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The cost-effective synthesis of flexible energy storage devices with high energy and power densities is a challenge in wearable electronics.

LS-007, an inhibitor of cyclin-dependent kinase 9 (CDK9), exhibits potential antitumor activity against chronic lymphocytic leukemia and ovarian cancer, but its effect on melanoma and tumor microenvironment (TME) has not been reported yet. This study aimed to investigate the role of LS-007 in B16F10 melanoma and relevant mechanisms. LS-007 significantly inhibited viability and induced apoptosis of B16F10 cells in a dose-dependent manner, which were accompanied with the increased ratio of Bax to Bcl-2 and decreased Mcl-1 mRNA level. Western blot analysis showed that LS-007 increased the expression of cleaved caspase-3 and poly ADP-ribose polymerase (PARP). Furthermore, flow cytometry analysis and qRT-PCR results showed that LS-007 treatment resulted in cell cycle arrest by changing cell cycle-related gene expression. Notably, in vivo evaluation showed that LS-007 significantly decreased the weight and volume of tumor and the expression of Ki67, promoted the expression of iNOS and inhibited the expression of CD206, suggesting that LS-007 might inhibit tumor growth by suppressing polarization of macrophages into tumor-associated macrophages (TAMs) in the TME. The increase in M1/M2 treated with LS-007 detected by flow cytometry hinted that macrophages were polarized towards an antitumor phenotype. In addition, LS-007 induced higher apoptotic rate of B16F10 cells when co-cultured B16F10 with BMDMs. LS-007 has inhibitory effects on B16F10 cells in vivo and in vitro via inducing apoptosis, cell cycle arrest, and changing macrophage function in the TME.

Two-dimensional (2D) transition metal oxides (TMOs) have attracted much attention for various applications, owing to the abundance of active sites, rapid ion transmission speed, and short carrier migration distance. However, the current preparation strategies are usually limited to producing intrinsically layered compounds or sacrificing template. Here, we report a universal strategy for preparing ultrathin porous 2D TMO nanosheets by chemical topological transformation of the corresponding transition metal selenides. We observed that the as-prepared 2D TMO nanosheets not only perfectly inherit the transition metal selenides’ 2D topological structure, but also possess numerous pore structures formed as a way to release the structural stress associated with lattice growth. As a proof of concept, ultrathin porous WO3, MoO3, and Co3O4 nanosheets were successfully prepared based on the in-situ oxidation of the corresponding ultrathin WSe2, MoSe2, and Co0.85Se, respectively. The outstanding sensing properties and photodetector performance displayed by the as-prepared porous 2D WO3 nanosheets further indicate the promising prospects of topology transformation for the preparation of porous 2D TMO nanosheets.

It remains contested whether Chinese public consultation practices can be called local deliberative democracy or a sort of consultative authoritarianism. Yet, these different evaluations lack an ap...

Microevolution studies can disclose more elaborate evolutionary mechanisms of genes, appearing especially important for genes with multifaceted function such as those encoding outer membrane proteins. However, in most cases, the gene is considered as a whole unit, and the evolutionary patterns are disclosed.

Land use pattern has always been affected by urban development, and its optimization is of great significance to high-quality urban development, but the land use structure in coal cities has been rarely explored. Changzhi City, as a central city in the southeast region of Shanxi Province, is a large coal province with a superior ecological environment. Under the background of land spatial planning and ecological civilization construction, the land use structure and ecological problems of this city have attracted great attention. This research aims to explore the land use structure optimization method and provide new ideas for the national territory spatial planning of Changzhi City. On the basis of the 2010–2018 land use data of Changzhi City, the current problems in land use are analyzed, the construction land intensiveness, the potential of cultivated land reserve resources, and the potential of rural construction land consolidation are evaluated, and GeoSOS-FLUS is used to justify the conversion of various land types, providing the focus and direction of land use structure optimization and layout adjustment. Results show that the spatial distribution of land in Changzhi City presents the “forest-farm-forest” characteristic, the construction land intensive utilization of Changzhi City is low, and the potential of rural construction land consolidation is high. In addition, the conversion probability of cultivated land in Tunliu district and the conversion probability of construction land close to Luzhou district are relatively higher, which can be used as key areas for the future development of Changzhi City. In the process of urban development, cultivated land protection and construction land demand should be balanced.

