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BackgroundGlioma is the most common intracranial malignancy, and the available treatment options are poor. Long noncoding RNAs (lncRNAs) have been reported to be involved in the malignant progression of glioma. The role of ZNF503-AS2 in glioma has not been reported.MethodsWe screened ZNF503-AS2 with upregulated expression in glioblastoma (GBM) by analyzing the TCGA, CGGA and GTEx databases. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the enrichment of immune cells and signaling pathways in glioma samples. Single-cell datasets were used to analyze the distribution of ZNF503-AS2. In vitro experiments were used to investigate the biological function of ZNF503-AS2.ResultsZNF503-AS2 was highly expressed in glioma and was associated with poor prognosis, malignant progression and infiltration of immunosuppressive cells. Single-cell transcriptomic analysis showed that ZNF503-AS2 was mainly expressed in macrophages and tumor cells. Further analysis revealed that immunotherapy may have better efficacy in patients with low ZNF503-AS2 expression. In vitro experiments showed that knockdown of ZNF503-AS2 reduced the proliferation, invasion and migration ability of glioma cells, induced G2/M cell cycle arrest and promoted apoptosis.ConclusionsZNF503-AS2 might be a valuable biomarker for predicting the prognosis of glioma patients and a potential target for glioma therapy.

A large number of joints and fissures are prevalent in the rock mass, which has an important influence on the mechanical properties of the rock mass. To study the failure mechanical characteristics of Y-cracked rocks, the paper analyzes the influence of different angles of prefabricated Y-cracked rocks on the mechanical strength characteristics of the rocks and the crack extension evolution through uniaxial compression indoor tests and discrete element PFC2D numerical simulation. The results indicate that the stress-strain curves of rocks containing prefabricated cracks exhibit five stages: the initial pore-fracture compaction stage, the elastic stage, the crack stable development stage, the crack unstable development stage, and the post-peak rupture. The peak strength of the specimen shows an evolutionary process of decreasing, then increasing, and then decreasing with the increase of the Y-shaped crack angle. The failure of the sample is mainly caused by the shear crack expansion at the crack tip. The different Angle cracks directly affect the mechanical properties of the sample and the generation and evolution of new cracks. The final failure of rock is mainly the result of microcrack propagation, convergence and penetration to form macroscopic damage zone. Finally, combined with PFC numerical simulation, the distribution of micro-cracks and the damage pattern of rock damage are compared and analyzed, and it is found that the two are in good agreement, which reflects the rationality of the model.

BackgroundDefinitive evidence to guide clinical practice on the principles of surgery for retroperitoneal sarcomas (RPSs) is still lacking. This study aims to summarise the available evidence to assess the relative benefits and disadvantages of an aggressive surgical approach with contiguous organ resection in patients with RPS, the association between surgical resection margins and survival outcomes, and the role of surgery in recurrent RPS.MethodsWe searched PubMed, the Cochrane Library, and EMBASE for relevant randomised trials and observational studies published from inception up to May 1, 2021. Prospective or retrospective studies, published in the English language, providing outcome data with surgical treatment in patients with RPS were selected. The primary outcome was overall survival (OS).FindingsIn total, 47 articles were analysed. There were no significant differences in the rates of OS (HR: 0.93; 95% CI: 0.83-1.03; P = 0.574) and recurrence-free survival (HR: 1.00; 95% CI: 0.74-1.27; P = 0.945) between the extended resection group and the tumour resection alone group. Organ resection did not increase postoperative mortality (OR: 1.00; 95% CI: 0.55-1.81; P = 0.997) but had a relatively higher complication rate (OR: 2.24, 95% CI: 0.94-5.34; P = 0.068). OS was higher in R0 than in R1 resection (HR: 1.34; 95% CI: 1.23-1.44; P < 0.001) and in R1 resection than in R2 resection (HR: 1.86; 95% CI: 1.35-2.36; P < 0.001). OS was also higher in R2 resection than in no surgery (HR: 1.26; 95% CI: 1.07-1.45; P < 0.001), however, subgroup analysis showed that the pooled HR in the trials reporting primary RPS was similar between the two groups (HR, 1.14; 95% CI, 0.87-1.42; P = 0.42). Surgical treatment achieves a significantly higher OS rate than does conservative treatment (HR: 2.42; 95% CI: 1.21-3.64; P < 0.001) for recurrent RPS.ConclusionsFor primary RPS, curative-intent en bloc resection should be aimed, and adjacent organs with evidence of direct invasion must be resected to avoid R2 resection. For recurrent RPS, surgical resection should be considered as a priority. Incomplete resection remains to have a survival benefit in select patients with unresectable recurrent RPS.

