Synergistic effects of α-Mangostin and sorafenib in hepatocellular carcinoma: New insights into α-mangostin cytotoxicity.

Sorafenib remains the standard first-line treatment for advanced hepatocellular carcinoma (HCC), although other clinical trials are currently underway for treatments that show better curative effects. However, some patients are not sensitive to sorafenib. α-Mangostin, extracted from the pericarp of the mangosteen, which is widely used as a traditional medicine, has anticancer and anti-proliferative properties in various types of cancers, including HCC. In the present study, we found that combining sorafenib and α-Mangostin could be synergistically toxic to HCC both in vitro and in vivo. We then demonstrated that the combination of sorafenib and α-Mangostin enhances the inhibition of cell proliferation in HCC cell lines. Combination therapy leads directly to apoptosis. In xenograft mouse models, the in vivo safety and effectivity was confirmed by a reduction in tumor size after combination treatment. RNA sequencing and protein testing showed that the expression of LRRC8A and RNF181 genes and mTOR and MAPK pathways may be associated with the synergistic effect of the two drugs. In conclusion, our results highlight the synergistic effect of the combination of sorafenib and α-Mangostin, which indicates a potential treatment for advanced HCC for patients that are not sensitive to sorafenib therapy.

Efficacy of Oxaliplatin/5-Fluorouracil/Capecitabine-Cetuximab Combination Therapy and Its Effects on K-Ras Mutations in Advanced Colorectal Cancer.

BACKGROUND The aim of this study was to perform an accurate exploration on the efficacy of oxaliplatin/5-fluorouracil/capecitabine-cetuximab combination therapy and its effects on K-Ras mutations in advanced colorectal cancer. MATERIAL AND METHODS Among 96 patients who suffered metastatic colorectal cancer without mutated K-Ras, 41 patients who were receiving treatment with oxaliplatin/5-fluorouracil/capecitabine and administered cetuximab as the initial treatment comprised the observation group; the remaining 55 patients receiving cetuximab as an alternative treatment comprised the control group. RESULTS The observation group experienced significantly higher objective response rates (ORRs), and disease control rates (DCRs), than the control group (P<0.05 for both). The median progression-free survival (PFS) rates of the observation group and the control groups were 11.2 months (95% confidence interval [CI]: 10.1-12.3 months) and 7.4 months (95% CI: 6.6-8.2 months). The median overall survival (OS) rates were 16.8 months (95% CI: 15.2-18.4 months) and 12.4 months (95% CI: 11.6-13.2 months), respectively. The observation group had significantly longer PFS and OS in comparison to the control group (P<0.05). The patients who underwent cetuximab treatment for ≥10 months had a slightly higher rate of K-Ras mutations than those treated with cetuximab for <10 months (9.1% versus 7.3%). CONCLUSIONS Oxaliplatin/5-fluorouracil/capecitabine plus cetuximab exhibited better efficacy as initial treatment than the alternative treatment; it was also highly safe. Unfortunately, some patients might develop K-Ras mutations after long duration of cetuximab treatment, suggesting that K-Ras mutations are correlated with tumor progression and depend on the duration or dose of cetuximab treatment.

The characteristics and algicidal mechanisms of cyanobactericidal bacteria, a review.

Cyanobacterial blooms are a worldwide problem, especially in freshwaters. As one of the most abundant co-existing organisms of algae, bacteria play critical roles in cyanobacteria growth, particularly the cyanobactericidal bacteria which can efficiently kill cyanobacteria. Recent years, cyanobactericidal bacteria are highly recognized as a method that could potentially block cyanobacterial blooms. Many studies have been conducted to assess their effects on the termination of cyanobacteria blooms and explore their cyanobactericidal mechanisms, e.g., attacking by cell to cell or releasing specific compounds, the physiological, metabolic, and transcriptional disturbance on cyanobacteria. In this review, the present state of research on cyanobactericidal bacteria for the bloom-causing cyanobacteria species is summarized. The challenges in applying cyanobactericidal bacteria in the control of natural cyanobacterial blooms are discussed.

