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Peroxidase-like catalysts are safe and low-cost candidates to tackle the dilemma in constructing sustainable cathodic heterogeneous electro-Fenton (CHEF) catalysts for water purification, but the elusive structure-property relationship of enzyme-like catalysts constitutes a pressing challenge for the advancement of CHEF processes in practically relevant water and wastewater treatment. Herein, we probe the origins of catalytic efficiency in the CHEF process by artificially tailoring the peroxidase-like activity of Fe3O4 through a series of acetylated chitosan-based hydrogels, which serve as ecofriendly alternatives to traditional carbon shells. The optimized acetylated chitosan wrapping Fe3O4 hydrogel on the cathode shows an impressive activity and stability in CHEF process, overcoming the complicated and environmentally unfavored procedures in the electro-Fenton-related processes. Structural characterizations and theoretical calculations reveal that the amide group in chitosan can modulate the intrinsic redox capacity of surficial Fe sites on Fe3O4 toward CHEF catalysis via the neutral hydrogen bond. This work provides a sustainable path and molecule-level insight for the rational design of high-efficiency CHEF catalysts and beyond.
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Vaccination is the most effective method to protect humans and animals from diseases. Anti-idiotype vaccines are safer due to their absence of pathogens. However, the commercial production of traditional anti-idiotype vaccines using monoclonal and polyclonal antibodies (mAb and pAb) is complex and has a high failure rate. The present study designed a novel, simple, low-cost strategy for developing anti-idiotype vaccines with nanobody technology. We used porcine circovirus type 2 (PCV2) as a viral model, which can result in serious economic loss in the pig industry. The neutralizing mAb-1E7 (Ab1) against PCV2 capsid protein (PCV2-Cap) was immunized in the camel. And 12 nanobodies against mAb-1E7 were screened. Among them, Nb61 (Ab2) targeted the idiotype epitope of mAb-1E7 and blocked mAb-1E7's binding to PCV2-Cap. Additionally, a high-dose Nb61 vaccination can also protect mice and pigs from PCV2 infection. Epitope mapping showed that mAb-1E7 recognized the 75NINDFL80 of PCV2-Cap and 101NYNDFLG107 of Nb61. Subsequently, the mAb-3G4 (Ab3) against Nb61 was produced and can neutralize PCV2 infection in the PK-15 cells. Structure analysis showed that the amino acids of mAb-1E7 and mAb-3G4 respective binding to PCV2-Cap and Nb61 were also similar on the amino acids sequences and spatial conformation. Collectively, our study first provided a strategy for producing nanobody-based anti-idiotype vaccines and identified that anti-idiotype nanobodies could mimic the antigen on amino acids and structures. Importantly, as more and more neutralization mAbs against different pathogens are prepared, anti-idiotype nanobody vaccines can be easily produced against the disease with our strategy, especially for dangerous pathogens.IMPORTANCEAnti-idiotype vaccines utilize idiotype-anti-idiotype network theory, eliminating the need for external antigens as vaccine candidates. Especially for dangerous pathogens, they were safer because they did not contact the live pathogenic microorganisms. However, developing anti-idiotype vaccines with traditional monoclonal and polyclonal antibodies is complex and has a high failure rate. We present a novel, universal, simple, low-cost strategy for producing anti-idiotype vaccines with nanobody technology. Using a neutralization antibody against PCV2-Cap, a nanobody (Ab2) was successfully produced and could mimic the neutralizing epitope of PCV2-Cap. The nanobody can induce protective immune responses against PCV2 infection in mice and pigs. It highlighted that the anti-idiotype vaccine using nanobody has a very good application in the future, especially for dangerous pathogens.
