RESUMEN
An unexpected, divergent and efficient approach toward furanoid-bridged fullerene dimers C120O and C120O2 was established under different solvent-free ball-milling conditions by simply using pristine C60 as the starting material, water as the oxygen source and FeCl3 as the mediator. The structures of C120O and C120O2 were unambiguously established by single-crystal X-ray crystallography. A plausible reaction mechanism is proposed on the basis of control experiments. Furthermore, C120O2 has been applied in organic solar cells as the third component and exhibits good performance.
RESUMEN
The photocatalytic efficiency can be improved by constructing a Z-scheme heterojunction, but hindered by the only half utilization efficiency of photogenerated carriers. Thus, a novel material, UiO-66-NH2@TAPB-BTCA-COP-Ag (U6N@COP-Ag), with surface plasmon resonance (SPR) effect synergistic Z-scheme heterostructure has been prepared by depositing Ag nanoparticles (Ag NPs) on TAPB-BTCA-COP (COP)-coated UiO-66-NH2. The deposited Ag NPs expand the range of light absorption and introduce more photogenerated electrons in the composite. The SPR effect of noble metal compensates for the limited utilization of the Z-scheme heterojunction photogenerated carriers and the increased density of semiconductor carriers at the reducing end, which is more conducive to the redox reaction of the catalyst. Without sacrificial agents, U6N@COP-Ag shows great photocatalytic nitrogen reduction conversion efficiency with the rate of NH4+ in ammonia water at 167.63µmol g-1h-1, which is 6.6 and 2.8 times that of the original UiO-66-NH2 and COP, respectively. In-situ XPS and Kelvin probe technology verify that UiO-66-NH2 and Ag nanoparticles provide more photogenerated electrons to COP. The cleavage and conversion of N2 to NH4+ on U6N@COP-Ag was confirmed by the enhancement of NH bonds and NH4+ characteristic absorption peaks in the in-situ diffuse reflectance infrared Fourier transform spectroscopy (in-situ DRIFTS). This work presents a great method to improve the Z-scheme heterojunction photogenerated carrier utilization and the density of semiconductor carriers at the reducing end by the noble metal SPR effect, which is more conducive to enhance the redox reaction of the catalyst.
RESUMEN
The blood-brain barrier is known to consist of a variety of cells and complex inter-cellular junctions that protect the vulnerable brain from neurotoxic compounds; however, it also complicates the pharmacological treatment of central nervous system disorders as most drugs are unable to penetrate the blood-brain barrier on the basis of their own structural properties. This dramatically diminished the therapeutic effect of the drug and compromised its biosafety. In response, a number of drugs are often delivered to brain lesions in invasive ways that bypass the obstruction of the blood-brain barrier, such as subdural administration, intrathecal administration, and convection-enhanced delivery. Nevertheless, these intrusive strategies introduce the risk of brain injury, limiting their clinical application. In recent years, the intensive development of nanomaterials science and the interdisciplinary convergence of medical engineering have brought light to the penetration of the blood-brain barrier for brain-targeted drugs. In this paper, we extensively discuss the limitations of the blood-brain barrier on drug delivery and non-invasive brain-targeted strategies such as nanomedicine and blood-brain barrier disruption. In the meantime, we analyze their strengths and limitations and provide outlooks on the further development of brain-targeted drug delivery systems.
RESUMEN
INTRODUCTION: Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab. METHODS: Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan-Meier method and Cox regression models. RESULTS: Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001-3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150-5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078-6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173-12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043). CONCLUSIONS: Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6-VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.
