Oxidative stress is associated with the pathogenesis of carbon disulfide (CS2) induced polyneuropathy. The nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in protecting cells against oxidative stress. However, whether there exists a Nrf2-mediated antioxidative machinery in CS2-induced neuropathy has not been elucidated. In the present study, male wistar rats were randomly divided into three experimental groups and one control group. The rats in experimental groups were treated with CS2 by gavage at dosages of 200, 400 and 600mg/kg/day respectively, six times per week for 6 weeks. Nrf2-keap1 antioxidative pathway and p62-related kinase signaling in rat nerve tissues was examined by western blotting and real-time PCR. The results demonstrated that CS2 treatment resulted in Nrf2 translocation from the cytosol to the nucleus in rat spinal cords. In the meantime, the expression of antioxidative enzymes such as NAD(P)H quinone oxidoreductase-1, heme oxygenase-1, and glutamate-cysteine ligase was significantly increased. Furthermore, CS2 treatment increased the level of p62 and its phosphorylation status, while decreased the level of keap1. In addition, CS2 also lead to the activation of CAMKK2 and ULK1 kinase signaling in rat spinal cords and sciatic nerves. Taken together, our results indicated that CS2 intoxication was associated with the activation of Nrf2-ARE antioxidative machinery, which might play a protective role against CS2-induced neuronal damage.

Phytoplankton are major contributors to labile organic matter in the upper ocean. Diverse heterotrophic bacteria successively metabolize these labile compounds and drive elemental biogeochemical cycling. We investigated the bioavailability of Synechococcus-derived organic matter (SOM) by estuarine and coastal microbes during 180-day dark incubations. Variations in organic carbon, inorganic nutrients, fluorescent dissolved organic matter (FDOM), and total/active microbial communities were monitored. The entire incubations could be partitioned into three phases (labeled I, II, and III) based on the total organic carbon (TOC) consumption rates of 6.38-7.01, 0.53-0.64, and 0.10-0.13 μmol C L-1 day-1, respectively. This corresponded with accumulation processes of NH4 +, NO2 -, and NO3 -, respectively. One tryptophan-like (C1) and three humic-like (C2, C3, and C4) FDOM components were identified. The intensity variation of C1 followed bacterial growth activities, and C2, C3, and C4 displayed labile, semi-labile, and refractory DOM characteristics, respectively. Alphaproteobacteria, Gammaproteobacteria, Bacteroidetes, and Actinobacteria dominated the quickly consumed process of SOM (phase I) coupled with a substantial amount of NH4 + generation. Thaumarchaeota became an abundant population with the highest activities in phase II, especially in the free-living size-fraction, and these organisms could perform chemoautotroph processes through the ammonia oxidation. Microbial populations frequently found in the dark ocean, even the deep sea, became abundant during phase III, in which Nitrospinae/Nitrospirae obtained energy through nitrite oxidation. Our results shed light on the transformation of different biological availability of organic carbon by coastal microorganisms which coupled with the regeneration of different form of inorganic nitrogen.

Radiotherapy with heavy ions is considered advantageous compared to irradiation with photons due to the characteristics of the Braggs peak and the high linear energy transfer (LET) value. To understand the mechanisms of cellular responses to different LET values and dosages of heavy ion radiation, we analyzed the proteomic profiles of mouse embryo fibroblast MEF cells exposed to two doses from different LET values of heavy ion 12C. Total proteins were extracted from these cells and examined by Q Exactive with Liquid Chromatography (LC)-Electrospray Ionization (ESI) Tandem MS (MS/MS). Using bioinformatics approaches, differentially expressed proteins with 1.5 or 2.0-fold changes between different dosages of exposure were compared. With the higher the dosage and/or LET of ion irradiation, the worse response the cells were in terms of protein expression. For instance, compared to the control (0 Gy), 771 (20.2%) proteins in cells irradiated at 0.2 Gy of carbon-ion radiation with 12.6 keV/μm, 313 proteins (8.2%) in cells irradiated at 2 Gy of carbon-ion radiation with 12.6 keV/μm, and 243 proteins (6.4%) in cells irradiated at 2 Gy of carbon-ion radiation with 31.5 keV/μm exhibited changes of 1.5-fold or greater. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Munich Information Center for Protein Sequences (MIPS) analysis, and BioCarta analysis all indicated that RNA metabolic processes (RNA splicing, destabilization and deadenylation) and proteasome pathways may play key roles in the cellular response to heavy-ion irradiation. Proteasome pathways ranked highest among all biological processes associated with heavy carbon-ion irradiation. In addition, network analysis revealed that cellular pathways involving proteins such as Col1a1 and Fn1 continued to respond to high dosages of heavy-ion irradiation, suggesting that these pathways still protect cells against damage. However, pathways such as those involving Ikbkg1 responded better at lower dosages than at higher dosages, implying that cell damage would occur when the networks involving these proteins stop responding. Our investigation provides valuable proteomic information for elucidating the mechanism of biological effects induced by carbon ions in general.

