[Discrimination of cultivation modes of Dendrobium nobile based on content of mineral elements and ratios of nitrogen stable isotopes].

This study explored the feasibility of mineral element content and ratios of nitrogen isotopes to discriminate the cultivation mode of Dendrobium nobile in order to provide theoretical support for the discrimination of the cultivation mode of D. nobile. The content of 11 mineral elements(N, K, Ca, P, Mg, Na, Fe, Cu, Zn, Mn, and B) and nitrogen isotope ratios in D. nobile and its substrate samples in three cultivation methods(greenhouse cultivation, tree-attached cultivation, and stone-attached cultivation) were determined. According to the analysis of variance, principal component analysis, and stepwise discriminant analysis, the samples of different cultivation types were classified. The results showed that the nitrogen isotope ratios and the content of elements except for Zn were significantly different among different cultivation types of D. nobile(P<0.05). The results of correlation analysis showed that the nitrogen isotope ratios, mineral element content, and effective component content in D. nobile were correlated with the nitrogen isotope ratio and mineral element content in the corresponding substrate samples to varying degrees. Principal component analysis can preliminarily classify the samples of D. nobile, but some samples overlapped. Through stepwise discriminant analysis, six indicators, including δ~(15)N, K, Cu, P, Na, and Ca, were screened out, which could be used to establish the discriminant model of D. nobile cultivation methods, and the overall correct discrimination rates after back-substitution test, cross-check, and external validation were all 100%. Therefore, nitrogen isotope ratios and mineral element fingerprints combined with multivariate statistical analysis could effectively discriminate the cultivation types of D. nobile. The results of this study provide a new method for the identification of the cultivation type and production area of D. nobile and an experimental basis for the quality evaluation and quality control of D. nobile.

[Effect of Plant Density and Harvest on Yield and Quality in Blumea balsamifera].

Objective: To study the effects of different plant density and harvest time on the yield and quality of Miao medicine Blumea balsamifera, in order to provide a theoretical basis for Good Agriculture Practice( GAP). Methods: Two factors trails were used to research the influence of plant density and harvest time on the yield and quality of Blumea balsamifera. The plant density were located at 50 cm × 90 cm,50 cm × 60 cm,50 cm × 30 cm and 30 cm × 30 cm, and the harvest time were set up at mid-October, mid-November and mid-December. The experiments were designed with randomized block design. Results: Yield and quality were both affected by the plant density and harvest time. Yield per unit area and volatile oil yield per unit area were increased significantly with the increasing of plant density. Yield per unit area and volatile oil yield per unit area were peaked at the plant density of 111 112 plants / hm~2 which could obtain high-yield at the mid-December, which were 1 546. 68 kg / hm~2 and 96. 6 L / hm~2,respectively. The content of total flavonoids were peaked at the plant density of 22 223 plants / hm~2 and 111 112 plants / hm~2,which were 2. 50 and 2. 53 mg/g,respectively. Harvest time had no significant effect on the flavonoids content. Conclusion: The suitable plant density of transplanted root tillers of Blumea balsamifera is 111 112 plants / hm~2 and the optimum harvest time is December.

[Comparative Analysis of Main Morphological Characters and Interrelationship in Blumea balsamifera].

Objective: To investigate the main morphological characters and interrelationship of Blumea bdsamifera, and to provide the guidance for selection and breeding of Blumea balsamifera. Methods: 19 main morphological characters and their interrelationship were analyzed by using correlation analysis,multiple stepwise regression analysis and factor analysis. Results: Variation coefficients of the morphological characters were big in Blumea balsamifera. Correlation coefficients for morphological characters were significant( P <0. 05 or P < 0. 01). Using factor analysis,19 morphological characters were classified into six principal divisors. Ten morphological characters, including length / wide of leaf,trunk diameter, leaf number of second branch, leaf number of first branch, number of trunk leaf, weight of strong leaf, weight of young leaf,weight of old leaf, number of first branch, leaf number of whole plant, were the main factors which influenced the weight of whole plant leaf. Conclusion: The variation of every morphological character of Blumea balsamifera is abundant in different population, and a certain correlation is existed among morphological characters. The morphological characters, length / wide of leaf, trunk diameter, number of first branch, number and weight of leaf, are the main factors which influenced the weight of whole plant leaf.

[Content of mineral elements of Gastrodia elata by principal components analysis].

