DrugMAP: molecular atlas and pharma-information of all drugs.

The efficacy and safety of drugs are widely known to be determined by their interactions with multiple molecules of pharmacological importance, and it is therefore essential to systematically depict the molecular atlas and pharma-information of studied drugs. However, our understanding of such information is neither comprehensive nor precise, which necessitates the construction of a new database providing a network containing a large number of drugs and their interacting molecules. Here, a new database describing the molecular atlas and pharma-information of drugs (DrugMAP) was therefore constructed. It provides a comprehensive list of interacting molecules for >30 000 drugs/drug candidates, gives the differential expression patterns for >5000 interacting molecules among different disease sites, ADME (absorption, distribution, metabolism and excretion)-relevant organs and physiological tissues, and weaves a comprehensive and precise network containing >200 000 interactions among drugs and molecules. With the great efforts made to clarify the complex mechanism underlying drug pharmacokinetics and pharmacodynamics and rapidly emerging interests in artificial intelligence (AI)-based network analyses, DrugMAP is expected to become an indispensable supplement to existing databases to facilitate drug discovery. It is now fully and freely accessible at: https://idrblab.org/drugmap/.

NPASS database update 2023: quantitative natural product activity and species source database for biomedical research.

Quantitative activity and species source data of natural products (NPs) are important for drug discovery, medicinal plant research, and microbial investigations. Activity values of NPs against specific targets are useful for discovering targeted therapeutic agents and investigating the mechanism of medicinal plants. Composition/concentration values of NPs in individual species facilitate the assessments and investigations of the therapeutic quality of herbs and phenotypes of microbes. Here, we describe an update of the NPASS natural product activity and species source database previously featured in NAR. This update includes: (i) new data of ∼95 000 records of the composition/concentration values of ∼1 490 NPs/NP clusters in ∼390 species, (ii) extended data of activity values of ∼43 200 NPs against ∼7 700 targets (∼40% and ∼32% increase, respectively), (iii) extended data of ∼31 600 species sources of ∼94 400 NPs (∼26% and ∼32% increase, respectively), (iv) new species types of ∼440 co-cultured microbes and ∼420 engineered microbes, (v) new data of ∼66 600 NPs without experimental activity values but with estimated activity profiles from the established chemical similarity tool Chemical Checker, (vi) new data of the computed drug-likeness properties and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties for all NPs. NPASS update version is freely accessible at http://bidd.group/NPASS.

SapBase: A central portal for functional and comparative genomics of Sapindaceae species.

The Sapindaceae family, encompassing a wide range of plant forms such as herbs, vines, shrubs, and trees, is widely distributed across tropical and subtropical regions. This family includes economically important crops like litchi, longan, rambutan, and ackee. With the wide application of genomic technologies in recent years, several Sapindaceae plant genomes have been decoded, leading to an accumulation of substantial omics data in this field. This surge in data highlights the pressing need for a unified genomic data center capable of storing, sharing, and analyzing these data. Here, we introduced SapBase, that is, the Sapindaceae Genome Database. SapBase houses seven published plant genomes alongside their corresponding gene structure and functional annotations, small RNA annotations, gene expression profiles, gene pathways, and synteny block information. It offers user-friendly features for gene information mining, co-expression analysis, and inter-species comparative genomic analysis. Furthermore, we showcased SapBase's extensive capacities through a detailed bioinformatic analysis of a MYB gene in litchi. Thus, SapBase could serve as an integrative genomic resource and analysis platform for the scientific exploration of Sapinaceae species and their comparative studies with other plants.

Database of space life investigations and information on spaceflight plant biology.

