ABSTRACT
Bacterial small molecule metabolites such as adenosine-diphosphate-d-glycero-ß-d-manno-heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STTR5 motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but also cytidine-diphosphate (CDP)- and uridine-diphosphate (UDP)-heptose. Both CDP- and UDP-heptoses are agonists that trigger stronger alpha-protein kinase 1 (ALPK1)-dependent immune responses than ADP-heptose in human and mouse cells and mice. We also produced ADP-heptose in archaea and verified its innate immune agonist functions. Hence, the ß-d-manno-heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.
Subject(s)
Heptoses , Nucleotidyltransferases , Pathogen-Associated Molecular Pattern Molecules , Animals , Humans , Mice , Amino Acid Motifs , Archaea/enzymology , Bacteria/enzymology , Bacteria/metabolism , Heptoses/biosynthesis , Heptoses/immunology , Immunity, Innate , Nucleotidyltransferases/chemistry , Nucleotidyltransferases/classification , Nucleotidyltransferases/genetics , Pathogen-Associated Molecular Pattern Molecules/immunology , Pathogen-Associated Molecular Pattern Molecules/metabolism , Protein Kinases/metabolism , Viruses/enzymologyABSTRACT
2D ferroelectric materials have attracted extensive research interest due to potential applications in nonvolatile memory, nanoelectronics and optoelectronics. However, the available 2D ferroelectric materials are scarce and most of them are limited by the uncontrollable preparation. Herein, a novel 2D ferroelectric material AgCrS2 is reported that are controllably synthesized in large-scale via salt-assist chemical vapor deposition growth. By tuning the growth temperature from 800 to 900 °C, the thickness of AgCrS2 nanosheets can be precisely modulated from 2.1 to 40 nm. Structural and nonlinear optical characterizations demonstrate that AgCrS2 nanosheet crystallizes in a non-centrosymmetric structure with high crystallinity and remarkable air stability. As a result, AgCrS2 of various thicknesses display robust ferroelectric polarization in both in-plane (IP) and out-of-plane (OOP) directions with strong intercorrelation and high ferroelectric phase transition temperature (682 K). Theoretical calculations suggest that the ferroelectricity in AgCrS2 originates from the displacement of Ag atoms in AgS4 tetrahedrons, which changes the dipole moment alignment. Moreover, ferroelectric switching is demonstrated in both lateral and vertical AgCrS2 devices, which exhibit exotic nonvolatile memory behavior with distinct high and low resistance states. This study expands the scope of 2D ferroelectric materials and facilitates the ferroelectric-based nonvolatile memory applications.
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Carbon dots (CDs) have rapidly emerged as a new family of carbon-based nanomaterials since their initial discovery two decades ago. Numerous appealing properties, such as precursor and synthesis process flexibility, tunable photoluminescence, and good biocompatibility, have enabled their widespread applications in sensing, catalysis, energy, and biomedical fields. As the field expands, notable efforts have recently focused on mechanistically elucidating the structural formation and optical behavior of CDs. However, the absence of "clean" CDs presents a major obstacle to achieving a solid understanding of these aspects. Often, the claimed CDs are, in fact, a mixture of small molecules, oligomers, nano-sized aggregates, or even microparticles. Such coexistence of impurities markedly impacts the physicochemical properties of resulting CD-based mixtures, hampering the resolution of key mechanistic questions. Here, we aim to address this fundamental shortcoming of the field, going beyond the customary focus of the existing reviews that predominantly cover synthesis, optical performance, and application prospects. We begin with an overview of CD synthesis and then thoroughly examine the purification methods, including filtration, dialysis, electrophoresis, and chromatography. The insights provided here will guide the researchers towards obtaining high-quality CDs, employing proper combinations of available tools, and ultimately paving the way for more demanding applications.
