ABSTRACT
The reinvigoration of anti-tumor T cells in response to immune checkpoint blockade (ICB) therapy is well established. Whether and how ICB therapy manipulates antibody-mediated immune response in cancer environments, however, remains elusive. Using tandem mass spectrometric analysis of modification of immunoglobulin G (IgG) from hepatoma tissues, we identified a role of ICB therapy in catalyzing IgG sialylation in the Fc region. Effector T cells triggered sialylation of IgG via an interferon (IFN)-γ-ST6Gal-I-dependent pathway. DC-SIGN+ macrophages represented the main target cells of sialylated IgG. Upon interacting with sialylated IgG, DC-SIGN stimulated Raf-1-elicited elevation of ATF3, which inactivated cGAS-STING pathway and eliminated subsequent type-I-IFN-triggered antitumorigenic immunity. Although enhanced IgG sialylation in tumors predicted improved therapeutic outcomes for patients receiving ICB therapy, impeding IgG sialylation augmented antitumorigenic T cell immunity after ICB therapy. Thus, targeting antibody-based negative feedback action of ICB therapy has potential for improving efficacy of cancer immunotherapies.
Subject(s)
Carcinoma, Hepatocellular , Interferon Type I , Liver Neoplasms , Humans , Immunoglobulin G , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Immunotherapy/methodsABSTRACT
Epigenetic evolution occurs over million-year timescales in Cryptococcus neoformans and is mediated by DNMT5, the first maintenance type cytosine methyltransferase identified in the fungal or protist kingdoms, the first dependent on adenosine triphosphate (ATP), and the most hemimethyl-DNA-specific enzyme known. To understand these novel properties, we solved cryo-EM structures of CnDNMT5 in three states. These studies reveal an elaborate allosteric cascade in which hemimethylated DNA binding first activates the SNF2 ATPase domain by a large rigid body rotation while the target cytosine partially flips out of the DNA duplex. ATP binding then triggers striking structural reconfigurations of the methyltransferase catalytic pocket to enable cofactor binding, completion of base flipping, and catalysis. Bound unmethylated DNA does not open the catalytic pocket and is instead ejected upon ATP binding, driving high fidelity. This unprecedented chaperone-like, enzyme-remodeling role of the SNF2 ATPase domain illuminates how energy is used to enable faithful epigenetic memory.
Subject(s)
Adenosine Triphosphate , Epigenome , Adenosine Triphosphatases/genetics , Adenosine Triphosphate/metabolism , Cytosine/chemistry , DNA/genetics , DNA Methylation , Methyltransferases/geneticsABSTRACT
Nuclear Argonaute proteins, guided by their bound small RNAs to nascent target transcripts, mediate cotranscriptional silencing of transposons and repetitive genomic loci through heterochromatin formation. The molecular mechanisms involved in this process are incompletely understood. Here, we show that the SFiNX complex, a silencing mediator downstream from nuclear Piwi-piRNA complexes in Drosophila, facilitates cotranscriptional silencing as a homodimer. The dynein light chain protein Cut up/LC8 mediates SFiNX dimerization, and its function can be bypassed by a heterologous dimerization domain, arguing for a constitutive SFiNX dimer. Dimeric, but not monomeric SFiNX, is capable of forming molecular condensates in a nucleic acid-stimulated manner. Mutations that prevent SFiNX dimerization result in loss of condensate formation in vitro and the inability of Piwi to initiate heterochromatin formation and silence transposons in vivo. We propose that multivalent SFiNX-nucleic acid interactions are critical for heterochromatin establishment at piRNA target loci in a cotranscriptional manner.
