Ship recognition is a fundamental and essential step in maritime activities, and it can be widely used in maritime rescue, vessel management, and other applications. However, most studies conducted ...in this area use synthetic aperture radar (SAR) images and space-borne optical images, and those studies utilizing visible images are limited to the coarse-grained level. In this study, we constructed a fine-grained ship dataset with real images and simulation images that consisted of five categories of ships. To solve the problem of low accuracy in fine-grained ship classification with different angles in visible images, a network based on domain adaptation and a transformer was proposed. Concretely, style transfer was first used to reduce the gap between the simulation images and real images. Then, with the goal of utilizing the simulation images to execute classification tasks on the real images, a domain adaptation network based on local maximum mean discrepancy (LMMD) was used to align the different domain distributions. Furthermore, considering the innate attention mechanism of the transformer, a vision transformer (ViT) was chosen as the feature extraction module to extract the fine-grained features, and a fully connected layer was used as the classifier. Finally, the experimental results showed that our network had good performance on the fine-grained ship dataset with an overall accuracy rate of 96.0%, and the mean average precision (mAP) of detecting first and then classifying with our network was 87.5%, which also verified the feasibility of using images generated by computer simulation technology for auxiliary training.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Increased expression of the transcription factor Forkhead box M1 (FOXM1) has been reported to play an important role in the progression and development of multiple tumors, but the molecular ...mechanisms that regulate FOXM1 expression remain unknown, and the role of FOXM1 in aerobic glycolysis is still not clear.
The expression of FOXM1 and NADPH oxidase 4 (NOX4) in normal brain tissues and glioma was detected in data from the TCGA database and in our specimens. The effect of NOX4 on the expression of FOXM1 was determined by Western blot, qPCR, reactive oxygen species (ROS) production assays, and luciferase assays. The functions of NOX4 and FOXM1 in aerobic glycolysis in glioblastoma cells were determined by a series of experiments, such as Western blot, extracellular acidification rate (ECAR), lactate production, and intracellular ATP level assays. A xenograft mouse model was established to test our findings in vivo.
The expression of FOXM1 and NOX4 was increased in glioma specimens compared with normal brain tissues and correlated with poor clinical outcomes. Aberrant mitochondrial reactive oxygen species (ROS) generation of NOX4 induced FOXM1 expression. Mechanistic studies demonstrated that NOX4-derived MitoROS exert their regulatory role on FOXM1 by mediating hypoxia-inducible factor 1α (HIF-1α) stabilization. Further research showed that NOX4-derived MitoROS-induced HIF-1α directly activates the transcription of FOXM1 and results in increased FOXM1 expression. Overexpression of NOX4 or FOXM1 promoted aerobic glycolysis, whereas knockdown of NOX4 or FOXM1 significantly suppressed aerobic glycolysis, in glioblastoma cells. NOX4-induced aerobic glycolysis was dependent on elevated FOXM1 expression, as FOXM1 knockdown abolished NOX4-induced aerobic glycolysis in glioblastoma cells both in vitro and in vivo.
Increased expression of FOXM1 induced by NOX4-derived MitoROS plays a pivotal role in aerobic glycolysis, and our findings suggest that inhibition of NOX4-FOXM1 signaling may present a potential therapeutic target for glioblastoma treatment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine the anatomical characteristics of the petrous ridge and trigeminal nerve in trigeminal neuralgia (TN) without neurovascular compression (NVC).
From May 2017 to March 2021, 66 patients ...(49 female and 17 male; mean age ± standard deviation SD, 56.8 ± 13.3 years) with TN without NVC and 57 controls (46 female and 11 male; 52.0 ± 15.6 years) were enrolled. The angle of the petrous ridge (APR) and angle of the trigeminal nerve (ATN) were measured using magnetic resonance imaging with a high-resolution three-dimensional T2 sequence. Data on the symptomatic side were compared with those on the asymptomatic side in patients and with the mean measurements of the bilateral sides in controls. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of APR and ATN in distinguishing TN patients from controls.
