HNRNPL facilitates ferroptosis in hepatocellular carcinoma cells by promoting S100A9 expression.

OBJECTIVE: This study probed into the effect of HNRNPL on ferroptosis in hepatocellular carcinoma (HCC) cells and related molecular mechanisms. METHODS: Expression patterns of HNRNPL, Recombinant S100 Calcium Binding Protein A9 (S100A9) were analyzed in HCC tissues or cells. Following transfection, HCC cell activity was analyzed, followed by detection of levels of ROS, iron content, LPO, MDA, and GSH as well as the expression of ferroptosis-related proteins. For molecular mechanism, RIP, RNA pull-down assay and actinomycin D assay were implemented to verify the binding relationship between HNRNPL and S100A9. Finally, in vivo nude mouse xenograft tumor experiments were performed for further validate the crucial role of HNENPL expression in HCC. RESULTS: HNRNPL and S100A9 were significantly overexpressed in HCC. sh-HNRNPL treatment led to a significant decrease in cellular activity, GSH content, and expression of GPX4 and SLC7A11, and a significant increase in iron content, LPO level, MDA, ROS content, and expression of ACSL4 and TFR1. In addition, after sh-HNRNPL was combined with oe-S100A9 or Fer-1, a ferroptosis inhibitor, both oe-S100A9 and Fer-1 reversed the promotional effect of sh-HNRNPL on ferroptosis of HCC cells when sh-HNRNPL acted alone. Mechanically, HNRNPL promoted S100A9 mRNA stability and expression through RBP. Furthermore, low expression of HNRNPL in vivo delayed the growth of xenograft tumors and the expression of ferroptosis-related proteins. CONCLUSION: HNRNPL promotes S100A9 mRNA stability and expression through RBP action, thereby promoting ferroptosis in HCC cells.

The complete plastid genome of Rhamnus leptacantha Schneid. (Rhamnaceae).

Rhamnus leptacantha C.K.Schneid. (1914). is a rare shrub species of the genus Rhamnus. The complete plastid genome of Rhamnus leptacantha was sequenced for the first time in this study. The total length of this genome is 161,248 bp with a large single copy (LSC) region (89,386 bp), a small single copy (SSC) region (19,000 bp), and two inverted repeat regions (IRs, 26,431 bp). A total of 133 functional genes were annotated, including 88 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Plastome of R. leptacantha displayed a conservative structure and gene order. Phylogenetic analysis strongly supported R. leptacantha clustered with other members of genus Rhamnus. This study provides a foundation for further investigation of the complete chloroplast genome in inferring the evolution within the Rhamnaceae family.

Transcatheter arterial chemoembolisation combined with lenvatinib plus camrelizumab as conversion therapy for unresectable hepatocellular carcinoma: a single-arm, multicentre, prospective study.

