Fully genotyping and screening of clinically important blood-group antigens by MALDI TOF mass spectrometry.

Several molecular biology methods are available for high-throughput blood typing. In this study, we aimed to build a high-throughput blood-group genetic screening system for high-frequency blood-group antigen-negative rare-blood groups in donors and patients. The amplification primers for all blood-type gene fragments involving the selected alleles were designed for detection. Single-base extend primers were also designed based on specific loci. DNA fragments were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) for the last nucleotide identification of amplification products in the extend step. The accuracy was verified by known samples. Thirty-six random samples were detected by serological tests and sequencing to verify the system stability. After verification, according to the collected known rare-blood-type samples, all the alleles designed to be detected matched with the validated single-nucleotide polymorphisms. The verification tests showed that all genotyping results of the random samples were in accordance with the findings of serotyping and sequencing. Then, 1258 random donor samples were screened by the built typing system after the verification. Three Fy(a-) and four s- were screened out in 1258 random blood samples. The multiple polymerase chain reaction-based MS detection system can be used in rare-blood-type screening with good accuracy and stability.

Research on double resonant excitation in a triangular electrode ion trap with asymmetric geometry.

RATIONALE: The triangular electrode linear ion trap with asymmetric geometry has been reported to possess a high ion unidirectional ejection efficiency and a reasonable mass resolution. To further improve its performance, a double resonant excitation method involving a dipolar and a quadrupolar resonant excitation was applied here. METHODS: The dipolar excitation method was carried out by applying a supplementary alternating voltage out of phase to one pair of the electrodes, whereas the quadrupolar excitation (QE) method was carried out by adding a supplementary alternating voltage in phase to another pair of electrodes. Numerical simulations were performed to explore the impact of the frequency difference between the alternating current (AC) and the QE voltage (∆ω), the frequency of the AC voltage (ωAC), and the QE voltage amplitude (VQE). RESULTS: The mass resolution could be improved to ~4700 m / ∆ m $$ \left(m/\Delta m\right) $$ , which was approximately twice compared to that with only dipolar resonant excitation, and the ion unidirectional ejection efficiency could be improved to 97%. Even with a high scan rate of 6000 Da/s, there was minimal loss of mass resolution caused by increased scan rate in double resonant excitation mode. CONCLUSIONS: By employing the double resonant excitation method, the mass resolution could be further increased while maintaining a considerably high ion unidirectional ejection efficiency, which might be a simple and practical approach for developing a high-performance miniature ion trap mass analyzer.

Retrospective analysis of 71 patients with cutaneous sporotrichosis.

OBJECTIVE: To summarise 71 cases of cutaneous sporotrichosis in Zhejiang over the past 9 years and analyse clinical and epidemiological characteristics. METHODS: This was a retrospective review of patients with cutaneous sporotrichosis attending the Department of Dermatology of the Hangzhou Third People's Hospital between 2013 and 2022. RESULTS: The male-to-female ratio was 1.15:1 among the 71 patients, with a mean age of 55.90 years (±2.02) and an age range of 3 to 94 years. The disease duration was unknown for 17 patients. The intermediate course for the remaining 54 patients lasted 11.90 months, ranging from 1 to 120 months. Thirty-four patients were involved in mixed occupations, 28 were farmers, 4 were housewives, 3 were manufacturing workers, and 2 were carpenters; 23.95% of cases had a history of trauma. The most common clinical manifestation was fixed cutaneous (69.01%), followed by lymphocutaneous (29.58%) and disseminated cutaneous (1.41%). There were 72 affected sites; the upper limbs (69.44%) were affected the most, followed by the face (16.67%) and lower limbs (12.50%). Forty-nine patients showed open lesions (69.01%), 15 showed mixed lesions (21.13%), and seven showed closed lesions (9.86%). Seventy-one patients were confirmed by biopsied tissue or tissue fluid culture. Forty-four patients underwent direct microscopy; of these, 18 (40.91%) were positive and 26 were negative. Molecular analysis confirmed that all fungal strains were Sporothrix globosa. Fifty-nine patients underwent histopathological examination, of whom 18 (18.64%) were positive for periodic acid-Schiff (PAS) staining. Eighteen patients were lost to follow-up; the remaining patients were cured. CONCLUSIONS: Consistent with the epidemiological situation of sporotrichosis in other areas of China, S. globosa is the primary pathogen in the Zhejiang province. The primary clinical form of sporotrichosis is fixed cutaneous. Susceptible subjects are mainly middle-aged and elderly rural populations, and males are affected more than females. Patients with cutaneous sporotrichosis do not commonly have a history of obvious trauma. Direct microscopy is important for the diagnosis of sporotrichosis, and itraconazole is a safe and effective treatment option.

