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Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality and morbidity globally, and with the prevalence of metabolic-related diseases, the incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) related hepatocellular carcinoma (MAFLD-HCC) continues to rise with the limited efficacy of conventional treatments, which has created a major challenge for HCC surveillance. Immune checkpoint inhibitors (ICIs) and molecularly targeted drugs offer new hope for advanced MAFLD-HCC, but the evidence for the use of both types of therapy in this type of tumour is still insufficient. Theoretically, the combination of immunotherapy, which awakens the body's anti-tumour immunity, and targeted therapies, which directly block key molecular events driving malignant progression in HCC, is expected to produce synergistic effects. In this review, we will discuss the progress of immunotherapy and molecular targeted therapy in MAFLD-HCC and look forward to the opportunities and challenges of the combination therapy.
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The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has been the most distinctive polymer protein complex. After recognizing the endogenous and exogenous danger signals, NLRP3 can cause inflammation by pyroptosis and secretion of mature, bioactive forms of IL-1ß and IL-18. The NLRP3 inflammasome is essential in the genesis and progression of infectious illnesses. Herein, we provide a comprehensive review of the NLRP3 inflammasome in infectious diseases, focusing on its two-sided effects. As an essential part of host defense with a protective impact, abnormal NLRP3 inflammasome activation, however, result in a systemic high inflammatory response, leading to subsequent damage. In addition, scientific evidence of small molecules, biologics, and phytochemicals acting on the NLRP3 inflammasome has been reviewed. We believe that the NLRP3 inflammasome helps us understand the pathological mechanism of different stages of infectious diseases and that inhibitors targeting the NLRP3 inflammasome will become a new and valuable research direction for the treatment of infectious diseases.
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Enfermedades Transmisibles , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Humanos , Inflamasomas/inmunología , Inflamasomas/metabolismo , Animales , Enfermedades Transmisibles/inmunología , Enfermedades Transmisibles/metabolismo , Inflamación/inmunología , Interleucina-1beta/metabolismo , Interleucina-1beta/inmunologíaRESUMEN
INTRODUCTION: Stroke is a leading cause of disability and mortality globally. This study aimed to develop a prognostic nomogram based on neutrophil-to-albumin ratio (NAR) and collateral status in acute ischemic stroke (AIS) patients with anterior large vessel occlusion (LVO). MATERIAL & METHOD: 590 AIS patients with LVO assessed for regional leptomeningeal collateral (rLMC) were retrospectively enrolled, and randomly divided into a training set (n = 414) and a testing set (n = 176). Unfavorable functional outcome was defined as a modified Rankin scale (mRS) score of 3 to 6 at 3 months. We assessed the accuracy and clinical utility of the nomogram using calibration plots, area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS: Both NAR and rLMC were independently associated with unfavorable outcome at 3 months (OR=8.96, p=0.0341; OR=0.89, p=0.0002, respectively). The developed nomogram (akaike information criterion (AIC)=398.77), which included NAR, rLMC and other factors, showed good performance (the AUC for the development and validation cohorts was 0.848 and 0.840 respectively) and improved the predictive value compared to a model without NAR and rLMC, according to an overall NRI of 3.27% (p=0.2401), overall IDI of 3.27% (p=0.2414), and a higher AUC (0.848 vs 0.831). CONCLUSIONS: NAR can serve as an independent predictor in AIS patients with anterior LVO, and the nomogram incorporating NAR and rLMC is reliable in predicting unfavorable outcome. Further studies with larger sample sizes are needed to validate and extend these findings.