Asunto(s)
Bevacizumab , Inestabilidad Cromosómica , Neoplasias Colorrectales , Hepatectomía , Neoplasias Hepáticas , Humanos , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/tratamiento farmacológico , Masculino , Femenino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Persona de Mediana Edad , Pronóstico , Anciano , Antineoplásicos Inmunológicos/uso terapéutico , Adulto , Interleucina-6/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Estudios RetrospectivosRESUMEN
Adsorptive ethylene separation from the C2H2/C2H4/C2H6/CO2 four-component gas mixture provides a low-energy input solution for industrial ethylene purification, yet it is still a great challenge. Herein, we report a facile scaled-up synthesis of a stable ultramicroporous coordination network of Zn-CO3-datz (Hdatz = 3,5-diamine-1,2,4-triazole), which enables selective adsorption of C2H2, C2H4 and CO2 over C2H4, thanks to its specific pore environment supported by GCMC simulation of gas adsorption sites. Dynamic breakthrough experiments exhibited efficient one-step production of polymer-grade (≥99.95%) C2H4 from the quaternary C2H4/C2H2/C2H6/CO2 (1/1/1/1) mixture, with excellent C2H4 productivity of 0.12 mol kg-1 at 298 K. Moreover, it can be easily synthesized in kilogram scale with an affordable and low-cost ligand, rendering its further potential industrial applications.
RESUMEN
Quantum dot sensitized solar cells (QDSCs) represent a promising third-generation photovoltaic technology, boasting a high theoretical efficiency of 44% and cost efficiency. However, their practical efficiency is constrained by reduced photovoltage (Voc) and fill factor (FF). One primary reason is the inefficient charge transfer and elevated recombination rates at the counter electrode (CE). In this work, a novel CE composed of a titanium mesh loaded with Co,NâC@MoS2 is introduced for the assembly of QDSCs. The incorporation of nanosized MoS2 enhances the density of catalytic sites, while the Co,NâC component ensures high conductivity and provides a substantial active surface area. Additionally, the titanium mesh's 3D structure serves as an effective electrical conduit, facilitating rapid electron transfer from the external circuit to the composite. These improvements in catalytic activity, charge transfer rate, and stability of the CE significantly enhance the photovoltaic performance of QDSCs. The optimized cells achieve a groundbreaking power conversion efficiency (PCE) of 16.39%, accompanied by a short-circuit current density (Jsc) of 27.26 mA cm-2, Voc of 0.818 V, and FF of 0.735. These results not only offer a new strategy for designing electrodes with high catalytic activity but also underscore the promising application of the Co,NâC@MoS2 composite in enhancing QDSC technology.
RESUMEN
Two dual fluorescent/phosphorescent tris-heteroleptic mononuclear Ru(ΙΙ) complexes (2 and 3) were designed and applied in amyloid-ß (Aß) sensing. These complexes have a general formula of [Ru(phen)(dppz)(L)](PF6)2, where L is (2-pyrazinyl)(2-pyridyl)(methyl)amine (H-L) with different substituents (-OMe for 2, -H for 3), phen is 1,10-phenanthroline, and dppz is dipyridophenazine, respectively. Compared with the previously reported ratiometric probe 1 with a di(pyrid-2-yl)(methyl)amine ligand, complex 2 can be employed for not only ratiometric emissive detection of Aß aggregation but also ratiometric imaging detection of Aß fibrils. In ratiometric emissive detection, as the incubation time of the Aß sample (Aß40 and Aß42) was prolonged, a new phosphorescence emission band appeared with gradual enhancement of the emission intensity, while the fluorescence emission was basically unchanged, which could be treated as an intrinsic internal reference signal. In comparison, a larger ratiometric photoluminescence enhancement (I640/I440) was observed for Aß40 aggregation with respect to Aß42. In ratiometric imaging detection, the imaging signals obtained from the phosphorescence emission are much brighter than the fluorescence emission in both Aß40 and Aß42 fibrils. As indicated by molecular docking results, stronger interactions were found between complex 2 with Aß40 fibrils, which included π/π, π/C-H, and π/H interactions between bidentate ligands dppz and phen with amino acid residues. Moreover, computational calculations were carried out to assist the interpretation of these experimental findings.
