Puckering the Planar Landscape of Fragments: Design and Synthesis of a 3D Cyclobutane Fragment Library

Fragment-based drug discovery (FBDD) has a growing need for unique screening libraries. The cyclobutane moiety was identified as an underrepresented yet attractive three-dimensional (3D) scaffold. Synthetic strategies were developed via a key 3-azido-cyclobutanone intermediate, giving potential access to a range of functional groups with accessible growth vectors. A focused set of 33 novel 3D cyclobutane fragments was synthesised, comprising three functionalities: secondary amines, amides, and sulfonamides. This library was designed using Principal Component Analysis (PCA) and an expanded version of the rule of three (RO3), followed by Principal Moment of Inertia (PMI) analysis to achieve both chemical diversity and high 3D character. Cis and trans ring isomers of library members were generated to maximise the shape diversity obtained, while limiting molecular complexity through avoiding enantiomers. Property analyses of the cyclobutane library indicated that it fares favourably against existing synthetic 3D fragment libraries in terms of shape and physicochemical properties.     

Non-Genetic Diversity in Chemosensing and Chemotactic Behavior

Non-genetic phenotypic diversity plays a significant role in the chemotactic behavior of bacteria, influencing how populations sense and respond to chemical stimuli. First, we review the molecular mechanisms that generate phenotypic diversity in bacterial chemotaxis. Next, we discuss the functional consequences of phenotypic diversity for the chemosensing and chemotactic performance of single cells and populations. Finally, we discuss mechanisms that modulate the amount of phenotypic diversity in chemosensory parameters in response to changes in the environment.     

Terpene Synthases in the Biosynthesis of Drimane-Type Sesquiterpenes across Diverse Organisms

Drimane-type sesquiterpenes (DTSs) are significant terpenoid natural products characterized by their unique C₁₅ bicyclic skeleton. They are produced by various organisms including plants, fungi, bacteria and marine organisms, and exhibit a diverse array of bioactivities. These bioactivities encompass antifeedant, anti-insecticidal, anti-bacterial, anti-fungal, anti-viral and anti-proliferative properties. Some DTSs contribute to the pungent flavor found in herb plants like water pepper, while others serve as active components responsible for the anti-cancer activities observed in medicinal mushrooms such as (−)-antrocin from Antrodia cinnamomea. Recently, DTS synthases have been identified in various organisms, biosynthesizing drimenol, drim-8-ene-11-ol and (+)-albicanol, which all possess the characteristic drimane skeleton. Interestingly, despite these enzymes producing chemical molecules with a drimane scaffold, they exhibit minimal amino acid sequence identity across different organisms. This Concept article focuses on the discovery of DTS synthases and the tailoring enzymes generating the chemical diversity of drimane natural products. We summarize and discuss their key features, including the chemical mechanisms, catalytic motifs and functional domains employed by these terpene synthases to generate DTS scaffolds.     

Extended-chain structure for isotactic polystyrene: additional X-ray diffraction and calorimetric results

The recently discovered extended-chain structure in isotatic polystyrene gels opens new horizons on the stereochemistry of the polyolefins and molecular organization in polymeric gels. New X-ray fibre diffraction patterns obtained from stretched gels formed in different solvents support the contention that the structure is produced by intramolecular forces between continguous units probably via adjacent aromatic appendages.     

聚乙烯醇/牛I型胶原支架材料的制备及评价

研究了一种聚乙烯醇(PVA)和胶原(COL)复合支架材料的制备方法。采用氨基硅烷对PVA海绵表面进行了氨基化修饰后，通过戊二醛溶液交联牛Ⅰ型胶原(COL)，最后通过赖氨酸溶液封闭，获得一种PVA/COL复合支架材料。采用扫描电镜(SEM)、X光电子能谱仪(XPS)、傅里叶红外光谱(FT-IR)等手段对支架材料的理化性能进行表征，并通过细胞实验对支架材料的生物学性能进行评价。结果表明，经过COL修饰的PVA孔隙率为21.33%，平均孔径为168.68 ?m且均匀分布，支架材料接触角为20.03°。对支架材料的生物学评价结果表明C3A细胞在复合材料上黏附良好，优于PVA组；CCK-8增殖检测结果表明细胞在复合材料上呈增殖生长趋势，与对照组PVA相比差异显著(P?0.01)。将PVA和COL复合制备得到的支架材料具有良好的理化及生物学特性，具有广阔的应用前景。     