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In this study, the effects of sea buckthorn oil (SBO), fish oil (FO) and an enzymatically synthesized structured lipid (SL) on serum, short-chain fatty acids (SCFAs) and intestinal microbiota in Sprague-Dawley (SD) rats were investigated. The results demonstrated that FO, SBO, and SL effectively reduced the levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the serum of SD rats. SBO increased serum triglyceride levels, while FO elevated total cholesterol levels. Furthermore, all three dietary lipids decreased short-chain fatty acid production and enhanced intestinal microbiota diversity. FO increased the abundance of intestinal microbiota including Romboutsia, Lactobacillus, Escherichia-Shigella, and Lachnospiraceae_NK4A136_group. Conversely, all three dietary lipids reduced the abundance of Klebsiella and Blautia. These findings provide a foundation for understanding the functionality of SBO and FO as well as their potential application in synthesizing novel SLs to regulate intestinal microbiota.
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The vertebral artery's morphological characteristics are crucial in spontaneous vertebral artery dissection (sVAD). We aimed to investigate morphologic features related to ischemic stroke (IS) and develop a novel prediction model. Out of 126 patients, 93 were finally analyzed. We constructed 3D models and morphological analyses. Patients were randomly classified into training and validation cohorts (3:1 ratio). Variables selected by LASSO - including five morphological features and five clinical characteristics - were used to develop prediction model in the training cohort. The model exhibited a high area under the curve (AUC) of 0.944 (95%CI, 0.862-0.984), with internal validation confirming its consistency (AUC = 0.818, 95%CI, 0.597-0.948). Decision curve analysis (DCA) indicated clinical usefulness. Morphological features significantly contribute to risk stratification in sVAD patients. Our novel developed model, combining interdisciplinary parameters, is clinically useful for predicting IS risk. Further validation and in-depth research into the hemodynamics related to sVAD are necessary.
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BACKGROUND: Inner Mongolia cashmere goat (IMCG), renowned for its superior cashmere quality, is a Chinese indigenous goat breed that has been developed through natural and artificial selection over a long period. However, recently, the genetic resources of IMCGs have been significantly threatened by the introduction of cosmopolitan goat breeds and the absence of adequate breed protection systems. RESULTS: In order to assess the conservation effectiveness of IMCGs and efficiently preserve and utilize the purebred germplasm resources, this study analyzed the genetic diversity, kinship, family structure, and inbreeding of IMCGs utilizing resequencing data from 225 randomly selected individuals analyzed using the Plink (v.1.90), GCTA (v.1.94.1), and R (v.4.2.1) software. A total of 12,700,178 high-quality SNPs were selected through quality control from 34,248,064 SNP sites obtained from 225 individuals. The average minor allele frequency (MAF), polymorphic information content (PIC), and Shannon information index (SHI) were 0.253, 0.284, and 0.530, respectively. The average observed heterozygosity (Ho) and the average expected heterozygosity (He) were 0.355 and 0.351, respectively. The analysis of the identity by state distance matrix and genomic relationship matrix has shown that most individuals' genetic distance and genetic relationship are far away, and the inbreeding coefficient is low. The family structure analysis identified 10 families among the 23 rams. A total of 14,109 runs of homozygosity (ROH) were identified in the 225 individuals, with an average ROH length of 1014.547 kb. The average inbreeding coefficient, calculated from ROH, was 0.026 for the overall population and 0.027 specifically among the 23 rams, indicating a low level of inbreeding within the conserved population. CONCLUSIONS: The IMCGs exhibited moderate polymorphism and a low level of kinship with inbreeding occurring among a limited number of individuals. Simultaneously, it is necessary to prevent the loss of bloodline to guarantee the perpetuation of the IMCGs' germplasm resources.
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Variación Genética , Cabras , Polimorfismo de Nucleótido Simple , Animales , Cabras/genética , Secuenciación Completa del Genoma , Frecuencia de los Genes , Endogamia , ChinaRESUMEN
The buried interface tens of nanometers beneath the solid-liquid junction is crucial for photocarrier extraction, influencing the overall efficiency of photoelectrochemical devices. Precise characterization of the interfacial properties is essential for device optimization but remains challenging. Here, we directly probe the in situ transformation of a CuxO interlayer at the NiO/n-Si interface by hard X-ray photoelectron spectroscopy. It is found that Cu(I) in the CuxO interlayer gradually transforms to Cu(II) with air exposure, forming an energetically more favorable interface and improving photoanode's efficiency. Based on this finding, a reactive e-beam evaporation process is developed for the direct deposition of a CuO interlayer, achieving a half-cell solar-to-hydrogen efficiency of 4.56% for the optimized NiO/CuO/n-Si heterojunction photoanode. Our results highlight the importance of precision characterization of interfacial properties with advanced hard X-ray photoelectron spectroscopy in guiding the design of efficient solar water-splitting devices.