Extensive spaceflight life investigations (SLIs) have revealed observable space effects on plants, particularly their growth, nutrition yield, and secondary metabolite production. Knowledge of these effects not only facilitates space agricultural and biopharmaceutical technology development but also provides unique perspectives to ground-based investigations. SLIs are specialized experimental protocols and notable biological phenomena. These require specialized databases, leading to the development of the NASA Science Data Archive, Erasmus Experiment Archive, and NASA GeneLab. The increasing interests of SLIs across diverse fields demand resources with comprehensive content, convenient search facilities, and friendly information presentation. A new database SpaceLID (Space Life Investigation Database http://bidd.group/spacelid/ ) was developed with detailed menu search tools and categorized contents about the phenomena, protocols, and outcomes of 459 SLIs (including 106 plant investigations) of 92 species, where 236 SLIs and 57 plant investigations are uncovered by the existing databases. The usefulness of SpaceLID as an SLI information source is illustrated by the literature-reported analysis of metabolite, nutrition, and symbiosis variations of spaceflight plants. In conclusion, this study extensively investigated the impact of the space environment on plant biology, utilizing SpaceLID as an information source and examining various plant species, including Arabidopsis thaliana, Brassica rapa L., and Glycyrrhiza uralensis Fisch. The findings provide valuable insights into the effects of space conditions on plant physiology and metabolism.

Cofactors as Molecular Fossils To Trace the Origin and Evolution of Proteins.

Due to their early origin and extreme conservation, cofactors are valuable molecular fossils for tracing the origin and evolution of proteins. First, as the order of protein folds binding with cofactors roughly coincides with protein-fold chronology, cofactors are considered to have facilitated the origin of primitive proteins by selecting them from pools of random amino acid sequences. Second, in the subsequent evolution of proteins, cofactors still played an important role. More interestingly, as metallic cofactors evolved with geochemical variations, some geochemical events left imprints in the chronology of protein architecture; this provides further evidence supporting the coevolution of biochemistry and geochemistry. In this paper, we attempt to review the molecular fossils used in tracing the origin and evolution of proteins, with a special focus on cofactors.

Identifying cancer prognostic modules by module network analysis.

BACKGROUND: The identification of prognostic genes that can distinguish the prognostic risks of cancer patients remains a significant challenge. Previous works have proven that functional gene sets were more reliable for this task than the gene signature. However, few works have considered the cross-talk among functional gene sets, which may result in neglecting important prognostic gene sets for cancer. RESULTS: Here, we proposed a new method that considers both the interactions among modules and the prognostic correlation of the modules to identify prognostic modules in cancers. First, dense sub-networks in the gene co-expression network of cancer patients were detected. Second, cross-talk between every two modules was identified by a permutation test, thus generating the module network. Third, the prognostic correlation of each module was evaluated by the resampling method. Then, the GeneRank algorithm, which takes the module network and the prognostic correlations of all the modules as input, was applied to prioritize the prognostic modules. Finally, the selected modules were validated by survival analysis in various data sets. Our method was applied in three kinds of cancers, and the results show that our method succeeded in identifying prognostic modules in all the three cancers. In addition, our method outperformed state-of-the-art methods. Furthermore, the selected modules were significantly enriched with known cancer-related genes and drug targets of cancer, which may indicate that the genes involved in the modules may be drug targets for therapy. CONCLUSIONS: We proposed a useful method to identify key modules in cancer prognosis and our prognostic genes may be good candidates for drug targets.

Evolutionary and genetic features of drug targets.

In the modern drug discovery pipeline, identification of novel drug targets is a critical step. Despite rapid progress in developing biomedical techniques, it is still a great challenge to find promising new targets from the ample space of human genes. This fact is partially responsible for the situation of "more investments, fewer drugs" in the pharmaceutical industry. A series of recent researches revealed that successfully targeted genes share some common evolutionary and genetic features, which means that the knowledge accumulated in modern evolutionary biology and genetics is very helpful to identify potential drug targets and to find new drugs as well. In this article, we comprehensively summarize the links between human drug targets and genetic diseases and their evolutionary origins, with an attempt to introduce these novel concepts and their medical implications to the biomedical community.

Identification of Non-Electrophilic Nrf2 Activators from Approved Drugs.

