Prognostic iron-metabolism signature robustly stratifies single-cell characteristics of hepatocellular carcinoma.

Cancer immunotherapy has shown to be a promising method in treating hepatocellular carcinoma (HCC), but suboptimal responses in patients are attributed to cellular and molecular heterogeneity. Iron metabolism-related genes (IRGs) are important in maintaining immune system homeostasis and have the potential to help develop new strategies for HCC treatment. Herein, we constructed and validated the iron-metabolism gene prognostic index (IPX) using univariate Cox proportional hazards regression and LASSO Cox regression analysis, successfully categorizing HCC patients into two groups with distinct survival risks. Then, we performed single-sample gene set enrichment analysis, weighted correlation network analysis, gene ontology enrichment analysis, cellular lineage analysis, and SCENIC analysis to reveal the key determinants underlying the ability of this model based on bulk and single-cell transcriptomic data. We identified several driver transcription factors specifically activated in specific malignant cell sub-populations to contribute to the adverse survival outcomes in the IPX-high subgroup. Within the tumor microenvironment (TME), T cells displayed significant diversity in their cellular characteristics and experienced changes in their developmental paths within distinct clusters identified by IPX. Interestingly, the proportion of Treg cells was increased in the high-risk group compared with the low-risk group. These results suggest that iron-metabolism could be involved in reshaping the TME, thereby disrupting the cell cycle of immune cells. This study utilized IRGs to construct a novel and reliable model, which can be used to assess the prognosis of patients with HCC and further clarify the molecular mechanisms of IRGs in HCC at single-cell resolution.

Silicon nutrition improves the quality and yield of rice under dry cultivation.

BACKGROUND: Dry cultivation of rice is a water-saving, emission reduction and labor-saving rice farming method. However, the development of rice under dry cultivation is hampered by the limitations of dry cultivation on rice yield and rice quality. We hypothesized that additional silicon (Si) would be a measure to address these limitations or challenges. RESULTS: In the present study, we set up field trials with three treatments: flooded cultivation (W), dry cultivation (D) and dry cultivation plus Si. Yield and quality were reduced under D treatment compared to W treatment. The addition of Si promoted root development, increased plant height and leaf area, increased photosynthetic enzyme activity, net photosynthetic rate and SPAD values, and increased biomass under dry crop conditions. Under the drought conditions, silica up-regulated the expression of AGPSI, SBEI, SBEIIb, SSI and SSII-1 genes and the activities of ADP-glucose pyrophosphorylase (AGPase), soluble starch synthetase (SSS) and starch branching enzyme (SBE) enzymes, which reduced protein, amylose, chalkiness percentage and chalkiness degree, increased brown rice rate, milled rice rate and head milled rice rate, and also improved rice quality. In addition, the increase of AGPase, SSS and SBE enzyme activities promoted the filling rate and the number of spikes was guaranteed, whereas the yield was improved by promoting the seed setting rate and 1000-grain weight. CONCLUSION: The results of the present study indicate that adding appropriate amounts of Si fertilizer can improve the yield and quality of rice under dry cultivation by regulating source supply capacity and grain starch synthesis. © 2023 Society of Chemical Industry.

Carotenoids in maternal and cord blood, breast milk and their association with maternal dietary intake: a longitudinal study in Shanghai, China.

Carotenoids are important bioactive substances in breast milk, the profile of which is seldom studied. This study aimed to explore the profile of carotenoids in breast milk and maternal/cord plasma of healthy mother-neonate pairs in Shanghai, China, and their correlation with dietary intake. Maternal blood, umbilical cord blood and breast milk samples from five lactation stages (colostrum, transitional milk and early-, mid- and late-term mature milk) were collected. Carotenoid levels were analysed by HPLC. Carotenoid levels in breast milk changed as lactation progressed (P < 0·001). ß-Carotene was the primary carotenoid in colostrum. Lutein accounted for approximately 50 % of total carotenoids in transitional milk, mature milk and cord blood. Positive correlations were observed between five carotenoids in umbilical cord blood and maternal blood (P all < 0·001). ß-Carotene levels were also correlated between maternal plasma and three stages of breast milk (r = 0·605, P < 0·001; r = 0·456, P = 0·011, r = 0·446; P = 0·013, respectively). Dietary carotenoid intakes of lactating mothers also differed across lactation stages, although no correlation with breast milk concentrations was found. These findings suggest the importance of exploring the transport mechanism of carotenoids between mothers and infants and help guide the development of formulas for Chinese infants as well as the nutritional diets of lactating mothers.

Enhancing nitrogen removal efficiency and anammox metabolism in microbial electrolysis cell coupled anammox through different voltage application.