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The design of hydrophilic polyvinylidene fluoride (PVDF) membranes with anti-fouling properties has been explored for decades. Surface modification and blending are typical strategies to tailor the hydrophilicity of PVDF membranes. Herein, cyclodextrin was used to improve the antifouling performance of PVDF membranes. Cyclodextrin-modified PVDF membranes were prepared by coupling PVDF amination (blending with branched polyethyleneimine) and activated cyclodextrin grafting. The blending of PEI in the PVDF casting solution preliminarily aminated the PVDF, resulting in PEI-crosslinked/grafted PVDF membranes after phase inversion. Aldehydes groups on cyclodextrin, introduced by oxidation, endow cyclodextrin to be grafted on the aminated PVDF membrane by the formation of imines. Borch reduction performed on the activated cyclodextrin-grafted PVDF membrane converted the imine bonds to secondary amines, ensuring the membrane stability. The resulting membranes possess excellent antifouling performance, with a lower protein adsorption capacity (5.7 µg/cm2, indicated by Bovine Serum Albumin (BSA)), and a higher water flux recovery rate (FRR = 96%). The proposed method provides a facial strategy to prepare anti-fouling PVDF membranes.
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Incrustaciones Biológicas , Ciclodextrinas , Interacciones Hidrofóbicas e Hidrofílicas , Membranas Artificiales , Polivinilos , Polivinilos/química , Incrustaciones Biológicas/prevención & control , Ciclodextrinas/química , Adsorción , Albúmina Sérica Bovina/química , Polímeros de FluorocarbonoRESUMEN
Hydrogen sulfide (H2S) is a key factor in various biological processes such as plant grow and its response to environmental stress. Here, we develop a novel near-infrared (NIR) fluorescent probe for detecting hydrogen sulfide based on the regulatory NIR dye pKa values. After triggering the H2S substitution response, probe A with introducing the cyano moiety not only exhibits a significant near-infrared emission (Emax: 724 nm) response in physiological environments, but also shows a fast response, high selectivity, and sensitivity (LOD as 0.52 µM). In addition, probe A with low biological cytotoxicity is successfully used for imaging detection of cellular exogenous and endogenous hydrogen sulfide. More importantly, in situ imaging of probe A tracks the H2S fluctuations in the rice root system and its response to environmental stress. Hence, this work offers a new NIR fluorescence imaging monitoring tool for hydrogen sulfide in biological systems.
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Colorantes Fluorescentes , Sulfuro de Hidrógeno , Oryza , Raíces de Plantas , Sulfuro de Hidrógeno/análisis , Sulfuro de Hidrógeno/metabolismo , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Oryza/química , Oryza/metabolismo , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Humanos , Espectroscopía Infrarroja Corta/métodos , Espectrometría de Fluorescencia , Imagen Óptica/métodos , Límite de DetecciónRESUMEN
To study the biocompatibility of nanohydroxyapatite (nmHA)-SiO2 fiber material and its efficacy in guided bone regeneration. â The cytotoxicity of the nmHA-SiO2 fiber material to MC3T3-E1 cells was determined by CCK-8 assay. The adhesion of cells on the surface of the material was observed. â¡ Bone defects were prepared in the skull of three groups of New Zealand white rabbits. The following treatments were administered: implantation of nmHA-SiO2, implantation of Bio-Oss, and no treatment. The defects were then covered with nmHA-SiO2 membrane or Hai'ao oral repair membrane. Animal samples were analyzed by gross observation, micro-computed tomography, hematoxylin-eosin staining and Masson staining. The data were statistically analyzed by multivariate analysis of variance to evaluate the repair of bone defects. â The nmHA-SiO2 fiber material has suitable biocompatibility. â¡ The nmHA-SiO2 fiber material performed more effectively as a barrier membrane than other bone substitute materials in GBR model rabbits.
