Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach

Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes. In our work, the way of combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction with competitive inhibitors. Firstly, the pharmacophore model of PTP1B inhibitors was built based on the common feature of sixteen compounds. It was found that the pharmacophore model consisted of five chemical features: one aromatic ring (R) region, two hydrophobic (H) groups, and two hydrogen bond acceptors (A). To further elucidate the binding modes of these inhibitors with PTP1B active sites, four docking programs (AutoDock 4.0, AutoDock Vina 1.0, standard precision (SP) Glide 9.7, and extra precision (XP) Glide 9.7) were used. The characteristics of the active sites were then described by the conformations of the docking results. In conclusion, a combination of various pharmacophore features and the integration information of structure activity relationship (SAR) can be used to design novel potent PTP1B inhibitors

Facile Preparation, Characterization, and Highly Effective Microwave Absorption Performance of CNTs/Fe 3

A facile method has been developed to synthesize light-weight CNTs/Fe3O4/PANI nanocomposites. The formation route was proposed as the coprecipitation of Fe2+ and Fe3+ and an additional process of in situ polymerization of aniline monomer. The structure and morphology of CNTs/Fe3O4/PANI were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) spectroscopy. The TEM investigation shows that the CNTs/Fe3O4/PANI nanocomposites exhibit less intertwined structure and that many more Fe3O4 particles are attached homogeneously on the surface of CNTs, indicating that PANI can indeed help CNTs to disperse in isolated form. The wave-absorbing properties were investigated in a frequency of 2–18 GHz. The results show that the CNTs/Fe3O4/PANI nanocomposites exhibit a super absorbing behavior and possess a maximum reflection loss of −48 dB at 12.9 GHz, and the bandwidth below −20 dB is more than 5 GHz. More importantly, the absorption peak frequency ranges of the CNTs/Fe3O4/PANI composites can be tuned easily by changing the wax weight ratio and thickness of CNTs/Fe3O4/PANI paraffin wax matrix

Experimental study on optimization of PDC cutting teeth for conglomerate layer

In order to obtain better drilling effect in the conglomerate layer, it is necessary to optimize the tooth shape and caster angle of PDC bit for the conglomerate layer. Single tooth rock breaking experiments are conducted on ordinary plane teeth, conical teeth and axe teeth in the conglomerate rock sample. Then the simulation analysis is conducted on the optimized axe teeth to optimize the optimal tooth surface angle of axe teeth. And the cutting simulation is conducted with ordinary plane teeth to verify the experimental results. The results show that the axe tooth has the highest cutting efficiency and the most stable stress in the conglomerate layer; the drilling effect of 140° axe tooth in conglomerate is better; and the cutting efficiency is the highest when 140° axe teeth are matched with 30° caster angle. Therefore, when optimizing the cutting tools for the conglomerate layer, it is necessary to reasonably select the teeth according to the formation characteristics. When applying axe teeth, in order to achieve high cutting efficiency, it is necessary to optimize the combination of tooth surface angle and caster angle

Nanomaterials in the Environment: Research Hotspots and Trends

Research on the field of nanomaterials in environment has continued to be a major area of interest in recent years. To present the up-to-date progress in this field, a bibliometric study is conducted to analyze 7087 related publications in the Science Citation Index (SCI) core collection of Web of Science based on the expanded SCI. These publications are identified through using representative keywords in the research directions environment of the Web of Science. This study finds that China and the United States dominate the field; one difference between them is that China issued more independent publications and the United States issued more cooperative publications. In addition, the number of the related publications in Asian countries has exceeded that of European and American ones. A Chinese institution, the Chinese Academy of Sciences, has an absolute dominance in this field. Traditional high-impact environmental journals have ruled this field. The number of publications in the Energy and Environmental Science field has gradually decreased. In addition, a co-citation analysis shows that previous studies in this field can be divided into four major branches, and that graphene oxide and nano-inorganic particles are increasingly becoming research hotspots

