Multiple Chemical Features Impact Biological Performance Diversity of a Highly Active Natural Product-Inspired Library

A systematic, diversity-oriented synthesis approach was employed to access a natural product-inspired flavonoid library with diverse chemical features, including chemical properties, scaffold, stereochemistry, and appendages. Using Cell Painting, the effects of these diversity elements were evaluated, and multiple chemical features that predict biological performance diversity were identified. Scaffold identity appears to be the dominant predictor of performance diversity, but stereochemistry and appendages also contribute to a lesser degree. In addition, the diversity of chemical properties contributed to performance diversity, and the driving chemical property was dependent on the scaffold. These results highlight the importance of key chemical features that may inform the creation of small-molecule, performance-diverse libraries to improve the efficiency and success of high-throughput screening campaigns.     

Allosteric p97 Inhibitors Can Overcome Resistance to ATP-Competitive p97 Inhibitors for Potential Anticancer Therapy

Abstract : A major challenge of targeted cancer therapy is the selection for drug-resistant mutations in tumor cells leading to loss of treatment effectiveness. p97/VCP is central regulator of protein homeostasis and a promising anticancer target because of its vital role in cell growth and survival. One ATP-competitive p97 inhibitor, CB-5083, has entered clinical trials. Selective pressure on HCT116 cells dosed with CB-5083 identified five different resistant mutants. Identification of p97 inhibitors with different mechanisms of action would offer the potential to overcome this class of resistance mutations. Our results demonstrate that two CB-5083 resistant p97 mutants, N660 K and T688 A, were also resistant to several other ATP-competitive p97 inhibitors, whereas inhibition by two allosteric p97 inhibitors NMS-873 and UPCDC-30245 were unaffected by these mutations. We also established a CB-5083 resistant cell line that harbors a new p97 double mutation (D649 A/T688 A). While CB-5083, NMS-873, and UPCDC-30245 all effectively inhibited proliferation of the parental HCT116 cell line, NMS-873 and UPCDC-30245 were 30-fold more potent in inhibiting the CB-5083 resistant D649 A/T688 A double mutant than CB-5083. Our results suggest that allosteric p97 inhibitors are promising alternatives when resistance to ATP-competitive p97 inhibitors arises during anticancer treatment.     

Controlled enzymatic hydrolysis on characteristic and antioxidant properties of soybean protein isolate-maltodextrin conjugates

This study aimed to investigate the effect of limited hydrolysis on conformational and antioxidant properties of soy protein isolate-maltodextrin (SPI-Md) conjugates. Extrinsic fluorescence analysis showed unfolding of the protein molecule and exposure of hydrophobic groups in SPI-Md conjugate hydrolysates. Free amino acid analysis showed that, the contents of hydrophobic amino acids in SPI-Md conjugates increased after hydrolysis. The contents of leucine, isoleucine, phenylalanine increased from 0.32, 0.30 and 0.54 to 1.36, 1.86 and 2.60, respectively, when the hydrolysis degree (DH) gradually increased from 0% to 5.7%. The FT-IR spectrum showed that C = O absorption of the amide group formed by glycosylation continued unabated after limited hydrolysis (DH 2.9%). The glycated SPI products showed good reducing power and superior resistance to lipid oxidation (34%, 12 mg mL^?1), whereas the limit hydrolysates (DH 2.9%) of SPI-Md conjugates showed more ef?cient radical-scavenging capacity (89.5%, at 12 mg mL^?1) and iron-chelation activity (91.3%, at 12 mg mL^?1). Results of this study indicated that, slight enzymatic hydrolysis (DH 0–2.9%) could help partially unfolding the globular structure of SPI-Md conjugates without deteriorating amide bonds and had a positive effect on their antioxidant properties.     

Living Materials Herald a New Era in Soft Robotics

Living beings have an unsurpassed range of ways to manipulate objects and interact with them. They can make autonomous decisions and can heal themselves. So far, a conventional robot cannot mimic this complexity even remotely. Classical robots are often used to help with lifting and gripping and thus to alleviate the effects of menial tasks. Sensors can render robots responsive, and artificial intelligence aims at enabling autonomous responses. Inanimate soft robots are a step in this direction, but it will only be in combination with living systems that full complexity will be achievable. The field of biohybrid soft robotics provides entirely new concepts to address current challenges, for example the ability to self‐heal, enable a soft touch, or to show situational versatility. Therefore, “living materials” are at the heart of this review. Similarly to biological taxonomy, there is a recent effort for taxonomy of biohybrid soft robotics. Here, an expansion is proposed to take into account not only function and origin of biohybrid soft robotic components, but also the materials. This materials taxonomy key demonstrates visually that materials science will drive the development of the field of soft biohybrid robotics.     

