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1.
J Colloid Interface Sci ; 678(Pt A): 970-978, 2025 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-39226837

RESUMEN

Designing highly effective, low-cost bifunctional electrocatalysts without noble metals for overall water splitting remains a significant challenge. In this work, interfacial coupling of Ce-doped CoSe2 nanoneedle arrays with MXene (Ce-CoSe2/MXene) is developed via the facile hydrothermal and selenization methods. The extensive specific surface area and favorable hydrophilicity of Ti3AlC2, combined with the optimized electronic structure and abundant active sites from Ce-doping and selenization, contribute to the exceptional bifunctional electrocatalytic performance of the Ce-CoSe2/MXene electrode. Specifically, this heterostructure achieves a low hydrogen evolution reaction (HER) overpotential of 34 mV at 10 mA cm-2, an oxygen evolution reaction (OER) overpotential of 279 mV at 100 mA cm-2, and an overall water splitting (OWS) potential as low as 1.45 V at 10 mA cm-2. In-situ Raman spectroscopy reveals that surface reconstruction would improve catalytic activity and stability. Theoretical calculations indicate that the Ce-CoSe2/MXene can improve the adsorption of intermediates and facilitate HER/OER process by lowering the kinetic barrier, thereby enhancing electrocatalytic activity. This research marks a substantial advancement in the development of low-cost, efficient electrocatalysts for overall water splitting.

2.
J Colloid Interface Sci ; 678(Pt B): 114-124, 2025 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-39241442

RESUMEN

Utilizing spontaneous polarization field to harness charge transfer kinetics is a promising strategy to boost photocatalytic performance. Herein, a novel Cu atom clusters/PtCu alloy nanocubes coloaded on nitrogen-rich triazole-based C3N5 (PtCu-C3N5) with dipole field was constructed through facile photo-deposition and impregnation method. The dipole field-drive spontaneous polarization in C3N5 acts as a charge-transfer bridge to promote directional electron migration from C3N5 to Cu atom clusters/PtCu alloy. Through the synergistic effects between Cu atom clusters, PtCu alloy and dipole field in C3N5, the optimized Pt2Cu3-C3N5 achieved a record-high performance with H2 formation rate of 4090.4 µmol g-1 h-1 under visible light, about 154.4-fold increase compared with pristine C3N5 (26.5 µmol g-1 h-1). Moreover, the apparent quantum efficiency was up to 25.33 % at 320 nm, which is greatly superior than most previous related-works. The directional charge transfer mechanism was analyzed in detail through various characterizations and DFT calculations. This work offers a novel pathway to construct high-efficiency multi-metal photocatalysts for solar energy conversion.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39356986

RESUMEN

Immunotherapy has fundamentally transformed the clinical cancer treatment landscape; however, achieving intricate and multifaceted modulation of the immune systems remains challenging. Here, a multipathway coordination of immunogenic cell death (ICD), autophagy, and indoleamine 2,3-dioxygenase-1 (IDO1) was achieved by a biomimetic nano-immunomodulator assembled from a chemotherapeutic agent (doxorubicin, DOX), small interfering RNA (siRNA) molecules targeting IDO1 (siIDO1), and the zeolitic imidazolate framework-8 (ZIF-8). After being camouflaged with a macrophage membrane, the biomimetic nanosystem, named mRDZ, enriched in tumors, which allowed synergistic actions of its components within tumor cells. The chemotherapeutic intervention led to a compensatory upregulation in the expression of IDO1, consequently exerting an inhibitory effect on the reactive oxygen species (ROS) and autophagic responses triggered by DOX and ZIF-8. Precise gene silencing of IDO1 by siIDO1 alleviated its suppressive influence, thereby facilitating increased ROS production and improved autophagy, ultimately bolstering tumor immunogenicity. mRDZ exhibited strong capability to boost potent local and systemic antitumor immune responses with a feature of memory, which led to the effective suppression of the growth, lung metastasis, and recurrence of the tumor. Serving as an exemplary model for the straightforward and potent reshaping of the immune system against tumors, mRDZ offers valuable insights into the development of immunomodulatory nanomaterials for cancer therapy.