Dirigent-jacalin (D-J) genes belong to the plant chimeric lectin family, and play vital roles in plant growth and resistance to abiotic and biotic stresses. To explore the functions of the D-J family in the growth and development of Moso bamboo (Phyllostachys edulis), their physicochemical properties, phylogenetic relationships, gene and protein structures, and expression patterns were analyzed in detail. Four putative PeD-J genes were identified in the Moso bamboo genome, and microsynteny and phylogenetic analyses indicated that they represent a new branch in the evolution of plant lectins. PeD-J proteins were found to be composed of a dirigent domain and a jacalin-related lectin domain, each of which contained two different motifs. Multiple sequence alignment and homologous modeling analysis indicated that the three-dimensional structure of the PeD-J proteins was significantly different compared to other plant lectins, primarily due to the tandem dirigent and jacalin domains. We surveyed the upstream putative promoter regions of the PeD-Js and found that they mainly contained cis-acting elements related to hormone and abiotic stress response. An analysis of the expression patterns of root, leaf, rhizome and panicle revealed that four PeD-J genes were highly expressed in the panicle, indicating that they may be required during the formation and development of several different tissue types in Moso bamboo. Moreover, PeD-J genes were shown to be involved in the rapid growth and development of bamboo shoots. Quantitative Real-time PCR (qRT PCR) assays further verified that D-J family genes were responsive to hormones and stresses. The results of this study will help to elucidate the biological functions of PeD-Js during bamboo growth, development and stress response.

BackgroundAlong with the vigorous development of Internet technology, increasing the functions of the various types of equipment, network communication easy and diversity, at the same time, the amount of data is very huge, under the network bandwidth limitations, through long lead to a data need to be cut into more, one by one, transfer times, information delay problems.ResultsAiming at the problems of poor data integrity, low efficiency and poor serialization efficiency of traditional data storage information, this article introduces Protobuf technology to study the serialization of data storage information. The serpentine gap method is used to complete the allocation interval of the sequence nodes, so that the working state and the resting state always maintain a dynamic balance. According to the first-level rules, the storage data of the completed target node is obtained, and the grammatical structure and the semantics of the target data are analyzed, Meanwhile corresponding correspondences are established, and the data storage information is serialized. In order to verify the effectiveness of Protobuf's data storage information serialization method, a comparative experiment is designed. By using three methods of HDVM, Redis and Protobuf to serialize JSON data, the comparative analysis shows that HDVM has the longest processing time and Protobuf has the shortest processing time, and the data integrity is not affected. The simulation data shows that the Protobuf serialization method has short conversion time, high space utilization, and the Obvious advantages in correctness and integrity. It is vary suitable for serialization of JSON data in the case of limited bandwidth.

This study determined the frequency and factors associated with EGFR testing rates and erlotinib treatment as well as associated survival outcomes in patients with non small cell lung cancer in Kentucky. Data from the Kentucky Cancer Registry (KCR) linked with health claims from Medicaid, Medicare and private insurance groups were evaluated. EGFR testing and erlotinib prescribing were identified using ICD-9 procedure codes and national drug codes in claims, respectively. Logistic regression analysis was performed to determine factors associated with EGFR testing and erlotinib prescribing. Cox-regression analysis was performed to determine factors associated with survival. EGFR mutation testing rates rose from 0.1% to 10.6% over the evaluated period while erlotinib use ranged from 3.4% to 5.4%. Factors associated with no EGFR testing were older age, male gender, enrollment in Medicaid or Medicare, smoking, and geographic region. Factors associated with not receiving erlotinib included older age, male gender, enrollment in Medicare or Medicaid, and living in moderate to high poverty. Survival analysis demonstrated EGFR testing or erlotinib use was associated with a higher likelihood of survival. EGFR testing and erlotinib prescribing were slow to be implemented in our predominantly rural state. While population-level factors likely contributed, patient factors, including geographic location (areas with high poverty rates and rural regions) and insurance type, were associated with lack of use, highlighting rural disparities in the implementation of cancer precision medicine.

