A new type of inorganic–organic hybrid materials—zirconium poly(styrene-phenylvinylphosphonate)-phosphate (ZPS-PVPA) was designed and synthesized. A series of new heterogeneous catalysts was obtained ...by grafting diamine or polyamine on ZPS-PVPA and subsequently axial coordination with chiral salen Mn(III) complexes. All the synthesized heterogeneous catalysts exhibited great activity and enantioselectivity in the asymmetric epoxidation of unfunctionalized olefins. Especially, in the epoxidation of
α-methylstyrene, both the conversion and enantiometric excess (ee) could exceed 99%. Furthermore, the catalysts were conveniently separated from the reaction system by simple precipitation in hexane and could be reused at least ten times without significant loss of activity and enantioselectivity.
New types of ZAMPS-PVPA-immobilized chiral salen Mn(III) complexes were synthesized and used as catalysts in the asymmetric epoxidation of unfunctionalized olefins.
Introduction Patients (pts) with high grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 gene rearrangements (double hit and triple hit (DH/TH)) have poor outcomes to standard R-CHOP. ...Retrospective studies reported improved disease-free survival (DFS) through intensification with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). This regimen was studied in a small prospective trial including 24 DH/TH and 19 single MYC rearranged (SH) lymphomas (Dunleavy, Lancet Haematol 2019). No prospective studies evaluating DA-EPOCH-R exclusively for pts with DH/TH HGBL have been reported. The HOVON-152 trial aimed to improve outcomes in untreated DH/TH HGBL pts by investigating the efficacy of the immune checkpoint inhibitor nivolumab as consolidation treatment in pts achieving complete metabolic response (CMR) after DA-EPOCH-R induction. Here, we present the efficacy and safety profile of the induction phase with DA-EPOCH-R. Methods HOVON-152 is a prospective, multi-center, single arm phase II trial. Inclusion criteria were pts with newly diagnosed HGBL-DH/TH (according to the WHO 2016 classification), age ≥ 18 years, WHO performance status (PS) 0-3 and Ann Arbor stage II-IV. During the screening period for rearrangement status, pts could receive 1 cycle of R-CHOP or DA-EPOCH-R, followed by 5 cycles of DA-EPOCH-R. All pts received intrathecal CNS prophylaxis. All diagnostic lymphoma samples were centrally reviewed. PET-CT scans were performed at diagnosis, after 3 cycles and at end-of-induction (local review, central review will be reported at the conference). Pts in CMR after induction treatment (Deauville 1-3 or a negative lymphoma biopsy in case of Deauville 4) proceeded to nivolumab consolidation (480 mg every 4 weeks for one year). The HOVON-152 aimed to improve 12 months DFS of pts in CMR after induction from an expected 70% to 85% with nivolumab consolidation. Secondary objectives included evaluation of response rates, overall survival (OS) and safety. With a power of 0.90 a sample size of 97 pts was calculated. Here, we report efficacy (CMR rate) and safety of DA-EPOCH-R induction treatment. Logistic univariate analysis is used to analyze baseline characteristics associated with response. Adverse events (AEs) were defined according to the common terminology criteria for adverse events (CTC AE 5.0), counted by the highest grade per system organ class per patient. Results From August 2018 - March 2022, 97 pts have been enrolled (study inclusion completed). One patient was excluded due to CNS localization. The median age was 62 years (range 35-79); 90 (83%) pts had stage III-IV disease and 52 (54%) had (intermediate-)high international prognostic index (IPI) (Table 1). Central pathology review confirmed DH/TH in all pts. 65 pts (67%) had a BCL2 DH, 11 (12%) a BCL6 DH and 16 (17%) a TH. Dose adjustments