4.
Toxins (Basel) ; 16(10)2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39453208

RESUMEN

The spleen is a primary target of deoxynivalenol (DON) toxicity, but its underlying molecular mechanisms remain unclear. This study investigates the effects of DON on inflammation, splenic macrophage polarization, endoplasmic reticulum (ER) stress, and transcriptome changes (mRNA and lncRNAs) in mouse spleen. We found that DON exposure at doses of 2.5 or 5 mg/kg BW significantly induced inflammation and polarized splenic macrophages towards the M1 phenotype. Additionally, DON activated PERK-eIF2α-ATF4-mediated ER stress and upregulated apoptosis-related proteins (caspase-12, caspase-3). The ER stress inhibitor, 4-Phenylbutyric acid, significantly alleviated DON-induced ER stress, apoptosis, and the M1 polarization of splenic macrophages. Transcriptome analysis identified 1968 differentially expressed (DE) lncRNAs and 2664 DE mRNAs in mouse spleen following DON exposure. Functional enrichment analysis indicated that the upregulated genes were involved in pathways associated with immunity, including Th17 cell differentiation, TNF signaling, and IL-17 signaling, while downregulated mRNAs were linked to cell survival and growth pathways. Furthermore, 370 DE lncRNAs were predicted to target 255 DE target genes associated with immune processes, including the innate immune response, interferon-beta response, cytokine production regulation, leukocyte apoptosis, and NF-κB signaling genes. This study provides new insights into the mechanisms underlying DON toxicity and its effects on the immune system.


Asunto(s)
Estrés del Retículo Endoplásmico , Inflamación , Macrófagos , ARN Largo no Codificante , Bazo , Tricotecenos , Animales , Bazo/efectos de los fármacos , Bazo/patología , Tricotecenos/toxicidad , Estrés del Retículo Endoplásmico/efectos de los fármacos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Inflamación/inducido químicamente , Inflamación/genética , Apoptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Masculino , Regulación de la Expresión Génica/efectos de los fármacos , Femenino
5.
Ecotoxicol Environ Saf ; 286: 117243, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39447294

RESUMEN

OBJECTIVE: Deoxynivalenol (DON) is a common fungal toxin that poses significant health risks to humans and animals. The present study aimed to investigate the adverse effects and molecular mechanisms of DON-induced kidney injury. METHODS: Male C57BL/6 mice aged 5-6 weeks were used to establish a DON-induced acute kidney injury model. Histological analysis, biochemical assays, molecular techniques, Western blot, RNA sequencing, and transmission electron microscopy were employed to analyze kidney damage, inflammation, oxidative stress, apoptosis, and endoplasmic reticulum (ER) stress. RESULTS: DON disrupted kidney morphology, induced inflammatory cell infiltration, and triggered inflammatory responses. DON increased MDA content while decreasing antioxidant enzyme activity (SOD and CAT). It also triggered apoptosis, evidenced by elevated levels of caspase-12, cleaved caspase-3, and BAX, and reduced levels of Bcl-2. Transcriptomic analysis identified distinct expression patterns in 1756 genes in DON-exposed mouse kidneys, notably upregulating ER stress-related genes. Further investigation revealed ultrastructural changes in the ER and mitochondrial damage induced by DON, along with increased levels of p-IRE1, p-PERK, and their downstream targets, indicating unfolded protein response (UPR) activation in the kidney. The ER stress inhibitor 4-Phenylbutyric acid (4-PBA) significantly mitigated DON-induced ER stress, oxidative damage, apoptosis, tissue injury, ER expansion, and mitochondrial damage. CONCLUSION: Our findings highlight the role of ER stress in DON-induced kidney injury and the protective effect of 4-PBA against these adverse effects.