Background: The synergistic effect of locoregional therapy in combination with systemic therapy as a conversion therapy for unresectable hepatocellular carcinoma (uHCC) is unclear. The purpose of this study was to evaluate the efficacy and safety of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and camrelizumab (TACE + LEN + CAM) as conversion therapy for uHCC. Methods: This single-arm, multicentre, prospective study was conducted at nine hospitals in China. Patients (aged 18-75 years) diagnosed with uHCC, an Eastern Cooperative Oncology Group performance score (ECOG-PS) of 0-1 and Child-Pugh class A received camrelizumab (200 mg, every 3 weeks) and lenvatinib (bodyweight ≥60 kg: 12 mg/day; <60 kg: 8 mg/day) after TACE treatment. Surgery was performed after tumour was assessed as meeting the criteria for resection. Patients who did not meet the criteria for surgery continued to receive triple therapy until disease progression or intolerable toxicity. Primary endpoints were objective response rate (ORR) according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and safety. Secondary endpoints included the surgical conversion rate, radical (R0) resection rate, and disease control rate (DCR). This study was registered with Chinese Clinical Trial Registry (ChiCTR2100050410). Findings: Between Oct 25, 2021, and July 20, 2022, 55 patients were enrolled. As of the data cutoff on June 1, 2023, the median follow-up was 13.3 months (IQR 10.6-15.9 months). The best tumour response to triple therapy was complete response (CR) in 9 (16.4%) patients, partial response (PR) in 33 (60.0%) patients, stable disease (SD) in 5 (9.1%) patients, or progressive disease (PD) in 7 (12.7%) patients. The ORR was 76.4% (42/55, 95% CI, 65.2-87.6%), and the DCR was 85.5% (47/55, 95% CI, 76.2-94.8%) per mRECIST. Twenty-four (43.6%) of the 55 patients suffered from grade 3-4 treatment-related adverse events (TRAEs). No grade 5 TRAEs occurred. A total of 30 (30/55, 54.5%) patients were converted to resectable HCC and 29 (29/55, 52.7%) patients underwent resection. The R0 resection rate was 96.6% (28/29). The major pathologic response (MPR) and pathologic complete response (pCR) rates in the surgery population were 65.5% (19/29) and 20.7% (6/29), respectively. Only one patient developed a Clavien-Dindo IIIa complication (abdominal infection). No Clavien-Dindo IIIb-V complications occurred. The median OS and median PFS were not reached. Interpretation: The triple therapy (TACE + LEN + CAM) is promising active for uHCC with a manageable safety. Moreover, triple therapy has good conversion efficiency and the surgery after conversion therapy is feasible and safe. To elucidate whether patients with uHCC accepting surgical treatment after the triple therapy can achieve better survival benefits than those who receive triple therapy only, well-designed randomised controlled trials are needed. Funding: This study was funded by the Natural Science Foundation of Fujian Province, China (2022J01691) and the Youth Foundation of Fujian Province Health Science and Technology Project, China (2022QNA035).

S100A9 promotes tumor-associated macrophage for M2 macrophage polarization to drive human liver cancer progression: An in vitro study.

Tumor-associated macrophages (TAMs) and M2 macrophage polarization have been documented for their implication in various malignancies, but their implication in liver cancer remains to be determined. This study is intended to explore the effect of S100A9 regulated TAMs and macrophage polarization in liver cancer progression. THP-1 cells were induced to differentiate into M1 and M2 macrophages, which were then cultured in liver cancer cell conditioned culture medium before the M1 and M2 macrophages were identified by measuring biomarkers using real-time polymerase chain reaction. The differential expressed genes in macrophages in Gene Expression Omnibus (GEO) databases were screened. S100A9 overexpression and knockdown plasmid were transfected into macrophages to determine the effect of S100A9 on M2 macrophage polarization of TAMs and on proliferation ability of liver cancer cells. The proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) abilities of liver cancer co-cultured with TAMs. M1 and M2 macrophages were successfully induced and liver cancer cell conditioned culture medium can increase polarization of macrophages into M2 macrophages, in which elevated expression of S100A9 was detected. Data in GEO database showed that tumor microenvironment (TME) upregulated S1000A9 expression. Suppression on S1000A9 can significantly suppress M2 macrophage polarization. TAM can provide the necessary microenvironment for liver cancer cells, HepG2 and MHCC97H by increasing cell proliferation, migration, and invasion ability, while suppression on S1000A9 can reverse this expression pattern. Suppression on S100A9 expression can regulate M2 macrophage polarization of TAMs to suppress the progression of liver cancer.

Pollution Characteristics and Risk Assessment of Soil Heavy Metals in the Areas Affected by the Mining of Metal-bearing Minerals in Southwest China.

Previous studies on the impact of the mining of metal-bearing minerals on surrounding soil mainly focused on single or a few areas. However, these studies' results cannot provide effective making-support for soil pollution control in large-scale areas, especially in cross-provincial scale. This study first collected 78 literature before 2020 on soil heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) affected by the mining of metal-bearing minerals in Southwest China. Then, the geo-accumulation index, ecological risk, and health risk were assessed based on the extracted heavy metal data. Results showed that As, Cd, Hg, and Pb should be selected as the preferentially controlled heavy metals; Yunnan and Guizhou Provinces should be selected as the preferentially concerned areas; children should be given priority attention. The results provided more effective decision support for reducing heavy metal pollution in the areas affected by the mining of metal-bearing minerals in Southwest China.

