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1.
J Am Chem Soc ; 146(11): 7467-7479, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38446421

RESUMEN

Interfacial interaction dictates the overall catalytic performance and catalytic behavior rules of the composite catalyst. However, understanding of interfacial active sites at the microscopic scale is still limited. Importantly, identifying the dynamic action mechanism of the "real" active site at the interface necessitates nanoscale, high spatial-time-resolved complementary-operando techniques. In this work, a Co3O4 homojunction with a well-defined interface effect is developed as a model system to explore the spatial-correlation dynamic response of the interface toward oxygen evolution reaction. Quasi in situ scanning transmission electron microscopy-electron energy-loss spectroscopy with high spatial resolution visually confirms the size characteristics of the interface effect in the spatial dimension, showing that the activation of active sites originates from strong interfacial electron interactions at a scale of 3 nm. Multiple time-resolved operando spectroscopy techniques explicitly capture dynamic changes in the adsorption behavior for key reaction intermediates. Combined with density functional theory calculations, we reveal that the dynamic adjustment of multiple adsorption configurations of intermediates by highly activated active sites at the interface facilitates the O-O coupling and *OOH deprotonation processes. The dual dynamic regulation mechanism accelerates the kinetics of oxygen evolution and serves as a pivotal factor in promoting the oxygen evolution activity of the composite structure. The resulting composite catalyst (Co-B@Co3O4/Co3O4 NSs) exhibits an approximately 70-fold turnover frequency and 20-fold mass activity than the monomer structure (Co3O4 NSs) and leads to significant activity (η10 ∼257 mV). The visual complementary analysis of multimodal operando/in situ techniques provides us with a powerful platform to advance our fundamental understanding of interfacial structure-activity relationships in composite structured catalysts.

2.
J Hepatol ; 80(5): 753-763, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38244845

RESUMEN

BACKGROUND & AIMS: Ectopic liver regeneration in the spleen is a promising alternative to organ transplantation for treating liver failure. To accommodate transplanted liver cells, the splenic tissue must undergo structural changes to increase extracellular matrix content, demanding a safe and efficient approach for tissue remodelling. METHODS: We synthesised sulphated hyaluronic acid (sHA) with an affinity for the latent complex of transforming growth factor-ß (TGF-ß) and cross-linked it into a gel network (sHA-X) via click chemistry. We injected this glycan into the spleens of mice to induce splenic tissue remodelling via supraphysiological activation of endogenous TGF-ß. RESULTS: sHA-X efficiently bound to the abundant latent TGF-ß in the spleen. It provided the molecular force to liberate the active TGF-ß dimers from their latent complex, mimicking the 'bind-and-pull' mechanism required for physiological activation of TGF-ß and reshaping the splenic tissue to support liver cell growth. Hepatocytes transplanted into the remodelled spleen developed into liver tissue with sufficient volume to rescue animals with a metabolic liver disorder (Fah-/- transgenic model) or following 90% hepatectomy, with no adverse effects observed and no additional drugs required. CONCLUSION: Our findings highlight the efficacy and translational potential of using sHA-X to remodel a specific organ by mechanically activating one single cytokine, representing a novel strategy for the design of biomaterials-based therapies for organ regeneration. IMPACT AND IMPLICATIONS: Cell transplantation may provide a lifeline to millions of patients with end-stage liver diseases, but their severely damaged livers being unable to accommodate the transplanted cells is a crucial hurdle. Herein, we report an approach to restore liver functions in another organ - the spleen - by activating one single growth factor in situ. This approach, based on a chemically designed polysaccharide that can mechanically liberate the active transforming growth factor-ß to an unusually high level, promotes the function of abundant allogenic liver cells in the spleen, rescuing animals from lethal models of liver diseases and showing a high potential for clinical translation.