6.
J Nutr ; 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39424071

RESUMEN

BACKGROUND: NAD+ level declines with age and boosting it can improve multi-organ functions and lifespan. OBJECTIVE: NMN (Nicotinamide mononucleotide), a natural NAD+ (Nicotinamide adenine dinucleotide)precursor with the ability to enhance NAD+ biosynthesis. Numerous studies have shown that a high-fat diet can accelerate the process of aging and many diseases. We hypothesized that long-term administration of NMN could exert protective effects on adipose, muscle, and kidney tissues in mice on a high-fat diet act by affecting the autophagic pathway. METHODS: Mice at 14 months of age were fed a high-fat diet and NMN was added to their drinking water at a dose of 400 mg/kg for 7 months. The locomotor ability of the mice was assessed by behavioral experiments such as grip test, wire hang test, rotarod, and beam-walking test. At the end of the behavioral experiments, the pathological changes of each peripheral organ and the expression of autophagy-related proteins as well as the markers of the senescence and inflammaging were analyzed by pathological staining, immunohistochemical staining and western blotting, respectively. RESULTS: We found that NMN supplementation increased NAD+ levels and ultimately attenuated age- and diet-related physiological decline in mice. NMN inhibited high-fat-diet-induced obesity, promoted physical activity, improved glucose and lipid metabolism, improved skeletal muscle function and renal damage as well as mitigated the senescence and inflammaging as demonstrated by p16, IL-1ß and TNF-α levels. In addition, the present study further emphasizes the potential mechanisms underlying the bidirectional relationship between NAD+ and autophagy. We detected changes in autophagy levels in various tissue organs, and NMN may play a protective role by inhibiting excessive autophagy induced by high-fat diet. CONCLUSION: Our findings demonstrated that NMN administration attenuated high fat diet-induced metabolic disorders and physiological decline in aging mice.

7.
Sci Rep ; 14(1): 19626, 2024 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-39179681

RESUMEN

MicroRNAs (miRNAs) are important regulators of gene expression and are involved in bacterial pathogenesis and host-pathogen interactions. In this study, we investigated the function of miRNAs in the regulation of host responses to Pasteurella multocida infection. Using next-generation sequencing, we analyzed miRNA expression pattern and identified differentially expressed miRNAs in Pasteurella multocida-infected goat lungs. In addition, we investigated the function of differentially expressed miRNAs andtheir targeted signaling pathways in bacterial infection processes. The results showed that Pasteurella multocida infection led to 69 significantly differentially expressed miRNAs, including 28 known annotated miRNAs with miR-497-3p showing the most significant difference. Gene target prediction and functional enrichment analyses showed that the target genes were mainly involved in cell proliferation, regulation of the cellular metabolic process, positive regulation of cellular process, cellular senescence, PI3K-Akt signaling pathway, FoxO signaling pathway and infection-related pathways. In conclusion, these data provide a new perspective on the roles of miRNAs in Pasteurella multocida infection.


Asunto(s)
Cabras , Pulmón , MicroARNs , Infecciones por Pasteurella , Pasteurella multocida , Animales , MicroARNs/genética , MicroARNs/metabolismo , Pasteurella multocida/genética , Infecciones por Pasteurella/veterinaria , Infecciones por Pasteurella/microbiología , Infecciones por Pasteurella/genética , Pulmón/microbiología , Pulmón/metabolismo , Pulmón/patología , Perfilación de la Expresión Génica , Transducción de Señal , Interacciones Huésped-Patógeno/genética , Regulación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedades de las Cabras/microbiología , Enfermedades de las Cabras/genética , Transcriptoma
8.
Artículo en Inglés | MEDLINE | ID: mdl-39185644

RESUMEN

INTRODUCTION: Nicotinamide Mononucleotide (NMN) has gained attention as a precursor to Nicotinamide Adenine Dinucleotide (NAD+) in recent years, commonly utilized in anti-aging therapies. The anti-aging effects of NMN on muscle and liver functions in middleaged and elderly people are still unclear. OBJECTIVE: Based on available randomized controlled trials, we conducted a meta-analysis to evaluate the impact of NMN on muscle and liver functions in middle-aged and elderly individuals. METHODS: We conducted searches on three electronic databases (PubMed, Embase, Web of Science) for randomized controlled trials involving NMN interventions in middle-aged and elderly populations. Through the Cochrane Handbook, we assessed the specific methodological quality. All statistical analyses were obtained by Stata15, and statistical significance was set as P<0.05. RESULTS: There were 412 participants from 9 studies in this meta-analysis. Based on changes in gait speed (SMD: 0.34 m/s, 95%CI [0.03, 0.66] p = 0.033), NMN had significant effects on muscle mass. Moreover, NMN had a better effect on ALT (SMD: -0.29 IU/L, 95%CI [-0.55, -0.03] p = 0.028). Subgroup analysis indicated that administering a small dose of NMN exerted the most prominent impact on Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). CONCLUSION: NMN has positive efficacy in enhancing muscle function, reducing insulin resistance and lowering aminotransferase levels in middle-aged and elderly individuals. NMN is an encouraging and considerable drug for anti-aging treatment.

