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1.
J Hazard Mater ; 472: 134440, 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38723480

RESUMEN

N6-methyladenosine (m6A) is the most common form of internal post-transcriptional methylation observed in eukaryotic mRNAs. The abnormally increased level of m6A within the cells can be catalyzed by specific demethylase fat mass and obesity-associated protein (FTO) and stay in a dynamic and reversible state. However, whether and how FTO regulates oxidative damage via m6A modification remain largely unclear. Herein, by using both in vitro and in vivo models of oxidative damage induced by arsenic, we demonstrated for the first time that exposure to arsenic caused a significant increase in SUMOylation of FTO protein, and FTO SUMOylation at lysine (K)- 216 site promoted the down-regulation of FTO expression in arsenic target organ lung, and therefore, remarkably elevating the oxidative damage via an m6A-dependent pathway by its specific m6A reader insulin-like growth factor-2 mRNA-binding protein-3 (IGF2BP3). Consequently, these findings not only reveal a novel mechanism underlying FTO-mediated oxidative damage from the perspective of m6A, but also imply that regulation of FTO SUMOylation may serve as potential approach for treatment of oxidative damage.

2.
Bioorg Med Chem Lett ; 105: 129752, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38631541

RESUMEN

The misfolding and aggregation of α-Syn play a pivotal role in connecting diverse pathological pathways in Parkinson's disease (PD). Preserving α-Syn proteostasis and functionality by inhibiting its aggregation or disaggregating existing aggregates using suitable inhibitors represents a promising strategy for PD prevention and treatment. In this study, a series of benzothiazole-polyphenol hybrids was designed and synthesized. Three identified compounds exhibited notable inhibitory activities against α-Syn aggregation in vitro, with IC50 values in the low micromolar range. These inhibitors demonstrated sustained inhibitory effects throughout the entire aggregation process, stabilizing α-Syn proteostasis conformation. Moreover, the compounds effectively disintegrated preformed α-Syn oligomers and fibers, potentially by binding to specific domains within the fibers, inducing fibril instability, collapse, and ultimately resulting in smaller-sized aggregates and monomers. These findings offer valuable insights into the therapeutic potential of polyphenol hybrids with 2-conjugated benzothiazole targeting α-Syn aggregation in the treatment of PD.


Asunto(s)
Benzotiazoles , Polifenoles , Agregado de Proteínas , alfa-Sinucleína , Benzotiazoles/química , Benzotiazoles/farmacología , Benzotiazoles/síntesis química , alfa-Sinucleína/antagonistas & inhibidores , alfa-Sinucleína/metabolismo , Polifenoles/química , Polifenoles/farmacología , Polifenoles/síntesis química , Humanos , Agregado de Proteínas/efectos de los fármacos , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo
3.
Acta Biomater ; 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38643815

RESUMEN

Obesity represents a growing public health concern and is closely associated with metabolic complications such as diabetes and fatty liver disease. Anti-obesity medications currently available have limited efficacy in weight loss and are often accompanied by adverse effects. This study proposes a localized photothermal therapy (PTT) combined with adipocyte-targeted delivery of rosiglitazone (RSG) to address obesity. Specifically, cationic albumin nanoparticles (cNPs) were synthesized to deliver RSG precisely to white adipocytes, stimulating the browning process. An IR780-loaded thermosensitive hydrogel was injected and allowed to gel in situ to afford a subcutaneous reservoir that enables localized PTT and controlled release of RSG cNPs. Notably, cNPs significantly enhanced the internalization efficiency in adipocytes in vitro and prolonged the therapeutic retention in the adipose tissue in vivo. Co-administration of RSG cNPs and PTT substantially reduced fat content, induced browning in white adipose tissue in diet-induced obese mice, and mitigated complications such as insulin resistance, fatty liver, and hyperlipidemia. The increased expression of uncoupling protein 1 contributes to enhancing energy expenditure and facilitating adipose metabolism, thereby effectively combating obesity. This therapeutic approach integrates localized PTT with adipocyte-targeted delivery to combat the global obesity epidemic thus offering a promising solution with reduced systemic toxicity and enhanced efficacy. STATEMENT OF SIGNIFICANCE: Cationic albumin nanoparticles are capable of efficient internalization in adipocytes, which may enhance drug targeting to adipose tissue. The combination of rosiglitazone-loaded cationic albumin nanoparticles and local hyperthermia effectively reduces lipid accumulation in adipocytes and induces an upregulated expression of uncoupling protein 1. The combination therapy effectively inhibits fat accumulation, induces adipocyte browning, and regulates systemic metabolism in diet-induced obese mice.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 434-438, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38660848

