Astragalus mongholicus Bunge and Curcuma aromatica Salisb. modulate gut microbiome and bile acid metabolism to inhibit colon cancer progression.

Introduction: Alterations in the gut microbiome and bile acid metabolism are known to play a role in the development and progression of colon cancer. Medicinal plants like Astragalus mongholicus Bunge and Curcuma aromatica Salisb. (AC) have shown preferable therapeutic effect on cancer therapy, especially digestive tract tumors like colon cancer. However, the precise mechanisms of AC inhibiting colon cancer, particularly in relation to the gut microbiome and bile acid dynamics, are not fully understood. Methods: Our research aimed to investigate the anti-tumor properties of AC in mice with CT26 colon cancer and further investigate its underlying mechanism via intestinal microbiota. The size and pathological changes of solid tumors in colon cancer are used to evaluate the inhibitory effect of AC on colon cancer. Metagenomics and 16s rRNA gene sequencing were employed to clarify the dysbiosis in the gut microbiome of colon cancer and its impact on colon cancer. The levels of bile acids (BAs) in the feces of mice from each group were measured using UPLC-Qtrap-MS/MS. Results: AC effectively suppressed the growth of colon cancer and reduced histological damage. Notably, AC treatment led to changes in the gut microbiome composition, with a decrease in pathogenic species like Citrobacter and Candidatus_Arthromitus, and an increase in beneficial microbial populations including Adlercreutzia, Lachnospiraceae_UCG-001, and Parvibacter. Additionally, AC altered bile acid profiles, resulting in a significant decrease in pro-carcinogenic bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA), while increasing the concentration of the cancer-inhibitory bile acid, ursodeoxycholic acid (UDCA). Tracking and analyzing the data, AC may mainly upregulate FabG and baiA genes by increasing the relative abundance of Adlercreutzia and Parvibacter bacteria, which promoting the metabolism of pro-carcinogenic LCA. Discussion: These findings provide strong evidence supporting the role of AC in regulating gut microbiome-mediated bile acid metabolism, which is crucial in impeding the progression of colon cancer.

Astragali Radix-Curcumae Rhizoma herb pair reduces the stemness of colorectal cancer cells through HIF-2α/ß-catenin pathway.

BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality and significantly impairs quality of life. Astragali Radix-Curcumae Rhizoma (AC) is widely employed in the treatment of CRC in Chinese medicine, but the precise mechanisms remain unclear. PURPOSE: This study aimed to elucidate the mechanisms by which AC inhibits CRC progression. METHODS: The active components of AC were identified using UPLC-MS/MS analysis. An orthotopic transplantation colorectal tumor model was established in BALB/c mice using the CT26-Lucifer cell line to evaluate the effects of AC. Tumor volumes were monitored using IVIS imaging technology. Histological examination of tumor morphology was performed with hematoxylin and eosin (H&E) staining. Transcriptomic sequencing of mouse tumor samples was conducted to identify critical pathways and molecular targets. The impact of AC on cell viability and migration was assessed using CCK-8 and wound healing assays, respectively. To investigate the effects of AC on CRC cells, an in vitro hypoxic model was established using cobalt chloride (CoCl2), a hypoxia inducer. HIF-2α overexpression was achieved by constructing stable lentiviral vectors. Key targets identified from RNA-seq, such as c-Myc, Ki-67, ß-catenin, cleaved caspase 3, CD133, and CD44, were evaluated using western blotting, qRT-PCR, and immunofluorescence assays. Epithelial-Mesenchymal Transition (EMT) and spheroid cloning assays were employed to evaluate phenotypic changes in cancer stem cells. RESULTS: Twelve components of AC were identified. AC effectively inhibited CRC progression in vivo. Transcriptomic analysis highlighted hypoxic signaling as a significantly enriched pathway, implicating its role in suppressing CRC progression by AC. In the hypoxic model, AC inhibited the proliferation and migration of CRC cells in vitro. Furthermore, AC reduced cancer stemness by downregulating stemness markers, inhibiting EMT, and decreasing tumor sphere formation. The downregulation of hypoxic responses and the shift in stemness by AC involved attenuation of HIF-2α and WNT/ß-catenin signaling. CONCLUSION: This study provides the first evidence that AC reduces the stemness of CRC and the inhibition of the transition of CRC to stem-like cells by AC is closely related to the downregulation of the HIF-2α/ß-catenin pathway, especially under hypoxic conditions.

