Urban airborne PM2.5 induces pulmonary fibrosis through triggering glycolysis and subsequent modification of histone lactylation in macrophages.

Airborne fine particulate matter (PM2.5) can cause pulmonary inflammation and even fibrosis, however, the underlying molecular mechanisms of the pathogenesis of PM2.5 exposure have not been fully appreciated. In the present study, we explored the dynamics of glycolysis and modification of histone lactylation in macrophages induced by PM2.5-exposure in both in vivo and in vitro models. Male C57BL/6 J mice were anesthetized and administrated with PM2.5 by intratracheal instillation once every other day for 4 weeks. Mouse RAW264.7 macrophages and alveolar epithelial MLE-12 cells were treated with PM2.5 for 24 h. We found that PM2.5 significantly increased lactate dehydrogenase (LDH) activities and lactate contents, and up-regulated the mRNA expression of key glycolytic enzymes in the lungs and bronchoalveolar lavage fluids of mice. Moreover, PM2.5 increased the levels of histone lactylation in both PM2.5-exposed lungs and RAW264.7 cells. The pro-fibrotic cytokines secreted from PM2.5-treated RAW264.7 cells triggered epithelial-mesenchymal transition (EMT) in MLE-12 cells through activating transforming growth factor-ß (TGF-ß)/Smad2/3 and VEGFA/ERK pathways. In contrast, LDHA inhibitor (GNE-140) pretreatment effectively alleviated PM2.5-induced pulmonary inflammation and fibrosis via inhibiting glycolysis and subsequent modification of histone lactylation in mice. Thus, our findings suggest that PM2.5-induced glycolysis and subsequent modification of histone lactylation play critical role in the PM2.5-associated pulmonary fibrosis.

Superconducting ScH3 and LuH3 at Megabar Pressures.

Rare-earth (RE) superhydrides have great potential as high-temperature superconductors, with recent discoveries almost achieving room-temperature superconductivity in compressed LaH10 and YH9. Here, we continue to study the rare-earth hydrides by focusing on the new hydrides that the lightest element Sc and the heaviest element Lu formed under pressure. Two new superconducting hydrides ScH3 (Tc ∼ 18.5 K at 131 GPa) and LuH3 (Tc ∼ 12.4 K at 122 GPa) have been identified both with cubic structure by combining X-ray diffraction and electrical resistance techniques. Among all of the REH3, only the superconducting properties of ScH3 and LuH3 have been experimentally confirmed. Our current results may offer guidance to other REH3, which were predicted to be superconductors but have not been experimentally confirmed.

Construction of a carbon-conserving pathway for glycolate production by synergetic utilization of acetate and glucose in Escherichia coli.

Glycolate is a bulk chemical which has been widely used in textile, food processing, and pharmaceutical industries. Glycolate can be produced from sugars by microbial fermentation. However, when using glucose as the sole carbon source, the theoretical maximum carbon molar yield of glycolate is 0.67 mol/mol due to the loss of carbon as CO2. In this study, a synergetic system for simultaneous utilization of acetate and glucose was designed to increase the carbon yield. The main function of glucose is to provide NADPH while acetate to provide the main carbon backbone for glycolate production. Theoretically, 1 glucose and 5 acetate can produce 6 glycolate, and the carbon molar yield can be increased to 0.75 mol/mol. The whole synthetic pathway was divided into two modules, one for converting acetate to glycolate and another to utilize glucose to provide NADPH. After engineering module I through activation of acs, gltA, aceA and ycdW, glycolate titer increased from 0.07 to 2.16 g/L while glycolate yields increased from 0.04 to 0.35 mol/mol-acetate and from 0.03 to 1.04 mol/mol-glucose. Module II was then engineered to increase NADPH supply. Through deletion of pfkA, pfkB, ptsI and sthA genes as well as upregulating zwf, pgl and tktA, glycolate titer increased from 2.16 to 4.86 g/L while glycolate yields increased from 0.35 to 0.82 mol/mol-acetate and from 1.04 to 6.03 mol/mol-glucose. The activities of AceA and YcdW were further increased to pull the carbon flux to glycolate, which increased glycolate yield from 0.82 to 0.92 mol/mol-acetate. Fed-batch fermentation of the final strain NZ-Gly303 produced 73.3 g/L glycolate with a productivity of 1.04 g/(L·h). The acetate to glycolate yield was 0.85 mol/mol (1.08 g/g), while glucose to glycolate yield was 6.1 mol/mol (2.58 g/g). The total carbon molar yield was 0.60 mol/mol, which reached 80% of the theoretical value.

