Fatty acid metabolism-related lncRNAs are potential biomarkers for survival prediction in clear cell renal cell carcinoma.

Metabolic reprogramming of energy is a newly recognized characteristic of cancer. In our current investigation, we examined the possible predictive importance of long noncoding RNAs (lncRNAs) associated to fatty acid metabolism in clear cell renal cell carcinoma (ccRCC). We conducted an analysis of the gene expression data obtained from patients diagnosed with ccRCC using the Cancer Genome Atlas (TCGA) database and the ArrayExpress database. We performed a screening to identify lncRNAs that are differentially expressed in fatty acid metabolism. Based on these findings, we developed a prognostic risk score model using these fatty acid metabolism-related lncRNAs. We then validated this model using Cox regression analysis, Kaplan-Meier survival analysis, and principal-component analysis (PCA). Furthermore, the prognostic risk score model was successfully validated using both the TCGA cohort and the E-MTAB-1980 cohort. We utilized gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to determine the correlation between fatty acid metabolism and the PPAR signaling pathway in patients with ccRCC at various clinical stages and prognoses. We have discovered compelling evidence of the interaction between immune cells in the tumor microenvironment and tumor cells, which leads to immune evasion and resistance to drugs. This was achieved by the utilization of advanced techniques such as the CIBERSORT method, ESTIMATE R package, ssGSEA algorithm, and TIMER database exploration. Ultimately, we have established a network of competing endogenous RNA (ceRNA) that is related to fatty acid metabolism. The findings of our study suggest that medicines focused on fatty acid metabolism could be clinically significant for individuals with ccRCC. The utilization of this risk model, which is centered around the lncRNAs associated with fatty acid metabolism, could potentially provide valuable prognostic information and hold immunotherapeutic implications for patients with ccRCC.

The Safety and Efficacy of Hepatic Arterial Infusion Chemotherapy Combined with PD-(L)1 Inhibitors and Molecular Targeted Therapies for the Treatment of Intermediate and Advanced Hepatocellular Carcinoma Unsuitable for Transarterial Chemoembolization.

Objective: To investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with PD-(L)1 inhibitors and molecular targeted therapies (MTT) for intermediate and advanced HCC that are unsuitable for transarterial chemoembolization (TACE). Methods: We conducted a retrospective analysis of data from patients with TACE-unsuitable HCC who were receiving triple therapy from January 2020 to December 2021 at two medical centers. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rates (ORR), disease control rates (DCR), and incidence of adverse events (AEs). Results: A total of 55 patients were enrolled in the study with median treatment periods of 4 and 6 for HAIC and PD-(L)1 inhibitors, respectively. The median OS and PFS were 15.0 and 10.0 months, respectively, with a median follow-up of 11.0 months (range: 4.0-27.5 months). According to the mRECIST criteria, the optimal ORR was 43.6% (24/55) and the DCR was 61.8% (34/55). The incidence of AEs was 58.2%, with grade 3 and above accounting for 20.0%; elevated AST (18.2%), hyperbilirubinemia (16.4%), and thrombocytopenia (16.4%) were most common. There were no treatment-related fatalities and all AEs were effectively managed. Multifactorial analysis showed that NLR > 3.82 (HR 2.380, 95% CI 1.116-2-5.079, P = 0.025), ECOG 1 (HR 2.906, 95% CI 1.373-6.154, P = 0.005), and extrahepatic metastases (HR 8.373, 95% CI 3.492-20.078, P < 0.001) were associated with the median OS. Conclusion: Triple therapy with HAIC, PD-(L)1 inhibitors, and MTT was safe and effective for patients with intermediate and advanced HCC for TACE-unsuitability.

Therapeutic Effects of Shenfu Injection in Shock.

