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BACKGROUND: The use of proteasome inhibitors (PIs), namely Bortezomib and Carfilzomib, revolutionized multiple myeloma (MM) treatment. Understanding their distinct adverse event (AE) profiles aids in tailored treatment plans. RESEARCH DESIGN AND METHODS: We analyzed FDA Adverse Event Reporting System (FAERS) data (Q1 2012-Q4 2023) for Bortezomib and Carfilzomib, utilizing reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). RESULTS: FAERS yielded 19,720 Bortezomib and 12,252 Carfilzomib AE reports. Males aged 45-65 exhibited higher AE susceptibility. Common AE systems included Infections, Nervous System Disorders, Blood Disorders, General Disorders, Cardiac Disorders, and Renal Disorders. New Bortezomib signals were sepsis and colitis. Carfilzomib exhibited elevated cardiac and renal toxicity but reduced peripheral neuropathy and thrombocytopenia. CONCLUSIONS: FAERS analysis revealed new AE signals (sepsis, colitis) for Bortezomib and highlighted Carfilzomib's heightened cardiac and renal risks compared to Bortezomib. Balancing PIs' benefits and risks is crucial for clinical decision-making.
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Introduction: Sepsis remains a major cause of death in Intensive Care Units. Sepsis is a life-threatening multi-organ dysfunction caused by a dysregulated systemic inflammatory response. Pattern recognition receptors, such as TLRs and NLRs contribute to innate immune responses. Upon activation, some NLRs form multimeric protein complexes in the cytoplasm termed "inflammasomes" which induce gasdermin d-mediated pyroptotic cell death and the release of mature forms of IL-1ß and IL-18. The NLRP6 inflammasome is documented to be both a positive and a negative regulator of host defense in distinct infectious diseases. However, the role of NLRP6 in polymicrobial sepsis remains elusive. Methods: We have used NLRP6 KO mice and human septic spleen samples to examine the role of NLRP6 in host defense in sepsis. Results: NLRP6 KO mice display enhanced survival, reduced bacterial burden in the organs, and reduced cytokine/chemokine production. Co-housed WT and KO mice following sepsis show decreased bacterial burden in the KO mice as observed in singly housed groups. NLRP6 is upregulated in CD3, CD4, and CD8 cells of septic patients and septic mice. The KO mice showed a higher number of CD3, CD4, and CD8 positive T cell subsets and reduced T cell death in the spleen following sepsis. Furthermore, administration of recombinant IL-18, but not IL-1ß, elicited excessive inflammation and reversed the survival advantages observed in NLRP6 KO mice. Conclusion: These results unveil NLRP6 as a negative regulator of host defense during sepsis and offer novel insights for the development of new treatment strategies for sepsis.
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Inmunidad Innata , Péptidos y Proteínas de Señalización Intracelular , Sepsis , Animales , Femenino , Humanos , Masculino , Ratones , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inmunidad Innata/genética , Inflamasomas/metabolismo , Inflamasomas/inmunología , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Superficie Celular , Sepsis/inmunología , Sepsis/microbiología , Bazo/inmunologíaRESUMEN
Background: Lymphangiogenesis (LYM) has an important role in tumor progression and is strongly associated with tumor metastasis. However, the clinical application of LYM has not progressed as expected. The potential value of LYM needs to be further developed in lung adenocarcinoma (LUAD) patients. Methods: The Sequencing data and clinical characteristics of LUAD patients were downloaded from The Cancer Genome Atlas and GEO databases. Multiple machine learning algorithms were used to screen feature genes and develop the LYM index. Immune cell infiltration, immune checkpoint expression, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and drug sensitivity analysis were used to explore the correlation of LYM index with immune profile and anti-tumor therapy. Results: We screened four lymphangiogenic feature genes (PECAM1, TIMP1, CXCL5 and PDGFB) to construct LYM index based on multiple machine learning algorithms. We divided LUAD patients into the high LYM index group and the low LYM index group based on the median LYM index. LYM index is a risk factor for the prognosis of LUAD patients. In addition, there was a significant difference in immune profile between high LYM index and low LYM index groups. LUAD patients in the low LYM index group seemed to benefit more from immunotherapy based on the results of TIDE algorithm. Conclusion: Overall, we confirmed that the LYM index is a prognostic risk factor and a valuable predictor of immunotherapy response in LUAD patients, which provides new evidence for the potential application of LYM.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Linfangiogénesis , Adenocarcinoma del Pulmón/terapia , Genes Reguladores , Inmunoterapia , Neoplasias Pulmonares/terapiaRESUMEN