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Background: The biochemical and genetic characteristics of four very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) patients, clarifying their pathogenic genetic factors and evaluating the application value of genetic diagnosis in the early diagnosis of VLCADD, are reported and discussed in this article. Methods: Patients underwent blood tandem mass spectrometry (MS/MS), urine gas chromatography (GC/MS), and high-throughput sequencing technology. New variants were analyzed for pathogenicity using bioinformatics software. Swiss-PdbViewer software was used to predict the effect of variants on the structure of the very-long-chain acyl-CoA dehydrogenase (VLCAD) protein. Result: A total of four VLCADD patients were diagnosed. They revealed elevated levels of C14, C14:1, C14:2, C14:1/C2, C14:1/C10, and C14:1/C12:1. Two patients were early-onset neonatal cases and died during infancy and the neonatal period, respectively. Seven kinds of variants were detected, including four novel variants. Bioinformatics software revealed that the variants were harmful, and the Swiss-PdbViewer results suggest that variation affects protein conformation. Conclusion: This study identified four novel ACADVL gene variants. These findings contribute to the understanding of the genetic basis and pathogenesis of VLCADD. Meanwhile, the study enriches the genetic mutation spectrum and the correlation between genotypes and phenotypes of VLCADD, indicating that genetic diagnosis plays an essential role in the early diagnosis and treatment of VLCADD.
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To elucidate the mechanism of biochar addition on carbon and nitrogen retention during distilled grain (DGW) composting, this study investigated the losses of carbon and nitrogen and functional genes related to carbon and nitrogen metabolisms between biochar-treated and control composts. The addition of biochar significantly increased carbon and nitrogen retention by 13.5% and 33.8%, respectively. The difference in core carbon metabolism genes indicated that biochar addition inhibited CO2 release and promoted carbon fixation during the later composting phase, leading to improved carbon retention. Nitrogen metabolism analysis indicated that biochar addition suppressed early-phase ammoniation and late-phase denitrification and promoted nitrification and ammonia assimilation during the later stages of composting, thereby preserving nitrogen. During the later composting phase, biochar addition enhanced carbon-nitrogen coupling metabolism activity, leading to the synchronous retention of carbon and nitrogen. These findings elucidate the mechanism of biochar addition on carbon and nitrogen retention during DGW composting.
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Macrophages show high plasticity and play a vital role in the progression of metabolic dysfunction-associated steatohepatitis (MASH). X-box binding protein 1 (XBP1), a key sensor of the unfolded protein response, can modulate macrophage-mediated pro-inflammatory responses in the pathogenesis of MASH. However, how XBP1 influences macrophage plasticity and promotes MASH progression remains unclear. Herein, we formulated an Xbp1 siRNA delivery system based on folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles (FT@XBP1) to explore the precise role of macrophage-specific Xbp1 deficiency in the progression of MASH. FT@XBP1 was specifically internalized into hepatic macrophages and subsequently inhibited the expression of spliced XBP1 both in vitro and in vivo. It promoted M1-phenotype macrophage repolarization to M2 macrophages, reduced the release of pro-inflammatory factors, and alleviated hepatic steatosis, liver injury, and fibrosis in mice with fat-, fructose- and cholesterol-rich diet-induced MASH. Mechanistically, FT@XBP1 promoted macrophage polarization toward the M2 phenotype and enhanced the release of exosomes that could inhibit the activation of hepatic stellate cells. A promising macrophage-targeted siRNA delivery system was revealed to pave a promising strategy in the treatment of MASH.
Subject(s)
Folic Acid , Macrophages , RNA, Small Interfering , X-Box Binding Protein 1 , Animals , Male , Mice , Endoplasmic Reticulum Stress/drug effects , Fatty Liver/metabolism , Folic Acid/chemistry , Macrophages/metabolism , Macrophages/drug effects , Mice, Inbred C57BL , Nanoparticles/chemistry , X-Box Binding Protein 1/metabolismABSTRACT
The detrimental growth of water pollutants such as heavy metals has become a life-threatening problem in the modern era. Challenges remain in the development of rapid and accurate methods for detecting pentavalent arsenic [As(V)] in environmental water. The octahedral Mn3O4 nanoparticles (NPs) did not display excellent laccase-mimicking catalytic activity, whereas the adsorbed As(V) on the surface significantly enhanced the catalytic activity. Meanwhile, the quinone imine generated from the substrates 2,4-dichlorophenol (2,4-DP) and 4-aminoantipyrine (4-AAP) catalyzed by octahedral Mn3O4 NPs further quenched the carbon dots fluorescence. Thus, it is possible to establish a fast and accurate dual-mode sensor for detecting As(V). The developed dual-mode method of As(V) detection has good sensitivity and selectivity. The limit of detection for As(V) in colorimetric mode is 6.96 µg·L-1, whereas in the fluorescent mode, it is as low as 2.56 µg·L-1. Moreover, the detection data obtained by the dual-mode method can be validated by each other, thereby ensuring the dependability of the sensing system. The constructed dual-mode method with merits of sensitivity, speed and accuracy can offer a powerful tool for As(V) detection in environmental water. Furthermore, the application of laccase-mimicking activity in dual-mode detection provides new strategies for other environmental hazard detection.
