Patient-derived iPSCs link elevated mitochondrial respiratory complex I function to osteosarcoma in Rothmund-Thomson syndrome

Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarcoma. Here, we generated RTS patient-derived induced pluripotent stem cells (iPSCs) to dissect the pathological signaling leading to RTS patient-associated osteosarcoma. RTS iPSC-derived osteoblasts showed defective osteogenic differentiation and gain of in vitro tumorigenic ability. Transcriptome analysis of RTS osteoblasts validated decreased bone morphogenesis while revealing aberrantly upregulated mitochondrial respiratory complex I gene expression. RTS osteoblast metabolic assays demonstrated elevated mitochondrial respiratory complex I function, increased oxidative phosphorylation (OXPHOS), and increased ATP production. Inhibition of mitochondrial respiratory complex I activity by IACS-010759 selectively suppressed cellular respiration and cell proliferation of RTS osteoblasts. Furthermore, systems analysis of IACS-010759-induced changes in RTS osteoblasts revealed that chemical inhibition of mitochondrial respiratory complex I impaired cell proliferation, induced senescence, and decreased MAPK signaling and cell cycle associated genes, but increased H19 and ribosomal protein genes. In summary, our study suggests that mitochondrial respiratory complex I is a potential therapeutic target for RTS-associated osteosarcoma and provides future insights for clinical treatment strategies

Biodegradation of Crude Oil Under Low Temperature by Mixed Culture Isolated from Alpine Meadow Soil

Petroleum hydrocarbons have been worldwide concern contaminants because of their mutagenicity and carcinogenicity. The potential biodegradation of petroleum hydrocarbons at low temperatures is important for petroleum contamination remediation in cold region. In this study, a mixed cold-adapted bacteria flora JY, including seven petroleum-degrading strains (B1, H1, H2, H3, R1, R2, and S), was isolated from Alpine Meadow soil. Based on their 16S rRNA sequence analysis, B1, R1, and H3 were identified as Arthrobacter sp.; R2, S, H1, and H2 were identified as Rhodococcus sp., Pseudomonas sp., Stenotrophomonas sp., and Sphingobacterium sp., respectively. The mixed flora demonstrated 53.68% of total petroleum hydrocarbons (TPH) removal of the contaminated water (1 g oil L-1) after 30 days of incubation under 10 degrees C. In the degradation process, alkanes were more preferred to be degraded by JY than polycyclic aromatic hydrocarbons (PAHs) and other polar component. During this period, the abundant bacteria in the flora were transformed from alkane degraders of Rhodococcus sp. and Sphingobacterium sp. to PAH degraders of Pseudomonas sp. and sheltered Arthrobacter sp. This study verified that a cold-adapted mixed culture JY isolated from alpines meadow soil was capable in degrading TPH under low temperature through flora cooperation

Comparative thermal research on chlorodinitromethyl and fluorodinitromethyl explosophoric groups based insensitive energetic materials

The introduction of highly oxidative explosophoric groups is an efficient strategy to enhance the detonation properties of energetic materials due to its improvement effect of oxygen balances. Chlorodinitromethyl and fluorodinitromethyl groups are widely applied as oxygen-rich building blocks for the construction of energetic materials and their combinations with FOX-7 derived 1,3,5-tetrahydrogentriazine backbone provide perfect structures for a systematic and comparative thermal study of these two similar explosophoric groups. Decomposition behaviors of the obtained insensitive energetic materials were investigated through DSC-TG approaches and chlorodinitromethyl based one exhibited sharper exothermic peak shape and higher heat release rate. Non-isothermal kinetics of the thermal decomposition was achieved based on DSC experiments under different heating rates, showing an observable melting process which could only be observed from the chlorodinitromethyl group based energetic structure under high the heating rates. Possible mechanism of the thermal decomposition was proposed by exploring the intermediates during the heating process through the combination of in-situ FTIR spectroscopy technology with calculation methods, which proved that the decompositions were triggered by the cleavage of nitro groups in chlorodinitromethyl and fluorodinitromethyl moieties. Despite their effectiveness to improve the energy density levels, this study showed the chlorodinitromethyl and fluorodinitromethyl explosophoric groups can also interact with the backbones under high temperatures, especially with the ones with active N-H moieties, and result in low decomposition temperatures which may greatly limit their applications

Nematode Community Characteristics Indicate Soil Restoration under Different Revegetation Approaches in the Semiarid Area of the Chinese Loess Plateau

