Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.     

Growth of InAsSb/InAs MQWs on GaSb for mid-IR photodetector applications

We report the OMVPE growth and characterization of InAsSb/InAs strain balanced multiple quantum wells lattice-matched to GaSb substrates for potential application as mid-infrared detectors for wavelengths beyond 4 μm$\mathrm{\mu }\mathrm{m}$. Detailed transmission electron microscopy measurements were performed to evaluate the degree of Ga and Sb intermixing at the GaSb/InAsSb and InAs/InAsSb interfaces. Photoluminescence emission up to 5 μm$\mathrm{\mu }\mathrm{m}$ was observed for superlattice structures with only 15% antimony. The dependence of PL on wavelength is red shifted compared to expectations based on type I band alignment.     

Advertibly complete locallym-convex two-sided algebras

Many results on two-sided Banach algebras remain valid form-convex normal ones; in particular, the commutativity modulo the Jacobson radical. Moreover advertible completeness appears to be sufficient.     

Potential Immunogenic Activity of Computationally Designed mRNA- and Peptide-Based Prophylactic Vaccines against MERS,SARS-CoV,and SARS-CoV-2: A Reverse Vaccinology Approach

The continued emergence of human coronaviruses (hCoVs) in the last few decades has posed an alarming situation and requires advanced cross-protective strategies against these pandemic viruses. Among these, Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) have been highly associated with lethality in humans. Despite the challenges posed by these viruses, it is imperative to develop effective antiviral therapeutics and vaccines for these human-infecting viruses. The proteomic similarity between the receptor-binding domains (RBDs) among the three viral species offers a potential target for advanced cross-protective vaccine designs. In this study, putative immunogenic epitopes including Cytotoxic T Lymphocytes (CTLs), Helper T Lymphocytes (HTLs), and Beta-cells (B-cells) were predicted for each RBD-containing region of the three highly pathogenic hCoVs. This was followed by the structural organization of peptide- and mRNA-based prophylactic vaccine designs. The validated 3D structures of these epitope-based vaccine designs were subjected to molecular docking with human TLR4. Furthermore, the CTL and HTL epitopes were processed for binding with respective human Lymphocytes Antigens (HLAs). In silico cloning designs were obtained for the prophylactic vaccine designs and may be useful in further experimental designs. Additionally, the epitope-based vaccine designs were evaluated for immunogenic activity through immune simulation. Further studies may clarify the safety and efficacy of these prophylactic vaccine designs through experimental testing against these human-pathogenic coronaviruses.     

Determination of pharmacokinetics of flurbiprofen in Pakistani population using modified HPLC method

Pharmacokinetics of flurbiprofen has been studied in different populations, especially in Caucasian. However, there are very few studies reported from Eastern part of world. Previous studies suggested that genetic and environmental factors may cause inter-individual differences in flurbiprofen disposition, so we investigated the pharmacokinetics of flurbiprofen in Pakistani subjects. A single oral dose of 100 mg of flurbiprofen was administered to 22 healthy male Pakistani adults after overnight fasting for 10 h. Periodical blood sampling was done at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, and 24 h after dosing. Plasma concentration of flurbiprofen was determined by a modified high-performance liquid chromatography method, which was simple, sensitive, less time consuming and economical with ordinary internal standard. The method was validated according to ICH guidelines and was found to be sensitive, accurate and precise. The pharmacokinetic parameters observed in Pakistani subjects when compared with other populations (USA, UK, Canadian, French, and Indian) did not show considerable ethnic differences. However, one subject's data was suggestive of being poor metabolizer of flurbiprofen which supports the presence of CYP2C9 polymorphism contributing to inter-individual differences in flurbiprofen disposition. Pharmacogenomic studies are needed to verify this hypothesis.     

Effect of high temperature on reduction-controlling reaction rate of agricultural waste chars and coke with steelmaking slag

In the present research, mechanical and thermal properties of high-density polyethylene/wood flour were improved by incorporating nanoclay (Cloisite 30B) and antioxidant (Irganox B225) in the compound. Design of experiments was carried out to optimize composition among nine compounds and to investigate the effect of nanoclay and antioxidant (0–5 phr) and (0–0.4 phr), respectively. The results of mechanical tests showed approximately 24% increase in the tensile strength of compounds containing 2.5 and 5.0 part per hundred (phr) of the nanoclay in the composite compared with the same samples without nanoclay. The tensile modulus of composites increased 7.3% by increasing the level of nanoclay from 0 to 2.5 phr. However, a further increase in the nanoclay content led to a 4.3% decrease in tensile modulus. Evaluation of the thermal oxidation stability of samples confirmed that the thermal oxidation of composites decreased with increasing nanoclay from 0 to 5.0 phr and increased significantly with the addition of the antioxidant.

     

不同流场下进气对质子交换膜燃料电池性能的影响

流场的结构对于质子交换膜燃料电池(PEMFC)的水管理和气体的传递具有十分重要的影响,相关研究一直是燃料电池的研究热点与重点.本文以纯氧气和空气作为阴极氧化剂,通过电池的性能测试、极化曲线和电化学阻抗分析等原位实验,分析了气体的流动与传输、不同流场下的电流密度、入口反应气体浓度等条件对电池性能的影响.实验结果表明,提高...     

A constraint on physical quantum states in cosmological space-times

The problem of constructing the Hilbert space of physical states for a free scalar quantum field propagating on a cosmological background is considered. The concept of energy-momentum for such a field is discussed and it is noted that, according to current renormalization theory, for a state ¦M to have finite energy density its associated anticommutator function must be of a particular form first discussed by Hadamard. This restriction is shown to lead to a constraint on the construction of the Hilbert space of physical states. This constraint is used to reject a recently proposed scheme for the construction of this space which was based on a principle of energy minimization.This essay received an honourable mention from the Gravity Research Foundation for the year 1984.-Ed.     

Feasibility study on optimization of a typical solar chimney power plant

The solar chimney which has been built in Kerman (Kerman city-Iran) is a small scale electrical power plant. The chimney of this unit has 60 m height and 3 m diameter. The collector of this unit is 40 m × 40 m square. To reach nominal power of this unit of power plant, parameters which are effective in optimization are studied. In this regard, we deliberate and propose suggestions to maximize usage of solar energy and kinetic energy. The calculation of maximum power is one of the objectives of this study, so the paper present economic analysis for Kerman solar chimney. A home code has been written for this modeling, in MATLAB.