OBJECTIVE: To study the content of mineral elements and the principal components in Gastrodia elata. METHOD: Mineral elements were determined by ICP and the data was analyzed by SPSS. RESULT: K element has the highest content-and the average content was 15.31 g x kg(-1). The average content of N element was 8.99 g x kg(-1), followed by K element. The coefficient of variation of K and N was small, but the Mn was the biggest with 51.39%. The highly significant positive correlation was found among N, P and K . Three principal components were selected by principal components analysis to evaluate the quality of G. elata. P, B, N, K, Cu, Mn, Fe and Mg were the characteristic elements of G. elata. CONCLUSION: The content of K and N elements was higher and relatively stable. The variation of Mn content was biggest. The quality of G. elata in Guizhou and Yunnan was better from the perspective of mineral elements.

[Effects of Different Planting Direction and Layer Combination on Gastrodia elata f. elata in Bionic Wild Cultivation].

OBJECTIVE: Combination of different planting direction and layer were set to choose the best technology of cultivation of Gastrodia elata f. elata. METHODS: To improve the yield and quality of Gastrodia elata f. elata, randomized block design experiments were carried out to investigate the yield and quality, and to analyze their economic effectiveness in bionic wild cultivation. RESULTS: Length, width, thickness and weight of southern direction's Gastrodia elata f. elata developed better than the northeast direction. The three planting layer levels on growth effect of Gastrodia elata f. elata was the 3rd layer > the 2nd layer > the 1st layer. In six treatments, combination of southern direction-the 3rd layer was the best technology of cultivation of Gastrodia elata f. elata, which had the best growth condition, the highest yield significantly higher than other treatments, and the best economic benefits. CONCLUSION: Southern direction associated with the 3rd layer is the best combination to planting Gastrodia elata f. elata in bionic wild cultivation. The planting ways not only improve the yield and quality, but also save land.

Nuclear factor-κB signaling pathway is involved in phospholipase Cε-regulated proliferation in human renal cell carcinoma cells.

Phospholipase Cε (PLCε), a downstream effector of small GTPase superfamily, has been identified to play a crucial role in tumorigenesis. Previously, our studies have showed that PLCε promotes proliferation of renal cell carcinoma (RCC) cells. However, the molecular mechanisms by which PLCε enhances the survival phenotype of RCC cells are still not fully instructed. In the present study, we first demonstrated that PLCε was highly expressed and had a close correlation with Ki67 protein expression in RCC tissue samples. Further, we found that downregulation of PLCε expression repressed growth and induced apoptosis in RCC cells. In addition, we reported a mechanism by which knockdown of PLCε gene potently suppressed the nuclear factor kappa (NF-κB) signaling pathway through action on inhibitor of κB kinase. Moreover, silencing PLCε gene decreased vascular endothelial growth factor (VEGF) expression, which was a downstream growth factor of NF-κB signaling pathway. Finally, downregulation of VEGF was severely enhanced by treatment cells with NF-κB specific inhibitor BAY11-7028 in PLCε knockdown cells. Taken together, these findings suggest that PLCε promotes RCC cell growth via NF-κB-mediated upregulation of VEGF.

[Research on life history and phenological period of wild-stimulated cultivated Gastrodia elata f. elata in Guizhou].

In order to get to know the imitation of wild Gastrodia elata in life history and phenology period, by G. elata f. elata forest wild simulated cultivation in Dafang county, Guizhou province, observing and recording its morphological characteristics of each growth and development stage. This experiment summarized the law of its life history over 24 months, amplified the characteristics of each 5 phenology periods over the sexual and asexual reproduction of wild simulated cultivated G. elata f. elata in Guizhou. Which the results could clear the process of wild simulated cultivated G. elata f. elata in Guizhou, and provide a theoretical support for the standard technical of the simulated wild G. elata.

Waterlogging in soil restricts the growth of Gleditsia sinensis seedlings and inhibits the accumulation of lignans and phenolic acids in thorns.

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.

[Influence of hepatocyte cell adhesion molecule on gene expression profile of human bladder transitional cell carcinoma cell line].

