The impact of indoor air pollution on children's health and well-being: the experts' consensus.

BACKGROUND: Pollution of the indoor environment represents a concern for human health, mainly in case of prolonged exposure such as in the case of women, children, the elderly, and the chronically ill, who spend most of their time in closed environments. MAIN BODY: The aim of the study is to organize a group of experts in order to evaluate the evidence and discuss the main risk factors concerning indoor air and the impact on human health as well as challenging factors regarding preventive strategies to reduce pollution. The experts highlighted the main risk factors concerning indoor air, including poor ventilation, climatic conditions, chemical substances, and socio-economic status. They discussed the impact on human health in terms of mortality and morbidity, as well as challenging factors regarding preventive strategies to reduce pollution. CONCLUSION: The experts identified strategies that can be reinforced to reduce indoor pollution and prevent negative consequences on human health at national and local levels.

Superior Mesenteric Artery Syndrome in Anorexia Nervosa: A Case Report and a Systematic Revision of the Literature.

BACKGROUND: Superior mesenteric artery syndrome (SMAS) is a rare condition caused by the compression of the duodenum, which may occur in the case of fast weight loss. Currently, the relationship between superior mesenteric artery syndrome and anorexia nervosa is still unclear. The aim of this study is to identify the precocious clinical signs and symptoms of SMAS in patients affected by anorexia nervosa so as not to delay the diagnosis. METHODS: We present the clinical case of a young female patient with anorexia nervosa complicated by SMAS. We performed a literature review of SMAS in children affected by anorexia nervosa between 1962 and 2023, according to the PRISMA Extension Guide for Scoping Reviews. RESULTS: Reviewing the literature, 11 clinical cases were described for the pediatric age. The median age at diagnosis was 17 years (ranging from 13 to 18 years). The diagnosis of SMAS may be challenging as symptoms overlap those of anorexia, but it should be kept in mind mostly in cases of post-prandial abdominal pain, anxiety or depression, nausea, vomiting, and weight loss. CONCLUSION: Even specific clinical symptoms may act as flag tags to drive attention to this rare but potentially fatal condition.

Regulatory molecule cAMP changes cell fitness of the engineered Escherichia coli for terpenoids production.

Terpenoids are a class of natural compounds with many important functions and applications. They are synthesized from a long synthetic pathway of isoprenyl unit coupling with the myriads of terpene synthases. Owing to the catalytic divergence of terpenoids synthesis, microbial production of terpenoids is compromised to the complexity of pathway engineering and suffers from the metabolic engineering burden. In this work, the adaptive Escherichia coli HP variant exhibited a general cell fitness in terpenoid synthesis. Especially, it could yield taxadiene of 193.2 mg/L in a test tube culture, which is a five-fold increase over the production in the wild type E. coli DH5α. Mutational analyses indicated that IS10 insertion in adenylate cyclase CyaA (CyaAHP) resulted in lowering intracellular cyclic AMP (cAMP), which could regulate its receptor protein CRP to rewire cell metabolism and contributed to the improved cell fitness. Our results suggested a way to manipulate cell fitness for terpenoids production and other products.

Crystal structure of geranylgeranyl pyrophosphate synthase (crtE) from Nonlabens dokdonensis DSW-6.

Isoprenoids comprise a diverse group of natural products with a broad range of metabolic functions. Isoprenoids are synthesized from prenyl pyrophosphates by prenyltransferases that catalyze the isoprenoid chain-elongation process to different chain lengths. We hereby present the crystal structure of geranylgeranyl pyrophosphate synthase from the marine flavobacterium Nonlabens dokdonensis DSW-6 (NdGGPPS). NdGGPPS forms a hexamer composed of homodimeric trimer, and the monomeric structure is composed of 15 α-helices (α1-α15). In this structure, we observed the binding of one pyrophosphate molecule and two glycerol molecules that mimicked substrate binding to the enzyme. The substrate binding site of NdGGPPS contains large hydrophobic residues such as Phe, His and Tyr, and structural and amino acids sequence analyses thereof suggest that the protein belongs to the short-chain prenyltransferase family.

Challenges and tackles in metabolic engineering for microbial production of carotenoids.

Naturally occurring carotenoids have been isolated and used as colorants, antioxidants, nutrients, etc. in many fields. There is an ever-growing demand for carotenoids production. To comfort this, microbial production of carotenoids is an attractive alternative to current extraction from natural sources. This review summarizes the biosynthetic pathway of carotenoids and progresses in metabolic engineering of various microorganisms for carotenoid production. The advances in synthetic pathway and systems biology lead to many versatile engineering tools available to manipulate microorganisms. In this context, challenges and possible directions are also discussed to provide an insight of microbial engineering for improved production of carotenoids in the future.

Microbial Platform for Terpenoid Production: Escherichia coli and Yeast.

Terpenoids, also called isoprenoids, are a large and highly diverse family of natural products with important medical and industrial properties. However, a limited production of terpenoids from natural resources constrains their use of either bulk commodity products or high valuable products. Microbial production of terpenoids from Escherichia coli and yeasts provides a promising alternative owing to available genetic tools in pathway engineering and genome editing, and a comprehensive understanding of their metabolisms. This review summarizes recent progresses in engineering of industrial model strains, E. coli and yeasts, for terpenoids production. With advances of synthetic biology and systems biology, both strains are expected to present the great potential as a platform of terpenoid synthesis.

Metabolic engineering of Escherichia coli for production of mixed isoprenoid alcohols and their derivatives.

BACKGROUND: Current petroleum-derived fuels such as gasoline (C5-C12) and diesel (C15-C22) are complex mixtures of hydrocarbons with different chain lengths and chemical structures. Isoprenoids are hydrocarbon-based compounds with different carbon chain lengths and diverse chemical structures, similar to petroleum. Thus, isoprenoid alcohols such as isopentenol (C5), geraniol (C10), and farnesol (C15) have been considered to be ideal biofuel candidates. NudB, a native phosphatase of Escherichia coli, is reported to dephosphorylate isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) into isopentenol. However, no attention has been paid to its promiscuous activity toward longer chain length (C10-C15) prenyl diphosphates. RESULTS: In this study, the promiscuous activity of NudB toward geranyl diphosphate (GPP) and farnesyl diphosphate (FPP) was applied for the production of isoprenoid alcohol mixtures, including isopentenol, geraniol, and farnesol, and their derivatives. E. coli was engineered to produce a mixture of C5 and C15 alcohols by overexpressing NudB (dihydroneopterin triphosphate diphosphohydrolase) and IspA (FPP synthase) along with a heterologous MVA pathway, which resulted in a total of up to 1652 mg/L mixture of C5 and C15 alcohols and their derivatives. The production was further increased to 2027 mg/L by overexpression of another endogenous phosphatase, AphA, in addition to NudB. Production of DMAPP- and FPP-derived alcohols and their derivatives was significantly increased with an increase in the gene dosage of idi, encoding IPP isomerase (IDI), indicating a potential modulation of the composition of the alcohols mixture according to the expression level of IDI. When IspA was replaced with its mutant IspA*, generating GPP in the production strain, a total of 1418 mg/L of the isoprenoid mixture was obtained containing C10 alcohols as a main component. CONCLUSIONS: The promiscuous activity of NudB was newly identified and successfully used for production of isoprenoid-based alcohol mixtures, which are suitable as next-generation biofuels or commodity chemicals. This is the first successful report on high-titer production of an isoprenoid alcohol-based mixture. The engineering approaches can provide a valuable platform for production of other isoprenoid mixtures via a proportional modulation of IPP, DMAPP, GPP, and FPP syntheses.