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Objective: The aim of this work was to identify the consensus immune subtypes and predict the response to immune checkpoint inhibitor (ICIs) therapy for MDM4 gain/amplification luminal A type breast cancer (BC). Materials and Methods: Luminal A type BC expression data, copy number and corresponding clinical information were downloaded and pre-processed for subsequently analysis from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Furthermore, gene set enrichment analysis (GSEA) was performed to identify transcripts functions between MDM4 gain/amplification and control samples. Subsequently, weighted gene co-expression network analysis (WGCNA) was applied to screen out gene modules related biomarkers for ICIs therapy response in luminal A type BC. We perform an unsupervised consensus clustering in MDM4 gain/amplification luminal A type BC from TCGA BC dataset based immune-related gene signatures (IRGs) and then used luminal A type BC from METABRIC BC as validation datasets. We performed the Tumor Immune Dysfunction and Exclusion (TIDE) analysis to predict ICIs response and explore significant relationship with immune subtype. Results: The results from GSEA indicated that luminal A type BC with MDM4 gain/amplification were significantly enriched in immunological signature gene sets. Significantly, we also identified three gene modules significantly association with immune checkpoint, DNA damage, and immune cell infiltering in luminal A type BC. Luminal A type BC could be categorized into two distinct immune subtypes based on the expression of IRGs. Luminal A type BC in one subtype showed high response to ICIs therapy, characterized by higher immune checkpoint genes score and CD8+ T-cell score compared to tumors in a second subtype. Conclusion: Our findings demonstrated that immune subtype for MDM4 gain/amplification luminal A type BC was beyond the current luminal A/B classification and a subset of luminal A type BC patients may benefit from ICIs therapy.

Background Clinical value of tumor necrosis factor (TNF) inhibitors in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with polycystic ovary syndrome (PCOS) was investigated in this study. Methods A retrospective analysis was performed on the clinical data of 100 PCOS patients who received IVF-ET for the first time at Hebei Institute of reproductive health science and technology from January 2010 to June 2020. The patients were divided into Inhibitor group and Control group according to whether they were treated with or without TNF inhibitors. Next, the two groups were subject to comparison in terms of the days of gonadotropin (Gn) use, total dosage of Gn, trigger time, hormone level and endometrial condition on the day of human chorionic gonadotropin (HCG) injection, the effects of two different regimens on controlled ovarian hyperstimulation (COH) and pregnancy outcomes. Results There were no significant differences in baseline characteristics between the two groups, including age, duration of infertility, body mass index (BMI), ovarian volume, antral follicle count, and basal hormone levels. Compared with the Control group, the days of Gn use and trigger time of patients in the Inhibitor group were significantly shortened, and the total Gn dosage was notably reduced. In terms of sex hormone levels on the HCG injection, the Inhibitor group displayed much lower serum estradiol levels while higher serum luteinizing hormone and progesterone (P) levels than the Control group. Notably, the high-quality embryo rate was also significantly increased with the use of TNF inhibitors. However, significant differences were not observed in endometrial thickness (on the day of HCG injection), proportion of endometrial A, B and C morphology (on the day of HCG injection), cycle cancellation rate, number of oocytes retrieved, fertilization rate, and cleavage rate between the two groups. Importantly, the clinical pregnancy rate in the Inhibitor group was significantly higher than that in the Control group, but there was no significant difference in the biochemical pregnancy rate, early abortion rate, multiple birth rate, ectopic pregnancy rate and number of live births between the two groups. Conclusion Collectively, after application of TNF-α inhibitor regimen, superior overall treatment effect can be observed in infertile PCOS patients receiving IVF-ET. Therefore, TNF inhibitors have certain application value in IVF-ET in infertile women with PCOS.

The loss of N in farmland is an important cause of agricultural non-point source pollution, which seriously impacts the aquatic environment. A two-year (2017–2018) experiment was conducted to investigate the characteristics of runoff and N losses under different tillage practices. Taking downslope ridge planting and cross ridge planting as the experimental treatments, the characteristics of surface runoff, interflow, and N losses in sloping farmlands with yellow soil were studied throughout the maize growth period. As the rainfall increased, the surface runoff and interflow also increased. The surface runoff and N losses in the surface runoff of downslope ridge planting were significantly higher than those of cross ridge planting. The interflow volumes and N losses in the 0–20 and 20–40 cm soil layers of the cross ridge planting were significantly higher than those of the downslope ridge planting. The total N (TN) losses from surface runoff accounted for 54.95–81.25% of the N losses from all pathways. Therefore, we inferred that surface runoff is the main pathway of N losses. Dissolved total N (DTN) was the main form of N loss under different tillage measures, as it accounted for 55.82–94.41% of the TN losses, and dissolved organic N accounted for 52.81–87.06% of the DTN losses. Thus, we inferred that dissolved N is the main form of N loss. Future research must focus on the prevention and control of the N losses during the maize seedling stage to reduce the environmental pollution caused by ammonium N through runoff.

The V617F mutation of Janus-associated kinase 2 (JAK2) is common in myeloproliferative neoplasms (MPN). JAK2 V617F mutation can be detected in patients withWe report a case of APL with both the t(15;17) translocation as well as the JAK2 V617F mutation that transformed into MPN (PV/ET).A

In the era of coronavirus disease 2019 (COVID-19) pandemic, imported COVID-19 cases pose great challenges to many countries. Chest CT examination is considered to be complementary to nucleic acid test for COVID-19 detection and diagnosis. We report the first community infected COVID-19 patient by an imported case in Beijing, which manifested as nodular lesions on chest CT imaging at the early stage. Deep Learning (DL)-based diagnostic systems quantitatively monitored the progress of pulmonary lesions in 6 days and timely made alert for suspected pneumonia, so that prompt medical isolation was taken. The patient was confirmed as COVID-19 case after nucleic acid test, for which the community transmission was prevented timely. The roles of DL-assisted diagnosis in helping radiologists screening suspected COVID cases were discussed.

