Molecular

Genome-wide association studies have revealed >270 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the molecular determinants behind this psychiatric condition. Epigenetic marks such as post-translational histone modifications remain largely plastic during development and adulthood, allowing a dynamic impact of environmental factors, including antipsychotic medications, on access to genes and regulatory elements. However, few studies so far have profiled cell-specific genome-wide histone modifications in postmortem brain samples from schizophrenia subjects, or the effect of antipsychotic treatment on such epigenetic marks...

Mitochondrial genomes have provided significant insights into the evolution of several insects. A typical mitogenome contains 37 genes, and variations in gene order can indicate evolutionary relationships between species. In this study, we have assembled the first complete mitogenomes of Endecous chape and E. onthophagus and analyzed the phylogenetic implications for the Gryllidea infraorder. We performed DNA extractions and genome sequencing for both Endecous species. Subsequently, we searched for raw data in the Sequence Read Archive (SRA) in NCBI...

Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Previous work showed dynamic interconversions between epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) defines the phenotypic landscape of prostate tumors, as a potential driver of emergence of therapeutic resistance. In this study, we use in vitro and in vivo preclinical MDA PCa PDX models of resistant human prostate cancer to determine molecular mechanisms of cross-resistance between anti-androgen therapy and taxane chemotherapy, underlying the therapeutically resistant phenotype...

Machine learning has the potential to provide tremendous value to life sciences by providing models that aid in the discovery of new molecules and reduce the time for new products to come to market. Chemical reactions play a significant role in these fields, but there is a lack of high-quality open-source chemical reaction data sets for training machine learning models. Herein, we present ORDerly, an open-source Python package for the customizable and reproducible preparation of reaction data stored in accordance with the increasingly popular Open Reaction Database (ORD) schema...

Understanding the structure-property relationship of lithium-ion conducting solid oxide electrolytes is essential to accelerate their development and commercialization. However, the structural complexity of nonideal materials increases the difficulty of study. Here, we develop an algorithmic framework to understand the effect of microstructure on the properties by linking the microscopic morphology images to their ionic conductivities. We adopt garnet and perovskite polycrystalline oxides as examples and quantify the microscopic morphologies via extracting determined physical parameters from the images...

The II-I phase transition of isotactic poly(1-butene) (iPBu) leads to improved mechanical performance. However, this will take several weeks and increase storage and processing costs. In this work, shear forces were introduced into the supercooled iPBu melt, and the effects of isothermal crystallization temperature (Tc ) and shear temperature (Tshear ) on crystallization and phase transition were explored. Shear-induced transcrystalline morphology of Form II with a significantly shortened crystallization induction period can be observed at relatively high Tc (105 °C)...

We recently reported that resistance to PD-1-blockade in a refractory lung cancer-derived model involved increased collagen deposition and the collagen-binding inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), and thus we hypothesized that LAIR1 and collagen cooperated to suppress therapeutic response. Here, we report LAIR1 is associated with tumor stroma and is highly expressed by intratumoral myeloid cells in both human tumors and mouse models of cancer. Stroma-associated myeloid cells exhibit a suppressive phenotype and correlate with LAIR1 expression in human cancer...

MOTIVATION: Accurate inference of potential Drug-protein interactions (DPIs) aids in understanding drug mechanisms and developing novel treatments. Existing deep learning models, however, struggle with accurate node representation in DPI prediction, limiting their performance. RESULTS: We propose a new computational framework that integrates global and local features of nodes in the drug-protein bipartite graph for efficient DPI inference. Initially, we employ pre-trained models to acquire fundamental knowledge of drugs and proteins and to determine their initial features...

Actin filaments and their associated actin-binding proteins (ABPs) play key roles in plant innate immune signaling. CAP1, or cyclase-associated protein 1, is an important regulatory factor of the actin cytoskeleton-associated signaling network, and was hypothesized here to be involved in resistance against wheat stripe rust because TaCAP1 expression was up-regulated in response to Puccinia striiformis f. sp. tritici (Pst). Down regulation of TaCAP1 expression led to decreased resistance against Pst, in contrast to increased resistance upon TaCAP1 overexpressing, as demonstrated by the changes of phenotypes and hyphal growth...

We present a novel three-layer approach based on multilevel density functional theory (MLDFT) and polarizable molecular mechanics to simulate the electronic excitations of chemical systems embedded in an external environment within the time-dependent DFT formalism. In our method, the electronic structure of a target system, the chromophore, is determined in the field of an embedded inactive layer, which is treated as frozen. Long-range interactions are described by employing the polarizable fluctuating charge (FQ) force field...

Single-stranded oligonucleotides (SSOs) are a rapidly expanding class of therapeutics that comprises antisense oligonucleotides, microRNAs, and aptamers, with ten clinically approved molecules. Chemical modifications such as the phosphorothioate backbone and the 2'- O -methyl ribose can improve the stability and pharmacokinetic properties of therapeutic SSOs, but they can also lead to toxicity in vitro and in vivo through nonspecific interactions with cellular proteins, gene expression changes, disturbed RNA processing, and changes in nuclear structures and protein distribution...