The assembly of complete and circularized mitochondrial genomes (mitogenomes) is essential for population genetics, phylogenetics and evolution studies. Recently, Song et al. developed a seed-free tool called MEANGS for de novo mitochondrial assembly from whole genome sequencing (WGS) data in animals, achieving highly accurate and intact assemblies. However, the suitability of this tool for marine fish remains unexplored. Additionally, we have concerns regarding the overlap sequences in their original results, which may impact downstream analyses. In this Letter to the Editor, the effectiveness of MEANGS in assembling mitogenomes of cartilaginous and ray-finned fish species was assessed. Moreover, we also discussed the appropriate utilization of MEANGS in mitogenome assembly, including the implementation of the data-cut function and circular detection module. Our observations indicated that with the utilization of these modules, MEANGS efficiently assembled complete and circularized mitogenomes, even when handling large WGS datasets. Therefore, we strongly recommend users employ the data-cut function and circular detection module when using MEANGS, as the former significantly reduces runtime and the latter aids in the removal of overlapped sequences for improved circularization. Furthermore, our findings suggested that approximately 2× coverage of clean WGS data was sufficient for MEANGS to assemble mitogenomes in marine fish species. Moreover, due to its seed-free nature, MEANGS can be deemed one of the most efficient software tools for assembling mitogenomes from animal WGS data, particularly in studies with limited species or genetic background information.
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Genoma Mitocondrial , Animales , Secuenciación Completa del Genoma/métodos , Programas Informáticos , FilogeniaRESUMEN
To analyze the independent risk factors for recurrent bleeding and death within 1 year after endoscopic treatment of esophagogastric varices hemorrhage (EGVB) in patients with liver cirrhosis, and to validate the predictive value of ALBI score for recurrent bleeding and death within 1 year after endoscopic treatment of EGVB in patients with liver cirrhosis. A total of 338 patients with EGVB who received endoscopic treatment for the first time in the Department of Gastroenterology, First Affiliated Hospital of Nanchang University from January 1, 2016 to March 1, 2020 were selected. A database was established to analyze the patients' demographic data, surgical variables and postoperative outcomes. All patients were contacted and followed up to verify the predictive value of ALBI score for recurrent bleeding and mortality. 130 patients had rebleeding within 1 year after surgery (38.5%). 66 patients died within 1 year after surgery (19.5%). Patients with ALBI grade 3 had significantly higher rebleeding and mortality rates than those with grades 1 and 2. The AUC was used to compare the predictive value of the four scores for rebleeding and mortality within one year after endoscopic surgery. Both ALBI scores had the largest AUC. The ALBI score has certain predictive value for rebleeding and mortality within 1 year after endoscopic therapy in patients with cirrhotic EGVB.
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Hemorragia , Cirrosis Hepática , Humanos , Pronóstico , Cirrosis Hepática/complicaciones , Factores de Riesgo , Bases de Datos FactualesRESUMEN
Introduction: Soybean root rot (SRR), caused by Fusarium oxysporum, is a severe soil-borne disease in soybean production worldwide, which adversely impacts the yield and quality of soybean. The most effective method for managing crop soil-borne diseases and decreasing reliance on chemical fungicides, such as Bacillus spp., is via microbial biocontrol agents. Methods and Results: In this study, a soil-isolated strain BVE7 was identified as B. velezensis, exhibiting broad-spectrum activity against various pathogens causing soybean root rot. BVE7 sterile filtrate, at a concentration of 10%, demonstrated significant antifungal activity by inhibiting the conidial germination, production, and mycelial growth of F. oxysporum by 61.11%, 73.44%, and 85.42%, respectively, causing hyphal malformations. The antifungal compound produced by BVE7 demonstrated adaptability to a standard environment. The pot experiment showed that BVE7 suspension could effectively control soybean root rot, with the highest control efficiency of 75.13%. Furthermore, it considerably enhanced the activity of catalase, phenylalanine ammonia lyase, superoxide dismutase, and peroxidase in soybean roots, while also preventing an increase in malondialdehyde activity. By improving the host resistance towards pathogens, the damage caused by fungi and the severity of soybean root rot have been reduced. Discussion: This study presents the innovative utilization of B. velezensis, isolated from soybean roots in cold conditions, for effectively controlling soybean root rot caused by F. oxysporum. The findings highlight the remarkable regional and adaptive characteristics of this strain, making it an excellent candidate for combating soybean root rot in diverse environments. In conclusion, B. velezensis BVE7 demonstrated potential in effectively reducing SRR incidence and can be considered as a viable option for SRR management.