In TN patients without NVC, the mean ± standard deviation (SD) of APR on the symptomatic side (98.40° ± 19.75°) was significantly smaller than that of the asymptomatic side (105.59° ± 22.45°,
= 0.019) and controls (108.44° ± 15.98°,
= 0.003). The mean ATN ± SD on the symptomatic side (144.41° ± 8.92°) was significantly smaller than that of the asymptomatic side (149.67° ± 8.09°,
= 0.003) and controls (150.45° ± 8.48°,
= 0.001). The area under the ROC curve for distinguishing TN patients from controls was 0.673 (95% confidence interval CI: 0.579-0.758) for APR and 0.700 (CI: 0.607-0.782) for ATN. The sensitivity and specificity using the diagnostic cutoff yielding the highest Youden index were 81.8% (54/66) and 49.1% (28/57), respectively, for APR (with a cutoff score of 94.30°) and 65.2% (43/66) and 66.7% (38/57), respectively, for ATN (cutoff score, 148.25°).
In patients with TN without NVC, APR and ATN were smaller than those in controls, which may explain the potential cause of TN and provide additional information for diagnosis.
Freezing construction in saline stratum under the action of groundwater is typical. To study the coupling effect of the groundwater velocity and salinity on the freezing in saline stratum, the ...freezing temperature of saline sand with different salinities was obtained through experiments. A controllable velocity double-pipe freezing physical model test system for saline sand was established. The temperature distribution in saturated saline sand under different salinities and velocities were studied. The test results showed that the temporal and spatial evolutions of the temperature field were affected by the velocity and salinity. Under the same boundary temperature, the higher the salinity, the lower the temperature at the measuring point on the main surface and interface. The overlapping time varies significantly. The analysis results showed that the larger velocity and the higher the salinity, the longer the overlapping time. The velocity and salinity inhibited the development of the frozen curtain. Under different test conditions, the development rate of the freezing curtain area was in the range of 3987–15,246 mm2/h.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Terminally differentiated cells can be generated by lineage reprogramming, which is, however, hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we ...demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated success in the treatment of hematological malignancies; however, its efficacy and applications in solid tumors remain limited. ...Immunosuppressive factors, particularly inhibitory checkpoint molecules, restrict CAR T cell activity inside solid tumors. The modulation of checkpoint pathways has emerged as a promising approach to promote anti-tumor responses in CAR T cells. Programmed cell death protein 1 (PD1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) are two critical immune-checkpoint molecules that suppress anti-tumor activity in T cells. Simultaneous targeting of these two inhibitory molecules could be an efficient checkpoint modulation strategy. Here, we developed a PD1-TIGIT chimeric immune-checkpoint switch receptor (CISR) that enhances the efficacy of CAR T cell immunotherapy by reversing the inhibitory checkpoint signals of PD1/PDL1 and/or TIGIT/CD155. In addition to neutralizing PDL1 and CD155, this chimeric receptor is engineered with the transmembrane region and intracellular domain of CD28, thereby effectively enhancing T cell survival and tumor-targeting functions. Notably, under simultaneous stimulation of PDL1 and CD155, CISR-CAR T cells demonstrate superior performance in terms of cell survival, proliferation, cytokine release, and cytotoxicity in vitro, compared with conventional CAR T cells. Experiments utilizing both cell line- and patient-derived xenotransplantation tumor models showed that CISR-CAR T cells exhibit robust infiltration and anti-tumor efficiency in vivo. Our results highlight the potential for the CISR strategy to enhance T cell anti-tumor efficacy and provide an alternative approach for T cell-based immunotherapies.
Human somatic cells can be reprogrammed to pluripotent stem cells by small molecules through an intermediate stage with a regeneration signature, but how this regeneration state is induced remains ...largely unknown. Here, through integrated single-cell analysis of transcriptome, we demonstrate that the pathway of human chemical reprogramming with regeneration state is distinct from that of transcription-factor-mediated reprogramming. Time-course construction of chromatin landscapes unveils hierarchical histone modification remodeling underlying the regeneration program, which involved sequential enhancer recommissioning and mirrored the reversal process of regeneration potential lost in organisms as they mature. In addition, LEF1 is identified as a key upstream regulator for regeneration gene program activation. Furthermore, we reveal that regeneration program activation requires sequential enhancer silencing of somatic and proinflammatory programs. Altogether, chemical reprogramming resets the epigenome through reversal of the loss of natural regeneration, representing a distinct concept for cellular reprogramming and advancing the development of regenerative therapeutic strategies.