Comparison of three-dimensional printing for fabricating silk fibroin-blended scaffolds

In this study, two types of scaffolds were fabricated by 3D printing. Morphology, physical properties, biochemical were evaluated. Cell morphology and distribution were observed. It was found that the silk fibroin/collagen (SF/C) scaffold-based material had significantly higher values than the silk fibroin/chitosan (SF/CS) scaffold-based material. Hematoxylin and eosin staining of the scaffolds revealed that the number of cells in the SF/C scaffold was higher. Cells grew well inside the SF/C scaffold as measured by scanning electron microscope. Reverse Transcriotion-Polymerase Chain Reaction (RT-PCR) and Western blot showed that type II collagen and Sox9 can be found in SF/C scaffold. Therefore, the SF/C scaffold exhibited better overall performance compared with the SF/CS scaffold.     

An assessment of biopolymer‐ and synthetic polymer‐based scaffolds for bone and vascular tissue engineering

The promise of tissue engineering is the combination of a scaffold with cells to initiate the regeneration of tissues or organs. Engineering of scaffolds is critical for success and tailoring of polymer properties is essential for their good performance. Many different materials of natural and synthetic origins have been investigated, but the challenge is to find those that have the right mix of mechanical performance, biodegradability and biocompatibility for biological applications. This article reviews key polymeric properties for bone and vascular scaffold eligibility with focus on biopolymers, synthetic polymers and their blends. The limitations of these polymeric systems and ways and means to improve scaffold performance specifically for bone and vascular tissue engineering are discussed. © 2013 Society of Chemical Industry     

Fabrication and properties of 3D printed zirconia scaffold coated with calcium silicate/hydroxyapatite

The scaffold of bone repair needs a variety of material combinations to meet its intended performance; a typical single material such as zirconia has excellent mechanical properties, while hydroxyapatite and calcium silicate are bioactive materials with different degradation rates. In this paper, porous zirconia scaffolds were fabricated using 3D printing technology. The surface of the scaffold was coated by dipping with different contents of calcium silicate and hydroxyapatite to improve the biological activity and mechanical properties. Mechanical tests show that the coating material can effectively fill the pores of the porous scaffold, increasing its compressive strength by an average of 55%. The simulated body fluid (SBF) test showed that the higher calcium silicate in the coating increased the degradation rate. Cell experiments showed that the coated scaffolds exhibited good cytocompatibility and were beneficial to the proliferation and differentiation of cells. In conclusion, coated scaffolds have potential applications in the field of bone repair.     

Synthesis and characterization of conductive neural tissue engineering scaffolds based on urethane-polycaprolactone

Polymeric biomaterials play a key role in enhancement of lengthy nerve regeneration and various types of scaffolds were used to pave the way for nerve regeneration. Electrospun fibrous scaffolds have special potential applicability in controlling the cell behaviors such as adhesion, growth, proliferation and function. This study attempted to design a conductive and porous fibrous scaffold containing polycaprolactone (PCL) and polyaniline (PANI) with controllable degradation rate by adding urethane groups in scaffold structures. FTIR and NMR analysis was used to characterize the chemical bonds. Morphology, porosity, conductivity and degradation rate of scaffolds were also evaluated. To assess the cell–scaffold interaction, PC-12 cell line was cultured on the scaffolds. Results showed that the degradation rate of composite samples significantly increased in 50 time period. It seems that these results suggest that the composite fibrous scaffolds having proportions of UPCL/PCL/PANI45:20:35 exhibit the most balanced properties that meet all of the required specifications for neural cells and possess a potential application in neural tissue engineering.     