OBJECTIVE: To investigate the changes of gene expression file in transitional cell carcinoma of bladder after hepatocyte cell adhesion molecule(hepaCAM) overexpression. METHODS: Affymetrix Human Genome U133 Plus 2.0 Array was used to investigate the changes of gene expression profile between adenovirus-green fluorescent protein(GFP) -hepaCAM group and GFP group in transitional cell carcinoma of bladder EJ cells.Significant Analysis of Microarray(SAM) was used to screen the differentially expressed genes, DAVID software was used to conduct gene ontology analysis and wikiPathway analysis based on the differentially expressed genes. Reverse transcription-polymerase chain reaction and Western blot were applied to verify microarray data. RESULTS: Compared with the GFP group, a total of 2469 genes were up-regulated or down-regulated by more than 2 times in the GFP-hepaCAM group. Among these genes, 1602 genes were up-regulated and 867 were down-regulated.Most of the differentially expressed genes were involved in the function of cell proliferation and cell cycle regulation. The mRNA expressions of nibrin, liver kinase B1, and cyclin D1 detected by reverse transcription-polymerase chain reaction in three different bladder cancer cell lines were consistent with the microarray data.The protein expressions of nibrin and liver kinase B1 in these three cell lines measured by Western blot were consistent with the mRNA expression. CONCLUSIONS: HepaCAM can alter the gene expression profile of bladder cancer EJ cells. The well-known anti-tumor effect of hepaCAM may be mediated by regulating the gene expression via multiple pathways.

[Habitat survey and biological characteristics study of Polygonum multiflorum germplasms in Guizhou region].

OBJECTIVE: To provide reference in selecting premium provenance and improve the cultivation techniques of Polygonum multiflorum. METHODS: Field survey, routine field-observation and sampling fixed plant for analysis in lab were adopted. RESULTS: The growing adaptability of Polygonum multiflorum was very strong, which growed flourishly in the condition with adequate light, ample rainfall, rich heat and fertile soil; Along with the lower of latitude, the vegetative period was prolonged and reproductive stage was delayed, which prolonged the time of roots' nutrition acquisition. Time for root shoot ratio increasing continuously of low latitude germplasms was higher than that of higher latitude germplasms. CONCLUSION: Polygonum multiflorum germplasms have different biological characteristics because of different regions and habitats, which can provide useful reference for selecting premium provenance and adjusting measures to local conditions in different areas.

Current Status and Influencing Factors of Readiness for Discharge of Elderly Patients with Chronic Obstructive Pulmonary Disease.

Objective: Readiness for hospital discharge is an important indicator of patients' transition from illness to health and can predict rehabilitation and prognosis. Identifying factors that influence readiness for discharge is crucial for developing effective nursing interventions. Therefore, this study aims to investigate the current status of discharge readiness and its influencing factors in elderly patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 311 elderly inpatients diagnosed with COPD were enrolled in this investigation at a tertiary hospital in Chengdu between December 2021 and June 2022. Questionnaires were designed to collect general information, disease-related information, and responses to the Readiness for Hospital Discharge Scale (RHDS) and the Quality of Discharge Teaching Scale (QDTS). Univariate and multivariate linear regression analyses were employed to further analyze factors related to discharge readiness and the correlation between discharge readiness and the quality of discharge guidance. Results: The total score of discharge readiness of elderly COPD patients was 77.72 ± 11.86 with a mean score of 6.48 ± 0.19 for each item. The quality of discharge instructions was 110.54 ± 15.66, with a mean score of 6.12 ± 0.15 for each item. Discharge preparation was positively correlated with the quality of discharge guidance. Multivariate analysis showed that marital status, admission mode, length of stay in hospital, Classification of Severity of Airflow Limitation, mMRC classification, number of medications taken with discharge, presence of inhalers in medication orders, mode of home oxygen therapy, and quality of discharge guidance were independent factors of discharge readiness in elderly COPD patients (P < 0.05). Conclusion: Both discharge readiness and the quality of discharge guidance for elderly COPD patients in China are currently suboptimal and need further improvement. The survey findings provide valuable insights that can guide future management practices and interventions aimed at improving discharge readiness.

Characterization of acute renal allograft rejection by proteomic analysis of renal tissue in rat.