were performed conform protocol. The maximum dose-level (DL) achieved was DL1 in 41 (43%), DL2 in 22 (23%), DL3 in 25 (25%), DL4 in 7 (7%) and DL5 in 1 (1%) of the pts. Vincristine dose was reduced in 28/81 (35%) pts. After DA-EPOCH-R induction, 63/96 (66%, 95% CI 55-75%) pts achieved CMR. WHO PS 2-3 (odds ratio (OR) 0.15, 95% CI 0.03-0.85, p=0.03), elevated LDH (OR 0.24, 95%CI 0.10-0.59, p=0.002) and bulky disease defined as ≥10 cm mass (OR 0.23, 95%CI 0.09-0.56, p=0.001), were significantly associated with a lower chance of achieving CMR. During treatment, 7 (7%) pts experienced a grade 5 AE (ileus, intestinal perforation, multi-organ failure/sepsis). Thereof, 4 patients died during DA-EPOCH-R and 3 patients died after DA-EPOCH-R. 31 (32%) experienced a grade 4 AE (e.g. sepsis, perforation, hemorrhage, thrombocytopenia and neutropenia), 21 (22%) a grade 3 AE (e.g. anemia, mucositis, infections and electrolyte disturbances) and 16 (17%) pts a grade 2 AE. Conclusion We report the largest prospective series of DH/TH HGBL patients treated with DA-EPOCH-R. DA-EPOCH-R induction was feasible, with toxicity and dose adjustments as previously described. The observed CMR rate of 66% was lower than previously reported in a prospective cohort of mixed DH/TH and SH patients (74%). For patients achieving CMR, the nivolumab consolidation phase is ongoing. Translational side studies investigating predictive factors to identify patients not achieving CMR are ongoing. For these patients, novel strategies to improve first-line treatment are warranted.
Sugarcane smut is a major fungal disease caused by Sporisorium scitamineum, which seriously reduces the yield and quality of sugarcane. In this study, 36 transcriptome data were collected from two ...sugarcane genotypes, YT93-159 (resistant) and ROC22 (susceptible) upon S. scitamineum infection. Data analysis revealed 20,273 (12,659 up-regulated and 7614 down-regulated) and 11,897 (7806 up-regulated and 4091 down-regulated) differentially expressed genes (DEGs) in YT93-159 and ROC22, respectively. A co-expression network was then constructed by weighted gene co-expression network analysis (WGCNA), which identified 5010 DEGs in 15 co-expressed gene modules. Four of the 15 modules, namely, Skyblue, Salmon, Darkorange, and Grey60, were significantly associated with smut resistance. The GO and KEGG enrichment analyses indicated that the DEGs involving in these four modules could be enriched in stress-related metabolic pathways, such as MAPK and hormone signal transduction, plant-pathogen interaction, amino acid metabolism, glutathione metabolism, and flavonoid, and phenylpropanoid biosynthesis. In total, 38 hub genes, including six from the Skyblue module, four from the Salmon module, 12 from the Darkorange module, and 16 from the Grey60 module, were screened as candidate hub genes by calculating gene connectivity in the corresponding network. Only 30 hub genes were amplifiable with RT-qPCR, of which 27 were up-regulated upon S. scitamineum infection. The results were consistent with the trend of gene expression in RNA-Seq, suggesting their positive roles in smut resistance. Interestingly, the expression levels of AOX, Cyb5, and LAC were higher in ROC22 than in YT93-159, indicating these three genes may act as negative regulators in response to S. scitamineum infection. This study revealed the transcriptome dynamics in sugarcane challenged by S. scitamineum infection and provided gene targets for smut resistance breeding in sugarcane.
•Three factors are ascertained to measure the effects of disruptions.•Real-time prediction requirements are particularly considered in the model.•The model shows high accuracy in predicting the ...effects of disruptions.•The model shows strong generalizability on two different high-speed railway lines.
