RESUMO
Mapping behavioural actions to neural activity is a fundamental goal of neuroscience. As our ability to record large neural and behavioural data increases, there is growing interest in modelling neural dynamics during adaptive behaviours to probe neural representations1-3. In particular, although neural latent embeddings can reveal underlying correlates of behaviour, we lack nonlinear techniques that can explicitly and flexibly leverage joint behaviour and neural data to uncover neural dynamics3-5. Here, we fill this gap with a new encoding method, CEBRA, that jointly uses behavioural and neural data in a (supervised) hypothesis- or (self-supervised) discovery-driven manner to produce both consistent and high-performance latent spaces. We show that consistency can be used as a metric for uncovering meaningful differences, and the inferred latents can be used for decoding. We validate its accuracy and demonstrate our tool's utility for both calcium and electrophysiology datasets, across sensory and motor tasks and in simple or complex behaviours across species. It allows leverage of single- and multi-session datasets for hypothesis testing or can be used label free. Lastly, we show that CEBRA can be used for the mapping of space, uncovering complex kinematic features, for the production of consistent latent spaces across two-photon and Neuropixels data, and can provide rapid, high-accuracy decoding of natural videos from visual cortex.
Assuntos
Fenômenos Biomecânicos , Aprendizado de Máquina , Neurônios , Córtex Visual , Animais , Cálcio/metabolismo , Sinalização do Cálcio , Conjuntos de Dados como Assunto , Eletrofisiologia , Neurônios/fisiologia , Fótons , Reprodutibilidade dos Testes , Gravação em Vídeo , Córtex Visual/citologia , Córtex Visual/fisiologia , Movimento/fisiologiaRESUMO
Lead halide perovskites are promising semiconducting materials for solar energy harvesting. However, the presence of heavy-metal lead ions is problematic when considering potential harmful leakage into the environment from broken cells and also from a public acceptance point of view. Moreover, strict legislation on the use of lead around the world has driven innovation in the development of strategies for recycling end-of-life products by means of environmentally friendly and cost-effective routes. Lead immobilization is a strategy to transform water-soluble lead ions into insoluble, nonbioavailable and nontransportable forms over large pH and temperature ranges and to suppress lead leakage if the devices are damaged. An ideal methodology should ensure sufficient lead-chelating capability without substantially influencing the device performance, production cost and recycling. Here we analyse chemical approaches to immobilize Pb2+ from perovskite solar cells, such as grain isolation, lead complexation, structure integration and adsorption of leaked lead, based on their feasibility to suppress lead leakage to a minimal level. We highlight the need for a standard lead-leakage test and related mathematical model to be established for the reliable evaluation of the potential environmental risk of perovskite optoelectronics.
RESUMO
Optoelectronic devices consist of heterointerfaces formed between dissimilar semiconducting materials. The relative energy-level alignment between contacting semiconductors determinately affects the heterointerface charge injection and extraction dynamics. For perovskite solar cells (PSCs), the heterointerface between the top perovskite surface and a charge-transporting material is often treated for defect passivation1-4 to improve the PSC stability and performance. However, such surface treatments can also affect the heterointerface energetics1. Here we show that surface treatments may induce a negative work function shift (that is, more n-type), which activates halide migration to aggravate PSC instability. Therefore, despite the beneficial effects of surface passivation, this detrimental side effect limits the maximum stability improvement attainable for PSCs treated in this way. This trade-off between the beneficial and detrimental effects should guide further work on improving PSC stability via surface treatments.
RESUMO
Anthocyanins play critical roles in protecting plant tissues against diverse stresses. The complicated regulatory networks induced by various environmental factors modulate the homeostatic level of anthocyanins. Here, we show that anthocyanin accumulation is induced by brassinosteroids (BRs) in Arabidopsis (Arabidopsis thaliana) shoots and shed light on the underlying regulatory mechanism. We observed that anthocyanin levels are altered considerably in BR-related mutants, and BRs induce anthocyanin accumulation by up-regulating the expression of anthocyanin biosynthetic genes. Our genetic analysis indicated that BRASSINAZOLE RESISTANT 1 (BZR1) and PRODUCTION OF ANTHOCYANIN PIGMENT 1 (PAP1) are essential for BR-induced anthocyanin accumulation. The BR-responsive transcription factor BZR1 directly binds to the PAP1 promoter, regulating its expression. In addition, we found that intense anthocyanin accumulation caused by the pap1-D dominant mutation is significantly reduced in BR mutants, implying that BR activity is required for PAP1 function after PAP1 transcription. Moreover, we demonstrated that BZR1 physically interacts with PAP1 to cooperatively regulate the expression of PAP1 target genes, such as TRANSPARENT TESTA 8 (TT8), DIHYDROFLAVONOL 4-REDUCTASE (DFR), and LEUKOANTHOCYANIDIN DIOXYGENASE (LDOX). Our findings indicate that BZR1 functions as an integral component of the PAP1-containing transcription factor complex, contributing to increased anthocyanin biosynthesis. Notably, we also show that functional interaction of BZR1 with PAP1 is required for anthocyanin accumulation induced by low nitrogen stress. Taken together, our results demonstrate that BR-regulated BZR1 promotes anthocyanin biosynthesis through cooperative interaction with PAP1 of the MBW complex.