Algicidal characterization and mechanism of Bacillus licheniformis Sp34 against Microcystis aeruginosa in Dianchi Lake.

Microcystis aeruginosa blooms are a worldwide serious environmental problem and bloom control with bacteria is promising. In this study, a Bacillus licheniformis strain Sp34 with potent algicidal and inhibitory effects on the microcystins synthesis against fast-growing M. aeruginosa was isolated from Dianchi Lake. Sp34 killed the bloom-causing algal strain M. aeruginosa DCM4 of Dianchi Lake with an initial Chlorophyll-a concentration of 2.0 mg/L at a cell density of no less than 1.35 × 105 CFU/ml. It can also efficiently kill some other harmful algal species, such as M. wesenbergii and Phormidium sp. The algicidal activity of Sp34 relied on the release of algicidal substances, which had good heat (-20°C to 121°C) and acid-base (pH 3-11) resistance. In addition, the high algicidal activity depended on the good growth of algae indicated by the significantly positive correlations between algal growth and algicidal ratio (p < .001). The algicidal effect of Sp34 involved causing oxidative stress, lipid peroxidation, and morphological injury of algal cells, along with DNA damage and dysfunction of DNA-repair function, weakening the photosynthesis system, and inhibiting microcystin synthesis. In general, Sp34 can kill fast-growing M. aeruginosa and inhibit algal microcystin synthesis efficiently, so, it is a promising biocontrol agent to mitigate cyanobacterial blooms.

Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma.

Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD-based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients.

Alanine aminotransferase to hemoglobin ratio is an indicator for disease progression for hepatocellular carcinoma patients receiving transcatheter arterial chemoembolization.

The prognosis of hepatocellular carcinoma (HCC) patients receiving transcatheter arterial chemoembolization (TACE) is far from being identified. The present study aimed to assess the role of blood cell counts, routine liver function tests, and alanine aminotransferase to hemoglobin ratio (AHR) in predicting the progression-free survival (PFS) of these patients. A total of 243 HCC patients receiving TACE were analyzed retrospectively. Cancer of the Liver Italian Program (CLIP) score system was indentified to be the best score system for this patient subgroup according to the Akaike information criterion (AIC) index and linear trend χ (2). Then, prognostic value of parameters was determined by integration into the CLIP score system. As a result, AHR was confirmed to be an independent predictor for the PFS of HCC patients receiving TACE (p = 0.001) with the other parameters failing to reach statistical significance. Moreover, AHR improved the performance of CLIP by adjusting into it, thus improving its discriminatory ability. AHR defined ≤0.4583 as low level and >0.4583 as high level. And, patients were also dichotomized into two groups accordingly. HCC patients receiving TACE with low AHR presented higher 1 year DCR (41.9 vs 18.1 %) compared with patients with high AHR levels. Furthermore, AHR level was associated with prognostic factors such as lower ALP, total bilirubin, and portal vein thrombosis. In summary, the present study firstly indentified AHR as an independent prognostic factor in HCC patients receiving TACE. The subgroup of HCC patients with lower AHR presented preferable disease control and were the idealistic candidates for TACE.

Platelet-to-lymphocyte ratio acts as a prognostic factor for patients with advanced hepatocellular carcinoma.

The platelet count, as an inflammation marker, is involved in the progress of tumor invasion. However, the prognostic value of platelet counts and the platelet-to-lymphocyte ratio (PLR) has not been investigated in patients with advanced hepatocellular carcinoma (HCC). This study aimed to determine the prognostic value of platelet counts and PLR in HCC patients. A total of 243 ethnic Chinese advanced HCC patients from two major hospitals, not receiving systemic sorafenib, were analyzed retrospectively. The prognostic value of differential blood cell counts and PLR for overall survival (OS) was determined by integrating the Cancer of the Liver Italian Program (CLIP) score system and model for end-stage liver disease by using a stepwise model of multivariate Cox regression. The Kaplan-Meier method and receiver operating characteristic (ROC) curves were utilized accordingly. PLR was confirmed to be an independent predictor for OS (p < 0.01), while the remaining parameters had no predictive value. Then, advanced HCC patients were dichotomized into two groups based on the PLR value (≤111.23 or >111.23), according to ROC analysis. Patients with a high PLR had a lower 3-month survival rate (37.6 vs. 57.6%) compared with patients with a low PLR. PLR was associated with aggressive malignant behavior, characterized by distant metastasis and portal vein thrombosis. Additionally, PLR was not associated with the CLIP score and Child-Pugh grade. PLR was identified as an independent prognostic factor for advanced HCC patients not receiving systemic sorafenib; the predictive ability of PLR partially relies on its association with the aggressive nature of HCC.

