BackgroundMicroalgal metabolic engineering holds great promise for the overproduction of a wide range of commercial bioproducts. It demands simultaneous manipulation of multiple metabolic nodes. However, high-efficiency promoters have been lacking.ResultsHere we report a strong constitutive promoter Pt211 in expressing multiple target genes in oleaginous microalga Phaeodactylum tricornutum. Pt211 was revealed to contain significant cis-acting elements. GUS reporter and principal genes glycerol-3-phosphate acyltransferase (GPAT) and diacylglycerol acyltransferase 2 (DGAT2) involved in triacylglycerol biosynthesis were tested under driven of Pt211 in P. tricornutum. GUS staining and qPCR analysis showed strong GUS expression. DGAT2 and GPAT linked with a designed 2A sequence exhibited higher transcript abundances than WT, while algal growth and photosynthesis were not impaired.ConclusionThe total lipid content increased notably by 2.6-fold compared to WT and reached up to 57.5% (dry cell weight). Overall, our findings report a strong promoter and a strategy for coordinated manipulation of complex metabolic pathways.

Heat shock protein 90 (Hsp90) has been identified as an essential host factor for the infection and replication of several viruses, including HSV-1. Recent works have clearly shown that Hsp90 plays a role in the early stages of HSV-1 infection, including nuclear import and DNA replication. However, the role of Hsp90 in the late stages of HSV-1 infection remains unclear. In this study, we found that Hsp90 was up-regulated during late viral infection. Treatment with the Hsp90 inhibitor AT-533 significantly decreased the intracellular and extracellular virus titers, and strongly inhibited nucleocapsid egress from the nucleus. More detailed studies revealed that AT-533 inhibited the nuclear egress of the viral nucleocapsid by suppressing the expression and translocation of nuclear-associated proteins pUL31 and pUL34. In addition, we found that AT-533 hindered the assembly of virus particles possibly though affecting the localization of glycoproteins in the endoplasmic reticulum and Golgi apparatus. These results thus invoke a new role for Hsp90 in the nucleocapsid egress and viral maturation of HSV-1, and further promote the development of Hsp90 inhibitors as potential anti-HSV-1 drugs.

Objective The IKBKE has been proven to be associated with systemic lupus erythematosus (SLE) in a genome-wide association study (GWAS) conducted by our group. The objective of the recent study is to investigate the contribution of IKBKE functional variants (rs2297550) to SLE. Methods We detected the regulatory effect of rs2297550 on IKBKE expression by expression quantitative trait loci (eQTL) study. Then, we investigated the differences of IKBKE mRNA expression levels in peripheral blood mononuclear cells (PBMCs) between 135 SLE patients and 130 healthy controls using quantitative real-time PCR (qRT-PCR). We further analyzed the association of SLE clinical characteristics with IKBKE mRNA expression and rs2297550 polymorphisms. Results The results of eQTL indicated the genotype "GG" of single-nucleotide polymorphism (SNP) rs2297550 was associated with lower expression levels of IKBKE (P = 0.022) in normal controls. Compared with the healthy control group, the expression levels of IKBKE mRNA in patients with SLE were significantly decreased (P = 2.32 × 10 −12). In clinical characteristics, we found that IKBKE mRNA expression levels were associated with vasculitis (P = 0.015) and increased C-reactive protein (CRP) (P = 0.021) in SLE patients. Conclusion In this study, we not only detected that the variant rs2297550 of IKBKE may be closely related to SLE, but also proposed functional hypotheses for the association signals. Key Points • The rs2297550 is located in a region with transcriptional regulatory function and may regulate the expression of IKBKE via these regulatory elements. • The genotype "GG" of SNP rs2297550 was associated with lower expression levels of IKBKE. • The expression of IKBKE mRNA was decreased in SLE patients compared with healthy controls. • IKBKE contributes to the clinical characteristics of SLE.