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BACKGROUND: Soteria houses and peer respites, collectively called Healing Houses, are alternatives to psychiatric hospitalisation. AIMS: The aim of this research is to review Healing Houses in relation to design characteristics (architectural and service), sustainability and development opportunities and barriers. METHODS: This systematic review followed a PROSPERO protocol (CRD42022378089). Articles were identified from journal database searches, hand searching websites, Google Scholar searches, expert consultation and backwards and forward citation searches. RESULTS: Eight hundred and forty-nine documents were screened in three languages (English, German and Hebrew) and 45 documents were included from seven countries. The review highlights 11 architectural design characteristics (atmosphere, size, soft room, history, location, outdoor space, cleanliness, interior design, facilities, staff only areas and accessibility), six service design characteristics (guiding principles, living and working together, consensual treatment, staff, supporting personal meaning making and power), five opportunities (outcomes, human rights, economics, hospitalization and underserved) and four types of barriers (clinical, economic and regulatory, societal and ideological). The primary sustainability issue was long-term funding. CONCLUSION: Future research should focus on operationalizing a "home-like" atmosphere and the impact of design features such as green spaces on wellbeing of staff and service users. Future research could also produce design guidelines for Healing Houses.
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OBJECTIVE: The aim of this study was to establish a simple and sensitive high-performance liquid chromatography method for therapeutic drug monitoring of venetoclax (VEN) and optimize regimens. METHODS: The analysis required the extraction of a 50â µl plasma sample and the precipitation of proteins using acetonitrile extraction. The chromatographic method employed a mobile phase of acetonitrile: 0.5% KH2PO4 (pH 3.5) (60/40, v/v) on a Diamond C18 (4.6â mmâ ×â 250â mm, 5â µm) column at a flow rate of 1.0â ml/min. The quantitative method was validated based on standards described in 'Bioanalytical Method Validation: Guidance for Industry' published by the US Food and Drug Administration (FDA). RESULTS: The calibration curve was linear (R2â =â 0.9998) over the range of 75-4800â ng/ml, with limits of quantification of 25â ng/ml. The coefficients of intraday and interday validation, specificity, recovery, and stability all met the criteria of FDA guidance. The method was successfully applied to analyze VEN concentrations in 30 cases of acute myeloid leukemia patients. The peak concentration (Cmax) was 1881.19â ±â 756.61â ng/ml, while the trough concentration (Cmin) was 1212.69â ±â 767.92â ng/ml in acute myeloid leukemia patients. CONCLUSION: Our study establishes a simple, precise, and sensitive high-performance liquid chromatography method for monitoring VEN and confirms its applicability for therapeutic drug monitoring of VEN in hematological cancers.