RESUMO
Enabling the precise control of protein functions with artificially programmed reaction patterns is beneficial for investigating biological processes. Although several strategies have been established that employ the programmability of nucleic acid, they have been limited to DNA hybridization without external stimuli or target binding. Here, we report an approach for the DNA-mediated control of the tripartite split-GFP assembly via aptamers with responsiveness to intracellular small molecules as stimuli. We designed a novel structure-switching aptamer-peptide conjugate as a hetero modulator for split GFP in response to ATP. By conjugating two peptides (S10/11) derived from the tripartite split-GFP to ATP aptamer, we achieved GFP reassembly using only ATP as a trigger molecule. The response to ATP at ≥4 mM concentrations indicated that it can be applied to respond to intracellular ATP in live cells. Furthermore, our hetero-modulator exhibited high and long-term stability, with a half-life of approximately four days in a serum stability assay, demonstrating resistance to nuclease degradation. We validated that our aptamer-modulator split GFP was successfully reconstituted in the cell in response to intracellular ATP levels. Our aptamer-modulated split GFP platform can be utilized to monitor a wide range of intracellular metabolites by replacing the aptamer sequence.
Assuntos
Trifosfato de Adenosina , Aptâmeros de Nucleotídeos , Proteínas de Fluorescência Verde , Peptídeos , Trifosfato de Adenosina/metabolismo , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Fluorescência Verde/genética , Humanos , Peptídeos/química , Peptídeos/metabolismo , DNA/química , DNA/metabolismo , Fluorescência , Células HeLaRESUMO
Antimicrobial resistance presents us with a potential global crisis as it undermines the abilities of conventional antibiotics to combat pathogenic microbes. The history of antimicrobial agents is replete with examples of scaffolds containing halogens. In this review, we discuss the impacts of halogen atoms in various antibiotic types and antimicrobial scaffolds and their modes of action, structure-activity relationships, and the contributions of halogen atoms in antimicrobial activity and drug resistance. Other halogenated molecules, including carbohydrates, peptides, lipids, and polymeric complexes, are also reviewed, and the effects of halogenated scaffolds on pharmacokinetics, pharmacodynamics, and factors affecting antimicrobial and antivirulence activities are presented. Furthermore, the potential of halogenation to circumvent antimicrobial resistance and rejuvenate impotent antibiotics is addressed. This review provides an overview of the significance of halogenation, the abilities of halogens to interact in biomolecular settings and enhance pharmacological properties, and their potential therapeutic usages in preventing a postantibiotic era. SIGNIFICANCE STATEMENT: Antimicrobial resistance and the increasing impotence of antibiotics are critical threats to global health. The roles and importance of halogen atoms in antimicrobial drug scaffolds have been established, but comparatively little is known of their pharmacological impacts on drug resistance and antivirulence activities. This review is the first to extensively evaluate the roles of halogen atoms in various antibiotic classes and pharmacological scaffolds and to provide an overview of their ability to overcome antimicrobial resistance.