Utilizing Ant Forest technology to foster sustainable behaviors: A novel approach towards environmental conservation.

Amidst mounting environmental threats and exacerbated global risks from climate change, the urgency for sustainable behaviors has never been more critical, demanding concerted efforts to cultivate individual actions for environmental conservation. Ant Forest technology, a groundbreaking innovation for sustainable lifestyles, stands at the forefront of this battle, harnessing technological advancements to drive positive environmental impact and must be championed. This research investigates the dynamics of environmental conservation behaviors facilitated by Ant Forest Technology. Employing a theoretical framework integrating the Technology Acceptance Model (TAM) and Self-Determination Theory (SDT), the study explores the impact of autonomous and controlled motivation on attitudes, intentions, and conservation behaviors. Furthermore, the research assesses the influence of knowledge disseminated through Ant Forest Technology on users' intentions and behavior toward conservation behaviors. The study utilized the partial least square structural equation modeling in its analysis. Findings reveal that both motivational factors and knowledge significantly shape users' engagement in conservation behaviors activities through perceived ease of use and usefulness. These insights contribute to the development of effective policies and interventions aimed at harnessing Ant Forest Technology as a powerful tool for fostering widespread environmental conservation behaviors.

Intelligence level evaluation and influencing factors analysis of equipment manufacturing industry in the Yangtze River Delta.

The Yangtze River Delta (YRD) bears the vital task of driving the growth of China's equipment manufacturing industry (EMI) intelligence as an advanced region. Fostering the transformation and upgrading of the EMI in the YRD and constructing a modern production mode is vital to developing and reforming China's manufacturing industry. This paper uses industrial robot data to assess the level of intelligence (LoI) in the EMI from 2016 to 2019. The OLS (ordinary least squares) model is used for the measurements, and the MQ (the modified contribution index) is used to estimate the degree of contribution from a host of variables. It is identified that the LoI is on the rise. However, excluding railways, aerospace, shipbuilding, and other transportation equipment manufacturing, the LoI is significantly higher than in other subsectors. It is also identified that technological innovation ability, human capital density, and enterprise cost pressure govern the industry's LoI. Moreover, while there is a difference in the main influencing factors in LoI within different industries, R&D investment, technological innovation ability, and enterprise cost pressure have the most significant impact across most equipment manufacturing sub-industries.

[Astragali Radix-Curcumae Rhizoma inhibits colon cancer progression and enhances 5-FU efficacy by regulating hypoxia-inducible factors and tumor stem cells].

The animal and cell models were used in this study to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in inhibiting colon cancer progression and enhancing the efficacy of 5-fluorouracil(5-FU) by regulating hypoxia-inducible factors and tumor stem cells. The animal model was established by subcutaneous transplantation of colon cancer HCT116 cells in nude mice, and 24 successfully modeled mice were randomized into model, 5-FU, HQEZ, and 5-FU+HQEZ groups. The tumor volume was measured every two days. Western blot was employed to measure the protein levels of epidermal growth factor receptor(EGFR), dihydropyrimidine dehydrogenase(DPYD), and thymidylate synthase(TYMS), the key targets of the hypoxic core region, as well as the hypoxia-inducible factors HIF-1α and HIF-2α and the cancer stem cell surface marker CD133 and SRY-box transcription factor 2(SOX2). The results of animal experiments showed that HQEZ slowed down the tumor growth and significantly increased the tumor inhibition rate of 5-FU. Compared with the model group, HQEZ significantly down-regulated the protein levels of EGFR and DPYD, and 5-FU+HQEZ significantly down-regulated the protein levels of EGFR and TYMS in tumors. Compared with the model group, HQEZ significantly down-regulated the protein levels of HIF-1α, HIF-2α, SOX2, and CD133 in the hypoxic core region. Compared with the 5-FU group, 5-FU+HQEZ lowered the protein levels of HIF-1α, HIF-2α, and SOX2. The cell experiments showed that the protein le-vels of HIF-1α and HIF-2α in HCT116 cells elevated significantly after low oxygen treatment. Compared with 5-FU(1.38 µmol·L~(-1)) alone, HQEZ(40 mg·mL~(-1)) and 5-FU+HQEZ significantly down-regulated the protein levels of HIF-1α, HIF-2α, and TYMS. In conclusion, HQEZ can inhibit the expression of hypoxia-responsive molecules in colon cancer cells and reduce the properties of cancer stem cells, thereby enhancing the therapeutic effect of 5-FU on colon cancer.