Despite years of research investigating osteoblast differentiation, the mechanisms by which transcription factors regulate osteoblast maturation, bone formation, and bone homeostasis is still unclear. It has been reported that runt-related transcription factor 1 (Runx1) is expressed in osteoblast progenitors, pre-osteoblasts, and mature osteoblasts; yet, surprisingly, the exact function of RUNX1 in osteoblast maturation and bone formation remains unknown. Here, we generated and characterized a pre-osteoblast and differentiating chondrocyte-specific Runx1 conditional knockout mouse model to study RUNX1's function in bone formation. Runx1 ablation in osteoblast precursors and differentiating chondrocytes via osterix-Cre (Osx-Cre) resulted in an osteoporotic phenotype and decreased bone density in the long bones and skulls of Runx1(f/f)Osx-Cre mice compared with Runx1(f/f) and Osx-Cre mice. RUNX1 deficiency reduced the expression of SRY-box transcription factor 9 (SOX9), Indian hedgehog signaling molecule (IHH), Patched (PTC), and cyclin D1 in the growth plate, and also reduced the expression of osteocalcin (OCN), OSX, activating transcription factor 4 (ATF4), and RUNX2 in osteoblasts. ChIP assays and promoter activity mapping revealed that RUNX1 directly associates with the Runx2 gene promoter and up-regulates Runx2 expression. Furthermore, the ChIP data also showed that RUNX1 associates with the Ocn promoter. In conclusion, RUNX1 up-regulates the expression of Runx2 and multiple bone-specific genes, and plays an indispensable role in bone formation and homeostasis in both trabecular and cortical bone. We propose that stimulating Runx1 activity may be useful in therapeutic approaches for managing some bone diseases such as osteoporosis.

Although there have been studies investigating the relationship between information disclosure and voluntary compliance behaviors, the terrain of such research is largely fragmented and has been rarely tested empirically in the pandemic contexts. This article reviewed the intervention and control of the pandemic from the perspective of information disclosure with reflections on the experience in China. Furthermore, the authors propose a comprehensive framework demonstrating the overall landscape of information disclosure and voluntary compliance behaviors with highlights on (a) the tensions between privacy and information transparency; (b) the trade-offs between policy rigorousness and compliance behaviors; (c) different sources of information and how they influence public behaviors differently; and most importantly, (d) how the variegated configurations and contextualization of factors result in different influencing and moderating mechanisms between information disclosure and voluntary compliance behaviors. In the end, the authors call for future research and reforms in pandemic control practice to focus on the dynamics of information disclosure, government actions, and public compliance behaviors, which has been largely neglected so far.

Two series of novel triazolo-pyridazine/-pyrimidine derivatives were designed, synthesized, and evaluated for their inhibitory activity against c-Met kinase, as well as three c-Met overexpressed cancer cell lines (A549, MCF-7, and HeLa) and one normal human hepatocytes cell line LO2 in vitro. The pharmacological data indicated that most of the tested compounds showed moderate cytotoxicity, and the most promising compound 12e exhibited significant cytotoxicity against A549, MCF-7, and HeLa cell lines with IC50 values of 1.06 ± 0.16, 1.23 ± 0.18, and 2.73 ± 0.33 μM, respectively. Moreover, the inhibitory activity of compound 12e against c-Met kinase (IC50 = 0.090 μM) was equal to that of Foretinib (IC50 = 0.019 μM). The result of the acridine orange (AO) single staining test demonstrated that compound 12e could remarkably induce apoptosis of A549 cells. The results of apoptosis and cycle distribution of cells showed that compound 12e could induce late apoptosis of A549 cells and stimulate A549 cells arresting in the G0/G1 phase. Structure-activity relationships (SARs), pharmacological results, and docking studies indicated that the introduction of 5-methylthiazole fragment to the five-atom moiety was beneficial for the activity. So far, the existing data indicated that compound 12e may become a potential class II c-Met inhibitor.

The neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) present significant morbidity and mortality due to frequent non-response or adverse effects of the current clinical drugs. The disruption of the blood-brain barrier (BBB) contributes to inflammatory NPSLE disease progression. K-7174, a highly piperazine-derived compound, inhibits leukocyte adhesion and inflammatory factor expression. The present study aimed to comprehensively assess the treatment effect of neurobehavioral deficits in MRL/lpr mice, a validated neuropsychiatric lupus model. The intraperitoneal injection of K-7174 alleviated lupus-like symptoms and improved cognitive dysfunction in MRL/lpr mice. Also, it significantly attenuated neuronal degeneration and decreased serum albumin deposition in the hippocampus. Furthermore, K-7174 acted directly on the brain microvascular endothelial bEnd.3 cells and reduced the BBB permeability, manifested by inhibiting the activation of brain microvascular endothelial cells and increasing the expression of tight junctions (TJs). Notably, in vitro experiments showed that K-7174 alleviates the decreased ZO1 and Occludin expression in bEnd.3 cells caused by lactate increase, improving cell permeability via the MCT4/NKAP/CREB signaling pathway. These findings suggested that K-7174 mediates the attenuation of NPSLE in MRL/lpr mice, indicating a promising therapeutic strategy for NPSLE.

Background Ventricular tachycardia (VT) with or without structural heart disease is uncommon but well-recognized clinically in children. With this retrospective study, we collected the data from the in-hospital pediatric patients of VT with catheter ablation therapy. The purpose of this study is to assess the acute results and the long-term outcome of catheter ablation in pediatric patients of VT in our single pediatric center. Methods This study included 53 consecutive children (male/female = 33/20, mean age = 8.2 ± 3.4 years, mean bodyweight = 32.6 ± 13.7 kg). All patients underwent electrophysiological study with an attempt of catheter ablation for clinical monomorphic VT. Acute and long-term success rate of catheter ablation for the treatment of VT were compared between right and left VT as well as fascicular VT (FVT) and nonfascicular VT. Results There were 53 idiopathic VT forms found in the children, including FVT (n = 32), outflow tract VT (n = 15), papillary muscle VT (n = 5), and bundle branch reentry VT (n = 1). Acute success of catheter ablations for VT was achieved in 57 of all the 59 ablation procedures (97%) with VT recurrence occurred in six of 53 patients (11%). During a mean follow-up period of 29.2 ± 21.7 months (range 1-76 months) after hospital discharge, ablations in nonfascicular VT were as successful as FVT. There was no significant difference in the success rate between the right and left VT. Conclusion Catheter ablation is an effective treatment for idiopathic VT in children. The acute and long-term success rates of catheter ablation for idiopathic VT in pediatric patients with normal heart structure are satisfying.

The grain refinement mechanism and texture evolution of electromagnetically formed polycrystalline Cu sheets were investigated using the electron back-scattered diffraction (EBSD) technique. It is found that the average grain size decreases from 35.88 μm to 8.77 μm. The grain refinement was mainly attributed to dynamic recrystallization (DRX) at the grain boundary regions of bulged Cu samples where the inhomogeneous dislocation density and the large lattice misorientation were observed. The DRX mechanisms at the grain boundaries were discussed with respect to the strain-induced grain boundary migration nucleation. Moreover, the orientation distribution function (ODF) of the sample with the strain of 50% demonstrated a strong {110} texture and a relatively weak {001} texture. The texture evolution was discussed using the plastic work values of the grains with various orientations, which were calculated according to the Taylor model and the virtual work principle. The experimental results show that the expended plastic work of the grains with {110} orientation is 9.69 MPa, which is distinctly higher than those of the grains with the {001} and {111} orientations. This indicates that the formation of the {110} orientated texture would be preferred with increasing strain in good agreement with the experimental result.