RESUMEN
The VCPIP1-P97/VCP (Valosin-Containing Protein) complex is required for post-mitotic Golgi cisternae reassembly and maintenance in interphase. However, the organization and mechanism of this complex in regulating Golgi membrane fusion is still elusive. Here, the cryo-electron microscopy (cryo-EM) structures of the human VCPIP1-P97/VCP complex are presented. These studies reveal that three independent VCPIP1 molecules sit over the C-terminal substrate exit tunnel formed by P97/VCP homo-hexamer, resulting in an unusual C3 to C6 symmetric barrel architecture. The UFD1 (unknown function domain 1) from VCPIP1, but not the N-terminal OTU domain and the C-terminal UBL domain, docks to the two adjacent D2 domains of P97/VCP, allosterically causing the cofactors binding domain-NTDs (N-terminal domains) of P97/VCP in a "UP" and D1 domain in an ATPase competent conformation. Conversely, VCPIP1 bound P97/VCP hexamer favors the binding of P47, and thus the intact SNARE complex, promoting Golgi membrane fusion. These studies not only reveal the unexpected organization of humanVCPIP1-P97/VCP complex, but also provide new insights into the mechanism of VCPIP1-P97/VCP mediated Golgi apparatus reassembly, which is a fundamental cellular event for protein and lipid processing.
RESUMEN
BACKGROUND: BCR::ABL1-like or Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) was first reported in 2009. Ph-like ALL is characterized by gene signature similar to Philadelphia chromosome ALL, but without BCR::ABL1 fusions. Molecularly, Ph-like ALL is divided into seven categories, with CRLF2 and ABL-class rearrangements being the two most common subtypes, exhibiting alterations in distinct downstream signaling cascades. CASE PRESENTATION: We report a rare case of pediatric Ph-like ALL with concomitant CRLF2 and ABL1 rearrangements. CRLF2 was fused with P2RY8, its most common fusion partner, whereas ABL1 was fused with MYO18B, a novel fusion partner that has not been previously reported. The 4-year-old female patient was treated using the national multicenter CCCG-ALL-2020 protocol with the addition of dasatinib at the end of induction when ABL1 rearrangement was confirmed by RNA-seq. Morphologically and molecularly, the patient remained in continuous remission until the last follow-up. To the best of our knowledge, this is the first case of Ph-like ALL harboring two distinct rearrangement categories. CONCLUSIONS: Our results identified that ABL1 rearrangement and CRLF2 rearrangement can coexist. The application of FISH, whole transcription sequencing, PCR can help us to have a more comprehensive understanding of ALL cytogenetics and molecular biology. Further studies are needed to explore the role of targeted therapies in such rare clinical scenarios.
Asunto(s)
Reordenamiento Génico , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Citocinas , Humanos , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Preescolar , Receptores de Citocinas/genética , Proteínas Proto-Oncogénicas c-abl/genéticaRESUMEN
Lithium-sulfur (Li-S) batteries are considered promising energy-storage systems because of their high theoretical energy density, low cost, and eco-friendliness. However, problems such as the shuttle effect can result in the loss of active materials, poor cyclability, and rapid capacity degradation. The utilization of a structural configuration that enhances electrochemical performance via dual adsorption-catalysis strategies can overcome the limitations of Li-S batteries. In this study, an integrated interlayer structure, in which hollow carbon fibers (HCFs) were modified with in-situ-generated Ni nanoparticles, was prepared by scalable one-step carbonization. Highly hierarchically porous HCFs act as the carbon skeleton and provide a continuous three-dimensional conductive network that enhances ion/electron diffusion. Ni nanoparticles with superior anchoring and catalytic abilities can prevent the shuttle effect and increase the conversion rate, thereby promoting the electrochemical performance. This synergistic effect resulted in a high capacity retention of 582 mAh g-1 at 1 C after 100 cycles, providing an excellent rate capability of up to 3 C. The novel structure, wherein Ni nanoparticles are embedded in cotton-tissue-derived HCFs, provides a new avenue for enhancing electrochemical performance at high C rates. This results in a low-cost, sustainable, and high-performance hybrid material for the development of practical Li-S batteries.