RESUMEN

OBJECTIVE: To detect the expression of L-type amino acid transporter 1 (LAT1) in non-Hodgkin's lymphoma (NHL) tissues, and analyze its effect on clinicopathological characteristics and prognosis of patients. METHODS: A total of 92 NHL patients who were treated in our hospital from January 2017 to April 2019 were collected. The expression of LAT1 in NHL tissue was detected by immunohistochemistry and compared between patients with different pathological features (including sex, Ann Arbor stage, extranodal infiltration, Ki-67). The risk factors affecting mortality were analyzed using univariate and multivariate Cox proportional hazards regression. Receiver operating characteristic (ROC) curve was used to detect the predictive value of percentage of LAT1-positive cells in NHL tissue for patient mortality, and analyzing the effect of percentage of LAT1-positive cells on survival rate. RESULTS: LAT1 was positively expressed in NHL tissue. The high expression rate of LAT1 in Ann Arbor stage III and IV groups were higher than that in Ann Arbor stage I group, that in extranodal infiltration group was higher than non-extranodal infiltration group, and that in Ki-67 positive expression group was higher than Ki-67 negative expression group (all P < 0.05). The remission rate after 3 courses of treatment in high-LAT1 expression group was 70.7%, which was lower than 91.2% in low-LAT1 expression group (P < 0.05). Ann Arbor stage III and IV, extranodal invasion, Ki-67 positive expression and increased expression of LAT1 (LAT1-positive cell percentage score ≥2) were risk factors for mortality. The cut-off value of percentage of LAT1-positive cells for predicting NHL death was 45.6%, and the area under the ROC curve was 0.905 (95%CI: 0.897-0.924). The 3-year survival rate of high-LAT1 level group (the percentage of LAT1-positive cells≥45.6%) was 50.00%, which was lower than 78.26% of low-LAT1 level group (P < 0.05). CONCLUSION: The expression level of LAT1 in NHL tissue increases, which affects Ann Arbor stage and extranodal infiltration of patients. LAT1 is a risk factor for death.


Asunto(s)
Transportador de Aminoácidos Neutros Grandes 1 , Linfoma no Hodgkin , Humanos , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/patología , Pronóstico , Masculino , Femenino , Factores de Riesgo , Tasa de Supervivencia , Estadificación de Neoplasias , Curva ROC , Persona de Mediana Edad
5.
Polymers (Basel) ; 16(7)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38611269

RESUMEN

"Interleaving" is widely used for interlaminar toughening of fiber-reinforced composites, and the structure of interleaving is one of the important factors affecting the toughening efficiency of laminates. Several experiments have demonstrated that compared to continuous and dense structures, toughening layers with structural heterogeneity can trigger multiple toughening mechanisms and have better toughening effects. On this basis, this work further investigates the application of heterogeneous toughening phases in interlaminar toughening of bidirectional GFRP. CNT was selected to construct toughening phases, which was introduced into the interlaminar of composites through efficient spraying methods. By controlling the amount of CNT, various structures of CNT toughening layers were obtained. The fracture toughness of modified laminates was tested, and their toughening mechanism was analyzed based on fracture surface observation. The results indicate that the optimal CNT usage (0.5 gsm) can increase the initial and extended values of interlayer fracture toughness by 136.0% and 82.0%, respectively. The solvent acetone sprayed with CNT can dissolve and re-precipitate a portion of the sizing agent on the surface of the fibers, which improves the bonding of the fibers to the resin. More importantly, larger discrete particles are formed between the layers, guiding the cracks to deflect in the orientation of the toughened layer. This generates additional energy dissipation and ultimately presents an optimal toughening effect.