[Meta-analysis of the Effects of Metal Mining on Soil Heavy Metal Concentrations in Southwest China].

Metal mining is one of the main contributors of soil heavy metals. Previous studies examining the impact of metal mining on surrounding soil have mainly focused on one or a few metal mining areas. However, such studies cannot effectively inform the management of heavy metal pollution in soil at an inter-provincial scale. As part of this study, literature was collected on soil heavy metals (i.e., As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) affected by metal mining in regions of Southwest China (i.e., Yunnan Province, Sichuan Province, Guizhou Province, Chongqing Municipality, and Tibet Autonomous Region); Next, the impact of metal mining on the soil concentrations of these metals was quantified through meta-analysis, and the relationships between the selected factors (i.e., different sub-regions, metal minerals, and land-use types) and soil heavy metal concentrations were explored. Finally, the literature data was tested for publication bias. The results showed that metal mining in Southwest China has significantly increased the concentrations of heavy metals in topsoil. The different metals were ranked according to their weight effect sizes (ES+) in the following order Cd > Pb > Hg > Zn > As > Cu > Ni > Cr. Metal mining in both Sichuan and Yunnan led to higher effect sizes of soil Cd (ES+Sichuan=4.16, ES+Yunnan=3.20) and Pb (ES+Sichuan=3.47, ES+Yunnan=2.54) than those of the other heavy metals, while metal mining in Guizhou led to a higher effect size of soil Hg (ES+=2.80). The effect size of metal mining on soil heavy metals was higher in cultivated soil (ES+=1.42) than in forested soil (ES+=0.50). The mining of lead-zinc and tin significantly increased the concentrations of soil Cd, Pb, and Zn, and the mining of copper significantly increased the concentrations of soil Cu, Cd, and Pb. Of the investigated soil heavy metals in Southwest China, Pb and Zn showed slight potential publication biases (P<0.05). The above results can provide more effective information for the environmental protection of soil in metal mining areas of Southwest China.

Caveolin-1 Knockdown Decreases SMMC7721 Human Hepatocellular Carcinoma Cell Invasiveness by Inhibiting Vascular Endothelial Growth Factor-Induced Angiogenesis.

Background: Recently, several studies have demonstrated that caveolin-1 overexpression is involved in apoptosis resistance, angiogenesis, and invasiveness in hepatocellular carcinoma (HCC). However, the mechanisms underlying caveolin-1-mediated tumor progression remain unclear. Methodogy. Lentiviral vectors were used to construct caveolin-1 small interfering RNA- (siRNA-) expressing cells. Secreted VEGF levels in SMMC7721 cells were evaluated by enzyme-linked immunosorbent assay (ELISA). SMMC7721 cell proliferation, cycle, apoptosis, and invasiveness were detected by MTT, flow cytometry, Annexin V-FITC/PI, and invasion assay, respectively. Phospho-eNOS levels in human umbilical vein endothelial cells (HUVECs) cocultured with SMMC7721 cell supernatants were analyzed by Western blot. Capillary-like tubule formation assay was performed to analyze endothelial tubular structure formation in HUVECs treated with supernatants from caveolin-1 siRNA-expressing SMMC7721 cells. SMMC7721 implantation and growth in nude mice were observed. Angiogenesis in vivo was analyzed by immunohistochemical angiogenesis assay. Results: Caveolin-1 siRNA-expressing SMMC7721 cells secreted reduced levels of VEGF. Caveolin-1 RNAi also caused an inhibition of SMMC7721 cell proliferation and cell cycle progression that was accompanied by increased apoptosis. Supernatants from caveolin-1 siRNA-expressing SMMC7721 cells inhibited cell cycle progression and decreased phospho-eNOS levels in HUVECs. Endothelial tubular structure formation in HUVECs treated with supernatants from caveolin-1 siRNA-expressing SMMC7721 cells was considerably reduced. Caveolin-1 siRNA-expressing SMMC7721 cells also showed reduced tumorigenicity and angiogenesis induction in vivo. Conclusion: Our results reveal a novel mechanism, whereby caveolin-1 positively regulates human HCC cell invasiveness by coordinating VEGF-induced angiogenesis.

