Association of FTH1-Expressing Circulating Tumor Cells With Efficacy of Neoadjuvant Chemotherapy for Patients With Breast Cancer: A Prospective Cohort Study.

BACKGROUND: The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. PATIENTS AND METHODS: This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. RESULTS: F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). CONCLUSIONS: The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer.

SCARECROW maintains the stem cell niche in Arabidopsis roots by ensuring telomere integrity.

Stem cells are the ultimate source of cells for various tissues and organs and thus are essential for postembryonic plant growth and development. SCARECROW (SCR) is a plant-specific transcription regulator well known for its role in stem cell renewal in plant roots, but the mechanism by which SCR exerts this function remains unclear. To address this question, we carried out a genetic screen for mutants that no longer express SCR in the stem cell niche of Arabidopsis (Arabidopsis thaliana) roots and characterized 1 of these mutants. Molecular genetics methods allowed us to pinpoint the causal mutation in this mutant in TELOMERIC PATHWAYS IN ASSOCIATION WITH STN 1 (TEN1), encoding a factor that protects telomere ends. Interestingly, TEN1 expression was dramatically reduced in the scr mutant. Telomerase and STN1 and CONSERVED TELOMERE MAINTENANCE COMPONENT 1 (CTC1), components of the same protein complex as TEN1, were also dramatically downregulated in scr. Loss of STN1, CTC1, and telomerase caused defects in root stem cells. These results together suggest that SCR maintains root stem cells by promoting expression of genes that ensure genome integrity. Supporting this conclusion, we demonstrated that the scr mutant accumulates more DNA damage than wild-type Arabidopsis and that this problem is aggravated after exposure to zeocin, a DNA damage reagent. Finally, we identified 2 previously uncharacterized motifs in TEN1 and provide evidence that a conserved amino acid residue in 1 of the motifs is indispensable for TEN1 function. SCR thus provides a connection between genome integrity and stem cell maintenance in Arabidopsis roots.

High Nitrate Accumulation in the Vadose Zone after Land-Use Change from Croplands to Orchards.

Additional evidence indicates that the nitrate stored in the deep soil profile has an important role in regulating the global nitrogen (N) cycle. This study assessed the effects of land-use changes from croplands to intensive orchards (LUCO) on N surplus, nitrate accumulation in deep soil, and groundwater quality in the kiwifruit belt of the northern slope region of the Qinling Mountains, China. LUCO resulted in comparatively high N surplus in orchards (282 vs 1206 kg ha-1 yr-1, respectively). The average nitrate accumulation within the 0-10 m profiles of orchards was 7113 kg N ha-1, which was equal to approximately the total N surplus of 6 years of the orchards. The total nitrate stock within 0-10 m soil profiles of the kiwifruit belt was 266.5 Gg N, which was 3.5 times higher than the total annual N input. The nitrate concentrations of 97% of groundwater samples exceeded the WHO standard. The LUCO resulted in large nitrate storage in the vadose zone and caused serious contamination of groundwater. Our study highlights that nitrate accumulation in the vadose zone of an intensive land-use system is one of the main fates of surplus N and also a hotspot of nitrate accumulation.

Atorvastatin induces autophagy in MDA-MB-231 breast cancer cells.

This article explores the effects of atorvastatin on cultured breast cancer cells. Our experiment demonstrated that atorvastatin triggered autophagy and inhibited proliferation in breast cancer cells. A CCK8 assay indicated that atorvastatin can inhibit the activity of MDA-MB-231 breast cancer cells. Western blotting results showed that atorvastatin increased the conversion of light chain 3 (LC3)-I to LC3-phosphatidylethanolamine conjugate (LC3-II). Confocal microscopy was used to reveal the appearance of a punctate structure in the cytoplasm, and electron microscopy was used to reveal the formation of double-membrane autophagosome. In conclusion, our study showed that atorvastatin may affect MDA-MB-231 breast cancer cells by inducing autophagy.

Novel IARS1 variants cause syndromic developmental disorder with epilepsy in a Chinese patient and the literature review.