Development of biodegradable scaffold using polylactic acid and polycaprolactone for cardiovascular application

The limitations of newly synthesized biodegradable stents are low mechanical strength, fracture stiffness, and fast degradability of the polymers. A cylindrical polymeric scaffold was proposed in combination of polylactic acid and polycaprolactone. The tensile strength of the blend was increased twice, though elongation has reduced threefold. The blend illustrated no chemical interaction between polymers. The scaffold was coated with docetaxel, and sustained release profile was observed for 56 days. The degradation of the scaffold was evaluated through change in mechanical properties, weight variation, and morphological studies. The developed hemocompatible polymeric scaffold may be used as for the cardiovascular application.     

聚磷腈的制备和性能研究进展

聚磷腈是一类新型无机有机复合功能高分子化合物,具有结构多样性,应用于航空航天、船舶制造、石油化工及生物医学等领域。介绍了聚磷腈的理化性质、用途、发展现状和制备方法。综述了聚磷腈的制备和性能研究进展。     

The Influence of Ecological and Conventional Plant Production Systems on Soil Microbial Quality under Hops (Humulus lupulus)

The knowledge about microorganisms—activity and diversity under hop production is still limited. We assumed that, different systems of hop production (within the same soil and climatic conditions) significantly influence on the composition of soil microbial populations and its functional activity (metabolic potential). Therefore, we compared a set of soil microbial properties in the field experiment of two hop production systems (a) ecological based on the use of probiotic preparations and organic fertilization (b) conventional—with the use of chemical pesticides and mineral fertilizers. Soil analyses included following microbial properties: The total number microorganisms, a bunch of soil enzyme activities, the catabolic potential was also assessed following Biolog EcoPlates^®. Moreover, the abundance of ammonia-oxidizing archaea (AOA) was characterized by terminal restriction fragment length polymorphism analysis (T-RFLP) of PCR ammonia monooxygenase α-subunit (amoA) gene products. Conventional and ecological systems of hop production were able to affect soil microbial state in different seasonal manner. Favorable effect on soil microbial activity met under ecological, was more probably due to livestock-based manure and fermented plant extracts application. No negative influence on conventional hopyard soil was revealed. Both type of production fulfilled fertilizing demands. Under ecological production it was due to livestock-based manure fertilizers and fermented plant extracts application.     

Rapid microwave-assisted synthesis of gold loaded hydroxyapatite collagen nano-bio materials for drug delivery and tissue engineering application

A rapid microwave assisted facile synthetic technique was adopted to load gold nanoparticles (Au) on hydroxyapatite (HAp) surface. HAp nanoparticles were primarily synthesized by wet precipitation technique and further used for gold loading and successive collagen coating for biomedical applications. The microwave-assisted controlled synthesis technique with three heating cycles allows the very fast growing of Au seeds over HAp facets. Different sophisticated analytical techniques and spectroscopic characterization were employed to confirm the structural, chemical, and morphological features. The synthesized different concentration “Au” loaded hetero nanostructures coated with collagen (Au–HAp–Col) optimized for drug (Doxorubicin: DOX) loading and releasing purposes for biomedical applications. The maximum drug-loading efficiency of ~58.22% and a pH responsive releasing of ~53% (at pH 4.5) was obtained for 0.1?wt% Au–HAp–Col nanoparticles. To study the cytotoxic effects from the hetero nanostructures, MG-63 osteoblast-like cells were exposed to different concentration ranges on Au–HAp, Au–HAp–Col, and DOX loaded Au–HAp–Col nanoparticles. The non-toxic and bioactive properties of the synthesized nanoparticle-fabricated scaffold promotes cellular attachment, growth, and proliferation. These results indicated that optimized Au–HAp–Col nanoparticles may be promising drug delivery and scaffold materials for multifunctional biomedical applications.     

