Resilience or efficiency? Strategic options for sustainable development of agricultural systems in ecologically fragile areas of China.

Sustainable development of agricultural systems is crucial for ensuring global food security, and resilience and efficiency are important topics for sustainable development of agricultural systems. Therefore, it is important to study the coupling and coordination relationship between agricultural system resilience and agricultural production efficiency, and explore the sustainable development model of agricultural system accordingly. Using statistical data from 2000 to 2020, we constructed a system of indicators for sustainable development of agricultural systems, and assessed the coordination status and interaction of agricultural system resilience and agricultural production efficiency in 49 county-level administrative units in the Loess Hilly Region Gansu Section (LHRGS) of China with the help of the coupling coordination degree (CCD) model, bivariate Moran's I index, and geographically weighted regression (GWR) model. The results show as follows: (1) The level of resilience of the LHRGS agricultural system and the level of agricultural production efficiency shows a continuous upward trend and a robust growth state. (2) High-value areas of the LHRGS agricultural system resilience are concentrated in counties with better resource endowment, and high-value areas of agricultural production efficiency are distributed in regions with stronger innovation capacity, and there is a moderate level of coupling relationship between them. (3) The sustainable development capacity of the agricultural system is gradually improving, but there is a certain degree of heterogeneity between agricultural system resilience and agricultural production efficiency. (4) Agricultural input factors have significant effects on the sustainable development of the agricultural systems, and significant spatial differences are found in the effects of different agricultural input factors on the sustainable development of agricultural systems. Based on the findings of this study, policy recommendations for the sustainable development of agricultural systems in ecologically fragile areas are proposed.

Effect of Self-Transcendence Theory Combined with Comprehensive Nursing Intervention under Tumor Nutrition Education on Symptom Improvement, Nutritional Status, and Positive Psychology of Elderly Patients with Gastric Cancer.

Objective: To explore the value of self-transcendence theory combined with comprehensive nursing intervention under oncological nutritional education on improvement in symptoms, nutritional status, and positive psychology of elderly patients with gastric cancer (GC). Methods: A total of 98 elderly patients with GC in the First Affiliated Hospital of Xi'an Jiaotong University from January 2021 to December 2021 were enrolled. All these patients were arbitrarily assigned into the observation group (n = 49) and control group (n = 49). The controlled patients accepted the regular oncological nutritional education. The cases of the observation group were given comprehensive nursing care based on the self-transcendence theory and oncological nutrition education. The symptom remission rate, subjective global assessment (PG-SGA) score, self-transcendence scale score, incidence of malnutrition, Hamilton Anxiety (HAMA) scale score, Hamilton Depression (HAMD) scale score, and Newcastle satisfaction with nursing scale (NSNS) score were observed. Results: The remission rate of symptoms in the observation group was higher than that of the control group after the nursing care. Following nursing, the PG-SGA score of the observation group was lower than that of the control group (p < 0.05). The score of the self-transcendence scale in the observation group was higher than that of the control group after nursing (p < 0.05). The incidence of malnutrition in the observation group was significantly lower than that of the control group. After nursing, the scores of the HAMA scale and HAMD scale in the observation group were lower than that of the control group (p < 0.05). The NSNS score of the observation group was statistically higher than that of the control group following nursing. Conclusion: The application value of self-transcendence theory combined with comprehensive nursing care under oncological nutritional education is more significant in elderly patients with GC, which is more helpful to enhance symptoms and nutritional status and control the incidence of malnutrition. Thus, it is able to reduce anxiety and depression and the rate of adverse reactions related to surgery-assisted chemotherapy as well.

Conversion of epithelial-to-mesenchymal transition to mesenchymal-to-epithelial transition is mediated by oxygen concentration in pancreatic cancer cells.

[This retracts the article DOI: 10.3892/ol.2018.8219.].

Collagen type IV alpha 1 (COL4A1) silence hampers the invasion, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cells through blocking Hedgehog signaling pathway.

