HKDC1 enhances the proliferation, migration and glycolysis of pancreatic adenocarcinoma and is linked to immune infiltration.

Background: Understanding the molecular mechanisms of pancreatic adenocarcinoma (PAAD) development is vital for treating this disease, as the current prognosis and treatment options are highly discouraging. Objective: This study aimed to examine the involvement of Hexokinase Domain Containing 1 (HKDC1) in the progression of PAAD. Methods: The study utilized bioinformatics techniques to evaluate the relationship between the expression of HKDC1 and clinical characteristics. In vitro experiments were conducted to investigate the molecular mechanisms and biological functions of HKDC1 in PAAD. Results: The findings of this research indicate that the expression of HKDC1 was increased in various types of human cancers, and a significant correlation was observed between elevated HKDC1 expression in PAAD and unfavorable prognosis. According to the findings from univariate and multivariate Cox regression analyses, HKDC1 could potentially serve as a standalone prognostic indicator for individuals diagnosed with PAAD. After performing calculations, we determined that the HKDC1 high-expression group exhibited lower immunologic score and higher ESTIMATE score, indicating a difference in immune infiltration score. In order to validate the expression of HKDC1 in PAAD cell lines, we analyzed the PAAD cell lines through qPCR and protein blotting. The expression of HKDC1 in human PAAD tissues was also detected by western blotting. Additionally, we explored the involvement of HKDC1 in PAAD by conducting experiments such as colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, and wound healing assays. In our study, we discovered that disruption of HKDC1 expression in PAAD cell types resulted in a decrease in cell growth rate and inhibited cell movement and invasion. Conclusion: To conclude, our findings indicate that HKDC1 has a significant impact on the tumor microenvironment (TME) of PAAD and could potentially be a promising target for PAAD treatment, offering fresh perspectives on the management of PAAD.

Unveiling the oncogenic role of CLDN11-secreting fibroblasts in gastric cancer peritoneal metastasis through single-cell sequencing and experimental approaches.

BACKGROUND: Fibroblasts are necessary to the progression of cancer. However, the role of fibroblasts in peritoneal metastasis (PM) of gastric cancer (GC) remains elusive. In this study, we would explore the role of fibroblasts mediated cell interaction in PM of GC. METHODS: Single-cell sequencing data from public database GSE183904 was used to explore the specific fibroblast cluster. Fibroblasts were extracted from PM and GC tissues. The expression level of CXCR7 was verified by western blot, immunohistochemistry. The role of CLDN11 was investigate through in vitro and in vivo study. Multiple immunohistochemistry was used to characterize the tumor microenvironment. RESULTS: CXCR7-positive fibroblasts were significantly enriched in PM of GC. CXCR7 could promote the expression of CLDN11 through activation of the AKT pathway in fibroblasts. Fibroblasts promote the GC proliferation and peritoneal metastasis by secreting CLDN11 in vitro and in vivo. Furthermore, it was revealed that CXCR7-positive fibroblasts were significantly associated with M2-type macrophages infiltration in tissues. CONCLUSION: CXCR7-positive fibroblasts play an essential role in PM of GC via CLDN11. Therapy targeting CXCR7-positive fibroblasts or CLDN11 may be helpful in the treatment of GC with PM.

N6-methyladenosine-modified MIB1 promotes stemness properties and peritoneal metastasis of gastric cancer cells by ubiquitinating DDX3X.

BACKGROUND: Peritoneal metastasis (PM), one of the most typical forms of metastasis in advanced gastric cancer (GC), indicates a poor prognosis. Exploring the potential molecular mechanism of PM is urgently necessary, as it has not been well studied. E3 ubiquitin ligase has been widely established to exert a biological function in various cancers, but its mechanism of action in GC with PM remains unknown. METHODS: The effect of MIB1 on PM of GC was confirmed in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrometry demonstrated the association between MIB1 and DDX3X. Western blot, flow cytometry and immunofluorescence determined that DDX3X was ubiquitylated by MIB1 and promoted stemness. We further confirmed that METTL3 promoted the up-regulation of MIB1 by RNA immunoprecipitation (RIP), luciferase reporter assay and other experiments. RESULTS: We observed that the E3 ubiquitin ligase Mind bomb 1 (MIB1) was highly expressed in PMs, and patients with PM with high MIB1 expression showed a worse prognosis than those with low MIB1 expression. Mechanistically, our study demonstrated that the E3 ubiquitin ligase MIB1 promoted epithelial-mesenchymal transition (EMT) progression and stemness in GC cells by degrading DDX3X. In addition, METTL3 mediated m6A modification to stabilize MIB1, which required the m6A reader IGF2BP2. CONCLUSIONS: Our study elucidated the specific molecular mechanism by which MIB1 promotes PM of GC, and suggested that targeting the METTL3-MIB1-DDX3X axis may be a promising therapeutic strategy for GC with PM.