Autophagic LC3B overexpression correlates with malignant progression and predicts a poor prognosis in hepatocellular carcinoma.

Autophagy is a process that involves lysosomal degradations of cellular organelles and closely related to tumor occurrence and progression. However, its importance in hepatocellular carcinoma (HCC) was still controversial. Therefore, this study is aimed to address the clinicopathologic effect of microtubule-associated protein 1 light chain 3B (LC3B) and Beclin-1, as autophagic markers, in HCC patients. Tissue microarray-based immunohistochemistry was used to examine the expression of LC3B and another autophagy key regulator (Beclin-1) in 156 operable HCC patients. Kaplan-Meier analysis, chi-square test, and Spearman's correlation analysis were used to analyze correlation of LC3B and Beclin-1 and their influence on clinical characteristics and prognosis. We found that the expression level of LC3B was significantly associated with vascular invasion (P = 0.008), lymph node metastasis (P < 0.001), and Beclin-1 expression level (P < 0.001). However, LC3B was not related to other clinicopathological features, including hepatitis B virus infection, liver cirrhosis, tumor number, tumor size, pathology grade, and tumor-node-metastasis (TNM) stage. Besides, correlation between the expression of Beclin-1 and clinicopathological features were not identified. Survival analysis showed that patients with high LC3B expression had a poorer 5-year overall survival (OS) rate than those with low LC3B expression (high vs. low: 79.5 % vs. 20.5 %, P = 0.026). And high LC3B expression tended to be related with shorter progression-free survival (PFS) (P = 0.074), whereas the expression level of Beclin-1 did not show statistically significant association with OS or PFS. Further multivariate analysis revealed that lymph node metastasis (P = 0.047) and LC3B expression level (P = 0.047) were independent factors to predict the prognosis of OS in all patients. Our study demonstrated that high expression of LC3B, correlated with vascular invasion and lymph node metastasis, might be a novel prognostic biomarker and would be a potential therapy target for HCC, especially in operable patients.

Neutrophil-to-lymphocyte ratio acts as a prognostic factor for patients with advanced hepatocellular carcinoma.

Few studies investigated the prognosis of patients with advanced hepatocellular carcinoma (aHCC). This study was aimed to determine the prognostic value of differential blood cell counts including blood white cells, neutrophil, lymphocyte, neutrophil-lymphocyte ratio (NLR), and platelet in patients with aHCC. A total of 205 ethnic Chinese aHCC patients receiving non-systematic sorafenib were analyzed retrospectively. The prognostic value of differential blood cell counts and NLR for overall survival (OS) was determined by integration into Cancer of the Liver Italian Program (CLIP) score system using backward elimination model of multivariate Cox regression. As a result, NLR was confirmed to be an independent predictor for OS (p = 0.001) with the rest parameters presented negative results. Then, aHCC patients were dichotomized into two groups according to NLR values ≤ 2.43 or >2.43. Patients with low NLR presented lower CLIP score and higher 6-month survival rate (56.1 vs 25.9%) compared with patients with high NLR level. Besides, low NLR level was associated with favorable prognostic factors such as lower α-fetoprotein, alkaline phosphatase, and total bilirubin, as well as decreased incidence of ascites, portal vein thrombosis, and metastasis. Besides, low NLR level was associated less white cells and neutrophil granulocytes, as well as more lymphocyte. In summary, the present study firstly indentified NLR as an independent prognostic factor in aHCC patients receiving no systematic sorafenib.