Subject(s)
Argonaute Proteins/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Gene Expression Regulation, Developmental/genetics , Gene Silencing/physiology , Multiprotein Complexes/metabolism , Animals , Dimerization , Drosophila Proteins/chemistry , Drosophila melanogaster/metabolism , Dyneins/metabolism , Multiprotein Complexes/chemistry , Multiprotein Complexes/genetics , Nuclear Proteins/chemistry , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Nucleocytoplasmic Transport Proteins/chemistry , Nucleocytoplasmic Transport Proteins/genetics , Nucleocytoplasmic Transport Proteins/metabolism , Protein Subunits/genetics , Protein Subunits/metabolism , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolismABSTRACT
The accurate segregation of chromosomes during meiosis-which is critical for genome stability across sexual cycles-relies on homologous recombination initiated by DNA double-strand breaks (DSBs) made by the Spo11 protein1,2. The formation of DSBs is regulated and tied to the elaboration of large-scale chromosome structures3-5, but the protein assemblies that execute and control DNA breakage are poorly understood. Here we address this through the molecular characterization of Saccharomyces cerevisiae RMM (Rec114, Mei4 and Mer2) proteins-essential, conserved components of the DSB machinery2. Each subcomplex of Rec114-Mei4 (a 2:1 heterotrimer) or Mer2 (a coiled-coil-containing homotetramer) is monodispersed in solution, but they independently condense with DNA into reversible nucleoprotein clusters that share properties with phase-separated systems. Multivalent interactions drive this condensation. Mutations that weaken protein-DNA interactions strongly disrupt both condensate formation and DSBs in vivo, and thus these processes are highly correlated. In vitro, condensates fuse into mixed RMM clusters that further recruit Spo11 complexes. Our data show how the DSB machinery self-assembles on chromosome axes to create centres of DSB activity. We propose that multilayered control of Spo11 arises from the recruitment of regulatory components and modulation of the biophysical properties of the condensates.
Subject(s)
DNA Breaks, Double-Stranded , DNA, Fungal/metabolism , Meiosis , Nuclear Proteins/metabolism , Nucleoproteins/metabolism , Recombinases/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae , DNA, Fungal/chemistry , Endodeoxyribonucleases/metabolism , Homologous Recombination , Nuclear Proteins/chemistry , Nucleoproteins/chemistry , Protein Binding , Protein Subunits/chemistry , Protein Subunits/metabolism , Recombinases/chemistry , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/chemistryABSTRACT
Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here, we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to the pseudoautosomal regions (PARs) of sex chromosomes. They also have delayed and/or fewer recombination sites but, paradoxically, more DSBs, suggesting DSB dysregulation. Unrepaired DSBs and pairing failures-stochastic on autosomes, nearly absolute on X and Y-cause meiotic arrest and sterility in males. Ankrd31-deficient females have reduced oocyte reserves. A crystal structure defines a pleckstrin homology (PH) domain in REC114 and its direct intermolecular contacts with ANKRD31. In vivo, ANKRD31 stabilizes REC114 association with the PAR and elsewhere. Our findings inform a model in which ANKRD31 is a scaffold anchoring REC114 and other factors to specific genomic locations, thereby regulating DSB formation.
Subject(s)
Cell Cycle Proteins/physiology , Homologous Recombination/genetics , Meiosis/genetics , Recombinases/chemistry , Animals , Cell Cycle Proteins/chemistry , Cell Cycle Proteins/genetics , Chromosome Pairing , Chromosome Segregation/genetics , Chromosomes , Crystallography, X-Ray , DNA Breaks, Double-Stranded , Female , Male , Mice , Protein Conformation , Recombinases/genetics , Spermatocytes/chemistry , Spermatocytes/metabolismABSTRACT
Microsporidia are intracellular eukaryotic pathogens that pose a substantial threat to immunocompromised hosts. The way these pathogens manipulate host cells during infection remains poorly understood. Using a proximity biotinylation strategy we established that microsporidian EnP1 is a nucleus-targeted effector that modifies the host cell environment. EnP1's translocation to the host nucleus is meditated by nuclear localization signals (NLSs). In the nucleus, EnP1 interacts with host histone H2B. This interaction disrupts H2B monoubiquitination (H2Bub), subsequently impacting p53 expression. Crucially, this inhibition of p53 weakens its control over the downstream target gene SLC7A11, enhancing the host cell's resilience against ferroptosis during microsporidian infection. This favorable condition promotes the proliferation of microsporidia within the host cell. These findings shed light on the molecular mechanisms by which microsporidia modify their host cells to facilitate their survival.