Mitogen-activated protein kinases (MAPKs) are important in regulating plant development as well as stress response. In this study, we genome-widely identified 56 MAPK genes in upland cotton. These MAPK genes unequally distribute on 22 chromosomes of cotton genome, but no MAPK gene is located on At_Chr6, Dt_Chr6, At_Chr13 and Dt_Chr13. The exons and introns in GhMAPK gene family vary widely at the position, number and length. Furthermore, GhMAPK family can be divided into 4 groups (A, B, C and D), and the TEY type of T-loop exists in three groups (A, B and C), but the TDY type of T-loop is only in group D. Further study revealed that some GhMAPK genes (including GhMPK6) are preferentially expressed in elongating fibers. GhMPK6 maintains a high phosphorylation level in elongating fibers, and its phosphorylation was enhanced in fibers by phytohormones brassinosteroid (BR), ethylene and indole-3-acetic acid (IAA). Additionally, GhMPK6 could interact with GhMKK2-2 and GhMKK4, suggesting that GhMKK2-2/4-GhMPK6 module may be involved in phosphorylation of its downstream proteins for regulating fiber elongation of cotton.

Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and attenuate inflammation. We aim to evaluate the effects of 9-PAHSA on DCVD and investigate the possible mechanisms underlying it. Firstly, serum 9-PAHSA levels in human were detected by HPLC-MS/MS analysis. Then 9-PAHSA was synthesized and purified. The synthesized 9-PAHSA was gavaged to db/db mice with 50 mg/kg for 4 weeks. The carotid arterial plaque and cardiac structure was assessed by ultrasound. Cardiac autophagy was tested by western blot analysis, electron microscope and iTRAQ. The results showed that 9-PAHSA, in patients with type 2 diabetes mellitus (T2DM), was significantly lower than that in non-diabetic subjects. Administration of 9-PAHSA for 2 weeks reduced blood glucose levels. Ultrasound observed that continue administration of 9-PAHSA for 4 weeks ameliorated carotid vascular calcification, and attenuated myocardial hypertrophy and dysfunction in db/db mice. Electron microscopy showed continue 9-PAHSA treatment significantly increased autolysosomes, while dramatically decreased greases in the myocardial cells of the db/db mice. Moreover, iTRAQ analysis exhibited that continue 9-PAHSA treatment upregulated BAG3 and HSPB8. Furthermore, western blot analysis confirmed that 9-PAHSA down-regulated Akt/mTOR and activated PI3KIII/BECN1 complex in diabetic myocardium. Thus, 9-PAHSA benefits DCVD in diabetic mice by ameliorating carotid vascular calcification, promoting autophagic flux and reducing myocardial hypertrophy.

Severe aplastic anemia (SAA) is a fatal bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a matched sibling donor is the first-line treatment for older SAA patients. However, the number of CD34A 45-year-old male patient with SAA was treated with a sibling-matched allo-HSCT. Due to the low amount of donor CD34This study provides evidence that UCB-derived HSCs have a higher capacity for hematopoietic reconstitution, suggesting that UCB plus an HLA-matched sibling donor is a good alternative for older patients with SAA.

In this paper, a class of new extended shift-splitting (NESS) preconditioners containing t > 0 are proposed for saddle point problems, which contain the existing shift-splitting-based preconditioners as special cases. The convergence properties of the NESS iteration and the spectral distribution of the NESS preconditioned matrix are investigated. We give an estimated bound for the real eigenvalues of the NESS preconditioned matrix whose left end is positive and show that the non-real eigenvalues of the NESS preconditioned matrix are located in an intersection of two rings, particularly, these non-real eigenvalues are located in an intersection of two rings and one circle if t ≥ 1 2 . Moreover, we show that under appropriate conditions our proposed eigenvalue bounds are tighter than the corresponding bounds given in Ren et al. (2017). Using Fourier analysis, we derive an optimized parameter t ∗ independent of the viscosity ν for the continuous version of the NESS preconditioned GMRES method for the 2D Stokes equation. Moreover, we find that the NESS preconditioned GMRES method with a constant multiple of the optimized parameter t ∗ is effective and robust to solve 2D Stokes problems in practice. Numerical experiments are used to verify our theoretical results.

A stable and simple Yb:YAG rod amplifier based on chirped pulse amplification in a water cooling system has been demonstrated. The output power of 38 W at a 250 kHz repetition rate with a spectrum width of 4 nm centered at 1030 nm, which support Fourier-transform limited pulse duration of 389 fs has been generated. The compressed power of 23.9 W with pulse duration of 985 fs has been obtained with a chirped volume Bragg grating compressor. The power stability is measured to be 1.414% when the output power is 35 W. The system is worthwhile to popularize for its good performance and inexpensive cost.