9.
J Environ Manage ; 368: 122259, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39180826

RESUMEN

Drylands provide a wide range of important ecosystem functions but are sensitive to environmental changes, especially human management. Two major land use types of drylands are grasslands and croplands, which are influenced by intensive grazing activities and agricultural management, respectively. However, little is known about whether the ecosystem functioning of these two land use types is predominated affected by human management, or environmental factors (intrinsic environmental factors and factors modified by human management). This limits our understanding of the ecosystem functions under intensive human management in drylands. Here we reported a study where we collected data from 40 grassland and 30 cropland sites along an extensive aridity gradient in China's drylands to quantify the effects of human management intensity, intrinsic environmental factors (i.e., aridity), and environmental factors modified by human management (i.e., soil bulk density and plant density) on specific ecosystem functions (ecosystem multifunctionality, productivity, carbon storage, soil water, and soil nutrients). We found that the relative importance of each function differed between croplands and grasslands. Ecosystem functions varied with human management intensity, with lower productivity and plant carbon storage in grasslands under high grazing intensity than un-grazed, while multifunctionality and carbon storage increased with greater fertilization only in arid croplands. Furthermore, among environmental factors, soil bulk density had the greatest negative effects, which directly reduced multifunctionality in grasslands and indirectly reduced multifunctionality in croplands via suppressing crop density. Crop density was the major environmental factor that positively related to multifunctionality in croplands. However, these effects would be exacerbated with increasing aridity. Our study demonstrated that compared with the direct impacts of human management, environmental factors modified by human management (e.g., soil bulk density) are the major drivers of ecosystem functions, indicating that improving soil structure by alleviating human interferences (e.g., reducing livestock trampling) would be an effective way to restore ecosystem functions in drylands under global warming and drying.


Asunto(s)
Agricultura , Conservación de los Recursos Naturales , Ecosistema , Suelo , China , Humanos , Suelo/química , Pradera , Carbono
10.
Curr Pharm Des ; 30(38): 3054-3070, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39171590

RESUMEN

BACKGROUND: The beneficial effects of nicotinamide mononucleotide (NMN) on heart disease have been reported, but the effects of NMN on high-fat diet-induced hypertrophic cardiomyopathy (HCM) and its mechanisms of action are unclear. In this study, we systematically explored the effects and mechanism of action of NMN in HCM using network pharmacology and molecular docking. METHODS: Active targets of NMN were obtained from SWISS, CNKI, PubMed, DrugBank, BingingDB, and ZINC databases. HCM-related targets were retrieved from GEO datasets combined with GeneCards, OMIM, PharmGKB, and DisGeNET databases. A Protein-protein Interaction (PPI) network was built to screen the core targets. DAVID was used for GO and KEGG pathway enrichment analyses. The tissue and organ distribution of targets was evaluated. Interactions between potential targets and active compounds were assessed by molecular docking. A molecular dynamics simulation was conducted for the optimal core protein-compound complexes obtained by molecular docking. RESULTS: In total, 265 active targets of NMN and 3918 potential targets of HCM were identified. A topological analysis of the PPI network revealed 10 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of NMN were mediated by genes related to inflammation, apoptosis, and oxidative stress, as well as the FOXO and PI3K-Akt signaling pathways. Molecular docking and molecular dynamics simulations revealed good binding ability between the active compounds and screened targets. CONCLUSION: The possible targets and pathways of NMN in the treatment of HCM have been successfully predicted by this investigation. It provides a novel approach for further investigation into the molecular processes of NMN in HCM treatment.


Asunto(s)
Cardiomiopatía Hipertrófica , Dieta Alta en Grasa , Simulación del Acoplamiento Molecular , Farmacología en Red , Mononucleótido de Nicotinamida , Cardiomiopatía Hipertrófica/tratamiento farmacológico , Cardiomiopatía Hipertrófica/metabolismo , Dieta Alta en Grasa/efectos adversos , Mononucleótido de Nicotinamida/farmacología , Mononucleótido de Nicotinamida/química , Humanos , Animales
11.
Sci Total Environ ; 945: 174017, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38897455