Homotherapy-for-heteropathy of Bupleurum Chinense DC.-Scutellaria baicalensis Georgi in treating depression and colorectal cancer: A network pharmacology and animal model approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC.-Scutellaria baicalensis Georgi (BS) is a classic drug pair that has good clinical effects on depression and many tumors. However, the concurrent targeting mechanism of how the aforementioned drug pair is valid in the two distinct diseases, has not been clarified yet. AIM OF THE STUDY: The components of BS were detected by LC-MS, combined with network pharmacology to explore the active ingredients and common targeting mechanism of its multi-pathway regulation of BS in treating depression and CRC, and to validate the dual effects of BS using the CUMS mice model and orthotopic transplantation tumor mice model of CRC. RESULTS: Twenty-nine components were screened, 84 common gene targets were obteined, and the top 5 key targets including STAT3, PIK3R1, PIK3CA, AKT1, IL-6 were identified by PPI network. GO and KEGG analyses revealed that PI3K/AKT and JAK/STAT signaling pathways might play a crucial role of BS in regulating depression and CRC. BS significantly modulated CUMS-induced depressive-like behavior, attenuated neuronal damage, and reduced serum EPI and NE levels in CUMS model mice. BS improved the pathological histological changes of solid tumors and liver tissues and inhibited solid tumors and liver metastases in tumor-bearing mice. BS significantly decreased the proteins' expression of IL-6, p-JAK2, p-STAT3, p-PI3K, p-AKT1 in hippocampal tissues and solid tumors, and regulated the levels of IL-2, IL-6 and IL-10 in serum of two models of mice. CONCLUSION: BS can exert dual antidepressant and anti-CRC effects by inhibiting the expression of IL-6/JAK2/STAT3 and PI3K/AKT pathway proteins and regulating the release of inflammatory cytokines.

The impacts of economic policy uncertainty on firm cash holding in China.

Cash holding is an important strategic decision of enterprises. As a macro-level factor, economic policy uncertainty causes risks, affecting enterprises' cash holdings. Taking the quarterly financial data of China's A-share non-financial listed firms for 2010-2020 as a sample, this study adopts the OLS and fixed effect models to investigate how corporate cash holdings are affected by economic policy uncertainty. The findings indicate that economic policy uncertainty is directly proportional to the level of cash that listed corporations hold. The higher the uncertainty, the more cash the company holds. Among them, state-owned enterprises and the manufacturing industry are more significantly affected by economic policy uncertainty. Finally, considering the regional marketization level and the differences in financing constraints enterprises face, it is concluded through grouping empirical studies that enterprises located in regions with lower marketization levels are more susceptible to policy uncertainty, while financially constrained enterprises are more susceptible to economic policy uncertainty. The study of economic policy uncertainty is helpful to guide enterprises to realize the importance of coping strategies in advance under the background of intensifying economic policy uncertainty. Therefore, this paper proposes to introduce policies on the premise of fully considering the smoothness of the economy and the differences in the conditions of firms of different natures, as well as some proposals to alleviate financing constraints, reduce the adverse effects of uncertainty on firms, and bolster the marketization process.

The Effect and Mechanism of Sancao Lichang Decoction on Diarrhea- Predominant Irritable Bowel Syndrome by Regulating Tlr4/Myd88/Nf-Κb Pathway.