Appalachian Kentucky (App KY) leads the nation in lung cancer incidence and mortality. Trace elements, such as As, have been associated with lung cancers in other regions of the country and we hypothesized that a population-based study would reveal higher trace element concentrations in App KY individuals with cancer compared to controls. Using toenail and drinking water trace element concentrations, this study investigated a possible association between lung cancer incidence and trace-element exposure in residents of this region. This population-based case-control study had 520 subjects, and 367 subjects provided toenail samples. Additionally, we explored the relationship between toenail and fingernail trace-element concentrations to determine if fingernails could be used as a surrogate for toenails when patients are unable to provide toenail samples. We found that, contrary to our initial hypothesis, trace element concentrations (Al, As, Cr, Mn, Co, Fe, Ni, Cu, Se, and Pb) were not higher in cancer cases than controls with the exception of Zn where concentrations were slightly higher in cases. In fact, univariate logistic regression models showed that individuals with lower concentrations of several elements (Al, Mn, Cr, and Se) were more likely to have lung cancer, although only Mn was significant in multivariate models which controlled for confounding factors. While drinking water concentrations of Al, Cr and Co were positively related to cancer incidence in univariate models, only Co remained significant in multivariate models. However, since the drinking water concentrations were extremely low and not reflected in the toenail concentrations, the significance of this finding is unclear. We also found that fingernail concentrations were not consistently predictive of toenail concentrations, indicating that fingernails should not be used as surrogates for toenails in future studies.

PURPOSE:Despite gains in life expectancy between 1992 to 2012, large disparities in life expectancy continue to exist in the United States between subgroups of the population. This study aimed to develop detailed life tables (LT), accounting for mortality differences by race, geography, and socio-economic status (SES), to more accurately measure relative cancer survival and life expectancy patterns in the United States. METHODS:We estimated an extensive set of County SES-LT by fitting Poisson regression models to deaths and population counts for U.S. counties by age, year, gender, race, ethnicity and county-level SES index. We reported life expectancy patterns and evaluated the impact of the County SES-LT on relative survival using data from the Surveillance Epidemiology and End Results (SEER) Program cancer registries. RESULTS:Between 1992 and 2012, the largest increase in life expectancy was among black men (6.8 years), however there were still large geographical differences. Life expectancy was highest for Asian or Pacific Islanders (API), and lowest for American Indians and Alaskan Natives (AIAN). In 2010, life expectancies by state ranged from 73 to 82 years for white males, 78 to 86 years for white females, 66 to 75 for black males, and 75 to 81 for black females. Comparisons of relative survival using National LT and the new County SES-LT showed that relative survival using County SES-LT improved relative survival estimates for some demographic groups, particularly in low and high SES areas, among Hispanics and AIAN, and among older male cancer patients. Relative survival using County SES-LT was 7.3% and 6.7% survival points closer to cause-specific survival compared to the National LT relative survival for AIAN and Hispanic cancer patients diagnosed between ages 75 and 84 years, respectively. Importantly, the County SES-LT relative survival estimates were higher in lower SES areas and lower in higher SES areas, reducing differences in relative survival comparisons. CONCLUSION:The use of these new socio-economic life tables (County SES-LT) can provide more accurate estimates of relative survival, improve comparisons of relative survival among registries, better illustrate disparities and cancer control efforts, and should be used as default for cancer relative survival using U.S. data.

BACKGROUND:Root-knot nematode (Meloidogyne spp., RKN) causes a disease that significantly reduces the yield of greenhouse cucumber crops year after year. Chemical control based on a single pesticide is now unreliable mainly due to pest resistance. Fumigant and non-fumigant pesticide combinations can potentially result in effective and economic RKN control. RESULTS:Combining the insecticide abamectin (ABM) with fumigants dazomet (DZ) or chloropicrin (CP) significantly extended the half-life of ABM by an average of about 1.68 and 1.56 times respectively in laboratory trials, and by an average of about 2.02 and 1.69 times respectively in greenhouse trials. Laboratory experiments indicated that all the low rate ABM combination treatments controlled RKN through a synergistic effect. ABM diffused into the nematode epidermis more rapidly when ABM was combined with DZ and CP, giving effective nematode control and an increase cucumber total yield, compared to the use of these products alone. ABM combined with CP or DZ produced significantly higher total cucumber yield than when these products were used alone. CONCLUSIONS:A low concentration of ABM combined with DZ in preference to CP would be an economic and practical way to control nematode and soilborne fungi in a greenhouse producing cucumbers.