Cotton, one of the most important crops in the world, produces natural fiber materials for the textile industry. WRKY transcription factors play important roles in plant development and stress responses. However, little is known about whether and how WRKY transcription factors regulate fiber development of cotton so far. In this study, we show that a fiber-preferential WRKY transcription factor, GhWRKY16, positively regulates fiber initiation and elongation. GhWRKY16-silenced transgenic cotton displayed a remarkably reduced number of fiber protrusions on the ovule and shorter fibers compared to the wild-type. During early fiber development, GhWRKY16 directly binds to the promoters of GhHOX3, GhMYB109, GhCesA6D-D11, and GhMYB25 to induce their expression, thereby promoting fiber initiation and elongation. Moreover, GhWRKY16 is phosphorylated by the mitogen-activated protein kinase GhMPK3-1 at residues T-130 and S-260. Phosphorylated GhWRKY16 directly activates the transcription of GhMYB25, GhHOX3, GhMYB109, and GhCesA6D-D11 for early fiber development. Thus, our data demonstrate that GhWRKY16 plays a crucial role in fiber initiation and elongation, and that GhWRKY16 phosphorylation by GhMPK3-1 is essential for the transcriptional activation on downstream genes during the fiber development of cotton.

We demonstrate a high-power, high-energy chirped-pulse amplification (CPA) system based on three Yb:YAG amplifiers and a chirped-volume Bragg grating (CVBG). With an all-fiber laser as the seed light, a Yb:YAG rod amplifier and two Yb:YAG single-crystal fiber (SCF) amplifiers as the amplification stages, a laser power of 96 W at 200 kHz repetition rate corresponding to a pulse energy of 0.48 mJ has been generated. The stability of different output power has been measured and compared. To the best of our knowledge, this is the first report on a stable 100 W-level laser with sub-mJ pulse energy based on SCF. The beam quality M 2 of different output lasers has also been measured, which is below 1.55 when the output power is 92 W. The amplified laser is seeded into the CVBG to be compressed, and a compression efficiency of 0.724 has been obtained with an output power of 67.8 W and pulse duration of 2.5 ps. The ultrafast CPA system delivering high pulse energy (sub-mJ) with hundreds of kHz repetition rate is expected to be used as the driving source of high-flux high-harmonic generation after further compression.

Background: Oral commensals contribute to microbe-host symbiosis in periodontal homeostasis, and Porphyromonas gingivalis (P. gingivalis) as the keystone pathogen critically accounts for the shift of symbiosis to dysbiosis and periodontal destruction. Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome-mediated interleukin-1β (IL-1β) is significantly involved in periodontal diseases, and notably P. gingivalis enables to modulate the induction and expression of NLRP3. Whereas, the exact mechanism by which NLRP3 inflammasome is regulated in response to commensal and pathogenic bacteria remains unclear. Methods: To examine the expression of IL-1β and NLRPs inflammasome in tissues with severe chronic periodontitis, and further investigate how Caspase-4-dependent non-canonical NLRP3 inflammasome pathways functioned during the interactions of Streptococcus mitis (S. mitis) and P. gingivalis with human THP-1 cells. Results: IL-1β and NLRP3, NLRP6, NLRP12, and absent in melanoma 2 (AIM2) inflammasomes are highly expressed in gingival tissues with severe chronic periodontitis. In human THP-1 cells, P. gingivalis activates the synthesis and secretion of IL-1β to higher levels than S. mitis. Importantly, NLRP3-, Caspase-1-, and Caspase-4-siRNA knockdown THP-1 cells treated with P. gingivalis exhibited a lower expression level of IL-1β as compared to the control cells. In addition, silencing of either CASP4 or CASP1 can lead to a concurrent or reciprocal decrease in the expression of the other. Of note, the IL-1β induction is not affected in the S. mitis-treated THP-1 cells with the silence of NLRP3, Caspase-1, and Caspase-4 genes. Conclusion: NLRP3/Caspase-4 and NLRP3/Caspase-1 dependent IL-1β production may crucially contribute to the dysregulated immuno-inflammatory response in periodontal pathogenesis.

Spatiotemporally regulated callose deposition is an essential, genetically programmed phenomenon that promotes pollen development and functionality. Severe male infertility is associated with deficient callose biosynthesis, highlighting the significance of intact callose deposition in male gametogenesis. The molecular mechanism that regulates the crucial role of callose in production of functional male gametophytes remains completely unexplored. Here, we provide evidence that the gradual upregulation of a previously uncharacterized cotton (Gossypium hirsutum) pollen-specific SKS-like protein (PSP231), specifically at the post pollen-mitosis stage, activates callose biosynthesis to promote pollen maturation. Aberrant PSP231 expression levels caused by either silencing or overexpression resulted in late pollen developmental abnormalities and male infertility phenotypes in a dose-dependent manner, highlighting the importance of fine-tuned PSP231 expression. Mechanistic analyses revealed that PSP231 plays a central role in triggering and fine-tuning the callose synthesis and deposition required for pollen development. Specifically, PSP231 protein sequesters the cellular pool of RNA-binding protein GhRBPL1 to destabilize GhWRKY15 mRNAs, turning off GhWRKY15-mediated transcriptional repression of GhCalS4/GhCalS8 and thus activating callose biosynthesis in pollen. This study showed that PSP231 is a key molecular switch that activates the molecular circuit controlling callose deposition toward pollen maturation and functionality and thereby safeguards agricultural crops against male infertility.