Shock is the clinical manifestation of acute circulatory failure, which results in inadequate utilization of cellular oxygen. It is a common condition with high mortality rates in intensive care units. The intravenous administration of Shenfu Injection (SFI) may attenuate inflammation, regulate hemodynamics and oxygen metabolism; inhibit ischemia-reperfusion responses; and have adaptogenic and antiapoptotic effects. In this review, we have discussed the clinical applications and antishock pharmacological effects of SFI. Further in-depth and large-scale multicenter clinical studies are warranted to determine the therapeutic effects of SFI on shock.

Comparative transcriptome analysis reveals physiological responses in liver tissues of Epinephelus coioides under acute hypoxia stress.

Hypoxia is a common stressor for aquatic animals, including Epinephelus coioides, with a considerable impact on sustainable aquaculture. E. coioides is a widely consumed fish in China owing to its high nutritious value and taste. However, water hypoxia caused by high density culture process has become a great threat to E. coioides culture, and its response to hypoxia stress has not been discussed before. Therefore, the aim of this study was to examine the response of E. coioides to acute hypoxia using transcriptomic techniques. To this end, RNA sequencing was performed on the liver tissues of fish exposed to normoxic and hypoxic conditions for 1 h. The results presented 503 differentially expressed genes (DEGs) in the liver tissue of fish exposed to hypoxic condition compared with those in the normoxic group. Enrichment analysis using the Gene Ontology database showed that the DEGs were mainly enriched for functions related to cell apoptosis signaling pathways, insulin resistance, antioxidant enzymes, and glycolysis/gluconeogenesis signaling pathways. KEGG enrichment analysis showed that HIF-1, PI3K-AKT, IL-17, NF-kappa B, and MAPK signaling pathways were significantly enriched by the DEGs. The DEGs were mainly involved in immune response, inflammatory response, cell apoptosis regulation, energy metabolism, and substance metabolism. Additionally, the hypoxia response in E. coioides was mainly regulated via the PI3K-AKT-HIF-1 signaling axis. Overall, the findings of this study contribute to the understanding of hypoxia stress response in E. coioides, and provides target genes for breeding hypoxia-tolerant Epinephelus spp.

In Situ Construction of Bronze/Anatase TiO2 Homogeneous Heterojunctions and Their Photocatalytic Performances.

Photocatalytic degradation is one of the most promising emerging technologies for environmental pollution control. However, the preparation of efficient, low-cost photocatalysts still faces many challenges. TiO2 is a widely available and inexpensive photocatalyst material, but improving its catalytic degradation performance has posed a significant challenge due to its shortcomings, such as the easy recombination of its photogenerated electron-hole pairs and its difficulty in absorbing visible light. The construction of homogeneous heterojunctions is an effective means to enhance the photocatalytic performances of photocatalysts. In this study, a TiO2(B)/TiO2(A) homogeneous heterojunction composite photocatalyst (with B and A denoting bronze and anatase phases, respectively) was successfully constructed in situ. Although the construction of homogeneous heterojunctions did not improve the light absorption performance of the material, its photocatalytic degradation performance was substantially enhanced. This was due to the suppression of the recombination of photogenerated electron-hole pairs and the enhancement of the carrier mobility. The photocatalytic ability of the TiO2(B)/TiO2(A) homogeneous heterojunction composite photocatalyst was up to three times higher than that of raw TiO2 (pure anatase TiO2).

Protective Effect of Shenfu Injection on Vascular Endothelial Damage in a Porcine Model of Hemorrhagic Shock.

