ABSTRACT
Hydroformylation is an industrial process for the production of aldehydes from alkenes1,2. Regioselective hydroformylation of propene to high-value n-butanal is particularly important, owing to a wide range of bulk applications of n-butanal in the manufacture of various necessities in human daily life3. Supported rhodium (Rh) hydroformylation catalysts, which often excel in catalyst recyclability, ease of separation and adaptability for continuous-flow processes, have been greatly exploited4. Nonetheless, they usually consist of rotationally flexible and sterically unconstrained Rh hydride dicarbonyl centres, only affording limited regioselectivity to n-butanal5-8. Here we show that proper encapsulation of Rh species comprising Rh(I)-gem-dicarbonyl centres within a MEL zeolite framework allows the breaking of the above model. The optimized catalyst exhibits more than 99% regioselectivity to n-butanal and more than 99% selectivity to aldehydes at a product formation turnover frequency (TOF) of 6,500 h-1, surpassing the performance of all heterogeneous and most homogeneous catalysts developed so far. Our comprehensive studies show that the zeolite framework can act as a scaffold to steer the reaction pathway of the intermediates confined in the space between the zeolite framework and Rh centres towards the exclusive formation of n-butanal.
ABSTRACT
Carotenoids are essential for photosynthesis and photoprotection. Plants must evolve multifaceted regulatory mechanisms to control carotenoid biosynthesis. However, the regulatory mechanisms and the regulators conserved among plant species remain elusive. Phytoene synthase (PSY) catalyzes the highly regulated step of carotenogenesis and geranylgeranyl diphosphate synthase (GGPPS) acts as a hub to interact with GGPP-utilizing enzymes for the synthesis of specific downstream isoprenoids. Here, we report a function of Nudix hydrolase 23 (NUDX23), a Nudix domain-containing protein, in post-translational regulation of PSY and GGPPS for carotenoid biosynthesis. NUDX23 expresses highly in Arabidopsis (Arabidopsis thaliana) leaves. Overexpression of NUDX23 significantly increases PSY and GGPPS protein levels and carotenoid production, whereas knockout of NUDX23 dramatically reduces their abundances and carotenoid accumulation in Arabidopsis. NUDX23 regulates carotenoid biosynthesis via direct interactions with PSY and GGPPS in chloroplasts, which enhances PSY and GGPPS protein stability in a large PSY-GGPPS enzyme complex. NUDX23 was found to co-migrate with PSY and GGPPS proteins and to be required for the enzyme complex assembly. Our findings uncover a regulatory mechanism underlying carotenoid biosynthesis in plants and offer promising genetic tools for developing carotenoid-enriched food crops.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Carotenoids , Gene Expression Regulation, Plant , Carotenoids/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Nudix Hydrolases , Chloroplasts/metabolism , Geranylgeranyl-Diphosphate Geranylgeranyltransferase/metabolism , Geranylgeranyl-Diphosphate Geranylgeranyltransferase/genetics , Farnesyltranstransferase/metabolism , Farnesyltranstransferase/genetics , Pyrophosphatases/metabolism , Pyrophosphatases/genetics , Protein Processing, Post-Translational , Plants, Genetically Modified , Plant Leaves/metabolism , Plant Leaves/geneticsABSTRACT
Traditional metallic glasses (MGs), based on one or two principal elements, are notoriously known for their lack of tensile ductility at room temperature. Here, we developed a multiprincipal element MG (MPEMG), which exhibits a gigapascal yield strength, significant strain hardening that almost doubles its yield strength, and 2% uniform tensile ductility at room temperature. These remarkable properties stem from the heterogeneous amorphous structure of our MPEMG, which is composed of atoms with significant size mismatch but similar atomic fractions. In sharp contrast to traditional MGs, shear banding in our glass triggers local elemental segregation and subsequent ordering, which transforms shear softening to hardening, hence resulting in shear-band self-halting and extensive plastic flows. Our findings reveal a promising pathway to design stronger, more ductile glasses that can be applied in a wide range of technological fields.