Subject(s)
Ferroptosis , Histones , Microsporidia , Ubiquitination , Microsporidia/metabolism , Microsporidia/genetics , Histones/metabolism , Humans , Fungal Proteins/metabolism , Fungal Proteins/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Host-Pathogen Interactions , Animals , Cell Nucleus/metabolism , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Microsporidiosis/metabolismABSTRACT
Genomic-scale somatic copy number alterations in healthy humans are difficult to investigate because of low occurrence rates and the structural variations' stochastic natures. Using a Tn5-transposase-assisted single-cell whole-genome sequencing method, we sequenced over 20,000 single lymphocytes from 16 individuals. Then, with the scale increased to a few thousand single cells per individual, we found that about 7.5% of the cells had large-size copy number alterations. Trisomy 21 was the most prevalent aneuploid event among all autosomal copy number alterations, whereas monosomy X occurred most frequently in over-30-yr-old females. In the monosomy X single cells from individuals with phased genomes and identified X-inactivation ratios in bulk, the inactive X Chromosomes were lost more often than the active ones.
Subject(s)
DNA Copy Number Variations , Genomics , Aneuploidy , Female , Humans , Lymphocytes , Whole Genome SequencingABSTRACT
Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.
Subject(s)
Carcinoma, Hepatocellular , MicroRNAs , Humans , NF-kappa B/genetics , NF-kappa B/metabolism , Carcinoma, Hepatocellular/pathology , Signal Transduction/physiology , MicroRNAs/genetics , MicroRNAs/metabolism , Macrophages/metabolism , Cell Line, Tumor , Tumor Microenvironment/geneticsABSTRACT
Peritumoral hepatocytes are critical components of the liver cancer microenvironment, However, the role of peritumoral hepatocytes in the local tumor immune interface and the underlying molecular mechanisms have not been elucidated. YTHDF2, an RNA N6-methyladenosine (m6A) reader, is critical for liver tumor progression. The function and regulatory roles of YTHDF2 in peritumoral hepatocytes are unknown. This study demonstrated that oxaliplatin (OXA) upregulated m6A modification and YTHDF2 expression in hepatocytes. Studies using tumor-bearing liver-specific Ythdf2 knockout mice revealed that hepatocyte YTHDF2 suppresses liver tumor growth through CD8+ T cell recruitment and activation. Additionally, YTHDF2 mediated the response to immunotherapy. Mechanistically, OXA upregulated YTHDF2 expression by activating the cGAS-STING signaling pathway and consequently enhanced the therapeutic outcomes of immunotherapeutic interventions. Ythdf2 stabilized Cx3cl1 transcripts in an m6A-dependent manner, regulating the interplay between CD8+ T cells and the progression of liver malignancies. Thus, this study elucidated the novel role of hepatocyte YTHDF2, which promotes therapy-induced antitumor immune responses in the liver. The findings of this study provide valuable insights into the mechanism underlying the therapeutic benefits of targeting YTHDF2.
Subject(s)
CD8-Positive T-Lymphocytes , Chemokine CX3CL1 , Hepatocytes , Liver Neoplasms , Oxaliplatin , RNA-Binding Proteins , Animals , Humans , Mice , Adenosine/analogs & derivatives , Adenosine/metabolism , Antineoplastic Agents/pharmacology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cell Line, Tumor , Chemokine CX3CL1/metabolism , Chemokine CX3CL1/genetics , Gene Expression Regulation, Neoplastic , Hepatocytes/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/immunology , Liver Neoplasms/metabolism , Liver Neoplasms/drug therapy , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice, Knockout , Oxaliplatin/pharmacology , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Signal Transduction/drug effects , Tumor Microenvironment/immunologyABSTRACT
The monitoring of hydrological elements in the polar region is the basis for the study of the dynamic environment under the ice. The traditional cross-season subglacial hydrological environment monitoring mainly relies on tether-type vertical profile measurement ice-based buoys, which have the advantages such as high reliability, high measurement accuracy, and real-time communication, while also has disadvantages of high-cost, large volume and weight, high power consumption, and complex layout. Therefore, it is urgent to develop a new type of ice-based profile buoy with low-cost, miniaturization, low power consumption, convenient deployment, and high reliability. In this paper, a novel optical fiber sensing scheme for ice-based buoy monitoring is proposed, which uses arrayed fiber grating to measure seawater temperature and depth profile and uses a dual-conduction mode resonance mechanism to measure seawater salinity. The temperature, depth, and salinity of seawater can be detected by an all-optical fiber technology in real-time. Preliminary experiments show that the temperature accuracy is ±0.1 °C in the range of -5â¼35 °C, the salinity accuracy is ±0.03 in the range of 30â¼40, and the vertical spatial resolution of depth can be adjusted in the range of 0â¼1000 m, which can better meet the requirements of polar hydrological multi-layer profile observation. It can provide an innovative technology and equipment support for studying the spatiotemporal change process of the polar subglacial ocean.