High adsorption capacity of Mg-Al-modified biochar for phosphate and its potential for phosphate interception in soil.

In this study, Mg and/or Al modified biochars (MABC1, MBC2, ABC3) prepared by co-precipitation were to explore their phosphate adsorption capacity from aqueous solution and the potential for soil phosphate interception. The results revealed that MABC composites contained more functional groups than MBC and showed a higher surface area than ABC. The surface of MABC contained dispersed MgAl2O4, Mg(OH)2, AlOOH and Al2O3 crystals that were associated with its enhanced maximum phosphate adsorption capacity (153.40 mg g-1). According to Langmuir model, the maximum adsorption capacity of MABC was 15.91, 1.85, and 93.54 times the capacity of MBC, ABC, and raw biochar (BC4), respectively. The addition of MABC in red soil could significantly slow down the release of soil phosphorus, and MABC also had a stronger phosphate interception capacity (59.89%) than other BCs. In summary, MABC exhibits superior phosphate adsorption and interception capacity, making it ideal for treatment and prevention of phosphorus-polluted water.

LncRNA-ZNF281 Interacts with miR-539 to Promote Hepatocellular Carcinoma Cell Invasion and Migration.

Background: LncRNA-ZNF281 suppresses glioma, whereas its role in hepatocellular carcinoma (HCC) is unclear. This study aimed to investigate the interaction between ZNF281 and miR-539 in HCC. Materials and Methods: This study included 66 HCC patients (40 men and 26 women; 36-68 years, 53.1 ± 6.2 years) who were selected from the 133 HCC cases admitted to The First Affiliated Hospital of Fujian Medical University from February 2011 to June 2014. Levels of ZNF281 and miR-539 expression in two types of tissues (HCC and nontumor) were measured by performing quantitative polymerase chain reaction (qPCR). Dual-luciferase assay was performed to analyze the interactions between miR-539 and ZNF281 in both SNU-475 and PLHC-1 cells. The effects of ZNF281 and miR-539 overexpression on the invasion and migration of HCC cells were analyzed by performing transwell assays. Results: The authors showed that ZNF281 was upregulated and miR-539 was downregulated in HCC tissues and were negatively correlated. High levels of ZNF281 and low levels of miR-539 predicted the poor survival of HCC patients. Overexpression analysis showed that ZNF281 and miR-539 overexpression led to the downregulation of each other. Transwell assays showed that ZNF281 overexpression led to enhanced and miR-539 overexpression led to suppressed HCC cell invasion and migration. In addition, miR-539 overexpression attenuated the effects of ZNF281 overexpression. Conclusions: Therefore, ZNF281 may interact with miR-539 to promote HCC cell invasion and migration.

Selenate Reduction and Selenium Enrichment of Tea by the Endophytic Herbaspirillum sp. Strain WT00C.

Herbaspirillum sp. WT00C is a tea-plant-specific endophytic bacterium. A genomic survey revealed an intact pathway for selenocompound metabolism in the genome of this bacterium. When it was cultured with sodium selenate, Herbaspirillum sp. WT00C was able to turn the culture medium to red. Electron microscopy and energy-dispersive X-ray spectroscopy confirmed that Herbaspirillum sp. WT00C reduced selenite (Se6+) to elemental selenium (Se0), and selenium nanoparticles (SeNPs) were secreted outside bacterial cells and grew increasingly larger to form Se-nanospheres and finally crystallized to form selenoflowers. Biochemical assays showed that selenospheres contained proteins but not carbohydrates or lipids. The improvement of selenium enrichment of tea plants by Herbaspirillum sp. WT00C was also tested. After Herbaspirillum sp. WT00C was inoculated into tea seedlings via needle injection and soaking tea-cutting methods, this endophytic bacterium markedly enhanced selenium enrichment of tea. When the tea seedlings inoculated by soaking tea-cutting mode were cultivated in the selenium-containing soils, selenium contents of tea leaves in three experimental groups were more than twofold compared to those of control groups. Our study demonstrates that the endophytic bacterium Herbaspirillum sp. WT00C has the ability to reduce selenate and improve selenium enrichment of tea.