ABSTRACT
Bacterial persister cells, a sub-population of dormant phenotypic variants highly tolerant to antibiotics, present a significant challenge for infection control. Investigating the mechanisms of antibiotic persistence is crucial for developing effective treatment strategies. Here, we found a significant association between tolerance frequency and previous infection history in bovine mastitis. Previous S. aureus infection led to S. aureus tolerance to killing by rifampicin in subsequent infection in vivo and in vitro. Actually, the activation of trained immunity contributed to rifampicin persistence of S. aureus in secondary infection, where it reduced the effectiveness of antibiotic treatment and increased disease severity. Mechanically, we found that S. aureus persistence was mediated by the accumulation of fumarate provoked by trained immunity. Combination therapy with metformin and rifampicin promoted eradication of persisters and improved the severity of recurrent S. aureus infection. These findings provide mechanistic insight into the relationship between trained immunity and S. aureus persistence, while providing proof of concept that trained immunity is a therapeutic target in recurrent bacterial infections involving persistent pathogens.
Subject(s)
Staphylococcal Infections , Staphylococcus aureus , Animals , Female , Cattle , Staphylococcus aureus/physiology , Rifampin/pharmacology , Rifampin/therapeutic use , Trained Immunity , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , BacteriaABSTRACT
The rapid advancement of intelligent manufacturing technology has enabled electronic equipment to achieve synergistic design and programmable optimization through computer-aided engineering. Three-dimensional (3D) printing, with the unique characteristics of near-net-shape forming and mold-free fabrication, serves as an effective medium for the materialization of digital designs into usable devices. This methodology is particularly applicable to gas sensors, where performance can be collaboratively optimized by the tailored design of each internal module including composition, microstructure, and architecture. Meanwhile, diverse 3D printing technologies can realize modularized fabrication according to the application requirements. The integration of artificial intelligence software systems further facilitates the output of precise and dependable signals. Simultaneously, the self-learning capabilities of the system also promote programmable optimization for the hardware, fostering continuous improvement of gas sensors for dynamic environments. This review investigates the latest studies on 3D-printed gas sensor devices and relevant components, elucidating the technical features and advantages of different 3D printing processes. A general testing framework for the performance evaluation of customized gas sensors is proposed. Additionally, it highlights the superiority and challenges of programmable and modularized gas sensors, providing a comprehensive reference for material adjustments, structure design, and process modifications for advanced gas sensor devices.
ABSTRACT
Protein synthesis in response to neuronal activity, known as activity-dependent translation, is critical for synaptic plasticity and memory formation. However, the signaling cascades that couple neuronal activity to the translational events remains elusive. In this study, we identified the role of calmodulin (CaM), a conserved Ca2+-binding protein, in rRNA biogenesis in neurons. We found the CaM-regulated rRNA synthesis is Ca2+-dependent and necessary for nascent protein synthesis and axon growth in hippocampal neurons. Mechanistically, CaM interacts with nucleolar DDX21 in a Ca2+-dependent manner to regulate nascent rRNA transcription within nucleoli. We further found CaM alters the conformation of DDX21 to liberate the DDX21-sequestered RPA194, the catalytic subunit of RNA polymerase I, to facilitate transcription of rDNA. Using high-throughput screening, we identified the small molecules Batefenterol and Indacaterol that attenuate the CaM-DDX21 interaction and suppress nascent rRNA synthesis and axon growth in hippocampal neurons. These results unveiled the previously unrecognized role of CaM as a messenger to link the activity-induced Ca2+ influx to the nucleolar events essential for protein synthesis. We thus identified the ability of CaM to transmit information to the nucleoli of neurons in response to stimulation.Significance statement Protein synthesis in response to neuronal activity, known as activity-dependent translation, is critical for synaptic plasticity and long-term memory formation. In this study, we identify the novel role of calmodulin (CaM), a highly conserved Ca2+-binding protein, which is well-known by regulating myriad vital biological processes, in activity-dependent translation by regulating rRNA synthesis in neurons. We find that CaM can shuttle into the nucleolus upon depolarization and modulate the activity-induced de novo rRNA biogenesis, which is associated with ribosome assembly and protein synthesis in neurons. Mechanistically, CaM interacts with DDX21, an RNA helicase directly associated with Pol I subunit, to regulate the transcription of rDNA. Our study demonstrates CaM as a messenger linking neuronal activity to ribosome-dependent protein biosynthesis.