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Materiales Biocompatibles , Regeneración Ósea , Durapatita , Dióxido de Silicio , Animales , Conejos , Dióxido de Silicio/química , Durapatita/química , Durapatita/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Regeneración Ósea/efectos de los fármacos , Microtomografía por Rayos X , Ensayo de Materiales , Ratones , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Cráneo/cirugía , Cráneo/diagnóstico por imagen , Propiedades de Superficie , MineralesRESUMEN
Objective: This meta-analysis aimed to determine the efficacy of curcumin in preventing liver fibrosis in animal models. Methods: A systematic search was conducted on studies published from establishment to November 2023 in PubMed, Web of Science, Embase, Cochrane Library, and other databases. The methodological quality was assessed using Sycle's RoB tool. An analysis of sensitivity and subgroups were performed when high heterogeneity was observed. A funnel plot was used to assess publication bias. Results: This meta-analysis included 24 studies involving 440 animals with methodological quality scores ranging from 4 to 6. The results demonstrated that curcumin treatment significantly improved Aspartate aminotransferase (AST) [standard mean difference (SMD) = -3.90, 95% confidence interval (CI) (-4.96, -2.83), p < 0.01, I2 = 85.9%], Alanine aminotransferase (ALT)[SMD = - 4.40, 95% CI (-5.40, -3.40), p < 0.01, I2 = 81.2%]. Sensitivity analysis of AST and ALT confirmed the stability and reliability of the results obtained. However, the funnel plot exhibited asymmetry. Subgroup analysis based on species and animal models revealed statistically significant differences among subgroups. Furthermore, curcumin therapy improved fibrosis degree, oxidative stress level, inflammation level, and liver synthesis function in animal models of liver fibrosis. Conclusion: Curcumin intervention not only mitigates liver fibrosis but also enhances liver function, while concurrently modulating inflammatory responses and antioxidant capacity in animal models. This result provided a strong basis for further large-scale animal studies as well as clinical trials in humans in the future. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024502671.
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BACKGROUND: In the context of increasing exposure to silica nanoparticles (SiNPs) and ensuing respiratory health risks, emerging evidence has suggested that SiNPs can cause a series of pathological lung injuries, including fibrotic lesions. However, the underlying mediators in the lung fibrogenesis caused by SiNPs have not yet been elucidated. RESULTS: The in vivo investigation verified that long-term inhalation exposure to SiNPs induced fibroblast activation and collagen deposition in the rat lungs. In vitro, the uptake of exosomes derived from SiNPs-stimulated lung epithelial cells (BEAS-2B) by fibroblasts (MRC-5) enhanced its proliferation, adhesion, and activation. In particular, the mechanistic investigation revealed SiNPs stimulated an increase of epithelium-secreted exosomal miR-494-3p and thereby disrupted the TGF-ß/BMPR2/Smad pathway in fibroblasts via targeting bone morphogenetic protein receptor 2 (BMPR2), ultimately resulting in fibroblast activation and collagen deposition. Conversely, the inhibitor of exosomes, GW4869, can abolish the induction of upregulated miR-494-3p and fibroblast activation in MRC-5 cells by the SiNPs-treated supernatants of BEAS-2B. Besides, inhibiting miR-494-3p or overexpression of BMPR2 could ameliorate fibroblast activation by interfering with the TGF-ß/BMPR2/Smad pathway. CONCLUSIONS: Our data suggested pulmonary epithelium-derived exosomes serve an essential role in fibroblast activation and collagen deposition in the lungs upon SiNPs stimuli, in particular, attributing to exosomal miR-494-3p targeting BMPR2 to modulate TGF-ß/BMPR2/Smad pathway. Hence, strategies targeting exosomes could be a new avenue in developing therapeutics against lung injury elicited by SiNPs.