OBJECTIVE: To investigate the effects of Shenfu Injection (, SFI) on endothelial damage in a porcine model of hemorrhagic shock (HS). METHODS: After being bled to a mean arterial pressure of 40±3 mm Hg and held for 60 min, 32 pigs were treated with a venous injection of either shed blood (transfusion group), shed blood and saline (saline group), shed blood and SFI (SFI group) or without resuscitation (sham group). Venous blood samples were collected and analyzed at baseline and 0, 1, 2, 4, and 6 h after HS. Tumor necrosis factor-α (TNF-α), serum interleuking (IL)-6, and IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM -1), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and Bcl-2, Bax, and caspase-3 proteins were determined by Western blot. RESULTS: The serum level of TNF-α in the SFI group was significantly lower than in the other groups at 0, 1, and 2 h after HS, while the level of IL-6 was lower at 4 and 6 h compared with the saline group (P<0.01 or P<0.05). The concentration of serum IL-10 was significantly higher in the SFI group than in the other groups at 0, 1, 4, and 6 h after HS (P<0.01). Western blot and immunohistochemistry of vascular tissue showed that the expression of caspase-3 was downregulated, and that of Bcl-2 and Bax was upregulated in the SFI group compared to other groups (P<0.05). CONCLUSION: SFI attenuated endothelial injury in the porcine model of HS by inhibiting cell apoptosis, suppressing the formation of proinflammatory cytokines, and reducing endothelial activation.

[Expression of glucocorticoid receptor in prostate cancer and its clinical significance].

OBJECTIVE: To investigate the expression of glucocorticoid receptor (GR) in the PCa tissue and its correlation with the clinicopathological characteristics and prognosis of PCa. METHODS: Using immunohistochemical staining, we determined the expression of GR in the PCa tissue and analyzed its correlation with the clininicopathological features and prognosis of the malignancy. RESULTS: The positive expression of GR in the PCa tissue was 64%, of which the strongly positive rate was 34.7%. The GR expression was positively correlated with preoperative androgen-deprivation therapy (ADT) (χ2 = 22.307, P < 0.01), Gleason grades (χ2 = 16.534, P = 0.002) and clinical stages of the tumor (χ2 = 9.969, P = 0.041). Kaplan-Meier analysis showed that the GR expression was correlated not with the overall survival (P = 0.156), but with the PSA progression-free survival rate of the PCa patients (P = 0.042), with a shorter PSA progression-free survival time in those with a higher GR expression. Multivariate COX regression analysis revealed that the expression of GR was not an independent prognostic factor for PSA progression-free survival of the PCa patients. CONCLUSION: The expression of GR is related with preoperative ADT, and closely with the biological behavior of the malignancy and treatment resistance of the patients. GR is expected to be a new effective therapeutic target and a prognostic biomarker for PCa.

Novel dynamic enhanced robust principal subspace discriminant analysis for high-dimensional process fault diagnosis with industrial applications.

Since the data are often polluted by numerous measured noise or outliers, traditional subspace discriminant analysis is difficult to extract optimal diagnostic information. To alleviate the impact of the problem, a robust principal subspace discriminant analysis algorithm for fault diagnosis is designed. On the premise of decreasing the impact of redundant information, the optimal latent features can be calculated. Specifically, in the algorithm, dual constraints of the weighted principal subspace center and l2,1-norm are introduced into the objective function to suppress outliers and noise. Besides, considering that the current changes of the data in a dynamic process rely on past observations, merely analyzing the current data may lead to an incorrect interpretation of the mechanism model, especially in the presence of similar variable data under the two different conditions. Therefore, based on the robust principal subspace discriminant analysis, we further develop its dynamic enhanced version. The dynamic enhanced method utilizes the dynamic augmented matrix to enhance the latent features of historical data into current shifted features, so as to enlarge the difference between similar modes. Finally, the experimental results arranged on the Tennessee Eastman process and a commercial multi-phase flow process demonstrate that the proposed method has advanced diagnostic performance and satisfactory convergence speed.

Modified canonical variate analysis based on dynamic kernel decomposition for dynamic nonlinear process quality monitoring.