Condyloma acuminatum (CA) of the anal canal is difficult to treat and subject to relapse.. We investigated the effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with oral acitretin during therapy of refractory CA in the anal canal. We also conducted a clinical retrospective study for the treatment of intra-anal CA.A total of 101 patients diagnosed with intra-anal CA were enrolled. All patients underwent liquid nitrogen cryotherapy as a basic treatment until visible wart clearance. Patients were divided into two groups depending on the treatment modality after cryotherapy. ALA-PDT group with 51 patients was given ALA-PDT treatment, and ALA-PDT plus acitretin group with 50 patients was given ALA-PDT treatment combined with oral acitretin. The cure rate, recurrence rate, and adverse reactions of the two groups were analyzed and recorded.The cure rate in the ALA-PDT plus acitretin group was 94% (47/50), which was significantly higher than 80.4% (41/51) in ALA-PDT group. The recurrence rate in the ALA-PDT plus acitretin group was 6% (3/50), which was lower than 19.6% (10/51) in ALA-PDT group (P0.05).ALA-PDT combined with oral acitretin is effective and safe in the treatment of refractory CA in anal canal, and with further study may become an option for these patients.

Bacterial porins serve as the interface interacting with extracellular environment, and are often found under positive selection to fit in different environmental stresses. Local recombination has been identified in a handful of porin genes to facilitate the rapid adaptation of bacterial cells. It remains unknown whether it is a common evolutionary mechanism in gram-negative bacteria for all or a majority of the outer membrane proteins. In this research, we investigated the β-barrel porin encoding genes inEscherichia colithat were reported under positive Darwinia selection. BesidesfhuAthat was found with ingenic local recombination predominantly previously, we identified four other genes, i.e.,lamB, ompA, ompCandompF, all showing the similar mosaic evolution patterns as infhuA. Comparative analysis of the protein sequences disclosed a list of highly variable regions in each protein family, which are mostly located in the convex of extracellular loops and coinciding with the binding sites of various bacteriophages. For each of the porin family, mosaic recombination leads to various combinations of the HVRs with different sequence patterns, generating diverse protein groups. Structure modeling further indicated the conserved global topology for various groups of each porin family, but the extracellular surface varies a lot that is formed by individual or combinatorial HVRs. The conservation of global tertiary structure ensures the channel activity while the wide diversity of HVRs may assist bacteria avoiding the invasion of phages, antibiotics or immune surveillance factors. In summary, the study identified multiple bacterial porin genes with mosaic evolution, a likely general strategy, by which outer membrane proteins could facilitate the host bacteria to both maintain normal life processes and evade the attack of unflavored environmental factors rapidly.ImportanceMicroevolution studies can disclose more elaborate evolutionary mechanisms of genes, appearing especially important for genes with multifaceted function such as those encoding outer membrane proteins. However, in most cases, the gene is considered as a whole unit and the evolutionary patterns are disclosed. In this research, we reported that multiple bacterial porin proteins follow mosaic evolution, with local ingenic recombination combined with spontaneous mutations based positive Darwinia selection, and conservation for most of the other regions. It could represent a common mechanism for bacterial outer membrane proteins. The study also provides insights on development of new anti-bacterial agent or vaccines.

Land-use patterns have always been affected by urban development, and their structural optimization is of great significance to high-quality urban development. However, since the establishment of the spatial planning system, there are still a lack of methods for optimizing the land-use structure. To this end, the research proposes an analysis framework, and proposes the direction of land-use structure adjustment through the status analysis, potential evaluation, and LUCC simulation model, and provides a new idea and method of spatial planning. The research uses an analytical framework to analyze the case of Changzhi City, Shanxi Province, puts forward the problems existing in the process of its land use, and further proposes the direction and focus of the adjustment of the land-use structure. Results show that the spatial distribution of land in Changzhi City presents a “forest-farm-forest” characteristic, and forest land, farmland and grassland account for 85% of its total area. From 2010 to 2018, the grassland area in Changzhi City decreased the most to 3486.13 hm2, and the comprehensive degree of land use increased from 235.88% to 236.73%; however, the cultivated land showed a downward trend. The construction land intensive utilization of Changzhi City is low, and the potential for rural construction land consolidation is high. In addition, the conversion probability of cultivated land in the Tunliu district and the conversion probability of construction land close to Luzhou district are relatively higher, which can be used as crucial areas for the future development of Changzhi City. In the process of urban development, cultivated land protection and construction land demand should be balanced.