Soil nematode communities can offer valuable indicators for monitoring the status of soil ecosystems. However, their potential for assessing soil restoration under revegetation has been neglected in temperate arid and semiarid areas. This study examined the characteristics of soil nematode communities and their relationships with soil physicochemical properties under five typical revegetation approaches in the semiarid Loess Plateau of China. The results showed that planting an artificial Caragana korshinskii forest led to the recovery of the soil food web, which significantly increased soil nematode abundance (138.10 ± 11.60 inds./100 g dry soil) and community diversity (Shannon-Wiener diversity: 2.48 ± 0.13; trophic diversity: 3.08 ± 0.02), associated with the high contents of SOC and NH4+-N. However, establishing an artificial Prunus sibirica forest improved neither soil properties nor nematode community characteristics, reflecting poor soil ecosystem restoration. After establishing an artificial Prunus davidiana forest (PD) and an artificial Medicago sativa grassland (MS), substantial increases in herbivorous and fungivorous nematodes were observed, respectively, likely due to the accumulation of particular genera that fed on roots (e.g., Pratylenchus) or their symbiotic fungi (e.g., Tylencholaimus), which might result in the deterioration (in MS) or restoration (in PD) of the soil food webs. Natural grassland restoration greatly improved soil properties (i.e., SOC, NH4+-N, microbial biomass carbon) but did not change the nematode community obviously, probably due to top-down predation in natural habitats. In conclusion, the characteristics of nematode communities can effectively indicate the restoration of soil food webs and identify their possible driving forces under revegetation, which have important implications for vegetation restoration in arid and semiarid regions

Bioremediation Strategies for Petroleum Removal and Bacterial Communities in Loess Under 10 degrees C

Selecting a desirable remediation technology is an emergency task for drought and infertile loess with serious dispersal of petroleum pollution in the region of Yanchang Oilfield, Yan'an, China. In this research, batch experiments were performed to investigate natural attenuation (NA), bioaugmentation (BA), and biostimulation combined with bioaugmentation (BSBA) effect on the degradation of petroleum hydrocarbons and indigenous microbial communities under low temperature (10 degrees C). Results showed that compared to NA, (1) BA with JY (mixed strains cultured in laboratory) inoculation lead to symplastic growth of specific low temperature tolerant oil degraders Variovorax, Methanobrevibacter, and Comamonas and thus a higher degradation efficiency of aromatics (62.34%) and polar components (63.64%); and (2) BSBA showed negligible community shift since the indigenous microbe competing ability was enhanced by NH4Cl addition, which contributes to an adding effect of JY and indigenous petroleum degraders for best performance in total petroleum hydrocarbon (34.76%), saturate (27.62%), and aromatic (70.13%) removal. This study demonstrated that BSBA had the best removal efficiency and BA was more suitable for purpose of some special fraction removal

Thermophilic fermentation of acetoin and 2,3-butanediol by a novel Geobacillus strain

BACKGROUND: Acetoin and 2,3-butanediol are two important biorefinery platform chemicals. They are currently fermented below 40°C using mesophilic strains, but the processes often suffer from bacterial contamination. RESULTS: This work reports the isolation and identification of a novel aerobic Geobacillus strain XT15 capable of producing both of these chemicals under elevated temperatures, thus reducing the risk of bacterial contamination. The optimum growth temperature was found to be between 45 and 55°C and the medium initial pH to be 8.0. In addition to glucose, galactose, mannitol, arabionose, and xylose were all acceptable substrates, enabling the potential use of cellulosic biomass as the feedstock. XT15 preferred organic nitrogen sources including corn steep liquor powder, a cheap by-product from corn wet-milling. At 55°C, 7.7 g/L of acetoin and 14.5 g/L of 2,3-butanediol could be obtained using corn steep liquor powder as a nitrogen source. Thirteen volatile products from the cultivation broth of XT15 were identified by gas chromatography–mass spectrometry. Acetoin, 2,3-butanediol, and their derivatives including a novel metabolite 2,3-dihydroxy-3-methylheptan-4-one, accounted for a total of about 96% of all the volatile products. In contrast, organic acids and other products were minor by-products. α-Acetolactate decarboxylase and acetoin:2,6-dichlorophenolindophenol oxidoreductase in XT15, the two key enzymes in acetoin metabolic pathway, were found to be both moderately thermophilic with the identical optimum temperature of 45°C. CONCLUSIONS: Geobacillus sp. XT15 is the first naturally occurring thermophile excreting acetoin and/or 2,3-butanediol. This work has demonstrated the attractive prospect of developing it as an industrial strain in the thermophilic fermentation of acetoin and 2,3-butanediol with improved anti-contamination performance. The novel metabolites and enzymes identified in XT15 also indicated its strong promise as a precious biological resource. Thermophilic fermentation also offers great prospect for improving its yields and efficiencies. This remains a core aim for future work