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Colágeno , Epigénesis Genética , Exosomas , Fibroblastos , Pulmón , MicroARNs , Nanopartículas , Transducción de Señal , Dióxido de Silicio , Factor de Crecimiento Transformador beta , Exosomas/metabolismo , Animales , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Dióxido de Silicio/química , Transducción de Señal/efectos de los fármacos , Ratas , Pulmón/metabolismo , Pulmón/patología , Colágeno/metabolismo , Humanos , Nanopartículas/química , MicroARNs/metabolismo , MicroARNs/genética , Línea Celular , Factor de Crecimiento Transformador beta/metabolismo , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/inducido químicamente , Masculino , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Ratas Sprague-Dawley , Epitelio/metabolismo , Epitelio/efectos de los fármacosRESUMEN
The toxicity of silica nanoparticles (SiNPs) to lung is known. We previously demonstrated that exposure to SiNPs promoted pulmonary impairments, but the precise pathogenesis remains elucidated. Ferroptosis has now been identified as a unique form of oxidative cell death, but whether it participated in SiNPs-induced lung injury remains unclear. In this work, we established a rat model with sub-chronic inhalation exposure of SiNPs via intratracheal instillation, and conducted histopathological examination, iron detection, and ferroptosis-related lipid peroxidation and protein assays. Moreover, we evaluated the effect of SiNPs on epithelial ferroptosis, possible mechanisms using in vitro-cultured human bronchial epithelial cells (16HBE), and also assessed the ensuing impact on fibroblast activation for fibrogenesis. Consequently, fibrotic lesions occurred in the rat lungs, concomitantly by enhanced lipid peroxidation, iron overload, and ferroptosis. Consistently, the in vitro data showed SiNPs triggered oxidative stress and caused the accumulation of lipid peroxides, resulting in ferroptosis. Importantly, the mechanistic investigation revealed miR-21-5p as a key player in the epithelial ferroptotic process induced by SiNPs via targeting GCLM for GSH depletion. Of note, ferrostatin-1 could greatly suppress ferroptosis and alleviate epithelial injury and ensuing fibroblast activation by SiNPs. In conclusion, our findings first revealed SiNPs triggered epithelial ferroptosis through miR-21-5p/GCLM signaling and thereby promoted fibroblast activation for fibrotic lesions, and highlighted the therapeutic potential of inhibiting ferroptosis against lung impairments upon SiNPs exposure.
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Células Epiteliales , Ferroptosis , Pulmón , MicroARNs , Nanopartículas , Transducción de Señal , Dióxido de Silicio , Ferroptosis/efectos de los fármacos , Animales , Humanos , MicroARNs/metabolismo , MicroARNs/genética , Ratas , Nanopartículas/química , Transducción de Señal/efectos de los fármacos , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Masculino , Glutamato-Cisteína Ligasa/metabolismo , Glutamato-Cisteína Ligasa/genética , Línea Celular , Ratas Sprague-Dawley , Estrés Oxidativo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Glutatión/metabolismo , Ciclohexilaminas/farmacología , FenilendiaminasRESUMEN
Micro- and nanoplastic pollution has emerged as a significant global concern due to their extensive presence in the environment and potential adverse effects on human health. Nanoplastics can enter the human circulatory system and accumulate in the liver, disrupting hepatic metabolism and causing hepatotoxicity. However, the precise mechanism remains uncertain. Lipophagy is an alternative mechanism of lipid metabolism involving autophagy. This study aims to explore how polystyrene nanoplastics (PSNPs) influence lipid metabolism in hepatocytes via lipophagy. Initially, it was found that PSNPs were internalized by human hepatocytes, resulting in decreased cell viability. PSNPs were found to induce the accumulation of lipid droplets (LDs), with autophagy inhibition exacerbating this accumulation. Then, PSNPs were proved to activate lipophagy by recruiting LDs into autophagosomes and block the lipophagic flux by impairing lysosomal function, inhibiting LD degradation. Ultimately, PSNPs were shown to activate lipophagy through the AMPK/ULK1 pathway, and knocking down AMPK exacerbated lipid accumulation in hepatocytes. Overall, these results indicated that PSNPs triggered lipophagy via the AMPK/ULK1 pathway and blocked lipophagic flux, leading to lipid accumulation in hepatocytes. Thus, this study identifies a novel mechanism underlying nanoplastic-induced lipid accumulation, providing a foundation for the toxicity study and risk assessments of nanoplastics.