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Infecciones por Circoviridae , Circovirus , Anticuerpos de Dominio Único , Vacunas Virales , Animales , Humanos , Ratones , Proteínas de la Cápside , Infecciones por Circoviridae/prevención & control , Infecciones por Circoviridae/veterinaria , Epítopos , Porcinos , Vacunas Virales/química , Vacunas Virales/inmunologíaRESUMEN
The potato's most devastating disease is late blight, which is caused by Phytophthora infestans. Whereas various resistance (R) genes are known, most are typically defeated by this fast-evolving oomycete pathogen. However, the broad-spectrum and durable R8 is a vital gene resource for potato resistance breeding. To support an educated deployment of R8, we embarked on a study on the corresponding avirulence gene Avr8. We overexpressed Avr8 by transient and stable transformation, and found that Avr8 promotes colonization of P. infestans in Nicotiana benthamiana and potato, respectively. A yeast-two-hybrid (Y2H) screen showed that AVR8 interacts with a desumoylating isopeptidase (StDeSI2) of potato. We overexpressed DeSI2 and found that DeSI2 positively regulates resistance to P. infestans, while silencing StDeSI2 downregulated the expression of a set of defense-related genes. By using a specific proteasome inhibitor, we found that AVR8 destabilized StDeSI2 through the 26S proteasome and attenuated early PTI responses. Altogether, these results indicate that AVR8 manipulates desumoylation, which is a new strategy that adds to the plethora of mechanisms that Phytophthora exploits to modulate host immunity, and StDeSI2 provides a new target for durable resistance breeding against P. infestans in potato.
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Phytophthora infestans , Solanum tuberosum , Fitomejoramiento , Inmunidad de la Planta , Solanum tuberosum/genética , Enfermedades de las PlantasRESUMEN
Separation of methanol/benzene azeotrope mixtures is very challenging not only by the conventional distillation technique but also by adsorbents. In this work, we design and synthesize a flexible Ca-based metal-organic framework MAF-58 consisting of cheap raw materials. MAF-58 shows selective methanol-induced pore-opening flexibility. Although the opened pores are large enough to accommodate benzene molecules, MAF-58 shows methanol/benzene molecular sieving with ultrahigh experimental selectivity, giving 5.1 mmol g-1 high-purity (99.99%+) methanol and 2.0 mmol g-1 high-purity (99.97%+) benzene in a single adsorption/desorption cycle. Computational simulations reveal that the preferentially adsorbed, coordinated methanol molecules act as the gating component to selectively block the diffusion of benzene, offering a new gating adsorption mechanism.
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Transition metal silicates (TMSs) are attempted for the electrocatalyst of oxygen evolution reaction (OER) due to their special layered structure in recent years. However, defects such as low theoretical activity and conductivity limit their application. Researchers always prefer to composite TMSs with other functional materials to make up for their deficiency, but rarely focus on the effect of intrinsic structure adjustment on their catalytic activity, especially anion structure regulation. Herein, applying the method of interference hydrolysis and vacancy reserve, new silicate vacancies (anionic regulation) are introduced in cobalt silicate hydroxide (CoSi), named SV-CoSi, to enlarge the number and enhance the activity of catalytic sites. The overpotential of SV-CoSi declines to 301 mV at 10 mA cm-2 compared to 438 mV of CoSi. Source of such improvement is verified to be not only the increase of active sites, but also the positive effect on the intrinsic activity due to the enhancement of cobalt-oxygen covalence with the variation of anion structure by density functional theory (DFT) method. This work demonstrates that the feasible intrinsic anion structure regulation can improve OER performance of TMSs and provides an effective idea for the development of non-noble metal catalyst for OER.
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Bacteria capable of direct ammonia oxidation (Dirammox) play important roles in global nitrogen cycling and nutrient removal from wastewater. Dirammox process, NH3 â NH2 OH â N2 , first defined in Alcaligenes ammonioxydans HO-1 and encoded by dnf gene cluster, has been found to widely exist in aquatic environments. However, because of multidrug resistance in Alcaligenes species, the key genes involved in the Dirammox pathway and the interaction between Dirammox process and the physiological state of Alcaligenes species remain unclear. In this work, ammonia removal via the redistribution of nitrogen between Dirammox and microbial growth in A. ammonioxydans HO-1, a model organism of Alcaligenes species, was investigated. The dnfA, dnfB, dnfC, and dnfR genes were found to play important roles in the Dirammox process in A. ammonioxydans HO-1, while dnfH, dnfG, and dnfD were not essential genes. Furthermore, an unexpected redistribution phenomenon for nitrogen between Dirammox and cell growth for ammonia removal in HO-1 was revealed. After the disruption of the Dirammox in HO-1, more consumed NH4 + was recovered as biomass-N via rapid metabolic response and upregulated expression of genes associated with ammonia transport and assimilation, tricarboxylic acid cycle, sulfur metabolism, ribosome synthesis, and other molecular functions. These findings deepen our understanding of the molecular mechanisms for Dirammox process in the genus Alcaligenes and provide useful information about the application of Alcaligenes species for ammonia-rich wastewater treatment.
