Discovery of a potent and selective cell division cycle 7 inhibitor from 6-(3-fluoropyridin4-yl)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as an orally active antitumor agent

To the Editor:Kinase cell division cycle 7(CDC7),a cell division cycle protein,takes a vital role in mediating DNA replication1.CDC7 complexes in the nucleus can phosphorylate the minichromosome maintenance complex(MCM)family members that bind to chromosomes.In addition,CDC7 kinase,as a molecular switch regulating DNA replication,can mediate DNA damage signaling pathways to stimulate cell cycle termination as well as DNA replication2.Studies have shown that CDC7 is overexpressed in many types of cancer cells,and its overexpression was related to poor patient survival,tumor grade,genetic instability,aneuploidy and so on3.Therefore,CDC7 is a promising target for antitumor therapy.

年龄组运动员长期培养的热点问题综述

通过文献梳理,对年龄组运动员的分组、运动技能学习、训练敏感期、运动员成长和培养、运动员培养的支持5个热点主题进行综述。发现:年龄组运动员的培养呈现精准化趋势;其训练需根据生理发育指标,抓住各素质发展的机会窗口,同时以提高技术为主线;年龄组运动员的培养需以学习教育为主安排运动训练;提供高效、低成本的退出保障机制,力争使各水平年龄组运动员通过不同形式转化为体育人口。

Non-Stoichiometry Effects on the Extreme Magnetoresistance in Weyl Semimetal WTe2

Non-stoiehiometry effect on the extreme magnetoresistanee is systematically investigated for the Weyl semimetal WTe2. Magnetoresistance and Hall resistivity are measured for the as-grown samples with a slight difference in Te vacancies and the annealed samples with increased Te vacancies. The fits to a two-band model show that the magnetoresistanee is strongly dependent on the residual resistivity ratio （i.e., the degree of non-stoichiometry）, which is eventually understood in terms of electron doping that not only breaks the balance between electron-type and hole-type carrier densities, but also reduces the average carrier mobility. Thus the compensation effect and ultrahigh mobility are probably the main driving force of the extreme magnetoresistance in WTe2.

Mechanism of the Formation of the East African Rift System

The East African Rift System(EARS)is located in East Africa,separating into two main branches,the eastern branch and the western branch.It is considered as an intracontinental ridge system,which meets the Red Sea and

Field-induced anisotropic magnetic phase transitions and tricritical phenomena in GdCr_(6)Ge_(6)

The interaction between complex magnetic structures and non-trivial band structures in ternary rare-earth GdCr_(6)Ge_(6) induces exotic and abundant electro-magnetic phenomena.In this work,we perform a systematical investigation on critical behaviors and magnetic properties of the single-crystal GdCr_(6)Ge_(6).The temperature,field,and angle dependence of magnetization unveils strong magnetic anisotropy along the c-axis and isotropic characteristic in the ab-plane.Critical exponentsβ=0.252(1),γ=0.905(9),δ=4.606(3)for H//ab,andβ=0.281(3),γ=0.991(8),δ=4.541(5)for H//c are obtained by the modified Arrott plot method(MAP)and critical isotherm(CI)analysis.The determined exponents for both directions are consistent with the theoretical prediction of a tricritical mean-field model.Based on detailed magnetization measurements and universality scaling,comprehensive magnetic phase diagrams of GdCr6Ge6for H//ab and H//c are constructed,which reveal that the external field induces a ferromagnetic(FM)transition for H//ab while a ferrimagnetic(FIM)one for H//c.Two tricritical points are determined for H//ab(11.2 K,266.3 Oe)and H//c(11.3 K,3.3 kOe)on the phase diagrams,respectively.The field-induced anisotropic magnetic configurations and multiple phases are clarified,where the moments of Gd and Cr form FM coupling for H//ab while FIM one for H//c via the interaction between Gd and Cr sublattices.

Two-dimensional ultrathin vanadium oxide nanosheets as catalytic bactericide

Infectious diseases caused by pathogenic bacteria are a serious threat to global public health.Nowadays,antibiotics and other clinical drugs suffer from some fundamental disadvantages such as narrow-spectrum antibacterial effect and the risk to induce drug resistance,while inorganic functional nanomaterials with biological catalytic activities have been developed as novel antibacterial agents.In this study,we prepared two-dimensional ultrathin vanadium oxide nanosheets(VO_(x)NSs)with mixed valence states from the oxidised layer of vanadium powder(bulk V)by ultrasonically assisted liquid exfoliation.By conveniently switching between V^(IV)and V^(V),VO_(x)NSs can efficiently catalyse H_(2)O_(2)enriched in bacterially infected areas to generate hydroxyl radicals(·OH),which induce bacterial oxidative stress and apoptosis.This process can occur in both weakly alkaline and acidic environments,thus being independent of the pH value in infection areas.In addition,contributed by the intrinsic characteristics of vanadium,two-dimensional morphology and reasonable valence state ratios,VO_(x)NSs exhibit the advantages of broad antibacterial spectrum,high catalytic activity and non-toxic by-products.This novel nanosheet offers a new strategy to heal infected wounds and extends the application of nanocatalytic medicine towards anti-infection.