Rapid and reliable biomarkers of renal allograft rejection have not been available. This study aimed to investigate biomarkers in renal allograft tissue using proteomic analysis. Orthotopic kidney transplantations were performed using Fisher (F344) or Lewis rats as donors and Lewis rats as recipients. Syngenic control group (Group I) constituted F344-to-F344 orthotopic kidney allo-transplantations (n = 8); and allogenic group (Group II) consisted of F344-to-Lewis orthotopic kidney allo-transplantations (n = 8). Renal tissues were harvested 7 days after transplantation. Samples were analyzed using 2-D electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry. 6 differentially expressed proteins were identified between allogenic group and syngenic control group. A rat model of acute renal allograft rejection was successfully set up. Differentially expressed proteins in renal allograft tissue of rat were detected using proteomic analysis and might serve as novel diagnostic and therapeutic targets in human. Quantitative proteomics, using MALDL-TOF-MS methodology has the potential to provide a profiling and a deeper understanding of acute renal rejection.

[Study on germination characteristics of Disporum cantoniense].

OBJECTIVE: To study the seed germination characteristic and optimal germination condition of wild Disporum cantoniense. METHODS: Used wild Disporum cantoniense seed as the test materials, the rate of water absorption of the seed was determined. The germination rates under different conditions, along a temperature gradient (15, 20, 25 and 30 degres C), in light or dark, on top or between wet filter papers, and keeping or removing the seed coat, were determined respectively using petri dish method. At the same time germination trends were observed. RESULTS: The thousand seed weight was 33.24 g, and the seed water-absorbing reached saturation pot after soaking for 30 h. Higher germination rates were respectively recorded at 25 degrees C, between filter papers, and in dark after 24 h soaking in the pretreatment solution. CONCLUSION: The optimal condition for the germination of the seed of wild Disporum cantoniense is as follow: keeping testa, seed soaking for 24 h in seed germination agent and being incubated between wet filter papers in dark at 25 degrees C.

Interlinked Microcone Resistive Sensors Based on Self-Assembly Carbon Nanotubes Film for Monitoring of Signals.

Flexible pressure sensors still face difficulties achieving a constantly adaptable micronanostructure of substrate materials. Interlinked microcone resistive sensors were fabricated by polydimethylsiloxane (PDMS) nanocone array. PDMS nanocone array was achieved by the second transferring tapered polymethyl methacrylate (PMMA) structure. In addition, self-assembly 2D carbon nanotubes (CNTs) networks as a conducting layer were prepared by a low-cost, dependable, and ultrafast Langmuir−Blodgett (LB) process. In addition, the self-assembled two-dimensional carbon nanotubes (CNTs) network as a conductive layer can change the internal resistance due to pressure. The results showed that the interlinked sensor with a nanocone structure can detect the external pressure by the change of resistivity and had a sensitive resistance change in the low pressure (<200 Pa), good stability through 2800 cycles, and a detection limit of 10 kPa. Based on these properties, the electric signals were tested, including swallowing throat, finger bending, finger pressing, and paper folding. The simulation model of the sensors with different structural parameters under external pressure was established. With the advantages of high sensitivity, stability, and wide detection range, this sensor shows great potential for monitoring human motion and can be used in wearable devices.

HepaCAM induces G1 phase arrest and promotes c-Myc degradation in human renal cell carcinoma.

Hepatocyte cell adhesion molecule (hepaCAM) encodes a generally inactive phosphorylated glycoprotein which mediates cancer cell proliferation, migration, and differentiation. We have reported that hepaCAM is down-regulated in renal cell carcinoma (RCC) and takes responsibility of cell growth inhibition. However, the precise mechanisms of hepaCAM inhibits cell growth is still unknown. In this study, we demonstrated that re-expression of hepaCAM can cause an accumulation in G0/G1 phase in 786-0 cells. This reaction was accompanied by a substantial reduction of c-Myc expression through using an ectopic hepaCAM expression system. Furthermore, we found a comparable decrease in proliferation and G0/G1 accumulation of 786-0 and RC-2 cells after treatment with a small molecule c-Myc inhibitor, 10058-F4. This indicated that the down regulation of c-Myc was an essential process in controlling growth inhibitory actions of hepaCAM. Nevertheless, re-expression of hepaCAM results in apparent reduction of c-Myc protein with no corresponding reduction of c-Myc mRNA. This suggests that this reaction might take place at a post-transcriptional level rather than transcriptional one. Consistent with these findings, hepaCAM decreased c-Myc stability by increasing the proportion of c-Myc phosphorylation on T58 which can be abrogated by a proteasomal inhibitor (MG132). Thus, our research implies that the decrease in c-Myc protein expression, resulting from ectopic expression of hepaCAM, may contribute to the inhibition of proliferation in these cells.