6.
Sci Total Environ ; 932: 172742, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38679098

RESUMEN

Wastewater monitoring may be a valuable early surveillance tool for studying mpox virus (MPXV) circulation in China, a country with high population density and very few mpox patients. To evaluate the effectiveness of wastewater monitoring for MPXV in detecting local hidden transmission of the epidemic in the early period, the Chinese Center for Disease Control and Prevention initiated a wastewater monitoring program for MPXV in China in July 2023. To enhance the monitoring sensitivity of the program, an MPXV monitoring point was established in a gathering place of high-risk mpox population. Three different concentration methods, PEG precipitation, ultrafiltration, and magnetic beads method were evaluated and compared. Due to its high recovery efficiency, low limit of detection, and high degree of automation, the magnetic beads method was selected for the daily surveillance of MPXV in wastewater. On September 5, 2023, MPXV DNA was detected at the MPXV monitoring point in Zibo City, marking the first instance of MPXV detection of MPXV in wastewater in China. Next-generation sequencing was conducted on the MPXV genome obtained from the positive wastewater, positive environmental samples, and the single case of mpox in Zibo in September. The results showed that the genotypes of these three genomes were different but all belong to the IIb branch of the C.1 lineage, indicating a probably hidden transmission of mpox. Wastewater monitoring is potentially an effective early surveillance tool for tracking the spread of MPXV in areas with high population density and very few mpox patients.

7.
Protein Expr Purif ; 219: 106477, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38527576

RESUMEN

Semaglutide is currently the most promising antidiabetic drug, especially for the treatment of type 2 diabetes mellitus, due to its excellent efficacy in glycemic control and weight loss. However, the production of semaglutide remains high cost, and high yield, low cost, and high purity still remains a challenge. Herein, we reported a convenient and high-yield strategy for the preparation of semaglutide through fragmented condensation coupling, involving solid-phase peptide synthesis of tetrapeptide and on-column refolding and on-column enzyme cleavage based inclusion body expression of Lys26Arg34GLP-1 (11-37) with fused protein tags in an X-Y-D4K-G pattern. The optimized N-terminal protein tag significantly boosts inclusion body expression level, while on-column refolding and on-column enzyme cleavage avoid precipitation, enhancing efficiency and yield together with one-step purification. The successful preparation of semaglutide is expected to achieve large-scale industrial production with low cost, high yield and high purity.


Asunto(s)
Péptidos Similares al Glucagón , Cuerpos de Inclusión , Técnicas de Síntesis en Fase Sólida , Péptidos Similares al Glucagón/química , Técnicas de Síntesis en Fase Sólida/métodos , Cuerpos de Inclusión/química , Escherichia coli/genética , Escherichia coli/metabolismo , Hipoglucemiantes/química , Humanos
8.
Eur J Med Chem ; 268: 116198, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38368711

RESUMEN

α-Syn fibers, the primary cause and central element of Lewy bodies (LB), play a pivotal role in the development of Parkinson's disease (PD). This research aims to identify more potent inhibitors of α-Syn aggregation. A series of N-aryl-3-aryl-pyrazole-5-carboxamide derivatives were designed and synthesized for this purpose. Among them, four candidate compounds, combining pyrazole and polyphenol blocks, were identified through screening, demonstrating good inhibitory effects with IC50 values in the low micromolar range (1.25-4.29 µM). Two candidates exhibited high permeability through the blood-brain barrier. Mechanistic studies using various methods revealed that the candidates preferentially bind to the aggregation-prone domains-proNAC or NAC domains of α-Syn. This binding hinders the conformational transition from random coil/α-helix to ß-sheet, preserving α-Syn proteostasis. As a result, it interferes with α-Syn nuclei formation, prolongs the lag phase, decelerates the elongation phase, and ultimately impedes the formation of α-Syn fibrils. Additionally, the candidates demonstrated promising results in the disaggregation of preformed α-Syn fibers, potentially by binding to specific sites near the ß-sheet domain within fibers. This reduces fiber stability, causing rapid collapse and yielding smaller aggregates and monomers. Crucially, the candidate compounds exhibited significant inhibitory efficacy against α-Syn aggregation within nerve cells with low cytotoxicity. This resulted in a notable inhibition of the formation of LB-like α-Syn inclusions. These compounds show considerable promise as potential therapeutic agents for the prevention and treatment of PD.