Higher trophic levels and species with poorer dispersal traits are more susceptible to habitat loss on island fragments.

Ongoing habitat loss and fragmentation caused by human activities represent one of the greatest causes of biodiversity loss. However, the effects of habitat loss and fragmentation are not felt equally among species. Here, we examined how habitat loss influenced the diversity and abundance of species from different trophic levels, with different traits, by taking advantage of an inadvertent experiment that created habitat islands from a once continuous forest via the creation of the Thousand Island Lake, a large reservoir in China. On 28 of these islands with more than a 9000-fold difference in their area (0.12-1154 ha), we sampled plants, herbivorous insects, and predatory insects using effort-controlled sampling and analyses. This allowed us to discern whether any observed differences in species diversity were due to passive sampling alone or to demographic effects that disproportionately influenced some species relative to others. We found that while most metrics of sampling effort-controlled diversity increased with island area, the strength of the effect was exacerbated for species in higher trophic levels. When we more explicitly examined differences in species composition among islands, we found that the pairwise difference in species composition among islands was dominated by species turnover but that nestedness increased with differences in island area, indicating that some species are more likely to be absent from smaller islands. Furthermore, by examining trends of several dispersal-related traits of species, we found that species with lower dispersal propensity tended to be those that were lost from smaller islands, which was observed for herbivorous and predatory insects. Our results emphasize the importance of incorporating within-patch demographic effects, as well as the taxa and traits of species when understanding the influence of habitat loss on biodiversity.

From imaging to clinical outcome: dual-region CT radiomics predicting FOXM1 expression and prognosis in hepatocellular carcinoma.

Background: Liver cancer, especially hepatocellular carcinoma (HCC), remains a significant global health challenge. Traditional prognostic indicators for HCC often fall short in providing comprehensive insights for individualized treatment. The integration of genomics and radiomics offers a promising avenue for enhancing the precision of HCC diagnosis and prognosis. Methods: From the Cancer Genome Atlas (TCGA) database, we categorized mRNA of HCC patients by Forkhead Box M1 (FOXM1) expression and performed univariate and multivariate studies to pinpoint autonomous HCC risk factors. We deployed subgroup, correlation, and interaction analyses to probe FOXM1's link with clinicopathological elements. The connection between FOXM1 and immune cells was evaluated using the CIBERSORTx database. The functions of FOXM1 were investigated through analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). After filtering through TCGA and the Cancer Imaging Archive (TCIA) database, we employed dual-region computed tomography (CT) radiomics technology to noninvasively predict the mRNA expression of FOXM1 in HCC tissues. Radiomic features were extracted from both tumoral and peritumoral regions, and a radiomics score (RS) was derived. The performance and robustness of the constructed models were evaluated using 10-fold cross-validation. A radiomics nomogram was developed by incorporating RS and clinical variables from the TCGA database. The models' discriminative abilities were assessed using metrics such as the area under the curve (AUC) of the receiver operating characteristic curves (ROC) and precision-recall (PR) curves. Results: Our findings emphasized the overexpression of FOXM1 as a determinant of poor prognosis in HCC and illustrated its impact on immune cell infiltration. After selecting arterial phase CT, we chose 7 whole-tumor features and 3 features covering both the tumor and its surroundings to create WT and WP models for FOXM1 prediction. The WT model showed strong predictive capabilities for FOXM1 expression by PR curve. Conversely, the WP model did not demonstrate the good predictive ability. In our study, the radiomics score (RS) was derived from whole-tumor regions on CT images. The RS was significantly associated with FOXM1 expression, with an AUC of 0.918 in the training cohort and 0.837 in the validation cohort. Furthermore, the RS was correlated with oxidative stress genes and was integrated with clinical variables to develop a nomogram, which demonstrated good calibration and discrimination in predicting 12-, 36-, and 60-month survival probabilities. Additionally, bioinformatics analysis revealed FOXM1's potential role in shaping the immune microenvironment, with its expression linked to immune cell infiltration. Conclusion: This study highlights the potential of integrating FOXM1 expression and radiomics in understanding HCC's complexity. Our approach offers a new perspective in utilizing radiomics for non-invasive tumor characterization and suggests its potential in providing insights into molecular profiles. Further research is needed to validate these findings and explore their clinical implications in HCC management.