BACKGROUND: Isoleucinyl-tRNA synthetase (IARS) is encoded by the IARS1 gene and catalyzes the binding of isoleucine to specific tRNA. OBJECTIVE: This study aims to investigate the pathogenicity of novel IARS1 variants and the genotype-phenotype association, in order to expand the spectrum of pathogenic variants and phenotypes of IARS1-related disease and provide new evidence for the phenotypic spectrum of IARS1 variants. METHODS: Clinical data of the proband were collected, and trio whole-exome sequencing (WES) was performed on the proband and the parents. Candidate variants were validated using Sanger sequencing. Bioinformatics software was utilized to analyze the functional consequences of identified variants and predict their potential deleteriousness. RESULTS: A 17-month-old female patient presented with microcephaly, left external ear malformation, decreased muscle strength and tone in all limbs, epileptic seizures, global developmental delay, and developmental regression. Trio WES identified compound heterozygous variants in the IARS1 gene, c.120-1G>A and c.2164C>A, which were novel pathogenic and likely pathogenic variants, respectively. The phenotype of developmental regression has not been reported before. Only one patient with IARS1 compound heterozygous variants has been reported in the world to have an epileptic phenotype, and this is the second patient with an epileptic phenotype. Bioinformatics analysis revealed that the splicing variant disrupted the canonical splice donor site, while the missense variant altered the local electrostatics of the IARS1 protein surface, potentially leading to functional abnormalities. CONCLUSION: This study identified novel IARS1 variants and the phenotype of developmental regression, expanding the spectrum of pathogenic variants and phenotypes of IARS1-related diseases and providing new evidence for the rare phenotype of epileptic seizures caused by IARS1 variants.

Effects of Magnesium Imbalance on Root Growth and Nutrient Absorption in Different Genotypes of Vegetable Crops.

Magnesium (Mg) plays a crucial role in crop growth, but how Mg supply level affects root growth and nutrient absorption in vegetable crops with different genotypes has not been sufficiently investigated. In this study, the responses of tomato (Solanum lycopersicum L.) and cucumber (Cucumis sativus L.) crops to different levels of Mg supply were explored. Four levels of Mg treatment (i.e., 0.2, 1.0, 2.0, 3.0 mmol/L) were applied under hydroponic conditions, denoted as Mg0.2, Mg1, Mg2, and Mg3, respectively. The results showed that with increasing Mg levels, the plant biomass, root growth, and nutrient accumulation in both vegetable crops all increased until reaching their maximum values under the Mg2 treatment and then decreased. The total biomass per tomato plant of Mg2 treatment was 30.9%, 14.0%, and 14.0% higher than that of Mg0.2, Mg1, and Mg3 treatments, respectively, and greater increases were observed in cucumber plant biomass (by 54.3%, 17.4%, and 19.9%, respectively). Compared with the Mg0.2 treatment, the potassium (K) and calcium (Ca) contents in various plant parts of both crops remarkably decreased under the Mg3 treatment. This change was accompanied by prominently increased Mg contents in various plant parts and para-hydroxybenzoic acid and oxalic acid contents in root exudates. Irrespective of Mg level, plant biomass, root growth, nutrient accumulation, and root exudation of organic acids were all higher in tomato plants than in cucumber plants. Our findings indicate that excessive Mg supply promotes the roots to exude phenolic acids and hinders the plants from absorbing K and Ca in different genotypes of vegetable crops despite no effect on Mg absorption. A nutritional deficiency of Mg stimulates root exudation of organic acids and increases the types of exuded organic acids, which could facilitate plant adaption to Mg stress. In terms of root growth and nutrient absorption, tomato plants outperform cucumber plants under low and medium Mg levels, but the latter crop is more tolerant to Mg excess.