OBJECTIVES:This systematic review and meta-analysis aims to determine the current evidence on risk factors for type II endoleaks after endovascular aneurysm repair (EVAR). MATERIALS AND METHODS:A systematic literature search was carried out for studies that evaluated the association of demographic, co-morbidity, and other patient-determined factors with the onset of type II endoleaks. Pooled prevalence of type II endoleaks after EVAR was updated. RESULTS:Among the 504 studies screened, 45 studies with a total of 36,588 participants were included in this review. The pooled prevalence of type II endoleaks after EVAR was 22% [95% confidence interval (CI), 19%-25%]. The main factors consistently associated with type II endoleaks included age [pooled odds ratio (OR), 0.37; 95% CI, 0.31-0.43; P

OBJECTIVE:General malnutrition usually occurs in critical limb ischemia (CLI) patients because of shortness of appetite and sleeplessness leaded by chronic pain. And amputation frequently is end-point of CLI patients. So the aim of this study was to assess the predictive ability of Geriatric nutritional risk index (GNRI) for predicting amputation in patients with CLI. METHODS:A retrospective study was designed. Demographics, history, comorbidity, and risk factors for peripheral vascular disease of admitted patients, and laboratory study were documented. Patients' height, weight and BMI were recorded. Amputation was identified as end-point during follow-up. Patients' amputation-free survival (AFS) was recorded. RESULT:172 patients were identified, with mean age 71.98±3.12. Geriatric nutritional risk index (GNRI) = 90 was taken as cutoff value of high risk of amputation for CLI patients via using receiver operating characteristic (ROC) curve. Span of follow-up was 12-48 months. During follow-up, 60 patients (36.04%) received amputation surgery. And analyzed by Cox proportional hazards model, it is found that GNRI was the independent predictive factor for amputation in long term. CONCLUSION:This study revealed that GNRI was a reliable and effective predictive marker for AFS. GNRI could identify patients with high risk for amputation in early time.

To evaluate the 8-year long-term outcome after internal iliac artery (IIA) coverage with or without embolization in EVAR.From January 2006 to December 2013, abdominal aortic aneurysm (AAA) subjects that underwent EVAR and IIA exclusion were recruited and analyzed retrospectively. All the subjects were divided into group A or B based on the presence or absence of intraoperative IIA embolization before coverage (group A: without embolization; group B: with embolization). The 30-day mortality, stent patency, and the incidences of endoleaks and ischemia of the buttocks and lower limbs were compared. The follow-up period was 96 months.There were 137 subjects (A: 74 vs. B: 63), 124 male (91.1%) and 13 female (9.5%), with a mean age of 71.6 years. There were no significant differences in the early outcomes of intraoperative blood loss (87.23±14.07 ml; A: 86.53±9.57 ml vs. B: 88.06±18.04 ml, p = .545) and surgery time (87.13±9.25 min; A: 85.99±7.07 min vs. B: 88.48±11.19 min, p = .130). However, there were significant differences in contrast consumption (65.18±9.85 ml; A: 61.89±7.95 ml vs. B: 69.05±10.50 ml, p

Huntingtin (Htt) is a 350 kD intracellular protein, ubiquitously expressed and mainly localized in the cytoplasm. Huntington's disease (HD) is caused by a CAG triplet amplification in exon 1 of the corresponding gene resulting in a polyglutamine (polyQ) expansion at the N-terminus of Htt. Production of full-length Htt has been difficult in the past and so far a scalable system or process has not been established for recombinant production of Htt in human cells. The ability to produce Htt in milligram quantities would be a prerequisite for many biochemical and biophysical studies aiming in a better understanding of Htt function under physiological conditions and in case of mutation and disease. For scalable production of full-length normal (17Q) and mutant (46Q and 128Q) Htt we have established two different systems, the first based on doxycycline-inducible Htt expression in stable cell lines, the second on "gutless" adenovirus mediated gene transfer. Purified material has then been used for biochemical characterization of full-length Htt. Posttranslational modifications (PTMs) were determined and several new phosphorylation sites were identified. Nearly all PTMs in full-length Htt localized to areas outside of predicted alpha-solenoid protein regions. In all detected N-terminal peptides methionine as the first amino acid was missing and the second, alanine, was found to be acetylated. Differences in secondary structure between normal and mutant Htt, a helix-rich protein, were not observed in our study. Purified Htt tends to form dimers and higher order oligomers, thus resembling the situation observed with N-terminal fragments, although the mechanism of oligomer formation may be different.