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In this study, we employ coarse-grained molecular dynamics simulations to explore the microstructure of MSA (methanesulfonic acid)-type electroplating solution, containing Sn(MSA)2 as the primary salt, MSA as the stabilizer, amphiphilic alkylphenol ethoxylate (APEO) as surfactants and cinnamaldehyde (CA) as the brightener agents, as well as water as the solvent. Our simulation indicates that temperature variations can significantly affect the structural properties of the electroplating solution and the adsorption behavior of its key components onto the substrate. Specifically, at low temperatures, the primary salt ions aggregate into ionic clusters, and the amphiphilic APEO surfactants and CA molecules form micelles composed of hydrophobic cores and hydrophilic shells, which reduces the uniformity of the solution and hinders the adsorption of ions, CA and surfactants onto the substrate. Appropriately increasing the temperature can weaken the aggregation of these components in bulk solution due to the accelerated molecular movements and arouse their adsorption. However, on further increasing the temperature, the elevated kinetic energy of the components thoroughly overwhelms the adsorption interactions, and therefore, the ions, surfactants, and CA desorb from the substrate and redissolve into the solution. We systematically analyze the complex interactions between these components at different temperatures and clarify the mechanism of the non-monotonic dependence of adsorption strength on the temperature at the molecular level. Our simulations demonstrate that there is low-temperature scope for reprocessing/recycling and intermediate-temperature scope for substrate-adsorptions of the key components. This study confers insights into a fundamental understanding of the microscopic mechanism for electroplating and can provide guidance for the development of precise electroplatings.
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Introduction: Lactococcus lactis (L.L) is safe and can be used as vehicle. In this study, the immunoregulatory effect of L.L on dendritic cell (DC) activation and mechanism were investigated. The immune responses and antigen cross-presentation mechanism of DC-based vaccine prepared with OVA recombinant L.L were explored. Methods: Confocal microscopy and flow cytometry were used to analyze the mechanism of L.L promoting DC maturation, phagosome membrane rupture and antigen presentation. The antitumor effect of DC vaccine prepared with L.L-OVA was assessed in the B16-OVA tumor mouse model. Results: L.L significantly promoted DC maturation, which was partially dependent on TLR2 and downstream MAPK and NF-κB signaling pathways. L.L was internalized into DCs by endocytosis and did not co-localized with lysosome. OVA recombinant L.L enhanced antigen cross-presentation of DCs through the phagosome-to-cytosol pathway in a reactive oxygen species (ROS)- and proteasome-dependent manner. In mouse experiments, L.L increased the migration of DCs to draining lymph node and DC vaccine prepared with OVA recombinant L.L induced strong antigen-specific Th1 and cytotoxic T lymphocyte responses, which significantly inhibited B16-OVA tumor growth. Conclusion: This study demonstrated that recombinant L.L as an antigen delivery system prepared DC vaccine can enhance the antigen cross-presentation and antitumor efficacy.
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Lactococcus lactis , Vacunas , Animales , Ratones , Presentación de Antígeno , Reactividad Cruzada , Lactococcus lactis/genética , Especies Reactivas de Oxígeno , Lisosomas , Células DendríticasRESUMEN
PURPOSE OF REVIEW: Recent technological advances have identified distinct subpopulations and roles of the cardiac innate immune cells, specifically macrophages and neutrophils. Studies on distinct metabolic pathways of macrophage and neutrophil in cardiac injury are expanding. Here, we elaborate on the roles of cardiac macrophages and neutrophils in concomitance with their metabolism in normal and diseased hearts. RECENT FINDINGS: Single-cell techniques combined with fate mapping have identified the clusters of innate immune cell subpopulations present in the resting and diseased hearts. We are beginning to know about the presence of cardiac resident macrophages and their functions. Resident macrophages perform cardiac homeostatic roles, whereas infiltrating neutrophils and macrophages contribute to tissue damage during cardiac injury with eventual role in repair. Prior studies show that metabolic pathways regulate the phenotypes of the macrophages and neutrophils during cardiac injury. Profiling the metabolism of the innate immune cells, especially of resident macrophages during chronic and acute cardiac diseases, can further the understanding of cardiac immunometabolism.