Gastric cancer (GC), which features high prevalence and mortality rate, remains the third most lethal cancer worldwide. The paper was designed to explore the impacts of collagen type IV alpha 1 (COL4A1) on GC, along with its potential mechanism. The mRNA and protein expressions of COL4A1 in GC cells were assessed using RT-qPCR and Western blot. After depleting COL4A1, RT-qPCR and Western blot were conducted again to check the transfection efficacy. With the application of CCK-8, wound healing and transwell, the capabilities of cells to proliferate, migrate and invade were appraised, respectively. Moreover, Western blot tested the protein levels of factors involved in migration, proliferation, epithelial-mesenchymal transition (EMT) and Hedgehog signaling. As a result, COL4A1 displayed elevated expression in GC tissues and cells, while its knockdown inhibited the cell viability, migration, invasion and EMT in GC. According to Gene Set Enrichment Analysis (GSEA), COL4A1 was involved in the regulation of Hedgehog signaling pathway, which was then further verified by the detection of Hedgehog-related proteins. To figure out the relationship between COL4A1 and Hedgehog signaling pathway, we used purmorphamine, an agonist of Hedgehog, to treat GC cells, finding that COL4A1 blocked Hedgehog signaling to inhibit the aggressive phenotypes of GC cells. In short, COL4A1 silence was testified to exhibit suppressive effects on the malignant process of GC, suggesting that COL4A1 might be a potent hallmark of GC therapy.

M2­TAM subsets altered by lactic acid promote T­cell apoptosis through the PD­L1/PD­1 pathway.

The aim of the study was to investigate the effects of lactic acid on the phenotypic polarization and immune function of macrophages. The human monocyte/macrophage cell line, THP­1, was selected and treated with lactic acid. Immunofluorescence staining, laser confocal microscopy, reverse­transcription polymerase chain reaction (RT­PCR), western blot, siRNA, and ELISA analyses were used to observe changes in the levels of cluster of differentiation (CD)68, CD163, hypoxia inducible factor (HIF)­1α, and programmed death ligand­1 (PD­L1) as well as those of cytokines, tumor necrosis factor (TNF)­α, interferon (IFN)­Î³, interleukin (IL)­12, and IL­10. THP­1 macrophages and T cells were co­cultured in vitro to observe the changes in proliferation and apoptosis of T cells. The results showed that, lactic acid (15 mmol/l) significantly upregulated the expression of the macrophage M2 marker CD163 (P<0.05), cytokines, IFN­Î³ and IL­10, secreted by M2­tumor­associated macrophages (TAM, P<0.05), and HIF­1α and PD­L1 (P<0.05), and downregulated the expression of cytokines, TNF­α and IL­12, secreted by M1­TAM (P<0.05). Redistribution of M2­TAM subsets and PD­L1 expression was reversed after further transfection of THP­1 cells with HIF­1α siRNA (P<0.05). After co­culturing, T­cell proliferation was inhibited and apoptosis was promoted. In summary, modulation of lactic acid level can redistribute M2­TAM subsets and upregulate PD­L1 to assist tumor immune escape. The HIF­1α signaling pathway may participate in this process, revealing that macrophages, as 'checkpoints' in organisms, are links that connect the immune status and tumor evolution, and can be used as a target in tumor treatment.

Association of family history of tumors with clinicopathological characteristics and prognosis of colorectal cancer.

To investigate the association of family history of malignant tumors with clinicopathological characteristics of colorectal cancer, and its effects on prognosis. We conducted a retrospective review of pathological and follow-up data of patients with colorectal cancer treated in our hospital from January 2010 to December 2015. Of 870 patients undergoing surgery, 737 received follow-up (84.7%). Among them, 192 (26.1%) were family history of malignant neoplasm-positive [MN-FH (+)] and 545 (73.9%) were family history of malignant neoplasm-negative [MN-FH (-)]. MN-FH (+) patients had earlier disease onset, smaller tumor diameter, lower rate of lymph node metastasis, and lower depth of invasion. There were significant differences in BMI between the groups (P<0.05) but no differences in sex or tumor differentiation grade (P>0.05). Rates of Her-2 and p53 protein expression in MN-FH (+) patients were 34.3 and 40.5%, respectively, compared with 22.2 and 26.3% in MN-FH (-) patients. In stage 3, significantly higher Her-2 and p53 protein expression rates were observed in MN-FH (+) than in MN-FH (-) patients. Fluorescence in-situ hybridization showed significantly higher Her-2 expression in MN-FH (+) than in MN-FH (-) patients. The 3 and 5-year overall survival, disease-free survival, and progression-free survival were significantly lower in MN-FH (+) than in MN-FH (-) patients (P<0.05). MN-FH (+) patients with colorectal cancer had earlier disease onset and smaller tumor area, lower invasion depth, a lower rate of lymph node metastasis, and earlier TNM tumor stage at diagnosis than MN-FH (-) patients. BMI value distribution significantly differed between groups. However, long-term prognosis was worse for MN-FH (+) than MN-FH (-) patients, suggesting that internal pathogenic genes play a more crucial role than external environmental factors in prognosis. Family history of tumors could be an independent prognostic factor for colon cancer.