Polyethylene glycol (PEG) non-covalent-functionalized multi-walled carbon nanotubes (MWCNT) membrane were prepared by vacuum filtration. The dispersion and stability of MWCNT non-covalent functionalized with PEG were all improved. TEM characterization and XPS quantitative analysis proved that the use of PEG to non-covalent functionalize MWCNT was successful. SEM image analysis confirmed that the pore size of PEG-MWCNT membrane was more concentrated and distributed in a narrower range of diameter. Contact angle measurement demonstrated that PEG non-covalent functionalization greatly enhanced the hydrophilicity of MWCNT membranes. The results of pure water flux showed that the PEG-MWCNT membranes could be categorized into low pressure membrane. PEG-MWCNT membrane had a better effect on the removal of humic acid (HA) and a lower TMP growth rate compared with a commercial 0.01-μm PVDF ultrafiltration membrane. During the filtration of bovine serum albumin (BSA), the antifouling ability of PEG-MWCNT membranes were obviously better than the raw MWCNT membranes. The TMP recovery rate of PEG-MWCNT membrane after cross flushing was 79.4%, while that of raw MWCNT-COOH and MWCNT membrane were only 14.9% and 28.3%, respectively. PEG non-covalent functionalization improved the antifouling ability of the raw MWCNT membranes and reduced the irreversible fouling, which effectively prolonged the service life of MWCNT membrane.

Heavy ion radiotherapy has shown great promise for cancer therapy. Understanding the cellular response mechanism to heavy ion radiation is required to explore measures of overcoming devastating side effects. Here, we performed a quantitative proteomic analysis to investigate the mechanism of carbon ion irradiation on human AHH-1 lymphoblastoid cells. We identified 4602 proteins and quantified 4569 proteins showing high coverage in the mitochondria. Data are available via ProteomeXchange with identifier PXD008351. After stringent filtering, 290 proteins were found to be significantly up-regulated and 16 proteins were down-regulated. Functional analysis revealed that these up-regulated proteins were enriched in the process of DNA damage repair, mitochondrial ribosome, and particularly mitochondrial respiratory chain, accounting for approximately 50% of the accumulated proteins. Bioinformatics and functional analysis demonstrated that these up-regulated mitochondrial respiratory chain proteins enhanced ATP production and simultaneously reactive oxygen species release. More importantly, increased reactive oxygen species led to secondary organelle injury and lagged DNA double-strand breaks. Consistently, the expression of antioxidant enzymes was up-regulated for free radical scavenging. The mechanism of lagged secondary injury originated from disturbances in the mitochondrial respiratory chain. Our results provided a novel target for cell self-repair against heavy ion radiation-induced cellular damage.

Corynebacterium glutamicum is an important industrial workhorse for production of amino acids and chemicals. Although recently developed genome editing technologies have advanced the rational genetic engineering of C. glutamicum, continuous genome evolution based on genetic mutators is still unavailable. To address this issue, the DNA replication and repair machinery of C. glutamicum was targeted in this study. DnaQ, the homolog of ϵ subunit of DNA polymerase III responsible for proofreading in Escherichia coli, was proven irrelevant to DNA replication fidelity in C. glutamicum. However, the histidinol phosphatase (PHP) domain of DnaE1, the α subunit of DNA polymerase III, was characterized as the key proofreading element and certain variants with PHP mutations allowed elevated spontaneous mutagenesis. Repression of the NucS-mediated post-replicative mismatch repair pathway or overexpression of newly screened NucS variants also impaired the DNA replication fidelity. Simultaneous interference with the DNA replication and repair machinery generated a binary genetic mutator capable of increasing the mutation rate by up to 2352-fold. The mutators facilitated rapid evolutionary engineering of C. glutamicum to acquire stress tolerance and protein overproduction phenotypes. This study provides efficient tools for evolutionary engineering of C. glutamicum and could inspire the development of mutagenesis strategy for other microbial hosts.

