Practical computational toolkits for dendrimers and dendrons structure design

Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface (GUI) toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.Peer reviewe

The impact of diurnal temperature range on the risk of hospitalizations in a low-income setting: the case of the Central Coast of Vietnam

The study aims to evaluate the effects of diurnal temperature range (DTR) on all causes, cardiovascular and respiratory conditions in the Central Coast of Vietnam, a tropical, low-income region with high DTR exposure but limited research. Daily hospital admission data from the largest hospitals in three provinces were analyzed alongside meteorological data. A time-series analysis using a generalized linear distributed lag model was conducted to examine the non-linear DTR-hospitalization association. A random-effect meta-analysis using restricted maximum likelihood was performed to calculate the pooled effects across three provinces. Stratified analyses by gender, age, season and natural disaster occurrence were conducted to identify vulnerable subpopulations. The multi-province pooled effects indicated that a 1 °C increase in DTR raised the risk of hospitalizations for all causes and respiratory diseases by 1.5% [1.2-1.8%] and 0.5% [0.0–1.0%], at lag 0–6 days. The effects of DTR on cardiovascular diseases, as well as those stratified by subgroups, were not statistically significant. Additionally, DTR had a greater adverse effect during the dry season and in the presence of natural disaster. Females and the elderly were slightly more susceptible to respiratory admissions, while males and younger individuals had a higher risk of all-cause admissions due to greater DTR effects. DTR was an independent risk factor for the exacerbation of all and specific causes, particularly among the susceptible subgroups. The findings suggested that it is necessary to take preventive measures to protect these at-risk populations from the adverse effects of extreme DTR exposure.No Full Tex