RESUMEN
ABSTRACT: This report presents a case of suspected Parkinson disease in a 76-year-old woman with a history of slurred speech, general weakness, unstable gait, and bradykinesia for months. A 99mTc-TRODAT-1 SPECT scan revealed a symmetrically decreased bilateral nigrostriatal system, including bilateral putamen and caudate nuclei. The scintigraphic findings may reflect normal aging or atypical parkinsonism. The bilateral frontal bones and left temporal bone exhibited increased uptake of 99mTc-TRODAT-1, and previous 99mTc-MDP bone scan and CT images were reviewed. Osteolytic lesions at the corresponding site indicated bone metastasis from breast cancer.
RESUMEN
BACKGROUND: Telomere shortening and epigenetic modifications are key factors in aging and hematologic diseases. This study investigates the relationship of telomere length and epigenetic age acceleration (EAA) with hematologic cancers, blood cells, and biochemical markers through the epigenetic clocks. METHODS: This study primarily utilizes genome-wide association studies of populations of European descent as instrumental variables, exploring the causal relationships between exposures and outcomes through a bidirectional two-sample Mendelian randomization (MR) approach. MR techniques include inverse variance weighted (IVW), MR Egger, and weighted median modes. Heterogeneity and pleiotropy in MR are assessed using Cochran's Q test and the MR Egger intercept, with the robustness of the conclusions further validated by multivariable MR (MVMR). RESULTS: Our research shows that longer telomere lengths significantly increase the risk of multiple myeloma, leukemia, and lymphoma (OR > 1, P < 0.05) and establish a causal relationship between telomere length and red blood cell indices such as RBC (OR = 1.121, PIVW = 0.034), MCH (OR = 0.801, PIVW = 2.046e-06), MCV (OR = 0.801, PIVW = 0.001), and MCHC (OR = 0.813, PIVW = 0.002). Additionally, MVMR analysis revealed an association between DNA methylation PhenoAge acceleration and alkaline phosphatase (OR = 1.026, PIVW = 0.007). CONCLUSION: The study clarifies the relationships between telomere length, EAA, and hematological malignancies, further emphasizing the prognostic significance of telomere length and EAA. This deepens our understanding of the pathogenesis of hematological diseases, which can inform risk assessment and therapeutic strategies.
Asunto(s)
Epigénesis Genética , Estudio de Asociación del Genoma Completo , Neoplasias Hematológicas , Análisis de la Aleatorización Mendeliana , Telómero , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Neoplasias Hematológicas/genética , Epigénesis Genética/genética , Estudio de Asociación del Genoma Completo/métodos , Telómero/genética , Metilación de ADN/genética , Femenino , Masculino , Homeostasis del Telómero/genética , Acortamiento del Telómero/genéticaRESUMEN
PURPOSE: To evaluate the therapeutic efficacy of intravenous amoxicillin clavulanate potassium combined with nebulized budesonide and ambroxol hydrochloride in pediatric community-acquired pneumonia (CAP) and its impact across various microbial strains and clinical symptoms. The primary objective of this study is to evaluate the efficacy of intravenous amoxicillin-clavulanate combined with nebulized budesonide and ambroxol hydrochloride in the treatment of pediatric community-acquired pneumonia (CAP), and to analyze their impact on different microbial strains and clinical symptoms. Secondary objectives include assessing the treatment's effect on the improvement of clinical symptoms, hospital stay duration, and the levels of inflammatory markers. DESIGN: Prospective, single-center study. METHODS: Fifty-six children with CAP, aged under 6 years, from Affiliated Maternity and Child Health Care Hospital of Nantong University were included. Patients were treated with conventional therapy and the study medication. Clinical characteristics, microbiological data, symptom improvement, and hospitalization times were analyzed. FINDINGS: Young children, particularly under 1 year, exhibited a higher incidence of multiple microbial infections and severe clinical manifestations. Treatment with budesonide and ambroxol hydrochloride led to significant clinical improvement across all age groups, with notable efficacy against various pathogens. CONCLUSIONS: Nebulized budesonide and ambroxol hydrochloride are effective in treating pediatric CAP, offering a promising therapeutic option, particularly for young children with severe presentations.