It is crucial to adopt an efficient process monitoring technique that ensures process operation safety and improves product quality. Toward this endeavor, a modified canonical variate analysis based on dynamic kernel decomposition (DKDCVA) approach is proposed for dynamic nonlinear process quality monitoring. Different from traditional canonical variate analysis and its expansive kernel methods, the chief intention of the our proposed method is to establish a partial-correlation nonlinear model between input dynamic kernel latent variables and output variables, and ensures the extracted feature information can be maximized. More specifically, the dynamic nonlinear model is orthogonally decomposed to obtain quality-related and independent subspace by singular value decomposition. From the perspective of quality monitoring, Hankel matrices of past and future vectors of quality-related subspace are derived in detail, and corresponding statistical metrics are constructed. Furthermore, given the existence of non-Gaussian process variables, kernel density estimation evaluates the upper control limit instead of traditional control limits. Finally, the experimental results conducted on a simple numerical example, the Tennessee Eastman process and the hot strip mill process indicate that the DKDCVA approach can be preferable to monitor abnormal operation for the dynamic nonlinear process.

Development of a Blocking Primer to Inhibit the PCR Amplification of the 18S rDNA Sequences of Litopenaeus vannamei and Its Efficacy in Crassostrea hongkongensis.

Diversity analyses of the eukaryotic microorganisms in the gut of marine animals is hampered by the presence of host DNA in the samples. PCR amplification of rRNA genes of eukaryotic microorganisms is inefficient with universal primers targeting 18S rRNA gene when the host DNA is dominant. In this study, we designed several blocking primers to inhibit PCR amplification of rRNA genes of the shrimp Litopenaeus vannamei, and tested their efficacy on the oyster Crassostrea hongkongensis. We first compared the intensity of PCR product bands obtained with and without the blocking primers. Then, one primer was selected for further verification using high-throughput sequencing. Our results showed that X-BP2-DPO was the most effective blocking primer in suppressing the host 18S amplification compared to nine other candidates. The inhibition rate was 99% for the amplification of shrimp rDNA, and 17% for the amplification of oyster rDNA. The concentration of the blocking primer in the PCR mixture was an important factor to be considered in the experimental design. The development of blocking primers provided a valid method to study the composition and characteristics of eukaryotic microorganisms in shrimp gut for a better understanding of its diets.

Insulated-tip knife combined with titanium clips and transparent cap in treatment of large pedunculated colorectal polyps / 中国内镜杂志

Objective To evaluate the efficacy and safety of combined use of insulated-tip knife, titanium clips and transparent caps in the resection of large pedunculated colorectal polyps. Methods Therapeutic method: with the assistance of transparent cap, 1~3 titanium clip(s) were applied to the base of the stalk to block blood supply of large polyps and then insulated-tip knife was utilized to resect polyps by cutting the stalk. Research method: retrospectively analyze the clinical data of 45 large pedunculated colorectal polyps (head ≥ 2.0 cm) which were treated by the method mentioned above from January 2014 to December 2015. Statistics of procedure time, clip numbers, complication rates were used to assess the effect of the treatment. Results 45 large polyps were successfully removed one time without any severe complications of bleeding or perforation during procedure except a very small amount of blood were oozing from the cutting edge in 3 cases. There were also no delayed complications of bleeding or perforation after procedure. The average number of titanium clip was 2.7 and the average operating time was (5.7 ± 1.2) min (range 3 ~ 12 min). Conclusion Combined application of insulated-tip knife, titanium clips and transparent cap inthe resection of large pedunculated colorectal polyps is safe, effective and convenient to conduct.

Insulated-tip knife combined with titanium clips and transparent cap in treatment of large pedunculated colorectal polyps / 中国内镜杂志