This study aimed to assess the overall diagnostic accuracy of magnetic beads-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MB-based MALDI-TOF MS) in identifying esophageal squamous cell carcinoma (ESCC). The PubMed/Medline, EMBASE, Cochrane Library, Science Direct, Google Scholar, China National Knowledge Infrastructure database and Wanfang Med Online were searched for potential studies up to 30 January 2018. Articles were screened manually on the basis of inclusion and exclusion criteria. Sensitivity, specificity, likelihood ratio or other indices reflecting the diagnostic accuracy of MB-based MALDI-TOF MS for ESCC were pooled and calculated. 16 studies involving 1 006 individuals were included. The values of pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 0.95 (95% CI: 0.90–0.98), 0.94 (95% CI: 0.90–0.96), 15.45 (95% CI: 8.93–26.72), 0.05 (95% CI: 0.03–0.10), 295.04 (95% CI: 103.79–838.71), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.98. In conclusion, MB-based MALDI-TOF MS could be an effective technique with high diagnostic accuracy for ESCC. Keywords: Diagnostic value, ESCC, MALDI-TOF MS, Magnetic beads, Meta-analysis

Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025–2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111–23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714–3.892; P

BACKGROUND Papillary thyroid cancer (PTC) is currently the most commonly diagnosed endocrine malignancy. In addition, the sex- and age-adjusted incidence of PTC has exhibited a greater increase over the last 2 decades than in many other malignancies. Thus, discovering noninvasive specific serum biomarker to distinguish PTC from cancer-free controls in its early stages remains an important goal. MATERIAL AND METHODS Serum samples from 88 PTC patients and 80 cancer-free controls were randomly allocated into training or validation sets. Serum peptide profiling was performed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) after using weak cation exchange magnetic beads (WCX-MB), and the results were evaluated by use of ClinProTools™ Software. To distinguish PTC from cancer-free controls, quick classifier (QC), supervised neural network (SNN), and genetic algorithm (GA) models were established. The models were blindly validated to verify their diagnostic capabilities. The most discriminative peaks were subsequently identified with a nano-liquid chromatography-electrospray ionization-tandem mass spectrometry system. RESULTS Six peptide ions were identified as the most discriminative peaks between the PTC and cancer-free control samples. The QC model exhibited satisfactory sensitivity and specificity among the 3 models that were validated. Two peaks, at m/z 2671.17 and m/z 1464.68, were identified as fragments of the alpha chain of fibrinogen, while a peak at m/z 1738.92 was a fragment of complement component 4A/B. CONCLUSIONS MS combined with ClinProTools™ software was able to detect peptide biomarkers in PTC patients. In addition, the constructed classification models provided a serum peptidome pattern for distinguishing PTC from cancer-free controls. Both fibrinogen a and complement C4A/B were identified as potential markers for diagnosis of PTC.

Appropriate environmentally friendly agricultural technologies and practices must be implemented in China (and many other countries) to reduce farmland non-point source pollution and meet sustainability objectives. A major hindrance to their implementation is that Chinese farmers have very low willingness to accept such practices. Discrete choice experiments (DCEs) have known value for identifying goods or policies with attractive attributes, and thus exploring target groups’ choice behavior and addressing such problems. Sound questionnaire design is of paramount importance for robust results. This article describes the nature and theoretical foundations of DCEs and considers their use in diverse applications abroad, and their limited but growing applications in China. It then presents a case study, focused on the detailed design of DCEs intended to gauge paddy farmers’ willingness to accept several agriculturally friendly techniques and related compensation methods, problems encountered, and predictions for future studies.

TO THE EDITOR: In a subset of patients with acute promyelocytic leukemia (APL), t(15;17)(q22;q12) and PML - RARA fusion cannot be detected.[1][1][⇓][2]-[3][3] To date, many RARA fusions have been reported with at least 12 alternative partner genes in APL.[1][1],[4][4][⇓][5][⇓][6][⇓][7

In this paper, we first propose three kinds of variants of the Uzawa method for solving three-order block saddle point problem and study the convergence conditions of the proposed methods. Second, we obtain the approximate optimal relaxation factors of the three proposed Uzawa type methods by using variable control method. Finally, the experimental results show that our proposed Uzawa type methods for solving three-order block saddle point problem have less workload per iteration step than the corresponding Uzawa type methods for solving standard saddle point problem, which explains that our proposed methods are feasible and efficient.

This study reports a single-arm trial in the interim phase in 4 patients with median age of 40.5 years who have undergone combined HLA-matched sibling donor (MSD) stem cell graft and an unrelated cord blood (UCB) unit for the treatment of severe aplastic anemia (SAA). The median time was 10 days for neutrophil engraftment (9-18 days) and 17 days for platelets (12-24 days). Median follow-up of 22 months (ranging from 16 to 29 months) showed survival of the 4 patients with complete hematological response. Acute graft-vs-host disease (GVHD) (grade II) occurred only in 1 patient, yet chronic GVHD was free. One patient showed a pattern of transient MSD graft followed by dominant UCB chimerism, and another 1 achieved mixed chimerism in the first 6 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT) then evolved to a stable MSD graft. The other 2 patients sustained a full MSD graft during the post-HSCT period. Nevertheless, none of the patients developed primary and secondary graft failure up to the final follow-up. Although this is a small cohort, the dual transplantation combining HLA-matched sibling allogeneic hematopoietic stem cell transplantation with unrelated cord blood unit may deserve further exploration for treatment of SAA patients aged 35 to 50 years old.