ABSTRACT
BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine-Optical Coherence Tomography Trial) and LoDoCo2 studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] µm versus 87.2 [95% CI, 69.9 to 104.5] µm; difference, 34.2 [95% CI, 9.7 to 58.6] µm; P=0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P=0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P=0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P=0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P=0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P=0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04848857.
ABSTRACT
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus, and the broad interspecies infection of SADS-CoV poses a potential threat to human health. This study provides experimental evidence to dissect the roles of distinct domains within the SADS-CoV spike S1 subunit in cellular entry. Specifically, we expressed the S1 and its subdomains, S1A and S1B. Cell binding and invasion inhibition assays revealed a preference for the S1B subdomain in binding to the receptors on the cell surface, and this unknown receptor is not utilized by the porcine epidemic diarrhea virus. Nanoparticle display demonstrated hemagglutination of erythrocytes from pigs, humans, and mice, linking the S1A subdomain to the binding of sialic acid (Sia) involved in virus attachment. We successfully rescued GFP-labeled SADS-CoV (rSADS-GFP) from a recombinant cDNA clone to track viral infection. Antisera raised against S1, S1A, or S1B contained highly potent neutralizing antibodies, with anti-S1B showing better efficiency in neutralizing rSADS-GFP infection compared to anti-S1A. Furthermore, depletion of heparan sulfate (HS) by heparinase treatment or pre-incubation of rSADS-GFP with HS or constituent monosaccharides could inhibit SADS-CoV entry. Finally, we demonstrated that active furin cleavage of S glycoprotein and the presence of type II transmembrane serine protease (TMPRSS2) are essential for SADS-CoV infection. These combined observations suggest that the wide cell tropism of SADS-CoV may be related to the distribution of Sia or HS on the cell surface, whereas the S1B contains the main protein receptor binding site. Specific host proteases also play important roles in facilitating SADS-CoV entry.IMPORTANCESwine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel pathogen infecting piglet, and its unique genetic evolution characteristics and broad species tropism suggest the potential for cross-species transmission. The virus enters cells through its spike (S) glycoprotein. In this study, we identify the receptor binding domain on the C-terminal part of the S1 subunit (S1B) of SADS-CoV, whereas the sugar-binding domain located at the S1 N-terminal part of S1 (S1A). Sialic acid, heparan sulfate, and specific host proteases play essential roles in viral attachment and entry. The dissection of SADS-CoV S1 subunit's functional domains and identification of cellular entry cofactors will help to explore the receptors used by SADS-CoV, which may contribute to exploring the mechanisms behind cross-species transmission and host tropism.
Subject(s)
Alphacoronavirus , Coronavirus Infections , Spike Glycoprotein, Coronavirus , Animals , Humans , Mice , Alphacoronavirus/chemistry , Alphacoronavirus/physiology , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Heparitin Sulfate , N-Acetylneuraminic Acid/metabolism , Peptide Hydrolases , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , SwineABSTRACT
BACKGROUND: Epidemiological studies have revealed a significant association between impaired kidney function and certain mental disorders, particularly bipolar disorder (BIP) and major depressive disorder (MDD). However, the evidence regarding shared genetics and causality is limited due to residual confounding and reverse causation. METHODS: In this study, we conducted a large-scale genome-wide cross-trait association study to investigate the genetic overlap between 5 kidney function biomarkers (eGFRcrea, eGFRcys, blood urea nitrogen (BUN), serum urate, and UACR) and 2 mental disorders (MDD, BIP). Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Psychiatric Genomics Consortium. RESULTS: Using LD score regression, we found moderate but significant genetic correlations between kidney function biomarker traits on BIP and MDD. Cross-trait meta-analysis identified 1 to 19 independent significant loci that were found shared among 10 pairs of 5 kidney function biomarkers traits and 2 mental disorders. Among them, 3 novel genes: SUFU, IBSP, and PTPRJ, were also identified in transcriptome-wide association study analysis (TWAS), most of which were observed in the nervous and digestive systems (FDR < 0.05). Pathway analysis showed the immune system could play a role between kidney function biomarkers and mental disorders. Bidirectional mendelian randomization analysis suggested a potential causal relationship of kidney function biomarkers on BIP and MDD. CONCLUSIONS: In conclusion, the study demonstrated that both BIP and MDD shared genetic architecture with kidney function biomarkers, providing new insights into their genetic architectures and suggesting that larger GWASs are warranted.
Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Genome-Wide Association Study , Humans , Depressive Disorder, Major/genetics , Depressive Disorder, Major/pathology , Bipolar Disorder/genetics , Bipolar Disorder/pathology , Polymorphism, Single Nucleotide/genetics , Kidney/physiopathology , Kidney/pathology , Genetic Predisposition to Disease , Biomarkers/blood , Glomerular Filtration Rate/genetics , Quantitative Trait Loci/genetics , Uric Acid/bloodABSTRACT
The mechanism connecting gut microbiota to appetite regulation is not yet fully understood. This study identifies specific microbial community and metabolites that may influence appetite regulation. In the initial phase of the study, mice were administered a broad-spectrum antibiotic cocktail (ABX) for 10 days. The treatment significantly reduced gut microbes and disrupted the metabolism of arginine and tryptophan. Consequently, ABX-treated mice demonstrated a notable reduction in feed consumption. The hypothalamic expression levels of CART and POMC, two key anorexigenic factors, were significantly increased, while orexigenic factors, such as NPY and AGRP, were decreased. Notably, the levels of appetite-suppressing hormone cholecystokinin in the blood were significantly elevated. In the second phase, control mice were maintained, while the ABX-treated mice received saline, probiotics, and short-chain fatty acids (SCFAs) for an additional 10 days to restore their gut microbiota. The microbiota reconstructed by probiotic and SCFA treatments were quite similar, while microbiota of the naturally recovering mice demonstrated greater resemblance to that of the control mice. Notably, the abundance of Akkermansia and Bacteroides genera significantly increased in the reconstructed microbiota. Moreover, microbiota reconstruction corrected the disrupted arginine and tryptophan metabolism and the abnormal peripheral hormone levels caused by ABX treatment. Among the groups, SCFA-treated mice had the highest feed intake and NPY expression. Our findings indicate that gut microbes, especially Akkermansia, regulate arginine and tryptophan metabolism, thereby influencing appetite through the microbe-gut-brain axis.
Subject(s)
Gastrointestinal Microbiome , Metabolome , Animals , Gastrointestinal Microbiome/drug effects , Mice , Male , Mice, Inbred C57BL , Anti-Bacterial Agents/pharmacology , Tryptophan/metabolism , Appetite/drug effects , Probiotics/pharmacology , Arginine/pharmacology , Arginine/metabolism , Hypothalamus/metabolism , Appetite Regulation/physiology , Fatty Acids, Volatile/metabolismABSTRACT
Dysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction-associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH-associated hepatocellular carcinoma (MASH-HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA-16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH-HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH-fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.