Conversion of epithelial-to-mesenchymal transition to mesenchymal-to-epithelial transition is mediated by oxygen concentration in pancreatic cancer cells.

Tumor metastasis is accompanied by a two-stage process of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). Currently, the exact mechanisms underlying EMT-MET conversion are unclear. In the present study, the mechanisms by which primary sites (hypoxic) and homing sites (normoxic or hyperoxic) participate in EMT-MET conversion were evaluated. Pancreatic cancer cells were grown under different oxygenation conditions. Cell morphology and epithelial (E)-cadherin and vimentin expression were examined. Transwell chambers were used to examine tumor invasiveness, and scratch assays were performed to examine cell migration. Reverse transcription-polymerase chain reaction and western blot analysis were used to quantitate the mRNA and protein expression of E-cadherin, vimentin, Snail and hypoxia-inducible factor (HIF)-1α. BxPc-3 and Panc-1 cells grown under hypoxic conditions demonstrated increased partial EMT, reduced E-cadherin expression, and increased vimentin expression, compared with cells grown under normoxic or hyperoxic conditions. Cells grown under hypoxic conditions also indicated increased migration and invasiveness. HIF-1α mRNA and protein expression was increased in cells grown under hypoxic conditions. These changes were reversed when a specific inhibitor of the HIF-1α receptor was used to block HIF-1α signaling. Differences in oxygen concentration at primary sites and homing sites are important in the EMT-MET process, and the underlying mechanism may involve HIF-1α-Snail signaling.

Impact of AQP-5 on the growth of colorectal cancer cells and the underlying mechanism.

Aquaporin 5 (AQP-5) is highly expressed in colorectal cancer tissue and associated with colorectal cancer development and prognosis. Here, we explored the effects of AQP-5 on colorectal cancer cell proliferation and apoptosis and the underlying mechanism by inhibiting endogenous AQP-5 expression in the human colorectal cancer cell lines COLO 205 and SW480. These cells were transfected with an AQP-5-siRNA, and transfection efficiency and its effects on AQP-5 expression were assessed by immunofluorescence and PCR, respectively. Then, cell proliferation was assessed via the MTT assay, apoptosis was assessed by Annexin V-FITC/PI and TUNEL assays, and expression changes in Bax and Bcl-2 were assessed by RT-PCR and western blotting. Transfection with AQP-5-siRNA reduced AQP-5 expression by up to 62%. The MTT assay showed that cell proliferation was significantly inhibited by AQP-5-siRNA transfection compared to that in NS-siRNA-transfected cells (P < 0.05). Flow cytometry analysis revealed that the percentage of apoptotic AQP-5-siRNA-transfected cells was significantly higher than that of NS-siRNA-transfected cells (P < 0.05). Real-time quantitative RT-PCR and western blotting showed that AQP-5-siRNA significantly increased the Bax/Bcl-2 mRNA and protein ratios compared with those following NS-siRNA transfection. Thus, AQP5-siRNA promotes apoptosis of colorectal cancer cells, which may be associated with Bax/Bcl expression.

[Role of aquaporin-5 in regulating colorectal cancer cell growth in vitro].