A novel peptide/Fe3O4@SiO2-Au nanocomposite-based fluorescence biosensor for the highly selective and sensitive detection of prostate-specific antigen.

Highly selective and sensitive detection methods are very important for the early diagnosis of prostate-specific antigen (PSA). Here, we present a novel peptide/Fe3O4@SiO2-Au nanocomposite-based fluorescence biosensor for highly selective and sensitive detection of PSA. The biosensor was made by self-organizing 5-FAM labeled peptides onto the surface of magnetic Fe3O4@SiO2-Au nanocomposites (MNCPs), resulting in efficient quenching of the FAM fluorescence. The PSA specifically recognized and cleaved the 5-FAM-labeled peptides, leading to the fluorescence recovery. This is the first report of the MNCPs by in situ growth of Au nanoparticles (AuNPs) on the SiO2 encapsulated single Fe3O4 nanocubes. The MNCPs feature robust salt stability, and allow for effective fluorescence quenching and easy magnetic separation, which greatly decrease the background fluorescence. The peptide/MNCPs-based fluorescence biosensor measure a wide range of concentrations of PSA, from 1.0 × 10-12 to 1.0 × 10-9g/mL, with a limit of detection (LOD) of 3.0 × 10-13g/mL in both standard solutions and serum samples, demonstrating the great potential of this biosensor platform for use in clinical and biological assays.

Sleep deprivation accelerates the progression of alzheimer's disease by influencing Aß-related metabolism.

Sleep disorders have previously been connected with the neurodegenerative pathology of Alzheimer's disease (AD) due to the aggregation of ß-amyloid(Aß)peptides and tau proteinsinduced by sleep deprivation (SD). However, the underlying mechanisms remain unclear. Therefore, this study was performed to clarify how Aß-related metabolism is regulated after SD. Three-month-old Sprague-Dawley rats (250-300g) were randomly divided into 5 groups: two SD groups(i.e.,SD-2d and SD-4d), two platform control groups(i.e.,PC-2d and PC-4d) and a home cage control group (CC). For the two SD groups, themodified multiple platform method (MMPM) was used to induce SD.Our experiments confirmed that SD impaired cognitive function and increased the levels of Aß peptides, a hallmark of AD. Additionally, we found that SD significantly increasedthe levels of the ß-site amyloid precursor protein (APP)-cleaving enzyme 1(BACE1, ß-secretase), but had little impacton the levels of Aß-degradationenzymes.This resultmay be the main cause of the over-expression of Aß1-42 and Aß1-40. Our results suggested that SD accelerates the progression of AD bymodulating Aß-related metabolism. This findinghasimportant implications for the diagnosis and prevention of AD.

[Effects of N application and maize growth on N2O emission from soil].

With pot experiment and using static chamber-GC technique, this paper studied the effects of N application (150 and 300 mg x kg(-1) soil) and maize growth on N2O emission from soil. In maize-planted soil, the N2O emission rate increased with increasing N application rate, its peak appeared at seedling stage, and there was no significant correlation between N2O emission and air temperature. Contrarily, in bare soil, the peak of N2O emission rate occurred at the anaphase of the experiment, and there was a significant exponential correlation between N2O emission and air temperature. The total amount of N2O emission increased remarkably with increasing N application rate in both planted and bare soils. In comparing with bare soil, maize-planting reduced N2O emission by 92% and 87%, respectively at high and low N application rates, which suggested that maize-planting not only affected the seasonal variation and magnitude of N2O emission from soil, but also altered the relationship between air temperature and soil N2O emission.