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OBJECTIVE: Mucinous breast cancer (MBC) is a kind of breast cancer (BC), which is rare in clinic, mainly for women, because of the low incidence rate, so there is no unified standard treatment protocol. Elderly patients have a poor prognosis due to their combined comorbidities. This study aims to investigate the effect of surgery and chemoradiotherapy on the prognosis of elderly female MBC patients and construct nomograms for predicting the OS and CSS in elderly female MBC patients. METHODS: Data for female MBC patients over 65 years are obtained from the Surveillance, Epidemiology and End Results (SEER) database, patients were divided into two groups: the training set and the validation set. External validation data of the prediction model were provided by Kunming Hospital of Traditional Chinese Medicine. We used Cox regression modeling, which was used to identify independent risk factors affecting patient prognosis. After avoiding confounding bias according to the multifactorial Cox regression model, we used these screened statistically significant results to construct column-line plots. The performance of the model was tested using the consistency index (c-index), the calibration curve, and the area under the operating characteristic curve of the receiver (AUC). Subsequently, we used decision curve analysis (DCA) to examine the potential clinical value of our nomograms. RESULTS: A total of 8103 elderly MBC female patients were extracted from the database SEER and were assigned to the training and validation set, randomly. A total of 83 patients from Kunming Hospital of Traditional Chinese Medicine were used in the external verification set. After multifactorial Cox regression analysis, we found that age, race, T-stage, M-stage, surgical approach, radiotherapy, and tumor size were independent risk factors for OS in elderly MBC patients. Similarly, independent risk factors of CSS included age, marital status, N stage, M stage, surgical approach, chemotherapy, and tumor size. The C-index for the OS training, validation, and external verification set were 0.731 (95%CI 0.715-0.747), 0.738 (95%CI 0.724-0.752), and 0.809 (95%CI 0.731-0.8874). The C-index of the training set, the validation set, and external verification set for CSS were 0.786 (95%CI 0.747-0.825), 0.776 (95%CI 0.737-0.815), and 0.84 (95%CI0.754-0.926), respectively. The AUC, calibration curves and DCA also showed good accuracy. CONCLUSIONS: In this study, we construct a new nomogram to predict the prognosis of elderly patients with MBC. The nomograms have undergone internal and external validation and have been confirmed to have good clinical applicability. At the same time, we found that for elderly female MBC patients, surgery and radiotherapy significantly benefit their survival, but chemotherapy is not conducive to patient survival.
Subject(s)
Adenocarcinoma, Mucinous , Breast Neoplasms , Nomograms , SEER Program , Humans , Female , Breast Neoplasms/therapy , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Aged , Retrospective Studies , SEER Program/statistics & numerical data , China/epidemiology , Adenocarcinoma, Mucinous/therapy , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/mortality , Prognosis , Aged, 80 and over , Risk Factors , Chemoradiotherapy/methodsABSTRACT
Thermophilic semi-continuous composting (TSC) is effective for kitchen waste (KW) treatment, but large amounts of NH3-rich odorous gas are generated. This study proposes a TSC-biofiltration (BF) two-stage process. Compost from the front-end TSC was used as the packing material in the BF to remove NH3 from the exhaust gas. The BF process was effective in removing up to 83.7 % of NH3, and the NH3 content was reduced to < 8 ppm. Seven days of BF improved the quality of the product from TSC by enhancing the germination index to 134.6 %, 36.5 % higher than that in the aerated-only group. Microbial community analysis revealed rapid proliferation and eventual dominance in the BF of members related to compost maturation and the nitrogen cycle from Actinobacteria, Proteobacteria, Chloroflexi, and Bacteroidetes. The results suggest that the TSC-BF two-stage process is effective in reducing NH3 emissions from TSC and improving compost quality.
Subject(s)
Ammonia , Composting , Fertilizers , Composting/methods , Filtration/methods , Refuse Disposal/methods , Temperature , Soil/chemistry , Bacteria/metabolismABSTRACT
Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1.
Subject(s)
Dioxygenases , Diterpenes , Epoxy Compounds , Phenanthrenes , Podocytes , Zonula Occludens-1 Protein , Podocytes/metabolism , Podocytes/drug effects , Podocytes/pathology , Zonula Occludens-1 Protein/metabolism , Phenanthrenes/pharmacology , Diterpenes/pharmacology , Epoxy Compounds/pharmacology , Dioxygenases/metabolism , Animals , DNA-Binding Proteins/metabolism , Mice , Proto-Oncogene Proteins/metabolism , Permeability/drug effects , Humans , DNA Methylation/drug effectsABSTRACT
The aim of this study was to explore the formation of volatile lipid oxidation products by the lipoxygenase (LOX)-hydroperoxide lyase (HPL)-mediated pathway in oat, barley and soy bean. LOX activity was found only in barley and soy bean samples, but the lipase and HPL activity was detected in all samples. HPL showed particularly high activity with 13-hydroperoxides, while the activity was quite low when using 9-hydroperoxides, especially in the oat and barley. The optimum pH for HPL in different samples was similar, i.e., pH 6-7. In this condition, the volatile compounds formed dramatically with aldehydes and furans as the dominant products. Furthermore, a remarkable enzymatic degradation of lipids occurred during the preparation of food models with highly refined rapeseed oil (RO) and rapeseed oil fatty acid (ROFA) emulsions, where the ROFAs were more prone to oxidation than RO. This study shows the significance of lipid-degrading enzymes in plant-food flavour formation.