Osteoarthritis (OA) is considered as a chronic disease without obvious symptoms in early stage, and incurable currently. It is necessary to find an ideal method that can efficiently diagnose OA at the early stage. Surface-enhanced Raman scattering (SERS) technique is widely used for detecting the biomarkers in the biological tissues because of its competitive advantages such as high efficiency and convenience. The SERS spectra of synovial fluid (SF) from three different OA stages were collected in this study, whose results indicate that the contents of protein and proteoglycan in SF has already changed at the beginning of OA, let alone that at advanced OA stage. The frequency shifts of Raman bands suggest that modifications of the structure and components in SF at different OA stages, showing the increase in protein abundance. This study demonstrates that much more information of SF can be clearly disclosed and SERS has great potential to be an efficient tool for OA screening and diagnosis.

Galanin receptor1 (GalR1) transcript levels are elevated in the rat ventral periaqueductal gray (vPAG) after chronic mild stress (CMS) and are related to depression-like behavior. To explore the mechanisms underlying the elevated GalR1 expression, we carried out molecular biological experiments in vitro and in animal behavioral experiments in vivo. It was found that a restricted upstream region of the GalR1 gene, from −250 to −220, harbors an E-box and plays a negative role in the GalR1 promoter activity. The transcription factor Scratch2 bound to the E-box to down-regulate GalR1 promoter activity and lower expression levels of the GalR1 gene. The expression of Scratch2 was significantly decreased in the vPAG of CMS rats. Importantly, local knockdown of Scratch2 in the vPAG caused elevated expression of GalR1 in the same region, as well as depression-like behaviors. RNAscope analysis revealed that GalR1 mRNA is expressed together with Scratch2 in both GABA and glutamate neurons. Taking these data together, our study further supports the involvement of GalR1 in mood control and suggests a role for Scratch2 as a regulator of depression-like behavior by repressing the GalR1 gene in the vPAG.

A new Co(II)-MOF [NH2(CH3)2][Co1.5(abtc)]·H2O (1) (H4abtc: 3,3′,5,5′‑azobenzenetetracarboxylic acid) has been solvothermally synthesized and characterized. Complex 1 is a three-dimensional {Co3}-based framework with one-dimensional channels bridged by the μ2-bridging abtc ligand, resulting in a (4, 8)-connected topology. Luminescent studies reveal that complex 1 shows weak emission in solid state at room temperature, but the emission intensities have greatly enhanced in both liquid suspensions and solid state after immersion in acetonitrile solvent.

Oral squamous cell carcinomas (OSCCs) are one of the most ubiquitous malignancies the world over, and are accompanied by a high mortality. microRNAs (miRNAs) have increasingly garnered attention with regards to the roles they play in initiation and progression of various kinds of cancers, including OSCC. It has been reported, that miR-23a-3p promotes the development of tumors for prostate cancer, gastric cancer and gliomas. The functions of miR-23a-3p in OSCC however, remain unclear. In this study, fibroblast growth factor 2 (FGF2) is revealed as a direct target of miR-23a-3p, based on luciferase assays and immunoblotting. The expression of miR-23a-3p and FGF2 were found to be significantly downregulated and upregulated in OSCC tissues respectively. This indicates a reverse correlation between miR-23a-3p and FGF2 levels. Using in vitro approaches we ascertained that miR-23a-3p might contribute to the inhibition of growth and inhibition through increasing apoptosis in OSCC cells; while an inhibitor of miR-23a-3p could reverse this effect. Examination of a clinical cohort of OSCC patients suggested that reduced expression of miR-23a-3p is correlated with more advanced cancerous stage and poorer differentiation of OSCC cell. Additionally, a survival analysis and the Cox-hazard regression model showed that higher levels of miR-23a-3p can be used reliably for prognosis of OSCC patients. This study indicates that miR-23a-3p might suppress tumor proliferation, invasion and promote apoptosis of OSCC by targeting FGF2. miR-23a-3p has the potential to be used as prognostic indicator, and could be exploited as a therapeutic reagent for OSCC in the future.