Oxidative damage can lead to a wide range of diseases. Nrf2 is an important transcription factor that regulates many of the cytoprotective enzymes involved in the oxidative stress response. Therefore, targeting the regulation of Nrf2 activation is one logical and effective strategy to prevent or lower the risk of oxidative stress-related diseases. Until now, most research has focused on electrophilic indirect Nrf2 activators, but the risk of 'off-target' effects may be associated with these activators. To find novel small non-electrophilic modulators of Nrf2, we started from chemical agents derived from a connectivity map (cMap) and identified 22 non-electrophilic potential Nrf2-activating drugs through a drug repositioning tactic. By determining the expression changes of antioxidant genes in MCF7 cells that were treated with the potential Nrf2 activators using quantitative real-time polymerase chain reaction RT-PCR (real-time polymerase chain reaction) (qRT-PCR), astemizole was found to have a greater scale of upregulating antioxidant genes NQO1, HO-1, and GCLM than the positive control d,l-sulforaphane, although the testing concentration was lower than that of the control. Astemizole is a good potential redox regulator and deserves more pharmacodynamic experimentation to test and verify its feasibility for use as an Nrf2 activator.

ATP selection in a random peptide library consisting of prebiotic amino acids.

Based upon many theoretical findings on protein evolution, we proposed a ligand-selection model for the origin of proteins, in which the most ancient proteins originated from ATP selection in a pool of random peptides. To test this ligand-selection model, we constructed a random peptide library consisting of 15 types of prebiotic amino acids and then used cDNA display to perform six rounds of in vitro selection with ATP. By means of next-generation sequencing, the most prevalent sequence was defined. Biochemical and biophysical characterization of the selected peptide showed that it was stable and foldable and had ATP-hydrolysis activity as well.

Prebiotic Synthesis of ATP: A Terrestrial Volcanism-Dependent Pathway.

Adenosine triphosphate (ATP) is a multifunctional small molecule, necessary for all modern Earth life, which must be a component of the last universal common ancestor (LUCA). However, the relatively complex structure of ATP causes doubts about its accessibility on prebiotic Earth. In this paper, based on previous studies on the synthesis of ATP components, a plausible prebiotic pathway yielding this key molecule is constructed, which relies on terrestrial volcanism to provide the required materials and suitable conditions.

Exploring outer space biophysical phenomena via SpaceLID.

Extensive investigations in outer space have revealed not only how life adapts to the space environment, but also that interesting biophysical phenomena occur. These phenomena affect human health and other life forms (animals, plants, bacteria, and fungi), and to ensure the safety of future human space exploration need to be further investigated. This calls for joint research efforts between biologists and physicists, as these phenomena present cross-disciplinary barriers. Various national organizations provide useful forums for bridging this gap. Additional discussion avenues and database resources are helpful for facilitating the interdisciplinary investigations of these phenomena. In this paper, we present the newly established Space Life Investigation Database (SpaceLID, https://bidd.group/spacelid/ ) which provides information about biophysical phenomena occurring in space. Examples obtained using the database are given while discussing the underlying causes of these phenomena and their implications for the physiology and health of life in space.

The Legend of ATP: From Origin of Life to Precision Medicine.

Adenosine triphosphate (ATP) may be the most important biological small molecule. Since it was discovered in 1929, ATP has been regarded as life's energy reservoir. However, this compound means more to life. Its legend starts at the dawn of life and lasts to this day. ATP must be the basic component of ancient ribozymes and may facilitate the origin of structured proteins. In the existing organisms, ATP continues to construct ribonucleic acid (RNA) and work as a protein cofactor. ATP also functions as a biological hydrotrope, which may keep macromolecules soluble in the primitive environment and can regulate phase separation in modern cells. These functions are involved in the pathogenesis of aging-related diseases and breast cancer, providing clues to discovering anti-aging agents and precision medicine tactics for breast cancer.

Database of space life investigations and bioinformatics of microbiology in extreme environments.