The adverse effects of microcystin (MC) produced by cyanobacteria have drawn considerable attention from the public. Yet it remains unclear whether MC confers any benefits to the cyanobacteria themselves. One suggested function of MC is complexation, which may influence the bioaccumulation and toxicity of trace metals. To test this hypothesis, we examined Cd toxicity to wild-type Microcystis aeruginosa PCC 7806 (WT) and its MC-lacking mutant (MT) under nutrient-enriched (+NP), phosphorus-limited (-P), and nitrogen-limited (-N) conditions. The accumulation of Cd and the biochemical parameters associated with its detoxification [total phosphorus (TP), inorganic polyphosphate (Poly-P), and glutathione (GSH) in the cells as well as intra- and extra-cellular carbohydrates] were quantified. Although the -P cyanobacteria accumulated less Cd than their +NP and -N counterparts, the different nutrient-conditioned cyanobacteria were similarly inhibited by similar free ion concentration of Cd in the medium ([Cd2+]F). Such good toxicity predictability of [Cd2+]F was ascribed to the synchronous decrease in the intracellular concentrations of Cd and TP. Nevertheless, Cd toxicity was still determined by the intracellular Cd to phosphorus ratio (Cd/P), in accordance with what has been reported in the literature. On the other hand, the concentrations of TP, Poly-P, and carbohydrates went up, but GSH concentration dropped down with the enhancement of [Cd2+]F, indicating their association with Cd detoxification. Although the inactivation of MC peptide synthetase gene had some nutrient and Cd concentration dependent effects on the parameters above, both cyanobacterial strains showed the same Cd accumulation ability and displayed similar Cd sensitivity. These results suggest that MC cannot affect metal toxicity either by regulating metal accumulation or by altering the detoxification ability of the cyanobacteria. Other possible functions of MC need to be further investigated.

The study on the lateral movement of soil organic carbon (SOC) during soil erosion can improve the understanding of global carbon budget. Simulated rainfall experiments on small field plots were conducted to investigate the SOC lateral movement under different rainfall intensities and tillage practices. Two rainfall intensities (High intensity (HI) and Low intensity (LI)) and two tillage practices (No tillage (NT) and Conventional tillage (CT)) were maintained on three plots (2 m width × 5 m length): HI-NT, LI-NT and LI-CT. The rainfall lasted 60 minutes after the runoff generated, the sediment yield and runoff volume were measured and sampled at 6-min intervals. SOC concentration of sediment and runoff as well as the sediment particle size distribution were measured. The results showed that most of the eroded organic carbon (OC) was lost in form of sediment-bound organic carbon in all events. The amount of lost SOC in LI-NT event was 12.76 times greater than that in LI-CT event, whereas this measure in HI-NT event was 3.25 times greater than that in LI-NT event. These results suggest that conventional tillage as well as lower rainfall intensity can reduce the amount of lost SOC during short-term soil erosion. Meanwhile, the eroded sediment in all events was enriched in OC, and higher enrichment ratio of OC (ERoc) in sediment was observed in LI events than that in HI event, whereas similar ERoc curves were found in LI-CT and LI-NT events. Furthermore, significant correlations between ERoc and different size sediment particles were only observed in HI-NT event. This indicates that the enrichment of OC is dependent on the erosion process, and the specific enrichment mechanisms with respect to different erosion processes should be studied in future.

