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.

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.

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.

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.

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.

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.

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.

Identification of Dacinostat as a potential anti-obesity compound through transcriptional activation of adipose thermogenesis in mice.

Obesity is a worldwide health problem. Activating fat mobilization and reducing fat synthesis is a promising strategy to mitigate obesity and its complicated metabolic diseases. However, few clinically effective and safe agents conform to the strategy.

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.

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.

Identification of NUDT5 Inhibitors From Approved Drugs.

Recent studies have revealed the important role of NUDT5 in estrogen signaling and breast cancer, but research on the corresponding targeted therapy has just started. Drug repositioning strategy can effectively reduce the time and economic resources spent on drug discovery. To find novel inhibitors of NUDT5, we investigated the previously identified connectivity map-based drug association models and found eighteen FDA approved drugs as candidates.

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice.

Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT).

Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production.

Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize that Aco2 may play a key role in the lipid synthesis. Here, we show that overexpression of Aco2 in 3T3-L1 cells significantly increased lipogenesis and adipogenesis, accompanied by elevated mitochondrial biogenesis and ATP production.

Isorhapontigenin Improves Diabetes in Mice via Regulating the Activity and Stability of PPARγ in Adipocytes.

Isorhapontigenin is a natural bioactive stilbene isolated from various plants and fruits. It has been reported to exhibit several physiological activities including anticancer and anti-inflammation activity in vitro and in experimental animal models. This study aimed to investigate whether isorhapontigenin exerts antidiabetic effects in vivo.

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.

A Potential Nutraceutical Candidate Lactucin Inhibits Adipogenesis through Downregulation of JAK2/STAT3 Signaling Pathway-Mediated Mitotic Clonal Expansion.

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia.

Phosphates as Energy Sources to Expand Metabolic Networks.

Phosphates are essential for modern metabolisms. A recent study reported a phosphate-free metabolic network and suggested that thioesters, rather than phosphates, could alleviate thermodynamic bottlenecks of network expansion. As a result, it was considered that a phosphorus-independent metabolism could exist before the phosphate-based genetic coding system.

Why the c-Fos/c-Jun complex is extremely conserved: An in vitro evolution exploration by combining cDNA display and proximity ligation.

Transcriptional regulation involves a series of sophisticated protein-protein and protein-DNA interactions (PPI and PDI). Some transcriptional complexes, such as c-Fos/c-Jun and their binding DNA fragments, have been conserved over the past one billion years. Considering the thermodynamic principle for transcriptional complex formation, we hypothesized that the c-Fos/c-Jun complex may represent a thermodynamic summit in the evolutionary space.

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.

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.

Activating or Inhibiting Nrf2?

Activating nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) is a widely recognized strategy for combating oxidative-stress-induced diseases. However, Nrf2 activation does not always bring advantageous effects. Therefore, before performing Nrf2-targeted therapy, we must pinpoint whether Nrf2 should be activated or inhibited.