RESUMEN

Schwertmannite (Sch), a typical Fe(III)-oxyhydroxysulphate mineral, is the precipitation reservoir of toxic elements in acid mine drainage (AMD). Acid-tolerant microbes in AMD can participate in the microbe-mediated transformation of Sch, while Sch affects the physiological characteristics of these acid-tolerant microbes. Based on our discovery of algae and Sch enrichment in a contaminated acid mine pit lake, we predicted the interaction between algae and Sch when incubated together. The acid-tolerant alga Graesiella sp. MA1 was isolated from the pit-lake surface water of an acidic mine and incubated with different contents of Sch. Sch was detected as the main product at the end of 81 d; however, there was a weak transformation. The presence of dissolved Fe(II) could be largely attributed to the photoreduction dissolution of Sch, which was promoted by Graesiella sp. MA1. The adaptation and growth phases of Graesiella sp. MA1 differed under Sch stress. The photosynthetic and metabolic activities increased and decreased at the adaptation and growth phases, respectively. The MDA contents and antioxidant activity of SOD, APX, and GSH in algal cells gradually enhanced as the Sch treatment content increased, indicating a defense strategy of Graesiella sp. MA1. Metabolomic analysis revealed that Sch affected the expression of significant differential metabolites in Graesiella sp. MA1. Organic carboxylic acid substances were essentially up-regulated in response to Sch stress. They were abundant in the medium-Sch system with the highest Fe(III) reduction, capable of complexing Fe(III), and underwent photochemical reactions via photo-induced charge transfer. The significant up-regulation of reducing sugars revealed the high energy requirement of Graesiella sp. MA1 under Sch stress. And first enriched KEGG pathway demonstrated the importance of sugar metabolism in Graesiella sp. MA1. Data acquired in this study provide novel insights into extreme acid stress adaptation of acid-tolerant algae and Sch, contributing to furthering understanding of AMD environments.


Asunto(s)
Compuestos de Hierro , Compuestos de Hierro/metabolismo , Contaminantes Químicos del Agua , Minería , Lagos/microbiología
12.
Cells ; 13(12)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38920660

RESUMEN

Skeletal muscle satellite cells, the resident stem cells in pig skeletal muscle, undergo proliferation and differentiation to enable muscle tissue repair. The proliferative and differentiative abilities of these cells gradually decrease during in vitro cultivation as the cell passage number increases. Despite extensive research, the precise molecular mechanisms that regulate this process are not fully understood. To bridge this knowledge gap, we conducted transcriptomic analysis of skeletal muscle satellite cells during in vitro cultivation to quantify passage number-dependent changes in the expression of genes associated with proliferation. Additionally, we explored the relationships between gene transcriptional activity and chromatin accessibility using transposase-accessible chromatin sequencing. This revealed the closure of numerous open chromatin regions, which were primarily located in intergenic regions, as the cell passage number increased. Integrated analysis of the transcriptomic and epigenomic data demonstrated a weak correlation between gene transcriptional activity and chromatin openness in expressed genic regions; although some genes (e.g., GNB4 and FGD5) showed consistent relationships between gene expression and chromatin openness, a substantial number of differentially expressed genes had no clear association with chromatin openness in expressed genic regions. The p53-p21-RB signaling pathway may play a critical regulatory role in cell proliferation processes. The combined transcriptomic and epigenomic approach taken here provided key insights into changes in gene expression and chromatin openness during in vitro cultivation of skeletal muscle satellite cells. These findings enhance our understanding of the intricate mechanisms underlying the decline in cellular proliferation capacity in cultured cells.


Asunto(s)
Proliferación Celular , RNA-Seq , Células Satélite del Músculo Esquelético , Células Satélite del Músculo Esquelético/metabolismo , Células Satélite del Músculo Esquelético/citología , Animales , Proliferación Celular/genética , Células Cultivadas , Porcinos , Cromatina/metabolismo , Transcriptoma/genética , Regulación de la Expresión Génica , Secuenciación de Inmunoprecipitación de Cromatina
13.
Adv Sci (Weinh) ; 11(29): e2403431, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38829272