The regeneration of tubular epithelial cells (TECs) after acute kidney injury (AKI) is crucial for the recovery of renal structure and function. The mechanism by which quiescent TECs re-obtain a potential to regenerate remains unknown. In this study, we observed a transient re-expression of embryonic gene Paired box 2 (Pax2) in adult rat TECs in vivo during ischemia-reperfusion induced AKI and most Pax2 positive TECs co-expressed kidney injury molecule-1 (KIM-1), a tubular injury marker. The re-expression of Pax2 was accompanied by increased levels of intrarenal Angiotensin II, which is a crucial injury factor of AKI. Furthermore, we also found a temporary re-expression of Pax2 in NRK-52E cells under the stimulation of Angiotensin II. This stimulatory effect could be blocked by PD123319 (Angiotensin II type 2 receptor (AT2R) inhibitor) and AG490 (Janus Kinase 2 (JAK2) inhibitor). As Pax2 is essential for the phenotypic conversion from mesenchymal stem cells to TECs during kidney development, we proposed that the re-expression of Pax2 in mature TECs may be an indicator of "atavistic" transition which mimics but reverses the processes of development of TECs. This could be proved by that a progenitor marker, CD24, was also found to be transiently expressed shortly after the expression of Pax2 in NRK-52E cells stimulated with Angiotensin II. The expression of CD24 was also suppressed by PD123319 and AG490. Moreover, knockdown of Pax2 by RNA interference could significantly reduce the expression of CD24 in NRK-52E cells stimulated with Angiotension II. Those findings suggest that mature TECs can trans-differentiate into progenitor-like cells by "atavistic transition", which may participate in the recovery of tissue structure and Pax2 may play a pivotal role in this process. That might have important implications for further understanding of tubular regeneration after injury.

Angiogenesis is a fundamental part of the response to tissue injury, which is involved in the development of hepatic fibrosis. Vascular endothelial growth factor plays an important role in angiogenesis. The expression of VEGF is increased during hepatic fibrogenesis and correlates with the micro-vessel density. In this study, we investigated the effects of bevacizumab, an anti-angiogenetic drug, on the formation of hepatic fibrosis. We found that bevacizumab could attenuate the development of hepatic fibrosis and contribute to the protection of liver function. Bevacizumab was also found to downregulate the expression α-SMA and TGF-β1, which have been reported to be profibrogenic genes in vivo. We also observed that the expression of VEGF increased significantly during the development of hepatic fibrosis and CCl4 was found to induce hepatocytes to secrete VEGF, which led to the activation and proliferation of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on the activation and proliferation of HSCs. Our results suggest that bevacizumab might alleviate liver fibrosis by blocking the effect of VEGF on HSCs. Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy.

Diabetes leads to exacerbating brain injury after ischemic stroke, but the underlying mechanisms and whether therapeutic intervention with anesthetic post-conditioning can induce neuroprotection in this population are not known. We tested the hypothesis that alteration of brain mitochondrial (mito) K(ATP) channels might cause exacerbating brain injury after ischemic stroke and attenuate anesthetic post-conditioning induced neuroprotection in diabetes. We also examined whether hyperglycemic correction with insulin would restore anesthetic post-conditioning in diabetes. Non-diabetic rats and diabetic rats treated with or without insulin were subjected to focal cerebral ischemia for 2 h followed by 24 h of reperfusion. Post-conditioning was performed by exposure to sevoflurane for 15 min, immediately at the onset of reperfusion. The role of the mitoK(ATP) channel was assessed by administration of a selective blocker 5-hydroxydecanoate (5-HD) before sevoflurane post-conditioning or by diazoxide (DZX), a mitoK(ATP) channel opener, given in place of sevoflurane. Compared with non-diabetic rats, diabetic rats had larger infarct volume and worse neurological outcome at 24 h after ischemia. Sevoflurane or DZX reduced the infarct volume and improved neurological outcome in non-diabetic rats but not in diabetic rats, and the protective effects of sevoflurane in non-diabetic rats were inhibited by pretreatment with 5-HD. Molecular studies revealed that expression of Kir6.2, an important mitoK(ATP) channel component, was decreased in the brain of diabetic rats as compared to non-diabetic rats. In contrast, hyperglycemic correction with insulin in diabetic rats normalized expression of brain Kir6.2, reduced ischemic brain damage and restored neuroprotective effects of sevoflurane post-conditioning. Our findings suggest that decreased brain mitoK(ATP) channel contributes to exacerbating ischemic brain injury and the failure of neuroprotection by anesthetic post-conditioning in diabetes. Insulin glycemic control in diabetes may restore the neuroprotective effects of anesthetic post-conditioning by modulation of brain mitoK(ATP) channel.

Although cancers are widely considered to be maintained by stem cells, the existence of stem cells in renal cell carcinoma (RCC) has seldom been reported, in part due to the lack of unique surface markers. We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line, contained the largest amount of SP cells as compared with other four cell lines. These 769P SP cells possessed characteristics of proliferation, self-renewal, and differentiation, as well as strong resistance to chemotherapy and radiotherapy that were possibly related to the ABCB1 transporter. In vivo experiments with serial tumor transplantation in mice also showed that 769P SP cells formed tumors in NOD/SCID mice. Taken together, these results indicate that 769P SP cells have the properties of cancer stem cells, which may play important roles in tumorigenesis and therapy-resistance of RCC.