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Compuestos de Amonio , Compuestos de Amonio/metabolismo , Alcaligenes/genética , Alcaligenes/metabolismo , Amoníaco/toxicidad , Amoníaco/metabolismo , Aguas Residuales , Nitrógeno/metabolismo , Desnitrificación , Oxidación-Reducción , Reactores BiológicosRESUMEN
SUMOylation, a post-translational modification involving the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to target substrates, plays a pivotal role at the intersection of gut health and disease, influencing various aspects of intestinal physiology and pathology. This review provides a comprehensive examination of SUMOylation's diverse roles within the gut microenvironment. We examine its critical roles in maintaining epithelial barrier integrity, regulating immune responses, and mediating host-microbe interactions, thereby highlighting the complex molecular mechanisms that underpin gut homeostasis. Furthermore, we explore the impact of SUMOylation dysregulation in various intestinal disorders, including inflammatory bowel diseases and colorectal cancer, highlighting its implications as a potential diagnostic biomarker and therapeutic target. By integrating current research findings, this review offers valuable insights into the dynamic interplay between SUMOylation and gut health, paving the way for novel therapeutic strategies aimed at restoring intestinal equilibrium and combating associated pathologies.
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Sumoilación , Humanos , Animales , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patologíaRESUMEN
Cotinine, the primary metabolite of nicotine in the human body, is an emerging pollutant in aquatic environments. It causes environmental problems and is harmful to the health of humans and other mammals; however, the mechanisms of its biodegradation have been elucidated incompletely. In this study, a novel Gram-negative strain that could degrade and utilize cotinine as a sole carbon source was isolated from municipal wastewater samples, and its cotinine degradation characteristics and kinetics were determined. Pseudomonas sp. JH-2 was able to degrade 100 mg/L (0.56 mM) of cotinine with high efficiency within 5 days at 30 â, pH 7.0, and 1% NaCl. Two intermediates, 6-hydroxycotinine and 6-hydroxy-3-succinoylpyridine (HSP), were identified by high-performance liquid chromatography and liquid chromatograph mass spectrometer. The draft whole genome sequence of strain JH-2 was obtained and analyzed to determine genomic structure and function. No homologs of proteins predicted in Nocardioides sp. JQ2195 and reported in nicotine degradation Pyrrolidine pathway were found in strain JH-2, suggesting new enzymes that responsible for cotinine catabolism. These findings provide meaningful insights into the biodegradation of cotinine by Gram-negative bacteria.
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Biodegradación Ambiental , Cotinina , Pseudomonas , Aguas Residuales , Pseudomonas/metabolismo , Pseudomonas/genética , Pseudomonas/aislamiento & purificación , Pseudomonas/clasificación , Cotinina/metabolismo , Cotinina/análogos & derivados , Aguas Residuales/microbiología , Nicotina/metabolismo , Nicotina/análogos & derivados , Piridinas/metabolismo , Genoma Bacteriano , Filogenia , SuccinatosRESUMEN
Although electro-Fenton (EF) processes can avoid the safety risks raised by concentrated hydrogen peroxide (H2O2), the Fe(III) reduction has always been either unstable or inefficient at high pH, resulting in catalyst deactivation and low selectivity of H2O2 activation for producing hydroxyl radicals (â¢OH). Herein, we provided a strategy to regulate the surface dipole moment of TiO2 by Fe anchoring (TiO2-Fe), which, in turn, substantially increased the H2O2 activation for â¢OH production. The TiO2-Fe catalyst could work at pH 4-10 and maintained considerable degradation efficiency for 10 cycles. Spectroscopic analysis and a theoretical study showed that the less polar Fe-O bond on TiO2-Fe could finely tune the polarity of H2O2 to alter its empty orbital distribution, contributing to better ciprofloxacin degradation activity within a broad pH range. We further verified the critical role of the weakened polarity of H2O2 on its homolysis into â¢OH by theoretically and experimentally investigating Cu-, Co-, Ni-, Mn-, and Mo-anchored TiO2. This concept offers an avenue for elaborate design of green, robust, and pH-universal cathodic Fenton-like catalysts and beyond.
