A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.     

Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.     

Dual effect synergistically triggered Ce:(Y,Tb)3(Al,Mn)5O12 transparent ceramics enabling a high color-rendering index and excellent thermal stability for white LEDs

Ce:Y₃Al₅O₁₂ transparent ceramics (TCs) with appropriate emission light proportion and high thermal stability are significant to construct white light emitting diode devices with excellent chromaticity parameters. In this work, strategies of controlling crystal-field splitting around Ce³⁺ ion and doping orange-red emitting ion, were adopted to fabricate Ce:(Y,Tb)₃(Al,Mn)₅O₁₂ TCs via vacuum sintering technique. Notably, 85.4 % of the room-temperature luminescence intensity of the TC was retained at 150 °C, and the color rendering index was as high as 79.8. Furthermore, a 12 nm red shift and a 16.2 % increase of full width at half maximum were achieved owing to the synergistic effects of Tb³⁺ and Mn²⁺ ions. By combining TCs with a 460 nm blue chip, a warm white light with a low correlated color temperature of 4155 K was acquired. Meanwhile, the action mechanism of Tb³⁺ ion and the energy transfer between Ce³⁺ and Mn²⁺ ions were verified in prepared TCs.     

深共融溶剂催化制备二酯类化合物

二酯类化合物广泛应用于有机中间体、药物、增塑剂、香料等领域,开发其绿色、高效的合成新方法具有重要意义.报道了以二元羧酸(或二羧酸酐)和脂肪醇为原料,以深共融溶剂(DESs)为催化剂催化合成二酯类化合物.以n(氯化胆碱):n(对甲苯磺酸)=1:2为催化剂,产率最高可达95％,并且DESs使用8次后产率仍保持在88％以上.运用1HNMR和13CNMR对产物进行了结构表征.该方法具有操作简单、产率高、易分离和催化剂可循环使用等优点.     

Biodegradable Polymeric Nanoparticles Containing an Immune Checkpoint Inhibitor (aPDL1) to Locally Induce Immune Responses in the Central Nervous System

Immunotherapy is an efficient approach to clinical oncology. However, the immune privilege of the central nervous system (CNS) limits the application of immunotherapeutic strategies for brain cancers, especially glioblastoma (GBM). Tumor resistance to immune checkpoint inhibitors is a further challenge in immunotherapies. To overcome the immunological tolerance of brain tumors, a novel multifunctional nanoparticle (NP) for highly efficient synergetic immunotherapy is reported. The NP contains an anti-PDL1 antibody (aPDL1), upconverting NPs, and the photosensitizer 5-ALA; the surface of the NP is conjugated with the B1R kinin ligand to facilitate transport across the blood-tumor-barrier. Upon irradiation with a 980 nm laser, 5-ALA is transformed into protoporphyrin IX, generating reactive oxygen species. Photodynamic therapy (PDT) further promotes intratumoral infiltration of cytotoxic T lymphocytes and sensitizes tumors to PDL1 blockade therapy. It is demonstrated that combining PDT and aPDL1 can effectively suppress GBM growth in mouse models. The proposed NPs provide a novel and effective strategy for boosting anti-GBM photoimmunotherapy.     

Turbulent boundary layer control with a spanwise array of DBD plasma actuators

The turbulent boundary layer control on NACA 0012 airfoil with Mach number ranging from 0.3 to 0.5 by a spanwise array of dielectric barrier discharge(DBD)plasma actuators by hot-film sensor technology is investigated.Due to temperature change mainly caused through heat produced along with plasma will lead to measurement error of shear stress measured by hot-film sensor,the correction method that takes account of the change measured by another sensor is used and works well.In order to achieve the value of shear stress change,we combine computational fluid dynamics computation with experiment to calibrate the hot-film sensor.To test the stability of the hot-film sensor,seven repeated measurements of shear stress at Ma = 0.3 are conducted and show that confidence interval of hot-film sensor measurement is from-0.18 to 0.18 Pa and the root mean square is 0.11 Pa giving a relative error 0.5％over all Mach numbers in this experiment.The research on the turbulent boundary layer control with DBD plasma actuators demonstrates that the control makes shear stress increase by about 6％over the three Mach numbers,which is thought to be reliable through comparing it with the relative error 0.5％,and the value is hardly affected by burst frequency and excitation voltage.     