Intensive phototherapy vs.exchange transfusion for the treatment of neonatal hyperbilirubinemia:a multicenter retrospective cohort study

Background:Intensive phototherapy(IPT)and exchange transfusion(ET)are the main treatments for extreme hyperbilirubinemia.However,there is no reliable evidence on determining the thresholds for these treatments.This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.Methods:This retrospective cohort study was conducted in seven centers from January 2015 to January 2018.Patients with extreme hyperbilirubinemia that met the criteria of ET were included.Patients were divided into three subgroups(low-,medium-,and high-risk)according to gestational week and risk factors.Propensity score matching(PSM)was performed to balance the data before treatment.Study outcomes included the development of bilirubin encephalopathy,duration of hospitalization,expenses,and complications.Mortality,auditory complications,seizures,enamel dysplasia,ocular motility disorders,athetosis,motor,and language development were evaluated during follow-up at age of 3 years.Results:A total of 1164 patients were included in this study.After PSM,296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-,medium-,and high-risk subgroups with 188,364,and 40 matched patients,respectively.No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity,complications,and sequelae.Hospitalization duration and expenses were lower in the low-and medium-risk subgroups in the IPT only group.Conclusions:In this study,our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia.The indication of ET for patients with hyperbilirubinemia could be stricter.However,it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors.If IPT can be guaranteed and proved to be therapeutic,ET should be avoided as much as possible.

Microstructural evolution of polymer-derived hexagonal boron nitride fibres under high-temperature stretching

High-temperature stretching plays a crucial role in enhancing the performance of fibres,while a quantitative investigation into the impacts of tension and stretching duration on the microstructure and performance of hexagonal boron nitride(h-BN)fibres remains absent.In this study,to elucidate the microstructural evolution of the h-BN fibres under thermal stretching,amorphous BN fibres were heated at 2000℃under tension of 30,50,and 70 N for 1,3,and 5 h in a nitrogen atmosphere.Subsequently,the grain size,pore structure,orientation degree,microscopic morphology,and mechanical properties were analysed at room temperature.The results show that high-temperature stretching enhances the orientation degree of the BN fibres,consequently elevating Young’s modulus.The maximum orientation degree of the BN fibres was 86%,aligning with a corresponding Young’s modulus of 206 GPa.Additionally,high-temperature stretching enlarged the sizes of grains and pores,a fact substantiated by the radial cracking of the fibres upon extending thermal stretching time.Owing to the expanded pore structure of the BN fibres and the inability to form a sufficiently strong“card structure”between shorter microfibre bundles,the tensile strength of the BN fibres did not increase continually,reaching a maximum of 1.0 GPa.Microstructural observations revealed that the BN fibres,composed of highly oriented lamellar h-BN grains,tend to form radial textures under high-tensile thermal stretching and onion-skin textures under prolonged thermal stretching.These findings offer a theoretical foundation for the preparation of high-performance h-BN fibres.

碳化锆陶瓷有机前驱体的热解过程

合成了碳化锆陶瓷有机前驱体,研究了其在热解过程中化学成分和物相组成变化,探讨了从有机高分子向无机陶瓷转化的机理,对碳热还原反应进行了热力学分析。结果表明,前驱体在600℃以下完成了有机结构的断裂、裂解碎片的重排与挥发,600℃以上裂解产物不再具备有机特征;随热解温度升高,无定型碳和单斜相ZrO2逐渐生成,大于1200℃时可检测到立方相ZrC,1400℃时单斜相ZrO2基本消失;1500℃时完成碳热还原反应,在远低于热力学反应温度的条件下生成了高度结晶的纳米尺寸的立方相碳化锆陶瓷。

Nanomedicine enables autophagy-enhanced cancer-cell ferroptosis

Ferroptosis and autophagy, playing significant roles in tumor treatment, are two typical forms of the programmed cell death. However, the rational combination of ferroptosis and autophagy for synergistic tumor therapy is still highly challenging. Herein, we report on an intriguing nanomedicine strategy for achieving autophagy-enhanced ferroptosis on efficiently combating cancer, which was based on the construction of trehalose-loaded mSiO_(2)@MnO_(x)-mPEG(Tre MMM) nanoparticles with satisfactory biocompatibility. The nanoparticles are endowed with high glutathione(GSH) consumption efficiency, thereby inducing cancer-cell ferroptosis via inactivating glutathione peroxidases 4(GPX4). Subsequently, the Tre MMM degradation due to the GSH depletion and p H sensitivity contributed to the trehalose release for inducing autophagy, promoting/enhancing ferroptosis by NCOA4-mediated degradation of ferritin.A substantial in vitro and in vivo antitumor effect was achieved by such an intriguing autophagyenhanced ferroptosis. Therefore, the rational combination of GSH-consumption-induced ferroptosis and trehalose-induced autophagy by nanomedicine design provides an alternative but effective strategy for tumor treatment.

Frictional response of a novel C/C-ZrB_(2)-ZrC-SiC composite under simulated braking

A novel braking material,C/C-ZrB_(2)-ZrC-SiC carbon fibre-reinforced hybrid ceramic matrix composite,was prepared by chemical vapour infiltration and polymeric precursor infiltration and pyrolysis.Investigation of the microstructure of C/C-ZrB_(2)-ZrC-SiC composite showed the homogenous dispersion of three-phase ceramic as the matrix.The frictional properties of the hybrid C/C-ZrB_(2)-ZrC-SiC ceramic matrix composite were measured by a disk-on-disk type dynamometer under dry and wet conditions to simulate the normal landing state of aircraft brake disk friction pairs.C/C-ZrB_(2)-ZrC-SiC ceramic matrix composite has a higher and more stable friction coefficient under wet condition than under dry condition,indicating that the composite has better performance compared with C/C or C/C-SiC braking materials.