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Proteínas Quinasas Activadas por AMP , Homólogo de la Proteína 1 Relacionada con la Autofagia , Autofagia , Hepatocitos , Metabolismo de los Lípidos , Poliestirenos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Poliestirenos/toxicidad , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Autofagia/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Gotas Lipídicas/metabolismo , Gotas Lipídicas/efectos de los fármacos , Nanopartículas/toxicidad , Transducción de Señal/efectos de los fármacos , Microplásticos/toxicidad , Células Hep G2 , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Supervivencia Celular/efectos de los fármacosRESUMEN
Phosphorene and fullerene are representative two-dimensional (2D) and zero-dimensional (0D) nanomaterials respectively, constructing their heterodimensional hybrid not only complements their physiochemical properties but also extends their applications via synergistic interactions. This is however challenging because of their diversities in dimension and chemical reactivity, and theoretical studies predicted that it is improbable to directly bond C60 onto the surface of phosphorene due to their strong repulsion. Here, we develop a facile electrosynthesis method to synthesize the first phosphorene-fullerene hybrid featuring fullerene surface bonding via P-C bonds. Few-layer black phosphorus nanosheets (BPNSs) obtained from electrochemical exfoliation react with C60 2- dianion prepared by electroreduction of C60, fulfilling formation of the "improbable" phosphorene-fullerene hybrid (BPNS-s-C60). Theoretical results reveal that the energy barrier for formation of [BPNS-s-C60]2- intermediate is significantly decreased by 1.88â eV, followed by an oxidization reaction to generate neutral BPNS-s-C60 hybrid. Surface bonding of C60 molecules not only improves significantly the ambient stability of BPNSs, but also boosts dramatically the visible light and near-infrared (NIR) photocatalytic hydrogen evolution rates, reaching 1466 and 1039â µmol h-1 g-1 respectively, which are both the highest values among all reported BP-based metal-free photocatalysts.
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Neutralizing antibodies targeting the spike (S) protein of SARS-CoV-2, elicited either by natural infection or vaccination, are crucial for protection against the virus. Nonetheless, the emergence of viral escape mutants presents ongoing challenges by contributing to breakthrough infections. To define the evolution trajectory of SARS-CoV-2 within the immune population, we co-incubated replication-competent rVSV/SARS-CoV-2/GFP chimeric viruses with sera from COVID-19 convalescents. Our findings revealed that the E484D mutation contributes to increased viral resistant against both convalescent and vaccinated sera, while the L1265R/H1271Y double mutation enhanced viral infectivity in 293T-hACE2 and Vero cells. These findings suggest that under the selective pressure of polyclonal antibodies, SARS-CoV-2 has the potential to accumulate mutations that facilitate either immune evasion or greater infectivity, facilitating its adaption to neutralizing antibody responses. Although the mutations identified in this study currently exhibit low prevalence in the circulating SARS-CoV-2 populations, the continuous and meticulous surveillance of viral mutations remains crucial. Moreover, there is an urgent necessity to develop next-generation antibody therapeutics and vaccines that target diverse, less mutation-prone antigenic sites to ensure more comprehensive and durable immune protection against SARS-CoV-2.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Mutación , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Humanos , COVID-19/inmunología , COVID-19/virología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Animales , Chlorocebus aethiops , Células Vero , Evasión Inmune , Células HEK293RESUMEN