Anther/pollen development is a highly programmed process in flowering plants. However, the molecular mechanism of regulating anther/pollen development is still largely unclear so far. Here, we report a cotton WRKY transcription factor (GhWRKY22) that functions in anther/pollen development. Quantitative RT-PCR and GUS activity analyses revealed that GhWRKY22 is predominantly expressed in the late developing anther/pollen of cotton. The transgenic Arabidopsis plants expressing GhWRKY22 displayed the male fertility defect with the fewer viable pollen grains. Expression of the genes involved in jasmonate (JA) biosynthesis was up-regulated, whereas expression of the JA-repressors (JAZ1 and JAZ8) was down-regulated in the transgenic Arabidopsis plants expressing GhWRKY22, compared with those in wild type. Yeast one-hybrid and ChIP-qPCR assays demonstrated that GhWRKY22 modulated the expression of JAZ genes by directly binding to their promoters for regulating anther/pollen development. Yeast two-hybrid assay indicated that GhMYB24 could interact with GhJAZ8-A and GhJAZ13-A. Furthermore, expression of AtMYB24, AtPAL2 and AtANS2 was enhanced in the transgenic Arabidopsis plants, owing to GhWRKY22 overexpression. Taking the data together, our results suggest that GhWRKY22 acts as a transcriptional repressor to regulate anther/pollen development possibly by modulating the expression of the JAZ genes.

The Fe nanowire arrays are prepared by the method of alternating current, constant voltage and constant current respectively. the morphology and composition of the Fe nanowires have been characterized By scanning electron microscope (SEM), Energy-dispersive X-ray spectroscopy (EDS). The Fe nanowires growth rate with different current density was studied in anodic aluminum oxide (AAO) template for pore diameter of 85 nm, pore depth of 55 μm under the same total charge. Research shows that the deposition rate of nanowires first slightly decreased, dramatically increased again and then reduced greatly with the increase of current density from 1 mA/cm2 ~ 5 mA/cm2.

We demonstrate a high repetition rate, high energy chirped pulse amplification (CPA) system based on single crystal fiber (SCF) amplifier. With home-made all-fiber laser as the seed laser and Yb:YAG rod, SCF as the amplification gain medium, an output power of 61.8 W at 200 kHz repetition rate has been obtained. To the best of our knowledge, this is the highest power based on SCF at hundreds of kHz repetition rate. The measured M2 values are approximately 1.241 in the horizontal and 1.186 in the vertical direction. The spectrum width is 3.8 nm, which support Fourier transform-limited pulse duration of 411 fs. An average power of 41.8 W with pulse duration of 1.5 ps has been obtained after the chirped volume Bragg grating (CVBG) compressor, which will be compressed to hundreds of fs with accurate chirp compensation.

As the important source of natural fibers in the textile industry, cotton fiber quality and yield are often restricted to drought conditions because most of cotton plants in the world grow in the regions with water shortage. WRKY transcription factors regulate multiple plant physiological processes, including drought stress response. However, little is known of how the WRKY genes respond to drought stress in cotton. Our previous study revealed GhWRKY33 is leaf-specific and induced by drought stress. In this study, our data showed GhWRKY33 protein localizes to the cell nucleus and is able to bind to “W-box” cis-acting elements of the target promoters. Under drought stress, GhWRKY33 overexpressing transgenic Arabidopsis was withered much more quickly than wild type due to faster water loss. Moreover, GhWRKY33 transgenic plants displayed more tolerance to abscisic acid (ABA), relative to wild type. Expression of some drought stress-related genes and ABA-responsive genes were changed in the GhWRKY33 transgenic Arabidopsis with drought or ABA treatment. Collectively, our findings indicate that GhWRKY33 may act as a negative regulator to mediate plant response to drought stress and to participate in the ABA signaling pathway.

Acute promyelocytic leukemia (APL) is a unique disease entity in acute myeloid leukemia (AML), characterized by the expansion of leukemic cell block at the promyelocytic stage. The vast majority of APL patients bear t(15;17)(q24;q21) involving the promyelocytic leukemia ( PML ) gene at chromosome

LIM domain proteins are cysteine-rich proteins, and are often considered as actin bundlers and transcription factors in plants. However, the roles of XLIM proteins in plants (especially in cotton) remain unexplored in detail so far. In this study, we identified a cotton XLIM protein (GhXLIM6) that is preferentially expressed in cotton fiber during whole elongation stage and early secondary cell wall (SCW) synthesis stage. The GhXLIM6-silenced transgenic cotton produces shorter fibers with thinner cell walls, compared with wild-type (WT). GhXLIM6 protein could directly bind F-actin and promote actin polymerization both in vitro and in vivo. It also acts as a transcription factor to suppress GhKNL1 expression through binding the PAL-box element of GhKNL1 promoter, and subsequently regulate the expression of CesA genes related to cellulose biosynthesis and deposition in SCWs of cotton fibers. The cellulose content in fibers of GhXLIM6RNAi cotton is lower than that in WT. Taken together, these data reveal the dual roles of GhXLIM6 in fiber development. On one hand, GhXLIM6 functions in fiber elongation through binding to F-actin to maintain the dynamic F-actin cytoskeleton. On the other hand, GhXLIM6 fine-tunes fiber SCW formation, probably through directly suppressing transcription of GhKNL1 to promote cellulose biosynthesis.

An unsymmetric tetracarboxylic ligand collaborates with 4,4′-bipyridine to induce spontaneous resolution to form homochiral 3D coordination frameworks, while the use of longer dipyridyl ligands instead of 4,4′-bipyridine leads to isoreticular but heterochiral frameworks.

