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1.
Phytother Res ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120474

RESUMEN

Calycosin (Caly), a flavonoid compound, demonstrates a variety of beneficial properties. However, the specific mechanisms behind Caly's anticancer effects remain largely unexplored. Network pharmacology was used to explore the potential targets of Caly in renal cancer. Additionally, RNA-seq sequencing was used to detect changes in genes in renal cancer cells after Caly treatment. Validation was carried out through quantitative reverse transcription-PCR and Western blot analysis. The luciferase reporter assay was applied to pinpoint the interaction site between MAZ and HAS2. Furthermore, the immunoprecipitation assay was utilized to examine the ubiquitination and degradation of MAZ. In vivo experiments using cell line-derived xenograft mouse models were performed to assess Calycosin's impact on cancer growth. Network pharmacology research suggests Caly plays a role in promoting apoptosis and inhibiting cell adhesion in renal cancer. In vitro, Caly has been observed to suppress proliferation, colony formation, and metastasis of renal cancer cells while also triggering apoptosis. Additionally, it appears to diminish hyaluronic acid synthesis by downregulating HAS2 expression. MAZ is identified as a transcriptional regulator of HAS2 expression. Calycosin further facilitates the degradation of MAZ via the ubiquitin-proteasome pathway. Notably, Caly demonstrates efficacy in reducing the growth of renal cell carcinoma xenograft tumors in vivo. Our findings indicate that Caly suppresses the proliferation, metastasis, and progression of renal cell carcinoma through its action on the MAZ/HAS2 signaling pathway. Thus, Caly represents a promising therapeutic candidate for the treatment of renal cell carcinoma.

2.
PLoS One ; 19(8): e0305188, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39167616

RESUMEN

This paper examines the long-term and short-run causative relationship among environmental sustainability, energy efficiency, renewable energy and carbon emissions from all over sources (coal, oil and fossil fuels) and sector wise division (heat and power, transportation, residential, manufacturing and other sectors. The empirical evidence presented in this study is derived from a balanced panel dataset spanning the annual periods from 2000 to 2021. The dataset specifically focuses on a selection of BRI Countries. The Kao test demonstrates the presence of cointegration across variables such as carbon dioxide emissions, environmental suitability, energy efficiency and renewable energy. The Panel Pooled Mean Group-Autoregressive Distributed Lag (PMG-ARDL) model indicates a statistically significant positive association between the environmental sustainability and disaggregated CO2 emissions over a long-term period. The study found a positive relationship between disaggregated CO2 emissions and environmental sustainability and energy efficiency, with renewable energy sources reducing emissions. It suggests a need for a structural transition from an energy-intensive economy to a decarbonized one, with sectors like heat and power positively impacting sustainability. Implementing measures to reduce emissions is crucial for tackling climate change.


Asunto(s)
Dióxido de Carbono , Cambio Climático , Energía Renovable , Dióxido de Carbono/análisis , Combustibles Fósiles , Desarrollo Sostenible , Conservación de los Recursos Energéticos , Conservación de los Recursos Naturales/métodos , Ambiente
4.
Org Lett ; 26(32): 6884-6888, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39087724

RESUMEN

The electron donor-acceptor (EDA) complexes have been extensively studied, which formed an electronically excited state, obviating the need for an exogenous photocatalyst. Herein, we report a mild and efficient strategy for photoinduced radical domino perfluoroalkylation/cyclization using N,N,N',N'-tetramethylethane-1,2-diamine (TMEDA) as an electron donor. This protocol could be well expanded to access various polycyclic quinazolinones containing perfluoroalkyl groups, exhibiting photocatalyst-free, good functional group tolerance, and environmentally friendly features.