Normal values for renal parenchymal volume and kidney length as measured by non-enhanced multidetector spiral computed tomography.

BACKGROUND: Renal parenchymal volume (RPV) is considered an important index for clinical decisions. However, normal values have not been established, which hinders the clinical application of RPV. PURPOSE: To test the accuracy and reproducibility of RPV and to investigate the normal values of RPV and kidney length as measured by non-enhanced multidetector computed tomography (CT). MATERIAL AND METHODS: An animal model study was performed to test the accuracy and repeatability of RPV measured by CT. RPV of porcine kidneys was measured by water displacement (actual values) and non-enhanced multidetector CT. Individual RPV and kidney length were measured by non-enhanced CT in patients with no clinical history of renal disease (n = 722). Patient height, age, weight, body surface area (BSA), and body mass index (BMI) were assessed before each patient's CT examination was performed. RESULTS: RPV obtained by the CT method was within 2% of the RPV determined by the water displacement method. The normal values of RPV (M ± 1.96 standard deviation [SD]) were 145.72 ± 54.37 mL for men and 132.46 ± 41.94 mL for women. The normal values of kidney length (M ± 1.96 SD) were 10.27 ± 1.98 cm for men and 9.93 ± 1.58 cm for women. RPV did not significantly correlate with BSA or weight in women, but correlated significantly with height and age in both men and women. Of the assessed factors age, weight, height, BSA, and BMI, age, and height were the independent factors that best reflected RPV, in both men and women. CONCLUSION: The present animal study results showed that non-enhanced multidetector CT findings accurately reflect the RPV. The subsequent study performed in humans showed that the RPV of the presently sampled Chinese population was lower than the commonly quoted reference values obtained from Western populations.

[Glycosyl-phosphatidylinositol-anchored interleukin-2 expressed on tumor-derived exosomes induces anti-tumor immune response].

OBJECTIVE: To prepare IL-2-anchored and tumor-derived exosomes vaccine, and investigate the antitumor efficiency of the special cytotoxic T-lymphocytes induced by Ex/GPI-IL-2. METHODS: To construct pEGFP-N1-IL2gpi plasmid coding a fusion gene of a DNA oligo encoding GPI-anchor signal sequence attaching to human IL-2 cDNA. Then T24 cell lines stably expressing GPI-IL-2 proteins (T24/GPI-IL-2) were established. Ex/GPI-IL-2 were isolated and purified by ultrafiltration and sucrose gradient centrifugation, and the morphology and molecule markers were analyzed. The mixed lymphocyte reaction study and cytotoxic study were performed to determine the proliferative effect of T lymphocytes and the cytotoxicity induced by Ex/GPI-IL-2. RESULTS: The pEGFP-N1-IL2gpi plasmid was successfully constructed, and cell lines stably expressing GPI-IL-2 fusion proteins were established. Ex/GPI-IL-2 were small vesicular and saucer-shaped in diameter of 30-90 nm, containing heat shock protein 70, intercellular adhesion molecule-1, MAGE-1 and GPI-IL-2. Ex/GPI-IL-2-pulsed could dendritic cells induce proliferation of T cells and cytotoxic immune response more efficiently (P<0.05). CONCLUSIONS: GPI-IL-2 gene-modified tumor cells can make the exosomes containing GPI-IL-2 with an increased anti-tumor effect. Our study provides a feasible approach for exosome-based tumor immunotherapy of bladder transitional cell tumors.

[Preparation of renal cancer vaccine of IL-12-anchored exosomes and its antitumor effect in vitro].