A novel pyroptosis-related signature predicts prognosis and indicates immunotherapy in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) has been recognized as a frequently occurring oral malignant tumor. Pyroptosis plays an extremely important role in the occurrence and development of cancer, but the role of pyroptosis in OSCC remains unclear. METHODS: OSCC-related data were obtained from the TCGA and GEO databases. A PSscore risk model was constructed through LASSO regression analysis. The GEO database was utilized as the validation set of the model. The "ESTIMATE" and "CIBERSORT" algorithms were utilized to additionally evaluate the relationship between the immune cell score and PSscore. TIDE and IPS algorithms were used to assess patient response to immunotherapy. In addition, Western blot analysis and MTT assay was used to further validate key genes. RESULTS: Comprehensive bioinformatics analysis showed that a low-PSscore had a significant survival advantage, richer immune cell infiltration, more active immune-related pathways, higher TME scores, and lower tumor purity. The results of TIDE and IPS analysis indicated that the high-PSscore group had higher immune escape potential and was less sensitive to immunotherapy. In contrast, the low-PSscore group patients might be more sensitive to PD1 and CTLA4 + PD1 immunotherapy. Univariate and multivariate COX results indicated that PSscore was an independent prognostic factor in OSCC patients. Another important finding is that BAK1 is a potential target of OSCC and is related to the Nod-like receptor signaling pathway. Knockdown of BAK1 can significantly reduce the proliferation of OSCC cells. CONCLUSION: The PSscore model could be utilized as a powerful prognostic indicator and can help in the development of new immunotherapies.

Correlation of TGF-ß signaling pathway gene polymorphisms with unexplained recurrent spontaneous abortion.

BACKGROUND: The association of key genes in the transforming growth factor-ß (TGF-ß) signaling pathway and their gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) is unclear. OBJECTIVE: To investigate the association of gene polymorphisms related to the TGF-ß signaling pathway in URSA women. METHODS: The study population consisted of 80 women with URSA and 90 normal control women, of which 10 women with URSA and 10 normal control women underwent high-throughput sequencing to select loci, and the remaining 70 women with URSA and 80 normal control women underwent flight mass spectrometry experiments to verify gene loci polymorphism. A total of 7 polymorphic loci in interleukin-6 (IL-6), TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes were screened by high-throughput sequencing combined with a review of databases. An SNP flight mass spectrometer (Mass ARRAY detection system) was applied to detect the polymorphisms and their frequencies in 70 women with URSA and 80 normal control women at the 7 gene loci. RESULTS: Among the 7 loci of IL-6, TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes, 2 loci were found to have significantly different allele and genotype frequency distributions between the 70 URSA and 80 normal controls, one was the IL-6 gene -174G/C locus (rs1800795), the risk of disease was 2.636 and 3.231 times higher in individuals carrying the C allele and CC genotype than in those carrying the G allele and GG genotype, respectively; the other was the TGF-ß1 gene -509T/C locus (rs1800469), and the risk of disease was 1.959 and 3.609 times higher in individuals carrying the T allele and TT genotype than in those carrying the C allele and CC genotype, respectively. The remaining 5 genetic loci have no statistically significant. CONCLUSION: IL-6 gene -174G/C locus (rs1800795) genotype CC and allele C may be the causative factor of URSA, TGF-ß1 gene -509T/C locus (rs1800469) genotype TT and allele T may be the causative factor of URSA, and polymorphisms of the 2 loci may be associated with URSA.

GSPT1 Functions as a Tumor Promoter in Human Liver Cancer.

OBJECTIVE: This study analyzed the role of G1 to S phase transition 1 protein (GSPT1) in promoting progression of liver cancer cells. METHODS: A bioinformatics database was used to analyze the expression levels of GSPT1 in liver cancer tissues and the prognosis of patients. Subsequently, Western blotting and quantitative PCR were used to verify the expression levels of GSPT1 between normal hepatocytes and hepatoma cells. We used a CRISPR/Cas9 system to construct knockouts of GSPT1 in HepG2 and HCCLM9 liver cancer cells. The effect of GSPT1 on liver cancer cell migration and invasion was analyzed using flow cytometry, migration, and tumor formation assays. RESULTS: The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset indicated that GSPT1 expression was upregulated in liver cancer cell lines, and patients with liver cancer had poor prognosis. Knockout of GSPT1 in cells significantly inhibited tumor proliferation, cell migration, and growth in vivo. CONCLUSION: In this study, we found that GSPT1 promotes the migration and invasion of liver cancer cells.

