Accelerated discovery of high-performance Al-Si-Mg-Sc casting alloys by integrating active learning with high-throughput CALPHAD calculations.

Scandium is the best alloying element to improve the mechanical properties of industrial Al-Si-Mg casting alloys. Most literature reports devote to exploring/designing optimal Sc additions in different commercial Al-Si-Mg casting alloys with well-defined compositions. However, no attempt to optimize the contents of Si, Mg, and Sc has been made due to the great challenge of simultaneous screening in high-dimensional composition space with limited experimental data. In this paper, a novel alloy design strategy was proposed and successfully applied to accelerate the discovery of hypoeutectic Al-Si-Mg-Sc casting alloys over high-dimensional composition space. Firstly, high-throughput CALculation of PHAse Diagrams (CALPHAD) solidification simulations of ocean of hypoeutectic Al-Si-Mg-Sc casting alloys over a wide composition range were performed to establish the quantitative relation 'composition-process-microstructure'. Secondly, the relation 'microstructure-mechanical properties' of Al-Si-Mg-Sc hypoeutectic casting alloys was acquired using the active learning technique supported by key experiments designed by CALPHAD and Bayesian optimization samplings. After a benchmark in A356-xSc alloys, such a strategy was utilized to design the high-performance hypoeutectic Al-xSi-yMg alloys with optimal Sc additions that were later experimentally validated. Finally, the present strategy was successfully extended to screen the optimal contents of Si, Mg, and Sc over high-dimensional hypoeutectic Al-xSi-yMg-zSc composition space. It is anticipated that the proposed strategy integrating active learning with high-throughput CALPHAD simulations and key experiments should be generally applicable to the efficient design of high-performance multi-component materials over high-dimensional composition space.

Effect of Process Parameters on the Microstructure and Properties of Cu-Cr-Nb-Ti Alloy Manufactured by Selective Laser Melting.

The fabrication of high-performance copper alloys by selective laser melting (SLM) is challenging, and establishing relationships between the process parameters and microstructures is necessary. In this study, Cu-Cr-Nb-Ti alloy is manufactured by SLM, and the microstructures of the alloy are investigated by X-ray diffraction (XRD), scanning electron microscope (SEM), and electron backscatter diffraction (EBSD). The effects of processing parameters such as laser power and scanning speed on the relative density, defects, microstructures, mechanical properties, and electrical conductivity of the Cu-Cr-Nb-Ti alloy are studied. The optimal processing window for fabricating Cu-Cr-Nb-Ti alloy by SLM is determined. Face-centered cubic (FCC) Cu diffraction peaks shifting to small angles are observed, and there are no diffraction peaks related to the second phase. The grains of XY planes have a bimodal distribution with an average grain size of 24-55 µm. Fine second phases with sizes of less than 50 nm are obtained. The microhardness, tensile strength, and elongation of the Cu-Cr-Nb-Ti alloy manufactured using the optimum processing parameters, laser power of 325 W and scanning speed of 800 mm/s, are 139 HV0.2, 416 MPa, and 27.8%, respectively, and the electrical conductivity is 15.6% IACS (International Annealed Copper Standard). This study provides a feasible scheme for preparing copper alloys with excellent performance and complex geometries.

A novel prognostic and therapeutic target biomarker based on complement-related gene signature in gastric cancer.

Background: Gastric cancer (GC) is one of the most prevalent cancer types that reduce human life expectancy. The current tumor-node-metastasis (TNM) staging system is inadequate in identifying higher or lower risk of GC patients because of tumor heterogeneity. Research shows that complement plays a dual role in the tumor development and progression of GC. Methods: We downloaded GC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A complement-related risk signature was constructed through bioinformatics analysis. Subsequently, the predictive ability of this signature was validated with GSE84437 dataset, and a nomogram integrating risk score and common clinical factors was established. Besides, we evaluated the association of risk score with the immune and stromal cell infiltration in TCGA. Furthermore, immunotherapy response prediction and drug susceptibility analysis were conducted to access the ability of the risk signature in predicting the therapeutic effect. Results: A complement-related gene (CRG) signature, based on six genes (SPLG, C9, ITIH1, ZFPM2, CD36, and SERPINE1), was established. In both the training and validation sets, the overall survival of GC patients in the high-risk group was lower than that of the low-risk group, and the nomogram to predict the 1-, 2-, and 3-year survival rates of GC patients was developed. In addition, CIBERSORT algorithm showed the high-risk patients had higher levels of immune cell infiltration than low-risk patients, and the ESTIMATE results implied that the high-risk group had more stromal component in tumor microenvironment. Besides, compared to the low-risk group, there were higher expressions of most immune checkpoint genes and HLA genes in the high-risk group, and the high-risk patients showed higher sensitivity to the chemotherapy and targeted drugs (axitinib, dasatinib, pazopanib, saracatinib, sunitinib and temsirolimus). Conclusions: The novel CRG signature may act as a reliable, efficient tool for prognostic prediction and treatment guidance in future clinical practice.