Subject(s)
Carcinoma, Hepatocellular , Dysbiosis , Gastrointestinal Microbiome , Liver Neoplasms , Mice, Inbred C57BL , Animals , Mice , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/microbiology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/etiology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/microbiology , Liver Neoplasms/etiology , Dysbiosis/microbiology , Male , Fatty Liver/metabolism , Fatty Liver/pathology , Fatty Liver/microbiology , Diet, High-Fat/adverse effects , Disease Models, Animal , Disease Progression , Lipid Metabolism , Liver/metabolism , Liver/pathologyABSTRACT
Trained immunity is mechanistically defined as the metabolically and epigenetically mediated long-term functional adaptation of the innate immune system, characterized by a heightened response to a secondary stimulation. Given appropriate activation, trained immunity represents an attractive anti-infective therapeutic target. Nevertheless, excessive immune response and subsequent inflammatory cascades may contribute to pathological tissue damage, indicating that the negative impacts of trained immunity appear to be significant. In this study, we show that innate immune responses such as the production of extracellular traps, pro-inflammatory cytokines, and autophagy-related proteins were markedly augmented in trained BMDMs. Furthermore, heat-killed C. albicans priming promotes the activation of the AIM2 inflammasome, and AIM2-/- mice exhibit impaired memory response induced by heat-killed C. albicans. Therefore, we establish that the AIM2 inflammasome is involved in trained immunity and emerges as a promising therapeutic target for potentially deleterious effects. Dihydroartemisinin can inhibit the memory response induced by heat-killed C. albicans through modulation of mTOR signaling and the AIM2 inflammasome. The findings suggest that dihydroartemisinin can reduce the induction of trained immunity by heat-killed C. albicans in C57BL/6 mice. Dihydroartemisinin is one such therapeutic intervention that has the potential to treat of diseases characterized by excessive trained immunity.
Subject(s)
Artemisinins , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Trained Immunity , Animals , Mice , Artemisinins/pharmacology , Candida albicans/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Inflammasomes/metabolism , Inflammasomes/drug effects , Mice, Inbred C57BL , Mice, Knockout , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Trained Immunity/drug effectsABSTRACT
Allergic asthma is a complex inflammatory disorder predominantly orchestrated by T helper 2 (Th2) lymphocytes. The anti-inflammatory protein Clara Cell 10-kDa (CC10), also known as secretoglobin family 1A member 1 (SCGB1A1), shows promise in modulating respiratory diseases. However, its precise role in asthma remains unclear. This study examines the potential of CC10 to suppress allergic asthma inflammation, specifically assessing its regulatory effects on Th2 cell responses and dendritic cells (DCs). Lower CC10 levels in asthma were observed and correlated with increased IgE and lymphocytes. Cc10-/- mice exhibited exacerbated allergic airway inflammation marked by increased inflammatory cell infiltration, Th2 cytokines, serum antigen-specific IgE levels, and airway hyperresponsiveness (AHR) in house dust mite (HDM)-induced models. Conversely, recombinant CC10 significantly attenuated these inflammatory responses. Intriguingly, CC10 did not directly inhibit Th cell activation but significantly downregulated the population of CD11b+CD103- DCs subsets in lungs of asthmatic mice and modulated the immune activation functions of DCs through NF-κB signaling pathway. The mixed lymphocyte response assay revealed that DCs mediated the suppressive effect of CC10 on Th2 cell responses. Collectively, CC10 profoundly mitigates Th2-type allergic inflammation in asthma by modulating lung DC phenotype and functions, highlighting its therapeutic potential for inflammatory airway conditions and other related immunological disorders.
Subject(s)
Asthma , Dendritic Cells , Lung , Th2 Cells , Uteroglobin , Animals , Dendritic Cells/immunology , Dendritic Cells/metabolism , Asthma/immunology , Asthma/pathology , Th2 Cells/immunology , Th2 Cells/metabolism , Uteroglobin/genetics , Uteroglobin/metabolism , Mice , Lung/pathology , Lung/immunology , Lung/metabolism , Mice, Inbred C57BL , Mice, Knockout , Inflammation/pathology , Inflammation/immunology , Inflammation/metabolism , Immunoglobulin E/immunology , Immunoglobulin E/blood , Pyroglyphidae/immunology , NF-kappa B/metabolism , Cytokines/metabolism , Female , Mice, Inbred BALB CABSTRACT
Rechargeable lithium-ion batteries are integral to contemporary energy storage, yet current anode material systems struggle to meet the increasing demand for extended range capabilities. This work introduces a novel composite anode material composed of one-dimensional 2H-phase tin disulfide (SnS2) nanoribbons enclosed within cavities of single-walled carbon nanotubes (SnS2@SWCNTs), achieved through precise atomic engineering. Employing aberration-corrected transmission electron microscopy, we precisely elucidated the crystal structure of SnS2 within the confines of the SWCNTs. This deliberate design effectively addresses the inherent limitations of SnS2 as a lithium-ion anode material, including its low electrical conductivity, considerable volume expansion effects, and unstable solid electrolyte interface membrane. Testing confirmed that SnS2 transforms into the Li5Sn2 alloy phase after full lithiation and back to SnS2 after delithiation, showing excellent reversibility. The composite also benefits from edge effects, improving lithium storage through stronger binding and lower migration barriers, which were supported by calculations. This pioneering work advances high-performance anode materials for applications.
