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Phytohormones, epigenetic regulation and environmental factors regulate fruit ripening but their interplay during strawberry fruit ripening remains to be determined. In this study, bagged strawberry fruit exhibited delayed ripening compared with fruit grown in normal light, correlating with reduced abscisic acid (ABA) accumulation. Transcription of the key ABA catabolism gene, ABA 8′‐hydroxylase FaCYP707A4, was induced in bagged fruit. With light exclusion whole genome DNA methylation levels were up‐regulated, corresponding to a delayed ripening process, while DNA methylation levels in the promoter of FaCYP707A4 were suppressed, correlating with increases in transcript and decreased ABA content. Experiments indicated FaCRY1, a blue light receptor repressed in bagged fruit and FaAGO4, a key protein involved in RNA‐directed DNA methylation, could bind to the promoter of FaCYP707A4. The interaction between FaCRY1 and FaAGO4, and an increased enrichment of FaAGO4 directed to the FaCYP707A4 promoter in fruit grown under light suggests FaCRY1 may influence FaAGO4 to modulate the DNA methylation status of the FaCYP707A4 promoter. Furthermore, transient overexpression of FaCRY1, or an increase in FaCRY1 transcription by blue light treatment, increases the methylation level of the FaCYP707A4 promoter, while transient RNA interference of FaCRY1 displayed opposite phenotypes. These findings reveal a mechanism by which DNA methylation influences ABA catabolism, and participates in light‐mediated strawberry ripening. [ABSTRACT FROM AUTHOR]

The faculty is the backbone and core of the school, and it is also a “power army” for the sustainable development of the university. The quality of the faculty is directly related to the comprehensive quality of a school. In the new era, the overall plan of deepening teaching evaluation reform should be implemented comprehensively, so it is necessary to grasp the development pulse of faculty construction and actively explore the new faculty, so as to lay the foundation for the national training of high-quality faculty.

Ecotourism is the main trend of global tourism development, and evaluating the ecotourism environmental carrying capacity (EECC) of ecologically fragile areas can provide a scientific basis for the sustainable development of regional tourism. This study uses the typical fragile mountain area, the Qilian Mountains (QLMs), as an example and analyzes the spatial and temporal changes in EECC by constructing an evaluation indicator system of EECC, which is based on the framework of "natural ecological environment support—socio-economic pressure—tourism activity pressure". In the results, it is found that the natural ecological environment support, socio-economic pressure, and tourism activity pressure in the QLMs all present a spatial distribution pattern of higher in the southeast and lower in the northwest. From a temporal perspective, most of the indicators of different subsystems show an increasing trend. The whole area of EECC in the QLMs shows an increasing trend in 85.4% of the region, while the EECC in some areas in the southeastern and northern parts shows a decreasing trend. Comparing different time periods, it is found that the EECC in the whole region shows an increasing trend from 2000 to 2010, while the proportion of areas with a decreasing trend in EECC from 2010 to 2018 reaches 67.1%. The research results can provide a scientific basis for the sustainable development of ecotourism in the QLMs and other similar regions in the world, and they further contribute to the protection of the ecological environment. [ABSTRACT FROM AUTHOR]