The pyridine moiety is a crucial structural component in various pharmaceuticals. While the direct ortho- and para-functionalization of pyridines is relatively straightforward, the meta-selective C-H functionalization remains a significant challenge. This review highlights dearomatization strategies as a key area of interest in expanding the application of meta-C-H functionalization of pyridines. Dearomatization enables the meta-functionalization through various catalytic methods that directly generate dearomatization products, and some products can be rearomatized back to pyridine derivatives...

Bispecific antibody (bsAb), a novel therapeutic modality, provides excellent treatment efficacy, yet poses numerous challenges to downstream process development, which are mainly due to the intricate diversity of bsAb structures and impurity profiles. Ceramic hydroxyapatite (CHT), a mixed-mode medium, allows proteins to interact with its calcium sites (C-sites) through metal affinity and/or its phosphate sites (P-sites) through cation exchange interactions. This dual-binding capability potentially offers unique bind and elute behaviours for different proteins of interest, resulting in optimal product purity when suitable elution conditions are employed...

Glycerol-assisted instant catapult steam explosion (ICSE) of lignocellulose is an effective pretreatment method for enhancing sugar production compared to glycerol-free ICSE. In this study, glycerol-assisted ICSE of corn stover was studied in order to understand the reaction mechanisms and further optimize the process. Results showed that water extraction of corn stover prior to ICSE reduced pseudo-lignin formation. The combination of water extraction and glycerol-assisted ICSE led to the formation of lignin with a lower molecular weight (Mw) of 2851 g/mol than 3521 g/mole of that from the combination of water extraction and glycerol-free ICSE...

Ulva is one of the main green algae causing green tide disasters. Ulvan is the primarily component polysaccharide of the cell wall of Ulva and its complex structure and monosaccharide composition resulted in various biological activities. However, the high-value and effective utilization of extracted ulvan have been obstructed by limitations ranging from large molecular weight and low solubility to poor bioavailability. Ulva oligosaccharide obtained by degrading ulvan can not only ideally retain the various biological activities of ulvan very well but also effectively solve the problems of low solubility and poor bioavailability...

Tobacco polysaccharides were extracted by hot water extraction, and purified and separated using DEAE-52 cellulose chromatography columns, and three purified polysaccharide fractions, YCT-1, YCT-2, and YCT-3, were finally obtained. The physicochemical properties of the three fractions were analyzed by ultraviolet spectroscopy, high-performance liquid chromatography and high-performance gel chromatography. The in vitro antioxidant activity of tobacco polysaccharides was compared among different fractions by using DPPH radical, hydroxyl radical scavenging assay and potassium ferricyanide method...

Monoclonal antibodies (mAbs) require a high level of purity for regulatory approval and safe administration. High-molecular weight (HMW) species are a common impurity associated with mAb therapies. Hydrophobic interaction chromatography (HIC) resins are often used to remove these HMW impurities. Determination of a suitable HIC resin can be a time and resource-intensive process. In this study, we modeled the chromatographic behavior of seven mAbs across 13 HIC resins using measurements of surface hydrophobicity, surface charge, and thermal stability for mAbs, and hydrophobicity and zeta-potential for HIC resins with high fit quality (adjusted R2  > 0...

Aflatoxin B1 (AFB1 ) is extremely hepatotoxic, a causative agent of liver cancer, and can cause symptoms of acute or chronic liver damage. Chito-oligosaccharides (COS), obtained from the degradation of chitosan derived from shrimp and crab shells, is a natural antioxidant substance and its antitumor properties have been widely studied, but less research has been done on the prevention of AFB1 -induced acute liver injury. In this study, rats were acutely exposed to 1 mg/kg BW AFB1 and simultaneously gavaged with different doses of COS for 8 days...

Multi-enzyme complexes designed based on scaffold proteins are a current topic in molecular enzyme engineering. They have been gradually applied to increase the production of enzyme cascades, thereby achieving effective biosynthetic pathways. This paper reviews the recent progress in the design strategy and application of multi-enzyme complexes. First, the metabolic channels in the multi-enzyme complex have been introduced, and the construction strategies of the multi-enzyme complex emerging in recent years have been summarized...

High-temperature stress poses a significant environmental challenge for aquatic organisms, including tsinling lenok trout (Brachymystax lenok tsinlingensis). This study aimed to investigate the role of microRNAs (miRNAs) in inducing liver inflammation in tsinling lenok trout under high-temperature stress. Tsinling lenok trout were exposed to high-temperature conditions (24 °C) for 8 h, and liver samples were collected for analysis. Through small RNA sequencing, we identified differentially expressed miRNAs in the liver of high-temperature-stressed tsinling lenok trout compared to the control group (maintained at 16 °C)...