Analysis of blocking antibodies and lymphocyte subsets in patients with recurrent reproductive failure.

This study aimed to explore the relationship between recurrent reproductive failure (RRF) and blocking antibody (BA) and lymphocytes, to explore the difference of immune status between recurrent spontaneous abortion (RSA) and recurrent implantation failure (RIF) patients. We undertook a retrospective analysis of BA and lymphocyte subsets detected by flow cytometry in 720 RRF patients (411 RSA and 309 RIF patients) who were treated at Shanxi Maternal and Child Health Hospital from April 2015 to October 2019. The BA negative rate of RRF patients was 81.80%, which was significantly higher than that of normal women (23.46%) (p < 0.05). There was no significant difference in BA negative rates between RSA and RIF patients. Compared with the normal value, the percentage of CD3+ T lymphocytes and CD3+CD4+ T lymphocytes in RRF patients were 71.1% (65.9-76.0) and 36.8% (32.5-41.9) respectively, which were significantly lower than the normal value (p < 0.05). The percentage of B cells in RSA patients [11.0 (8.8-13.9)] was significantly lower than that in RIF patients [11.9 (9.4-14.8)]. The occurrence of RRF is related to the lack of BA and the change of lymphoid subsets. There are some differences in immune status between RSA and RIF patients.

Comprehensive Analysis of Transcriptomics and Genetic Alterations Identifies Potential Mechanisms Underlying Anthracycline Therapy Resistance in Breast Cancer.

Anthracycline is a mainstay of treatment for breast cancer patients because of its antitumor activity. However, anthracycline resistance is a critical barrier in treating breast cancer. Thus, it is of great importance to uncover the molecular mechanisms underlying anthracycline resistance in breast cancer. Herein, we integrated transcriptome data, genetic alterations data, and clinical data of The Cancer Genome Atlas (TCGA) to identify the molecular mechanisms involved in anthracycline resistance in breast cancer. Two hundred and four upregulated genes and 1376 downregulated genes were characterized between the anthracycline-sensitive and anthracycline-resistant groups. It was found that drug resistance-associated genes such as ABCB5, CYP1A1, and CYP4Z1 were significantly upregulated in the anthracycline-resistant group. The gene set enrichment analysis (GSEA) suggested that the P53 signaling pathway, DNA replication, cysteine, and methionine metabolism pathways were associated with anthracycline sensitivity. Somatic TP53 mutation was a common genetic abnormality observed in the anthracycline-sensitive group, while CDH1 mutation was presented in the anthracycline-resistant group. Immune infiltration patterns were extremely different between the anthracycline-sensitive and anthracycline-resistant groups. Immune-associated chemokines and cytokines, immune regulators, and human leukocyte antigen genes were significantly upregulated in the anthracycline-sensitive group. These results reveal potential molecular mechanisms associated with anthracycline resistance.

Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3.

Most cancer-related deaths are a result of metastasis. The development of small molecular inhibitors reversing cancer metastasis represents a promising therapeutic opportunity for cancer patients. This pan-cancer analysis identifies oncogenic roles of membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3), which is crucial for cancer metastasis. Small molecules targeting PITPNM3 must be explored further. Here, PITPNM3-selective small molecular inhibitors are reported. These compounds exhibit target-specific inhibition of PITPNM3 signaling, thereby reducing metastasis of breast cancer cells. Besides, by using nanoparticle-based delivery systems, these PITPNM3-selective compounds loaded nanoparticles significantly repress metastasis of breast cancer in mouse xenograft models and organoid models. Notably, the results establish an important metastatic-promoting role for PITPNM3 and offer PITPNM3 inhibition as a therapeutic strategy in metastatic breast cancer.

Clinical outcomes of dialysis patients with COVID-19 in the initial phase of the COVID-19 outbreak in Wuhan, China.