Fabrication of Cell-Laden Hydrogel Fibers with Controllable Diameters

Cell-laden hydrogel fibers are widely used as the fundamental building blocks to fabricate more complex functional three-dimensional (3D) structures that could mimic biological tissues. The control on the diameter of the hydrogel fibers is important so as to precisely construct structures in the above 3D bio-fabrication. In this paper, a pneumatic-actuated micro-extrusion system is developed to produce hydrogel fibers based on the crosslinking behavior of sodium alginate with calcium ions. Excellent uniformity has been obtained in the diameters of the fabricated hydrogel fibers as a proportional-integral-derivative (PID) control algorithm is applied on the driving pressure control. More importantly, a linear relationship has been obtained between the diameter of hydrogel fiber and the driving pressure. With the help of the identified linear model, we can precisely control the diameter of the hydrogel fiber via the control of the driving pressure. The differences between the measured and designed diameters are within ±2.5%. Finally, the influence of the calcium ions on the viability of the encapsulated cells is also investigated by immersing the cell-laden hydrogel fibers into the CaCl2 bath for different periods of time. LIVE/DEAD assays show that there is little difference among the cell viabilities in each sample. Therefore, the calcium ions utilized in the fabrication process have no impact on the cells encapsulated in the hydrogel fiber. Experimental results also show that the cell viability is 83 ± 2% for each sample after 24 h of culturing

Recent Advances in Gold(I)-Catalyzed Approaches to Three-Type Small-Molecule Scaffolds via Arylalkyne Activation

Gold catalysts possess the advantages of water and oxygen resistance, with the possibility of catalyzing many novel chemical transformations, especially in the syntheses of small-molecule skeletons, in addition to achieving the rapid construction of multiple chemical bonds and ring systems in one step. In this feature paper, we summarize recent advances in the construction of small-molecule scaffolds, such as benzene, cyclopentene, furan, and pyran, based on gold-catalyzed cyclization of arylalkyne derivatives within the last decade. We hope that this review will serve as a useful reference for chemists to apply gold-catalyzed strategies to the syntheses of related natural products and active molecules, hopefully providing useful guidance for the exploration of additional novel gold-catalyzed approaches

Research on the Spatial Sequence of Building Facades in Huizhou Regional Traditional Villages

Under the influences of the regional environment, building communities within traditional villages exhibit regional styles and features. Based on the research team’s early studies, and given the protection and renewal practices of Huizhou traditional villages in Southern Anhui Province, China, this study investigated the spatial sequences of building facades and explicated the laws of these spatial sequences. This research involved a series of technical steps. First, in the case selection stage, typical traditional villages and spatial sequence paths were established. Second, in the data acquisition stage, 3D laser scanning technology was used to acquire building elevation data and conduct 3D modelling. Finally, the measurement indices were determined by vector analysis of the data. Factor analysis and cluster analysis were suitable for the reduction and classification of the above data in order to explore the constitution law of building units. Meanwhile, the regularity of the facade organization of building groups was further quantified by examining the combination and connection relationships between the building and spatial patterns. Then, the laws of facade organization of the building groups were explicated. The purpose of this study is not only to achieve accurate inheritance of historical data information, but also to explore the centralized contiguity mechanism behind the traditional villages through external features from the perspective of rescue. The results demonstrated that there are spatial sequences represented by building facades in Huizhou traditional villages. Moreover, internal laws of “largely identical but with minor differences” in the building unit composition and building group organization were identified. These findings: (1) provide a deeper understanding of the regional characteristics of Huizhou traditional villages in Southern Anhui Province, China; (2) offer a foundation for practical administration requirements; and (3) recognize a novel research perspective and a feasible technical route for the protection of traditional villages in other regions, with an appreciation for the value of spatial sequences

Guanidine-modified albumin-MMAE conjugates with enhanced endocytosis ability

AbstractAiming to address the insufficient endocytosis ability of traditional albumin drug conjugates, this paper reports elegant guanidine modification to improve efficacy for the first time. A series of modified albumin drug conjugates were designed and synthesized with different structures, including guanidine (GA), biguanides (BGA) and phenyl (BA), and different quantities of modifications. Then, the endocytosis ability and in vitro/vivo potency of albumin drug conjugates were systematically studied. Finally, a preferred conjugate A4 was screened, which contained 15 BGA modifications. Conjugate A4 maintains spatial stability similar to that of the unmodified conjugate AVM and could significantly enhance endocytosis ability (p*** = 0.0009) compared with the unmodified conjugate AVM. Additionally, the in vitro potency of conjugate A4 (EC50 = 71.78 nmol in SKOV3 cells) was greatly enhanced (approximately 4 times) compared with that of the unmodified conjugate AVM (EC50 = 286.00 nmol in SKOV3 cells). The in vivo efficacy of conjugate A4 completely eliminated 50% of tumors at 33 mg/kg, which was significantly better than the efficacy of conjugate AVM at the same dose (P** = 0.0026). In addition, theranostic albumin drug conjugate A8 was designed to intuitively realize drug release and maintain antitumor activity similar to conjugate A4. In summary, the guanidine modification strategy could provide new ideas for the development of new generational albumin drug conjugates