OBJECTIVE: To evaluate the effect of Sancao Lichang decoction as traditional Chinese medicine on diarrhea-predominant irritable bowel syndrome (IBS-D) and TLR4/MyD88/NF-κB pathway. BACKGROUND: Traditional Chinese medicine has made significant progress in preventing and treating irritable bowel syndrome, and its efficacy has been validated by clinical practice. Sancao Lichang decoction is an empirical prescription developed by professor Tang Decai that has been used for many years to treat chronic diarrhoea with good curative effec. Still, its mechanism of action on IBS-D is unknown. METHODS: The study sample of Fifty SD rats was randomly divided into a blank group, model group, low-dose group, medium-dose group, and high-dose group (n = 10). The IBS-D rat models were established by restraining stress method and acetic acid enema. After different treatments, defecation frequency, fecal water content (FWC), serum IL-6 and TNF-α contents, and protein level of TLR4/MyD88/NF-κB in colon tissues were detected separately. RESULTS: The indexes of rats in each group were significantly different. The increase in body weight in the medium-dose and high-dose groups was significantly higher than that in the model group (p < 0.05). Compared with the model group, the medium and high dose groups had lower diarrhea frequency, FWC, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) (p < 0.05). The expression levels of TLR4, MyD88, and NF-κB protein in the colon of the three groups treated with Sancao-Lichan decoction were significantly lower than those in the model group (p < 0.01). After different treatments, the colonic mucosa of rats in each group was stained with HE, which proved that the structural damage of colonic mucosa was improved after treatment with Sancao Lichang decoction, and the improvement effect was dose-dependent. CONCLUSION: Sancao Lichang decoction may reduce IBS-D by inhibiting TLR4/MyD88/NF-κB pathway, inhibiting the inflammatory response, and improving intestinal mucosal barrier function.

[Astragali Radix-Curcumae Rhizoma combination inhibits proliferation, migration, and invasion of colon cancer HT-29 cells by regulating EMT].

This study aims to investigate the effect of Astragali Radix-Curcumae Rhizoma(AC) combination on the proliferation, migration, and invasion of colon cancer HT-29 cells based on epithelial-mesenchymal transition(EMT). HT-29 cells were respectively treated with 0, 3, 6 and 12 g·kg~(-1) AC-containing serum for 48 h. The survival and growth of cells were measured by thiazole blue(MTT) colorimetry, and the proliferation, migration, and invasion of cells were detected by 5-ethynyl-2'-deoxyuridine(EdU) test and Transwell assay. Cell apoptosis was examined by flow cytometry. The BALB/c nude mouse model of subcutaneous colon cancer xenograft was established, and then model mice were classified into blank control group, 6 g·kg~(-1) AC group, and 12 g·kg~(-1) AC group. The tumor weight and volume of mice were recorded, and the histopathological morphology of the tumor was observed based on hematoxylin-eosin(HE) staining. The expression of apoptosis-associated proteins B-cell lymphoma-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), and cleaved caspase-3, and EMT-associated proteins E-cadherin, MMP9, MMP2 and vimentin in HT-29 cells and mouse tumor tissues after the treatment of AC was determined by Western blot. The results showed that cell survival rate and the number of cells at proliferation stage decreased compared with those in the blank control group. The number of migrating and invading cells reduced and the number of apoptotic cells increased in the administration groups compared with those in the blank control group. As for the in vivo experiment, compared with the blank control group, the administration groups had small tumors with low mass and shrinkage of cells and karyopycnosis in the tumor tissue, indicating that the AC combination may improve EMT. In addition, the expression of Bcl2 and E-cadherin increased and the expression of Bax, caspase-3, cleaved caspase-3, MMP9, MMP2, and vimentin decreased in HT-29 cells and tumor tissues in each administration group. In summary, the AC combination can significantly inhibit the proliferation, invasion, migration, and EMT of HT-29 cells in vivo and in vitro and promote the apoptosis of colon cancer cells.

Implementation effect of China's green finance pilot policy based on synthetic control method: a green innovation perspective.