5.
Sci Rep ; 14(1): 18255, 2024 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107357

RESUMEN

Polyhydroxyalkanoates (PHAs) could be used to make sustainable, biodegradable plastics. However, the precise and accurate mechanistic modeling of PHA biosynthesis, especially medium-chain-length PHA (mcl-PHA), for yield improvement remains a challenge to biology. PHA biosynthesis is typically triggered by nitrogen limitation and tends to peak at an optimal carbon-to-nitrogen (C/N) ratio. Specifically, simulation of the underlying dynamic regulation mechanisms for PHA bioprocess is a bottleneck owing to surfeit model complexity and current modeling philosophies for uncertainty. To address this issue, we proposed a quantum-like decision-making model to encode gene expression and regulation events as hidden layers by the general transformation of a density matrix, which uses the interference of probability amplitudes to provide an empirical-level description for PHA biosynthesis. We implemented our framework modeling the biosynthesis of mcl-PHA in Pseudomonas putida with respect to external C/N ratios, showing its optimization production at maximum PHA production of 13.81% cell dry mass (CDM) at the C/N ratio of 40:1. The results also suggest the degree of P. putida's preference in channeling carbon towards PHA production as part of the bacterium's adaptative behavior to nutrient stress using quantum formalism. Generic parameters (kD, kN and theta θ) obtained based on such quantum formulation, representing P. putida's PHA biosynthesis with respect to external C/N ratios, was discussed. This work offers a new perspective on the use of quantum theory for PHA production, demonstrating its application potential for other bioprocesses.


Asunto(s)
Nitrógeno , Polihidroxialcanoatos , Pseudomonas putida , Pseudomonas putida/metabolismo , Pseudomonas putida/genética , Polihidroxialcanoatos/biosíntesis , Polihidroxialcanoatos/metabolismo , Nitrógeno/metabolismo , Carbono/metabolismo , Teoría Cuántica , Nutrientes/metabolismo , Modelos Biológicos
6.
Aging Cell ; : e14309, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39135295

RESUMEN

Atrial fibrillation (AF) has been receiving a lot of attention from scientists and clinicians because it is an extremely common clinical condition. Due to its special hemodynamic changes, AF has a high rate of disability and mortality. So far, although AF has some therapeutic means, it is still an incurable disease because of its complex risk factors and pathophysiologic mechanisms, which is a difficult problem for global public health. Age is an important independent risk factor for AF, and the incidence of AF increases with age. To date, there is no comprehensive review on aging-associated AF. In this review, we systematically discuss the pathophysiologic evidence for aging-associated AF, and in particular explore the pathophysiologic mechanisms of mitochondrial dysfunction, telomere attrition, cellular senescence, disabled macroautophagy, and gut dysbiosis involved in recent studies with aging-associated AF. We hope that by exploring the various dimensions of aging-associated AF, we can better understand the specific relationship between age and AF, which may be crucial for innovative treatments of aging-associated AF.

7.
Heliyon ; 10(15): e34879, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39157340

RESUMEN

The majority of previous studies have asserted that the high quality of local institutions can improve the productivity effects of trade policies; yet, only a few studies have acknowledged the heterogeneous impact of these institutions. Using data from Chinese manufacturing plants, we examine the moderating effects of regional-level regulations on the effectiveness of national services trade policy. The key findings are threefold: First, as the initial degree of service liberalization advances, the productivity effect of trade liberalization diminishes. Second, opening access to foreign enterprises can substitute for pro-competitive regulatory reform. Regardless of whether the regulatory institutions related to administrative processes, law enforcement, and commercial service have improved, services trade liberalization can have significant productivity effects. Third, in contrast, when regulations to protect for local incumbents impose prohibitive costs for new entrants, the impact of services trade liberalization is highly contingent on local regulatory improvement. The confirmation that trade liberalization can potentially serve as an alternative measure for local regulation reform in Chinese context distinguishes this study from others.

8.
J Med Genet ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39209701

RESUMEN

BACKGROUND: Recurrent preimplantation embryo developmental arrest (RPEA) is the most common phenotype in assisted reproductive technology treatment failure associated with identified genetic abnormalities. Currently known maternal genetic variants explain only a limited number of cases. Variants of the ß-tubulin subunit gene, TUBB8, cause oocyte meiotic arrest and RPEA through a broad spectrum of spindle defects. In contrast, α-tubulin subunit genes are poorly studied in the context of preimplantation embryonic development. METHODS: Whole exome sequencing was performed on the PREA cohort. Functional characterisations of the identified candidate disease-causing variants were validated using Sanger sequencing, bioinformatics, in vitro functional analyses and single-cell RNA-sequencing of arrested embryos. RESULTS: Four homozygous variants were identified in the PREA cohort: two of TUBA1C (p.Gln358Ter and p.Asp444Metfs*42) and two of TUBA4A (p.Arg339Cys and p.Tyr440Ter). These variants cause varying degrees of spindle assembly defects. Additionally, we characterised changes in the human arrested embryo transcriptome carrying TUBA4A variants, with a particular focus on spindle organisation, chromosome segregation and mRNA decay. CONCLUSION: Our findings identified TUBA1C as a novel genetic marker and expanded the genetic and phenotypic spectrum of TUBA4A in female infertility and RPEA, which altogether highlighted the importance of α-tubulin isotypes in preimplantation embryonic development.