Asunto(s)
Ambroxol , Budesonida , Infecciones Comunitarias Adquiridas , Nebulizadores y Vaporizadores , Humanos , Ambroxol/administración & dosificación , Ambroxol/uso terapéutico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Femenino , Masculino , Preescolar , Lactante , Estudios Prospectivos , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Resultado del Tratamiento , Administración por Inhalación , Combinación Amoxicilina-Clavulanato de Potasio/administración & dosificación , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Niño , Neumonía/tratamiento farmacológico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Expectorantes/administración & dosificación , Expectorantes/uso terapéutico , Biomarcadores/sangre , Quimioterapia Combinada , Tiempo de InternaciónRESUMEN
OBJECTIVE: To investigate the effects of visualized precision electrophysiological diagnosis and transcutaneous low-frequency electrical stimulation (TES) on hypoxia-induced ED in high-altitude areas. METHODS: This study included 152 ED patients from high-altitude hypoxic areas treated by TES based on the parameters obtained from visualized precision electrophysiological diagnosis. We followed up the patients for 1 to 3 months and compared their IIEF-5 scores, nocturnal penile tumescence and rigidity (NPTR) and infrared thermal metabolic technology (TMT)-based temperature of the whole body and diseased parts before and after treatment. RESULTS: All the patients successfully completed 1 to 3 courses of TES. There were no statistically significant differences in the IIEF-5 scores (P<0.05) and penile tip optimal erection rigidity and duration (P<0.01) of the patients before and after treatment. TMT images indicated a temperature change of >1.5 â in the penis and bilateral inguinal regions after treatment, suggesting the effectiveness of electrical stimulation. No recurrence was observed during the follow-up. CONCLUSION: TES based on the parameters obtained from visualized precision electrophysiological diagnosis has a definite effect on hypoxia-induced ED by enhancing oxygen supply to the penile corpus cavernosum and improving its function and structure.
Asunto(s)
Altitud , Disfunción Eréctil , Hipoxia , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Masculino , Estimulación Eléctrica Transcutánea del Nervio/métodos , Disfunción Eréctil/terapia , Disfunción Eréctil/diagnóstico , Pene/fisiopatología , Erección Peniana , Resultado del TratamientoRESUMEN
The adsorbed nanobubbles inside the nanochannels can cause fluid transport blockages, which will obviously degrade the nanodevice performance and reduce the lifetime. However, due to small-scale effects, the removal of nanobubbles is a huge challenge at the nanoscale. Herein, molecular dynamics simulations are carried out to study the effect of the electrostatic field on underwater nitrogen nanobubbles confined in nanochannels. It is found that the nanobubbles will collapse under an appropriate electrostatic field, thereby unblocking the transport of water in the nanochannels. The formation of ordered water structures induced by electrostatic fields plays an important role in the removal of nanobubbles from the nanochannels. Our findings provide a convenient, controllable, and remote way to address the blockage problem of nanobubbles in nanochannels, which may have potential applications in improving the performance of fuel cells.
RESUMEN
In this paper, N-vinylpyrrolidone was copolymerized with acrylic acid and itaconic acid by free radical polymerization, and a series of polyacrylic acid-co-itaconic acid-co-N-vinylpyrrolidone (PAIN) dispersants with different pyrrolidone ligand contents were synthesized and characterized. Then, the cobalt blue nano-pigment slurry (20 wt%) was prepared through a water-based grinding method, and the optimum grinding technology was explored and determined as follows: PAIN2 as a dispersant, a dispersant dosage of 10 wt%, and a grinding time of 480 min. According to this optimum grinding technology, the prepared pigment slurry had a significantly decreased agglomeration, the D90 of which was 82 nm, and separately increased to 130 nm and 150 nm after heat storage for 3 and 7 days, exhibiting excellent heat storage stability. Additionally, its TSI value was also the lowest (1.9%), indicating good dispersion stability. The QCM and adorption capacity measuring results showed PAIN2 had a larger adsorption capacity, and the formed adsorption layer had a higher rigidity and was not easy to fall off. This was caused by both the interaction of carboxyl groups and the pyrrolidone ligand (strong coordination interaction) in PAIN2 with cobalt blue. The XPS and FT-IR measurements further proved the above-mentioned adsorption mechanism.