PURPOSE: Since the end of 2019, dialysis patients have been at risk of coronavirus disease 2019 (COVID-19) as well as other potential complications. Hence, we sought to describe the clinical characteristics of dialysis patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We reviewed clinical outcomes, which consisted of clinical data extracted from the medical records of 695 registered dialysis patients at the Dialysis Center of Central Hospital of Wuhan from January 13th, 2020, to February 29th, 2020, and performed statistical analysis. According to the results, there were 447, 227 and 21 hemodialysis (HD), peritoneal dialysis (PD) and combined HD and PD (HD&PD) cases, respectively. RESULTS: During the outbreak of COVID-19, 36 dialysis patients were infected by SARS-CoV-2. Among those 36 patients, 32 (7.2%) were on HD, and 4 (1.8%) were on PD. When comparing SARS-CoV-2 infection between HD and PD, the relative risk was 4.07 (RR = 4.07, 95% CI 1.46-11.35). We noted a median age of 66 years during the observation period, and the number of male patients was 23 (63.9%). There were 15 fatal cases tested positive for SARS-CoV-2 (13 cases on HD and 2 cases on PD). By comparing mortality in the same period of 2018, 2019 and 2020, the all-cause mortality of hemodialysis patients was significantly higher in 2020 (4.89%) than in either 2018 (2.55%) or 2019 (1.97%). There was no significant difference in mortality from all causes excluding COVID-19, during the same period among the 3-year period. However, during the COVID-19 outbreak, the mortality from all causes excluding COVID-19 was 2.73%, which was slightly higher than that from COVID-19 (2.16%). CONCLUSIONS: Although COVID-19 seriously threatens the health of people with uremia, deaths from all causes excluding COVID-19 during the epidemic cannot be ignored.

Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer.

BACKGROUND: In locally advanced rectal cancer (LARC), preoperative short-course radiotherapy (SCRT) with delayed surgery has been shown to be as effective as long-course chemoradiotherapy, with only modest benefits. This study aimed to evaluate the efficacy and safety of preoperative SCRT combined with subsequent CAPOX (capecitabine and oxaliplatin) and the anti-PD-1 antibody camrelizumab in patients with LARC. METHODS: This was a prospective, single-arm, phase II trial. Treatment-naïve patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma received 5×5 Gy SCRT with two subsequent 21-day cycles of CAPOX plus camrelizumab after 1 week, followed by radical surgery after 1 week. The primary endpoint was pathological complete response (pCR) rate. Biomarker analysis was performed to identify a potential predictor of pCR to treatment. RESULTS: From November 7, 2019 to September 14, 2020, 30 patients were enrolled, and 27 patients received at least one dose of CAPOX plus camrelizumab. Surgery was performed in 27 (100%) patients. The pCR (ypT0N0) rate was 48.1% (13/27), including 46.2% (12/26) for proficient mismatch repair (MMR) tumors and 100% (1/1) for deficient MMR tumors. Immune-related adverse events were all grade 1-2, with the most common being reactive cutaneous capillary endothelial proliferation (81.5%). No grade 4/5 adverse events occurred. Biomarker analysis showed patients without FGFR1-3 deletions had a better tendency for pCR. CONCLUSIONS: SCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery showed a favorable pCR rate with good tolerance in patients with LARC, especially in the proficient MMR setting. A randomized controlled trial is ongoing to confirm these results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04231552.

LncRNA H19 diminishes dopaminergic neuron loss by mediating microRNA-301b-3p in Parkinson's disease via the HPRT1-mediated Wnt/ß-catenin signaling pathway.

Long non-coding RNAs (lncRNA) and microRNAs (miRNAs) are a subject of active investigation in neurodegenerative disorders including Parkinson's disease (PD). We hypothesized a regulatory role of lncRNA H19 with involvement of hypoxanthine phosphoribosyltransferase 1 (HPRT1) in dopaminergic neuron loss in PD model mice obtained by 6-hydroxydopamine (6-OHDA) lesions. We predicted the differentially expressed genes and related mechanisms by microarray analysis. We measured the expression of tyrosine hydroxylase (TH) and proneural genes in the substantia nigra of lesioned mice before and after treatment with lentiviral oe-HPRT1, agomir-miR-301b-3p and inhibition of the Wnt/ß-catenin pathway. We also evaluated the relationship among lncRNA H19, HPRT1 and miR-301b-3p as well as the Wnt/ß-catenin signaling pathway in these mice. The obtained results predicted and further confirmed a low level of HPRT1 in lesioned mice. We found low expression of lncRNA H19 and showed that its forced overexpression regulated HPRT1 by binding to miR-301b-3p. The overexpression of HPRT1 increased TH expression and inhibited dopaminergic neuron loss via activating the Wnt/ß-catenin pathway, as reflected by increased expressions of Nurr-1, Pitx-3, Ngn-2 and NeuroD1. Thus, overexpressed lncRNA H19 protects against dopaminergic neuron loss in this PD model through activating the Wnt/ß-catenin pathway via impairing miR-301b-3p-targeted inhibition of HPRT1 expression.