Assuntos
Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Halogênios/química , Halogenação , Relação Estrutura-AtividadeRESUMO
The enzyme-linked immunosorbent spot (ELISpot) assay is a powerful in vitro immunoassay that enables cost-effective quantification of antigen-specific T-cell reactivity. It is used widely in the context of cancer and infectious diseases to validate the immunogenicity of predicted epitopes. While technological advances have kept pace with the demand for increased throughput, efforts to increase scale are bottlenecked by current assay design and deconvolution methods, which have remained largely unchanged. Current methods for designing pooled ELISpot experiments offer limited flexibility of assay parameters, lack support for high-throughput scenarios and do not consider peptide identity during pool assignment. We introduce the ACE Configurator for ELISpot (ACE) to address these gaps. ACE generates optimized peptide-pool assignments from highly customizable user inputs and handles the deconvolution of positive peptides using assay readouts. In this study, we present a novel sequence-aware pooling strategy, powered by a fine-tuned ESM-2 model that groups immunologically similar peptides, reducing the number of false positives and subsequent confirmatory assays compared to existing combinatorial approaches. To validate ACE's performance on real-world datasets, we conducted a comprehensive benchmark study, contextualizing design choices with their impact on prediction quality. Our results demonstrate ACE's capacity to further increase precision of identified immunogenic peptides, directly optimizing experimental efficiency. ACE is freely available as an executable with a graphical user interface and command-line interfaces at https://github.com/pirl-unc/ace.
Assuntos
Benchmarking , Imunoadsorventes , Epitopos , PeptídeosRESUMO
Measuring cellular and tissue mechanics inside intact living organisms is essential for interrogating the roles of force in physiological and disease processes. Current agents for studying the mechanobiology of intact, living organisms are limited by poor light penetration and material stability. Magnetomotive ultrasound is an emerging modality for real-time in vivo imaging of tissue mechanics. Nonetheless, it has poor sensitivity and spatiotemporal resolution. Here we describe magneto-gas vesicles (MGVs), protein nanostructures based on gas vesicles and magnetic nanoparticles that produce differential ultrasound signals in response to varying mechanical properties of surrounding tissues. These hybrid nanomaterials significantly improve signal strength and detection sensitivity. Furthermore, MGVs enable non-invasive, long-term and quantitative measurements of mechanical properties within three-dimensional tissues and in vivo fibrosis models. Using MGVs as novel contrast agents, we demonstrate their potential for non-invasive imaging of tissue elasticity, offering insights into mechanobiology and its application to disease diagnosis and treatment.
Assuntos
Nanopartículas , Nanoestruturas , Diagnóstico por Imagem/métodos , Proteínas/química , Acústica , Nanopartículas/químicaRESUMO
Conducting polymers are mixed ionic-electronic conductors that are emerging candidates for neuromorphic computing, bioelectronics and thermoelectrics. However, fundamental aspects of their many-body correlated electron-ion transport physics remain poorly understood. Here we show that in p-type organic electrochemical transistors it is possible to remove all of the electrons from the valence band and even access deeper bands without degradation. By adding a second, field-effect gate electrode, additional electrons or holes can be injected at set doping states. Under conditions where the counterions are unable to equilibrate in response to field-induced changes in the electronic carrier density, we observe surprising, non-equilibrium transport signatures that provide unique insights into the interaction-driven formation of a frozen, soft Coulomb gap in the density of states. Our work identifies new strategies for substantially enhancing the transport properties of conducting polymers by exploiting non-equilibrium states in the coupled system of electronic charges and counterions.
RESUMO
Children with sickle cell disease (SCD) demonstrate cerebral hemodynamic stress and are at high risk of strokes. We hypothesized that curative hematopoietic stem cell transplant (HSCT) normalizes cerebral hemodynamics in children with SCD compared with pre-transplant baseline. Whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were measured by magnetic resonance imaging 1 to 3 months before and 12 to 24 months after HSCT in 10 children with SCD. Three children had prior overt strokes, 5 children had prior silent strokes, and 1 child had abnormal transcranial Doppler ultrasound velocities. CBF and OEF of HSCT recipients were compared with non-SCD control participants and with SCD participants receiving chronic red blood cell transfusion therapy (CRTT) before and after a scheduled transfusion. Seven participants received matched sibling donor HSCT, and 3 participants received 8 out of 8 matched unrelated donor HSCT. All received reduced-intensity preparation and maintained engraftment, free of hemolytic anemia and SCD symptoms. Pre-transplant, CBF (93.5 mL/100 g/min) and OEF (36.8%) were elevated compared with non-SCD control participants, declining significantly 1 to 2 years after HSCT (CBF, 72.7 mL/100 g per minute; P = .004; OEF, 27.0%; P = .002), with post-HSCT CBF and OEF similar to non-SCD control participants. Furthermore, HSCT recipients demonstrated greater reduction in CBF (-19.4 mL/100 g/min) and OEF (-8.1%) after HSCT than children with SCD receiving CRTT after a scheduled transfusion (CBF, -0.9 mL/100 g/min; P = .024; OEF, -3.3%; P = .001). Curative HSCT normalizes whole-brain hemodynamics in children with SCD. This restoration of cerebral oxygen reserve may explain stroke protection after HSCT in this high-risk patient population.