Effect of Heat Treatment on Cr2Nb Phase and Properties of Spark Plasma Sintered Cu-2Cr-1Nb Alloy.

Achieving a good match between strength and conductivity is a challenge of the development of the high-performance Cu-Cr-Nb alloy for aerospace and fusion energy. The effect of heat treatment on Cr2Nb phase, strength and conductivity of spark plasma sintered (SPSed) Cu-2Cr-1Nb (at%) alloy was investigated. The results illustrated that Cr2Nb phase of Cu-2Cr-1Nb alloy can be regulated by heat treatment, multi-scale Cr2Nb phase with sizes of 0.10-0.50 µm, 30-100 nm and less than 30 nm was obtained, and the strength and conductivity were significantly increased after heat treatment at 500 °C for 2 h, the room temperature tensile strength and conductivity were 332 MPa and 86.7% IACS, 2.5% and 34.8% higher than those of as-SPSed alloy; the tensile strength at 700 °C was 76 MPa. Increasing heat treatment temperature and time, the tensile strength of the alloy was reduced by 1.5%, 4.3% and 12.3% after heat treatment at 500 °C, 700 °C and 950 °C for 72 h. The good match between strength and conductivity of Cu-Cr-Nb alloy was obtained by reducing the content of alloying elements (Cr and Nb) and microstructure regulation. This approach can be used to prepare structural/functional materials with excellent strength and conductivity.

Cracking Behavior of René 104 Nickel-Based Superalloy Prepared by Selective Laser Melting Using Different Scanning Strategies.

Eliminating cracks is a big challenge for the selective laser melting (SLM) process of low-weldable Nickel-based superalloy. In this work, three scanning strategies of the snake, stripe partition, and chessboard partition were utilized to prepare René 104 Ni-based superalloy, of which the cracking behavior and the residual stress were investigated. The results showed that the scanning strategies had significant effects on the cracking, residual stress, and relative density of the SLMed René 104 superalloy. The scanning strategies with more partitions boosted the emergence of cracks, as high-density cracks occurred in these samples. The overlapping zone (OZ) of the scanning partition was also susceptible to cracking, which increased the size, number, and density of the cracks. The cracking performance was relatively moderate in the snake-scanned samples, while that in the chessboard-partition-scanned samples was the most severe. It is concluded that the partition scanning strategies induced more cracks in the SLMed René 104 superalloy, of which the residual stress was apparently reduced. Therefore, it is necessary to design scanning strategies with optimized scanning partitions and overlaps to avoid cracking and acquire a high-quality, near fully dense, low-weldable Nickel-based superalloy using SLM.

Synthesis of (hetero)arylated pyridazin-3(2H)-ones via Negishi reaction involving zincated pyridazin-3(2H)-ones.

Zincated pyridazin-3(2H)-ones generated via bromine-magnesium exchange followed by transmetalation using ZnCl(2) or via lactam-directed ortho C4-H zincation with TMPZnCl·LiCl have been synthesized. These in situ created organometallics can be used in Negishi reactions with iodo(hetero)arenes delivering a new approach toward (hetero)arylpyridazin-3(2H)-ones.

Synthesis of functionalized pyridazin-3(2H)-ones via selective bromine-magnesium exchange and lactam directed ortho C-H magnesiation.