Objective To evaluate the efficacy and safety of combined use of insulated-tip knife, titanium clips and transparent caps in the resection of large pedunculated colorectal polyps. Methods Therapeutic method: with the assistance of transparent cap, 1~3 titanium clip(s) were applied to the base of the stalk to block blood supply of large polyps and then insulated-tip knife was utilized to resect polyps by cutting the stalk. Research method: retrospectively analyze the clinical data of 45 large pedunculated colorectal polyps (head ≥ 2.0 cm) which were treated by the method mentioned above from January 2014 to December 2015. Statistics of procedure time, clip numbers, complication rates were used to assess the effect of the treatment. Results 45 large polyps were successfully removed one time without any severe complications of bleeding or perforation during procedure except a very small amount of blood were oozing from the cutting edge in 3 cases. There were also no delayed complications of bleeding or perforation after procedure. The average number of titanium clip was 2.7 and the average operating time was (5.7 ± 1.2) min (range 3 ~ 12 min). Conclusion Combined application of insulated-tip knife, titanium clips and transparent cap inthe resection of large pedunculated colorectal polyps is safe, effective and convenient to conduct.

Braided thin-walled biodegradable ureteral stent: preliminary evaluation in a canine model.

OBJECTIVES: To evaluate a novel designed degradable ureteral stent. METHODS: A total of 24 male Beagles, each with bilateral stents implanted (a biodegradable ureteral 4.5-Fr stent and a standard 4-Fr biostable stent) were divided into four groups. Intravenous pyelography, B-mode ultrasonography, and blood and urine tests were carried out before the procedure (0 weeks), and at 1-, 2-, 3- and 4-week intervals. Meanwhile, the mechanical characteristics of stents were tested, and scanning electron microscopy images of the biodegradable braided stents were obtained at different time-points postoperatively. In addition, histopathological changes were compared between the two different stents. RESULTS: All biodegradable braided stents began degrading at 1 week, and had completely degraded by 4 weeks. Hydronephrosis was equivalent during the first 2 weeks, but less with the biodegradable stents than with the control biostable stents at 3 and 4 weeks. Preoperative and postoperative blood and urine results were similar. The mechanical properties of the biodegradable stents were better than conventional biostable stents. Scanning electron microscopy images obtained at different weekly intervals showed that stents degraded in a predictable fashion. Histological testing of the urinary tract showed that the stent-related tissue reactivity of the two different stents were similar. CONCLUSIONS: Our novel braided thin-walled biodegradable stents provide temporary renal drainage as good as commercially available biostable stents. They also have good biocompatibility and physical characteristics. Therefore, they might have clinical application.

Antinociceptive effect of berberine on visceral hypersensitivity in rats.

AIM: To assess the protective effect of berberine administration and the role of nitric oxide (NO) in visceral hypersensitivity. METHODS: Fifty male Sprague-Dawley rats were randomly assigned to five groups. An inflammatory bowel disease model was induced in rats by intracolonic instillation of 1 mL 4% acetic acid at 8 cm proximal to the anus for 30 s and restraint stress. After subsidence of inflammation on day 7 of the experiment, the rats were subjected to rectal distension, performed by a balloon (6-Fr, 2 mm external diameter, disposable silicon balloon-urethral catheter for pediatric use) which was rapidly inflated with increasing volumes of prewarmed (37 °C) water (0.1, 0.2, 0.3, 0.4, 0.6, 0.8 and 1 mL) for 30 s at four-minute intervals, and then the abdominal withdrawal reflex (AWR) and the level of fecal output were measured, respectively. AWR scores either 0, 1, 2, 3 or 4 were obtained by blinded observers. Rats had been pretreated with berberine or aminoguanidine (NO synthetase inhibitor) or berberine + aminoguanidine before measurement. RESULTS: The rats in the placebo group showed a hypersensitive response to rectal distension (2.69 ± 0.08 vs 1.52 ± 0.08, P = 0.000) and defecated more frequently than those in the control group (5.0 ± 0.16 vs 0.44 ± 0.16, P = 0.000). Comparing the berberine with placebo group, the AWR scores were reduced for all distension volumes and were significant at 0.2-1 mL (1.90 ± 0.08 vs 2.69 ± 0.08, P = 0.000), while the numbers of hard pellets, soft pellets, formless stools, and total fecal output in the placebo group were significantly larger than in the berberine group (5.0 ± 0.16 vs 2.56 ± 0.16, P = 0.000). Administration of aminoguanidine or berberine + aminoguanidine before VH score measurement reversed the antinociceptive effect of berberine (2.52 ± 0.08 vs 1.90 ± 0.08, P = 0.000; 2.50 ± 0.08 vs 1.90 ± 0.08, P = 0.000). The numbers of hard pellets, soft pellets, formless stool, and total of fecal output in aminoguanidine group were significantly larger than the corresponding values in control group, berberine group, and berberine + aminoguanidine group (4.81 ± 0.16 vs 0.44 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 2.56 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 3.75 ± 0.16, P = 0.000). The berberine and berberine + aminoguanidine groups showed reduced defecation, but aminoguanidine alone did not reduce defecation (2.56 ± 0.16 vs 4.81 ± 0.16, P = 0.000; 3.75 ± 0.16 vs 4.81 ± 0.16, P = 0.000). CONCLUSION: Berberine had an antinociceptive effect on visceral hypersensitivity, and NO might play a role in this effect.