Asunto(s)
Enfermedad de Parkinson , alfa-Sinucleína , Humanos , alfa-Sinucleína/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Neuronas/metabolismo , Transporte Biológico
9.
Microorganisms ; 12(2)2024 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-38399812

RESUMEN

The Gram-negative marine bacterium GXY010T, which has been isolated from the surface seawater of the western Pacific Ocean, is aerobic, non-motile and non-flagellated. Strain GXY010T exhibits growth across a temperature range of 10-42 °C (optimal at 37 °C), pH tolerance from 7.0 to 11.0 (optimal at 7.5) and a NaCl concentration ranging from 1.0 to 15.0% (w/v, optimal at 5.0%). Ubiquinone-8 (Q-8) was the predominant isoprenoid quinone in strain GXY010T. The dominant fatty acids (>10%) of strain GXY010T were iso-C15:0 (14.65%), summed feature 9 (iso-C17:1ω9c and/or 10-methyl C16:0) (12.41%), iso-C17:0 (10.85%) and summed feature 3 (C16:1ω7c and/or C16:1ω6c) (10.41%). Phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), unidentifiable glycolipid (GL) and four non-identifiable aminolipids (AL1-AL4) were the predominant polar lipids of strain GXY010T. The genomic DNA G+C content was identified as a result of 48.0% for strain GXY010T. The strain GXY010T genome consisted of 2,766,857 bp, with 2664 Open Reading Frames (ORFs), including 2586 Coding sequences (CDSs) and 78 RNAs. Strain GXY010T showed Average Nucleotide Identity (ANI) values of 73.4% and 70.6% and DNA-DNA hybridization (DDH) values of 19.2% and 14.5% with reference species Pseudidiomarina tainanensis MCCC 1A02633T (=PIN1T) and Pseudidiomarina taiwanensis MCCC 1A00163T (=PIT1T). From the results of the polyphasic analysis, a newly named species, Pseudidiomarina fusca sp. nov. within the genus Pseudidiomarina, was proposed. The type strain of Pseudidiomarina fusca is GXY010T (=JCM 35760T = MCCC M28199T = KCTC 92693T).

10.
Langmuir ; 40(9): 4871-4880, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38377364

RESUMEN

The unclear understanding of the water diffusion behavior posts a big challenge to the manipulation of water absorption properties in epoxy resins. Herein, we investigated the water diffusion behavior and its relationship with molecule structures inside an epoxy resin mainly by the nonequilibrium molecular dynamics and experiments. It is found that at the initial rapid water absorption stage, bound water and free water both contribute, while at the later slow water absorption stage, free water plays a dominant role. The observed evolution of free water and bound water cannot be explained by the traditional Langmuir model. In addition, molecule polarity, free volume, and segment mobility can all influence the water diffusion process. Hence, the epoxy resin with low polarity and high molecular segment mobility is endowed with higher diffusion coefficients. The saturated water absorption content is almost dependent on the polarity. The understanding of how water diffuses and what decides the diffusion process is critical to the rational design of molecule structures for improving the water resistance in epoxy resin.

11.
ACS Appl Bio Mater ; 7(2): 1271-1289, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38315869

RESUMEN

Adipose tissue macrophages (ATMs) are crucial in maintaining a low-grade inflammatory microenvironment in adipose tissues (ATs). Modulating ATM polarization to attenuate inflammation represents a potential strategy for treating obesity with insulin resistance. This study develops a combination therapy of celastrol (CLT) and phenformin (PHE) using chondroitin sulfate-derived micelles. Specifically, CLT-loaded 4-aminophenylboronic acid pinacol ester-modified chondroitin sulfate micelle (CS-PBE/CLT) and chondroitin sulfate-phenformin conjugate micelles (CS-PHE) were synthesized, which were shown to actively target ATs through CD44-mediated pathways. Furthermore, the dual micellar systems significantly reduced inflammation and lipid accumulation via protein quantification and Oil Red O staining. In preliminary in vivo studies, we performed H&E staining, immunohistochemical staining, insulin tolerance test, and glucose tolerance test, and the results showed that the combination therapy using CS-PBE/CLT and CS-PHE micelles significantly reduced the average body weight, white adipose tissue mass, and liver mass of high-fat diet-fed mice while improving their systemic glucose homeostasis. Overall, this combination therapy presents a promising alternative to current treatment options for diet-induced obesity.