Selective bromine-magnesium exchange on 2-benzyl-5-bromo-4-methoxypyridazin-3(2H)-one could be achieved when MesMgBr was used as reagent. With more nucleophilic RMgCl species (R = Bu, i-Pr, Ph) both nucleophilic addition-elimination at C-4 and bromine-magnesium exchange at C-5 occurred. In 2-benzyl-5-bromopyridazin-3(2H)-one, which does not contain a substituent at C-4, addition could not be suppressed. Less nucleophilic Mg amides (TMPMgCl·LiCl) allowed regioselective C-H magnesiation at the C-4 position in such substrates, as exemplified for 2-benzyl-5-chloro- and 2-benzyl-6-chloropyridazin-3(2H)-one. Quenching of the magnesiated pyridazinones with electrophiles gives access to a variety of hitherto unknown pyridazin-3(2H)-one derivatives.

[Detecting and identifying 3 novel single nucleotide polymorphisms in DNA sequence of epidermal growth factor precursor from Buyi and Han individuals].

OBJECTIVE: To examine the single nucleotide polymorphism (SNP) distributed in exon 20, 21 and intron 20 of epidermal growth factor precursor gene (preproEGF) of Buyi and Han individuals. METHODS: Eleven primer sets were designed and synthesized for PCR, that genomic DNA of Buyi or Han individual was used as the template, to amplify and sequence respectively the large fragment DNA from preproEGF gene. BLAST programs were applied to compare and identify the SNPs from the sequenced PCR products or amplified DNA fragments. RESULTS: 4.5 kb DNA fragments long over 20th, 21st exon and 20th intron structures of preproEGF gene were got by PCR respectively from genomic DNAs of Buyi and Han individuals. Results of DNA sequencing showed two SNPs in 4. 5 kb fragment of Han individual, of which one was sited at C86380T of preproEGF gene and another positioned at 84580 bp (T/-), while one SNP was observed in Buyi individual, which was located at T84329C of preproEGF gene. GenBank dbSNP database showed that C86380T SNP in 20th intron of preproEGF gene has not been reported yet from Han group and other cohorts except it has been reported from European and Sub-Saharan groups; and also that T84329C SNP has not been reported yet from Buyi group although it has been reported from Han group. CONCLUSIONS: Our study demonstrates that the Han individual is with C86380T SNP located in 20th intron of human preproEGF gene; and that the Buyi individual has the T84329C SNP sited in 20th intron of human preproEGF gene. However, another Han SNP (T/-) positioned at 84580 bp need to be further confirmed.

Synthesis and fungicidal activities of new 1,2,4-triazolo[1,5-a]pyrimidines.

A series of new acetohydrazone-containing 1,2,4-triazolo[1,5-a]pyrimidine derivatives were designed and synthesized for the purpose of searching for novel agrochemicals with higher fungicidal activity. Their in vitro fungicidal activities against Rhizoctonia solani were evaluated, and the most promising compound, 2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2'-[(2-hydroxyphenyl)methylidene]acetohydrazide (2-17), showed a lower EC(50) value (5.34 microg ml(-1)) than that of commercial carbendazim (EC(50)=7.62 microg ml(-1)). Additionally, compound 2-17 was also found to display broad-spectrum fungicidal activities, and its EC(50) value (4.56 microg ml(-1)) against Botrytis cinereapers was very similar to that of carbendazim. Qualitative structure-activity relationships (QSARs) of the synthesized compounds were also discussed.

Synthesis, fungicidal, and insecticidal activities of beta-Methoxyacrylate-containing N-acetyl pyrazoline derivatives.

1-Acetyl-3,-5-diarylpyrazolines have received considerable interests from the fields of medicinal and agricultural chemistry due to their broad spectrum of biological activities. To discover new lead compounds exhibiting both fungicidal and insecticidal activities, a series of pyrazoline derivatives were designed and synthesized by introducing the beta-methoxyacrylate pharmacophore into the scaffold of 1-acetyl-3,5-diarylpyrazoline. The fungicidal activities against Pseudoperoniospora cubensis, Sphaerotheca fuliginea, Botrytis cinerea, and Rhizoctonia solani and the insecticidal activities against Aphis medicagini, Nilaparvata legen, Mythima separata, and Tetranychus cinnabarnus were screened. The most potent compound 13, 1-aceto-3-[m-[o-(E-1-methoxycarboxyl-2-methoxy)-1-yl]benzyloxy]phenyl-5-(benzo-[1,3]-dioxolyl)-4,5-dihydro- pyrazoline, was identified. Its fungicidal IC(50) values against P. cubensis and S. fuliginea are 26.6 and 57.6 microg mL(-1), respectively, while its insecticidal LC(50) value against M. separata is 26.6 microg mL(-1). These results indicated that compound 13 could be used as a lead for further developing new pyrazoline type products exhibiting both fungicidal and insecticidal activities.