OBJECTIVE: To prepare a vaccine of IL-12-anchored exosomes derived from renal cancer cells and to evaluate its antitumor effect in vitro. METHODS: A mammalian co-expression plasmid of glycolipid-anchor-IL-12 (GPI-IL-12) was constructed by subcloning IL-12A chain gene (P35 subunit) and a fusion gene containing GPI-anchor signal sequence and IL-12B chain gene (P40 subunit) in pBudCE4.1. Confocal laser scanning microscopy and flow cytometry were used to analyze the expression of the fusion proteins. Transmission electron microscopy and Western blot were used to identify the morphology and characteristic molecules of exosomes separated by ultrafiltration and sucrose gradient centrifugation. The function of IL-12-anchored exosomes was determined by IFN-gamma release assay. RESULTS: Mammalian co-expression plasmids were successfully constructed. Confocal laser scanning microscopy and flow cytometric analysis of the RC-2-GPI-IL-12 transfectants showed the expression of IL-12 on the cell surface. Exosomes were purified by ultrafiltration and sucrose gradient centrifugation, which were 30-80 nm in diameter, typically saucer-shaped, and expressing HSP70, ICAM-1, G250 and GPI-IL-12. (80.0 +/- 9.6) pg/ml of IL-12 was detected in 10 microg/ml exosomes and it significantly induced the release of IFN-gamma. Stimulation with EXO-IL-12 could efficiently induce antigen-specific cytotoxic T lymphocytes (CTL), resulting in more significant cytotoxic effects in vitro. CONCLUSION: A vaccine of exosomes-GPI-IL-12 can be obtained from the culture supernatant of renal cancer cells modified to express anchored IL-12. This vaccine expressing IL-12 and tumor associated antigen G250 may become a new strategy for the treatment of renal cancer.

Mixed adenoneuroendocrine carcinoma of the liver: A rare case report.

A 55-year-old woman presented with chest and back pain of unknown cause. Contrast-enhanced computed tomography revealed two low-density tumors, sized 4.6 and 4.4 cm, in the hepatic caudate and left inner lobes, respectively. There are multiple enlarged lymph nodes around the abdominal aorta, hepatogastric ligament and gastrosplenic ligament. At the same time, there were multiple enlarged lymph nodes between the portal vein and the vena cava. Upper gastrointestinal endoscopy revealed chronic non-atrophic gastritis and esophagitis (grade B). Endoscopic examination of the lower digestive tract revealed polyps of the colon, diagnosed as tubular adenomas following biopsy and histopathological examination. The patient underwent left three hepatic resection (including left inner lobe, left outer lobe and right anterior lobe resection), abdominal lymph node dissection, right liver tumor radiofrequency ablation, hepatic caudate lobe resection, intestinal adhesion release, vena cava formation, portal vein repair and hilar cholangioplasty. The pathological examination of the resected specimens revealed intrahepatic bile duct carcinoma and hepatic parenchymal neuroendocrine tumor (NET). In addition, liver solid portions consisted of tumor cells with characteristic salt-and-pepper nuclei. Immunohistochemical examination revealed expression of the neuroendocrine marker synaptophysin in this solid component, confirming the diagnosis of NET. Furthermore, the MIB-1 proliferation index of the NET was higher compared with that of the adenocarcinoma, and lymph node invasion by the NET component was detected, indicating a neuroendocrine carcinoma (NEC, or NET G3). The diagnosis of mixed adenoneuroendocrine carcinoma of the liver was confirmed based on the World Health Organization 2010 criteria. Taking into consideration the patient's poor general condition, only symptomatic supportive treatment was administered postoperatively, without chemotherapy. Contrast-enhanced computed tomography at 45 days postoperatively revealed disease progression, with metastases in the liver stump, abdominal lymph nodes, spine and pelvis. The patient remained on symptomatic supportive treatment and succumbed to disease progression 3 months after surgery.

PLCε knockdown prevents serine/glycine metabolism and proliferation of prostate cancer by suppressing YAP.

The metabolic reprogramming is an important basis for the development of many tumors, including prostate cancer (PCa). Metabolic changes in many amino acids consist of serine and glycine affect the biological behavior of them. Phospholipase C epsilon (PLCε) plays an important role as an oncogene. However, its role in regulating amino acid metabolism remains unclear. In this study, results found significantly positive correlation between PLCε and Yes-associated protein (YAP) in PCa tissues. LC-MS/MS and GC-MS results further displayed abnormally elevated levels of serine, glycine and its some downstream metabolites in the blood of PCa patients. Secondly, PLCε knockdown can inhibit serine/glycine producing and proliferation of PCa both in vivo and in vitro. Mechanistically, PLCε may affect the serine/glycine metabolism by regulating dephosphorylation and nuclear translocation of YAP. More interestingly, verteporfin (VP, a specific inhibitor of YAP) could effectively enhance the PLCε-depletion induced inhibition of serine/glycine secretion and growth. Overall, this research revealed the possibility of anomalous serine/glycine levels in the blood for the diagnosis of PCa, identified the important role of the PLCε/YAP axis in regulating serine/glycine metabolism, cell proliferation and tumor growth, and suggested the combination of VP with PLCε-depletion may provide a new idea for the treatment of PCa.