Eucalyptol antagonized the apoptosis and immune dysfunction of grass carp hepatocytes induced by tetrabromobisphenol A by regulating ROS/ASK1/JNK pathway.

Tetrabromobisphenol A (TBBPA) is a common environmental pollutant which has multi-organ toxicity to mammals. Eucalyptol (EUC) has super antioxidant biological activity. However, in this experimental study, we probed into the mechanism of toxic of TBBPA exposure on Grass carp hepatocytes (L8824 cells) and the antagonistic impact of EUC on TBBPA. We treated L8824 cells with 8 µg/ml TBBPA and/or 20 µM EUC for 24 h in this test research. The experiment results suggested that TBBPA exposure induced elevated levels of reactive oxygen species (ROS), led to oxidative stress, decreased SOD and CAT activities, decreased GSH and T-AOC contents, exacerbated MDA accumulation, activated ASK1/JNK signaling pathway, and further increased the contents of mitochondrial dependent apoptosis pathway related indicators (Cyt-C, Bax, Caspase 9, Caspase 3), while Bcl-2 expression decreased. In addition, TBBPA exposure induced increased expression of TNF-α, IL-6, IL-1ß, and decreased expression of IL-2, IFN-γ, Hepcidin, ß-defensin, LEAP2. The oxidative stress level, ASK1/JNK signal pathway expression level, apoptosis ratio and cellular immune function of cells exposed to EUC alone did not change significantly. Combined exposure of TBBPA and EUC significantly reduced the proportion of apoptosis and restored cellular immune function. Therefore, these results suggest that EUC can effectively antagonize TBBPA-induced apoptosis and immune dysfunction of L8824 cells by regulating ROS/ASK1/JNK signaling pathway.

Tannic acid through ROS/TNF-α/TNFR 1 antagonizes atrazine induced apoptosis, programmed necrosis and immune dysfunction of grass carp hepatocytes.

Atrazine (ATR) is a commonly used triazine herbicide, which will remain in the water source, soil and biological muscle tissue for a long time, threatening the survival of related organisms and future generations. Tannic acid (TAN), a glucosyl compound found in gallnuts, has previously been shown to antagonize heavy metal toxicity, antioxidant activity, and inflammation. However, it is unclear whether TAN can antagonize ATR-induced Grass carp hepatocytes (L8824 cells) cytotoxicity. Therefore, we treated L8824 cells with 3 µg mL-1 ATR for 24 h to establish a toxic group model. The experimental data of flow cytometry and AO/EB staining together showed that the ratio of apoptosis and necrosis in L8824 cells after ATR exposure was significantly higher than that in the control group. Furthermore, RT-qPCR showed that inflammatory factors (TNF-α, IL-1ß, IL-6, INF-γ) were up-regulated and antimicrobial peptides (hepcidin, ß-defensin and LEAP2) were induced down-regulated in L8824 cells, leading to immune dysfunction. The measurement results of oxidative stress-related indicators showed that the levels of ROS and MDA increased after ATR exposure, the overall anti-oxidative system was down-regulated. Western blotting confirmed that TNF-α/TNFR 1-related genes were also up-regulated. This indicates that ATR stimulates oxidative stress in L8824 cells, which in turn promotes the binding of TNF-α to TNFR 1. In addition, TRADD, FADD, Caspase-3, P53, RIP1, RIP3 and MLKL were found to be significantly up-regulated by Western blotting and RT-qPCR. Conditioned after ATR exposure compared to controls. It indicates that ATR activates apoptosis and necrosis of TNF-α/TNFR 1 pathway by inducing oxidative stress in L8824 cells. Furthermore, the use of TAN (5 µM) significantly alleviated the toxic effects of ATR on L8824 cells mentioned above. In conclusion, TAN restrains ATR-induced apoptosis, programmed necrosis and immune dysfunction through the ROS/TNF-α/TNFR 1 pathway.