Thermophilic fermentation of acetoin and 2,3-butanediol by a novel <it>Geobacillus</it> strain

Abstract Background Acetoin and 2,3-butanediol are two important biorefinery platform chemicals. They are currently fermented below 40°C using mesophilic strains, but the processes often suffer from bacterial contamination. Results This work reports the isolation and identification of a novel aerobic Geobacillus strain XT15 capable of producing both of these chemicals under elevated temperatures, thus reducing the risk of bacterial contamination. The optimum growth temperature was found to be between 45 and 55°C and the medium initial pH to be 8.0. In addition to glucose, galactose, mannitol, arabionose, and xylose were all acceptable substrates, enabling the potential use of cellulosic biomass as the feedstock. XT15 preferred organic nitrogen sources including corn steep liquor powder, a cheap by-product from corn wet-milling. At 55°C, 7.7 g/L of acetoin and 14.5 g/L of 2,3-butanediol could be obtained using corn steep liquor powder as a nitrogen source. Thirteen volatile products from the cultivation broth of XT15 were identified by gas chromatography–mass spectrometry. Acetoin, 2,3-butanediol, and their derivatives including a novel metabolite 2,3-dihydroxy-3-methylheptan-4-one, accounted for a total of about 96% of all the volatile products. In contrast, organic acids and other products were minor by-products. α-Acetolactate decarboxylase and acetoin:2,6-dichlorophenolindophenol oxidoreductase in XT15, the two key enzymes in acetoin metabolic pathway, were found to be both moderately thermophilic with the identical optimum temperature of 45°C. Conclusions Geobacillus sp. XT15 is the first naturally occurring thermophile excreting acetoin and/or 2,3-butanediol. This work has demonstrated the attractive prospect of developing it as an industrial strain in the thermophilic fermentation of acetoin and 2,3-butanediol with improved anti-contamination performance. The novel metabolites and enzymes identified in XT15 also indicated its strong promise as a precious biological resource. Thermophilic fermentation also offers great prospect for improving its yields and efficiencies. This remains a core aim for future work.</p

Study on the Evolution Law and the Orientation Criterion of a Plastic Zone in Rock Surrounding a Circular Roadway in a Three-Dimensional Non-Isobaric Stress Field

The original rock stress field is mainly divided into the σHZ-dominant stress field, the σZ-dominant stress field, and the σH-dominant stress field. Via theoretical analysis, the plastic zone morphology and the orientation of roadway surrounding rock under a three-dimensional stress field are studied in depth, and the theory is verified by numerical simulation. The results show that in the σHZ-dominant stress field, the plastic failure mode changes from elliptical to quasi-circular to butterfly, and the optimized angle range of the roadway orientation is determined by three principal stresses. In the σZ-dominant stress field, the shape of the plastic zone transforms from butterfly to ellipse, the optimized angle range of the roadway orientation is 50–90°, and the butterfly hidden danger zone is in the 0–50° range. In the σH-dominated stress field, the shape of the plastic zone transits from ellipse to butterfly. The optimized angle range of the roadway orientation is 0–40°, and 50–90° is the butterfly hidden danger zone

Study on the Evolution Law and the Orientation Criterion of a Plastic Zone in Rock Surrounding a Circular Roadway in a Three-Dimensional Non-Isobaric Stress Field

The original rock stress field is mainly divided into the &sigma;HZ-dominant stress field, the &sigma;Z-dominant stress field, and the &sigma;H-dominant stress field. Via theoretical analysis, the plastic zone morphology and the orientation of roadway surrounding rock under a three-dimensional stress field are studied in depth, and the theory is verified by numerical simulation. The results show that in the &sigma;HZ-dominant stress field, the plastic failure mode changes from elliptical to quasi-circular to butterfly, and the optimized angle range of the roadway orientation is determined by three principal stresses. In the &sigma;Z-dominant stress field, the shape of the plastic zone transforms from butterfly to ellipse, the optimized angle range of the roadway orientation is 50&ndash;90&deg;, and the butterfly hidden danger zone is in the 0&ndash;50&deg; range. In the &sigma;H-dominated stress field, the shape of the plastic zone transits from ellipse to butterfly. The optimized angle range of the roadway orientation is 0&ndash;40&deg;, and 50&ndash;90&deg; is the butterfly hidden danger zone