Fatigue Fracture Analysis on 2524 Aluminum Alloy with the Influence of Creep-Aging Forming Processes.

The different creep-aging forming processes of 2524 aluminum alloy were taken as the research object, and the effects of creep-aging temperature and creep stress on the fatigue-crack propagation properties of the alloy were studied. The research results showed the following under the same sintering time of 9 h, at creep-aging temperatures of 100 °C, 130 °C, 160 °C, and 180 °C, respectively, with an increase in creep-aging temperature: the fatigue-crack propagation rate was promoted, the spacing of fatigue striations increased, and the sizes of dimples decreased while the number was enlarged; this proves that the fatigue property of the alloy was weakened. Compared with the specimens with creep deformation radii of 1000 mm and 1500 mm, the creep deformation stress was the smallest when the forming radius was 1800 mm, with a higher threshold value of fatigue-crack growth in the near-threshold region of fatigue-crack propagation (ΔK ≤ 8 MPa·m1/2). Under the same fatigue cycle, the specimens under the action of larger creep stress endured a longer fatigue stable-propagation time and a faster fracture speed. Comparing the effect of creep-aging temperature and creep stress, the creep-aging temperature plays a dominant role in the fatigue-crack propagation of creep-aged 2524 aluminum alloy.

Improving the immunomodulatory function of mesenchymal stem cells by defined chemical approach.

Mesenchymal stem cell (MSC) is a potential therapeutic material that has self-renewal, multilineage differentiation, and immunomodulation properties. However, the biological function of MSCs may decline due to the influence of donor differences and the in vitro expansion environment, which hinders the advancement of MSC-based clinical therapy. Here, we investigated a method for improving the immunomodulatory function of MSCs with the help of small-molecule compounds, A-83-01, CHIR99021, and Y27632 (ACY). The results showed that small-molecule induced MSCs (SM-MSCs) could enhance their immunosuppressive effects on T cells and macrophages. In vivo studies showed that, in contrast to control MSCs (Ctrl-MSCs), SM-MSCs could inhibit the inflammatory response in mouse models of delayed hypersensitivity and acute peritonitis more effectively. In addition, SM-MSCs showed the stronger ability to inhibit the infiltration of pro-inflammatory T cells and macrophages. Thus, small-molecule compounds ACY could better promote the immunomodulatory effect of MSCs, indicating it could be a potential improving method in MSC culture.

Algicidal effect of tryptoline against Microcystis aeruginosa: Excess reactive oxygen species production mediated by photosynthesis.

Cyanobacterial blooms significantly decrease water quality and can damage ecosystems and, as such, require efficient control methods. Algicidal bacteria and their associated substances are promising tools for controlling cyanobacterial blooms; however, their specific algicidal mechanisms remain unclear. Therefore, the current study sought to investigate the algicidal mechanism of tryptoline (1,2,3,4-tetrahydro-9 h-pyrido[3,4-b]indole) against Microcystis aeruginosa, with a specific focus on the contribution made by reactive oxygen species (ROS), the underlying mechanisms of ROS increase, as well as the photosystem response. Results show that the algicidal ratio of tryptoline significantly and positively correlates with algal ROS. Moreover, 93.79% of the algicidal ratio variation is attributed to ROS in the tryptoline group, while only 47.75% can be attributed to ROS in the tryptoline + N-acetyl-L-cysteine (NAC) group, where ROS are partially scavenged by NAC. In the presence of tryptoline, algicidal effect and ROS levels were significantly enhanced in the presence of light as compared to those in the dark (P < 0.001). Hence, the increase in ROS production attributed to tryptoline is primarily affected by the presence of light and photosynthesis. Additionally, tryptoline significantly reduces Fv/Fm, PIABS, ETo/RC, and the expression of psaB and psbA genes related to photosynthesis, while increasing Vj and DIo/RC (P < 0.05). These results suggest that tryptoline hinders algal photosynthesis by significantly decreasing photosynthetic efficiency and carbon assimilation, inhibiting photochemical electron transfer, and increasing closed reaction centers and energy loss. Moreover, following partial blockade of the photosynthetic electron transfer from QA to QB by diuron (3-(3-4-dichlorophenyl)-1,1-dimethylurea), the ROS of algae exposed to tryptoline is significantly decreased. Thus, tryptoline inhibits electron transfer downstream of QA, which increase the number of escaping electron and thereby increase ROS generation. Collectively, this study describes the algicidal mechanism of tryptoline against M. aeruginosa and highlights the critical factors associated with induction of algicidal activity.