ABSTRACT
Increasing evidence indicates that 2-hydroxyglutarate (2HG) is an oncometabolite that drives tumour formation and progression. Due to mutations in isocitrate dehydrogenase (IDH) and the dysregulation of other enzymes, 2HG accumulates significantly in tumour cells. Due to its structural similarity to α-ketoglutarate (αKG), accumulated 2HG leads to the competitive inhibition of αKG-dependent dioxygenases (αKGDs), such as KDMs, TETs, and EGLNs. This inhibition results in epigenetic alterations in both tumour cells and the tumour microenvironment. This review comprehensively discusses the metabolic pathways of 2HG and the subsequent pathways influenced by elevated 2HG levels. We will delve into the molecular mechanisms by which 2HG exerts its oncogenic effects, particularly focusing on epigenetic modifications. This review will also explore the various methods available for the detection of 2HG, emphasising both current techniques and emerging technologies. Furthermore, 2HG shows promise as a biomarker for clinical diagnosis and treatment. By integrating these perspectives, this review aims to provide a comprehensive overview of the current understanding of 2HG in cancer biology, highlight the importance of ongoing research, and discuss future directions for translating these findings into clinical applications.
ABSTRACT
Halophyte Halogeton glomeratus mostly grows in saline desert areas in arid and semi-arid regions and is able to adapt to adverse conditions such as salinity and drought. Earlier transcriptomic studies revealed activation of the HgS2 gene in the leaf of H. glomeratus seedlings when exposed to saline conditions. To identify the properties of HgS2 in H. glomeratus, we used yeast transformation and overexpression in Arabidopsis. Yeast cells genetically transformed with HgS2 exhibited K+ uptake and Na+ efflux compared with control (empty vector). Stable overexpression of HgS2 in Arabidopsis improved its resistance to salt stress and led to a notable rise in seed germination in salinity conditions compared to the wild type (WT). Transgenic Arabidopsis regulated ion homeostasis in plant cells by increasing Na+ absorption and decreasing K+ efflux in leaves, while reducing Na+ absorption and K+ efflux in roots. In addition, overexpression of HgS2 altered transcription levels of stress response genes and regulated different metabolic pathways in roots and leaves of Arabidopsis. These results offer new insights into the role of HgS2 in plants' salt tolerance.
Subject(s)
Amaranthaceae , Arabidopsis , Gene Expression Regulation, Plant , Plant Proteins , Plants, Genetically Modified , Salt Tolerance , Amaranthaceae/genetics , Amaranthaceae/physiology , Arabidopsis/genetics , Arabidopsis/physiology , Germination/genetics , Germination/drug effects , Plant Leaves/genetics , Plant Leaves/physiology , Plant Leaves/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Roots/genetics , Plant Roots/physiology , Plant Roots/metabolism , Potassium/metabolism , Salt Tolerance/genetics , Salt-Tolerant Plants/genetics , Salt-Tolerant Plants/physiology , Salt-Tolerant Plants/metabolism , Sodium/metabolism , Sodium Chloride/pharmacologyABSTRACT
As part of a program evaluation of the New York City Test & Trace program (T2)-one of the largest such programs in the USA-we conducted a study to assess how implementing organizations (NYC Health + Hospitals, government agencies, CBOs) communicated information about the T2 program on Twitter. Study aims were as follows: (1) quantify user engagement of posts ("tweets") about T2 by NYC organizations on Twitter and (2) examine the emotional tone of social media users' T2-related tweets in our sample of 1987 T2-related tweets. Celebrities and CBOs generated more user engagement (0.26% and 0.07%, respectively) compared to government agencies (e.g., Mayor's Office, 0.0019%), reinforcing the value of collaborating with celebrities and CBOs in social media public health campaigns. Sentiment analysis revealed that positive tweets (46.5%) had higher user engagement than negative tweets (number of likes: R2 = .095, p < .01), underscoring the importance of positively framing messages for effective public health campaigns.