Soil salinity is one of the most serious threats in world agriculture, and often influences cotton growth and development, resulting in a significant loss in cotton crop yield. WRKY transcription factors are involved in plant response to high salinity stress, but little is known about the role of WRKY transcription factors in cotton so far. In this study, a member (GhWRKY34) of cotton WRKY family was functionally characterized. This protein containing a WRKY domain and a zinc-finger motif belongs to group III of cotton WRKY family. Subcellular localization assay indicated that GhWRKY34 is localized to the cell nucleus. Overexpression of GhWRKY34 in Arabidopsis enhanced the transgenic plant tolerance to salt stress. Several parameters (such as seed germination, green cotyledons, root length and chlorophyll content) in the GhWRKY34 transgenic lines were significantly higher than those in wild type under NaCl treatment. On the contrary, the GhWRKY34 transgenic plants exhibited a substantially lower ratio of Na(+)/K(+) in leaves and roots dealing with salt stress, compared with wild type. Growth status of the GhWRKY34 transgenic plants was much better than that of wild type under salt stress. Expressions of the stress-related genes were remarkably up-regulated in the transgenic plants under salt stress, compared with those in wild type. Based on the data presented in this study, we hypothesize that GhWRKY34 as a positive transcription regulator may function in plant response to high salinity stress through maintaining the Na(+)/K(+) homeostasis as well as activating the salt stress-related genes in cells.

In this paper, Uzawa-Low method for three-order block saddle point problem is presented and the corresponding convergence conditions are established. Furthermore, by introducing a preconditioner, we propose centered preconditioned Uzawa-Low method (CPU-Low method) and obtain its convergence conditions as well. Experimental results show that the two proposed methods are more efficient than Uzawa-Low method for the original saddle point problem and the CPU-Low method is superior to the Uzawa-Low method for three-order block saddle point problem.

Cotton (Gossypium hirsutum) as one of the most important economic crop in the world is often suffering from biotic and abiotic stresses during its growth seasons. Mitogen-activated protein kinase (MAPK) cascades participate in signal transduction of extracellular stimuli and regulate multiple biotic and abiotic stress responses in plants. In this study, a MAPK gene (GhMPK4) belonging to the group B of MAPK family was identified in cotton. Quantitative RT-PCR analysis showed that expression of GhMPK4 was induced by high salinity and osmotic stresses. Overexpression of GhMPK4 in Arabidopsis significantly enhanced the transgenic plants’ sensitivity to salt and osmotic stresses and exogenous abscisic acid (ABA). Under NaCl, mannitol and ABA treatments, the rates of seed germination and cotyledon expansion/greening of the GhMPK4 overexpression transgenic lines were remarkably declined compared with those of wild type, and roots of the GhMPK4 overexpression transgenic seedlings were shorter than those of wild type. Chlorophyll and proline contents in leaves of the GhMPK4 transgenic lines were obviously lower than those in wild type. Growth status of the GhMPK4 transgenic plants was worse than that of wild type when being subjected to drought and salinity stresses. Furthermore, the expression levels of the stress-related genes were altered in the transgenic plants under NaCl, mannitol and ABA treatments, compared with those in wild type. Taken the data together, it is suggested that GhMPK4 as a negative regulator may participate in response to salt and osmotic stresses and ABA signaling through affecting the expression of the stress-related genes in plants.

Reprimo (RPRM) is a novel tumor suppressor. However, the expression and molecular function of RPRM in pediatric acute myeloid leukemia (AML) is still unknown. We observed hypermethylation of the RPRM promoter in 8/11 leukemia cell lines and in 44.8% (47/105) of pediatric AML samples compared with 6.7% (2/30) of control samples. Bisulfite genomic sequencing analysis showed that the RPRM promoter was methylated in the majority of AML samples (66.2-83.1%), whereas RPRM was almost unmethylated in normal bone marrow samples (20.0-27.7%). Kaplan-Meier survival analysis revealed poor survival outcomes in samples with RPRM promoter methylation (p0.001). Proliferation of AML cells was inhibited in a dose-dependent manner (p0.05) after RPRM overexpression with lentivirus transfection. Apoptosis was up-regulated in RPRM-overexpressing AML cells. Real-time polymerase chain reaction array analysis revealed 50 dysregulated genes that might be implicated in apoptosis of RPRM-induced AML cells. RPRM may be a putative tumor suppressor in pediatric AML.

Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor, however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35, p &lt, 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy, however, the underlying mechanisms remain to be determined.

This study aims to investigate the effects of microRNA-335-5p (miR-335-5p) on lower-extremity deep vein thrombosis (LEDVT) by targeting PAI-1 through the TLR4 signaling pathway in rat models. siRNA, mimic, and inhibitor were used for transfection. The miR-335-5p expression was detected by in situ hybridization. CCK-8 assay and flow cytometry were adopted to detect proliferation, cell cycle, and apoptosis, respectively. Scratch test and Matrigel-based tube formation assay were used to detect the effect of miR-335-5p on cell migration ability and tube formation ability. A miR-335-5p lentivirus plasmid was constructed and injected into LEDVT rats. The length and weight of thrombus were measured, changes of thrombus recanalization were observed by CD34 immunohistochemistry, and levels of PAI-1 and inflammatory factors in femoral vein blood were detected by ELISA. LEDVT rats showed a higher AOD value of PAI-1, higher expression of PAI-1, NF-κB, Rac1, IL-1β, and TLR4 and a lower miR-335-5p expression. PAI-1 and miR-335-5p were negatively correlated. Compared to the blank and siRNA-NC groups, the miR-335-5p mimic and siRNA-PAI-1 groups showed declined expression of PAI-1, TLR4, NF-κB, Rac1, and IL-1β, increased proliferation and tube formation abilities, less cells in G0/G1 phase, and decreased apoptosis, decreased length and weight of thrombus, organized thrombus, increased new blood vessels, and decreased levels of PAI-1, IL-1, IL-6, and Tnf-a. miR-335-5p may suppress the occurrence and development of LEDVT in rats by repressing the activation of the TLR4 signaling pathway by targeted inhibition of PAI-1.