In order to develop green finance and realize the coordinated development of the environment and economy, China established green finance reform and innovation pilot zones in 2017. Green innovation has problems such as low financing utilization rate and lack of market competitiveness. The green finance pilot policies (GFPP) based on government management provide solutions to these problems. It is of great significance to measure and provide feedback on the implementation effect of GFPP in China for policy-making and green development. This article focuses on the influence of the construction of GFPP by using the five pilot zones as the study area and constructs the green innovation level indicator. Based on the synthetic control method, it chooses provinces that do not carry out the pilot policy as a control group. After that, assign weights to the control region to fit a synthetic control group with resembling characteristics to simulate the five pilot provinces without implementing the policy. Then, compare it with its current policy effect and highlight the policy implementation effect on green innovation. The placebo test and robustness test were conducted to prove the reliability of the conclusions. The results show that since the implementation of GFPP, the level of green innovation in the five pilot cities has shown an overall rising trend. Furthermore, we found that the balance of credit and investment in science and technology has a negative moderating effect on the implementation of GFPP, while the per capita GDP has a significant positive moderating effect.

Air Pollution, Environmental Protection Tax and Well-Being.

The effective control of air pollution to advance human health and improve well-being has risen to the forefront of discussion in recent years. Based on China's 2019 environmental protection tax data and China Social Survey (CSS) data, this paper studies the effects of subjective air pollution and the environmental protection tax on residents' well-being using an econometric mediation effect model. The research conclusions are as follows: (1) Subjective air pollution can significantly reduce residents' well-being, (2) an environmental protection tax can significantly improve residents' well-being and it can eliminate some of the negative influence of subjective air pollution on residents' well-being, and (3) the grouping test of residents' income, regional distribution, urban and rural structure, age structure, gender structure, and other variables shows that the effects of subjective air pollution on residents' well-being are heterogeneous among different populations. After further endogeneity testing with the instrumental variables method, adjusting the primary variables, and altering the research procedures, the results are still robust. Based on these findings, we should vigorously promote the development of ecological civilization and good air quality and support reforming the environmental protection tax system to enhance well-being. It is also necessary to shift from a crude development model to a green industry and business model. While emphasizing social equity and production efficiency, we should ensure the synchronous development of cities and villages. Additionally, tangible steps should be implemented to raise people's incomes, expand young people's work options, and enhance their satisfaction. The article focuses on the impact of subjective air pollution on residents' well-being, adding air pollution to the factors affecting well-being. Furthermore, the article finds that the environmental protection tax has two advantages: it can govern air pollution and promote green development, and, at the same time, it can enhance social harmony and improve residents' well-being.

Degradation of HIF-1α induced by curcumol blocks glutaminolysis and inhibits epithelial-mesenchymal transition and invasion in colorectal cancer cells.

Colorectal cancer (CRC) has high morbidity and mortality. Epithelial-mesenchymal transition (EMT) is associated with CRC progression and metastasis. Glutaminolysis is essential for malignancy of cancer cells. Here, we examined the effects of curcumol on CRC EMT. We observed that curcumol suppressed invasion and migration in human CRC cells associated with upregulation of epithelial markers E-cadherin and Zonula occludens 1 and downregulation of mesenchymal markers N-cadherin and Vimentin as well as EMT-related transcription factors Snail and Twist. Curcumol increased intracellular levels of glutamine but decreased intracellular levels of glutamate, α-ketoglutarate, ATP, glutathione, and tricarboxylic acid cycle metabolites, suggesting interruption of glutaminolysis. Next, curcumol repressed glutaminase 1 (Gls1) mRNA and protein expression, and overexpression of Gls1 promoted EMT and abolished curcumol effects on CRC cell EMT. Molecular examinations showed that curcumol stimulated protein degradation of hypoxia-inducible factor-1α (HIF-1α) and prevented its nuclear accumulation in CRC cells. HIF-1α agonist deferoxamine (DFO) promoted HIF-1α binding to Gls1 promoter and increased Gls1 expression but abolished curcumol's inhibitory effects on Gls1 expression. DFO also enhanced EMT and invasion and migration in CRC cells and eliminated curcumol effects. Furthermore, mouse CRC models were established with in vivo overexpression of HIF-1α and Gls1. Curcumol effectively inhibited CRC growth, metastasis, and EMT in mice, which was abrogated by overexpression of HIF-1α or Gls1. Altogether, stimulation of HIF-1α degradation was required for curcumol to disrupt EMT and repress invasion and migration in CRC cells through inhibiting Gls1-mediated glutaminolysis. Curcumol could be a promising candidate for intervention of CRC metastasis. • Curcumol inhibits EMT and blocks glutaminolysis in CRC cells. • Inhibition of Gls1 is required for curcumol blockade of glutaminolysis and EMT. • Curcumol induces HIF-1α degradation leading to inhibition of Gls1 and blockade of glutaminolysis and EMT. • Curcumol suppresses CRC growth and metastasis via inhibiting HIF-1α, glutaminolysis and EMT in mice.