Statistical Piezotronic Effect in Nanocrystal Bulk by Anisotropic Geometry Control

Utilizing inner-crystal piezoelectric polarization charges to control carrier transport across a metal-semiconductor or semiconductor–semiconductor interface, piezotronic effect has great potential applications in smart micro/nano-electromechanical system (MEMS/NEMS), human-machine interfacing, and nanorobotics. However, current research on piezotronics has mainly focused on systems with only one or rather limited interfaces. Here, the statistical piezotronic effect is reported in ZnO bulk composited of nanoplatelets, of which the strain/stress-induced piezo-potential at the crystals’ interfaces can effectively gate the electrical transport of ZnO bulk. It is a statistical phenomenon of piezotronic modification of large numbers of interfaces, and the crystal orientation of inner ZnO nanoplatelets strongly influence the transport property of ZnO bulk. With optimum preferred orientation of ZnO nanoplatelets, the bulk exhibits an increased conductivity with decreasing stress at a high pressure range of 200–400 MPa, which has not been observed previously in bulk. A maximum sensitivity of 1.149 µS m⁻¹ MPa⁻¹ and a corresponding gauge factor of 467–589 have been achieved. As a statistical phenomenon of many piezotronic interfaces modulation, the proposed statistical piezotronic effect extends the connotation of piezotronics and promotes its practical applications in intelligent sensing.     

Dry Fractionation Approach in Concentrating Tocopherols and Tocotrienols from Palm Fatty Acid Distillate: A Green Pretreatment Process for Vitamin E Extraction

Palm fatty acid distillate (PFAD) is a rich source of vitamin E. As compared to other vegetable oil, PFAD has higher tocotrienol (70–80%) over tocopherol content, which makes it a valuable source for vitamin E extraction. Current vitamin E extraction methods are not sustainable due to the intensive usage of chemical and high operational cost. Hence, the present study investigated for the first time using dry fractionation process as a green and economical pretreatment method for separating solid fraction (stearin) and liquid fraction (olein) in order to concentrate vitamin E from PFAD in olein fraction. We examined the dry fractionation conditions: crystallization ending temperature (36–44 °C), cooling rate (0.3 and 1.5°C min⁻¹), stirring speed (20–125 rpm), and holding time (0–60 min) on the composition of unsaturated and saturated fatty acids as well as vitamin E content in liquid fraction (olein) and solid fraction (stearin) using gas chromatography and high performance liquid chromatography, respectively. In most of these conditions, vitamin E was ultimately higher in olein fraction as compared to stearin fraction, which is correlated with the high degree of unsaturation. Under a cooling rate of 0.3°C min⁻¹, 90 rpm stirring speed, and ending crystallization of 38 °C, the highest vitamin E rich olein fraction was attained with 1479 ± 10.51 ppm in 50 g olein fraction as compared to 1366 ± 7.94 ppm in 500 g of unfractionated PFAD.     

梯度铝蜂窝夹芯板的力学行为

梯度分层铝合金蜂窝板是一种有效的吸能结构,本工作在梯度铝蜂窝结构的基础上根据梯度率的概念,通过改变蜂窝芯层的胞壁长度,设计了4种质量相同、梯度率不同的铝蜂窝夹芯结构。通过准静态压缩实验,并结合非线性有限元模拟准静态及冲击态下梯度铝蜂窝夹芯结构的变形情况及其力学性能,分析对比了相同质量下梯度铝蜂窝夹芯结构在准静态下的变形模式以及冲击载荷下分层均质蜂窝结构和不同梯度率的分层梯度蜂窝结构的动态响应和能量吸收特性。结果表明:在准静态压缩过程中,铝蜂窝梯度夹芯板的变形具有明显的局部化特征,蜂窝芯的变形为低密度优先变形直至密实,层级之间的密实化应变差随芯层密度的增大而逐渐减小;在高速冲击下,梯度蜂窝板并非严格按照准静态过程中逐级变形直至密实,而是在锤头冲击惯性及芯层密度的相互作用下整体发生的线弹性变形、弹性屈曲、塑性坍塌及密实化;另外,在本工作所设计的梯度率中,当梯度率为γ₁=0.0276时,梯度蜂窝夹芯板的吸能性达到最好,相较于同等质量下的均质蜂窝夹芯板,能量吸收提高了10.63%。     

纯电环卫车箱体轻量化的有限元分析方法研究

以16t纯电环卫车箱体为研究对象,通过有限元分析方法的研究,在实现轻量化设计的同时解决了箱体开裂的问题,经实车验证强度满足,同时实现降重40kg,为纯电环卫车的轻量化设计提供了一条可行的途径.