OBJECTIVE: To study the role of aquaporin 5(AQP5) in regulating the cell proliferation and apoptosis of human colorectal cancer cells and explore the possible mechanism. METHODS: A small interfering RNA (siRNA) targeting AQP5 was used to suppress endogenous AQP5 expression in the human colorectal cancer cell lines COLO 205 and SW480, and the transfection efficiency of AQP5 siRNA was determined using immunofluorescence assay and PCR. The changes in the proliferation of the transfected cells was evaluated with MTT assay, and the cell apoptosis was analyzed using Annexin V-FITC/PI and TUNEL assays; the changes of Bax and Bcl2 expressions in the cells were determined using RTPCR and Western blotting. RESULTS: Transfection with AQP-5-siRNA resulted in a significant reduction (up to 90%) of AQP-5 expression in COLO 205 and SW480 cells. MTT assay showed that AQP-5-siRNA transfection significantly inhibited the cell proliferation compared NS siRNA transfection (P<0.05). Flow cytometric analysis revealed significantly increased apoptotic rate of cells following AQP-5-siRNA transfection compared with NS?siRNA transfection(P<0.05). Real-time quantitative RT-PCR and Western blotting demonstrated that AQP-5-siRNA transfection significantly increased Bax and Bcl-2 expressions at both mRNA and protein levels in the cells. CONCLUSION: AQP5-siRNA can promote apoptosis of colorectal cancer cells in vitro possibly in relation to its effects on Bax and Bcl expressions.

Cancer-associated fibroblasts enhance pancreatic cancer cell invasion by remodeling the metabolic conversion mechanism.

We investigated the mechanism of cancer-associated fibroblasts (CAFs) in promoting the invasion and metastasis of pancreatic cancer cells in a non-vascular manner. We verified the original generation of isolated cultured CAFs and normal fibroblasts (NFs) based on the expression of α-SMA and vimentin, and we examined the cell glycolysis level through glucose consumption and lactate production experiments. The mRNA and protein expression of CAF glycolytic enzymes, lactate dehydrogenase and pyruvate kinase m2, were examined by RT-PCR and western blotting, respectively. In vitro culture first-generation pancreatic CAFs were collected and cultured together with pancreas cancer BxPc-3 and Panc-1 cells. Cell invasion and migration were assessed using a Transwell assay and scratch test, respectively. Mitochondrial activity was assessed by experimentally determining oxidative phosphorylation (OP) activity. The aerobic oxidation index of cancer cells was also examined. Succinate dehydrogenase, fumarate hydratase (FH), and monocarboxylate transporter 1 (MCT1) expression were examined using an MCT1-specific inhibitor to remove 'tumor-stromal' metabolic coupling to observe the influence of cell interstices on pancreas cancer progression. First-generation isolated cultured CAFs and NFs both grew well, and showed active proliferation. Glucose absorption and lactate production were significantly enhanced in CAFs compared with that in NFs. PCR and western blotting showed that the lactate dehydrogenase and pyruvate kinase m2 mRNA and protein expression levels were increased in the CAFs. After indirect co-culture, OP was increased in the BxPc-3 and Panc-1 cells; correspondingly, succinate dehydrogenase, FH and MCT expression were increased. After the MCT1-specific inhibitor removed 'tumor-stromal' metabolic coupling, the migration and invasion abilities of the pancreatic cancer cells were decreased. Pancreatic CAFs can alter metabolism as well as communicate with and respond to cancer cell migration and invasion. This may be an important mechanism for promoting tumor progression in a non-vascular manner in the tumor microenvironment. The mechanism by which CAFs reshape metabolic transition requires further analysis.

Prometastatic mechanisms of CAF-mediated EMT regulation in pancreatic cancer cells.

Tumor metastasis are accompanied by the EMT (epithelial-mesenchymal transition)-MET (mesenchymal-epithelial transition) two-step process. In this study, we investigated the importance of cancer associated fibroblasts (CAF) in the process. First, the primary cultures of isolated pancreatic CAF, fibroblasts of normal pancreatic tissues (NF), and normal hepatic stellate cells (HSF) were identified and verified via the expression of α-SMA and vimentin. Using an indirect three-dimensional co-culture model, the morphological changes were observed by light microscopy and laser scanning confocal microscopy. The invasive and migration capacity of pancreatic cancer cells was determined by Transwell chamber migration assay or scratch assay. The mRNA and protein expression levels of E-cadherin, vimentin, and Gli1 were determined by RT-PCR and western blotting. Primary cultures of isolated CAF, NF, HSF showed satisfactory growth with active proliferation. Indirect co-culture with CAF, BxPc-3 and Panc-1 cells showed significant partial EMT, reduced E-cadherin expression, and enhanced vimentin expression as compared with the single culture and NF/HSF co-culture groups, with corresponding increases in migratory and invasive capacities. PCR and western blotting results showed that mRNA and protein expression levels of Gli1 in CAF and Snail in cancer cells were increased. This process could be reversed by inhibition of hedgehog (HH) signaling in CAF. In the tumor microenvironment, activation of CAF is the key event in mediating partial EMT, and its mechanism may be associated with paracrine action after activation of HH signaling in CAF.