Multivariate analysis of the correlation between noctuidae subfamilies and the chemical structure of their sex pheromones or male attractants

Female-emitted pheromones and sex attractants of Noctuidae were investigated using a specific computer procedure to analyze data collected from the literature. Correspondence analysis was used to survey the structure-activity relationships of sex pheromones in seven subfamilies. Structural, stereochemical, and functional features of active molecules were related to taxonomy. This multidimensional analysis revealed that the prevalent chemical frame of noctuid moth pheromones was a monounsaturated acetate withZ stereochemistry and a double bond on the fifth carbon closest to the nonfunctional branch of the molecule. Possible phylogenetic relationships within Noctuidae and between Noctuidae and other families are discussed in light of the sex pheromone biochemistry. Female sex pheromones appeared to be an additional character to be considered in the classification of noctuid moths.     

Biomimetic mineralization of chitosan/gelatin cryogels and in vivo biocompatibility assessments for bone tissue engineering

The objective of this study is to develop biomimetic chitosan: gelatin (CH:Gel) cryogels for bone tissue engineering, combining the biological recognition of natural polymers with the distinguished interconnected porosity of cryogels, and biomimicking properties of bone like hydroxyapatite. The control of the biomineralization process onto biomaterials should be evaluated before clinical application. Therefore, the effect of chitosan and gelatin ratios on the final properties of the cryogels were investigated. FTIR, XRD, and SEM analysis indicated that the SBF coating exhibited similar characteristics to hydroxyapatite. The cryogels showed good biocompatibility with L929 mouse fibroblasts. Clinical outcomes and gross pathological examination showed that neither necrosis nor foreign body reaction was noted at the end of implantation. The biomimetically mineralized scaffold was found to be non-irritant and non-toxic for bone tissue. The biological performance and favorable properties demonstrated that the SBF coated CH:Gel cryogel can be a promising biomimetic scaffold for bone tissue engineering applications.     

Novel β-TCP scaffold production using NaCl as a porogen for bone tissue applications

There are numerous methods for producing scaffolds to be applied in bone tissue engineering. However, the best method of scaffold production is essential to consider, with respect to their chemical composition and mechanical and structural properties, so that debris is not produced when the scaffolds are evaluated in vitro or in vivo.The primary aim of the present investigation was to produce six novel β-TCP scaffold compositions, using sodium chloride as a porogen, with two different particle sizes, measuring 1–2 mm and 750 mm-1mm, and at varied concentrations (30, 50, and 70 wt %). Physical, chemical, mechanical, and in vitro characterizations were then performed on each scaffold composition, using artificial saliva, for 7 and 14 days, with promising results. The XRD diffractograms showed the formation of two new crystalline phases (NaCaPO₄ and Ca₅[PO₄]₃Cl) in the scaffolds, after their production. In addition, scaffold porosity, Young's modulus, and the maximum resistance of compression values were in the trabecular bone range and the in vitro test, using artificial saliva, was favorable in relation to scaffold bioactivity.     

6-Substituted pyrrolo[3,4-c]pyrazoles: an improved class of CDK2 inhibitors

We have recently reported a new class of CDK2/cyclin A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. The introduction of small alkyl or cycloalkyl groups in position 6 of this scaffold allowed variation at the other two diversity points. Conventional and polymer-assisted solution phase chemistry provided a way of generating compounds with improved biochemical and cellular activity. Optimization of the physical properties and pharmacokinetic profile led to a compound which exhibited good efficacy in vivo on A2780 human ovarian carcinoma.     