Asunto(s)
Sulfatos de Condroitina , Micelas , Triterpenos Pentacíclicos , Animales , Ratones , Fenformina/metabolismo , Tejido Adiposo/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Inflamación , Dieta Alta en Grasa/efectos adversos
12.
Bioorg Med Chem Lett ; 99: 129618, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38219887

RESUMEN

This study focuses on the discovery of new potential drugs for treating PD by targeting the aggregation of α-Syn. A series of hybrids combining Coumarin and phenolic acid were designed and synthesized. Four particularly promising compounds were identified, showing strong inhibitory effects with IC50 values ranging from low micromolar to submicromolar concentrations, as low as 0.63 µM. These compounds exhibited a higher binding affinity to α-Syn residues and effectively hindered the entire aggregation process, maintaining the proteostasis conformation of α-Syn and preventing the formation of ß-sheet aggregates. This approach holds significant promise for PD prevention. Additionally, these candidate compounds demonstrated the ability to break down preformed α-Syn oligomers and fibrils, resulting in the formation of smaller aggregates and monomers. Moreover, the candidate compounds showed impressive effectiveness in inhibiting α-Syn aggregation within nerve cells, thereby reducing the likelihood of α-Syn inclusion formation resembling Lewy bodies, which highlights their potential for treating PD.


Asunto(s)
Neuronas , alfa-Sinucleína , alfa-Sinucleína/metabolismo , Unión Proteica , Neuronas/metabolismo , Cumarinas/farmacología
13.
Environ Sci Ecotechnol ; 20: 100340, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38162402

RESUMEN

Microplastics (MPs), recognized as an emerging global environmental concern, have been extensively detected worldwide, with specific attention directed towards the Yangtze River Estuary (YRE) and East China Sea (ECS) regions. Despite their critical research significance, there remains a knowledge gap concerning the distribution of MPs in the benthic layer within this area, particularly regarding interactions governing their occurrence. Here we illuminate the distribution of MPs within the benthic layer and unravel the intricate interplay between bottom water and sediment in the YRE and ECS. We find that MPs are notably more abundant in bottom water, ranging from 8 to 175 times higher than in surface water. These MPs predominantly consist of polyester fibers, exhibit a size range between 0.5 and 5.0 mm, and display distinct coloration. Co-occurrence network analysis and Principal Coordinate Analysis confirm a robust correlation between MPs in bottom water and sediment, signifying the pivotal role of bottom water in mediating the distribution and transportation of MPs within the benthic layer. Furthermore, a positive correlation between MPs in sediment and bottom water turbidity underscores the impact of surface sediment resuspension and upwelling on MPs distribution. This study clarifies the intricate interactions within the benthic layer and highlights the crucial role of bottom water as a mediator in the vertical distribution of MPs, advancing our understanding of the "source-to-sink" transport processes governing MPs within water-sediment systems.

14.
Angew Chem Int Ed Engl ; 63(5): e202315269, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38065839

RESUMEN

The beauty of one-pot cascade reaction lies in the efficient disconnection and construction of several bonds in a single reaction flask, without the isolation of any intermediates. Herein, we report the first photoinduced thermally promoted cascade reactions of readily available aromatic ketones and aromatic gem-difluoroalkenes for the synthesis of phenanthrenes which possess potential utility in drug design and materials science. The reaction combines carbonyl-olefin metathesis (cascade photoinduced [2+2] cyclization and thermally controlled retro [2+2] cyclization) and dehydrogenative cyclization (cascade photoinduced conrotatory 6π electrocyclization and collidine-promoted dehydrogenative aromatization) together in one pot. The oxidant-free, acid-free and metal-free reaction shows broad substrate scope and wide functional group tolerance.