RESUMEN
Ni/Ni3Al heterogeneous multilayer structures are widely used in aerospace manufacturing because of their unique coherent interfaces and excellent mechanical properties. Revealing the deformation mechanisms of interfacial structures is of great significance for microstructural design and their engineering applications. Thus, this work aims to establish the connection between the evolution of an interfacial misfit dislocation (IMD) network and tensile deformation mechanisms of Ni/Ni3Al multilayer structures. It is shown that the decomposition of IMD networks dominates the deformation of Ni/Ni3Al multilayer structures, which exhibits distinct effects on crystallographic orientation and layer thickness. Specifically, the Ni/Ni3Al (100) multilayer structure achieves its maximum yield strength of 5.28 GPa at the layer thickness of 3.19 nm. As a comparison, the (110) case has a maximum yield strength of 4.35 GPa as the layer thickness is 3.01 nm. However, the yield strength of the (111) one seems irrelevant to layer thickness, which fluctuates between 10.89 and 11.81 GPa. These findings can provide new insights into a deep understanding of the evolution and deformation of the IMD network of Ni/Ni3Al multilayer structures.
RESUMEN
This study primarily investigated the improvement of high-dose Epigallocatechin-3-Gallate (EGCG)-induced deterioration of MP gel by soy protein isolate (SPI) addition. The results showed that EGCG could interact with MP, SPI, and HSPI (heated), indicating the competitive ability of SPI/HSPI against EGCG with MP. EGCG was encapsulated by SPI/HSPI with high encapsulation efficiency and antioxidation, with antioxidant activities of 78.5% â¼ 79.2%. FTIR and molecular docking results revealed that MP, SPI, and HSPI interacted with EGCG through hydrogen bonding and hydrophobic interactions. SPI/HSPI competed with MP for EGCG, leading to the restoration of MHC and Actin bands, alleviating the aggregation caused by EGCG and oxidation. Additionally, SPI/HSPI-E significantly reduced the high cooking loss (23.71 and 26.65%) and gel strength (13.60 and 17.02%) induced by EGCG. Hence, SPI competed with MP for EGCG binding site to ameliorate MP gel properties, thereby alleviating the detrimental changes in MP caused by high-dose EGCG and oxidation.
Asunto(s)
Catequina , Geles , Simulación del Acoplamiento Molecular , Proteínas de Soja , Catequina/química , Catequina/análogos & derivados , Catequina/metabolismo , Catequina/farmacología , Proteínas de Soja/química , Proteínas de Soja/metabolismo , Geles/química , Antioxidantes/química , Antioxidantes/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Animales , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Culinaria , Unión ProteicaRESUMEN
DSR2, a Sir2 domain-containing protein, protects bacteria from phage infection by hydrolyzing NAD+. The enzymatic activity of DSR2 is triggered by the SPR phage tail tube protein (TTP), while suppressed by the SPbeta phage-encoded DSAD1 protein, enabling phages to evade the host defense. However, the molecular mechanisms of activation and inhibition of DSR2 remain elusive. Here, we report the cryo-EM structures of apo DSR2, DSR2-TTP-NAD+ and DSR2-DSAD1 complexes. DSR2 assembles into a head-to-head tetramer mediated by its Sir2 domain. The C-terminal helical regions of DSR2 constitute four partner-binding cavities with opened and closed conformation. Two TTP molecules bind to two of the four C-terminal cavities, inducing conformational change of Sir2 domain to activate DSR2. Furthermore, DSAD1 competes with the activator for binding to the C-terminal cavity of DSR2, effectively suppressing its enzymatic activity. Our results provide the mechanistic insights into the DSR2-mediated anti-phage defense system and DSAD1-dependent phage immune evasion.