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Lesiones Cardíacas , Macrófagos , Humanos , Macrófagos/fisiología , Monocitos/fisiología , Corazón , Neutrófilos/fisiología , Lesiones Cardíacas/metabolismo , Inmunidad InnataRESUMEN
BACKGROUND: "Primary papillary epithelial tumor of the sella (PPETS)" is a recently described rare tumor entity of the central nervous system (CNS) with stereotypic location in the sella. Comprehensive molecular investigations and epigenetic profiles of PPETS have not been performed to date. METHODS: We report a comprehensive clinical, histopathologic, and molecular assessment of 5 PPETS cases in comparison with a cohort composed of 7 choroid plexus papilloma (CPP), 7 central neurocytoma (CN), 15 posterior pituitary tumor (PPT) including 4 pituicytoma, 6 granular cell tumors of the sellar region (GCT), and 5 spindle cell oncocytoma. RESULTS: All PPETS had good outcomes. Immunohistochemically, PPETS tumors showed positive staining with TTF1, EMA, AE1/AE3, MAP2, and Vimentin, but were negatively stained with Syn, GFAP, CgA, and S100, and sporadically stained with Ki-67. In unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analyses of DNA-methylation data, PPETS and PPT tumors formed a distinct cluster irrespective of their histologic types. However, PPETS tumors did not cluster together with CPP and CN samples. Similar findings were obtained when our samples were projected into the reference cohort of the brain tumor classifier. Substantial fractions of the PPETS and PPT tumors shared broadly similar chromosomal copy number alterations. No mutations were detected using targeted next-generation sequencing. CONCLUSIONS: Though more cases are needed to further elucidate the molecular pathogenesis of these tumors, our findings indicate that PPETS and PPT tumors may constitute a single neurooncological entity.
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Adenoma Oxifílico , Neoplasias Glandulares y Epiteliales , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Adenoma Oxifílico/genética , Adenoma Oxifílico/patología , Metilación de ADN , Sistema Nervioso Central/patologíaRESUMEN
We determined the changes that occurred in fungal community structures and their functions in conventional and bioreactor composting systems. The Illumina MiSeq platform was employed to sequence cDNA by reverse transcription to conduct metatranscriptomics analysis of RNA, and the FUNGuild tool was applied. The α-diversity of fungi in the bioreactor composter increased throughout composting, especially in the initial three phases, but decreased in the conventional composting system. The three dominant phyla in the bioreactor system were Ascomycota (30.27%-68.50%), Mortierellomycota (3.81%-39.51%), and Basidiomycota (9.17%-30.86%). Ascomycota (76.96%-97.18%) was the main phylum in the conventional composting system. Mortierella, Guehomyces, Plectosphaerella, Chaetomium, Millerozyma, and Coprinopsis were the main genera in the bioreactor composter. In the same phase, significant differences in the fungal functions were found between the two composting methods. Available phosphorus was the main factor that affected the community structures and functions of fungi in the bioreactor composter.
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Ascomicetos , Basidiomycota , Compostaje , Micobioma , Suelo , Microbiología del Suelo , Hongos/genéticaRESUMEN
Gastrointestinal nematode infections cause morbidity and socioeconomic loss in the most deprived communities. The shift in the context of obesity has led to spatial overlap with endemic gastrointestinal nematode regions resulting in the emergence of a novel comorbidity. Despite this, the impact of a high-fat diet (HFD) on immune-regulated protection against gastrointestinal infections remains largely unknown. We employed the murine model of nematode infection, Trichuris muris, to investigate the effect of an HFD on the immune response against chronic infection. Surprisingly, diet-induced obesity drove parasite expulsion in both single and repeated trickle low doses of T. muris eggs. Mechanistically, an HFD increased the expression of the ST2 receptor on CD4+ T cells, priming an enhanced type 2 helper T (Th2) cell cytokine production following interleukin (IL)-33 stimulation ex vivo. Despite IL-33-/- mice demonstrating that IL-33 is not critical for host protective immunity to T. muris under a conventional diet, HFD-fed T-cell deplete mice adoptively transferred with ST2-/- CD4 T cells were unable to expel a T. muris infection unlike those transferred with ST2-sufficient cells. Collectively, this study demonstrates that an HFD primes CD4+ T cells to utilize the IL-33-ST2 axis in a novel induction of type 2 immunity, providing insights into the emerging comorbidities of obesity and nematode infection.