Cognitive-behavioral therapy for the management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common disorder, reported to be found in 5%-20% of the general population. Its management accounts for up to 25% of a gastroenterologist's workload in the outpatient department, and the main symptoms are abdominal pain, bloating, and altered bowel habits. Despite a great amount of available pharmacological treatments aimed at a wide variety of gastrointestinal and brain targets, many patients have not shown adequate symptom relief. In recent years, there has been increasing evidence to suggest that psychological treatments, in particular cognitive-behavioral therapy (CBT), are effective for the management of IBS. This review discusses CBT for the management of IBS. CBT has proved to be effective in alleviating the physical and psychological symptoms of IBS and has thus been recommended as a treatment option for the syndrome.

[Effects of nitrogen application rate on soil nitrate nitrogen accumulation under vegetable-paddy rice rotation system].

A 2-year field experiment of mustard-cabbage-early rice rotation was conducted to investigate the effects of nitrogen application on yield and accumulation of nitrate nitrogen in the soil. The results showed that the applications of 150 kg N x hm(-2) for mustard and cabbage respectively and 90 kg N x hm(-2) for early rice were the best economic application mode, which could increase the net profit by 0.2%-75.6% compared with other application modes. Nitrogen application rates were positively correlated with NO3(-)-N concentration in the soil and in the percolating water. The vegetable-paddy rice rotation decreased the surplus of nitrogen in the soil. The average soil NO3(-)-N concentration was 29.7 mg x kg(-1) under the rotation of mustard-cabbage-early rice, which was only 84.4% of that under the continuous cropping of mustard-cabbage. The average NO3(-)-N concentration in the percolating water under mustard-cabbage-early rice rotation was little different from that in basal soil. Therefore, with the optimum nitrogen application mode, the vegetable-paddy rice rotation could gain the best economic benefit while significantly decrease the accumulation of nitrate nitrogen in the soil to effectively control non-point source pollution of nitrogen from vegetable fields.

The orphan receptor TR3 suppresses intestinal tumorigenesis in mice by downregulating Wnt signalling.