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Peróxido de Hidrógeno , Titanio , Peróxido de Hidrógeno/química , Concentración de Iones de Hidrógeno , Titanio/química , Hierro/química , Radical Hidroxilo/química , Catálisis , ElectrodosRESUMEN
Metal-organic frameworks (MOFs) have a variety of structures and unique properties that make them suitable for use in gas sensors. Herein, In2O3/Fe2O3 was successfully synthesized using simple solvothermal and impregnation methods. The response to 100 ppm of ethanol gas reached 67.5 at an optimum working temperature of 200 °C, and the response/recovery time was 9 s/236 s. The composite also exhibited excellent selectivity, repeatability, and long-term stability. SEM, TEM, XRD, and XPS were used for the characterization of materials. The excellent sensing performance of the sensors is attributed to the construction of n-n heterojunctions, an increase in oxygen vacancies, and the unique structural characteristics of MOFs. The above experimental results indicate that In-MIL-68-derived In2O3/Fe2O3 is a promising ethanol sensing material.
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Due to the sustained proliferative potential of cancer cells, inducing cell death is a potential strategy for cancer therapy. Paraptosis is a mode of cell death characterized by endoplasmic reticulum (ER) and/or mitochondrial swelling and cytoplasmic vacuolization, which is less investigated. Considerable evidence shows that paraptosis can be triggered by various chemical compounds, particularly in cancer cells, thus highlighting the potential application of this non-classical mode of cell death in cancer therapy. Despite these findings, there remain significant gaps in our understanding of the role of paraptosis in cancer. In this review, we summarize the current knowledge on chemical compound-induced paraptosis. The ER and mitochondria are the two major responding organelles in chemical compound-induced paraptosis, which can be triggered by the reduction of protein degradation, disruption of sulfhydryl homeostasis, overload of mitochondrial Ca2+, and increased generation of reactive oxygen species. We also discuss the stumbling blocks to the development of this field and the direction for further research. The rational use of paraptosis might help us develop a new paradigm for cancer therapy.
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Neoplasias , Paraptosis , Línea Celular Tumoral , Muerte Celular , Especies Reactivas de Oxígeno/metabolismo , Retículo Endoplásmico/metabolismo , Apoptosis , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismoRESUMEN
In order to explore the extraction and activity of macroalge glycolipids, six macroalgae (Bangia fusco-purpurea, Gelidium amansii, Gloiopeltis furcata, Gracilariopsis lemaneiformis, Gracilaria sp. and Pyropia yezoensis) glycolipids were extracted with five different solvents firstly. Considering the yield and glycolipids concentration of extracts, Bangia fusco-purpurea, Gracilaria sp. and Pyropia yezoensis were selected from six species of marine macroalgae as the raw materials for the extraction of glycolipids. The effects of the volume score of methanol, solid-liquid ratio, extraction temperature, extraction time and ultrasonic power on the yield and glycolipids concentration of extracts of the above three macroalgae were analyzed through a series of single-factor experiments. By analyzing the antioxidant activity in vitro, moisture absorption and moisturizing activity, the extraction process of Bangia fusco-purpurea glycolipids was further optimized by response surface method to obtain suitable conditions for glycolipid extraction (solid-liquid ratio of 1:27 g/mL, extraction temperature of 48 °C, extraction time of 98 min and ultrasonic power of 450 W). Bangia fusco-purpurea extracts exhibited a certain scavenging effect on DPPH free radicals, as well as good moisture-absorption and moisture retaining activities. Two glycolipids were isolated from Bangia fusco-purpurea by liquid-liquid extraction, silica gel column chromatography and thin-layer chromatography, and they showed good scavenging activities against DPPH free radicals and total antioxidant capacity. Their scavenging activities against DPPH free radicals were about 60% at 1600 µg/mL, and total antioxidant capacity was better than that of Trolox. Among them, the moisturizing activity of a glycolipid was close to that of sorbierite and sodium alginate. These two glycolipids exhibited big application potential as food humectants and antioxidants.