Syntheses of diheterocyclic compounds based on 2-thioacetohydrazide-5,7-dimethyl-1,2,4-triazolo[1,5-a]- pyrimidine.

The syntheses of some diheterocyclic compounds from 2-thioacetohydrazide- 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (1) are described. Compound 1 can be converted into triazoles, 1,3,4-oxadiazoles, and 1,3,4-thiadiazoles. The structures of the intermediates and the target compounds were confirmed by (1)H-NMR, MS and elemental analyses.

Blue organic light-emitting supramolecular microfibers: the self-assembly of a 1,2,4-triazolo[1,5-a]pyrimidine derivative.

The design and synthesis of 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-thioaceto-(2-fluorobenzyl) hydrazone (TPTH), which self-assembled into supramolecular microfibers with blue organic light-emitting properties, is reported. This is the first occurrence of the molecular self-assembly of 1,2,4-triazolo[1,5-a]pyrimidine derivatives.

Synthesis, antifungal activity and CoMFA analysis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives.

In order to search novel agrochemicals with higher antifungal activity, a series of new 1,2,4-triazolo[1,5-a]pyrimidine derivatives bearing 1,3,4-oxadiazole moieties were designed and synthesized. Their antifungal activities against Rhizoctonia solani were evaluated in vitro. By determining the EC(50) values of all the newly synthesized compounds and 10 formerly synthesized compounds, compound 8r, 2-((5-(sec-butylthio)-1,3,4-oxadiazol-2-yl)-methylthio)-5-dimethyl-1,2,4-triazolo-[1,5-a]pyrimidine, was found to display the highest antifungal activity (EC(50)=6.57 microg mL(-1)). Based on the quantitative structure-activity relationships analyses, 2-(1-(5-(sec-butylthio)-1,3,4-oxadiazol-2-yl)ethylthio)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (9j) was designed and synthesized, which was found to display much higher activity (EC(50)=3.34 microg mL(-1)) than compound 8r and the control. To further explore the comprehensive structure-activity relationships, a 3D-QSAR analysis using the method of comparative molecular field analysis (CoMFA) was performed and a statistically reliable model with good predictive power (r(2)=0.929, q(2)=0.588) was achieved on the basis of the common substructure-based alignment. According to the CoMFA model, the structure-antifungal activity relationship was explained reasonably.

Design, synthesis, and fungicidal activities of new strobilurin derivatives.

Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin analogues with high activity against resistant pathogens, a series of new strobilurin derivatives bearing structurally diverse heterocycle side chains 3a-m and 4a-g were designed and synthesized via a microwave-assisted procedure. The advantages, such as good to excellent yields, shorter reaction times, mild reaction conditions, and simple purification procedures, distinguish the present synthetic protocol as a highly efficient method for the preparation of strobilurin thioether derivatives. Bioassays indicated that most of the compounds showed broad-spectrum fungicidal activity in vitro. Interestingly, as compared to the control of a commercial strobilurin fungicide, Kresoxim-methyl, compounds 3b, 3g, 4c, and 4d possessed remarkably higher in vitro fungicidal activity against six kinds of tested fungi. Exhilaratingly, compound 3g exhibited higher in vivo activity against Sphaerotheca fuliginea and Pseudoperoniospora cubensis than Kresoxim-methyl, and the in vivo fungicidal activities of compound 4d and Kresoxim-methyl against S. fuliginea and P. cubensis are at the same level. The present work demonstrated that strobilurin analogues containing benzothiazole side chains could be used as a lead structure for further developing novel fungicides.