Assuntos
Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Acidente Vascular Cerebral , Humanos , Criança , Anemia Falciforme/terapia , Acidente Vascular Cerebral/prevenção & controle , Hemodinâmica , Oxigênio , Circulação CerebrovascularRESUMO
BACKGROUND: Platelet adhesion and aggregation play a crucial role in arterial thrombosis and ischemic stroke. Here, we identify platelet ERO1α (endoplasmic reticulum oxidoreductase 1α) as a novel regulator of Ca2+ signaling and a potential pharmacological target for treating thrombotic diseases. METHODS: Intravital microscopy, animal disease models, and a wide range of cell biological studies were utilized to demonstrate the pathophysiological role of ERO1α in arteriolar and arterial thrombosis and to prove the importance of platelet ERO1α in platelet activation and aggregation. Mass spectrometry, electron microscopy, and biochemical studies were used to investigate the molecular mechanism. We used novel blocking antibodies and small-molecule inhibitors to study whether ERO1α can be targeted to attenuate thrombotic conditions. RESULTS: Megakaryocyte-specific or global deletion of Ero1α in mice similarly reduced platelet thrombus formation in arteriolar and arterial thrombosis without affecting tail bleeding times and blood loss following vascular injury. We observed that platelet ERO1α localized exclusively in the dense tubular system and promoted Ca2+ mobilization, platelet activation, and aggregation. Platelet ERO1α directly interacted with STIM1 (stromal interaction molecule 1) and SERCA2 (sarco/endoplasmic reticulum Ca2+-ATPase 2) and regulated their functions. Such interactions were impaired in mutant STIM1-Cys49/56Ser and mutant SERCA2-Cys875/887Ser. We found that ERO1α modified an allosteric Cys49-Cys56 disulfide bond in STIM1 and a Cys875-Cys887 disulfide bond in SERCA2, contributing to Ca2+ store content and increasing cytosolic Ca2+ levels during platelet activation. Inhibition of Ero1α with small-molecule inhibitors but not blocking antibodies attenuated arteriolar and arterial thrombosis and reduced infarct volume following focal brain ischemia in mice. CONCLUSIONS: Our results suggest that ERO1α acts as a thiol oxidase for Ca2+ signaling molecules, STIM1 and SERCA2, and enhances cytosolic Ca2+ levels, promoting platelet activation and aggregation. Our study provides evidence that ERO1α may be a potential target to reduce thrombotic events.
Assuntos
AVC Isquêmico , Trombose , Animais , Camundongos , Plaquetas/metabolismo , Sinalização do Cálcio , Dissulfetos , AVC Isquêmico/metabolismo , Ativação PlaquetáriaRESUMO
The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS-CoV-2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS-CoV-2 viral titres. We investigate the potential viral proteins involved in abrogating tetherin function and find that SARS-CoV-2 ORF3a reduces tetherin localisation within biosynthetic organelles where Coronaviruses bud, and increases tetherin localisation to late endocytic organelles via reduced retrograde recycling. We also find that expression of Spike protein causes a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS-CoV-2 and highlight the multiple distinct mechanisms by which SARS-CoV-2 subverts tetherin function.
Assuntos
Antígeno 2 do Estroma da Médula Óssea , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Liberação de Vírus , Humanos , Antígeno 2 do Estroma da Médula Óssea/antagonistas & inibidores , Antígeno 2 do Estroma da Médula Óssea/metabolismo , COVID-19/virologia , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Carbon allotropes have contributed to all aspects of people's lives throughout human history. As emerging carbon-based low-dimensional materials, graphyne family members (GYF), represented by graphdiyne, have a wide range potential applications due to their superior physical and chemical properties. In particular, graphdiyne (GDY), as the leader of the graphyne family, has been practically applied to various research fields since it was first successfully synthesized. GYF have a large surface area, both sp and sp2 hybridization, and a certain band gap, which was considered to originate from the overlap of carbon 2pz orbitals and the inhomogeneous π-bonds of carbon atoms in different hybridization forms. These properties mean GYF-based materials still have many potential applications to be developed, especially in energy storage and catalytic utilization. Since most of the GYF have yet to be synthesized and applications of successfully synthesized GYF have not been developed for a long time, theoretical results in various application fields should be shared to experimentalists to attract more intentions. In this Review, we summarized and discussed the synthesis, structural properties, and applications of GYF-based materials from the theoretical insights, hoping to provide different viewpoints and comments.