Land-use change from arable lands to orchards reduced soil erosion and increased nutrient loss in a small catchment.

China has been undergoing dramatic land-use change since the1980s. More arable lands have been converted to orchards to produce high-value fruits. There is an urgent need to assess the effects of these land-use changes on soil erosion and nutrient loss in the country. In this study, the Revised Universal Soil Loss Equation model, geographical information systems, and, remote sensing data were used to evaluate the effects of land-use change on soil erosion and nutrient loss in the Yujiahe Catchment, where a significant portion of the arable land that grew wheat and maize between1957 and 1989 was converted to kiwifruit orchards between 1990 and 2013. The total soil erosion from the catchment during 1957-2013 was in line with the sediments in the reservoir at the catchment outlet. Arable land was the major source of soil erosion and its erosion intensity was approximately ten times that of the orchards. The land-use change from arable land to orchard land since 1990 has reduced soil erosion intensity from severe to moderate. The arable land covering 28% of the catchment contributed to 81.3% of total organic matter loss and 80.4% of total nitrogen loss. However, the loss of available phosphorus mainly occurred in the orchards, representing 66.7% of the available phosphorus loss in the catchment. The soil erosion intensity of the arable land was highly sensitive to the land slope. We concluded that land use change from arable land to orchard land reduced soil erosion and increased the risk of nutrient loss from the catchment.

Atorvastatin Inhibits Breast Cancer Cells by Downregulating PTEN/AKT Pathway via Promoting Ras Homolog Family Member B (RhoB).

BACKGROUND: Breast cancer (BC) is one of the most common malignant tumors in women around the world. Atorvastatin (ATO) was found to be associated with a decreased risk of recurrence and mortality in cancer. But the exact mechanism of its carcinostatic effects is unclear. The expression level of Ras homolog family member B (RhoB) in breast cancer cells was found to be upregulated after being treated with ATO. Thus, we conjecture that altered expression of RhoB induced by ATO may be decisive for the migration and progression of breast cancer. METHODS: The effects of ATO on breast tumor cells in vivo and in vitro were detected by clone formation assay, CCK-8 assay, flow cytometry, wound healing, transwell assays, tumor xenograft model, and immunohistochemistry. Distribution of RhoB in different breast cancer tissues and its influence on prognosis were analyzed using the data from TCGA or GEO databases. The relationship between RhoB and PTEN/AKT pathway was detected by Western blotting and RT-qPCR. RESULTS: ATO inhibits proliferation, invasion, EMT, and PTEN/AKT pathway and promotes apoptosis in breast tumor cells. In addition, ATO inhibits the volume and weight of breast tumor in tumor-bearing mice and upregulated RhoB in tumor tissues. The expression of RhoB in mRNA and protein level was upregulated in statin-treated breast cancer cells and downregulated in cancer tissues. Low expression of RhoB links with poor prognosis in patients with breast cancer (HR = 0.74[0.66-0.83], p =7e-8, log-rank test). Further research found that RhoB inhibits the proliferation, invasion, EMT, and PTEN/AKT signal pathway in breast tumor cells. CONCLUSIONS: The exact mechanism of ATO's carcinostatic effects in breast cancer is related to downregulating PTEN/AKT pathway via promoting RhoB. Our study also demonstrates the potential applicability of RhoB as a therapeutic target for breast cancer.

Summer fallow increases loss of residual nitrogen fertilizer in dryland of the Loess Plateau: a 15N-labeled method.