Investigating the differences in grassland growth and its response to advancing spring phenology and climate change across various spatiotemporal scales is crucial for the sustainable development of alpine mountain regions under a warming and wetting climate. This study analyzed the growth dynamics of grassland in the Qilian Mountains from 2000 to 2019 at seasonal and periodic scales. Using partial wavelet coherency and partial correlation analysis, we investigated the influence of temperature, precipitation, and spring phenology on grassland growth. Additionally, we quantified the dominant factors affecting grassland growth in different ecological zones and elevational gradient. The results indicated that the mean normalized difference vegetation index increased at an average rate of 1.1 and 2.8 × 10−3/year for grassland in spring and summer, respectively. Furthermore, the start of vegetation growing season (SOS) has advanced 6.0 days during 2000–2019. The dominant factor for grassland growth shifted from spring temperature to summer precipitation. The importance of SOS ranked second, significantly influencing 29.3% and 25.1% of grassland during spring and summer, respectively. Grasslands situated above 4,000 m above sea level (ASL) were more sensitive to climate change, with SOS exerting the greatest influence within the elevation range of 2,800–4,000 m ASL. Additionally, the phase difference in the time‐frequency scale of partial wavelet coherency revealed a lag effect of approximately 1 month for summer grassland growth to respond to precipitation. These findings can provide a scientific basis for optimizing global vegetation models and predicting the productivity of alpine mountain grasslands. Plain Language Summary: The Qilian Mountains are considered one of the most sensitive areas to climate warming. This study quantitatively compared the relative importance of spring phenology, temperature, and precipitation on the growth of grasslands in spring and summer from multiple temporal and spatial perspectives. The findings revealed a notable trend of warming and wetting since 2000, resulting in a significant increase in vegetation cover and an advancement in spring phenology. The response of vegetation to driving factors showed seasonal differences, multitemporal scale characteristics, and legacy effects. Notably, this study confirmed the significant role of spring phenology in grassland growth, with its contribution ranking just below that of temperature in spring and precipitation in summer. The dominant factors influencing grassland growth exhibited spatial heterogeneity and elevational gradient effects. In areas below 4,000 m above sea level, spring phenology, along with temperature and precipitation, collectively dominated grassland growth. Key Points: The response of vegetation to driving factors showed seasonal variations, multitemporal characteristics, and time‐lag effectsThe primary driving factors for grassland growth shifted from temperature in spring to precipitation in summerThe significance of spring phenology ranked second only to the primary climatic drivers [ABSTRACT FROM AUTHOR]

The development of a reasonable landscape ecological risk (LER) assessment system is the key means to establish an eco‐safety early warning mechanism, promote ecological protection, and achieve sustainable management of regional ecosystems. Based on the Cellular Automaton‐Markov (CA‐Markov) model, we predicted the land use/cover changes (LUCC) in 2026 and 2034 in the typical arid and semiarid mountainous area of the Qilian Mountains. We constructed an LER model to analyze the spatial–temporal changes in LER, quantified the driving mechanism, and synthesized the constraining effect of terrain features. The results showed that the study area was dominated by ecologically stable areas in 1980–2000 and 2010–2018. Ecologically improved and deteriorated areas in the central and northwest expanded in 2000–2010 and 2018–2036, which was attributed to ecological restoration policies (returning farmland to forest and grassland, closing mountains to forest and grassland, etc.) and economic development (livestock and mineral development, etc.). Due to the frequent interference of human activities in flat and complex terrain areas, the degree of landscape fragmentation, separation, and vulnerability is enhanced, and the ecological conditions of bare land and snow cover are relatively fragile, resulting in high ecological risk. Therefore, we could focus on zoning management and rational land use planning. This study provides a new framework for controlling LER in the Qilian Mountains, and will provide a scientific reference for the formulation of risk mitigation strategies in other arid and semiarid mountains worldwide. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that the T-cell receptor (TCR) repertoire is associated with prognosis and immune therapy response in several types of cancer. However, the comprehensive features of TCR repertoire in tumor-infiltrating and circulating T cells, as well as its clinical significance of diagnosis in hepatocellular carcinoma (HCC) patients, are still unknown. In this study, we perform paired tumor/peritumoral tissues and peripheral blood samples from 58 patients with HCC and sequenced them with high-throughput TCR to comprehensively analyze the characteristics of TCR and the clinical significance of peripheral TCR sequence. By exploring the abundance and diversity of TCR repertoires, we observe that there was a significantly higher TCR diversity in peripheral blood than in tumoral and peritumoral tissues, while tumoral and peritumoral tissues showed similar TCR diversity. A substantial difference in the usage frequencies of several Vβ, Jβ genes, and TCRβ VJ pairings was found among three types of tissues. Moreover, we reveal that HCC patients have a unique profile of TCR repertoire in peripheral blood in contrast to healthy individuals. We further establish an HCC diagnostic model based on TCRβ VJ pairing usage in peripheral blood, which yields a best-fit area under the curve (AUC) of 0.9746 ± 0.0481 (sensitivity = 0.9675 ± 0.0603, specificity = 0.9998 ± 0.0007, average of 100 repeats) in the test set. Our study describes the characteristics of tissue infiltration and circulating T-cell bank in patients with HCC and shows the potential of using circulating TCR sequence as a biomarker for the non-invasive diagnosis of patients with HCC. [ABSTRACT FROM AUTHOR]

