCL23 drives liver cancer progression by coordinating immune evasion and metastasis initiation. Targeting the ESR1/CCL23/CCR1/AKT regulatory axis could be an effective therapeutic strategy.
Downregulated expression of CCL23 is associated with poor prognosis in liver cancer. Loss of CCL23 drives liver cancer progression by coordinating immune evasion and metastasis initiation. Mechanistic study reveals an ESR1/CCL23/CCR1/AKT feedback loop.
Model evaluation of water retention (WR) services has been commonly applied for national or global scientific assessment and decision making. However, evaluation results from different models are ...significantly uncertain, especially on a small regional scale. We compared the spatial–temporal variations and driving factors of the WR service by five models (i.e., the InVEST model (InVEST), precipitation storage model (PRS), water balance model I (WAB I), water balance model II (WAB II), and NPP-based surrogate model (NBS) based on partial correlation analysis and spatial statistics on the Ramsar international alpine wetland region of the Qinghai–Tibetan Plateau (QTP). The results showed that the wetland area continued to decrease, and built-up land increased from 2000 to 2015. The average WR volume ranged from 2.50 to 13.65 billion m3·yr−1, with the order from high to low being the PRS, WAB I, WAB II, and InVEST models, and the average total WR capacity was 2.21 × 109 by the NBS model. The WR service followed an increasing trend from north to south by the InVEST, PRS, WAB I, and WAB II models, while the NBS model presented a river network pattern of high values. The WR values were mainly reduced from 2000 to 2010 and increased from 2010 to 2015 in the PRS, WAB I, WAB II, and InVEST models, but the NBS model showed the opposite trend. Precipitation determined the spatial distribution of WR service in the InVEST, PRS, WAB I, and WAB II models. Still, the spatial variation was affected by climate factors, while the NPP data influenced the NBS model. In addition, the InVEST model in estimating WR values in wetlands and the PRS and WAB I models poorly estimate runoff, while the WAB II model might be the most accurate. These findings help clarify the applicability of the WR models in an alpine wetland region and provide a valuable background for improving the effectiveness of model evaluation.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Lysosomes are organelles that play an important role in cancer progression by breaking down biomolecules. ...However, the molecular mechanisms of lysosome-related genes in HCC are not fully understood.
We downloaded HCC datasets from TCGA and GEO as well as lysosome-related gene sets from AIMGO. After univariate Cox screening of the set of lysosome-associated genes differentially expressed in HCC and normal tissues, risk models were built by machine learning. Model effects were assessed using the concordance index (C-index), Kaplan-Meier (K-M) and receiver operating characteristic curves (ROC). Additionally, we explored the biological function and immune microenvironment between the high- and low-risk groups, and analyzed the response of the high- and low-risk groups to immunotherapy responsiveness and chemotherapeutic agents. Finally, we explored the function of a key gene (RAMP3) at the cellular level.
Univariate Cox yielded 46 differentially and prognostically significant lysosome-related genes, and risk models were constructed using eight genes (RAMP3, GPLD1, FABP5, CD68, CSPG4, SORT1, CSPG5, CSF3R) derived from machine learning. The risk model was a better predictor of clinical outcomes, with the higher risk group having worse clinical outcomes. There were significant differences in biological function, immune microenvironment, and responsiveness to immunotherapy and drug sensitivity between the high and low-risk groups. Finally, we found that RAMP3 inhibited the proliferation, migration, and invasion of HCC cells and correlated with the sensitivity of HCC cells to Idarubicin.
Lysosome-associated gene risk models built by machine learning can effectively predict patient prognosis and offer new prospects for chemotherapy and immunotherapy in HCC. In addition, cellular-level experiments suggest that RAMP3 may be a new target for the treatment of HCC.
The voltage-gated calcium channel (VGCC) β subunit (Cavβ) protein is a kind of cytosolic auxiliary subunit that plays an important role in regulating the surface expression and gating characteristics ...of high-voltage-activated (HVA) calcium channels. Ditylenchus destructor is an important plant-parasitic nematode. In the present study, the putative Cavβ subunit gene of D. destructor, namely, DdCavβ, was subjected to molecular characterization. In situ hybridization assays showed that DdCavβ was expressed in all nematode tissues. Transcriptional analyses showed that DdCavβ was expressed during each developmental stage of D. destructor, and the highest expression level was recorded in the third-stage juveniles. The crucial role of DdCavβ was verified by dsRNA soaking-mediated RNA interference (RNAi). Silencing of DdCavβ or HVA Cavα1 alone and co-silencing of the DdCavβ and HVA Cavα1 genes resulted in defective locomotion, stylet thrusting, chemotaxis, protein secretion and reproduction in D. destructor. Co-silencing of the HVA Cavα1 and Cavβ subunits showed stronger interference effects than single-gene silencing. This study provides insights for further study of VGCCs in plant-parasitic nematodes.