Based on the Bayesian network (BN) paradigm, we propose a hybrid model to predict the three main consequences of disruptions and disturbances during train operations, namely, the primary delay (L), the number of affected trains (N), and the total delay times (T). To obtain an effective BN structure, we first analyze the dependencies of the involved factors on each station and among adjacent stations, given domain knowledge and expertise about operational characteristics. We then put forward four candidate BN structures, integrating expert knowledge, the interdependencies learned from real-world data, and real-time prediction and operational requirements. Next, we train the candidate structures based on a 5-fold cross-validation method, using the operational data from Wuhan-Guangzhou (W-G) and Xiamen-Shenzhen (X-S) high-speed railway (HSR) lines in China. The best performing structure is nominated to predict the consequences of disruptions and disturbances in the two HSR lines. Comparisons results show that the proposed model outperforms three other commonly used predictive models, reaching an average prediction accuracy of 96.6%, 74.8%, and 91.0% on the W-G HSR line, and 94.8%, 91.1%, and 87.9% on the X-S HSR line for variables L, N, and T, respectively.
Emerging evidence of crosstalk between glomerular cells in pathological settings provides opportunities for novel therapeutic discovery. Here we investigated underlying mechanisms of early events ...leading to filtration barrier defects of podocyte and glomerular endothelial cell crosstalk in the mouse models of primary podocytopathy (podocyte specific transforming growth factor-β receptor 1 signaling activation) or Adriamycin nephropathy. We found that glomerular endothelial surface layer degradation and albuminuria preceded podocyte foot process effacement. These abnormalities were prevented by endothelin receptor-A antagonism and mitochondrial reactive oxygen species scavenging. Additional studies confirmed increased heparanase and hyaluronoglucosaminidase gene expression in glomerular endothelial cells in response to podocyte-released factors and to endothelin-1. Atomic force microscopy measurements showed a significant reduction in the endothelial surface layer by endothelin-1 and podocyte-released factors, which could be prevented by endothelin receptor-A but not endothelin receptor-B antagonism. Thus, our studies provide evidence of early crosstalk between activated podocytes and glomerular endothelial cells resulting in loss of endothelial surface layer, glomerular endothelial cell injury and albuminuria. Hence, activation of endothelin-1-endothelin receptor-A and mitochondrial reactive oxygen species contribute to the pathogenesis of primary podocytopathies in experimental focal segmental glomerulosclerosis.
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•Deep learning models were employed to predict train delays.•Train operations were modeled as sequences.•Interactions were captured from train groups in the prediction model.•The proposed model shows ...satisfactory performance on different railway lines.
This paper presents a carefully designed train delay prediction model, called FCLL-Net, which combines a fully-connected neural network (FCNN) and two long short-term memory (LSTM) components, to capture operational interactions. The performance of FCLL-Net is tested using data from two high speed railway lines in China. The results show that FCLL-Net has significantly improved prediction performance, over 9.4% on both lines, in terms of the selected absolute and relative metrics compared to the commonly used state-of-the-art models. Additionally, the sensitivity analysis demonstrates that interactions of train operations and weather-related features are of great significance to consider in delay prediction models.
Sugarcane smut caused by
Sporisorium scitamineum
is one of the most severe fungal diseases worldwide. In this study, a cross was made between a smut-resistant variety YT93-159 and a smut-susceptible ...variety ROC22, and 312 progenies were obtained. Two bulks of progenies were then constructed, one consisted of 27 highly smut resistant progenies and the other 24 smut susceptible progenies. Total RNAs of the progenies of each bulk, were pooled and subject to bulked segregant RNA-sequence analysis (BSR-Seq). A total of 164.44 Gb clean data containing 2,341,449 SNPs and 64,999 genes were obtained, 7,295 of which were differentially expressed genes (DEGs). These DEGs were mainly enriched in stress-related metabolic pathways, including carbon metabolism, phenylalanine metabolism, plant hormone signal transduction, glutathione metabolism, and plant-pathogen interactions. Besides, 45,946 high-quality, credible SNPs, a 1.27 Mb region at
Saccharum spontaneum
chromosome Chr5B (68,904,827 to 70,172,982), and 129 candidate genes were identified to be associated with smut resistance. Among them, twenty-four genes, either encoding key enzymes involved in signaling pathways or being transcription factors, were found to be very closely associated with stress resistance. RT-qPCR analysis demonstrated that they played a positive role in smut resistance. Finally, a potential molecular mechanism of sugarcane and
S. scitamineum
interaction is depicted that activations of MAPK cascade signaling, ROS signaling, Ca
2+
signaling, and PAL metabolic pathway and initiation of the glyoxalase system jointly promote the resistance to
S. scitamineum
in sugarcane. This study provides potential SNP markers and candidate gene resources for smut resistance breeding in sugarcane.