The slow growth and difficulty in cultivating anammox bacteria limit the rapid start-up of anammox process and effective microbial enrichment. In this study, microbial electrolysis cell (MEC) was coupled with anammox to investigate the effects of different applying voltage methods on substrate removal efficiency and rates, microbial community structure, anammox metabolism and metabolic pathways. The results showed that applying voltage not only improved NH4+-N removal efficiency and removal rates, but also promoted electron transfer efficiency, key enzyme activity and extracellular polymeric substances (EPS) secretion in the systems. Step-up voltage was more conducive to the growth of Candidatus_Kuenenia in the cathode, which promoted the rapid start-up of anammox and treating wastewater with low ammonia concentration. The main metabolic pathway in step-up voltage operation was hydrazine to nitrogen, while in constant voltage operation was hydroxylamine oxidation pathway. These findings provided a new insight into the enhancement and operation of anammox system.

Androgen Receptor Transcriptionally Inhibits Programmed Death Ligand-1 Expression and Influences Immune Escape in Bladder Cancer.

In multiple clinical trials, immune checkpoint blockade-based immunotherapy has shown significant therapeutic efficacy in bladder cancer (BCa). Sex is closely related to the incidence rate and prognosis of BCa. As one of the sex hormone receptors, the androgen receptor (AR) is a well-known key regulator that promotes the progression of BCa. However, the regulatory mechanism of AR in the immune response of BCa is still unclear. In this study, the expression of AR and programmed death ligand 1 (PD-L1) was negatively correlated in BCa cells, clinical tissues, and tumor data extracted from The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort. A human BCa cell line was transfected to alter the expression of AR. The results show that AR negatively regulated PD-L1 expression by directly binding to AR response elements on the PD-L1 promoter region. In addition, AR overexpression in BCa cells significantly enhanced the antitumor activity of cocultured CD8+ T cells. Injection of anti-PD-L1 monoclonal antibodies into C3H/HeN mice significantly suppressed tumor growth, and stable expression of AR dramatically enhanced the antitumor activity in vivo. In conclusion, this study describes a novel role of AR in regulating the immune response to BCa by targeting PD-L1, thus providing potential therapeutic strategies for immunotherapy in BCa.

X-box binding protein 1 (XBP1): a potential role in chemotherapy response, clinical pathologic features, non-inflamed tumour microenvironment for breast cancer.

X-box binding protein 1 (XBP1) is mainly expressed in breast cancer (BC) in human cancers. Its tumorigenesis and favourable prognosis are contradictory, and its essential role in chemotherapeutic response and immunosuppression is unknown in BC. The study firstly identified XBP1 who received neoadjuvant chemotherapy (NAC) from GSE25055 and GSE24460. Associations between XBP1 expression and clinicopathological characteristics was investigated using Oncomine, TCGA, UALCAN and bc-GenExMiner. The prognostic value of XBP1 was assessed using the Kaplan-Meier Plotter, bc-GenExMiner, GSE25055, and GSE25056. Furthermore, we systematically correlated XBP1 and immunological characteristics in the BC tumour microenvironment (TME) using TISIDB, TIMER, GSE25055, GSE25056 and TCGA dataset. Finally, an essential role of XBP1 in chemotherapy response was evaluated based on GSE25055, GSE25065, GSE24460, GSE5846, ROC Plotter and CELL databases. Furthermore, XBP1 mRNA expression levels were obviously highest in BC among human cancers and were significantly related to a good prognosis. In addition, XBP1 mRNA and protein levels were higher in the luminal subtype than in normal tissues and basal-like subtype, which might be attributed to membrane transport-related processes. Apart from BC, negative immunological correlations of XBP1 were not observed in other malignancies. XBP1 might shape the non-inflamed TME in BC. Finally, XBP1 expression was higher in chemo-resistive than chemo-sensitive cases, it had a predictive value and could independently predict chemotherapy response in BC patients receiving NAC. Our study suggests that the essential role of XBP1 in clinical pathologic features, non-inflamed TME, chemotherapy response in BC.

Chromosome-Level Genome Assembly for Acer pseudosieboldianum and Highlights to Mechanisms for Leaf Color and Shape Change.

Acer pseudosieboldianum (Pax) Komarov is an ornamental plant with prominent potential and is naturally distributed in Northeast China. Here, we obtained a chromosome-scale genome assembly of A. pseudosieboldianum combining HiFi and Hi-C data, and the final assembled genome size was 690.24 Mb and consisted of 287 contigs, with a contig N50 value of 5.7 Mb and a BUSCO complete gene percentage of 98.4%. Genome evolution analysis showed that an ancient duplication occurred in A. pseudosieboldianum. Phylogenetic analyses revealed that Aceraceae family could be incorporated into Sapindaceae, consistent with the present Angiosperm Phylogeny Group system. We further construct a gene-to-metabolite correlation network and identified key genes and metabolites that might be involved in anthocyanin biosynthesis pathways during leaf color change. Additionally, we identified crucial teosinte branched1, cycloidea, and proliferating cell factors (TCP) transcription factors that might be involved in leaf morphology regulation of A. pseudosieboldianum, Acer yangbiense and Acer truncatum. Overall, this reference genome is a valuable resource for evolutionary history studies of A. pseudosieboldianum and lays a fundamental foundation for its molecular breeding.