Plant hemoglobin shows great potential as a food additive to circumvent the controversy of using animal materials. Microbial fermentation with engineered microorganisms is considered as a promising strategy for sustainable production of hemoglobin. As an endotoxin-free and GRAS (generally regarded as safe) bacterium, Corynebacterium glutamicum is an attractive host for hemoglobin biosynthesis.

Heme is an important tetrapyrrole compound, and has been widely applied in food and medicine industries. Although microbial production of heme has been developed with metabolic engineering strategies during the past 20 years, the production levels are relatively low due to the multistep enzymatic processes and complicated regulatory mechanisms of microbes. Previous studies mainly adopted the strategies of strengthening precursor supply and product transportation to engineer microbes for improving heme biosynthesis. Few studies focused on the engineering and screening of efficient enzymes involved in heme biosynthesis. Herein, a growth-coupled, high-throughput selection platform based on the detoxification of Zinc-protoporphyrin IX (an analogue of heme) was developed and applied to directed evolution of coproporphyrin ferrochelatase, catalyzing the insertion of metal ions into porphyrin ring to generate heme or other tetrapyrrole compounds. A mutant with 3.03-fold increase in k cat/K M was selected. Finally, growth-coupled directed evolution of another three key enzymes involved in heme biosynthesis was tested by using this selection platform. The growth-coupled selection platform developed here can be a simple and effective strategy for directed evolution of the enzymes involved in the biosynthesis of heme or other tetrapyrrole compounds.

Viral abundance in deep-sea environments is high. However, the biological, ecological and biogeochemical roles of viruses in the deep sea are under debate. In the present study, microcosm incubations of deep-sea bacterioplankton (2,000 m deep) with normal and reduced pressure of viral lysis were conducted in the western Pacific Ocean. We observed a negative effect of viruses on prokaryotic abundance, indicating the top-down control of bacterioplankton by virioplankton in the deep-sea. The decreased bacterial diversity and a different bacterial community structure with diluted viruses indicate that viruses are sustaining a diverse microbial community in deep-sea environments. Network analysis showed that relieving viral pressure decreased the complexity and clustering coefficients but increased the proportion of positive correlations for the potentially active bacterial community, which suggests that viruses impact deep-sea bacterioplankton interactions. Our study provides experimental evidences of the crucial role of viruses in microbial ecology and biogeochemistry in deep-sea ecosystems.

As the most abundant and genetically diverse biological entities, viruses significantly influence ecological, biogeographical and evolutionary processes in the ocean. However, the biogeography of marine viruses and the drivers shaping viral community are unclear. Here, the biogeographic patterns of T4-like viruses and the relative impacts of deterministic (environmental selection) and dispersal (spatial distance) processes were investigated in the northern South China Sea. The dominant viral operational taxonomic units were affiliated with previously defined Marine, Estuary, Lake and Paddy Groups. A clear viral biogeographic pattern was observed along the environmental gradient from the estuary to open sea. Marine Groups I and IV had a wide geographical distribution, whereas Marine Groups II, III and V were abundant in lower-salinity continental or eutrophic environments. A significant distance-decay pattern was noted for the T4-like viral community, especially for those infecting cyanobacteria. Both deterministic and dispersal processes influenced viral community assembly, although environmental selection (e.g. temperature, salinity, bacterial abundance and community, etc.) had a greater impact than spatial distance. Network analysis confirmed the strong association between viral and bacterial community composition, and suggested a diverse ecological relationship (e.g. lysis, co-infection or mutualistic) between and within viruses and their potential bacterial hosts.

Membranes for organic solvent nanofiltration (OSN) or solvent-resistant nanofiltration (SRNF) offer unprecedented opportunities for highly efficient and cost-competitive solvent recovery in the pharmaceutical industry. Here, we describe small-flake graphene oxide (SFGO) membranes for high-performance OSN applications. Our strategy exploits lateral dimension control to engineer shorter and less tortuous transport pathways for solvent molecules. By using La3+ as a cross-linker and spacer for intercalation, the SFGO membrane selective layer was stabilized, and size-dependent ultrafast selective molecular transport was achieved. The methanol permeance was up to 2.9-fold higher than its large-flake GO (LFGO) counterpart, with high selectivity toward three organic dyes. More importantly, the SFGO-La3+ membrane demonstrated robust stability for at least 24 hours under hydrodynamic stresses that are representative of realistic OSN operating conditions. These desirable attributes stem from the La3+ cross-linking, which forms uniquely strong coordination bonds with oxygen-containing functional groups of SFGO. Other cations were found to be ineffective.