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Antioxidantes , Glucolípidos , Algas Marinas , Glucolípidos/química , Glucolípidos/aislamiento & purificación , Glucolípidos/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Algas Marinas/química , Rhodophyta/química , Solventes/química , Picratos/químicaRESUMEN
Background: Cardiovascular diseases are the leading cause of death among patients on hemodialysis, with approximately 40% of the cardiovascular deaths linked to acute coronary syndrome. We aimed to investigate the incidence and risk factors of acute coronary syndrome in patients undergoing hemodialysis. Methods: Patients undergoing hemodialysis were prospectively enrolled from January 2018. Data regarding hospitalization due to acute coronary syndrome were collected at 3-month intervals through December 31, 2021. Cox regression model was used to estimate the association between baseline factors and incident acute coronary syndrome during follow-up. Results: Patients' mean age was 66 years, 48% were men, and 16% had a history of coronary artery disease at enrolment. Over a median follow-up of 1,187 days, 85 patients were hospitalized due to acute coronary syndrome. Left main or triple vessel disease was identified in 67 patients. Risk factors associated with incident acute coronary syndrome included aging, male sex, smoking, low diastolic blood pressure, and baseline comorbidities, in addition to dialysis factors including low urea clearance, central venous catheter use, and history of dialysis access dysfunction. After multivariate analysis, age, diabetes, hyperlipidemia, smoking, and frequent interventions for vascular access remained significant risk factors. Conclusions: A high acute coronary syndrome incidence was observed in our cohort, with traditional risk factors playing a consistent role with that in the general population. A history of frequent dialysis access dysfunction was also associated with incident acute coronary syndrome.
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Singlet oxygen (1O2) is an exceptional reactive oxygen species in advanced oxidation processes for environmental remediation. Despite single-atom catalysts (SACs) representing the promising candidate for the selective generation of 1O2 from peroxymonosulfate (PMS), the necessity to meticulously regulate the coordination environment of metal centers poses a significant challenge in the precisely-controlled synthetic method. Another dilemma to SACs is their high surface free energy, which results in an inherent tendency for the surface migration and aggregation of metal atoms. We here for the first time reported that Ru nanoparticles (NPs) synthesized by the facile pyrolysis method behave as robust Fenton-like catalysts, outperforming Ru SACs, towards efficient activation of PMS to produce 1O2 with nearly 100 % selectivity, remarkably improving the degradation efficiency for target pollutants. Density functional theory calculations have unveiled that the boosted PMS activation can be attributed to two aspects: (i) enhanced adsorption of PMS molecules onto Ru NPs, and (ii) decreased energy barriers by offering adjacent sites for promoted dimerization of *O intermediates into adsorbed 1O2. This study deepens the current understanding of PMS chemistry, and sheds light on the design and optimization of Fenton-like catalysts.