RESUMEN

As an efficient and environmental-friendly strategy, electrocatalytic oxidation can realize biomass lignin valorization by cleaving its aryl ether bonds to produce value-added chemicals. However, the complex and polymerized structure of lignin presents challenges in terms of reactant adsorption on the catalyst surface, which hinders further refinement. Herein, NiCo-based metal-organic frameworks (MOFs) are employed as the electrocatalyst to enhance the adsorption of reactant molecules through π-π interaction. More importantly, lattice strain is introduced into the MOFs via curved ligand doping, which enables tuning of the d-band center of metal active sites to align with the reaction intermediates, leading to stronger adsorption and higher electrocatalytic activity toward bond cleavage within lignin model compounds and native lignin. When 2'-phenoxyacetophenone is utilized as the model compound, high yields of phenol (76.3%) and acetophenone (21.7%) are achieved, and the conversion rate of the reactants reaches 97%. Following pre-oxidation of extracted poplar lignin, >10 kinds of phenolic compounds are received using the as-designed MOFs electrocatalyst, providing ≈12.48% of the monomer, including guaiacol, vanillin, eugenol, etc., and p-hydroxybenzoic acid dominates all the products. This work presents a promising and deliberately designed electrocatalyst for realizing lignin valorization, making significant strides for the sustainability of this biomass resource.

14.
Plant Physiol Biochem ; 211: 108684, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38710113

RESUMEN

Abscisic acid-, stress-, and ripening-induced (ASR) proteins in plants play a significant role in plant response to diverse abiotic stresses. However, the functions of ASR genes in maize remain unclear. In the present study, we identified a novel drought-induced ASR gene in maize (ZmASR1) and functionally characterized its role in mediating drought tolerance. The transcription of ZmASR1 was upregulated under drought stress and abscisic acid (ABA) treatment, and the ZmASR1 protein was observed to exhibit nuclear and cytoplasmic localization. Moreover, ZmASR1 knockout lines generated with the CRISPR-Cas9 system showed lower ROS accumulation, higher ABA content, and a higher degree of stomatal closure than wild-type plants, leading to higher drought tolerance. Transcriptome sequencing data indicated that the significantly differentially expressed genes in the drought treatment group were mainly enriched in ABA signal transduction, antioxidant defense, and photosynthetic pathway. Taken together, the findings suggest that ZmASR1 negatively regulates drought tolerance and represents a candidate gene for genetic manipulation of drought resistance in maize.


Asunto(s)
Ácido Abscísico , Sequías , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Zea mays , Zea mays/genética , Zea mays/metabolismo , Zea mays/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Abscísico/metabolismo , Estrés Fisiológico/genética , Especies Reactivas de Oxígeno/metabolismo
15.
Angew Chem Int Ed Engl ; 63(26): e202404388, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38641988

RESUMEN

Photoinduced Pd-catalyzed bisfunctionalization of butadienes with a readily available organic halide and a nucleophile represents an emerging and attractive method to assemble versatile alkenes bearing various functional groups at the allylic position. However, enantiocontrol and/or diastereocontrol in the C-C or C-X bond-formation step have not been solved due to the open-shell process. Herein, we present a cascade asymmetric dearomatization reaction of indoles via photoexcited Pd-catalyzed 1,2-biscarbonfunctionalization of 1,3-butadienes, wherein asymmetric control on both the nucleophile and electrophile part is achieved for the first time in photoinduced bisfunctionalization of butadienes. This method delivers structurally novel chiral spiroindolenines bearing two contiguous stereogenic centers with high diastereomeric ratios (up to >20 : 1 dr) and good to excellent enantiomeric ratios (up to 97 : 3 er). Experimental and computational studies of the mechanism have confirmed a radical pathway involving excited-state palladium catalysis. The alignment and non-covalent interactions between the substrate and the catalyst were found to be essential for stereocontrol.

16.
Support Care Cancer ; 32(4): 237, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509239

RESUMEN

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/complicaciones , Calidad de Vida , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Esofagectomía/efectos adversos , Examen Físico , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del Tratamiento
17.
J Am Chem Soc ; 146(8): 5081-5087, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38358355

RESUMEN

The asymmetric hydrogenation (AH) of N-unprotected indoles is a straightforward, yet challenging method to access biologically interesting NH chiral indolines. This method has for years been limited to 2/3-monosubstituted or 2,3-disubstituted indoles, which produce chiral indolines bearing endocyclic chiral centers. Herein, we have reported an innovative Pd-catalyzed AH of racemic α-alkyl or aryl-substituted indole-2-acetates using an acid-assisted dynamic kinetic resolution (DKR) process, affording a range of structurally fascinating chiral indolines that contain exocyclic stereocenters with excellent yields, diastereoselectivities, and enantioselectivities. Mechanistic studies support that the DKR process relies on a rapid interconversion of each enantiomer of racemic substrates, leveraged by an acid-promoted isomerization between the aromatic indole and nonaromatic exocyclic enamine intermediate. The reaction can be performed on a gram scale, and the products can be derivatized into non-natural ß-amino acids via facile debenzylation and amino alcohol upon reduction.