Source identification and risk assessment of heavy metals are ongoing hot topics in current research, but few studies have been performed on the linkage mechanism between them. In the past, the amount of heavy metals discharged was the identification criterion for high‐risk source but failed to consider different toxicity of heavy metals in the risk level of each pollution source. Therefore, it is impossible to accurately determine high‐risk pollution source. For this situation, this study introduced a risk assessment model based on the source apportionment model, which can quantitatively analyze the source‐based risk. Meanwhile, pollution assessment indexes and a risk assessment model were applied to evaluate the levels of pollution and risk of heavy metals, showing that lead (Pb) caused relatively serious pollution and arsenic (As) generated the highest ecological risk and noncarcinogenic risk. Positive matrix factorization (PMF) model identified and quantified the sources of heavy metals (coal‐related activities source, mixed source of mining and traffic emissions, industrial activity source, agricultural source related to the application of agrochemicals) with the corresponding contributions of 42, 30, 26, and 2%, respectively. Then PMF was combined with potential ecological risk index and human health risk assessment model to quantify the risk from pollution sources, indicating that the coal‐related activities source was the largest pollution source (31–36%) that caused human health risks, while the mixed source of mining and transportation emissions posed the greatest threat (29%) to the ecosystem health. Therefore, both sources should be identified as the priority pollution sources. Core Ideas: The emission of Pb and As should be the focus of heavy metal pollution control.The larger risk levels mainly occurred in the soil near the motorway.Four pollution sources were identified and apportioned.A reasonable and reliable source risk analysis tool was provided for environmental managers.The priority pollution sources were determined by the positive matrix factorization–risk index and positive matrix factorization–health risk assessment models. [ABSTRACT FROM AUTHOR]

• Four methods were combined to extract phenological metrics. • GeoDetector was used to quantify the contribution of climatic factors and interaction of two factors. • The phenological sensitivity of grassland was highest. • The interaction between climatic factors played a critical role. Mountain ecosystems are highly susceptible to climate change. The climate tends to be warm and wet in the arid mountains of China because of the intensified water cycle under global warming, and the vegetation is undergoing profound changes. However, how vegetation phenology responds to climate change is not been entirely understood. Using MODIS-NDVI during 2000–2019, we analyzed the spatiotemporal variations in the SOS, EOS, and LOS in the Qilian Mountains (QLMs), China. These parameters were extracted using four methods, and geographic detector model was used to quantify the explanatory power of climatic factors on phenological change. The results showed that the SOS was advanced by an average of 0.26 d/yr, the EOS was delayed by an average of 0.12 d/yr, and the LOS was prolonged by an average of 0.38 d/yr during 2000–2019. The phenological characteristics of different vegetation types differed in their sensitivities to climatic factors, and the sensitivity of grassland to climatic factors was higher than those of other vegetation types. The preseason temperature and sunshine duration contributed more to SOS and EOS changes of forests than that of other vegetation types. Moreover, the SOS was more sensitive to preseason precipitation, and it was the main SOS determinant across grassland and meadows. The EOS was more sensitive to the daily minimum temperature. More importantly, climatic factors did not act independently on vegetation phenological changes. The interactions between preseason precipitation and temperature and between preseason sunshine duration and temperature had significantly affected the changes in the SOS and EOS, respectively. The results of this study highlight the response of different vegetation types to climate change in the arid mountainous areas, which is significant for improving the performance of phenology models. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8+ T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8+ T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8+ T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse. • ScRNA-seq reveals a distinct immune ecosystem in early-relapse HCC • Decreased Tregs, increased DCs, and CD8+ T cells were observed in early-relapse HCC • CD8+ T cells have an innate-like, low cytotoxic, and low clonal expansion phenotype • Recurrent malignant cells mediate the compromised antitumor immune response Single-cell analysis of primary and relapsed hepatocellular carcinoma tumors from patients reveal innate-like CD8+ T cells with low cytotoxicity and clonal expansion in the latter that may explain the compromised antitumor immunity and poor prognosis associated with liver cancer. [ABSTRACT FROM AUTHOR]