Rationale: Monoclonal gammopathy of renal significance (MGRS) represents a group of disorders caused by monoclonal immunoglobulin (M protein) secreted by B cells or plasma cells. Proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID) is a glomerular disease and a form of MGRS. Here, we presented a rare case of a patient with IgM kappa PGNMID complicated with nocardiosis dermatitis. Patient concerns and diagnoses: A 56-year-old man was admitted to the hospital because of cutaneous purpura and proteinuria. His initial pathological diagnosis indicated membranous proliferative glomerulonephritis, IgM(++), and subacute interstitial nephritis. Based on further examination, he was finally diagnosed to have IgM kappa PGNMID and subacute interstitial nephritis. After the initial diagnosis, the patient received hormonal therapy. During the treatment, nocardiosis dermatitis emerged as a complication, and the hormonal therapy was gradually reduced. The patient refused further treatment with rituximab, and his health is currently stable. Outcomes: IgM kappa PGNMID complicated with nocardiosis dermatitis is an extremely rare occurrence. Laboratory examination and pathological analysis are required to confirm the diagnosis of this disorder. Timely and accurate diagnosis is essential for the appropriate treatment of PGNMID.
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BACKGROUND: Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described. RESULTS: We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation. CONCLUSIONS: Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products.
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Ferroptosis , Sobrecarga de Hierro , MicroARNs , Nanopartículas , Humanos , Miocitos Cardíacos , Dióxido de Silicio/metabolismo , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/patología , Hierro/metabolismo , Hierro/farmacología , MicroARNs/metabolismo , Nanopartículas/toxicidadRESUMEN
Bisulfite (HSO3-) and biological thiols molecules, such as glutathione (GSH), cysteine (Cys), and homocysteine (Hcy), play important roles in organisms. Developing a fluorescent probe that can simultaneously detect and distinguish HSO3- and biological thiols is of great significance. In this study, ethyl(2E,4Z)-5-chloro-2-cyano-5-(7-(diethylamino)-2-oxo-2 H-chromen-3-yl)penta-2,4-dienoate (CCO) as a novel enhanced fluorescence probe was synthesized by integrating coumarin derivatives and ethyl cyanoacetate, which can simultaneous detection and discrimination of hydrogen bisulfite anions and glutathione. The sensing mechanism was elucidated through spectral analysis and some control experiments. In weakly alkaline environments, the probe not only has good selectivity for HSO3- and GSH, but also has a lower detection limits of 0.0179 µM and 0.2034 µM. The probe exhibited fuorescent turn-on for distinguishing with 296 and 28 fold the fluorescent intensity increase at 486 and 505 nm, respectively, through diferent excitation wavelengths. This provides a new method for simultaneous detection and discrimination of HSO3- and biological thiol cell levels and further applications.
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In the emerging Sb2S3-based solar energy conversion devices, a CdS buffer layer prepared by chemical bath deposition is commonly used to improve the separation of photogenerated electron-hole pairs. However, the cation diffusion at the Sb2S3/CdS interface induces detrimental defects but is often overlooked. Designing a stable interface in the Sb2S3/CdS heterojunction is essential to achieve high solar energy conversion efficiency. As a proof of concept, this study reports that the modification of the Sb2S3/CdS heterojunction with an ultrathin Al2O3 interlayer effectively suppresses the interfacial defects by preventing the diffusion of Cd2+ cations into the Sb2S3 layer. As a result, a water-splitting photocathode based on Ag:Sb2S3/Al2O3/CdS heterojunction achieves a significantly improved half-cell solar-to-hydrogen efficiency of 2.78% in a neutral electrolyte, as compared to 1.66% for the control Ag:Sb2S3/CdS device. This work demonstrates the importance of designing atomic interfaces and may provide a guideline for the fabrication of high-performance stibnite-type semiconductor-based solar energy conversion devices.