ACLY promotes gastric tumorigenesis and accelerates peritoneal metastasis of gastric cancer regulated by HIF-1A.

Mounting evidence indicates the potential involvement of ATP-citrate lyase (ACLY) in the modulation of various cancer types. Nevertheless, the precise biological significance of ACLY in gastric cancer (GC) remains elusive. This study sought to elucidate the biological function of ACLY and uncover its influence on peritoneal metastasis in GC. The expression of ACLY was assessed using both real-time quantitative PCR and western blot techniques. To investigate the impact of ACLY on the proliferation of gastric cancer (GC) cells, colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed. The migratory and invasive abilities of GC were evaluated using wound healing and transwell assays. Additionally, a bioinformatics analysis was employed to predict the correlation between ACLY and HIF-1A. This interaction was subsequently confirmed through a chromatin immunoprecipitation (ChIP) assay. ACLY exhibited upregulation in gastric cancer (GC) as well as in peritoneal metastasis. Its overexpression was found to facilitate the proliferation and metastasis of GC cells in both in vitro and in vivo experiments. Moreover, ACLY was observed to play a role in promoting angiogenesis and epithelial-mesenchymal transition (EMT). Notably, under hypoxic conditions, HIF-1A levels were elevated, thereby acting as a transcription factor to upregulate ACLY expression. Under the regulatory influence of HIF-1A, ACLY exerts a significant impact on the progression of gastric cancer, thereby facilitating peritoneal metastasis.

Peritoneal high-fat environment promotes peritoneal metastasis of gastric cancer cells through activation of NSUN2-mediated ORAI2 m5C modification.

Peritoneal metastasis (PM) is an important metastatic modality of gastric cancer (GC).It is associated with poor prognosis. The underlying molecular mechanism of PM remains elusive. 5-Methylcytosine (m5C), a posttranscriptional RNA modification, involves in the progression of many tumors. However, its role in GC peritoneal metastasis remains unclear. In our study, transcriptome results suggested that NSUN2 expression was significantly upregulated in PM. And patients with high NSUN2 expression of PM predicted a worse prognosis. Mechanistically, NSUN2 regulates ORAI2 mRNA stability by m5C modification, thereby promoting ORAI2 expression and further promoting peritoneal metastasis and colonization of GC. YBX1 acts as a "reader" by binding to the ORAI2 m5C modification site. Following the uptake of fatty acids from omental adipocytes by GC cells, the transcription factor E2F1 was upregulated, which further promoted the expression of NSUN2 through cis-element. Briefly, these results revealed that peritoneal adipocytes provide fatty acid for GC cells, thus contributing to the elevation of E2F1 and NSUN2 through AMPK pathway, and upregulated NSUN2 activates the key gene ORAI2 through m5C modification, thereby promoting peritoneal metastasis and colonization of gastric cancer.

Contribution of agricultural land conversion to global GHG emissions: A meta-analysis.

Greenhouse gases (GHG) have extensive environmental effects by trapping heat and causing climate change and air pollution. Land plays a key role in the global cycles of GHG (i.e., carbon dioxide (CO2), methane (CH4), and nitrogen oxide (N2O)), and land use change (LUC) can lead to the release of such gases into the atmosphere or the removal of them from the atmosphere. One of the most common forms of LUC is agricultural land conversion (ALC) where agricultural lands are converted for other uses. This study aimed to review 51 original papers from 1990 to 2020 that investigate the contribution of ALC to GHG emissions from a spatiotemporal perspective using a meta-analysis method. The results of spatiotemporal effects on GHG emissions showed that the effects were significant. The emissions were affected by different continent regions representing the spatial effects. The most significant spatial effect was relevant to African and Asian countries. In addition, the quadratic relationship between ALC and GHG emissions had the highest significant coefficients, showing an upward concave curve. Therefore, increasing ALC to more than 8 % of available land led to increasing GHG emissions during the economic development process. The implications of the current study are important for policymakers from two perspectives. First, to achieve sustainable economic development, policymaking should prevent the conversion of more than 90 % of agricultural land to other uses based on the turning point of the second model. Second, policies to control global GHG emissions should take into account spatial effects (e.g., continental Africa and Asia), which show the highest contribution to GHG emissions.

Visible-light-responsive reduced graphene oxide/g-C3N4/TiO2 composite nanocoating for photoelectric stimulation of neuronal and osteoblastic differentiation.