Pyroptosis, a form of programmed cell death, that plays a significant role in the occurrence and progression of tumors, has been frequently investigated recently. However, the prognostic significance and therapeutic value of pyroptosis in glioma remain undetermined. In this research, we revealed the relationship of pyroptosis-related genes to glioma by analyzing whole transcriptome data from The Cancer Genome Atlas (TCGA) dataset serving as the training set and the Chinese Glioma Genome Atlas (CGGA) dataset serving as the validation set. We identified two subgroups of glioma patients with disparate prognostic and clinical features by performing consensus clustering analysis on nineteen pyroptosis-related genes that were differentially expressed between glioma and normal brain tissues. We further derived a risk signature, using eleven pyroptosis-related genes, that was demonstrated to be an independent prognostic factor for glioma. Furthermore, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to implement functional analysis of our gene set, and the results were closely related to immune and inflammatory responses in accordance with the characteristics of pyroptosis. Moreover, Gene Set Enrichment Analysis (GSEA) results showed that that the high-risk group exhibited enriched characteristics of malignant tumors in accordance with its poor prognosis. Next, we analyzed different immune cell infiltration between the two risk groups using ssGSEA. Finally, CASP1 was identified as a core gene, so we subsequently selected an inhibitor targeting CASP1 and simulated molecular docking. In addition, the inhibitory effect of belnacasan on glioma was verified at the cellular level. In conclusion, pyroptosis-related genes are of great significance for performing prognostic stratification and developing treatment strategies for glioma.

NiMo-based nanostructures are among the most active hydrogen evolution reaction (HER) catalysts under an alkaline environment due to their strong water dissociation ability. However, these nanostructures are vulnerable to the destructive effects of H2 production, especially at industry-standard current densities. Therefore, developing a strategy to improve their mechanical strength while maintaining or even further increasing the activity of these nanocatalysts is of great interest to both the research and industrial communities. Here, a hierarchical interconnected NiMoN (HW-NiMoN-2h) with a nanorod-nanowire morphology was synthesized based on a rational combination of hydrothermal and water bath processes. HW-NiMoN-2h is found to exhibit excellent HER activity due to the accomodation of abundant active sites on its hierarchical morphology, in which nanowires connect free-standing nanorods, concurrently strengthening its structural stability to withstand H2 production at 1 A cm-2. Seawater is an attractive feedstock for water electrolysis since H2 generation and water desalination can be addressed simultaneously in a single process. The HER performance of HW-NiMoN-2h in alkaline seawater suggests that the presence of Na+ ions interferes with the reation kinetics, thus lowering its activity slightly. However, benefiting from its hierarchical and interconnected characteristics, HW-NiMoN-2h is found to deliver outstanding HER activity of 1 A cm-2 at 130 mV overpotential and to exhibit excellent stability at 1 A cm-2 over 70 h in 1 M KOH seawater.

Pervasive environmental contamination due to the uncontrolled dispersal of 2,4-dinitrotoluene (2,4-DNT) represents a substantial global health risk, demanding urgent intervention for the removal of this detrimental compound from affected sites and the promotion of ecological restoration. Conventional methodologies, however, are energy-intensive, susceptible to secondary pollution, and may inadvertently increase carbon emissions. In this study, a 2,4-DNT degradation module is designed, assembled, and validated in rice plants. Consequently, the modified rice plants acquire the ability to counteract the phytotoxicity of 2,4-DNT. The most significant finding of this study is that these modified rice plants can completely degrade 2,4-DNT into innocuous substances and subsequently introduce them into the tricarboxylic acid cycle. Further, research reveals that the modified rice plants enable the rapid phytoremediation of 2,4-DNT-contaminated soil. This innovative, eco-friendly phytoremediation approach for dinitrotoluene-contaminated soil and water demonstrates significant potential across diverse regions, substantially contributing to carbon neutrality and sustainable development objectives by repurposing carbon and energy from organic contaminants.