Although the focus in the area of health research may be shifting from infectious to non-communicable diseases, the infectious diseases of poverty remain a major burden of disease of global health concern. A global platform to communicate and share the research on these diseases is needed to facilitate the translation of knowledge into effective approaches and tools for their elimination. Based on the “One health, One world” mission, a new, open-access journal, Infectious Diseases of Poverty (IDP), was launched by BioMed Central in partnership with the National Institute of Parasitic Diseases (NIPD), Chinese Center for Disease Control and Prevention (China CDC) on October 25, 2012. Its aim is to identify and assess research and information gaps that hinder progress towards new interventions for a particular public health problem in the developing world. From the inaugural IDP issue of October 25, 2012, a total of 256 manuscripts have been published over the following five years. Apart from a small number of editorials, opinions, commentaries and letters to the editor, the predominant types of publications are research articles (69.5%) and scoping reviews (21.5%). A total of 1 081 contributing authors divided between 323 affiliations across 68 countries, territories and regions produced these 256 publications. The journal is indexed in major international biomedical databases, including Web of Science, PubMed, Scopus and Embase. In 2015, it was assigned its first impact factor (4.11), which is now 2.13. During the past five years, IDP has received manuscripts from 90 countries, territories and regions across six continents with an annual acceptance rate of all contributions maintained at less than 40%. Content analysis shows that neglected tropical diseases (NTDs), followed by the “Big Three” (HIV/AIDS, malaria and tuberculosis) and infectious diseases in general comprise 88% of all publications. In addition, a series of 10 thematic issues, covering 118 publications in all, was published as separate parts of the first five volumes. These publications were cited 975 times, which equals an average of 8.3 times per publication. The current challenge is to identify cutting-edge research topics and attract and to publish first-rate publications leading to increasing importance and impact of the journal in its field. Electronic supplementary material The online version of this article (doi:10.1186/s40249-017-0310-6) contains supplementary material, which is available to authorized users.

Background Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear. Methods Leukemia cell growth and apoptosis following LEE011 treatment was assessed through CCK-8 and annexin V/propidium iodide staining assays. Cell senescence was assessed by β-galactosidase staining and p16INK4a expression analysis. Gene expression profiles of LEE011 treated HL-60 cells were investigated using an Arraystar Human LncRNA array. Gene ontology and KEGG pathway analysis were then used to analyze the differentially expressed genes from the cluster analysis. Results Our studies demonstrated that LEE011 inhibited proliferation of leukemia cells and could induce apoptosis. Hoechst 33,342 staining analysis showed DNA fragmentation and distortion of nuclear structures following LEE011 treatment. Cell cycle analysis showed LEE011 significantly induced cell cycle G1 arrest in seven of eight acute leukemia cells lines, the exception being THP-1 cells. β-Galactosidase staining analysis and p16INK4a expression analysis showed that LEE011 treatment can induce cell senescence of leukemia cells. LncRNA microarray analysis showed 2083 differentially expressed mRNAs and 3224 differentially expressed lncRNAs in LEE011-treated HL-60 cells compared with controls. Molecular function analysis showed that LEE011 induced senescence in leukemia cells partially through downregulation of the transcriptional expression of MYBL2. Conclusions We demonstrate for the first time that LEE011 treatment results in inhibition of cell proliferation and induction of G1 arrest and cellular senescence in leukemia cells. LncRNA microarray analysis showed differentially expressed mRNAs and lncRNAs in LEE011-treated HL-60 cells and we demonstrated that LEE011 induces cellular senescence partially through downregulation of the expression of MYBL2. These results may open new lines of investigation regarding the molecular mechanism of LEE011 induced cellular senescence. Electronic supplementary material The online version of this article (doi:10.1186/s12935-017-0405-y) contains supplementary material, which is available to authorized users.

A high-performance liquid chromatography (HPLC) method was established to detect Xeljanz enantiomers in active pharmaceutical ingredients (APIs) and tablets. The separation was achieved on a Chiralpak IC column using a mobile phase of hexane-ethanol-diethylamine (65:35:0.1, v/v). The detection wavelength was 289 nm. The peak areas and the enantiomer concentrations in the range of 0.15–2.25 μg•mL−1 were in high linearity, with correlation coefficients higher than 0.999. The recoveries were 86.44% at the concentrations of 7.5, 18.75, and 37.5 μg•mL−1. The limit of detection (LOD) and limit of quantification (LOQ) were 0.042 and 0.14 μg•mL−1, respectively. This HPLC method is suitable for detecting the enantiomers of Xeljanz in its APIs and tablets. Chirality 27:235–238, 2015. © 2014 Wiley Periodicals, Inc.