Subject(s)
COVID-19 , Social Media , Humans , New York City , COVID-19/psychology , COVID-19/epidemiology , SARS-CoV-2 , COVID-19 Testing/methods , Program Evaluation , Health Promotion/methods , Information Dissemination/methodsABSTRACT
Mycobacterial AdnAB is a heterodimeric helicase-nuclease that initiates homologous recombination by resecting DNA double-strand breaks. The AdnB subunit hydrolyzes ATP to drive single-nucleotide steps of 3'-to-5' translocation of AdnAB on the tracking DNA strand via a ratchet-like mechanism. Trp325 in AdnB motif III, which intercalates into the tracking strand and makes a π stack on a nucleobase 5' of a flipped-out nucleoside, is the putative ratchet pawl without which ATP hydrolysis is mechanically futile. Here, we report that AdnAB mutants wherein Trp325 was replaced with phenylalanine, tyrosine, histidine, leucine, or alanine retained activity in ssDNA-dependent ATP hydrolysis but displayed a gradient of effects on DSB resection. The resection velocities of Phe325 and Tyr325 mutants were 90% and 85% of the wild-type AdnAB velocity. His325 slowed resection rate to 3% of wild-type and Leu325 and Ala325 abolished DNA resection. A cryo-EM structure of the DNA-bound Ala325 mutant revealed that the AdnB motif III peptide was disordered and the erstwhile flipped out tracking strand nucleobase reverted to a continuous base-stacked arrangement with its neighbors. We conclude that π stacking of Trp325 on a DNA nucleobase triggers and stabilizes the flipped-out conformation of the neighboring nucleoside that underlies formation of a ratchet pawl.
Subject(s)
Bacterial Proteins/metabolism , DNA Helicases/metabolism , DNA, Bacterial/metabolism , DNA, Single-Stranded/metabolism , Mycobacterium/genetics , DNA Breaks, Double-Stranded , DNA Repair , Endonucleases , Protein Binding , Structure-Activity RelationshipABSTRACT
The Shieldin complex, composed of REV7, SHLD1, SHLD2, and SHLD3, protects DNA double-strand breaks (DSBs) to promote nonhomologous end joining. The AAA+ ATPase TRIP13 remodels Shieldin to regulate DNA repair pathway choice. Here we report crystal structures of human SHLD3-REV7 binary and fused SHLD2-SHLD3-REV7 ternary complexes, revealing that assembly of Shieldin requires fused SHLD2-SHLD3 induced conformational heterodimerization of open (O-REV7) and closed (C-REV7) forms of REV7. We also report the cryogenic electron microscopy (cryo-EM) structures of the ATPγS-bound fused SHLD2-SHLD3-REV7-TRIP13 complexes, uncovering the principles underlying the TRIP13-mediated disassembly mechanism of the Shieldin complex. We demonstrate that the N terminus of REV7 inserts into the central channel of TRIP13, setting the stage for pulling the unfolded N-terminal peptide of C-REV7 through the central TRIP13 hexameric channel. The primary interface involves contacts between the safety-belt segment of C-REV7 and a conserved and negatively charged loop of TRIP13. This process is mediated by ATP hydrolysis-triggered rotatory motions of the TRIP13 ATPase, thereby resulting in the disassembly of the Shieldin complex.