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It is of great significance to understand the pattern of soil respiration rate in fragmented forests for further revealing terrestrial ecosystem carbon cycling. With different habitats (island vs. mainland, island edge vs. island interior) of the artificial land-bridge island system in Thousand Island Lake (TIL) region as the objects, we analyzed the seasonal dynamics of soil respiration rate and its relationships with soil physicochemical factors. The results showed that: 1) Soil respiration rates varied significantly across different seasons, with an order of summer (3.74 µmol·m-2·s-1) > autumn (2.30 µmol·m-2·s-1) > spring (1.82 µmol·m-2·s-1) > winter (1.40 µmol·m-2·s-1). 2) Forest fragmentation had significant effects on soil respiration rate, with soil respiration rate of island (2.37 µmol·m-2·s-1) being significantly higher than that of mainland (2.08 µmol·m-2·s-1) and the soil respiration rate of island edge (2.46 µmol·m-2·s-1) being significantly higher than that of island interior (2.03 µmol·m-2·s-1). 3) Soil temperature significantly promoted soil respiration rate, explaining 56.1% of the total variation. 4) There was a significant positive correlation between soil respiration rate and soil total carbon, ammo-nium nitrogen content, and vegetation coverage. The soil total carbon and ammonium nitrogen content of island edge were significantly higher than those of island interior. In all, forest fragmentation promoted soil respiration rate, with soil physicochemical factors as the drivers for its variation.

Understanding global and regional patterns of termite diversity and regional functional traits.

Our understanding of broad-scale biodiversity and functional trait patterns is largely based on plants, and relatively little information is available on soil arthropods. Here, we investigated the distribution of termite diversity globally and morphological traits and diversity across China. Our analyses showed increasing termite species richness with decreasing latitude at both the globally, and within-China. In addition, we detected obvious latitudinal trends in the mean community value of termite morphological traits on average, with body size and leg length decreasing with increasing latitude. Furthermore, temperature, NDVI and water variables were the most important drivers controlling the variation in termite richness, and temperature and soil properties were key drivers of the geographic distribution of termite morphological traits. Our global termite richness map is one of the first high resolution maps for any arthropod group and especially given the functional importance of termites, our work provides a useful baseline for further ecological analysis.

PROZ Associated with Sorafenib Sensitivity May Serve as a Potential Target to Enhance the Efficacy of Combined Immunotherapy for Hepatocellular Carcinoma.

Targeted combined immunotherapy has significantly improved the prognosis of patients with advanced hepatocellular carcinoma and has now become the primary treatment for advanced hepatocellular carcinoma. However, some patients still have poor efficacy or are resistant to treatment. The further exploration of molecular markers related to efficacy or finding molecular targets to increase efficacy is an urgent problem that needs to be resolved. In this research, we found that PROZ was a gene related to KDR expression that had significantly low expression in cancer tissue by analyzing the differential genes of cancer tissue and adjacent tissue and the intersection of KDR-related genes in hepatocellular carcinoma. The correlation analysis of clinical data showed that the low expression of PROZ was significantly correlated with the poor prognosis of hepatocellular carcinoma, and further studies found that PROZ was closely related to the expression of p-ERK and VEGFR2 in hepatocellular carcinoma. In addition, intracellular detection also showed that the expression of p-ERK increased and VEGFR2 expression decreased after PROZ interference, and PROZ downregulation with increased p-ERK and decreased VEGFR2 was also detected in sorafenib-resistant strains. At the same time, our analysis found that PROZ was negatively correlated with genes related to immunotherapy efficacy such as CD8A, CD274 and GZMA, and was also negatively correlated with T-cell infiltration in tumor tissue. Conclusion: PROZ is a gene related to the prognosis of hepatocellular carcinoma and it is closely related to the efficacy of sorafenib and immunotherapy. It may serve as a potential molecular target to improve the efficacy of targeted combined immunotherapy.