Fabrication and performance of calcium phosphate cement/small intestinal submucosa composite bionic bone scaffolds with different microstructures

The microstructure of the tissue has a very important determining effect on its performance. Herein, two calcium phosphate cement (CPC)/small intestinal submucosa(SIS) composites bionic bone scaffolds with different microstructures were fabricated by rolling or/ and assembling method. The microstructure, 3D morphology, the crystal phase and mechanical properties of the scaffolds were investigated by micro CT, XRD, FIIR, SEM and electronic universal testing machines respectively. The results showed that the pore size of all scaffolds are in the range of 100–400?µm, which are beneficial to cells growth, migration, and tissue vascularization. Their porosity and the specific surface area were 14.53?±?0.76%, 8.74?±?1.38?m²/m³ and 32?±?0.58%, 26.75?±?2.69?m²/m³ separately. The high porosity and the large specific surface area can provide a larger space and contact area for cells adhesion and proliferation. Meanwhile, compressive strength of the scaffolds soaked were 10?MPa and 27?MPa, about 1.2 folds and 3.2 folds of the original scaffolds, respectively. The results are derived from different microstructures of the scaffolds and chemical bonds between SIS and new phases (hydroxyapatite), and the scaffolds performance steadily increased at near the physiological conditions. Finally, biocompatibility of the scaffolds was evaluated by CCK8, bionic microstructure scaffolds are no cytotoxicity and their biocompatibility is favorable. Based on the microstructure, compressive strength and cytotoxicity of the scaffolds, bionic Harvarsin microstructure CPC/SIS composite scaffold is expected to turn into a scaffold with the excellent properties of real bone.     

Phenological,Nutritional and Molecular Diversity Assessment among 35 Introduced Lentil (Lens culinaris Medik.) Genotypes Grown in Saudi Arabia

Morphological, nutritional and molecular analyses were carried out to assess genetic diversity among 35 introduced lentil genotypes (Lens culinaris Medik.). The genotypes exhibited significant differences for their field parameters and some of them showed noticeable superiority. The nutritional and proximate analysis showed that some genotypes were excellent sources of proteins, essential amino acids, minerals, anti-oxidants, total phenolic contents (TPC) and total flavonoid contents (TFC) and hence, highlights lentil nutritional and medicinal potential. Sequence-related amplified polymorphism (SRAP) and amplified fragments length polymorphism (AFLP) markers were used to estimate the genetic variability at the molecular level. The existence of a considerable amount of genetic diversity among the tested lentil genotypes was also proven at the molecular level. A total of 2894 polymorphic SRAP and 1625 AFLP loci were successfully amplified using six SRAP and four AFLP primer pair combinations. Polymorphism information content (PIC) values for SRAP and AFLP markers were higher than 0.8, indicating the power and higher resolution of those marker systems in detecting molecular diversity. UPGMA (unweighted pair group method with arithmetic average) cluster analysis based on molecular data revealed large number of sub clusters among genotypes, indicating high diversity levels. The data presented here showed that FLIP2009-64L and FLIP2009-69L could be used as a significant source of yield, total protein, essential amino acids, and antioxidant properties. The results suggest potential lentil cultivation in the central region of Saudi Arabia for its nutritional and medicinal properties, as well as sustainable soil fertility crop.     

The effect of chemistry on the polymerization, thermo-mechanical properties and degradation rate of poly(β-amino ester) networks

Poly(β-amino ester) networks are gaining attention as a scaffold material for tissue engineering applications where it is important to have tailorable degradation rate and elastic modulus. The objective of this work is to characterize and understand the relationships between chemical structure, polymerization, thermo-mechanical properties, and degradation in poly(β-amino esters) networks. The networks were synthesized from a primary amine with systematically varied molar ratios and chemical structures of diacrylates. Fundamental trends were established between the chemical structure, conversion during polymerization, macromer molecular weight, rubbery modulus, and degradation rate. The thermo-mechanical properties were dependent upon both polymerization steps. The rubbery modulus was tailorable over a range of several MPa by changing molar ratio and diacrylate molecular weight. The degradation rate ranged from hours to months depending upon the composition. Select chemical structures showed degradation rate independent of modulus. This work provides a basis for designing poly(β-amino esters) networks with specific thermo-mechanical properties and degradation rates for biomedical scaffolds.