How Do Environmental Regulations and Outward Foreign Direct Investment Impact the Green Total Factor Productivity in China? A Mediating Effect Test Based on Provincial Panel Data.

This paper investigates the impact of two types of environmental regulations (ERs), command-and-control environmental regulation (CACER) and market-incentive environmental regulation (MIER), on green total factor productivity (GTFP) through outward foreign direct investment (OFDI) in 30 provinces in China for the period of 2006-2019. The Global Malmquist-Luenberger (GML) Index based on non-radial directional distance function (NDDF) considering undesired outputs is used to measure GTFP growth at the provincial level. To explore the mediating effect of OFDI, the two-step econometric model and the non-linear mediating effect model are employed. The empirical results show that CACER has an inverted U-shaped impact on OFDI and a U-shaped impact on GTFP, while MIER has a linearly positive effect on OFDI and GTFP. The current intensity of CACER lies on the left side of the inflection point of the U-shaped curve. OFDI significantly positively influences the increase in GTFP and is a significant mediating variable in the relationship between ERs and GTFP. Moreover, the introduction of OFDI delays the appearance of the inflection point. Further analysis, taking into account the regional heterogeneity, indicates that the inverted U-shaped and U-shaped curve is still valid in the eastern and western area and that the mediating effect of OFDI on ERs in the western area is stronger than that in the eastern area. Based on these conclusions, policy implications are provided to improve GTFP in China.

The Effect of Green Finance on the Ecological and Environmental Quality of the Yangtze River Economic Belt.

Since China's reform and opening up, the speed of economic development has increased significantly. However, at the same time, there are also serious environmental pollution problems. To resolve the deep-seated contradiction between economic growth and environmental protection, green finance has gradually gained attention in China's development. Based on this, the paper explores the impact of green finance on the quality of the ecological environment in the Yangtze River Economic Belt. The main part of the paper is based on panel data of eleven provinces and cities in China's 2011-2020 Yangtze River Economic Belt. Seven indicators, including chemical oxygen demand COD, harmless treatment rate of domestic waste, and green coverage rate of built-up, were used to construct an ecological and environmental quality evaluation index system. The entropy method is used to measure the ecological environment quality level and green finance development level of various provinces and cities in the Yangtze River Economic Belt. The impact of green finance development on ecological environment quality is analyzed using a panel data model. The research results show that: (1) The development level of green finance and the quality of the ecological environment in the Yangtze River Economic Belt have improved between 2011 and 2020. (2) The development of green finance has a significant positive impact on the quality of the ecological environment in the Yangtze River Economic Belt. In addition, related research has focused on the impact of green finance on a certain branch of ecological and environmental quality and lacks an analysis of the overall impact. Therefore, this paper constructs a comprehensive evaluation system for ecological environment quality and analyzes the overall impact of green finance on ecological environment quality in the region.

Influence of Green Finance on Ecological Environment Quality in Yangtze River Delta.

Along with the development of society and the deepening contradiction between economic growth and natural resources, green finance has attracted more and more attention. As an area of great strategic significance in China's modernization, the development of green finance can improve the quality of its ecological environment and find new economic growth points for it. Based on the index system of pressure state response and while considering the scientific nature and desirability of the indicators, this paper selects 12 indicators to construct an index system of eco-environmental quality. It uses the entropy method to calculate the level of eco-environmental quality. Then, three control variables are selected, and the difference-in-difference model is used for empirical analysis. It is found that green finance positively affects the ecological environment quality of the Yangtze River Delta. In addition, the level of opening to the outside world and the level of economic development also have a positive effect on the quality of the ecological environment to a certain extent. Still, the impact of industrial structure on it is negative. Therefore, this paper puts forward some suggestions for strengthening the disclosure of green financial information, paying attention to the concept of green development and strengthening regional cooperation and exchange to promote the development of green finance further and promote the coordination of economic development and ecological protection in the Yangtze River Delta.