• The increase trend of NDVI in the northwest is greater than that in the southeast. • NDVI fluctuated greatly and the growth rate was greater at low-altitude. • Vegetation in the QLMs is mainly affected by the time-accumulation of PRE and the time-lag of TMP. • Compared with PRE, TMP was the dominant factor of the greening in the QLMs. Understanding the trend of vegetation change and its reaction to climate variation is important for revealing the mechanism of ecosystem behavior. However, current research rarely systematically analyzes the time effects of climate variation on vegetation dynamics (time-lag and time-accumulation effects), especially in arid and semi-arid mountainous terrain. The typical mountainous terrain—the Qilian Mountains was taken as the study area, and the spatiotemporal changes and vertical zonality distributions of the normalized vegetation index (NDVI) were explored. This study explored the time-lag and time-accumulation effects of the NDVI response to climate factors (precipitation, temperature), identified the main controlling factors that influence the variation of NDVI. The results show that in the growing season from 2000 to 2019, the NDVI represented an overall upward trend, especially in the northwest, and the growth rate of NDVI at low-altitude was greater. The time-accumulation effect of precipitation has an obvious effect on vegetation, especially on deserta and meadow; and the time-lag and time-accumulation effects of temperature have an obvious influence. Regarding the climate-vegetation response mechanism, this study finds that considering the optimal time effect is of great significance. In addition, compared with precipitation, the temperature has a more significant promotion effect on vegetation growth in the Qilian Mountains. The above results indicate that when the existing climate models study vegetation-climate interactions, considering the time effects of vegetation response to climate is of great significance for accurately monitoring vegetation dynamics under environmental changes. [ABSTRACT FROM AUTHOR]

• Established an ecological security evaluation framework based onLULC data. • The ecological security index increased from 2000 to 2010, and decreased afer 2010. • Using the results of ecological security assessment to extract ecological sources in Hexi Region. • The protection of ecosystems in areas with intensive human activities should be strengthened. Ecological security assessments are used to reflect the regional ecological security situation because they can provide a basis for the construction of regional ecological security patterns (ESPs). Using the land use/land cover (LULC) data, the ecological security status of the Hexi Region was analyzed. On this basis, the ecological source was extracted, the ecological resistance surface was established, and the ecological corridor and node were identified, and constructed the ESP of the Hexi Region. The results show that: 1) During 2000–2015, approximately 70% of the study area's ecological security index values were <0.1. The ecosystem security levels were higher in the southeast and lower in the northwest. 2) The total area of ecological sources was 6828.75 km2, and it is less distributed in the west; the interconnection degree among the sources was low; and patch fragmentation was obvious. 3) A total of 134 ecological corridors were extracted, with a total length of 15572.8 km2, and 44 ecological nodes were identified. The distributions of the ecological corridors and nodes had spatial consistency and were mainly concentrated in the central and southern parts of the Qilian Mountains. The method of ecological security assessment based on LULC data can be popularized and applied to the evaluation of the ecological security in regions having a lack of research data or difficulty in obtaining data. This study can provide guiding significance for the optimization of ecosystem elements and the improvement of regional ESPs in the study area or other arid areas. [ABSTRACT FROM AUTHOR]

The determination of spatiotemporal variation in ecosystem service value and its drivers is fundamental to ecosystem service management and decision-making. This paper selects a typical oasis irrigation district in the arid regions of northwest China as the research object. Using the benefit transfer method to evaluate the ecosystem service value variation caused by land use and land cover change and characteristics of its spatial distribution based on multi-temporal land use and land cover data sets (1977, 1987, 1997, 2007, 2017). Meanwhile, the contributions of factors driving ecosystem service value and their interactions were explored using geographical detector. The results showed the following: 1) The land use and land cover structure was stable from 1977 to 2017, and the overall ecosystem service value increased slightly. The services provided by the oasis ecosystem dominated the fluctuations in ecosystem service value throughout the study region. 2) Ecosystem service value exhibited a strong positive spatial autocorrelation. The high values were concentrated in the oasis area in the north of the study area, while the low values mainly appeared in the desert ecosystem. 3) The land use degree and human activity intensity index of human factors are the main factors leading to the differentiation of ecosystem service value. Synergized interactions among human activities, changes in landscape patterns, and natural factors produced the spatial differentiation in ecosystem service value of the study region. The results suggest that in future decision-making for ecosystem management, the direction of human activities within the ecological environment should be controlled. Improve the diversity of patches, reduce the degree of landscape fragmentation, improve the ecosystem service function of LULC, optimize the allocation of ecological landscape resources. [ABSTRACT FROM AUTHOR]