9.
J Virol ; : e0129324, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39212447

RESUMEN

Reassortant Eurasian avian-like H1N1 (rEA H1N1) viruses carrying the internal genes of H1N1/2009 virus have been circulating in pigs for more than 10 years and have caused sporadic human infections. The enhanced virulence phenotype of the rEA H1N1 viruses highlights potential risks to public health. However, the molecular mechanism underlying the viral pathogenicity of the currently circulating rEA H1N1 viruses remains unclear. In this study, we found that two naturally isolated rEA H1N1 swine influenza viruses, A/swine/Liaoning/FX38/2017 (FX38) and A/swine/Liaoning/SY72/2018 (SY72), possessed similar genetic characteristics but exhibited significantly different pathogenicity in a mouse model. Using reverse genetics, we demonstrated that amino acid mutations at positions 100 and 122 in the polymerase acidic (PA) protein had individual and synergistic effects on the polymerase activity and viral replication capacity in vitro, as well as the viral pathogenicity in mice. Furthermore, we revealed that amino acid residue 100 in PA influenced the transcription of viral RNA (vRNA) by altering the endonuclease activity, and amino acid residue 122 affected the synthesis of complementary RNA and messenger RNA by altering the RNA-binding ability and endonuclease activity of the PA protein. Taken together, we identified that two naturally occurring amino acid mutations in PA derived from H1N1/2009 virus are crucial determinants of the virulence of rEA H1N1 viruses and revealed the differential mechanism by which these two mutations affect the transcription and replication of vRNA. These findings will extend our understanding of the roles of PA in the virulence of influenza A viruses.IMPORTANCEMultiple genetic determinants are involved in the virulence of influenza A viruses. In this study, we identified two naturally occurring amino acid mutations, located at residues 100 and 122 in the polymerase acidic (PA) protein, which are associated with viral polymerase activity, replication competence, and pathogenicity in mice. In particular, we clarified the specific mechanism by which the two residues play an important role in viral transcription and replication. These findings will help to improve understanding the functions of amino acid residues in the N-terminal region of the PA protein involved in the pathogenicity of influenza A viruses.

10.
Biomed Mater ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39208842

RESUMEN

Medical dressings with multifunctional properties, including potent regeneration capability and good biocompatibility, are increasingly needed in clinical practice. In this study, we reported a novel hybrid wound dressing (PCL/SerMA/DMOG) that combines electrospun PCL membranes with DMOG-loaded methacrylated sericin (SerMA) hydrogel. In such a design, DMOG molecules are released from the hybrid dressing in a sustained manner in vitro. A series of in vitro assays demonstrated that DMOG-loaded hybrid dressing has multiple biological functions, including promotion of human umbilical vein endothelial cells (HUVECs) proliferation and migration, in vitro vascularization, and the generation of intracellular NO. When applied to the cutaneous wound, the PCL/SerMA/DMOG dressing significantly accelerated wound closure and tissue regeneration by promoting angiogenesis in the wound area, collagen deposition, and cell proliferation within the wound bed. These results highlight the potential clinical application of PCL/SerMA/DMOG hybrid dressings as promising alternatives for accelerating wound healing via improved biocompatibility and angiogenesis amelioration.

11.
Exp Appl Acarol ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39150623

RESUMEN

The two-spotted spider mite (Tetranychus urticae Koch, TSSM) is recognized as one of the most problematic spider mite pests. However, the precise gene expression patterns across its key developmental stages remain elusive. Here, we performed a comprehensive transcriptome analysis of TSSM eggs, nymphs and adult females using publicly available RNA sequencing (RNA-seq) data to elucidate the overarching transcriptomic differences between these developmental stages. Principal component analysis and hierarchical clustering analysis unveiled distinct separations among samples across different developmental stages, regardless of their Wolbachia infection status. Differential expression analysis revealed 4,089,2,762, and 1,282 core genes specifically enriched in eggs, nymphs, and adults, respectively. KEGG and GO enrichment analyses showed upregulation of genes in eggs are associated with proteolysis, Wnt signaling pathway, DNA transcription, RNA biosynthetic and metabolic processes, as well as protein folding, sorting, and degradation pathways. Meanwhile, nymphs exhibited increased abundance of genes related to chitin/amino sugar metabolic processes, G protein-coupled receptor signaling pathways, monoatomic ion transport, and neurotransmitter transport pathways. Pathways involving sphingolipid and carbohydrate metabolic processes, proteolysis, lipid transport, and localization were particularly enriched in older females. Altogether, our findings suggest that the egg stage exhibits higher activity in cell differentiation processes, the nymph stage is more involved in chitin development, and the adult stage shows increased metabolic and reproductive activity. This study enhances our understanding of the molecular mechanisms underlying TSSM development and paves the way for further research into the intricate physiological processes of TSSM.