Eucalyptol relieves the toxicity of diisobutyl phthalate in Ctenopharyngodon idellus kidney cells through Keap1/Nrf2/HO-1 pathway: Apoptosis-autophagy crosstalk and immunoregulation.

Diisobutyl phthalate (DiBP), one of the commonly used plasticizers in industry, is an endocrine disruptor and environmental contaminant that can persist in water and threaten the health of aquatic creatures. Eucalyptol (Euc), a monoterpenoid extracted from plants, has been proved to have anti-inflammatory, antioxidant, and detoxification properties. However, the protective mechanism of Euc against cell injury caused by DiBP exposure and the involvement of apoptosis, autophagy, and immunity remains unknown. In the current investigation, 27.8 µg/mL DiBP or/and 20 µM Euc has been applied to Ctenopharyngodon idellus kidney (CIK) cells for 24 h. The findings showed that exposure to DiBP raised intracellular ROS levels, inducing oxidative stress, and enhanced the rate of apoptosis as well as the expression of the apoptotic markers Bax, Caspase3, Caspase9, and Cytc while decreasing the expression of Bcl-2. Furthermore, DiBP inhibited IL-2, IFN-γ, Hepcidin-1, and ß-defensin expression and elevated TNF-α, and IL-1ß levels, causing immune dysfunction. DiBP and Euc co-treatment significantly activated the Keap1/Nrf2/HO-1 pathway, restored antioxidant enzyme activity, and elevated autophagy pathway-associated genes ATG5, Beclin1, and LC3B decreased p62 expression, enhanced cell autophagy, reduced apoptosis, and improved immunity. In conclusion, Euc promotes autophagy, alleviates DiBP-induced apoptosis, and improves immunological dysfunction in CIK cells by regulating the Keap1/Nrf2/HO-1 pathway. These results demonstrated the threat of DiBP exposure to fish while providing a theoretical foundation for using Euc in aquaculture.

Vacancy-Rich and Porous NiFe-Layered Double Hydroxide Ultrathin Nanosheets for Efficient Photocatalytic NO Oxidation and Storage.

An appealing strategy in the direction of circular chemistry and sustainable nitrogen exploitation is to efficiently convert NOx pollutants into low-toxic products and simultaneously provide crop plants with metabolic nitrogen. This study demonstrates that such a scenario can be realized by a defect- and morphology-coengineered Ni-Fe-layered double hydroxide (NiFe-LDH) comprising ultrathin nanosheets. Rich oxygen vacancies are introduced onto the NiFe-LDH surface, which facilitate charge carrier transfer and enable photocatalytic O2 activation into superoxide radicals (•O2-) under visible light. •O2- on NiFe-LDH thermodynamically oxidizes NO into nitrate with selectivity over 92%, thus suppressing dangerous NO2 emissions. By merit of abundant mesopores on NiFe-LDH ultrathin nanosheets bearing a high surface area (103.08 m2/g), nitrate can be readily stored without compromising the NO oxidation reactivity or selectivity for long-term usage. The nitrate species can be easily washed off the NiFe-LDH surface and then enriched in the liquid form as easy-to-use chemicals.

Traceable Scheme of Public Key Encryption with Equality Test.

Public key encryption supporting equality test (PKEwET) schemes, because of their special function, have good applications in many fields, such as in cloud computing services, blockchain, and the Internet of Things. The original PKEwET has no authorization function. Subsequently, many PKEwET schemes have been proposed with the ability to perform authorization against various application scenarios. However, these schemes are incapable of traceability to the ciphertexts. In this paper, the ability of tracing to the ciphertexts is introduced into a PKEwET scheme. For the ciphertexts, the presented scheme supports not only the equality test, but also has the function of traceability. Meanwhile, the security of the proposed scheme is revealed by a game between an adversary and a simulator, and it achieves a desirable level of security. Depending on the attacker's privileges, it can resist OW-CCA security against an adversary with a trapdoor, and can resist IND-CCA security against an adversary without a trapdoor. Finally, the performance of the presented scheme is discussed.