Subject(s)
ATPases Associated with Diverse Cellular Activities/metabolism , Adenosine Triphosphate/metabolism , Cell Cycle Proteins/metabolism , DNA-Binding Proteins/metabolism , Mad2 Proteins/metabolism , ATPases Associated with Diverse Cellular Activities/chemistry , Cell Cycle Proteins/chemistry , DNA-Binding Proteins/chemistry , Humans , Hydrolysis , Mad2 Proteins/chemistry , Models, Molecular , Protein ConformationABSTRACT
AIMS: To explore the impact of psychological empowerment on nurses' intent to stay in military hospitals as well as the mediating effects of the practice environment and burnout in this context. DESIGN: This study employed a cross-sectional survey approach and followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting. METHODS: A total of 1225 nurses from nine military hospitals were recruited via convenience sampling. Questionnaires were distributed and collected via the Questionnaire Star platform. The study variables, including psychological empowerment, the practice environment, burnout and intent to stay, were assessed via self-report questionnaires. SPSS 23.0 software was used to conduct descriptive and correlation analyses. Additionally, PROCESS Model 6 was employed to examine the mediating effects. RESULTS: Psychological empowerment is positively associated with nurses' intent to stay. Mediation analysis revealed that the practice environment, burnout and the chain mediating effect of the practice environment and burnout accounted for 54.5%, 2.8% and 1.5% of the total effect respectively. CONCLUSION: Psychological empowerment affects nurses' intent to stay not only directly but also indirectly via the practice environment and burnout. IMPLICATIONS FOR THE PROFESSION: Nursing managers may consider utilising psychological empowerment as a management strategy to enhance nurses' perceived practice environment, reduce burnout and ultimately increase nurses' intent to stay. This approach has the potential to lower turnover rates among nurses. PATIENT OR PUBLIC CONTRIBUTION: Questionnaires completed by nurses were used to explore the relationships among psychological empowerment, the practice environment, burnout and intent to stay in this context.
ABSTRACT
Drought stress is a major meteorological threat to crop growth and yield. Barley (Hordeum vulgare L.) is a vital cereal crop with strong drought tolerance worldwide. However, the underlying growth properties and metabolomic regulatory module of drought tolerance remains less known. Here, we investigated the plant height, spike length, effective tiller, biomass, average spikelets, 1000-grain weight, number of seeds per plant, grain weight per plant, ash content, protein content, starch content, cellulose content, and metabolomic regulation mechanisms of drought stress in barley. Our results revealed that the growth properties were different between ZDM5430 and IL-12 under drought stress at different growth stages. We found that a total of 12,235 metabolites were identified in two barley genotype root samples with drought treatment. More than 50% of these metabolites showed significant differences between the ZDM5430 and IL-12 roots. The Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 368 differential metabolites mainly involved in starch and sucrose metabolism, the pentose phosphate pathway, pyrimidine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis in ZDM5430 under drought stress, whereas the different metabolites of IL-12 under drought stress related to starch and sucrose metabolism, the pentose phosphate pathway, 2-oxocarboxylic acid metabolism, cutin, suberine and wax biosynthesis, carbon metabolism, fatty acid biosynthesis, and C5-branched dibasic acid metabolism. These metabolites have application in the tricarboxylic cycle, the urea cycle, the met salvage pathway, amino acid metabolism, unsaturated fatty acid biosynthesis, phenolic metabolism, and glycolysis. On the other hand, the expression patterns of 13 genes related to the abovementioned bioprocesses in different barley genotypes roots were proposed. These findings afford an overview for the understanding of barley roots' metabolic changes in the drought defense mechanism by revealing the differently accumulated compounds.