Photosynthesis measurements are traditionally taken under steady-state conditions; however, leaves in crop fields experience frequent fluctuations in light and take time to respond. This slow response reduces the efficiency of carbon assimilation. Transitions from low to high light require photosynthetic induction, including the activation of Rubisco and the opening of stomata, whereas transitions from high to low light require the relaxation of dissipative energy processes, collectively known as non-photochemical quenching (NPQ). Previous attempts to assess the impact of these delays on net carbon assimilation have used simplified models of crop canopies, limiting the accuracy of predictions. Here, we use ray tracing to predict the spatial and temporal dynamics of lighting for a rendered mature Glycine max (soybean) canopy to review the relative importance of these delays on net cumulative assimilation over the course of both a sunny and a cloudy summer day. Combined limitations result in a 13% reduction in crop carbon assimilation on both sunny and cloudy days, with induction being more important on cloudy than on sunny days. Genetic variation in NPQ relaxation rates and photosynthetic induction in parental lines of a soybean nested association mapping (NAM) population was assessed. Short-term NPQ relaxation (<30 min) showed little variation across the NAM lines, but substantial variation was found in the speeds of photosynthetic induction, attributable to Rubisco activation. Over the course of a sunny and an intermittently cloudy day these would translate to substantial differences in total crop carbon assimilation. These findings suggest an unexplored potential for breeding improved photosynthetic potential in our major crops.

CD44 is associated with a variety of human diseases and plays a potential role in tumorigenesis, however, the mechanism of its role in osteosarcoma remains unclear. We analyzed the expression of CD44 in the Cancer Genome Atlas (TCGA) and genotype-tissue expression pan-cancer data and found that it was highly expressed in most tumors, including sarcoma. The expression of CD44 in osteosarcoma cell lines was higher than that in human osteoblast cell line in the results of the Western blot and Immunohistochemical staining assay. The results of colony formation assay and CCK 8 showed that CD44 improved the proliferation capacity of osteosarcoma cells, transwell assay and wound healing assay showed that CD44 improved the migration capacity of osteosarcoma cells. Further studies revealed that CD44 exerts its influence on the biological behavior of osteosarcoma cells through the Wnt/β-catenin signaling pathway. Since CD44 may be involved in the immune response, we analyzed the correlation between CD44 expression and immune cell infiltration in TCGA database using the previous cluster analyzer R software package, TIMER2.0 database and, GEPIA2 database, and found its involvement in the immune infiltration of osteosarcoma. Therefore, we believe that CD44 could be a potential target for the treatment of osteosarcoma patients and may be a candidate biomarker for immune infiltration-related prognosis.

2,3-Butanediol (BD) is considered as one of the key platform chemicals used in a variety of industrial applications. It is crucial to find an efficient sugar-utilizing strain and feasible carbon source for the economical production of BD.

5-Aminolevulinic acid (5-ALA) is a promising biostimulant, feed nutrient, and photodynamic drug with wide applications in modern agriculture and therapy. Considering the complexity and low yield of chemical synthesis methods, bioproduction of 5-ALA has drawn intensive attention recently. However, the present bioproduction processes use refined glucose as the main carbon source and the production level still needs further enhancement.

Adipose derived mesenchymal stem cells (ADMSCs), carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4) in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway.

We investigated ATP-binding cassette transporters A1/G1 expression and function in mediating cholesterol efflux by examining the macrophages of cigarette-smoking patients with coronary artery disease (CAD) before and after smoking abstinence. Peripheral blood monocyte cells were collected from nonsmokers (n = 17), non-CAD (NCAD) smokers (n = 35), and CAD smokers (n = 32) before and after 3 months of smoking cessation. We found that the ABCA1 expression level was lower in macrophages from NCAD and CAD smokers than from nonsmokers at baseline. The ABCA1 function of mediating cholesterol efflux was reduced in NCAD and CAD smokers as compared with nonsmokers. After 3 months of smoking cessation, ABCA1 expression and function were improved in CAD smokers. However, ABCG1 expression and function did not change after smoking cessation. Furthermore, ABCA1 expression was inhibited by tar in human acute monocytic leukemia cell line THP-1-derived macrophages through the inhibition of liver X receptors. Nicotine and carbon monoxide did not inhibit ABCA1 expression. Our results indicate that chronic cigarette smoking impaired ABCA1-mediated cholesterol efflux in macrophages and that tobacco abstinence reversed the function and expression of ABCA1, especially in CAD patients. It was tobacco tar, rather than nicotine or carbon monoxide, that played a major role in the tobacco-induced disturbance of cellular cholesterol homeostasis.