Blood group-related antigen Ley on human platelets and its involvement in platelet aggregation via a possible interaction with CD61.

BACKGROUND: The Ley antigen is a carbohydrate chain belonging to the ABH-Lewis blood group family. Ley has been reported to be present on red blood cells (RBCs) and granulocytes, but its distribution and function in platelets remain unknown. There are a variety of glycoproteins on platelets, which may carry the Ley antigen. This study aims to investigate the expression pattern and the function of Ley in human platelets. STUDY DESIGN AND METHODS: Flow cytometry, Western blot, and immunofluorescence assays were performed to determine Ley expression on human platelets. ADP (1.25-10 µM) and thrombin (0.05-1 IU/mL) were used to activate platelets in the presence or absence of prostaglandin E1 (PGE1) and the Ley expression was evaluated again by flow cytometry. Blockade was performed with an anti-Ley monoclonal antibody to verify the role of this epitope in platelet function. Finally, coimmunoprecipitation was performed to identify glycoproteins associated with Ley . RESULTS: Ley was expressed on human platelets independent of ABO blood type. Ley expression was decreased in a dose-dependent manner after activation with either ADP or thrombin, and this effect could be partially reversed by PGE1. Anti- Ley mAb treatment increased alpha-granule release and neutralized the inhibitory effect of the anti-CD61 antibody on platelet aggregation. In addition, Ley was proven to interact and colocalize with CD61. CONCLUSIONS: These results demonstrate nondifferential expression of Ley in platelets of different ABO blood types and suggest the involvement of Ley in platelet function, possibly via interaction with CD61.

Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes.

Context: Oridonin exhibits various pharmacological and physiological activities, including antioxidant, antibacterial, anti-inflammatory, pro-apoptotic, anticancer and neurological effects. However, its role in rheumatoid arthritis (RA) is yet to be revealed.Objective: We evaluated the effects of oridonin on the survival and autophagy of RA-fibroblast-like synoviocytes (FLSs).Materials and methods: RA-FLSs were treated with oridonin at serial concentrations of 0, 2, 4, 6, 8 and 10 µg/mL for 24, 48 and 72 h. Then, cell proliferation and apoptosis were measured. A GFP-LC3 plasmid was transfected into the cells to determine autophagy.Results: Oridonin suppressed RA-FLS proliferation in a dose-dependent manner. The half maximal inhibitory concentrations (IC50) of oridonin at 24, 48 and 72 h were 8.28, 7.88 and 8.35 µg/mL, respectively. Treatment with oridonin for 24 h increased apoptosis by 4.1%, and increased the protein levels of Bax and cleaved caspase-3 but significantly decreased the levels of IL-1ß in the culture supernatant (p < 0.05). In addition, 6 h of oridonin treatment significantly decreased the number of GFP-LC3 punctate dots and inhibited the protein levels of ATG5 and Beclin1 by 80.01% and 42.12%, respectively. Chloroquine (CQ) significantly reinforced the effects of oridonin on inhibition of autophagy, suppression of proliferation, and induction of apoptosis in RA-FLSs (p < 0.05).Conclusions: Our results indicate that treatment with oridonin in combination with CQ inhibits autophagy and cell proliferation and induces apoptosis in RA-FLSs more effectively than treatment oridonin alone. This finding indicates that oridonin is a potential therapeutic agent for RA.

Molecular cloning and functional characterization of a seed-specific VvßVPE gene promoter from Vitis vinifera.