Restoration of nerve supply in newly formed bone is critical for bone defect repair. However, nerve regeneration is often overlooked when designing bone repair biomaterials. In this study, employing graphitic carbon nitride (g-C3N4) as a visible-light-driven photocatalyst and reduced graphene oxide (rGO) as a conductive interface, an rGO/g-C3N4/TiO2 (rGO/CN/TO) ternary nanocoating with photoelectric conversion ability was fabricated on a Ti-based orthopedic implant for photoelectric stimulation of both bone and nerve repair. Compared with g-C3N4/TiO2 (CN/TO) and TiO2 nanocoatings, the ternary nanocoating exhibited stronger visible-light absorption as well as higher transient photocurrent density and open circuit potential under blue LED exposure. The improved photo-electrochemical properties of the ternary nanocoating were attributed to the enhanced separation of photogenerated carriers at the heterointerface. For the tested nanocoatings, introducing blue LED light irradiation enhanced MC3T3-E1 osteoblastic differentiation and neurite outgrowth of PC12 cells. Among them, the rGO/CN/TO nanocoating exerted the greatest enhancement. In a coculture system, PC12 cells on the ternary nanocoating released a higher amount of neurotransmitter calcitonin gene-related peptide (CGRP) under light irradiation, which in turn significantly enhanced osteoblastic differentiation. The results may provide a prospective approach for targeting nerve regeneration to stimulate osteogenesis when designing bone repair biomaterials.

Zn-doped MnO2 nanocoating with enhanced catalase-mimetic activity and cytocompatibility protects pre-osteoblasts against H2O2-induced oxidative stress.

Therapeutic application in prevention and treatment of bone diseases, particularly osteoporosis, has recently started to emerge for manganese dioxide (MnO2) nanoparticles and nanocoatings whereby their antioxidant catalase-mimetic property can be exploited to control oxidative stress by reducing the amount of H2O2. Doping is an efficient method to enhance the catalase-mimetic activity of MnO2, which can potentially ameliorate osteogenesis under oxidative stress. Herein, Zn2+ doped MnO2 (Zn-MnO2) nanocoating was fabricated on orthopedic titanium implant by a facile UV-photolysis reaction. The Zn-MnO2 nanocoating showed better cytocompatibility than the MnO2 nanocoating, as indicated by enhanced cell proliferation, differentiation and mineralization of MC3T3-E1 pre-osteoblasts. This was probably due to the increased surface hydrophilicity as well as the combination effect of released Zn2+ and Mn2+ from the Zn-MnO2 nanocoating. Importantly, the Zn-MnO2 nanocoating with enhanced catalase-like activity exerted greater effects to suppress the intracellular oxidation products generation and prevent the depletion of dismutase superoxide levels under H2O2-induced oxidative stress, which in turn protected MC3T3-E1 pre-osteoblast functions. Overall, surface modification of titanium implants with the Zn-MnO2 nanocoating could be utilized to ameliorate oxidative stress-inhibited osteogenesis.

An efficient method to improve the production of methane from anaerobic digestion of waste activated sludge.

Methane production from waste activated sludge (WAS) anaerobic digestion is always low due to slow hydrolysis rate and inappropriate ratio of carbon to nitrogen (C/N). In this work, a novel approach, i.e., co-digestion of WAS and tobacco waste (TW) using ozone pretreatment, to greatly enhance the production of methane is reported. Experimental results showed the optimal C/N and ozone dosage for methane production was 24:1 and 90 mg/g suspended solids, and the corresponding methane production was 203.6 mL/g volatile suspended solids, which was 1.3-fold that in mono-WAS digestion. Further investigation showed the co-digestion of WAS and TW was beneficial to the consumptions of protein and cellulose; also, the presence of ozone enhanced the disruption of organic substrates and production of short chain fatty acids, which provided sufficient digestion substrates for methane generation. Analysis of microbial community structure suggested that members of the phyla Bacteroidetes and Firmicutes were the dominant species when ozone pretreatment was applied. The findings obtained in this work might be of great importance for the treatment of WAS and TW.

How Does the Concentration of Determinants Affect Industrial Innovation Performance? - An Empirical Analysis of 23 Chinese Industrial Sectors.

The agglomeration of innovation determinants has a significant influence on the innovation performance of industries and enterprises. Such an effect has received less attention in empirical research studies. This study involves a survey of the agglomeration effect of two important innovation determinants, R&D investment and R&D personnel, and its influence on innovation performance from the perspective of the industrial level. We analysed the agglomeration features based on the panel data of 23 Chinese industrial sectors from 2001~2013. An interpretation model is proposed to examine the agglomeration effect on innovation performance for 4 industrial groups: state-owned enterprises, individual enterprises, foreign-owned enterprises and enterprises as a whole. We found two main results. First, the agglomeration of determinants has a clear positive effect on the innovation performance of all 4 groups but affects individual enterprises more significantly, followed by state-owned and foreign-owned enterprises. Second, the state-owned enterprises show a much higher concentration of R&D investment and R&D personnel than other groups. However, the induced innovation efficiency in the state-owned enterprises is worse than in the individual enterprises. The advantage of resources and capital does not translate into corresponding innovation output. The privately owned small and medium-sized enterprises (SMEs) show a high capability of technological innovation and mercerization but have limited innovation resources.