Diffuse midline glioma with the H3.3 histone A (H3F3A) or H3 clustered histone 2/3 (HIST1H3B/C) K27M mutation occurs primarily in children and less frequently in adults involving the midline ...structures of the central nervous system. This case report describes an adult patient with a diffuse midline glioma H3 K27M mutant in the prepontine cistern, which is an unusual site in clinical practice. The clinical, radiographic and histopathological data from the case are presented. Magnetic resonance imaging showed a progressively enlarged and enhanced nodule in the right prepontine cistern, with diffuse involvement of the meninges and communicating hydrocephalus. Analysis of the cerebrospinal fluid occasionally found suspiciously atypical cells with hyperchromatic nuclei and multiple nucleoli, as well as a severely elevated opening pressure and protein level, slightly elevated white cell count and decreased chloride level. Empirical antituberculosis treatment was administered but eventually proved to be ineffective. The definite diagnosis was made by histopathological analysis of the lesion based on the features of positive H3 K27M mutant protein and diffusely infiltrating growth. A diffuse midline glioma with the H3 K27M mutation may rarely present in an unusual site. A biopsy is recommended at an early stage for suspected cases to facilitate a definite diagnosis.
Antimony selenosulfide (Sb2(S,Se)3), a simple alloyed compound containing earth‐abundant constituents, with a tunable bandgap and high absorption coefficient has attracted significant attention in ...high‐efficiency photovoltaic applications. Optimizing interfacial defects and absorber layers to a high standard is essential in improving the efficiency of Sb2(S,Se)3 solar cells. In particular, the electron transport layer (ETL) greatly affects the final device performance of the superstrate structure. In this study, a simple and effective hydrazine hydrate (N2H4) solution post‐treatment is proposed to modify CdS ETL in order to enhance Sb2(S,Se)3 solar cell efficiency. By this process, oxides and residual chlorides, caused by CdCl2 treated CdS under a high temperature over 400 °C in air, are appropriately removed, rendering smoother and flatter CdS ETL as well as high‐quality Sb2(S,Se)3 thin films. Furthermore, the interfacial energy band alignment and recombination loss are both improved, resulting in an as‐fabricated FTO/CdS‐N2H4/Sb2(S,Se)3/spiro‐OMeTAD/Au solar cell with a high PCE of 10.30%, placing it in the top tier of Sb‐based solar devices. This study provides a fresh perspective on interfacial optimization and promotes the future development of antimony chalcogenide‐based planar solar cells.
In this paper, a new method termed hydrazine hydrate (N2H4) assisted solution treatment (HHST) is first introduced to improve CdS electron transport layers (ETLs) quality, which enables over 10.30% planar Sb2(S,Se)3 solar cells, achieves a smoother CdS and Sb2(S,Se)3 surface, tailors the elemental composition, optimizes the defect properties and improves interfacial quality.
Background
Spinal cord stimulation (SCS) can improve the level of awareness of prolonged disorder of consciousness (pDOC), but its application is restricted due to damage of invasive operation. ...Short-term spinal cord stimulation (st-SCS) in a minimally invasive manner will better balance the benefits and risks.
Objectives
This study focuses on the safety and efficacy of st-SCS for pDOC and reveals the modulation characteristics of different frequencies of SCS.
Methods
31 patients received 2-week st-SCS treatment and 3-months follow-up. All patients were divided into two types of frequency treatment groups of 5 Hz and 70 Hz according to the postoperative electroencephalography (EEG) test. The efficacy was assessed based on the revised coma recovery scale (CRS-R).
Results
The results showed a significant increase in CRS-R scores after treatment (Z = −3.668,
p
< 0.001) without significant adverse effects. Univariate analysis showed that the minimally conscious state minus (MCS–) benefits most from treatment. Furthermore, two frequency have a difference in the time-point of the CRS-R score increase. 5 Hz mainly showed a significant increase in CRS-R score at 2 weeks of treatment (
p
= 0.027), and 70 Hz additionally showed a delayed effect of a continued significant increase at 1 week after treatment (
p
= 0.004).
Conclusion
st-SCS was safe and effective in improving patients with pDOC levels of consciousness, and was most effective for MCS–. Both 5 Hz and 70 Hz st-SCS can promote consciousness recovery, with 70 Hz showing a delayed effect in particular.
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