Background: Various epigenetic regulations systematically govern gene expression in cells involving various biological processes. Dysregulation of the epigenome leads to aberrant transcriptional programs and subsequently results in diseases, such as cancer. Therefore, comprehensive profiling epigenomics is essential for exploring the mechanisms underlying gene expression regulation during development and disease., Methods: In this study, we developed single-cell chromatin proteins and accessibility tagmentation (scCPA-Tag), a multi-modal single-cell epigenetic profile capturing technique based on barcoded Tn5 transposases and a droplet microfluidics platform. scCPA-Tag enables the simultaneous capture of DNA profiles of histone modification and chromatin accessibility in the same cell., Results: By applying scCPA-Tag to K562 cells and a hepatocellular carcinoma (HCC) sample, we found that the silence of several chromatin-accessible genes can be attributed to lysine-27-trimethylation of the histone H3 tail (H3K27me3) modification. We characterized the epigenetic features of the tumour cells and different immune cell types in the HCC tumour tissue by scCPA-Tag. Besides, a tumour cell subtype (C2) with more aggressive features was identified and characterized by high chromatin accessibility and a lower abundance of H3K27me3 on tumour-promoting genes., Conclusions: Our multi-modal scCPA-Tag provides a comprehensive approach for exploring the epigenetic landscapes of heterogeneous cell types and revealing the mechanisms of gene expression regulation during developmental and pathological processes at the single-cell level., Highlights: scCPA-Tag offers a highly efficient and high throughput technique to simultaneously profile histone modification and chromatin accessibility within a single cell. scCPA-Tag enables to uncover multiple epigenetic modification features of cellular compositions within tumor tissues. scCPA-Tag facilitates the exploration of the epigenetic landscapes of heterogeneous cell types and provides the mechanisms governing gene expression regulation., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background and Aims: Circulating tumor cells (CTCs) are precursors of cancer metastasis. However, how CTCs evade immunosurveillance during hematogenous dissemination remains unclear., Approach and Results: We identified CTC-platelet adhesions by single-cell RNA sequencing and multiplex immunofluorescence of blood samples from multiple cancer types. Clinically, CTC-platelet aggregates were associated with significantly shorter progression-free survival and overall survival in patients with HCC. In vitro, ex vivo, and in vivo assays demonstrated direct platelet adhesions gifted cancer cells with an evasive ability from NK cell killing by upregulating inhibitory checkpoint CD155 (PVR cell adhesion molecule), therefore facilitating distant metastasis. Mechanistically, CD155 was transcriptionally regulated by the FAK/JNK/c-Jun cascade in a platelet contact-dependent manner. Further competition assays and cytotoxicity experiments revealed that CD155 on CTCs inhibited NK-cell cytotoxicity only by engaging with immune receptor TIGIT, but not CD96 and DNAM1, another 2 receptors for CD155. Interrupting the CD155-TIGIT interactions with a TIGIT antibody restored NK-cell immunosurveillance on CTCs and markedly attenuated tumor metastasis., Conclusions: Our results demonstrated CTC evasion from NK-cell-mediated innate immunosurveillance mainly through immune checkpoint CD155-TIGIT, potentially offering an immunotherapeutic strategy for eradicating CTCs., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Primary liver cancers (PLCs) are a broad class of malignancies that include HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular and intrahepatic cholangiocarcinoma. PLCs are often associated with a poor prognosis due to their high relapse and low therapeutic response rates. Importantly, PLCs exist within a dynamic and complex tumor ecosystem, which includes malignant, immune, and stromal cells. It is critical to dissect the PLC tumor ecosystem to uncover the underlying mechanisms associated with tumorigenesis, relapse, and treatment resistance to facilitate the discovery of novel therapeutic targets. Single-cell and spatial multi-omics sequencing techniques offer an