Clean hydrogen production in a full biological microbial electrolysis cell

The recent interest in microbial electrolysis cell (MEC) technology has led the research platform to develop full biological MECs (bioanode-biocathode, FB-MEC). This study focused on biohydrogen production from a biologically catalyzed MEC. A bioanode and a biocathode were initially enriched in a half biological MFC (bioanode-abiocathode, HB-MFC) and a half biological MEC (abioanode-biocathode, HB-MEC), respectively. The FB-MEC was established by transferring the biocathode of the HB-MEC and the bioanode of the HB-MFC to a two-chamber MEC. The FB-MEC was operated under batch (FB-MEC-B) and recirculation batch (FB-MEC-RB) modes of operation in the anodic chamber. The FB-MEC-B reached a maximum current density of 1.5 A/m² and the FB-MEC-RB reached a maximum current density of 2.5 A/m² at a similar applied voltage while the abiotic control system showed the maximum of 0.2 A/m². Hydrogen production rate decreased in the FB-MEC compared to that of the HB-MEC. However, the cathodic hydrogen recovery increased from 42% obtained in the HB-MEC to 56% in the FB-MEC-B and 65% in the FB-MEC-RB, suggesting the efficient oxidation and reduction rates in the FB-MEC compared to the HB-MEC. The onset potential for hydrogen evolution reaction detected by linear sweep voltammetry analysis were −0.780 and −0.860 V vs Ag/AgCl for the FB-MEC-RB and the FB-MEC-B (−1.26 for the abiotic control MEC), respectively. Moreover, the results suggested that the FB-MEC worked more efficiently when the biocathode and the bioanode were enriched initially in half biological systems before transferring to the FB-MEC compared to that of the simultaneously enriched in one system.     

Synthesis,Anticancer Activity,Structure-Activity Relationship and Mechanistic Investigations of Falcarindiol Analogues

Forty samples of optically active falcarindiol analogues are synthesized by using the easily available C2 symmetric (R)- and (S)-1,1’-binaphth-2-ol (BINOL) in combination with Ti(OⁱPr)₄, Zn powder and EtI. Their anticancer activities on Hccc-9810, HepG2, MDA-MB-231, Hela, MG-63 and H460 cells are assayed to elucidate their structure-activity relationships. These results showed that the falcarindiol analogue (3R,8S)- 2 i with the terminal double bond has the most potent anti-proliferation effect on Hccc-9810 cells with IC₅₀ value of 0.46 μM. The falcarindiol analogue (3R,8S)- 2 i can induce obvious Hccc-9810 cell apoptosis in a concentration-dependent manner by Hoechst staining and flow cytometry analysis. The proposed mechanism suggests that the falcarindiol analogue (3R,8S)- 2 i increases LDH release and MDA content, and reduces the levels of SOD activity, which lead to the accumulation of oxidative stress and induce apoptosis in Hccc-9810 cells.     

From sustainability to sustainizability

Following the recent introduction of the Sustainability over Sets (SOS) concept as a sustainability analysis tool with broad flexibility in incorporating human input, in this work, the concepts of Sustainizability (SIZ) and Sustainizability over Sets (SIZOS) are introduced, as novel frameworks for sustainable system synthesis. Springing off the conceptual foundation of sustainability, SIZ (and SIZOS) refers to the existence of allowable external actions, and/or design changes that can render sustainable (sustainable over a set) an unsustainable (unsustainable over a set) system. Utilizing earlier mathematical results for SOS, rigorous necessary and sufficient conditions for SIZOS are presented. Two case studies, on a two-dimensional biological waste treatment system, and a three-dimensional food chain system, are then presented to illustrate the developed necessary and sufficient conditions for SIZOS.     

大规模生物网络马尔可夫聚类的并行化算法

马尔可夫聚类算法（MCL）是在大规模生物网络中寻找模块的一个有效方法，能够挖掘网络结构和功能影响力较大的模块。算法涉及到大规模矩阵计算，因此复杂度可达立方阶次。针对复杂度高的问题，提出了基于消息传递接口（MPI）的并行化马尔可夫聚类算法以提高算法的计算性能。首先，生物网络转化成邻接矩阵；然后，根据算法的特性，按照矩阵的规模判断并重新生成新矩阵以处理非平方倍数矩阵的计算；其次，并行计算通过按块分配的方式能够有效地实现任意规模矩阵的运算；最后，循环并行计算直至收敛，得到网络聚类结果。通过模拟网络和真实生物网络数据集的实验结果表明，与全块集体式通信（FCC）并行方法相比，平均并行效率提升了10个百分点以上，因此可以将该优化算法应用在不同类型的大规模生物网络中。     

填料生物转盘对农村家庭生活污水的处理

根据目前我国农村生活污水处理的现状以及农村家庭污水水量、水质的特点,提出了一种家庭生活污水处理装置-填料生物转盘。该装置采用生物膜法工艺,结合生物转盘与生物滤池工艺的特点,运用设备一体化的设计理念,设计了一种运行管理简单、结构紧凑的一体化装置。通过实际运行考察了装置用于农村家庭生活污水处理的挂膜启动情况,以及污染物的去除效果。结果表明:填料生物转盘生物膜的驯化培养需要20天的时间,稳定运行期间对COD、NH4+-N、TN、TP的平均去除率分别稳定在75%、85%、65%和75%以上,出水COD、NH4+-N、TN优于城镇污水处理厂污染物排放标准(GB 18918-2002)一级A标准,出水TP达到一级B标准。装置运行管理操作简单,不需要专业技术人员,适合农村家庭污水的处理。