15.
Nat Chem Biol ; 20(2): 142-150, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37460675

RESUMEN

G-protein-coupled receptors (GPCRs) mediate many critical physiological processes. Their spatial organization in plasma membrane (PM) domains is believed to encode signaling specificity and efficiency. However, the existence of domains and, crucially, the mechanism of formation of such putative domains remain elusive. Here, live-cell imaging (corrected for topography-induced imaging artifacts) conclusively established the existence of PM domains for GPCRs. Paradoxically, energetic coupling to extremely shallow PM curvature (<1 µm-1) emerged as the dominant, necessary and sufficient molecular mechanism of GPCR spatiotemporal organization. Experiments with different GPCRs, H-Ras, Piezo1 and epidermal growth factor receptor, suggest that the mechanism is general, yet protein specific, and can be regulated by ligands. These findings delineate a new spatiomechanical molecular mechanism that can transduce to domain-based signaling any mechanical or chemical stimulus that affects the morphology of the PM and suggest innovative therapeutic strategies targeting cellular shape.


Asunto(s)
Receptores Acoplados a Proteínas G , Transducción de Señal , Membrana Celular/metabolismo , Receptores Acoplados a Proteínas G/metabolismo
16.
Small ; 20(10): e2305641, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37914667

RESUMEN

As a remarkable structure, 2D magnetic heterojunctions have attracted researchers' attention owing to their controlled manipulation in the electronic device. However, successful fabrication as well as modulation of their structure and compound remain challenging. Herein, a novel method is designed to obtain a CoCl2 /Co3 O4 heterojunction on Si/SiO2 substrate with the assistance of supercritical CO2 (SC CO2 ), and the as-fabricated sample has significantly increased coercivity and saturation magnetization, which is 11 times higher than pure Co3 O4 . Further, it can be found that the CO2 pressure has the decisive effect on the saturation magnetization of the sample. Therefore, it suggests that the tunable electronic-magnetic device can be anticipated to be obtained in the future.

17.
J Control Release ; 365: 544-557, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38052255

RESUMEN

Recent advances in adoptive T-cell therapy have delivered impressive therapeutic outcomes by instigating enduring anti-tumor responses. Nonetheless, achieving specific T-cell activation remains a challenge due to several factors. Some cancer cells evade T-cell recognition due to the scarcity of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) presentation. Notably underestimated is the impact of waning T-cell receptor (TCR) expression and the constrained formation of immune synapses (IS) between dendritic cells (DCs) and T cells, impairing T-cell activation. Addressing these complexities, we introduce a pioneering approach featuring the deployment of a gel implant. This implant establishes an on-site antigen reservoir, efficiently targets DCs in lymph nodes, and facilitates calcium ion (Ca2+) delivery. Engineered with controlled swelling, poroelasticity, and resilience, the gel is suitable for surgical implantation. Its ample encapsulation capacity accommodates both photosensitizers and nanoparticles. Upon in situ photothermal irradiation, the gel generates tumor-specific antigens. Furthermore, cationic albumin nanoparticles (cNPs) co-loaded with monophosphoryl lipid A (MPLA) and ionomycin are released, guiding antigens to tumor-draining lymph nodes for DCs maturation. This meticulous process fosters the formation of IS thereby amplifying antigen-specific T-cell activation.


Asunto(s)
Células Dendríticas , Neoplasias , Humanos , Animales , Ratones , Ionóforos de Calcio/metabolismo , Linfocitos T , Presentación de Antígeno , Inmunoterapia , Antígenos de Neoplasias , Neoplasias/metabolismo , Ratones Endogámicos C57BL
18.
Angew Chem Int Ed Engl ; 63(11): e202319685, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38151975