12.
Zhonghua Nan Ke Xue ; 30(1): 77-82, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-39046418

RESUMEN

Prostate cancer (PCa) is one of the common tumors in the genitourinary system, with an increasing morbidity and mortality in China. Recent studies show that autophagy plays an important pathophysiological role in many diseases, including cancers. Besides, some miRNAs are also key regulatory factors for autophagy in PCa cells, and play an important role in the development, progression, diagnosis and treatment of PCa. In-depth studies of miRNAs may contribute to the discovery of some valuable diagnostic methods and novel treatment strategies. This article reviews the progress in researches on the role of autophagy-related miRNAs in PCa, aiming to provide some reference for the diagnosis and treatment of the malignancy.


Asunto(s)
Autofagia , MicroARNs , Neoplasias de la Próstata , Humanos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Autofagia/genética , MicroARNs/genética , Masculino , Regulación Neoplásica de la Expresión Génica
13.
Phytochemistry ; 226: 114216, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38972444

RESUMEN

Artemisia annua L. ("Qinghao" in Chinese) is a famous traditional Chinese medicinal herb and has been used to treat malaria and various tumors. Our preliminary screening indicated that the EtOAc extract of A. annua manifested activity against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 53.2%, 52.1%, and 59.6% at 200 µg/mL, respectively. Bioassay-guided isolation of A. annua afforded 14 unusual cadinane-involved sesquiterpenoid dimers, artemannuins A‒N (1-14), of which the structures were elucidated by extensive spectral analyses, ECD calculations, and single-crystal X-ray diffraction. Structurally, these compounds were classified into five different types based on the coupled modes of two monomeric sesquiterpenoids. Among them, compounds 1-9 represented the first examples of sesquiterpenoid dimers formed via the C-3‒C-3' single bond of two 5(4 â†’ 3)-abeo-cadinane sesquiterpenoid monomers, while compounds 13 and 14 were dimers fused by cadinane and humulane sesquiterpenoids via an ester bond. Methylated derivatives of 1, 4, 6, and 8 showed antihepatoma activity against HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values ranging from 30.5 to 57.2 µM.


Asunto(s)
Artemisia annua , Sesquiterpenos Policíclicos , Sesquiterpenos , Humanos , Artemisia annua/química , Sesquiterpenos Policíclicos/farmacología , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/aislamiento & purificación , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Estructura Molecular , Dimerización , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral
14.
Sci Total Environ ; 949: 174909, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39059646

RESUMEN

Accurately capturing the urbanization process is essential for planning sustainable cities and realizing the United Nations Sustainable Development Goal 11. However, until recently, most of the studies on urban expansion in the world have focused on area growth but have little knowledge of height dynamics. This study mapped the spatial distribution of urban built-up areas (UBA) in the Yangtze River Delta (YRD), one of the most urbanized regions in China, to investigate the spatio-temporal evolution in both the horizontal and vertical directions from 1990 to 2020. We coupled and analyzed the horizontal and vertical urban expansion from the 3-D perspective and identified the dominant types. The results showed that 30 cities (73.17 % of the total number of cities) were increasing in the 3-D combined expansion intensity. The decreasing cities were mainly located in Anhui Province. Despite the increasing number of skyscrapers, horizontal growth has dominated urban expansion over the past three decades. The UBA area of the YRD has grown from 4,855.30 km2 to 44,447.15 km2, while the average building height has slowly decreased by 1.26 m. Significant unevenness and differences existed in horizontal and vertical expansions of varying provinces and cities. Our study can accurately grasp the 3-D urban expansion process in the YRD and could promote the efficient development and sustainable utilization of urban land resources in China and beyond.