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•Human chemical reprogramming activates regeneration gene program•Epigenome remodeling of regeneration gene program with enhancer recommissioning•Chemically resetting epigenome through reversal of the loss of natural regeneration•Regeneration program activation requires silencing somatic and inflammatory programs
By performing single-cell transcriptomic and histone modification profiling of the chemical reprogramming process, Wang et al. unveil the epigenome remodeling underlying activation of the regeneration program. They discover that sequential enhancer recommissioning and promoter activation mirrors a reversed pathway of regeneration loss in organism maturation and demonstrate the intrinsic barriers to this process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Glioma, the most common primary malignant tumor of the central nervous system, lacks effective targeted therapies. This study investigates the role of SOAT1, a key gene involved in cholesterol ...esterification, in glioma prognosis and its association with ferroptosis. Although the impact of SOAT1 on glioma prognosis has been recognized, its precise mechanism remains unclear. In this study, we demonstrate that inhibiting SOAT1 increases the sensitivity of glioma cells to ferroptosis, both in vitro and in vivo. Mechanistically, SOAT1 positively modulates the expression of SLC40A1, an iron transporter, resulting in enhanced intracellular iron outflow, reduced intracellular iron levels, and subsequent disruption of ferroptosis. Importantly, we find that SOAT1 regulates ferroptosis independently of SREBPs, which are known to be involved in ferroptosis regulation. Furthermore, we identify the involvement of the PI3K-AKT-mTOR signaling pathway in mediating the regulatory effects of SOAT1 on SLC40A1 expression and ferroptosis sensitivity. These findings highlight the contribution of intracellular signaling cascades in the modulation of ferroptosis by SOAT1. We show that inhibiting SOAT1 enhances the efficacy of radiotherapy in gliomas, both in vitro and in vivo, by promoting sensitivity to ferroptosis. This suggests that targeting SOAT1 could potentially improve therapeutic outcomes for glioma patients. In summary, this study uncovers the pivotal role of SOAT1 as a link between cholesterol esterification and ferroptosis in glioma. Our findings underscore the potential of SOAT1 as a promising clinical therapeutic target, providing new avenues for the development of effective treatments for glioma. Further research is warranted to unravel the complete regulatory mechanisms of SOAT1 and explore its clinical applications.
Groundwater velocity has significant effects on the formation of a frozen curtain during freezing. In order to study the influence of the velocity on a frozen curtain, a large physical model test ...platform was established for double-pipe freezing. Based on this platform, freezing tests for different velocities were carried out. Quartz sand was selected as a similar material. The freezing temperature of the saturated sand layer was found by analyzing the results of the nuclear magnetic resonance (NMR). Based on the study of the thermal physical properties of the sand layer, the freezing test results were analyzed, and the results showed that the flow led to the differential development of the temperature between the upstream and downstream sections of the freezing pipes. Moreover, the larger the velocity, the greater the difference. The flow prolonged the overlapping time of the frozen curtains. Additionally, the flow slowed down the development of the frozen curtain area and the frozen curtain thickness. The larger the flow velocity, the greater the inhibition of the flow on the development of the frozen curtain. The test results can provide more references for the design and construction of freezing engineering with flowing groundwater.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Ferroptosis is a form of cell death characterized by lipid peroxidation. Previous studies have reported that knockout of NF-κB activating protein (NKAP), an RNA-binding protein, increased ...lipid peroxidation level in naive T cells and induced cell death in colon cancer cells. However, there was no literature reported the relationship between NKAP and ferroptosis in glioblastoma cells. Notably, the mechanism of NKAP modulating ferroptosis is still unknown. Here, we found NKAP knockdown induced cell death in glioblastoma cells. Silencing NKAP increased the cell sensitivity to ferroptosis inducers both in vitro and in vivo. Exogenous overexpression of NKAP promoted cell resistance to ferroptosis inducers by positively regulating a ferroptosis defense protein, namely cystine/glutamate antiporter (SLC7A11). The regulation of SLC7A11 by NKAP can be weakened by the m
6
A methylation inhibitor cycloleucine and knockdown of the m
6
A writer METTL3. NKAP combined the “RGAC” motif which was exactly in line with the m
6
A motif “RGACH” (R = A/G, H = A/U/C) uncovered by the m
6
A-sequence. RNA Immunoprecipitation (RIP) and Co-Immunoprecipitation (Co-IP) proved the interaction between NKAP and m
6
A on SLC7A11 transcript. Following its binding to m
6
A, NKAP recruited the splicing factor proline and glutamine-rich (SFPQ) to recognize the splice site and then conducted transcription termination site (TTS) splicing event on SLC7A11 transcript and the retention of the last exon, screened by RNA-sequence and Mass Spectrometry (MS). In conclusion, NKAP acted as a new ferroptosis suppressor by binding to m
6
A and then promoting SLC7A11 mRNA splicing and maturation.
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