AQP5: a novel biomarker that predicts poor clinical outcome in colorectal cancer.

The aquaporins (AQPs) are water channel proteins that exhibit several properties related to tumor development. However, the expression and clinical significance of AQP5 in colorectal cancer, particularly the correlation with circulating tumor cells (CTCs), has not been elucidated. The aim of the present study was to determine whether or not the expression of AQP5 is a strong prognostic biomarker for colorectal cancer. The results showed that of 45 tumor specimens, 14 (31.1%) had high levels of expression of AQP5, 29 (64.4%) exhibited a moderate (intermediate) level of staining, and 2 (4.4%) had an absence of AQP5 staining. AQP5 was only occasionally detected in para-neoplastic [3/45 (6.67%)] and normal tissues [3/45 (6.67%)]. AQP5 protein overexpression frequently accompanied gene amplification detection with fluorescence in situ hybridization (FISH). Moreover, AQP5 expression in colorectal cancer cells was upregulated compared to normal colon cells. AQP5 overexpression was also associated with TNM stage (P=0.002), lymph node metastasis (P=0.016), and distant metastasis (P=0.000). The relationships between age, gender, histologic grade and tumor size with expression of AQP5 were not significant (P>0.05). A positive correlation between the number of CTCs and AQP5 expression (P<0.05) was demonstrated. In addition, patients who did not express AQP5 had a superior cumulative survival rate compared to patients with AQP5 positivity. AQP5 may be used as a novel biomarker for colorectal cancer aggressiveness and metastasis, but it does not reflect drug resistance.

α-Mangostin suppresses human gastric adenocarcinoma cells in vitro via blockade of Stat3 signaling pathway.

AIM: To investigate the anti-tumor effects of α-mangostin, a major xanthone identified in the pericarp of mangosteen (Garcinia mangostana Linn), against human gastric adenocarcinoma cells in vitro, and the mechanisms of the effects. METHODS: Human gastric adenocarcinoma cell lines BGC-823 and SGC-7901 were treated with α-mangostin. The cell viability was measured with MTT assay, and cell apoptosis was examined using flow cytometry and TUNEL assay. The expression of the relevant proteins was detected using Western blot. RESULTS: Treatment with α-mangostin (3-10 µg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners. Furthermore, α-mangostin (7 µg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm. Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells. CONCLUSION: The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to blockade of Stat3 signaling pathway.

Novel regulatory program for norepinephrine-induced epithelial-mesenchymal transition in gastric adenocarcinoma cell lines.

Norepinephrine and epinephrine, catecholamine hormones that are major mediators for chronic stress-induced cancers, are implicated in the progression of a number of cancer cells, including gastric adenocarcinoma. However, the underlying mechanisms of these hormones have not been well elucidated. Epithelial-mesenchymal transition (EMT) is a crucial event responsible for cancer cell invasion and metastasis. The hypothesis regarding whether the promotive effects of norepinephrine (NE) on cancer are in part due to its ability to induce an EMT program has not been proven. In this study, we show that NE does not only obviously induce EMT alterations in the morphological characteristics of gastric adenocarcinoma cells, but also increases the markers of EMT, including vimentin expression, and decreases E-cadherin expression, further resulting in cell motility and invasiveness. We also reveal that these actions are mainly mediated through the activation of ß2 -AR-HIF-1α-Snail signaling pathways. In summary, this study implies that NE induces EMT in gastric adenocarcinoma through the regulation of ß2 -AR-HIF-1α-Snail activity. The data provide a new perspective on chronic stress in a negative social and psychological state, which may be a risk factor for cancer development and progression.