The functions of transformer oil in the transformer were insulation and cooling, its position was very important. Oil usually keeps its good oxidation resistance by adding antioxidants, the most common used antioxidants in the transformer oil was T501, the oxidation rate of oil could be delayed significantly by adding it, thereby the life of oil would be prolonged. But the electrochemical performance of oil would be affected by the excessive addition of antioxidants, so it was important to determine the content antioxidant precisely. This paper mainly studied under the three electrode system, the determined electrode material and electrode size, studied the influence of support electrolyte species on the determination of T501 by electrochemical methods, choose the most suitable electrolyte solution type. It was further demonstrated that the working electrode was a 4 mm-diameter graphite electrode, Pt coil was used as the counter electrode, the reference electrode was a calomel electrode, the optimum electrolyte was KOH, optimum organic solvent was 98% ethanol solution.

WRKY proteins that contain highly conserved WRKYGQK sequence and zinc-finger-like motif belong to a large transcription factor family in plants. In this study, 26 genes encoding putative WRKY proteins were identified in cotton (Gossypium hirsutum). On the basis of their conserved WRKY domain sequences, all of the GhWRKY proteins can be assigned to the previously defined groups I–III. Among 26 members of cotton WRKY family, five with two WRKY domains belong to group I, sixteen contribute to group II, and five containing C2HC zinc-finger pattern fall into group III. Phylogenetic analysis of GhWRKY proteins with Arabidopsis WRKYs revealed that they were indeed classified into three groups, and also their relative distance can be used as clues to confer their putative functions. Quantitative RT-PCR analysis showed that the isolated GhWRKY genes were expressed differentially in different tissues (such as leaves, roots, cotyledons, petals, anthers, or/and fibers), suggesting they may have an impact on cotton development. Under NaCl, mannitol and abscisic acid treatments, expressions of the GhWRKY genes are up-regulated in roots, cotyledons and/or hypocotyls of cotton seedlings, suggesting that the isolated GhWRKY genes may take part in plant response to abiotic stress during cotton development. Thus, our results may provide a valuable reference data set as the basis for further studying the roles of these WRKY genes in cotton.

T501 is an antioxidant widely used in transformer oil. The content of T501 in transformer oil can be detected by electrochemical techniques, however, in the process of condition optimizing for electrochemical measurement, people haven’t done in-depth study the effect of working electrode on T510 antioxidant electrochemical measurement. This paper mainly introduced the alternative working electrodes for the determination of the antioxidant content. Through researching the electrochemical properties of T501 antioxidant by the electrochemical workstation, it is confirmed that the graphite electrode is the best working electrode in the electrochemical measurement of T501 antioxidant content.

Under the actions of dissolved oxygen, temperature, electric field, electric arc, moisture, impurities and metal catalysts, transformer oil in operation will undergo oxidation and cracking, which may result in production of large quantities of peroxides, alcohols, aldehydes, ketones and acids. To improve the oxidation stability of oil, the antioxidants should be added into the transformer oil before operation. This paper mainly introduced the oxidation process of transformer oil, the harm of transformer oil oxidation and the method for the determination of the T501 antioxidants content in transformer oil. It also forecast the development trend of the electrochemical test in the determination of T501 antioxidants content.

Two new sesquiterpenes, innatifolone A (1) and pinnatifolone B (2), along with 6 known compounds, furostan (3), isocalamendiol (4), pluviatolide (5), (8S,8'R,9S)-cubebin (6), 2-(4-hydroxy-3-methoxybenzyl)-3-(3,4-dimethoxybenzyl) tetrahydrofuran (7), and methyl 3-acetoxy-12-oleanen-28-oate (8), were isolated from Mongolian herb Syringa pinnatifolia.

According to the principle of the train longitudinal dynamics, the heavy haul longitudinal dynamics nonlinear model is established to analyze the influences of the load distribution pattern and the locomotive position on train longitudinal dynamics. The study of this paper is divided into two parts. The first, train model is composed by a locomotive and six trailers, researching the influences of the load distribution pattern on train longitudinal dynamics, the analysis results show that, the best load distribution pattern is the descending from head to tail of the train, in this case, the coupler force is minimum, and the train longitudinal dynamics is best; the second, train model is composed by two locomotives and five trailers, researching the influences of the position of the locomotive on train longitudinal dynamics. The analysis results show that, if the first locomotive is at the head of the train, then the second locomotives best position is at the end of the train, in this case, the coupler is minimum. But the train longitudinal dynamics performance is the worst with two locomotives are located in the head.

LIM-domain proteins play important roles in cellular processes in eukaryotes. In this study, a LIM protein gene, GhWLIM5, was identified in cotton. Quantitative RT-PCR analysis showed that GhWLIM5 was expressed widely in different cotton tissues and had a peak in expression during fiber elongation. GFP fluorescence assay revealed that cotton cells expressing GhWLIM5:eGFP fusion gene displayed a network distribution of eGFP fluorescence, suggesting that GhWLIM5 protein is mainly localized to the cell cytoskeleton. When GhWLIM5:eGFP transformed cells were stained with rhodamine-phalloidin there was consistent overlap in eGFP and rhodamine-palloidin signals, demonstrating that GhWLIM5 protein is colocalized with the F-actin cytoskeleton. In addition, high-speed cosedimentation assay verified that GhWLIM5 directly bound actin filaments, while low cosedimentation assay and microscopic observation indicated that GhWLIM5 bundled F-actin in vitro. Increasing amounts of GhWLIM5 protein were able to protect F-actin from depolymerization in vitro in the presence of Lat B (an F-actin depolymerizer). Our results contribute to a better understanding of the biochemical role of GhWLIM5 in modulating the dynamic F-actin network in cotton.