Evidence of nutrient translocation in response to smoke exposure by the East African ant acacia, Vachellia drepanolobium.

Fire is a major selective force on arid grassland communities, favoring traits such as the smoke-induced seed germination response seen in a wide variety of plant species. However, little is known about the relevance of smoke as a cue for plants beyond the seedling stage.We exposed a fire-adapted savanna tree, Vachellia (=Acacia) drepanolobium, to smoke and compared nutrient concentrations in leaf and root tissues to unexposed controls. Experiments were performed on three age cohorts: 2-year-old, 9-month-old, and 3-month-old plants.For the 2-year-old plants exposed to smoke, carbon and nitrogen concentrations were lower in the leaves and higher in the roots than controls. Less pronounced trends were found for boron and magnesium.In contrast, smoke-exposed 3-month-old plants had lower root nitrogen concentrations than controls. No significant differences were found in the 9-month-old plants, and no significant shifts in other nutrient concentrations were observed between plant tissues for any of the three age cohorts. Synthesis: Our findings are consistent with smoke-induced translocation of nutrients from leaves to roots in 2-year-old V. drepanolobium. This could represent a novel form of fire adaptation, with variation over the course of plant development. The translocation differences between age cohorts highlight the need to investigate smoke response in older plants of other species. Accounting for this adaptation could better inform our understanding of savanna community structure and nutrient flows under fire regimes altered by anthropogenic land use and climate change.

MicroRNA-126 Inhibit Viability of Colorectal Cancer Cell by Repressing mTOR Induced Apoptosis and Autophagy.

OBJECTIVE: Colorectal cancer (CRC) is a fatal disease, and tumor development is a complex cellular event involving a multistep cascade process involving proliferation, invasion, and migration. In recent years, it has been shown that microRNA-126 (miR-126) plays a key role in the tumorigenesis of CRC, but further studies are required to investigate the regulatory mechanisms through which this miRNA affects cell viability, autophagy, and apoptosis in CRC. We aimed to study the effect of miR-126 in gene regulation in CRC HCT116 cells. METHODS: CRC biopsy samples and normal colorectal tissue samples were used for miRNA profiling. Real-time quantitative PCR and WB were utilized to detect RNA and protein levels. MTT and colony formation assays were performed to examine cell viability. Furthermore, an immunofluorescence assay and Annexin V/PI flow cytometry were performed to detect autophagy and apoptosis, respectively. RESULTS: The expression of miR-126 was downregulated in CRC biopsies and cell lines compared with that in normal cells and tissues. The upregulation of miR-126 resulted in impaired viability and growth of CRC cells. Furthermore, with the overexpression of miR-126, cell autophagy was increased, as evidenced by LC3-I/II transformation and p62 degradation. Meanwhile, apoptosis induction was also observed because of the increased miR-126 levels. The autophagy inhibitor Bafilomycin A1 (BafA1) repressed both autophagy and apoptosis, indicating that miR-126 induced autophagy was responsible for the induction of apoptosis. A dual-luciferase reporter assay (DLRA) and bioinformatics prediction revealed that miR-126 silenced the mTOR gene by targeting the 3'-UTR. mTOR mRNA levels in CRC biopsy tissues and cell lines were upregulated to a greater extent than that in normal cells and tissues. Furthermore, HCT116 cells transfected with an miR-126 mimic showed a decreased expression of mTOR. In addition, the overexpression of mTOR counteracted miR-126 on autophagy and apoptosis. CONCLUSION: Our study demonstrated that miR-126-induced can regulate the activity of CRC cells via autophagy and apoptosis and suggested a new mechanism of miR-126-mTOR interaction in CRC pathogenesis.