RESUMO
BACKGROUND: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings. OBJECTIVE: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods. DESIGN: Binational, longitudinal, propensity-matched cohort study. SETTING: Nationwide claims-based databases in South Korea (K-COV-N cohort) and Japan (JMDC cohort). PARTICIPANTS: 10 027 506 Korean and 12 218 680 Japanese patients aged 20 years or older, including those with COVID-19 between 1 January 2020 and 31 December 2021, matched to patients with influenza infection and to uninfected control patients. MEASUREMENTS: The primary outcome was onset of AIRD (per appropriate codes from the International Classification of Diseases, 10th Revision) 1, 6, and 12 months after COVID-19 or influenza infection or the respective matched index date of uninfected control patients. RESULTS: Between 2020 and 2021, among the 10 027 506 Korean participants (mean age, 48.4 years [SD, 13.4]; 50.1% men), 394 274 (3.9%) and 98 596 (0.98%) had a history of COVID-19 or influenza, respectively. After propensity score matching, beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25 [95% CI, 1.18 to 1.31]) and influenza-infected control patients (adjusted hazard ratio, 1.30 [CI, 1.02 to 1.59]). The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort. LIMITATIONS: Referral bias due to the pandemic; residual confounding. CONCLUSION: SARS-CoV-2 infection was associated with increased risk for incident AIRD compared with matched patients without SARS-CoV-2 infection or with influenza infection. The risk for incident AIRD was higher with greater severity of acute COVID-19. PRIMARY FUNDING SOURCE: National Research Foundation of Korea.
Assuntos
COVID-19 , Influenza Humana , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , COVID-19/epidemiologia , Estudos de Coortes , SARS-CoV-2 , Estudos LongitudinaisRESUMO
High power conversion efficiency (PCE) and long-term stability are essential prerequisites for the commercialization of polymer solar cells (PSCs). Small-molecule acceptors (SMAs) are core materials that have led to recent, rapid increases in the PCEs of the PSCs. However, a critical limitation of the resulting PSCs is their poor long-term stability. Blend morphology degradation from rapid diffusion of SMAs with low glass transition temperatures (Tgs) is considered the main cause of the poor long-term stability of the PSCs. The recent emergence of oligomerized SMAs (OSMAs), composed of two or more repeating SMA units (i.e., dimerized and trimerized SMAs), has shown great promise in overcoming these challenges. This innovation in material design has enabled OSMA-based PSCs to reach impressive PCEs near 19% and exceptional long-term stability. In this review, we summarize the evolution of OSMAs, including their research background and recent progress in molecular design. In particular, we discuss the mechanisms for high PCE and stability of OSMA-based PSCs and suggest useful design guidelines for high-performance OSMAs. Furthermore, we reflect on the existing hurdles and future directions for OSMA materials towards achieving commercially viable PSCs with high PCEs and operational stabilities.
RESUMO
Halide perovskite-based resistive switching memory (memristor) has potential in an artificial synapse. However, an abrupt switch behavior observed for a formamidinium lead triiodide (FAPbI3)-based memristor is undesirable for an artificial synapse. Here, we report on the δ-FAPbI3/atomic-layer-deposited (ALD)-SnO2 bilayer memristor for gradual analogue resistive switching. In comparison to a single-layer δ-FAPbI3 memristor, the heterojunction δ-FAPbI3/ALD-SnO2 bilayer effectively reduces the current level in the high-resistance state. The analog resistive switching characteristics of δ-FAPbI3/ALD-SnO2 demonstrate exceptional linearity and potentiation/depression performance, resembling an artificial synapse for neuromorphic computing. The nonlinearity of long-term potentiation and long-term depression is notably decreased from 12.26 to 0.60 and from -8.79 to -3.47, respectively. Moreover, the δ-FAPbI3/ALD-SnO2 bilayer achieves a recognition rate of ≤94.04% based on the modified National Institute of Standards and Technology database (MNIST), establishing its potential in an efficient artificial synapse.