Combined transcriptome and metabolome integrated analysis of Acer mandshuricum to reveal candidate genes involved in anthocyanin accumulation.

The red color formation of Acer mandshuricum leaves is caused by the accumulation of anthocyanins primarily, but the molecular mechanism researches which underlie anthocyanin biosynthesis in A. mandshuricum were still lacking. Therefore, we combined the transcriptome and metabolome and analyzed the regulatory mechanism and accumulation pattern of anthocyanins in three different leaf color states. In our results, 26 anthocyanins were identified. Notably, the metabolite cyanidin 3-O-glucoside was found that significantly correlated with the color formation, was the predominant metabolite in anthocyanin biosynthesis of A. mandshuricum. By the way, two key structural genes ANS (Cluster-20561.86285) and BZ1 (Cluster-20561.99238) in anthocyanidin biosynthesis pathway were significantly up-regulated in RL, suggesting that they might enhance accumulation of cyanidin 3-O-glucoside which is their downstream metabolite, and contributed the red formation of A. mandshuricum leaves. Additionally, most TFs (e.g., MYBs, bZIPs and bHLHs) were detected differentially expressed in three leaf color stages that could participate in anthocyanin accumulation. This study sheds light on the anthocyanin molecular regulation of anthocyanidin biosynthesis and accumulation underlying the different leaf color change periods in A. mandshuricum, and it could provide basic theory and new insight for the leaf color related genetic improvement of A. mandshuricum.

Identification of potential therapeutic targets in urothelial bladder carcinoma of Chinese population by targeted next-generation sequencing.

Patients with urothelial carcinoma (UC) of the bladder have a high risk of death in China. However, a lack of comprehensive molecular profiling in Chinese Han population hinders the development of targeted therapies for bladder cancer. In our present study, we collected fresh bladder tumors from low-grade (T1, N0, M0, G1) non-muscle invasive bladder cancer (NMIBC) patients (n = 16) and high-grade (T2-4, N0, M0, Gx) muscle-invasive bladder cancer (MIBC) patients (n = 16) with their paired normal bladder tissues, and subjected the total genomic DNAs to targeted next-generation sequencing (NGS) for 94 cancer-associated genes. NGS results showed that 30.9% of detected genes (29/94) was mutated in 32 urothelial carcinoma bladder tissues. Furthermore, our results and ICGC database showed that FGFR3, KMT2D, TP53, KDM6A, and ARID1A were the most frequently mutated genes in UC patients. Of note, NMIBC and MIBC displayed distinguishable genomic alterations. FGFR3, KMT2D, AKT1, ARID1A, and STAG2 were the most frequently mutated genes in NMIBC patients, whereas mutations of TP53, CREBBP, FGFR3, KDM6A, KMT2D, and ARID1A were frequently detected in MIBC. Intriguingly, gene ontology and clustering analysis revealed that these frequently mutated genes were highly enriched in signaling pathways responsible for cancer development. Taken together, the mutation frequency of genes associated with UC development in NMIBC and MIBC was screened out in Chinese Han population and elucidation of the related mechanisms provides theoretical basis and technical support for the development of early diagnosis and therapeutic strategies in UC.

[Enzymatic production of arginine derivatives: a review].

L-arginine (L-Arg) is an alkaline amino acid that possesses various function groups and acts as an important precursor for useful chemical synthesis. L-Arg derivatives are widely applied in pharmaceutical, food and cosmetic industries. Environment friendly and cost-effective production of L-Arg derivatives by enzymatic catalysis provides significant advantages over chemical synthesis and microbial fermentation. In this article, several typical L-Arg derivatives and their enzymatic production processes are highlighted. Furthermore, prospect is also addressed about enzymatic production of L-Arg derivatives.

Enzymatic Production of Ascorbic Acid-2-phosphate by Recombinant Acid Phosphatase.

In this study, an environmentally friendly and efficient enzymatic method for the synthesis of l-ascorbic acid-2-phosphate (AsA-2P) from l-ascorbic acid (AsA) was developed. The Pseudomonas aeruginosa acid phosphatase (PaAPase) was expressed in Escherichia coli BL21. The optimal temperature, optimal pH, Km, kcat, and catalytic efficiency of recombinant PaAPase were 50 °C, 5.0, 93 mM, 4.2 s-1, and 2.7 mM-1 min-1, respectively. The maximal dry cell weight and PaAPase phosphorylating activity reached 8.5 g/L and 1127.7 U/L, respectively. The highest AsA-2P concentration (50.0 g/L) and the maximal conversion (39.2%) were obtained by incubating 75 g/L intact cells with 88 g/L AsA and 160 g/L sodium pyrophosphate under optimal conditions (0.1 mM Ca2+, pH 4.0, 30 °C) for 10 h; the average AsA-2P production rate was 5.0 g/L/h, and the AsA-2P production system was successfully scaled up to a 7.5 L fermenter. Therefore, the enzymatic process showed great potential for production of AsA-2P in industry.