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Helmintos , Tricuriasis , Ratones , Animales , Interleucina-33 , Dieta Alta en Grasa , Proteína 1 Similar al Receptor de Interleucina-1 , Trichuris , Citocinas/metabolismoRESUMEN
We previously demonstrated that Pleurotus ferulae polysaccharide (PFPS) promoted dendritic cell (DC) maturation through the TLR4 signaling pathway. To improve PFPS activity and bioavailability, gold nanoparticles with PFPS (PFPS-Au NPs) were synthesized. Of note, although the polysaccharide content of PFPS-Au NPs was only one tenth of PFPS, PFPS-Au NPs enhanced the immunostimulatory activities of PFPS in the maturation and function of dendritic cells (DCs) by TLR4 and NLRP3 signaling pathways, evidenced by stronger activation of the down-stream MAPK and NF-κB pathways and NLRP3 inflammasome pathway. More importantly, PFPS-Au NPs enhanced DC migration and murine immunity, particularly in type 1 T-helper cell responses. Moreover, the half-life of PFPS-Au NPs (2.217 ± 0.187 h) was longer than that of PFPS (1.39 ± 0.257 h) in the blood and the distribution of PFPS-Au NPs (19.8 %) in the spleen was significantly increased compared with PFPS (13.3 %), indicating the improved bioavailability in vivo. PFPS-Au NPs as an adjuvant promoted antigen-specific cellular immune responses to an HPV DC-based vaccine, which significantly inhibited the growth of TC-1 tumors in mice. All results suggest that the prepared Au NPs could enhance PFPS-immunostimulatory activity, which will pave the way for PFPS-Au NPs to be applied in clinical trials.
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Nanopartículas del Metal , Nanopartículas , Pleurotus , Animales , Ratones , Pleurotus/metabolismo , Oro/farmacología , Oro/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptor Toll-Like 4/metabolismo , Polisacáridos/farmacología , Polisacáridos/metabolismo , Células DendríticasRESUMEN
Innate immune cells play important roles in tissue injury and repair following acute myocardial infarction (MI). Although reprogramming of macrophage metabolism has been observed during inflammation and resolution phases, the mechanistic link to macrophage phenotype is not fully understood. In this study, we found that myeloid-specific deletion (mKO) of mitochondrial complex I protein, encoded by Ndufs4, reproduced the proinflammatory metabolic profile in macrophages and exaggerated the response to LPS. Moreover, mKO mice showed increased mortality, poor scar formation, and worsened cardiac function 30 days after MI. We observed a greater inflammatory response in mKO mice on day 1 followed by increased cell death of infiltrating macrophages and blunted transition to the reparative phase during post-MI days 3-7. Efferocytosis was impaired in mKO macrophages, leading to lower expression of antiinflammatory cytokines and tissue repair factors, which suppressed the proliferation and activation of myofibroblasts in the infarcted area. Mitochondria-targeted ROS scavenging rescued these impairments, improved myofibroblast function in vivo, and reduced post-MI mortality in mKO mice. Together these results reveal a critical role of mitochondria in inflammation resolution and tissue repair via modulation of efferocytosis and crosstalk with fibroblasts. These findings have potential significance for post-MI recovery as well as for other inflammatory conditions.
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Macrófagos , Mitocondrias , Infarto del Miocardio , Animales , Ratones , Complejo I de Transporte de Electrón/metabolismo , Inflamación/etiología , Inflamación/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitocondrias/patología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/metabolismo , FagocitosisRESUMEN
Breast cancer (BC) is one of the most common malignancies affecting women. Ferroptosis is a novel cancer treatment option. The present study is aimed to identify suitable ferroptosis-related lncRNAs to predict and diagnose BC. Differential expression and Cox regression analyses were used to screen suitable prognostic biomarkers and construct a suitable risk model. We identified four ferroptosis-related differentially expressed lncRNAs (FR-DELs) (LINC01152, AC004585.1, MAPT-IT1, and AC026401.3), which were independently correlated with the overall survival of BC patients. The area under the curve value of the prognostic model using those four biomarkers was over 0.60 in all three groups. The sensitivity and specificity of the diagnostic model using those four biomarkers were 86.89% and 86.73%, respectively. Our present study indicated that these four FR-DELs (LINC01152, AC004585.1, MAPT-IT1, and AC026401.3) could be prognostic biomarkers for BC, although clinical validation studies are required.