Astragalus mongholicus Bunge and Curcuma aromatica Salisb. inhibits liver metastasis of colon cancer by regulating EMT via the CXCL8/CXCR2 axis and PI3K/AKT/mTOR signaling pathway.

BACKGROUND: One of the most challenging aspects of colon cancer (CC) prognosis and treatment is liver-tropic metastasis. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (AC) is a typical medication combination for the therapy of many malignancies. Our previous studies found that AC intervention inhibits liver metastasis of colon cancer (LMCC). Nevertheless, the comprehensive anti-metastasis mechanisms of AC have not been uncovered. METHODS: In bioinformatics analysis, RNA-seq data of CC and LMCC patients were collected from TCGA and GEO databases, and differentially expressed genes (DEGs) were identified. The biological processes and signaling pathways involved in DEGs were enriched by GO and KEGG. The protein-protein interaction (PPI) network of DEGs was established and visualized using the Cytocape software, followed by screening Hub genes in the PPI network using Degree value as the criterion. Subsequently, the expression and survival relevance of Hub gene in COAD patients were verified. In the experimental study, the effects of AC on the inhibition of colon cancer growth and liver metastasis were comprehensively evaluated by cellular and animal models. Finally, based on the results of bioinformatics analysis, the possible mechanisms of AC inhibition of colon cancer EMT and liver metastasis were explored by in vivo and in vitro pharmacological experiments. RESULTS: In this study, we obtained 2386 DEGs relevant to LMCC from the COAD (colon adenocarcinoma) and GSE38174 datasets. Results of GO gene function and KEGG signaling pathway enrichment analysis suggested that cellular EMT (Epithelial-mesenchymal transition) biological processes, Cytokine-cytokine receptor interaction and PI3K/Akt signaling pathways might be closely related to LMCC mechanism. We then screened for CXCL8, the core hub gene with the highest centrality within the PPI network of DEGs, and discovered that CXCL8 expression was negatively correlated with the prognosis of COAD patients. In vitro and in vivo experimental evidence presented that AC significantly inhibited colon cancer cell proliferation, migration and invasion ability, and suppressed tumor growth and liver metastasis in colon cancer orthotopic transplantation mice models. Concomitantly, AC significantly reduced CXCL8 expression levels in cell supernatants and serum. Moreover, AC reduced the expression and transcription of genes related to the PI3K/AKT pathway while suppressing the EMT process in colon cancer cells and model mice. CONCLUSIONS: In summary, our research predicted the potential targets and pathways of LMCC, and experimentally demonstrated that AC might inhibit the growth and liver metastasis in colon cancer by regulating EMT via the CXCL8/CXCR2 axis and PI3K/AKT/mTOR signaling pathway, which may facilitate the discovery of mechanisms and new therapeutic strategies for LMCC.

Influencing Factors on the Household-Waste-Classification Behavior of Urban Residents: A Case Study in Shanghai.

As the process of urbanization in China continues to accelerate, the amount of domestic waste generated correspondingly increases and directly affects the living space of residents. This indirectly implies that to reduce the production of municipal solid waste and the need for garbage disposal and recycling, household-waste-classification activities by the residents are of great significance. Using Shanghai as a case study, this study investigated the influencing factors on residents' household waste classification by conducting a survey. Statistical analysis was then adopted, which is specified below. First, this study proposed research hypotheses related to the influencing factors of residents' domestic-waste-sorting behavior from three levels: government, society and individuals. Second, the study designed a questionnaire from five perspectives: individual characteristic variables, government, society, residents and classification behavior. Then, SPSS software was used to carry out descriptive statistical, reliability and validity assessments using ANOVA, correlation and regression analyses on the sample data obtained from the questionnaire. The results suggested that the research hypotheses were statistically significant: (1) females and residents with higher education were more likely to participate in domestic waste classification; (2) reward and punishment measures had the most significant impact on residents' waste-classification behavior; and (3) publicity and education, classification standards, classification facilities, the recycling system, subjective norms, environmental knowledge and environmental attitudes all had a positive effect on residents' household waste classification. Finally, based on the results of the empirical analysis, this paper provides reference suggestions for the further development of domestic waste classification in Shanghai.