Subject(s)
Droughts , Hordeum , Metabolomics , Hordeum/genetics , Hordeum/metabolism , Hordeum/growth & development , Hordeum/physiology , Metabolomics/methods , Gene Expression Regulation, Plant , Stress, Physiological , Metabolome , Plant Roots/metabolism , Plant Roots/growth & development , Plant Roots/genetics , Starch/metabolism , Drought ResistanceABSTRACT
BACKGROUND: The optimal intervals for follow-up after hepatocellular carcinoma (HCC) patients undergo curative liver resection (LR) remain unclear. This study aimed to establish a risk-based post-resection follow-up strategy. METHODS: Patients that were diagnosed with HCC and received LR from three hospitals in China were included. The risk-based strategy was established based on the random survival forest model and compared with a fixed strategy both internally and externally. RESULTS: In total, 3447 patients from three hospitals were included. The authors' strategy showed superiority in the early detection of tumor relapse compared with fixed surveillance. Under fewer total visits, risk-based strategy achieved analogous survival time compared to the total 20 times follow-ups based on fixed strategy. Twelve total visits (five, three, one, two, and one visits in years 1-5, respectively) for American Joint Committee on Cancer/International Union Against Cancer T1a stage patients, 13 total visits (five, four, one, two, and one visits in years 1-5, respectively) for T1b stage patients, 15 total visits (eight, three, three, zero, and one visits in years 1-5, respectively) for T2 stage patients, and 15 total visits (eight, four, one, one, and one visits in years 1-5, respectively) for T3 stage patients were advocated. The detailed follow-up arrangements were available to the public through an interactive website (https://sysuccfyz.shinyapps.io/RiskBasedFollowUp/). CONCLUSION: This risk-based surveillance strategy was demonstrated to detect relapse earlier and reduce the total number of follow-ups without compromising on survival. Based on the strategy and methodology of the authors, surgeons or patients could choose more intensive or flexible schedules depending on the requirements and economic conditions. PLAIN LANGUAGE SUMMARY: A risk-based post-resection follow-up strategy was established by random survival forest model using a larger hepatocellular carcinoma population The strategy was demonstrated to detect tumor relapse earlier and reduce the total number of follow-ups without compromising on survival Our strategy and methodology could be widely applied by other surgeons and patients.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Follow-Up Studies , Retrospective Studies , Neoplasm Recurrence, Local/pathology , HepatectomyABSTRACT
In consideration of high specific capacity and low redox potential, lithium metal anodes have attracted extensive attention. However, the cycling performance of lithium metal batteries generally deteriorates significantly under the stringent conditions of high temperature due to inferior heat tolerance of the solid electrolyte interphase (SEI). Herein, controllable SEI nanostructures with excellent thermal stability are established by the (trifluoromethyl)trimethylsilane (TMSCF3 )-induced interface engineering. First, the TMSCF3 regulates the electrolyte decomposition, thus generating an SEI with a large amount of LiF, Li3 N, and Li2 S nanocrystals incorporated. More importantly, the uniform distributed nanocrystals have endowed the SEI with enhanced thermostability according to the density functional theory simulations. Particularly, the sub-angstrom visualization on SEI through a conventional transmission electron microscope (TEM) is realized for the first time and the enhanced tolerance to the heat damage originating from TEM imaging demonstrates the ultrahigh thermostability of SEI. As a result, the highly thermostable interphase facilitates a substantially prolonged lifespan of full cells at a high temperature of 70 °C. As such, this work might inspire the universal interphase design for high-energy alkali-metal-based batteries applicated in a high-temperature environment.
ABSTRACT
Sodium (Na) metal is able to directly use as a battery anode but have a highly reductive ability of unavoidably occurring side reactions with organic electrolytes, resulting in interfacial instability as a primary factor in performance decay. Therefore, building stable Na metal anode is of utmost significance for both identifying the electrochemical performance of laboratory half-cells employed for quantifying samples and securing the success of room-temperature Na metal batteries. In this work, we propose an NaF-rich interface rapidly prepared by pressure and diglyme-induced defluorination reaction for stable Na metal anode. Once the electrolyte is dropped into the coin-type cells followed by a slight squeeze, the Na metal surface immediately forms a protective layer consisting of amorphous carbon and NaF, effectively inhibiting the dendrite growth and dead Na. The resultant Na metal anode exhibits a long-term cycling lifespan over 1800 h even under the area capacity of 3.0 mAh cm-2 . Furthermore, such a universal and facile method is readily applied in daily battery assembly regarding Na metal anode.