unprecedented opportunity to elucidate spatiotemporal interactions among heterogeneous cell types within the complex tumor ecosystem. In this review, we describe the latest advances in single-cell and spatial technologies and review their applications with respect to dissecting liver cancer tumor ecosystems., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Recently, increasing evidence suggests that DNA methylation plays a crucial role in fruit ripening. However, the role of DNA methylation in regulating specific traits, such as flavor, remains unclear. Here, we report a role of DNA methylation in affecting furanone biosynthesis in strawberry. Strawberry quinone oxidoreductase (FaQR) is a key enzyme in furanone biosynthesis. There are four FaQR homologs in strawberry cultivar 'Yuexin', and one of them, FaQR3 , contributes ~50% of FaQR transcripts, indicating a major role of FaQR3 in furanone biosynthesis. Through characterization of levels of DNA methylation and FaQR3 transcript and furanone contents during fruit ripening and after the application of DNA methylation inhibitor, we found that the DNA methylation level of the FaQR3 promoter was negatively correlated with FaQR3 expression and furanone accumulation, suggesting that DNA methylation may be involved in furanone biosynthesis through adjusting FaQR3 expression, and responded to different temperatures consistently. In addition, transient expression of a gene in the RNA-directed DNA methylation (RdDM) pathway, FaAGO4 , and enrichment analysis of the 24-nucleotide siRNAs suggested that DNA methylation in the FaQR3 promoter is mediated by the RdDM pathway. Transient RNA interference (RNAi) of FaDML indicated that the demethylation pathway may be involved in regulating furanone accumulation. These findings provide new insights into the role of DNA methylation and demethylation in affecting flavor quality in strawberry during fruit ripening., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Objective: To compare freehand minimally invasive pedicle screw fixation (freehand MIPS) combined with percutaneous vertebroplasty (PVP), minimally invasive decompression, and partial tumor resection with open surgery for treatment of thoracic or lumbar vertebral metastasis of hepatocellular carcinoma (HCC) with symptoms of neurologic compression, and evaluate its feasibility, efficacy, and safety. Methods: Forty-seven patients with 1-level HCC metastatic thoracolumbar tumor and neurologic symptoms were included between February 2015 and April 2017. Among them, 21 patients underwent freehand MIPS combined with PVP, minimally invasive decompression, and partial tumor resection (group 1), while 26 patients were treated with open surgery (group 2). Duration of operation, blood loss, times of fluoroscopy, incision length, and stay in hospital were compared between the two groups. Pre- and postoperative visual analog scale (VAS) pain score, Oswestry Disability Index (ODI), American Spinal Injury Association (ASIA) grade, ambulatory status, and urinary continence were also recorded. The Cobb angle and central and anterior vertebral body height were measured on lateral radiographs before surgery and during follow-ups. Results: Patients in group 1 showed significantly less blood loss (195.5 ± 169.1 ml vs. 873.1 ± 317.9 ml, P = 0.000), shorter incision length (3.4 ± 0.3 vs. 13.6 ± 1.8 cm, P = 0.000), shorter median stay in hospital (4-8/6 vs. 8-17/12 days, P = 0.000), more median times of fluoroscopy (5-11/6 vs. 4-7/5 times, P = 0.000), and longer duration of operation (204.8 ± 12.1 vs. 171.0 ± 12.0 min, P = 0.000) than group 2. Though VAS significantly decreased after surgery in both groups, VAS of group 1 was significantly lower than that of group 2 immediately after surgery and during follow-ups ( P < 0.05). Similar results were found in ODI. No differences in the neurological improvement and spinal stability were observed between the two groups. Conclusion: Freehand MIPS combined with PVP, minimally invasive decompression, and partial tumor resection is a safe, effective, and minimally invasive method for treating thoracolumbar metastatic tumors of HCC, with less blood loss, better pain relief, and shorter length of midline incision and stay in hospital., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fan, Zhou, Li, Sun and Gu.)