15.
Biomimetics (Basel) ; 9(6)2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38921190

RESUMEN

Standard alternating leg motions serve as the foundation for simple bipedal gaits, and the effectiveness of the fixed stimulus signal has been proved in recent studies. However, in order to address perturbations and imbalances, robots require more dynamic gaits. In this paper, we introduce dynamic stimulus signals together with a bipedal locomotion policy into reinforcement learning (RL). Through the learned stimulus frequency policy, we induce the bipedal robot to obtain both three-dimensional (3D) locomotion and an adaptive gait under disturbance without relying on an explicit and model-based gait in both the training stage and deployment. In addition, a set of specialized reward functions focusing on reliable frequency reflections is used in our framework to ensure correspondence between locomotion features and the dynamic stimulus. Moreover, we demonstrate efficient sim-to-real transfer, making a bipedal robot called BITeno achieve robust locomotion and disturbance resistance, even in extreme situations of foot sliding in the real world. In detail, under a sudden change in torso velocity of -1.2 m/s in 0.65 s, the recovery time is within 1.5-2.0 s.

16.
J Proteome Res ; 23(7): 2641-2650, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38906844

RESUMEN

To investigate the mechanisms underlying the differences in the freezability of boar semen, Yorkshire boars with freezing-tolerant semen (YT, n = 3), Yorkshire boars with freezing-sensitive semen (YS, n = 3), Landrace boars with freezing-tolerant semen (LT, n = 3), and Landrace boars with freezing-sensitive semen (LS, n = 3) were selected for this study. Their sperm was subjected to protein extraction, followed by data-independent acquisition proteomics and functional bioinformatics analysis. A total of 3042 proteins were identified, of which 2810 were quantified. Some key KEGG pathways were enriched, such as starch and sucrose metabolism, carbohydrate digestion and absorption, mineral absorption, the HIF-1 signaling pathway, and the necroptosis pathways. Through PRM verification, we found that several proteins, such as α-amylase and epididymal sperm-binding protein 1, can be used as molecular markers of the freezing resistance of boar semen. Furthermore, we found that the addition of α-amylase to cryoprotective extender could significantly improve the post-thaw motility and quality of boar semen. In summary, this study revealed some molecular markers and potential molecular pathways contributing to the high or low freezability of boar sperm, identifying α-amylase as a key protein. This study is valuable for optimizing boar semen cryopreservation technology.


Asunto(s)
Criopreservación , Proteómica , Preservación de Semen , Motilidad Espermática , Espermatozoides , alfa-Amilasas , Animales , Masculino , Espermatozoides/metabolismo , Proteómica/métodos , Porcinos , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Criopreservación/veterinaria , alfa-Amilasas/metabolismo , Congelación , Crioprotectores/farmacología , Análisis de Semen/métodos , Análisis de Semen/veterinaria , Proteoma/metabolismo , Proteoma/análisis
17.
Ecotoxicol Environ Saf ; 280: 116559, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38865937

RESUMEN

2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.


Asunto(s)
Retardadores de Llama , Melatonina , Mitocondrias , Oocitos , Animales , Melatonina/farmacología , Ratones , Oocitos/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Femenino , Retardadores de Llama/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Organofosfatos/toxicidad , Daño del ADN/efectos de los fármacos , Apoptosis/efectos de los fármacos , Compuestos Organofosforados/toxicidad
18.
Emerg Microbes Infect ; 13(1): 2364732, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38832658

RESUMEN

Recently, an outbreak of highly pathogenic avian influenza A (H5N1), which carries the clade 2.3.4.4b hemagglutinin (HA) gene and has been prevalent among North American bird populations since the winter of 2021, was reported in dairy cows in the United States. As of 24 May 2024, the virus has affected 63 dairy herds across nine states and has resulted in two human infections. The virus causes unusual symptoms in dairy cows, including an unexpected drop in milk production, and thick colostrum-like milk. Notably, The US Food and Drug Administration reported that around 20% of tested retail milk samples contained H5N1 viruses, with a higher percentage of positive results from regions with infected cattle herds. Data are scant regarding how effectively pasteurization inactivates the H5N1 virus in milk. Therefore, in this study, we evaluated the thermal stability of the H5 clade 2.3.4.4b viruses, along with one human H3N2 virus and other influenza subtype viruses, including H1, H3, H7, H9, and H10 subtype viruses. We also assessed the effectiveness of pasteurization in inactivating these viruses. We found that the avian H3 virus exhibits the highest thermal stability, whereas the H5N1 viruses that belong to clade 2.3.4.4b display moderate thermal stability. Importantly, our data provide direct evidence that the standard pasteurization methods used by dairy companies are effective in inactivating all tested subtypes of influenza viruses in raw milk. Our findings indicate that thermally pasteurized milk products do not pose a safety risk to consumers.