In the present work, a two-layer hydroxyapatite (HA)/Cu-doped TiO2 composite coating was prepared via one-step micro-arc oxidation in an aqueous electrolyte containing calcium acetate, sodium di-hydrogen phosphate and ethylene diamine tetraacetic acid cupric disodium (CuNa2-EDTA) at a constant current density of 100 mA/cm2. After micro-arc oxidation for 20 min, Cu species incorporate into the TiO2 as CuO and Cu2O, resulting in the formation of Cu-doped TiO2-based coating. In addition, spherical-shaped HA phase of nanometre scale is also present on the Cu-doped TiO2-based coating. With HA phase boosting osseointegration and Cu species killing pathogenic microbes, a bi-functional coating fabricated by one-step micro-arc oxidation is of promising potential application in the bio-medical field.

As a new group of important effector molecules involved in multiple cancer types, including breast cancer, lung cancer and oral squamous cell carcinoma, long noncoding RNAs (lncRNAs) have attracted considerable attention recently. However, the underlying cause that induces the dysregulated lncRNAs in cancer remains poorly understood. In the present study, the regulatory model of the lncRNA placenta-specific protein 2 (PLAC2) upregulation in oral squamous cell carcinoma (OSCC) was investigated and its biological functions in OSCC malignant progression was identified. A reverse transcription-quantitative polymerase chain reaction assay identified that PLAC2 is upregulated in OSCC cell lines and primary tissue samples. Furthermore, bioinformatic analysis followed by chromatin immunoprecipitation verified an enriched histone H3 on lysine 27 (H3K27) acetylation (H3K27ac) at the promoter region of the PLAC2 gene. Knockdown of cAMP-response element binding protein-binding protein (CBP) significantly reduced the enrichment level of H3K27ac, and thereby induced a decreased expression of PLAC2. Functionally, overexpression of PLAC2 promotes OSCC cell proliferation, migration and invasion, whereas knockdown of PLAC2 exerted an opposite effect. Furthermore, the Wnt/β-catenin signaling pathway was activated by PLAC2 and mediated the PLAC2-induced malignant progress of OSCC. In conclusion, the present results indicated that lncRNA PLAC2 is transcriptionally activated by H3K27ac modification at the promoter region in OSCC, and promotes cell growth and metastasis via activating Wnt/β-catenin signaling pathway. Therefore, PLAC2 may serve as a promising biomarker for OSCC prognosis and therapy.

Cutaneous blastomycosis is endemic to North America and is often caused by dimorphic fungi with spores that are inhaled, inoculated spores, or hyphae that infect immunosuppressed and healthy people. It is sporadic and described as a universal imitator with morphological manifestations as erythema, nodules, and ulcers. Our case demonstrated a 69-year-old female bitten by her pet dog who was then diagnosed with cutaneous blastomycosis through social history and detailed laboratory examinations. She experienced a prolonged failure with antibacterial treatment, negative stool and tissue culture, and chronic inflammatory cell infiltrates on tissue pathology. High-throughput sequencing was performed and showed evidence of Blastomyces dermatitidis aetiology. Photodynamic therapy combined with oral itraconazole was administered, and the patient recovered in a short time. Our case presents inoculated cutaneous blastomycosis and a treatment approach in which photodynamic therapy combined with oral itraconazole significantly reduced the duration of disease treatment and affords a promising choice for the treatment of cutaneous blastomycosis.

To explore the genetic basis for 7 patients with Alström syndrome.DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549CT (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819CT (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379CT (p.Gln3127*), c.12115CT (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825CT (p.Arg3609*) and c.3902CA (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379CT, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379CT and c.12115CT variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4).ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.

Phenyl (6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl)carbamate (7) was an important intermediate of many antitumor drugs, especially, it is widely used in small molecular inhibitors of anti-tumor. Compound 7 was synthesized from 6-chloropyrimidine-4-amine by acylation and nucleophilic substitution. The structures of the intermediates were confirmed by MS and 1H NMR. Furthermore, the synthetic method was optimized.