RESUMEN

Glycerol is a byproduct of biodiesel production. Selective photoelectrochemical oxidation of glycerol to high value-added chemicals offers an economical and sustainable approach to transform renewable feedstock as well as store green energy at the same time. In this work, we synthesized monoclinic WO3 nanosheets with exposed (002) facets, which could selectively oxidize glycerol to glyceric acid (GLYA) with a photocurrent density of 1.7 mA cm-2 , a 73 % GLYA selectivity and a 39 % GLYA Faradaic efficiency at 0.9 V vs. reversible hydrogen electrode (RHE) under AM 1.5G illumination (100 mW cm-2 ). Compared to (200) facets exposed WO3 , a combination of experiments and theoretical calculations indicates that the superior performance of selective glycerol oxidation mainly originates from the better charge separation and prolonged carrier lifetime resulted from the plenty of surface trapping states, lower energy barrier of the glycerol-to-GLYA reaction pathway, more abundant active sites and stronger oxidative ability of photogenerated holes on the (002) facets exposed WO3 . Our findings show great potential to significantly contribute to the sustainable and environmentally friendly chemical processes via designing high performance photoelectrochemical cell via facet engineering for renewable feedstock transformation.

19.
Bioorg Med Chem Lett ; 97: 129564, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-38000482

RESUMEN

The aggregation of α-Syn is a pivotal mechanism in Parkinson's disease (PD). Effectively maintaining α-Syn proteostasis involves both inhibiting its aggregation and promoting disaggregation. In this study, we developed a series of aromatic amide derivatives based on Rhein. Two of these compounds, 4,5-dihydroxy-N-(3-hydroxyphenyl)-9,10-dioxo-9,10-dihydroanthracene-2-carboxamide (a5) and 4,5-dihydroxy-N-(2-hydroxy-4-chlorophenyl)-9,10-dioxo-9,10-dihydroanthracene-2-carboxamide (a8), exhibited good binding affinities to α-Syn residues, demonstrating promising inhibitory activity against α-Syn aggregation in vitro, with low IC50 values (1.35 and 1.08 µM, respectivly). These inhibitors acted throughout the entire aggregation process by stabilizing α-Syn's conformation and preventing the formation of ß-sheet aggregates. They also effectively disassembled preformed α-Syn oligomers and fibrils. Preliminary mechanistic insights indicated that they bound to the specific domain within fibrils, inducing fibril instability, collapse, and the formation of smaller aggregates and monomeric α-Syn units. This research underscores the therapeutic potential of Rhein's aromatic amides in targeting α-Syn aggregation for PD treatment and suggests broader applications in managing and preventing neurodegenerative diseases.


Asunto(s)
Antracenos , Enfermedad de Parkinson , Humanos , alfa-Sinucleína , Antraquinonas/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/prevención & control , Enfermedad de Parkinson/metabolismo , Antracenos/química , Antracenos/farmacología
20.
Biomed Rep ; 20(1): 11, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38124772

RESUMEN

Changes in heart structure and function after lung resection in patients with lung cancer are challenging to manage. Therefore, a non-invasive and reliable measurement tool to gauge such changes is critical. The purpose of the present study was to compare cardiological changes before and after lung resection using tissue Doppler imaging (TDI). A total of 43 patients (19 men and 24 women) with primary non-small cell lung cancer (n=37) and metastatic cancer in the lungs (n=6) were enrolled in the study.nTDI was used to determine the thickness of the ascending aorta, the open size of the ascending valve, the anterior-oposterior diameters of the left atrium and left ventricle, and the thickness of the ventricular septum and right ventricle before and after lung resection. Left ventricular (LV) ejection fraction (EF), pulmonary valve flow rate, tricuspid annular or mitral leaflet tip early (E) peak/late (A) diastolic blood flow velocities, tricuspid regurgitation flow, the lateral mitral annulus early (e') diastolic velocity and mitral E/e' ratio were used to determine LV filling pressure. Results revealed no significant differences between male and female patients in terms of the open size of the ascending valve, the anterior-posterior diameter of the left ventricle and the mitral E/e' ratio. Significant differences were found in the width of the ascending aorta, anterior-posterior diameter of the left atrium, width of the LV septum and right ventricular (RV) diameter before and after lung resection. Finally, there were significantchanges in EF and tricuspid pressure. The results indicated that TDI was useful as a non-invasive method for assessing left and right heart function following lung resection. The LV and RV dimensions were affected, but LV filling pressure was preserved after lobectomy.

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