AIMS: Wnt signalling is involved in cellular homeostasis and development. Dysregulation of the Wnt signalling pathway has been linked to colorectal cancer. The orphan nuclear receptor TR3 plays important roles in proliferation and apoptosis. In this study, we investigated how TR3 suppresses intestinal tumorigenesis by regulating Wnt signalling. METHODS: Intestinal polyps were quantified in Apc(min/+), Apc(min/+)/TR3(-/-) and Apc(min/+)/villin-TR3 mice. Wnt signalling activity was evaluated by assessing ß-galactosidase activity in a BAT-Gal reporter strain. The TR3 agonist cytosporone B was used to evaluate the role of TR3 in intestinal tumorigenesis. Crosstalk between TR3 and ß-catenin/TCF4 was analysed by molecular methods in colorectal cancer cells. The phosphorylation of TR3 by glycogen synthase kinase (GSK) 3ß and the correlation between GSK3ß activity and TR3 phosphorylation were evaluated in clinical samples and colorectal cancer cells. RESULTS: TR3 was found to significantly suppress Wnt signalling activity and the proliferation of intestinal epithelial cells. Apc(min/+)/TR3(-/-) mice developed more intestinal polyps than Apc(min/+)/TR3(+/+) mice, whereas either transgenic overexpression of TR3 in the intestine or treatment with cytosporone B in Apc(min/+) mice significantly decreased intestinal tumour number. Mechanistically, TR3 disrupted the association of ß-catenin and TCF4 on chromatin and facilitated the recruitment of transcriptional co-repressors to the promoters of Wnt signalling target genes. However, TR3 was phosphorylated by GSK3ß in most clinical colorectal cancers, which attenuated the inhibitory activity of TR3 towards Wnt signalling. CONCLUSIONS: TR3 is a negative regulator of Wnt signalling and thus significantly suppresses intestinal tumorigenesis in Apc(min/+) mice. This inhibitory effect of TR3 may be paradoxically overcome through phosphorylation by GSK3ß in clinical colorectal cancers.

[Desorption characteristics of inorganic nitrogen in vegetable garden soil and their effects on soil NO3- -N loss potential].

With pot experiment and soil nitrogen desorption model, this paper studied the characteristics of nitrogen desorption in vegetable garden soil, and their effects on the NO3- -N concentration of soil leachate. The results showed that soil leachate NO3- -N concentration had a non-linear relationship with the parameters Q, Cli and C1/lamda of soil nitrogen, but the relationship became linear when these eigenvalues were relatively low. A conception of hi-curve cross point was put forward to assess the soil NO3- -N loss potential. When the eigenvalues were higher than the hi-curve cross point X0, the NO3- -N concentration in soil leachate would be increased rapidly in non-linear form, while on the contrary, the increase would be maintained at a lower level.

RXRalpha acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells.

Retinoid X receptor (RXR) plays a crucial role in the cross talk between retinoid receptors and other hormone receptors including the orphan receptor TR3, forming different heterodimers that transduce diverse steroid/thyroid hormone signaling. Here we show that RXRalpha exhibits nucleocytoplasmic shuttling in MGC80-3 gastric cancer cells and that RXRalpha shuttling is energy-dependent through a nuclear pore complex (NPC)-mediated pathway for its import and an intact DNA binding domain-mediated pathway for its export. In the presence of its ligand 9-cis retinoic acid, RXRalpha was almost exclusively located in the cytoplasm. More importantly, we also show that RXRalpha acts as a carrier to assist translocation of TR3, which plays an important role in apoptosis. Both RXRalpha and TR3 colocalized in the nucleus; however, upon stimulation by 9-cis retinoic acid they cotranslocated to the cytoplasm and then localized in the mitochondria. TR3 export depends on RXRalpha, as in living cells GFP-TR3 alone did not result in export from the nucleus even in the presence of 9-cis retinoic acid, whereas GFP-TR3 cotransfected with RXRalpha was exported out of the nucleus in response to 9-cis retinoic acid. Moreover, specific reduction of RXRalpha levels caused by anti-sense RXRalpha abolished TR3 nuclear export. In contrast, specific knockdown of TR3 by antisense-TR3 or TR3-siRNA did not affect RXRalpha shuttling. These results indicate that RXRalpha is responsible for TR3 nucleocytoplasmic translocation, which is facilitated by the RXRalpha ligand 9-cis retinoic acid. In addition, mitochondrial TR3, but not RXRalpha, was critical for apoptosis, as TR3 mutants that were distributed in the mitochondria induced apoptosis in the presence or absence of 9-cis retinoic acid. These data reveal a novel aspect of RXRalpha function, in which it acts as a carrier for nucleocytoplasmic translocation of orphan receptors.