Biological experiments performed in space crafts like space stations, space shuttles, and recoverable satellites has enabled extensive spaceflight life investigations (SLIs). In particular, SLIs have revealed distinguished space effects on microbial growth, survival, metabolite production, biofilm formation, virulence development and drug resistant mutations. These provide unique perspectives to ground-based microbiology and new opportunities for industrial pharmaceutical and metabolite productions. SLIs are with specialized experimental setups, analysis methods and research outcomes, which can be accessed by established databases National Aeronautics and Space Administration (NASA) Life Science Data Archive, Erasmus Experiment Archive, and NASA GeneLab. The increasing research across diverse fields may be better facilitated by databases of convenient search facilities and categorized presentation of comprehensive contents. We therefore developed the Space Life Investigation Database (SpaceLID) http://bidd.group/spacelid/, which collected SLIs from published academic papers. Currently, this database provides detailed menu search facilities and categorized contents about the studied phenomena, materials, experimental procedures, analysis methods, and research outcomes of 448 SLIs of 90 species (microbial, plant, animal, human), 81 foods and 106 pharmaceuticals, including 232 SLIs not covered by the established databases. The potential applications of SpaceLID are illustrated by the examples of published experimental design and bioinformatic analysis of spaceflight microbial phenomena.

Protein Homochirality May Be Derived from Primitive Peptide Synthesis by RNA.

Homochirality is a feature of life, but its origin is still disputed. Recent theories indicate that the origin of homochirality coincided with that of the RNA world, but proteins have not yet been incorporated into the story. Ribosome is considered a living fossil that survived the RNA world and records the oldest interaction between RNA and proteins. Inspired by several ribosome-related findings, we propose a hypothesis as follows: the substrate chirality preference of some primitive peptide synthesis ribozymes can mediate the chirality transmission from RNA to protein. In return, the chiral preference of protective peptide-RNA interaction can bring these ribozymes an evolutionary advantage and facilitate the expansion of enantiomeric excess in peptides. Monte Carlo simulation results show that this system's chemistry model is plausible. This model can be further tested through investigation of the chirality preference for the interactions between d/l-ribose-composed rRNA homologs and l/d-amino acid-composed peptides.

Diosmetin Protects Against Obesity and Metabolic Dysfunctions Through Activation of Adipose Estrogen Receptors in Mice.

SCOPE: Obesity is a major public health and economic problem of global significance. Here, we investigate the role of diosmetin, a natural flavonoid presents mainly in citrus fruits, in the regulation of obesity and metabolic dysfunctions in mice. METHODS AND RESULTS: Eight-week-old male C57BL/6 mice fed a high-fat diet (HFD) or 5-week-old male ob/ob mice fed a normal diet are treated with diosmetin (50 mg kg-1 daily) or vehicle for 8 weeks. Diosmetin treatment decreases body weight and fat mass, improves glucose tolerance and insulin resistance in obese mice. These metabolic benefits are mainly attributed to increase energy expenditure via enhancing thermogenesis in brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Mechanistically, diosmetin acts as an agonist for estrogen receptors (ERs), and subsequently elevates adipose expressions of ERs in mice and in cultured adipocytes. When ERs are blocked by their antagonist fulvestrant in mice, diosmetin loses its beneficial effects, suggesting that ERs are indispensable for the metabolic benefits of diosmetin. CONCLUSION: The results indicate that diosmetin may be a potential anti-obesity nutritional supplement and could be explored for low ERs-related obesity populations.

Facilitating Antiviral Drug Discovery Using Genetic and Evolutionary Knowledge.