Prostate cancer (PCa) remains as one of the most common cause of cancer related death among men in the US. The widely used prostate specific antigen (PSA) screening is limited by low specificity. The diagnostic value of other biomarkers such as RAS association domain family protein 1 A (RASSF1A) promoter methylation in prostate cancer and the relationship between RASSF1A methylation and pathological features or tumor stage remains to be established. Therefore, a meta-analysis of published studies was performed to understand the association between RASSF1A methylation and prostate cancer. In total, 16 studies involving 1431 cases and 565 controls were pooled with a random effect model in this investigation. The odds ratio (OR) of RASSF1A methylation in PCa case, compared to controls, was 14.73 with 95% CI = 7.58-28.61. Stratified analyses consistently showed a similar risk across different sample types and, methylation detection methods. In addition, RASSF1A methylation was associated with high Gleason score OR=2.35, 95% CI: 1.56-3.53. Furthermore, the pooled specificity for all included studies was 0.87 (95% CI: 0.72-0.94), and the pooled sensitivity was 0.76 (95% CI: 0.55-0.89). The specificity in each subgroup stratified by sample type remained above 0.84 and the sensitivity also remained above 0.60. These results suggested that RASSF1A promoter methylation would be a potential biomarker in PCa diagnosis and therapy.

Rice restorer lines play an important role in three-line hybrid rice production. Previous research based on molecular tagging has suggested that the restorer lines used widely today have narrow genetic backgrounds. However, patterns of genetic variation at a genome-wide scale in these restorer lines remain largely unknown. The present study performed re-sequencing and genome-wide variation analysis of three important representative restorer lines, namely, IR24, MH63, and SH527, using the Solexa sequencing technology. With the genomic sequence of the Indica cultivar 9311 as the reference, the following genetic features were identified: 267,383 single-nucleotide polymorphisms (SNPs), 52,847 insertion/deletion polymorphisms (InDels), and 3,286 structural variations (SVs) in the genome of IR24; 288,764 SNPs, 59,658 InDels, and 3,226 SVs in MH63; and 259,862 SNPs, 55,500 InDels, and 3,127 SVs in SH527. Variations between samples were also determined by comparative analysis of authentic collections of SNPs, InDels, and SVs, and were functionally annotated. Furthermore, variations in several important genes were also surveyed by alignment analysis in these lines. Our results suggest that genetic variations among these lines, although far lower than those reported in the landrace population, are greater than expected, indicating a complicated genetic basis for the phenotypic diversity of the restorer lines. Identification of genome-wide variation and pattern analysis among the restorer lines will facilitate future genetic studies and the molecular improvement of hybrid rice.

Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors.In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis.These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation.

Chronic inflammation-promoted metastasis has been considered as a major challenge in cancer therapy. Pro-inflammatory cytokine TNFα can induce cancer invasion and metastasis associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanisms are not entirely clear. In this study, we showed that TNFα induces EMT in human HCT116 cells and thereby promotes colorectal cancer (CRC) invasion and metastasis. TNFα-induced EMT was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin and fibronectin with a concomitant decrease of E-cadherin and Zona occludin-1(ZO-1). TNFα treatment also increased the expression of transcription factor Snail, but not Slug, ZEB1 and Twist. Overexpression of Snail induced a switch from E-cadherin to N-cadherin expression in HCT116 cells, which is a characteristic of EMT. Conversely, knockdown of Snail significantly attenuated TNFα-induced EMT in HCT116 cells, suggesting that Snail plays a crucial role in TNFα-induced EMT. Interestingly, exposure to TNFα rapidly increased Snail protein expression and Snail nuclear localization but not mRNA level upregulation. Finally, we demonstrated that TNFα elevated Snail stability by activating AKT pathway and subsequently repressing GSK-3β activity and decreasing the association of Snail with GSK-3β. Knockdown of GSK-3β further verified our finding. Taken together, these results revealed that AKT/GSK-3β-mediated stabilization of Snail is required for TNFα-induced EMT in CRC cells. Our study provides a better understanding of inflammation-induced CRC metastasis.