Asunto(s)
Leche , Pasteurización , Animales , Pasteurización/métodos , Leche/virología , Bovinos , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Humanos , Gripe Aviar/virología , Gripe Aviar/transmisión , Gripe Aviar/prevención & control , Gripe Aviar/epidemiología , Inactivación de Virus , Estados Unidos , Gripe Humana/virología , Gripe Humana/transmisión , Gripe Humana/prevención & control , Virus de la Influenza A/genética , Virus de la Influenza A/aislamiento & purificación , Femenino
19.
ACS Nano ; 18(24): 15416-15431, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38840269

RESUMEN

The accumulation of amyloid-ß (Aß) peptides is a major hallmark of Alzheimer's disease (AD) and plays a crucial role in its pathogenesis. Particularly, the structured oligomeric species rich in ß-sheet formations were implicated in neuronal organelle damage. Addressing this formidable challenge requires identifying candidates capable of inhibiting peptide aggregation or disaggregating preformed oligomers for effective antiaggregation-based AD therapy. Here, we present a dual-functional nanoinhibitor meticulously designed to target the aggregation driving force and amyloid fibril spatial structure. Leveraging the exceptional structural stability and facile tailoring capability of endohedral metallofullerene Gd@C82, we introduce desired hydrogen-binding sites and charged groups, which are abundant on its surface for specific designs. Impressively, these designs endow the resultant functionalized-Gd@C82 nanoparticles (f-Gd@C82 NPs) with high capability of redirecting peptide self-assembly toward disordered, off-pathway species, obstructing the early growth of protofibrils, and disaggregating the preformed well-ordered protofibrils or even mature Aß fibrils. This results in considerable alleviation of Aß peptide-induced neuronal cytotoxicity, rescuing neuronal death and synaptic loss in primary neuron models. Notably, these modifications significantly improved the dispersibility of f-Gd@C82 NPs, thus substantially enhancing its bioavailability. Moreover, f-Gd@C82 NPs demonstrate excellent cytocompatibility with various cell lines and possess the ability to penetrate the blood-brain barrier in mice. Large-scale molecular dynamics simulations illuminate the inhibition and disaggregation mechanisms. Our design successfully overcomes the limitations of other nanocandidates, which often overly rely on hydrophobic interactions or photothermal conversion properties, and offers a viable direction for developing anti-AD agents through the inhibition and even reversal of Aß aggregation.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Neuronas , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/química , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Humanos , Gadolinio/química , Gadolinio/farmacología , Nanopartículas/química , Fulerenos/química , Fulerenos/farmacología , Agregado de Proteínas/efectos de los fármacos , Ratones , Diseño de Fármacos , Supervivencia Celular/efectos de los fármacos , Ratas
20.
J Hazard Mater ; 474: 134829, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38865924

RESUMEN

Selective catalytic oxidation of the hazardous DMF exhaust gas presents a significant challenge in balancing oxidation activity and products selectivity (CO, NOx, N2, etc.). It is found that Cu/H-MOR demonstrates superior performance for DMF oxidation compared to CuO on other supports (γ-Al2O3, HY, ZSM-5) in terms of product selectivity and stability. The geometric and electronic structures of CuO active sites in Cu/H-MOR have been regulated by CeO2 promoter, leading to an increase in the ratio of active CuO (highly dispersed CuO and Cu+ specie). As a result, the oxidation activity and stability of the Cu/H-MOR catalyst were enhanced for DMF selective catalytic oxidation. However, excessive CuO or CeO2 content led to decreased N2 selectivity due to over-high oxidation activity. It is also revealed that Ce3+ species, active CuO species, and surface acid sites play a critical role in internal selective catalytic reduction reaction during DMF oxidation. The 10Cu-Ce/H-MOR (1/4) catalyst exhibited both high oxidation activity and internal selective catalytic reduction activity due to its abundance of active CuO specie as well as Ce3+ species and surface acid sites. Consequently, the 10Cu-Ce/H-MOR (1/4) catalyst demonstrated the widest temperature window for DMF oxidation with high N2 selectivity. These findings emphasize the importance of surface active sites modification for DMF selective catalytic oxidation.

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