Aim: To explore the underlying influence of HSV type-1 (HSV-1) infection on the energy metabolism of human umbilical cord-derived mesenchymal stem cells (UCMSCs). Methods: UCMSCs (derived from different donors) were isolated from umbilical cord tissue, cultured and infected with HSV-1. Various virology and biochemical assays were used to assess cell viability and function, such as plaque formation assay and mitochondrial mass assay. Results: HSV-1 infection sharply activated mitochondrial biogenesis, increased glucose consumption, oxidative phosphorylation and glycolysis of UCMSCs. Treatment with rotenone (a metabolism antagonist) and iodoacetic acid significantly blocked the proliferation of HSV-1 in UCMSCs. Conclusion: This study demonstrates, for the first time, that HSV-1 infection affects the energy metabolism process of UCMSCs. Treatment with the appropriate metabolism antagonists might improve the safety and efficacy of clinical stem cell therapies.

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<p>Flight delays are one of the major concerns in air traffic management. The impact of flight delays represents financial and time losses and may derive in loss of reputation of the air traffic business. On average weather accounts for roughly one-third of ATFM (Air Traffic Flow Management) delays (25% for en-route and ~50% for the airports). Examining only the top ten days with highest delays due to weather regulations from the first half of 2018, strong convective activity throughout Europe was the principal cause, with estimated cost due to airport and en-route delays reaching almost €130 million (roughly 10% of the weather delay in 2018 concentrated in only 10 days). Given these large cost figures, even minor improvement in prediction and performance of ATFM operations during significant convective weather events will yield to substantial yearly savings for the ATM (Air Traffic Management) system. Designing an efficient value chain for ATFM, that propagates weather forecasts into a series of tools to select mitigation measures at local and network levels in a collaborative ATFM operations paradigm, requires a multidisciplinary approach to gather the different stakeholders. Such an approach has been developed in the SESAR ISOBAR project, whose aim is to integrate enhanced convective weather forecasts for predicting imbalances between air traffic capacity and demand (requests to fly by airspace users, mainly airlines) and to select appropriate mitigation measures. The value chain developed in the framework of ISOBAR leverages the power of Artificial Intelligence (AI) in the different stages. AI engine is trained using a dataset of selected convective events in summer 2019, which includes forecasts from high resolution ensemble prediction systems (IFS, γ-SREPS and AROME-EPS), declared capacity in air traffic flow and initial air traffic demand. The value chain produces a solution for tactical (day 0) and pre-tactical (day -1) ATFM operations. A validation exercise was organised at EUROCONTROL Innovation Hub in March 2022 with the collaboration of ATC (Air Traffic Control) operational staff and Air Traffic Controllers from Spain, France and Europe air traffic network management. AI Engine was run for some high convective situations over Europe, which were characterised by high delays due to weather regulations. Offline simulations highlighted the added value of the solutions assessed by ATC experts. The predicted air traffic delay has been drastically cut by up 75%.</p>

Background The development of affordable strategy to concurrently enhance microalgal biomass and biocomponents is warranted for commercial applications. Here, we investigated the efficacy of a cheap and natural polyphenol, tannic acid, on regulating metabolic and physiological properties of oleaginous microalga Phaeodactylum tricornutum to overproduce biocompounds. Result Tannic acid provision regulated the key metabolic pathways to enhance algal biomass and lipids in a dose-dependent manner without direct impact on photosynthesis. It reduced oxidative stress and reallocated carbon precursors towards lipogenesis. Lipidomic analyses showed that tannic acid provision unprecedentedly regulated the key lipogenic pathways, enhanced glyco- and neutral-lipids by 1.29- and 1.54-fold, respectively, whereas phospholipids were significantly altered. Tannic acid facilitated polyunsaturated fatty acid overproduction with a specific increment of EPA and DHA by 1.18- and 2.25-fold, respectively. Transcriptomic analysis demonstrated that tannic acid upregulated the expression of multiple genes involved in lipogenesis. Conclusion Here, we dissected the potential of tannic acid, a natural and cheaper polyphenol, on concurrently enhancing lipids and PUFAs without impairing physiological properties in P. tricornutum. The findings provide novel insights into the mechanistic roles of polyphenol as a potential chemical modulator.