Over the course of human history, billions of people worldwide have been infected by various viruses. Despite rapid progress in the development of biomedical techniques, it is still a significant challenge to find promising new antiviral targets and drugs. In the past, antiviral drugs mainly targeted viral proteins when they were used as part of treatment strategies. Since the virus mutation rate is much faster than that of the host, such drugs feature drug resistance and narrow-spectrum antiviral problems. Therefore, the targeting of host molecules has gradually become an important area of research for the development of antiviral drugs. In recent years, rapid advances in high-throughput sequencing techniques have enabled numerous genetic studies (such as genome-wide association studies (GWAS), clustered regularly interspersed short palindromic repeats (CRISPR) screening, etc.) for human diseases, providing valuable genetic and evolutionary resources. Furthermore, it has been revealed that successful drug targets exhibit similar genetic and evolutionary features, which are of great value in identifying promising drug targets and discovering new drugs. Considering these developments, in this article the authors propose a host-targeted antiviral drug discovery strategy based on knowledge of genetics and evolution. We first comprehensively summarized the genetic, subcellular location, and evolutionary features of the human genes that have been successfully used as antiviral targets. Next, the summarized features were used to screen novel druggable antiviral targets and to find potential antiviral drugs, in an attempt to promote the discovery of new antiviral drugs.

Plausibility of Early Life in a Relatively Wide Temperature Range: Clues from Simulated Metabolic Network Expansion.

The debate on the temperature of the environment where life originated is still inconclusive. Metabolic reactions constitute the basis of life, and may be a window to the world where early life was born. Temperature is an important parameter of reaction thermodynamics, which determines whether metabolic reactions can proceed. In this study, the scale of the prebiotic metabolic network at different temperatures was examined by a thermodynamically constrained network expansion simulation. It was found that temperature has limited influence on the scale of the simulated metabolic networks, implying that early life may have occurred in a relatively wide temperature range.

Development of specific and selective bactericide by introducing exogenous metabolite of pathogenic bacteria.

The widespread and repeated use of broad-spectrum bactericides has led to an increase in resistance. Developing novel broad-spectrum bactericides cannot solve the resistance problem, and may even aggravate it. The design of specific and selective bactericides has become urgent. A specific bactericidal design strategy was proposed by introducing exogenous metabolites in this study. This strategy was used to optimize two known antibacterial agents, luteolin (M) and Isoprothiolane (D), against Xoo. Based on the prodrug principles, target compound MB and DB were synthesized by combing M or D with exogenous metabolites, respectively. Bactericidal activity test results demonstrated that while the antibacterial ability of target compounds was significantly improved, their selectivity was also well enhanced by the introducing of exogenous metabolites. Comparing with the original compound, the antibacterial activity of target compound was significantly increased 92.0% and 74.5%, respectively. The optimized target compounds were more easily absorbed, and the drug application concentrations were much lower than those of the original agents, which would greatly reduce environmental pollution and relieve resistance risk. Our proposed strategy is of great significance for exploring the specific and selective bactericides against other pathogens.

Human accelerated genome regions with value in medical genetics and drug discovery.

Accumulated evolutionary knowledge not only benefits our understanding of the pathogenesis of diseases, but also help in the search for new drug targets. This is further supported by the recent finding that human accelerated regions (HARs) identified by comparative genomic studies are linked to human neural system evolution and are also associated with neurological disorders. Here, we analyze the associations between HARs and diseases and drugs. We found that 32.42% of approved drugs target at least one HAR gene, which is higher than the ratio of in-research drugs. More interestingly, HAR gene-targeted drugs are most significantly enriched with agents treating neurological disorders. Thus, HAR genes have important implications in medical genetics and drug discovery.

Co-treatment of Waste From Steelmaking Processes: Steel Slag-Based Carbon Capture and Storage by Mineralization.

The iron and steel industry is an energy-intensive sector, and large amounts of waste/ by-products are generated during the steelmaking process, such as CO2, metallurgical slag, and wastewater. Enhancing the development and deployment of treating waste from the steelmaking process will be environment friendly and resource-saving. Capturing CO2 by steel slag (SS) via mineralization is regarded to be an excellent choice due to the high basicity of the slag. In this paper, recent research on the steel slag-based carbon capture and storage (SS-CCS) by mineralization was summarized. Three routes of SS-CCS are compared including, direct gas-solid carbonation, direct aqueous carbonation, and indirect carbonation, respectively. Furthermore, the challenges and prospects for further development of the SS-CCS were discussed.