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In our previous study, we found that small ubiquitin‐related modifier (SUMO)‐activating enzyme ubiquitin‐associated‐2 domain (UBA2) was upregulated in hepatocellular carcinoma (HCC) patients who were insensitive to chemoembolization. In this study, we aimed to investigate the role of UBA2 in HCC progression. Three cohorts were used to evaluate the efficacy of UBA2 as a prognostic factor for HCC. Our results indicated that UBA2 was associated with aggressive clinical behaviors and was a strong indicator of poor prognosis in HCC. In vitro experiments demonstrated that UBA2 accelerated cell growth, invasion, and migration. These results were further supported by in vivo experiments. RNA‐sequencing analysis indicated NQO1 as a target of UBA2, with its levels altering following UBA2 manipulation. The results were verified by western blotting (WB) and quantitative PCR. The SUMOplot Analysis Program predicted lysine residue K240 as a modification target of UBA2, which was confirmed by immunoprecipitation (IP) assays. Subsequent mutation of NQO1 at K240 in HCC cell lines and functional assays revealed the significance of this modification. In addition, the oncogenic effect of UBA2 could be reversed by the SUMO inhibitor ML792 in vivo and in vitro. In conclusion, our study elucidated the regulatory mechanism of UBA2 in HCC and suggested that the SUMO inhibitor ML792 may be an effective combinatory treatment for patients with aberrant UBA2 expression. [ABSTRACT FROM AUTHOR]

Clarifying the spatiotemporal evolution of sustainable water resources utilization (SWU) and its decoupling effects from economic growth (EG) is essential for the effective management of water ecosystems and sustainable development of basins. However, the traditional Ecological Footprint model limits the ability to compare SWU within a basin, and existing studies need to pay more attention to the importance of water renewability in quantifying SWU. Based on the capital flow and capital stock perspectives, this study constructed an evaluation method for SWU and its decoupling effect from EG by combining the three-dimensional Water Ecological Footprint (WEF), sustainable reclassification, and the Tapio model, and explored different types of SWU enhancement strategies. The results indicate that: (1) From 2010 to 2022, the SWU of the Yellow River Basin (YRB) shows a decreasing and then increasing trend and is generally in water ecological deficit, with a lower SWU in the middle and lower reaches. Overall, the per capita WEF size decreased by 0.73% per year, while the WEF depth increased by 0.26% per year, the pressure and stress on the SWU of the YRB are still significant. (2) Agricultural freshwater use and domestic greywater discharge dominate the WEF of the basin, and the problem of inversion of the water use structure with the industrial structure is evident. (3) Spatial differentiation within the basin is apparent, and SWU shows a spatial distribution of western strength and eastern weakness, with significant consumption of water capital stock due to insufficient water capital flow as the main reason. (4) Topio decoupling analysis shows that WEF and EG are mainly strongly decoupled, with WEF lagging behind EG; the decoupling relationship between SWU and EG evolves from END-SD-WD, reduces the consumption of water capital stock and increasing water capital flow is a reasonable way to realise its stable strong decoupling. This study is essential for SWU studies of large river basins in arid and semi-arid regions. It provides insights into the sustainable management and rational allocation of water resources in the YRB and other similar basins worldwide. • A three-dimensional water ecological footprint model is used to assess the SWU. • The decoupling of WEF size and WEF depth from economic growth is taken into account. • Water stress remains high, and SWU's spatial differentiation is evident. • Inadequate water capital flow leading to consumption of water capital stock is the main reason for the impact on SWU. • Strong decoupling of WEF from economic growth, unstable decoupling of SWU from economic growth. [ABSTRACT FROM AUTHOR]

Hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment strategy for hepatocellular carcinoma (HCC), but a detailed understanding of the multicellular ecosystem after HAIC treatment is lacking. Here, we collected tumor samples from treatment-naïve primary and post-HAIC HCC, and integrated single-nucleus RNA sequencing with spatial transcriptomics to characterize the tumor ecosystem in the post-HAIC HCC. Increased fractions and enhanced cellular communication of CD4 + T, CD20 + B, and dendritic cell subtypes were identified in post-HAIC tumors. Moreover, it is substantiated that HAIC promoted tertiary lymphoid structures (TLS) formation, and addressed the roles of TLSs as spatial niches of cellular communication. Specifically, intermediate exhausted CD8 + T cells expressing Granzyme-K and PD-1 (PD-1 + CD8 + Tex-int) expanded following HAIC and exhibited a functionally antitumor phenotype. PD-1 + CD8 + Tex-int accumulated in the TLS vicinity and disseminated throughout the tumor microenvironment, demonstrating potential as an effective biomarker for HAIC-based treatment in HCC. This study provides valuable resources and biological insights in the cellular underpinnings of HAIC treatment., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Efficient conversion of lignocellulosic biomass to optically pure lactic acid is a key challenge for the economical production of biodegradable poly-lactic acid. A recently isolated strain, Thermoanaerobacterium aotearoense SCUT27, is promising as an efficient lactic acid production bacterium from biomass due to its broad substrate specificity. Additionally, its strictly anaerobic and thermophilic characteristics suppress contamination from other microoragnisms. Herein, we report the significant improvements of concentration and yield in lactic acid production from various lignocellulosic derived sugars, achieved by the carbon flux redirection through homologous recombination in T. aotearoense SCUT27., Results: T. aotearoense SCUT27 was engineered to block the acetic acid formation pathway to improve the lactic acid production. The genetic manipulation resulted in 1.8 and 2.1 fold increase of the lactic acid yield using 10 g/L of glucose or 10 g/L of xylose as substrate, respectively. The maximum l-lactic acid yield of 0.93 g/g glucose with an optical purity of 99.3% was obtained by the engineered strain, designated as LA1002, from 50 g/L of substrate, which is very close to the theoretical value (1.0 g/g of glucose). In particular, LA1002 produced lactic acid at an unprecedented concentration up to 3.20 g/L using 10 g/L xylan as the single substrate without any pretreatment after 48 h fermentation. The non-sterilized fermentative production of l-lactic acid was also carried out, achieving values of 44.89 g/L and 0.89 g/g mixed sugar for lactic acid concentration and yield, respectively., Conclusions: Blocking acetic acid formation pathway in T. aotearoense SCUT27 increased l-lactic acid production and yield dramatically. To our best knowledge, this is the best performance of fermentation on lactic acid production using xylan as the sole carbon source, considering the final concentration, yield and fermentation time. In addition, it should be mentioned that the performance of non-sterilized simultaneous fermentation from glucose and xylose was very close to that of normal sterilized cultivation. All these results used the mutant strain, LA1002, indicated that it is a new promising candidate for the effective production of optically pure l-lactic acid from lignocellulosic biomass.