Higher order, non-Gaussian aspects of the large-scale structure carry valuable information on structure formation and cosmology, which is complementary to second-order statistics. In this work, we ...measure second- and third-order weak-lensing aperture-mass moments from the Canada–France–Hawaii Lensing Survey (CFHTLenS) and combine those with cosmic microwave background (CMB) anisotropy probes. The third moment is measured with a significance of 2σ. The combined constraint on Σ8 = σ8(Ωm/0.27)α is improved by 10 per cent, in comparison to the second-order only, and the allowed ranges for Ωm and σ8 are substantially reduced. Including general triangles of the lensing bispectrum yields tighter constraints compared to probing mainly equilateral triangles. Second- and third-order CFHTLenS lensing measurements improve Planck CMB constraints on Ωm and σ8 by 26 per cent for flat Λ cold dark matter. For a model with free curvature, the joint CFHTLenS–Planck result is Ωm = 0.28 ± 0.02 (68 per cent confidence), which is an improvement of 43 per cent compared to Planck alone. We test how our results are potentially subject to three astrophysical sources of contamination: source-lens clustering, the intrinsic alignment of galaxy shapes, and baryonic effects. We explore future limitations of the cosmological use of third-order weak lensing, such as the non-linear model and the Gaussianity of the likelihood function.
We derived constraints on cosmological parameters using weak lensing peak statistics measured on the ∼ 130 deg2 of the Canada–France–Hawaii Telescope Stripe 82 Survey. This analysis demonstrates the ...feasibility of using peak statistics in cosmological studies. For our measurements, we considered peaks with signal-to-noise ratio in the range of ν = 3, 6. For a flat Λ cold dark matter model with only (Ωm, σ8) as free parameters, we constrained the parameters of the following relation Σ8 = σ8(Ωm/0.27)α to be Σ8 = 0.82 ± 0.03 and α = 0.43 ± 0.02. The α value found is considerably smaller than the one measured in two-point and three-point cosmic shear correlation analyses, showing a significant complement of peak statistics to standard weak lensing cosmological studies. The derived constraints on (Ωm, σ8) are fully consistent with the ones from either WMAP9 or Planck. From the weak lensing peak abundances alone, we obtained marginalized mean values of
$\Omega _{\rm m}=0.38^{+0.27}_{-0.24}$
and σ8 = 0.81 ± 0.26. Finally, we also explored the potential of using weak lensing peak statistics to constrain the mass–concentration relation of dark matter haloes simultaneously with cosmological parameters.
Mosaic is one of the most important sugarcane diseases, caused by single or compound infection of Sugarcane mosaic virus (SCMV), Sorghum mosaic virus (SrMV), and/or Sugarcane streak mosaic virus ...(SCSMV). The compound infection of mosaic has become increasingly serious in the last few years. The disease directly affects the photosynthesis and growth of sugarcane, leading to a significant decrease in cane yield and sucrose content, and thus serious economic losses. This review covers four aspects of sugarcane mosaic disease management: first, the current situation of sugarcane mosaic disease and its epidemic characteristics; second, the pathogenicity and genetic diversity of the three viruses; third, the identification methods of mosaic and its pathogen species; and fourth, the prevention and control measures for sugarcane mosaic disease and potential future research focus. The review is expected to provide scientific literature and guidance for the effective prevention and control of mosaic through resistance breeding in sugarcane.
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