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Background Preoperative assessment of follicular thyroid neoplasms is challenging using the current US risk stratification systems (RSSs) that are applicable to papillary thyroid neoplasms. Purpose To develop a US feature-based RSS for differentiating between follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC) in biopsy-proven follicular neoplasm and compare it with existing RSSs. Materials and Methods This retrospective multicenter study included consecutive adult patients who underwent conventional US and received a final diagnosis of follicular thyroid neoplasm from seven centers between January 2018 and December 2022. US images from a pretraining data set were used to improve readers' understanding of the US characteristics of the FTC and FTA. Univariable and multivariable logistic regression analyses were used to assess the association of qualitative US features with FTC in a training data set. Features with P < .05 were used to construct a prediction model (follicular tumor model, referred to as F model) and RSS for follicular neoplasms using the Thyroid Imaging Reporting and Data System (TI-RADS). Area under the receiver operating characteristic curve (AUC) was compared between follicular TI-RADS (hereafter, F-TI-RADS) and existing RSS (American College of Radiology [ACR] TI-RADS, Korean Society of Thyroid Radiology and Korean Society of Radiology TI-RADS [hereafter, referred to as K-TI-RADS], and Chinese TI-RADS [hereafter, referred to as C-TI-RADS]) in a validation data set. Results The pretraining, training, and validation data sets included 30 (mean age, 47.6 years ± 16.0 [SD]; 16 male patients; FTCs, 30 of 60 [50.0%]), 703 (mean age, 47.9 years ± 14.5; 530 female patients; FTCs, 188 of 703 [26.7%]), and 155 (mean age, 49.9 years ± 13.3 [SD]; 155 female patients; FTCs, 43 of 155 [27.7%]) patients. In the validation data set, the F-TI-RADS showed improved performance for differentiating between FTA and FTC (AUC, 0.81; 95% CI: 0.71, 0.86) compared with ACR TI-RADS (AUC, 0.74; 95% CI: 0.66, 0.80; P = .02), K-TI-RADS (AUC, 0.69; 95% CI: 0.61, 0.76; P = .002), and C-TI-RADS (AUC, 0.68; 95% CI: 0.60, 0.75; P = .002). Conclusion F-TI-RADS outperformed existing RSSs for differentiating between FTC and FTA. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Baumgarten in this issue.
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Neoplasias de la Tiroides , Adulto , Humanos , Femenino , Masculino , Persona de Mediana Edad , Neoplasias de la Tiroides/diagnóstico por imagen , Proyectos de Investigación , Medición de RiesgoRESUMEN
Caterpillar oral secretion (OS) contains active molecules that modulate plant defense signaling. We isolated an effector-like protein (Highly Accumulated Secretory Protein 1, HAS1) from cotton bollworm (Helicoverpa armigera) that is the most highly accumulated secretory protein of the nondigestive components in OS and belongs to venom R-like protein. Elimination of HAS1 by plant-mediated RNA interference reduced the suppression of OS on the defense response in plants. Plants expressing HAS1 are more susceptible to insect herbivory accompanied by the reduced expressions of multiple defense genes. HAS1 binds to the basic helix-loop-helix (bHLH) transcription factors, including GoPGF involved in pigmented gland formation and defense compounds biosynthesis in cotton and MYC3/MYC4 the main regulators in jasmonate (JA) signaling in Arabidopsis. The binding activity is required for HAS1 to inhibit the activation of bHLHs on plant defense gene expressions. Together with our previous study that another venom R-like protein HARP1 in cotton bollworm OS blocks JA signaling by interacting with JASMONATE-ZIM-domain repressors, we conclude that the venom R-like proteins in OS interfere with plant defense in a dual suppression manner. Considering the venom proteins in parasitic wasp assault the immune system of its host animal, our investigation reveals their conserved function in carnivorous and herbivorous insects.
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Proteínas de Arabidopsis , Arabidopsis , Mariposas Nocturnas , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Transactivadores/metabolismo , Proteínas Represoras/metabolismo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas/metabolismo , Gossypium/genética , Gossypium/metabolismoRESUMEN
Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.
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Antígeno B7-H1 , Linfocitos T CD8-positivos , Humanos , Animales , Ratones , Línea Celular Tumoral , Inmunoterapia , Microambiente Tumoral , Quimiocina CXCL10/farmacologíaRESUMEN
OBJECTIVE: Previous studies on arteriovenous fistulas have demonstrated the potential benefit of drug coated balloons (DCBs) in maintaining the patency of dialysis access. However, stenoses involving stent grafts were excluded from these studies. Therefore, the aim was to evaluate the effectiveness of DCBs in treating stent graft stenosis. METHODS: This was a prospective, single blinded, randomised controlled study. From March 2017 to April 2021, 40 patients with dysfunctional vascular access owing to stent graft stenosis were randomised to treatment with a DCB or conventional balloon. Clinical follow up was scheduled at one, three, and six months, and angiographic follow up was performed six months after the intervention. The primary outcome was angiographic late luminal loss at six months, and secondary outcomes included target lesion and access circuit primary patency at six months. RESULTS: Thirty-six participants completed follow up angiography. The DCB group had a superior mean late luminal loss at six months compared with the control group (1.82 mm ± 1.83 mm vs. 3.63 mm ± 1.08 mm, respectively, p = .001). All 40 patients completed clinical follow up. The DCB group had a superior six month target lesion primary patency compared with the control group [hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.07 - 0.71; p = .005). Additionally, the DCB group had a numerically higher six month access circuit primary patency rate than the control group, although the difference was not statistically significant (HR 0.54, 95% CI 0.26 - 1.11, p = .095). CONCLUSION: Conventional balloon angioplasty is not durable in stent graft stenosis treatment. Treatment with DCBs provides less angiographic late luminal loss and potentially superior primary patency of the target lesion than treatment with conventional balloons. [ClinicalTrials ID: NCT03360279.].