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Neoplasias de la Mama , Ferroptosis , ARN Largo no Codificante , Humanos , Femenino , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Estimación de Kaplan-Meier , PronósticoRESUMEN
The inverse vulcanization (IV) of elemental sulfur to generate sulfur-rich functional polymers has attracted much recent attention. However, the harsh reaction conditions required, even with metal catalysts, constrains the range of feasible crosslinkers. We report here a photoinduced IV that enables reaction at ambient temperatures, greatly broadening the scope for both substrates and products. These conditions enable volatile and gaseous alkenes and alkynes to be used in IV, leading to sustainable alternatives for environmentally harmful plastics that were hitherto inaccessible. Density functional theory calculations reveal different energy barriers for thermal, catalytic and photoinduced IV processes. This protocol circumvents the long curing times that are common in IV, generates no H2S by-products, and produces high-molecular-weight polymers (up to 460,000 g mol-1) with almost 100% atom economy. This photoinduced IV strategy advances both the fundamental chemistry of IV and its potential industrial application to generate materials from waste feedstocks.
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Polímeros , Azufre , Alquenos , Plásticos , CatálisisRESUMEN
The Sn-Ag-Cu (SAC) solder alloys with a low Ag (Ag < 3 wt.%) content have attracted great attention owing to their low cost, increased ability in bulk compliance, and plastic energy dissipation. However, some of their mechanical properties are generally lower than the SAC alloys with a higher Ag content. Adding alloying elements is an effective approach for improving the mechanical properties of the SAC alloys. In this study, the effect of Bi, Sb, and Ti on Sn-1 wt.%Ag-0.5 wt.%Cu (SAC105) solder alloys was investigated. The SAC solders with four compositions: SAC105-1 wt.%Bi, SAC105-1 wt.%Sb, SAC105-1 wt.%Bi-1 wt.%Sb, SAC105-1 wt.%Bi-1 wt.%Sb-0.4 wt.%Ti were prepared. The microstructure and phase compositions were characterized using electron scanning microscopy, and X-ray diffraction. The thermal properties and wettability were also examined. Uniaxial tensile tests and nano-indentation tests were conducted to evaluate the mechanical properties. The results show that adding Bi or Sb could increase the strength of SAC105 alloys mainly due to the solid solution strengthening effect. The creep resistance of SAC105 alloys was also improved with the additions of Bi and Sb. The co-additions of Bi and Sb into SAC105 alloys exhibit an enhanced creep resistance than that calculated by the theoretical calculation. The further addition of Ti into SAC105-1Bi-1Sb alloys demonstrated a much-improved creep resistance, which could be attributed to the synergistic effects of both solid solution strengthening and the precipitation hardening effects.
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Low molecular weight fucoidan (LMWF) has been reported to have immunomodulation effects through the increase of the activation and function of macrophages. In this study, the regulating effect of LMWF from Undaria pinnatifida grown in New Zealand on dendritic cells (DCs) was investigated. We discovered that LMWF could stimulate DCs' maturation and migration, as well as CD4+ and CD8+ T cells' proliferation in vitro. We proved that this immune promoting activity is activated through TLR4 and its downstream MAPK and NF-κB signaling pathways. Further in vivo (mouse model) investigation showed that LMWF has a strong immunological boosting effect, such as facilitating the proliferation of immune cells and increasing the index of immune organs. These findings suggest that LMWF has a positive immunomodulatory effect and is a promising candidate to supplement cancer immunotherapy.
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Células Dendríticas/efectos de los fármacos , Factores Inmunológicos/farmacología , Polisacáridos/farmacología , Undaria , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Dendríticas/metabolismo , Factores Inmunológicos/química , Subunidad p40 de la Interleucina-12/metabolismo , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Peso Molecular , FN-kappa B/metabolismo , Nueva Zelanda , Polisacáridos/química , Bazo/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of possible animal-to-human (zoonotic) and human-to-animal (zooanthroponotic) transmission and potential spread within animal species. A range of animal species have been verified for SARS-CoV-2 susceptibility, either in vitro or in vivo. However, the molecular bases of such a broad host spectrum for the SARS-CoV-2 remains elusive. Here, we structurally and genetically analysed the interaction between the spike protein, with a particular focus on receptor binding domains (RBDs), of SARS-CoV-2 and its receptor angiotensin-converting enzyme 2 (ACE2) for all conceivably susceptible groups of animals to gauge the structural bases of the SARS-CoV-2 host spectrum. We describe our findings in the context of existing animal infection-based models to provide a foundation on the possible virus persistence in animals and their implications in the future eradication of COVID-19.