MAIN CONCLUSION: The grapevine VvßVPE promoter is specifically expressed in the seed. The - 1306~- 1045 bp core region restricts expression in other tissues and organs. Vacuolar processing enzyme (VPE) is a cysteine proteinase regulating vacuolar protein maturation and executing programmed cell death (PCD) in plants. Vitis vinifera (Vv)ßVPE is a ß-type VPE showing seed-specific expression that processes seed proteins during ovule development. However, the regulation of the seed-specific gene expression is far from understood. In this study, we characterize VvßVPE promoter (pVvßVPE) from 12 seeded and seedless grape genotypes. 94.56% of the pVvßVPE coding sequence is consistent. Two ßVPE promoters were constructed and transformed into Arabidopsis thaliana via ß-glucuronidase (GUS) fused expression vectors, using cv. Pinot Noir and cv. Thompson as seed and seedless candidates. GUS staining in different tissues and organs revealed that VvßVPE expresses specifically in the embryo, including the cotyledon, hypocotyl and suspensor, but not in the leaf, stem, root or flowers of the seedling. Using promoter deletion analysis, we created four incomplete VvßVPE promoters and found each pVvßVPE deletion could drive GUS gene to express in seeds. Interestingly, seed specificity disappeared when the promoter missed the core - 1306~- 1045 bp region. All deletion promoters presenting various quantified GUS activities indicate that the region - 1704~- 1306 bp inhibits, and the region - 705~- 861 bp promotes gene expression of VvßVPE. Our results demonstrate that pVvßVPE is a seed-specific promoter in both seeded and seedless grapes. Moreover, the core region of pVvßVPE (- 1306~- 1045 bp) is the key one responsible for seed-specific expression.

In vitro evaluation of the internalization and toxicological profile of silica nanoparticles and submicroparticles for the design of dermal drug delivery strategies.

The use of colloidal silica nanoparticles and sub-microparticles (SiPs) have been considered a very interesting strategy for drug delivery applications. In the present study, we have focused our attention on the suitability of these nanomaterials as potential carriers for dermal drug delivery, thus studying their toxicological profile in vitro, cellular uptake and intracellular localization in both human keratinocytes (K17) and human dermal fibroblasts (HDF) as a function of their particle size (SiPs of 20, 70, 200 and 500 nm). Full characterization of these aspects enabled us to observe a strong cell-type dependency in terms of cytotoxicity and cell internalization, whereas particle size was only relevant for ultra-small SiPs (20 nm), being the most toxic SiPs. For 70, 200 and 500 nm SiPs, the differences in uptake and intracellular trafficking determined the different toxicological profiles in K17 and HDF. In addition, these characteristics can further define different drug delivery strategies. Hence, phagocytosis has been identified as the main internalization mechanism for K17, and caveolae-mediated endocytosis for HDF. This relevant information led us to conclude that fibroblasts would be optimal targets for delivering delicate therapeutic molecules such as proteins or genetic material using SiPs while maintaining a low toxicity profile, whereas keratinocytes could enable accelerated drug release therapies based on SiPs.

KIF2A overexpression and its association with clinicopathologic characteristics and unfavorable prognosis in colorectal cancer.

Kinesin superfamily protein 2A (KIF2A), an M type nonmotile microtubule depolymerase, has received attention for its role in carcinogenesis and prognostic value in several types of cancer. In this study, we evaluated the expression of KIF2A and its potential and robustness to predict clinical outcomes in colorectal cancer (CRC) patients. The messenger RNA (mRNA) expression of KIF2A was determined in 20 pairs of cancerous and adjacent nontumor tissues by real-time polymerase chain reaction. KIF2A immunohistochemistry was performed on tissue microarray (TMA), composed of 182 CRC and 179 matched adjacent nontumor tissues from surgery, 23 chronic colitis, 43 low-grade, and 18 high-grade intraepithelial neoplasias acquired through intestinal endoscopic biopsy. Univariate and multivariate Cox regression models were used to perform survival analyses. Both KIF2A mRNA and protein product exhibited CRC tissue-preferred expression, when compared with benign tissues. The high KIF2A expression was significantly correlated to TNM stage (P = 0.046) and tumor status (T) (P = 0.007). In univariate and multivariate analyses, high KIF2A expression showed a major prognostic value regarding 5-year survival. The influences of KIF2A expression on the survival were further proven by Kaplan-Meier survival analysis. This study demonstrated CRC tissue-preferred expression pattern of the KIF2A and suggested that high KIF2A expression might serve as an independent maker for poor prognosis in CRC patients.

Combined effects of PLGA and vascular endothelial growth factor promote the healing of non-diabetic and diabetic wounds.