New xylose transporters support the simultaneous consumption of glucose and xylose in Escherichia coli.

Glucose and xylose are two major components of lignocellulose. Simultaneous consumption of glucose and xylose is critical for engineered microorganisms to produce fuels and chemicals from lignocellulosic biomass. Although many production limitations have been resolved, glucose-induced inhibition of xylose transport remains a challenge. In this study, a cell growth-based screening strategy was designed to identify xylose transporters uninhibited by glucose. The glucose pathway was genetically blocked in Escherichia coli so that glucose functions only as an inhibitor and cells need xylose as the carbon source for survival. Through adaptive evolution, omics analysis and reverse metabolic engineering, a new phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS) galactitol transporter (GalABC, encoded by EcolC_1640, EcolC_1641, and EcolC_1642 genes) that is not inhibited by glucose was identified. Inactivation of adenylate cyclase led to increased expression of the EcolC_1642 gene, and a point mutation in gene EcolC_1642 (N13S) further enhanced xylose transport. During the second round of gene mining, AraE and a new ABC transporter (AraFGH) of xylose were identified. A point mutation in the transcription regulator araC (L156I) caused increased expression of araE and araFGH genes without arabinose induction, and a point mutation in araE (D223Y) further enhanced xylose transport. These newly identified xylose transporters can support the simultaneous consumption of glucose and xylose and have potential use in producing chemicals from lignocellulose.

Risk of lung cancer due to external environmental factor and epidemiological data analysis.

Lung cancer is a cancer with the fastest growth in the incidence and mortality all over the world, which is an extremely serious threat to human's life and health. Evidences reveal that external environmental factors are the key drivers of lung cancer, such as smoking, radiation exposure and so on. Therefore, it is urgent to explain the mechanism of lung cancer risk due to external environmental factors experimentally and theoretically. However, it is still an open issue regarding how external environment factors affect lung cancer risk. In this paper, we summarize the main mathematical models involved the gene mutations for cancers, and review the application of the models to analyze the mechanism of lung cancer and the risk of lung cancer due to external environmental exposure. In addition, we apply the model described and the epidemiological data to analyze the influence of external environmental factors on lung cancer risk. The result indicates that radiation can cause significantly an increase in the mutation rate of cells, in particular the mutation in stability gene that leads to genomic instability. These studies not only can offer insights into the relationship between external environmental factors and human lung cancer risk, but also can provide theoretical guidance for the prevention and control of lung cancer.

A New Type of Electron Relay Station in Proteins: Three-Piece S:Π∴S↔S∴Π:S Resonance Structure.

A type of relay station for electron transfer in proteins, three-piece five-electron bonding, is introduced in this paper, which is also first proposed here. The ab initio calculations predict the formation of S:Π∴S↔S∴Π:S resonance binding with an aromatic ring located in the middle of two sulfur-containing groups, which may participate in electron-hole transport in proteins. These special structures can lower the local ionization energies to capture electron holes efficiently and may be easily formed and broken because of their proper binding energies. In addition, the UV-vis spectra provide evidence of the formations of the three-piece five-electron binding. The cooperation of three adjacent pieces may be advantage to promote electron transfer a longer distance.

Two Aromatic Rings Coupled a Sulfur-Containing Group to Favor Protein Electron Transfer by Instantaneous Formations of π∴S:π↔π:S∴π or π∴π:S↔π:π∴S Five-Electron Bindings.

The cooperative interactions among two aromatic rings with a S-containing group are described, which may participate in electron hole transport in proteins. Ab initio calculations reveal the possibility for the formations of the π∴S:π↔π:S∴π and π∴π:S↔π:π∴S five-electron bindings in the corresponding microsurrounding structures in proteins, both facilitating electron hole transport as efficient relay stations. The relay functionality of these two special structures comes from their low local ionization energies and proper binding energies, which varies with the different aromatic amino acids, S-containing residues, and the arrangements of the same aromatic rings according to the local microsurroundings in proteins.