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Methylation of microRNAs (miRNAs) is a post-transcriptional modification that affects miRNA activity by altering the specificity of miRNAs to target mRNAs. Abnormal methylation of miRNAs in cancer suggests their potential as a tumor marker. However, the traditional methylated miRNA detection mainly includes mass spectrometry, sequencing and others; complex procedures and reliance on large instruments greatly limit their application in point-of-care testing (POCT). Based on this, we developed DNAzyme-RCA-based gold nanoparticle (AuNP) colorimetric and lateral flow dipstick (LFD) assays to achieve convenient detection of exosomal 5-methylcytosine miRNA-21 (m5C-miRNA-21) for the first time. The two assays achieved specific recognition and linear amplification of m5C-miRNA-21 through the DNAzyme triggered RCA reaction and color output with low background interference through AuNP aggregation induced by base complementary pairing. The lowest concentration of m5C-miRNA-21 visible to the naked eye of the two assays can reach 1 pM and 0.1 pM, respectively. Detection of exosomal m5C-miRNA-21 in clinical blood samples showed that the expression level of m5C-miRNA-21 in colorectal cancer patients was significantly higher than that in healthy individuals. This approach not only demonstrates a new strategy for the detection of colorectal cancer but also provides a reference for the development of novel diagnostic tools for other miRNA methylation-related diseases.
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Liver fibrosis, a progressive process of fibrous scarring, results from the accumulation of extracellular matrix proteins (ECM). If left untreated, it often progresses to diseases such as cirrhosis and hepatocellular carcinoma. Lycorine, a natural alkaloid derived from medicinal plants, has shown diverse bioactivities by targeting JAK2/STAT3 signaling, but its pharmacological effects and potential molecular mechanisms in liver fibrosis remains largely unexplored. The purpose of this study is to elucidate the pharmacological activity and molecular mechanism of lycorine in anti-hepatic fibrosis. Findings indicate that lycorine significantly inhibited hepatic stellate cells (HSCs) activation by reducing the expression of α-SMA and collagen-1. In vivo, lycorine treatment alleviated carbon tetrachloride (CCl4) -induced mice liver fibrosis, improving liver function, decreasing ECM deposition, and inhibiting fibrosis-related markers' expression. Mechanistically, it was found that lycorine exerts protective activity through the JAK2/STAT3 and PI3K/AKT signaling pathways, as evidenced by transcriptome sequencing technology and small molecule inhibitors. These results underscore lycorine's potential as a therapeutic drug for liver fibrosis.
Subject(s)
Amaryllidaceae Alkaloids , Carbon Tetrachloride , Hepatic Stellate Cells , Janus Kinase 2 , Liver Cirrhosis , Phenanthridines , Proto-Oncogene Proteins c-akt , STAT3 Transcription Factor , Signal Transduction , Animals , Janus Kinase 2/metabolism , STAT3 Transcription Factor/metabolism , Amaryllidaceae Alkaloids/pharmacology , Carbon Tetrachloride/toxicity , Signal Transduction/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Mice , Male , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Liver Cirrhosis/drug therapy , Liver Cirrhosis/chemically induced , Liver Cirrhosis/pathology , Liver Cirrhosis/metabolism , Phenanthridines/pharmacology , Phenanthridines/therapeutic use , Phosphatidylinositol 3-Kinases/metabolism , Mice, Inbred C57BL , Cell LineABSTRACT
Anaerobic digestion (AD) is an effective and applicable technology for treating organic wastes to recover bioenergy, but it is limited by various drawbacks, such as long start-up time for establishing a stable process, the toxicity of accumulated volatile fatty acids and ammonia nitrogen to methanogens resulting in extremely low biogas productivities, and a large amount of impurities in biogas for upgrading thereafter with high cost. Microbial electrolysis cell (MEC) is a device developed for electrosynthesis from organic wastes by electroactive microorganisms, but MEC alone is not practical for production at large scales. When AD is integrated with MEC, not only can biogas production be enhanced substantially, but also upgrading of the biogas product performed in situ. In this critical review, the state-of-the-art progress in developing AD-MEC systems is commented, and fundamentals underlying methanogenesis and bioelectrochemical reactions, technological innovations with electrode materials and configurations, designs and applications of AD-MEC systems, and strategies for their enhancement, such as driving the MEC device by electricity that is generated by burning the biogas to improve their energy efficiencies, are specifically addressed. Moreover, perspectives and challenges for the scale up of AD-MEC systems are highlighted for in-depth studies in the future to further improve their performance.