ABSTRACT
BACKGROUND: Calmodulins (CaMs)/CaM-like proteins (CMLs) are crucial Ca2+-binding sensors that can decode and transduce Ca2+ signals during plant development and in response to various stimuli. The CaM/CML gene family has been characterized in many plant species, but this family has not yet been characterized and analyzed in peanut, especially for its functions in response to Ralstonia solanacearum. In this study, we performed a genome-wide analysis to analyze the CaM/CML genes and their functions in resistance to R. solanacearum. RESULTS: Here, 67, 72, and 214 CaM/CML genes were identified from Arachis duranensis, Arachis ipaensis, and Arachis hypogaea, respectively. The genes were divided into nine subgroups (Groups I-IX) with relatively conserved exonâintron structures and motif compositions. Gene duplication, which included whole-genome duplication, tandem repeats, scattered repeats, and unconnected repeats, produced approximately 81 pairs of homologous genes in the AhCaM/CML gene family. Allopolyploidization was the main reason for the greater number of AhCaM/CML members. The nonsynonymous (Ka) versus synonymous (Ks) substitution rates (less than 1.0) suggested that all homologous pairs underwent intensive purifying selection pressure during evolution. AhCML69 was constitutively expressed in different tissues of peanut plants and was involved in the response to R. solanacearum infection. The AhCML69 protein was localized in the cytoplasm and nucleus. Transient overexpression of AhCML69 in tobacco leaves increased resistance to R. solanacearum infection and induced the expression of defense-related genes, suggesting that AhCML69 is a positive regulator of disease resistance. CONCLUSIONS: This study provides the first comprehensive analysis of the AhCaM/CML gene family and potential genetic resources for the molecular design and breeding of peanut bacterial wilt resistance.
Subject(s)
Arachis , Ralstonia solanacearum , Arachis/metabolism , Ralstonia solanacearum/genetics , Plant Breeding , Gene Duplication , Introns , Plant Diseases/genetics , Plant Diseases/microbiologyABSTRACT
BACKGROUND: Gibberella ear rot (GER) is one of the most devastating diseases in maize growing areas, which directly reduces grain yield and quality. However, the underlying defense response of maize to pathogens infection is largely unknown. RESULTS: To gain a comprehensive understanding of the defense response in GER resistance, two contrasting inbred lines 'Nov-82' and 'H10' were used to explore transcriptomic profiles and defense-related phytohormonal alterations during Fusarium graminearum infection. Transcriptomic analysis revealed 4,417 and 4,313 differentially expressed genes (DEGs) from the Nov-82 and H10, respectively, and 647 common DEGs between the two lines. More DEGs were obviously enriched in phenylpropanoid biosynthesis, secondary metabolites biosynthesis, metabolic process and defense-related pathways. In addition, the concentration of the defense-related phytohormones, jasmonates (JAs) and salicylates (SAs), was greatly induced after the pathogen infection. The level of JAs in H10 was more higher than in Nov-82, whereas an opposite pattern for the SA between the both lines. Integrated analysis of the DEGs and the phytohormones revealed five vital modules based on co-expression network analysis according to their correlation. A total of 12 hub genes encoding fatty acid desaturase, subtilisin-like protease, ethylene-responsive transcription factor, 1-aminocyclopropane-1-carboxylate oxidase, and sugar transport protein were captured from the key modules, indicating that these genes might play unique roles in response to pathogen infection, CONCLUSIONS: Overall, our results indicate that large number DEGs related to plant disease resistance and different alteration of defensive phytohormones were activated during F. graminearum infection, providing new insight into the defense response against pathogen invasion, in addition to the identified hub genes that can be further investigated for enhancing maize GER resistance.