RESUMO
In this study, we examined the nanostructured molecular packing and orientations of poly[[N,N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)] (P(NDI2OD-T2)) films formed on water for the application of nanotechnology-based organic electronic devices. First, the nanoscale molecule-substrate interaction between the polymer and water was modulated by controlling the alkyl side chain length in NDI-based copolymers. Increasing alkyl side chain lengths induced a nanomorphological transition from face-on to edge-on orientation, confirmed by molecular dynamics simulations revealing nanostructural behavior. Second, the nanoscale intermolecular interactions of P(NDI2OD-T2) were controlled by varying the volume ratio of the high-boiling-point additive solvent in the binary solvent blends. As the additive solvent ratio increased, the nanostructured molecular orientation of the P(NDI2OD-T2) films on water changed remarkably from edge-on to bimodal with more face-on crystallites, thereby affecting charge transport. Our finding provides essential insights for precise nanoscale morphological control on water substrates, enabling the formation of high-performance polymer films for organic electronic devices.
RESUMO
Electrochemical CO2 reduction reaction (eCO2RR) over Cu-based catalysts is a promising approach for efficiently converting CO2 into value-added chemicals and alternative fuels. However, achieving controllable product selectivity from eCO2RR remains challenging because of the difficulty in controlling the oxidation states of Cu against robust structural reconstructions during the eCO2RR. Herein, we report a novel strategy for tuning the oxidation states of Cu species and achieving eCO2RR product selectivity by adjusting the Cu content in CuMgAl-layered double hydroxide (LDH)-based catalysts. In this strategy, the highly stable Cu2+ species in low-Cu-containing LDHs facilitated the strong adsorption of *CO intermediates and further hydrogenation into CH4. Conversely, the mixed Cu0/Cu+ species in high-Cu-containing LDHs derived from the electroreduction during the eCO2RR accelerated C-C coupling reactions. This strategy to regulate Cu oxidation states using LDH nanostructures with low and high Cu molar ratios produced an excellent eCO2RR performance for CH4 and C2+ products, respectively.
RESUMO
BACKGROUND: Homologous recombination deficiency (HRD) stands as a clinical indicator for discerning responsive outcomes to platinum-based chemotherapy and poly ADP-ribose polymerase (PARP) inhibitors. One of the conventional approaches to HRD prognostication has generally centered on identifying deleterious mutations within the BRCA1/2 genes, along with quantifying the genomic scars, such as Genomic Instability Score (GIS) estimation with scarHRD. However, the scarHRD method has limitations in scenarios involving tumors bereft of corresponding germline data. Although several RNA-seq-based HRD prediction algorithms have been developed, they mainly support cohort-wise classification, thereby yielding HRD status without furnishing an analogous quantitative metric akin to scarHRD. This study introduces the expHRD method, which operates as a novel transcriptome-based framework tailored to n-of-1-style HRD scoring. RESULTS: The prediction model has been established using the elastic net regression method in the Cancer Genome Atlas (TCGA) pan-cancer training set. The bootstrap technique derived the HRD geneset for applying the expHRD calculation. The expHRD demonstrated a notable correlation with scarHRD and superior performance in predicting HRD-high samples. We also performed intra- and extra-cohort evaluations for clinical feasibility in the TCGA-OV and the Genomic Data Commons (GDC) ovarian cancer cohort, respectively. The innovative web service designed for ease of use is poised to extend the realms of HRD prediction across diverse malignancies, with ovarian cancer standing as an emblematic example. CONCLUSIONS: Our novel approach leverages the transcriptome data, enabling the prediction of HRD status with remarkable precision. This innovative method addresses the challenges associated with limited available data, opening new avenues for utilizing transcriptomics to inform clinical decisions.
Assuntos
Recombinação Homóloga , Neoplasias , Transcriptoma , Humanos , Transcriptoma/genética , Recombinação Homóloga/genética , Neoplasias/genética , Algoritmos , Feminino , Perfilação da Expressão Gênica/métodosRESUMO
In many cases of traumatic brain injury (TBI), conspicuous abnormalities, such as scalp wounds and intracranial hemorrhages, abate over time. However, many unnoticeable symptoms, including cognitive, emotional, and behavioral dysfunction, often last from several weeks to years after trauma, even for mild injuries. Moreover, the cause of such persistence of symptoms has not been examined extensively. Recent studies have implicated the dysregulation of the molecular system in the injured brain, necessitating an in-depth analysis of the proteome and signaling pathways that mediate the consequences of TBI. Thus, in this study, the brain proteomes of two TBI models were examined by quantitative proteomics during the recovery period to determine the molecular mechanisms of TBI. Our results show that the proteomes in both TBI models undergo distinct changes. A bioinformatics analysis demonstrated robust activation and inhibition of signaling pathways and core proteins that mediate biological processes after brain injury. These findings can help determine the molecular mechanisms that underlie the persistent effects of TBI and identify novel targets for drug interventions.