The Effect and Related Mechanism of Action of Astragalus Compatible with Curcumin against Colon Cancer Metastasis in Mice.

Colon cancer (CC) is the third most common tumor worldwide. Colon carcinogenesis is strongly linked to inflammation. The initiation and progression of colon cancer may be influenced by epigenetic processes. Cancer metastasis is a multistep process involving several genes and their products. During tumor metastasis, cancer cells first enhance their proliferative capacity by lowering autophagy and apoptosis, and then, their capacity is stimulated by boosting tumors' ability to take nutrients from the outside via angiogenesis. Traditional treatment focuses on eliminating tumor cells by triggering cell death or activating the immune system, which often results in side effects or chemoresistance recurrence. On the contrary, Chinese medicine theory considers the patient's entire inner system and aids in tumor shrinkage while also taking into account the mouse' general health. Because many Chinese herbal medicines (CHM) are consumed as food, using edible CHMs as a diet resource therapy for colon cancer treatment is a viable option. Two traditional Chinese herbs, Astragalus membranaceus and Curcuma zedoaria, are commonly utilized jointly in colon cancer preventive therapy. As a result, the anticancer effect of astragalus and curcumin (AC) on colon cancer suppression in an 18-week AOM-DSS colon cancer mouse model is investigated in this research. These findings may offer a scientific foundation for investigating colon cancer diagnostic biomarkers and therapeutic application of AC in colon cancer treatment. These studies also highlighted the potential effect and mechanism of AC in the treatment of colon cancer, as well as providing insight into how to effectively use it.

Research on Digital Inclusive Finance Promoting the Integration of Rural Three-Industry.

The development of digital financial inclusion helps create a healthy rural financial ecological environment and plays an important role in integrating rural tertiary industries. This paper incorporates digital financial inclusion into the rural tertiary industry integration research framework. Furthermore, it adopts the double-difference method to empirically analyze the impact of the development of digital financial inclusion on rural tertiary industry integration from the perspective of policy impact. In addition, it considers regional differences in the financial ecological environment; robustness tests were carried out using methods such as placebo tests and validated the conduction mechanism. The study through the double-difference model found that digital financial inclusion is very conducive to promoting rural tertiary industry integration; using the quantile DID (difference in differences) method to analyze the heterogeneity, it is concluded that there is a heterogeneous impact on rural tertiary industry integration. It exerts a more significant improvement in provinces and cities with higher rural tertiary industry integration levels. Constructing an intermediary effect model to verify the transmission mechanism concludes that the policy has promoted the improvement of rural tertiary industry integration efficiency by promoting technological innovation, improving agricultural modernization, and building a risk-sharing mechanism. Finally, it puts forward policy recommendations from optimizing the financial ecological environment, rationally allocating financial resources, and perfecting the transmission mechanism.

Impact of Industrial Structure Upgrading on Green Total Factor Productivity in the Yangtze River Economic Belt.

The Yangtze River economic belt is an inland river economic belt with international influence composed of 11 provinces and municipalities in the Yangtze River Basin. This paper uses the super-efficiency model to calculate the green total factor productivity of 11 provinces and municipalities in the Yangtze River economic belt (YREB). Then we establish a model to study the impact of industrial structure upgrading, industrial structure rationalization, and environmental regulation on green total factor productivity (GTFP). Empirical analysis shows that the industrial structure upgrading and environmental regulation have a significant impact on GTFP and show regional characteristics. The more developed the economy and the higher the industrial structure, the greater the impact of upgrading and environmental regulation on GTFP. Compared with other control variables, the urbanization rate impacts GTFP, followed by regional economic development.