Summer fallow is very common in dryland agriculture to conserve rainwater and replenish soil fertility. However, bare land and intensive rainfall during summer fallow might result in a potential risk of N loss. We used a 15N-labelling method to study the loss of residual N fertilizer during summer fallow and its use by next wheat in the Loess Plateau. Our study included three treatments: without the addition of N (N0W0), with the addition of 50 kg ha-1 N (NW0) and with the addition of 50 kg ha-1 N plus 35% more water (NW). The N fertilizer (K15NO3) in solution was injected into the soil at a depth of 35 cm of the polyvinyl chloride (PVC) columns in field. The fates of 15N were followed after summer fallow and in the next season's wheat (Triticum aestivum L.). The summer fallow of this study was a dry summer; however, fertilizer 15N was still leached down to 40-cm depth for the NW0 treatment; and for the NW treatment, the peak of 15N fertilizer was approximately 20 cm deeper. After summer fallow, the loss of the initially applied 15N was 26% in the soil profile for the NW0 treatment; and for the NW treatment, it increased to 37%. Soil 15N abundance in 0-20 cm of the NW0 and NW treatments was higher than the N0W0 treatment, indicating the upward movement of 15N in summer fallow. After the next wheat harvest, 15N uptake by wheat in the NW treatment decreased from 21.0 to 18.6% compared to the NW0 treatment. High rainfall during summer fallow increased residual N loss during summer fallow but decreased its use by the next crop.

P21-activated kinase 7 (PAK7) interacts with and activates Wnt/ß-catenin signaling pathway in breast cancer.

Background: Breast cancer is the highest incidence of tumor in women, which seriously threaten women's health. The occurrence and progression of breast cancer is linked to inactivation or downregulation of tumor suppressors, and activation or upregulation of oncogenes. However, the mechanism of PAK7 involving in the occurrence and progression of breast cancer is not yet fully understood. Methods: PAK7 expression was analyzed by RT-qPCR and immunohistochemistry and correlated with clinicopatholgical parameters in breast cancer tissue microarray. The effects of PAK7 on breast cancer cells were detected by CCK-8 assay, colon formation assay, wound healing and transwell assays, and flow cytometry. The relationship between PAK7 and Wnt/ß-catenin signaling pathway was determined by western blotting, TOP/FOP flash, co-Immunoprecipitation and co-localization assays. Results: PAK7 expression was significantly increased in breast cancer tissues and positively correlated with pathological differentiation and TNM stage of breast cancer. Overexpression of PAK7 could significantly promote proliferation and migration of breast cancer cells, and inhibit apoptosis. In contrast, PAK7 knockdown significantly inhibited the proliferation and migration of breast cancer cells and promoted apoptosis. In addition, PAK7 could activate Wnt/ß-catenin signaling pathway in breast cancer cells. Further study found that PAK7 could directly bind to GSK3ß and ß-catenin, and regulate ß-catenin degradation by phosphorylating GSK3ß. Conclusions: Our study demonstrated that PAK7, as an oncogene, involved in breast cancer progression by activating the Wnt/ß-catenin signaling pathway, suggesting that the potential applicability of PAK7 as a target for breast cancer treatment.

[Identification of a novel HLA allele B 4446 by sequencing-based typing].

OBJECTIVE: To identify a novel HLA allele in Chinese population. METHODS: A new HLA-B allele was initially detected by an usual PCR-SSP and PCR-SSOP in routine typing HLA allele. Sequence-based typing (SBT) was used to identify and analysis the difference between the new allele and HLA-B 4409 allele. RESULTS: The HLA-B exon 3 nucleotide sequence of the novel allele was different from all other known alleles. The allele had 3 nucleotides replaced of the closest matching B 4409 allele at nt538(G>C), nt539(A>T) and nt540 (C>G) in exon 3, resulting in an amino acid change from D(GAC) to L(CTG) at codon 180. CONCLUSION: A novel HLA allele was confirmed by the SBT and it was officially designated as HLA-B 4446 by WHO Nomenclature Committee for Factors of the HLA System in September,2005.