Subject(s)
Bioelectric Energy Sources , Biofuels , Electrolysis , Anaerobiosis , Bioelectric Energy Sources/microbiology , Bioreactors , Methane/metabolismABSTRACT
Using hybrid density functional theory calculations, we systematically study the biaxial strain and electric field modulated electronic properties of g-ZnO/SnS2, g-ZnO/SnSe2, and g-ZnO/SnSSe S-scheme van der Waals heterostructures (vdWHs). g-ZnO/SnS2 and g-ZnO/SnSSe are found to be promising photocatalysts for water splitting with high solar-to-hydrogen efficiencies, even under acidic, alkaline, and high-stress conditions. The strain effect on the bandgaps of g-ZnO/SnXY is explained in detail according to the correlation between geometry structure and orbital hybridization of SnXY, which could help understand the strain-induced band structure evolutions in other SnXY (X, Y = S, Se)-based vdWHs. It is surprising that under an external electric field, g-ZnO/SnS2, g-ZnO/SnSe2, and g-ZnO/SnSSe can offer the occupied nearly free-electron (NFE) states. In many materials, NFE states are usually unoccupied and is not conducive to the charge transport. The NFE state in g-ZnO/SnSe2 is the most sensitive to the electric field and might be promising electron transport channel in nanoelectronic devices. g-ZnO/SnSe2 might also have application potential in gas sensors and high-temperature superconductors.
ABSTRACT
BACKGROUND: The production of succinic acid (SA) from biomass has attracted worldwide interest. Saccharomyces cerevisiae is preferred for SA production due to its strong tolerance to low pH conditions, ease of genetic manipulation, and extensive application in industrial processes. However, when compared with bacterial producers, the SA titers and productivities achieved by engineered S. cerevisiae strains were relatively low. To develop efficient SA-producing strains, it's necessary to clearly understand how S. cerevisiae cells respond to SA. RESULTS: In this study, we cultivated five S. cerevisiae strains with different genetic backgrounds under different concentrations of SA. Among them, KF7 and NBRC1958 demonstrated high tolerance to SA, whereas NBRC2018 displayed the least tolerance. Therefore, these three strains were chosen to study how S. cerevisiae responds to SA. Under a concentration of 20 g/L SA, only a few differentially expressed genes were observed in three strains. At the higher concentration of 60 g/L SA, the response mechanisms of the three strains diverged notably. For KF7, genes involved in the glyoxylate cycle were significantly downregulated, whereas genes involved in gluconeogenesis, the pentose phosphate pathway, protein folding, and meiosis were significantly upregulated. For NBRC1958, genes related to the biosynthesis of vitamin B6, thiamin, and purine were significantly downregulated, whereas genes related to protein folding, toxin efflux, and cell wall remodeling were significantly upregulated. For NBRC2018, there was a significant upregulation of genes connected to the pentose phosphate pathway, gluconeogenesis, fatty acid utilization, and protein folding, except for the small heat shock protein gene HSP26. Overexpression of HSP26 and HSP42 notably enhanced the cell growth of NBRC1958 both in the presence and absence of SA. CONCLUSIONS: The inherent activities of small heat shock proteins, the levels of acetyl-CoA and the strains' potential capacity to consume SA all seem to affect the responses and tolerances of S. cerevisiae strains to SA. These factors should be taken into consideration when choosing host strains for SA production. This study provides a theoretical basis and identifies potential host strains for the development of robust and efficient SA-producing strains.