Growth factor therapies to induce angiogenesis and thereby enhance the blood perfusion, hold tremendous potential to address the shortcomings of current impaired wound care modalities. Vascular endothelial growth factor stimulates (VEGF) wound healing via multiple mechanisms. Poly(lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. Hence, we hypothesized that the administration of VEGF encapsulated in PLGA nanoparticles (PLGA-VEGF NP) would promote fast healing due to the sustained and combined effects of VEGF and lactate. In a splinted mouse full thickness excision model, compared with untreated, VEGF and PLGA NP, PLGA-VEGF NP treated wounds showed significant granulation tissue formation with higher collagen content, re-epithelialization and angiogenesis. The cellular and molecular studies revealed that PLGA-VEGF NP enhanced the proliferation and migration of keratinocytes and upregulated the expression of VEGFR2 at mRNA level. We demonstrated the combined effects of lactate and VEGF for active healing of non-diabetic and diabetic wounds. FROM THE CLINICAL EDITOR: The study of wound healing has been under a tremendous amount of research over recent years. In diabetic wounds, vasculopathy leading to localized ischemia would often result in delayed wound healing. In this article, the authors encapsulated vascular endothelial growth factor stimulates (VEGF) in PLGA nanoparticles and studies the potential pro-healing effects. It was found that the combination of these two components provided synergistic actions for healing. The encouraging results should provide a basis for combination therapy in the future.

Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer.

Melanoma-associated antigens (MAGEs) are a group of well-characterized members of the cancer/testis antigen (CTA) family, which is one of the largest groups of human tumor-associated antigens. MAGE-A9 is a particular member in the context of the MAGE-A gene family and was defined as presenting prognostic relevance in certain type of human cancer. However, the expression of MAGE-A9 in invasive ductal breast cancer (IDC) and the relationship with the clinical attributes of IDC, especially prognostic characteristic, remain poorly understood. In this present study, one-step quantitative reverse transcription polymerase chain reaction (18 fresh-frozen IDC tissues and corresponding non-cancerous tissues) and immunohistochemistry by tissue microarrays (82 IDC tissue samples and 70 matched tumor-adjacent non-cancerous tissue samples) were performed to characterize expression of the MAGE-A9 gene in IDC. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. The results of qPCR and IHC analysis showed that the expression of MAGE-A9 in IDC was significantly higher than that in corresponding non-cancerous tissue. Moreover, the expression level of MAGE-A9 protein in IDC was significantly related to histological grade (p = 0.011) and distant metastasis (p = 0.019). Multivariate analysis with the Cox regression model showed that MAGE-A9 protein expression (p = 0.009), histological grade (p = 0.014), lymph node metastasis (p = 0.012) and distant metastasis (p = 0.011) were independent prognostic factors for overall survival of IDC patients. The data suggest that MAGE-A9 expression is correlated with malignant attributes of IDC and it may serve as a novel prognostic factor and an ideal candidate for targeted therapy in IDC treatment.

Dissipation and residue of metalaxyl and cymoxanil in pepper and soil.

A simple and accurate method of determining metalaxyl and cymoxanil in pepper and soil was developed by ultra-performance liquid chromatography-photodiode array detection. The limits of detection were 0.015 mg/kg for metalaxyl and 0.003 mg/kg for cymoxanil. The limits of quantification were 0.05 mg/kg for metalaxyl in pepper and soil as well as 0.01 mg/kg for cymoxanil in pepper and soil. Recoveries of pepper and soil were investigated at three spiking levels and ranged within 77.52 to 102.05 % for metalaxyl and 87.15 to 103.21 % for cymoxanil, with relative standard deviations below 9.30 %. For field experiments, the half-lives of metalaxyl were 3.2 to 3.9 days in pepper and 4.4 to 9.5 days in soil at the three experimental locations in China. At harvest, pepper samples were found to contain metalaxyl and cymoxanil well below the maximum residue limit MRLs of the European Union (EU) following the recommended dosage and the interval of 21 days after last application.

Dissipation rate and residue distribution of dufulin in tomato and soil under field conditions.