Subject(s)
Disease Resistance , Fusarium , Gene Expression Profiling , Plant Diseases , Plant Growth Regulators , Zea mays , Zea mays/microbiology , Zea mays/genetics , Plant Diseases/microbiology , Plant Diseases/genetics , Plant Growth Regulators/metabolism , Disease Resistance/genetics , Gene Expression Regulation, Plant , Transcriptome , Gibberella/geneticsABSTRACT
Depression frequently occurs in patients with liver cirrhosis, yet the reasons for this correlation are not fully understood. Dysbiosis of gut microbiota has been implicated in depression through the gut-brain axis via the vagus nerve. This study explored the potential role of the gut-liver-brain axis via the vagus nerve in depression-like phenotypes in mice with liver cirrhosis. These mice underwent common bile duct ligation (CBDL), a method used to stimulate liver cirrhosis. To assess depression-like behaviors, behavioral tests were conducted 10 days following either sham or CBDL surgeries. The mice with CBDL displayed symptoms such as splenomegaly, elevated plasma levels of interleukin-6 and tumor necrosis factor-α, depression-like behaviors, decreased levels of synaptic proteins in the prefrontal cortex (PFC), disrupted gut microbiota balance, and changes in blood metabolites (or lipids). Additionally, there were positive or negative correlations between the relative abundance of microbiome and behavioral data or blood metabolites (or lipids). Significantly, these changes were reversed in CBDL mice by performing a subdiaphragmatic vagotomy. Intriguingly, depression-like phenotypes in mice with CBDL were improved after a single injection of arketamine, a new antidepressant. These results suggest that CBDL-induced depression-like phenotypes in mice are mediated through the gut-liver-brain axis via the subdiaphragmatic vagus nerve, and that arketamine might offer a new treatment approach for depression in liver cirrhosis patients.
Subject(s)
Brain-Gut Axis , Depression , Mice , Humans , Animals , Depression/etiology , Common Bile Duct/pathology , Common Bile Duct/physiology , Liver Cirrhosis/pathology , Vagus Nerve , Ligation , Brain/pathology , LipidsABSTRACT
OBJECTIVES: Reference materials for in-vitro diagnostic reagents play a critical role in determining the quality of reagents and ensuring the accuracy of clinical test results. This study aimed to establish a national reference material (NRM) for detecting cytochrome P450 (CYP) genes related to drug metabolism by screening databases on the Chinese population to identify CYP gene polymorphism characteristics. METHODS: To prepare the NRM, we used DNA extracted from healthy human immortalized B lymphoblastoid cell lines as the raw material. Samples of these cell lines were obtained from the Chinese Population PGx Gene Polymorphism Biobank. Further, we used Sanger sequencing, next-generation sequencing, and commercial assay kits to validate the polymorphic genotypes. RESULTS: Among the CYP superfamily genes, we confirmed 24 riboswitch loci related to drug metabolism, with evidence levels of 1A, 2A, 3, and 4. We confirmed the polymorphic loci and validated their genotypes using various sequencing techniques. Our results were consistent with the polymorphism information of samples obtained from the biobank, thus demonstrating high precision and stability of the established NRM. CONCLUSION: An NRM (360 056-202 201) for CYP genetic testing covering 24 loci related to drug metabolism was established and approved to assess in-vitro diagnostic reagents containing CYP family gene polymorphisms and perform clinical inter-room quality evaluations.