18.
Biomater Sci ; 12(4): 1016-1030, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38206081

RESUMEN

Nano-biointerfaces play a pivotal role in determining the functionality of engineered therapeutic nanoparticles, particularly in the context of designing nanovaccines to effectively activate immune cells for cancer immunotherapy. Unlike involving chemical reactions by conventional surface decorating strategies, cell membrane-coating technology offers a straightforward approach to endow nanoparticles with natural biosurfaces, enabling them to mimic and integrate into the intricate biosystems of the body to interact with specific cells under physiological conditions. In this study, cell membranes, in a hybrid formulation, derived from cancer and activated macrophage cells were found to enhance the interaction of nanoparticles (HMP) with dendritic cells (DCs) and T cells among the mixed immune cells from lymph nodes (LNs), which could be leveraged in the development of nanovaccines for anti-tumor therapy. After loading with an adjuvant (R837), the nanoparticles coated with a hybrid membrane (HMPR) demonstrated effectiveness in priming DCs both in vitro and in vivo, resulting in amplified anti-tumor immune responses compared to those of nanoparticles coated with a single type of membrane or those lacking a membrane coating. The elevated immunoactivity of nanoparticles achieved by incorporating a hybrid membrane biosurface provides us a more profound comprehension of the nano-immune interaction, which may significantly benefit the development of bioactive nanomaterials for advanced therapy.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Neoplasias/terapia , Membrana Celular , Inmunoterapia , Células Dendríticas , Inmunidad
19.
Int J Microbiol ; 2024: 6631882, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38229736

RESUMEN

Influenza pandemic with H1N1 (H1N1pdms) causes severe lung damage and "cytokine storm," leading to higher mortality and global health emergencies in humans and animals. Explaining host antiviral molecular mechanisms in response to H1N1pdms is important for the development of novel therapies. In this study, we organised and analysed multimicroarray data for mouse lungs infected with different H1N1pdm and nonpandemic H1N1 strains. We found that H1N1pdms infection resulted in a large proportion of differentially expressed genes (DEGs) in the infected lungs compared with normal lungs, and the number of DEGs increased markedly with the time of infection. In addition, we found that different H1N1pdm strains induced similarly innate immune responses and the identified DEGs during H1N1pdms infection were functionally concentrated in defence response to virus, cytokine-mediated signalling pathway, regulation of innate immune response, and response to interferon. Moreover, comparing with nonpandemic H1N1, we identified ten distinct DEGs (AREG, CXCL13, GATM, GPR171, IFI35, IFI47, IFIT3, ORM1, RETNLA, and UBD), which were enriched in immune response and cell surface receptor signalling pathway as well as interacted with immune response-related dysregulated genes during H1N1pdms. Our discoveries will provide comprehensive insights into host responding to pandemic with influenza H1N1 and find broad-spectrum effective treatment.

20.
Ambio ; 52(12): 1928-1938, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37907802

RESUMEN

Ecological civilization has emerged as an innovative form of civilization in China, and sustainable development has been widely recognized as a globally leading development model. These two concepts are closely related. The international English literature focuses on hot topics in the field of sustainable development such as climate change, urbanization, government management, and ecosystems, while the Chinese literature emphasizes ecological civilization concepts with Chinese characteristics, such as green development, beautiful China, and scientific development concepts. Ecological civilization and sustainable development are both responses to resource, environmental, and ecological crises and have emerged from the same historical background. The two concepts complement each other, with ecological civilization providing an ideological foundation for sustainable development, and sustainable development serving as the implementation path and concrete manifestation of ecological civilization. To deepen research on ecological civilization and sustainable development, it is necessary to build a global community with a shared future, address the major strategic needs of different countries or regions, innovate and develop interdisciplinary theories, methods, and technologies, strengthen international cooperation, provide disciplinary support for ecological civilization and sustainable development research, and provide country-specific research solutions for global and regional sustainable development.


Asunto(s)
Ecosistema , Desarrollo Sostenible , Bibliometría , Cooperación Internacional , China , Civilización , Conservación de los Recursos Naturales
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