Dissipation rate and residue distribution of dufulin in tomato and soil under field conditions were investigated in Guiyang, Tianjin, and Haikou during 2011-2012, using ultra-performance liquid chromatography. Average recoveries of dufulin in tomato and soil ranged from 91.03 % to 95.16 % and 94.35 % to 98.34 %, respectively, with relative standard deviations of 1.16 %-3.97 %. Dufulin dissipation followed first-order kinetics. Dufulin had half-lives of 2.8, 4.7, and 9.0 days in tomato and 6.1, 8.2, and 17.2 days in soil in Guiyang, Tianjin, and Haikou, respectively. At harvest, dufulin residues in tomato samples collected 5 days after the last application at 3 times recommended dosage applied every 5 days were below 1.0 mg kg(-1).

[Prognostic significance of CXCR2 expression in pancreatic ductal carcinoma].

OBJECTIVE: To explore the relationship between the expression of CXC chemokine receptor 2 (CXCR2) and the clinicopathologic features with prognosis in pancreatic ductal carcinoma (PDAC) tissues. METHODS: The CXCR2 expression in 161 PDAC tissues were detected with immunohistochemistry using anti-human CXCR2 antibody and tissues microarray. RESULTS: The expression of CXCR2 in PDAC tumor tissues was higher than that in normal pancreatic tissues (χ(2) = 11.437, P = 0.001). The comparison of clinicopathologic characteristics and immunohistochemistry by χ(2) test analysis showed that a high expression of CXCR2 in PDAC was correlated with vascular invasion (χ(2) = 6.489, P = 0.011) and late TNM stage (χ(2) = 6.205, P = 0.013). Kaplan-Meier survival and Cox regression analyses showed that a high expression of CXCR2 (HR: 5.514, P = 0.016) was an independent prognostic factor. CONCLUSION: A high expression of CXCR2 denotes a poor prognosis in PDAC.

Chondroitin polymerizing factor (CHPF) promotes the progression of colorectal cancer through ASB2-mediated ubiquitylation of SMAD9.

Chondroitin polymerizing factor (CHPF) has been reported to play a pivotal role in the progression of multiple cancers, however, the relationship between CHPF and colorectal cancer (CRC) progression has not been fully understood. The current study revealed that CHPF expression was upregulated in patients with CRC and correlated with an unfavorable prognosis. Also, CHPF knockdown effectively suppressed the viability and mobility of CRC cells and the growth of xenograft tumors. Additionally, SMAD9 was identified as a downstream target of CHPF. SMAD9 knockdown successfully abrogated the promotion of CHPF overexpression in CRC progression, indicating that CHPF regulated the development of CRC through SMAD9. Mechanistically, SMAD9 is ubiquitinated by ASB2, and the regulatory effect of CHPF on SMAD9 activity was exerted via its mediation of ASB2. Collectively, CHPF functioned as a promising prognostic biomarker and tumor-promoter of CRC by regulating the ASB2-mediated ubiquitination of SMAD9.

Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.

AURKA is a threonine or serine kinase that needs to be activated by TPX2, Bora and other factors. AURKA is located on chromosome 20 and is amplified or overexpressed in many human cancers, such as breast cancer. AURKA regulates some basic cellular processes, and this regulation is realized via the phosphorylation of downstream substrates. AURKA can function in either the cytoplasm or the nucleus. It can promote the transcription and expression of oncogenes together with other transcription factors in the nucleus, including FoxM1, C-Myc, and NF-κB. In addition, it also sustains carcinogenic signaling, such as N-Myc and Wnt signaling. This article will focus on the role of AURKA in the nucleus and its carcinogenic characteristics that are independent of its kinase activity to provide a theoretical explanation for mechanisms of resistance to kinase inhibitors and a reference for future research on targeted inhibitors.

AURKA plays an important role in the control of the proliferation, invasion, cell cycle regulation and self-renewal of cancer stem cells.Small molecule kinase inhibitors targeting AURKA have been developed, but the overall response rate of patients in clinical trials is not ideal, prompting us to pay attention to the non-kinase activity of AURKA.This review focuses on the nuclear function of AURKA and its oncogenic properties independent of kinase activity, demonstrating that the nuclear substrate of AURKA and the remote allosteric site of the kinase may be targets of anticancer therapy.