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Angioplastia de Balón , Derivación Arteriovenosa Quirúrgica , Humanos , Constricción Patológica , Diálisis Renal/efectos adversos , Grado de Desobstrucción Vascular , Estudios Prospectivos , Derivación Arteriovenosa Quirúrgica/efectos adversos , Resultado del Tratamiento , Angioplastia de Balón/efectos adversos , Stents , Materiales Biocompatibles Revestidos , PaclitaxelRESUMEN
The ethanol/water separation challenge highlights the adsorption capacity/selectivity trade-off problem. We show that the target guest can serve as a gating component of the host to block the undesired guest, giving molecular sieving effect for the adsorbent possessing large pores. Two hydrophilic/water-stable metal azolate frameworks were designed to compare the effects of gating and pore-opening flexibility. Large amounts (up to 28.7â mmol g-1 ) of ethanol with fuel-grade (99.5 %+) and even higher purities (99.9999 %+) can be produced in a single adsorption process from not only 95 : 5 but also 10 : 90 ethanol/water mixtures. More interestingly, the pore-opening adsorbent possessing large pore apertures showed not only high water adsorption capacity but also exceptionally high water/ethanol selectivity characteristic of molecular sieving. Computational simulations demonstrated the critical role of guest-anchoring aperture for the guest-dominated gating process.
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BACKGROUND: High yield and quality are essential goals of wheat (Triticum aestivum L.) breeding. Kernel length (KL), as a main component of kernel size, can indirectly change kernel weight and then affects yield. Identification and utilization of excellent loci in wheat genetic resources is of great significance for cultivating high yield and quality wheat. Genetic identification of loci for KL has been performed mainly through genome-wide association study in natural populations or QTL mapping based on genetic linkage map in high generation populations. RESULTS: In this study, an F3 biparental population derived from the cross between an EMS mutant BLS1 selected from an EMS-induced wheat genotype LJ2135 (derived from the hybrid progeny of a spelt wheat (T. spelta L.) and a common wheat) mutant bank and a local breeding line 99E18 was used to rapidly identify loci controlling KL based on Bulked Segregant Analysis (BSA) and the wheat 660 K single-nucleotide polymorphism (SNP) array. The highest ratio of polymorphic SNPs was located on chromosome 4A. Linkage map analysis showed that 33 Kompetitive Allele Specific PCR markers were linked to the QTL for KL (Qkl.sicau-BLE18-4A) identified in three environments as well as the best linear unbiased prediction (BLUP) dataset. This QTL explained 10.87-19.30% of the phenotypic variation. Its effect was successfully confirmed in another F3 population with the two flanking markers KASP-AX-111536305 and KASP-AX-110174441. Compared with previous studies and given that the of BLS1 has the genetic background of spelt wheat, the major QTL was likely a new one. A few of predicted genes related to regulation of kernel development were identified in the interval of the detected QTL. CONCLUSION: A major, novel and stable QTL (Qkl.sicau-BLE18-4A) for KL was identified and verified in two F3 biparental populations across three environments. Significant relationships among KL, kernel width (KW) and thousand kernel weight (TKW) were identified. Four predicted genes related to kernel growth regulation were detected in the interval of Qkl.sicau-BLE18-4A. Furthermore, this study laid foundation on subsequent fine mapping work and provided a possibility for breeding of elite wheat varieties.