Subject(s)
Cytochrome P-450 Enzyme System , Genetic Testing , Humans , Cytochrome P-450 Enzyme System/genetics , Genetic Testing/standards , Genetic Testing/methods , High-Throughput Nucleotide Sequencing/standards , Polymorphism, Genetic , Genotype , Reference Standards , Asian People/genetics , Cell Line , ChinaABSTRACT
A number of studies have confirmed that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)-transcriptional enhanced associate domain (TEAD) activity is the driver of cancer development. However, the role and mechanism of the YAP/TAZ-TEAD pathway in cervical intraepithelial neoplasia (CIN) remain to be clarified. Therefore, this study was designed to observe the effect of YAP/TAZ-TEAD activity on the development of CIN and provide new ideas for the diagnosis and treatment of CIN. Firstly, cervical tissues were collected from CIN patients in different stages [CIN grade 1 (CIN1) tissue, CIN grade 2/3 (CIN 2/3) and squamous cell carcinoma (SCC)] and healthy volunteers. Next, the expression levels of YAP, TAZ and TEAD in cervical tissues and cells were observed by immunohistochemistry, qRT-PCR and western blot. Besides, Z172 and Z183 cells were transfected with siRNA-YAP/TAZ (si-YAP/TAZ) and YAP/TAZ overexpression vector (YAP-5SA). Also, Z172 cells were co-transfected with YAP-5SA and si-TEAD2/4. Subsequently, the stemness characteristics, glycolysis level and malignant transformation of cells in each group were observed by sphere-formation assay, commercial kit, MTT, Transwell, scratch experiment, xenotransplantation and western blot.The expression of YAP, TAZ and TEAD increased significantly in cervical cancer tissue and cell line at the stage of CIN2/3 and SCC. When YAP/TAZ was knocked down, the stemness characteristics, glycolysis level and malignant transformation of cancer cells were notably inhibited; while activating YAP/TAZ exhibited a completely opposite result. In addition, activating YAP/TAZ and knocking down the TEAD expression at the same time significant weakened the effect of activated YAP/TAZ signal on precancerous cells and reduced inhibitory effect of knocking down TEAD alone. YAP/TAZ-TEAD signal activates the characteristics and Warburg effect of cancer stem cells, thereby promoting the malignant transformation of CIN.
Subject(s)
Adaptor Proteins, Signal Transducing , Cell Transformation, Neoplastic , Neoplastic Stem Cells , Trans-Activators , Transcription Factors , Transcriptional Coactivator with PDZ-Binding Motif Proteins , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , YAP-Signaling Proteins , Humans , Female , Transcription Factors/genetics , Transcription Factors/metabolism , YAP-Signaling Proteins/metabolism , YAP-Signaling Proteins/genetics , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/genetics , Uterine Cervical Dysplasia/metabolism , Animals , Trans-Activators/genetics , Trans-Activators/metabolism , TEA Domain Transcription Factors/metabolism , Cell Line, Tumor , Mice , Warburg Effect, Oncologic , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Cell Proliferation/genetics , Mice, Nude , Gene Expression Regulation, Neoplastic , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathologyABSTRACT
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the synovial tissue and joint bone destruction, often leading to significant disability. The main pathological manifestation of joint deformity in RA patients is bone destruction, which occurs due to the differentiation and proliferation of osteoclasts. The transcription factor nuclear factor-activated T cell 1 (NFATc1) plays a crucial role in this process. The regulation of NFATc1 in osteoclast differentiation is influenced by three main factors. Firstly, NFATc1 is activated through the upstream nuclear factor kappa-B ligand (RANKL)/RANK signaling pathway. Secondly, the Ca2+-related co-stimulatory signaling pathway amplifies NFATc1 activity. Finally, negative regulation of NFATc1 occurs through the action of cytokines such as B-cell Lymphoma 6 (Bcl-6), interferon regulatory factor 8 (IRF8), MAF basic leucine zipper transcription factor B (MafB), and LIM homeobox 2 (Lhx2). These three phases collectively govern NFATc1 transcription and subsequently affect the expression of downstream target genes including TRAF6 and NF-κB. Ultimately, this intricate regulatory network mediates osteoclast differentiation, fusion, and the degradation of both organic and inorganic components of the bone matrix. This review provides a comprehensive summary of recent advances in understanding the mechanism of NFATc1 in the context of RA-related bone destruction and discusses potential therapeutic agents that target NFATc1, with the aim of offering valuable insights for future research in the field of RA. To assess their potential as therapeutic agents for RA, we conducted a drug-like analysis of potential drugs with precise structures.