Single-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer evolution. Unfortunately, classical DNA amplification-based methods have low throughput and introduce coverage bias during sample preamplification. We developed a single-cell DNA library preparation method without preamplification in nanolitre scale (scDPN) to address these issues. The method achieved a throughput of up to 1800 cells per run for copy number variation (CNV) detection. Also, our approach demonstrated a lower level of amplification bias and noise than the multiple displacement amplification (MDA) method and showed high sensitivity and accuracy for cell line and tumor tissue evaluation. We used this approach to profile the tumor clones in paired primary and relapsed tumor samples of hepatocellular carcinoma (HCC). We identified three clonal subpopulations with a multitude of aneuploid alterations across the genome. Furthermore, we observed that a minor clone of the primary tumor containing additional alterations in chromosomes 1q, 10q, and 14q developed into the dominant clone in the recurrent tumor, indicating clonal selection during recurrence in HCC. Overall, this approach provides a comprehensive and scalable solution to understand genome heterogeneity and evolution., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

BRCA1-associated protein 1 (BAP1) or its mutants have been known to play critical regulatory roles in tumor biology, yet their role in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we detected the mutations of all the exons of BAP1 in 105 HCC patients using Sanger sequencing, and found eight somatic mutations in 6 (5.71%) patients. We also found that the mRNA and protein levels of BAP1 were markedly downregulated in HCC versus the adjacent non-tumor tissues. Wild-type BAP1 but not mutant BAP1 significantly inhibited HCC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) in vitro , and tumor progression and metastasis in vivo . Mechanistically, BAP1 complexed with PTEN and stabilized PTEN via deubiquitination and, furthermore, negatively regulated HCC cell EMT by deactivating the AKT/GSK-3β/Snail pathway. However, those tumor-inhibitory effects of BAP1 were abolished by inactivating mutations. Clinically, low BAP1 expression was positively correlated to aggressive tumor phenotypes, which also independently associated with poorer recurrence-free survival and overall survival after curative hepatectomy. Conclusively, our results indicate that BAP1, significantly downregulated, somatically mutated and negatively regulating EMT in HCC, serves as a tumor suppressor of HCC by deubiquitinating and stabilizing PTEN., Competing Interests: None., (AJCR Copyright © 2021.)

The prognosis of hepatocellular carcinoma (HCC) is closely associated with the occurrence of distant metastases, which is likely due to circulating tumor cells (CTCs). However, the low number of CTCs is the main obstacle limiting research of the mechanism of CTC metastasis. Here, We evaluated the role of ubiquitin-specific protease 1 (USP1) in promoting CTC survival during blood-borne metastases. We observed that USP1 was frequently upregulated in CTCs and correlated with metastasis and a reduced overall survival rate of patients. Additionally, genetic knockout of USP1 the survival rate of CTCs. Further analyses showed that USP1 mediates oncogenic activity by deubiquitinating and stabilizing transducin β-like 1 X-linked receptor 1 (TBLR1), which plays essential roles in regulating Wnt signaling. These results demonstrated that USP1 may act as an essential factor in promoting the survival of CTCs and suggest that inhibition of USP1 is a potential strategy for HCC treatment., (Copyright © 2020 Li, Xu, Gao, Sun, Zhou, Wang, Cheng, Guo, Ya, Fan and Yang.)

Glycogen phosphorylase kinase β-subunit (PHKB) is a regulatory subunit of phosphorylase kinase (PHK), involving in the activation of glycogen phosphorylase (GP) and the regulation of glycogen breakdown. Emerging evidence suggests that PHKB plays a role in tumor progression. However, the function of PHKB in HCC progression remains elusive. Here, our study revealed that the expression of PHKB significantly decreased in HCC tissues, and the low expression of PHKB could serve as an independent indicator for predicting poor prognosis in HCC. Functional experiments showed that PHKB knockdown significantly promoted cell proliferation both in vitro and in vivo , whereas PHKB overexpression resulted in opposing effects. Additionally, in vitro assays revealed that the over (or high) expression of PHKB greatly hindered HCC cell invasion and increased apoptosis rates. Also, we found that the over (or high) expression of PHKB effectively suppressed the epithelial-mesenchymal transition, which was further confirmed by our clinical data. Intriguingly, the biological function of PHKB in HCC was independent of glycogen metabolism. Mechanically, PHKB could inhibit AKT and STAT3 signaling pathway activation in HCC. Collectively, our data demonstrate that PHKB acts as a novel prognostic indicator for HCC, which exerts its suppression function via inactivating AKT and STAT3. Our data might provide novel insights into progression and facilitate the development of a new therapeutic strategy for HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)