Asunto(s)
Hiperplasia Nodular Focal , Hepatopatías , Humanos , Ratones , Animales , Regeneración Hepática/fisiología , Bazo , Factor de Crecimiento Transformador beta/metabolismo , Hígado/metabolismo , Hepatopatías/metabolismo , Factores de Crecimiento Transformadores/metabolismo , Factores de Crecimiento Transformadores/farmacología , Factor de Crecimiento Transformador beta1/metabolismo
3.
Pestic Biochem Physiol ; 203: 105968, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39084809

RESUMEN

Insects rely primarily on a robust and precise olfactory recognition system to detect chemicals and environmental signals. Olfaction is mediated mainly by various odorant receptors (ORs) expressed on olfactory neurons. The odorant co-receptor (Orco) is a highly conserved and obligatory subunit of ORs, and its combination with conventional ORs to form ligand-gated ion channel heterodimeric complexes plays a crucial role in odor recognition. Anoplophora glabripennis Is a major quarantinable pest that affects broadleaved tree species worldwide. Odorant binding proteins (OBPs) and ORs have been identified in the A. glabripennis genome and the binding properties of some OBPs and their cognate ligands have been clarified. The role of the OR-mediated recognition pathway, however, remains largely uncharacterized. Here, we cloned and sequenced the full-length Orco gene sequence of A. glabripennis and performed structural characterization of the protein. We found that AglaOrco has high sequence homology with Orco from other orders of insects, and that it is highly conserved. Spatio-temporal differential expression analysis revealed that AglaOrco is highly expressed in adult antennae, and that expression at the sexually mature stage is significantly higher than at other developmental stages. There was no significant difference in expression between sexes. Silence AglaOrco using RNAi revealed that expression levels of AglaOrco mRNA fell significantly in both males and females at 72 h post-injection of 5 µg of dsOrco, with no obvious effect on expression of most other olfactory-related genes; however, some were up-or downregulated. For example, silenced Orco-expressing males and females showed a significant reduction in antennal potential responses to the odorants 3-carene, Ocimene, and 4-heptyloxy-1-butanol. Overall, the data suggest that AglaOrco plays an important role in mediating olfactory perception in A. glabripennis, and also identifies potential target genes for environmentally friendly pest control strategies.


Asunto(s)
Proteínas de Insectos , Feromonas , Receptores Odorantes , Animales , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Feromonas/farmacología , Femenino , Masculino , Compuestos Orgánicos Volátiles/farmacología , Compuestos Orgánicos Volátiles/metabolismo , Escarabajos/genética , Escarabajos/efectos de los fármacos , Interferencia de ARN
4.
Pestic Biochem Physiol ; 203: 105975, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39084766

RESUMEN

The pinewood nematode Bursaphelenchus xylophilus (Steiner and Buhrer 1934) causes pine wilt disease, which severely affects the biodiversity and economy of Eurasian coniferous forests. Monochamus saltuarius (Coleoptera, Cerambycidae) was first identified as nematode vectors in Liaoning Province, China, in 2017. M. saltuarius has high mating efficiency and reproductive capabilities, pheromones are crucial in these processes. However, the mechanisms of pheromone synthesis in M. saltuarius are unclear. This study performed morphometric and transcriptomic analyses of the internal reproductive systems of males and females at different developmental stages and analyzed mate selection behavior. We found a significant difference in the morphology of internal reproductive systems between sexually immature and mature insects. A total of 58 and 64 pheromone biosynthesis genes were identified in females and males, respectively. The expression of the analyzed genes differed between males and females in the initial and subsequent synthesis processes. Interference experiment indicated that knocking down SDR1 gene in male M. saltuarius reduces the content of pheromones. Behavioral analyses found that males preferred virgin females. This study identified key pheromone genes and synthesis pathway that could serve as potential targets for disrupting mating in M. saltuarius through the development of novel biological agents using genetic engineering techniques.


Asunto(s)
Escarabajos , Conducta Sexual Animal , Animales , Escarabajos/genética , Escarabajos/fisiología , Masculino , Femenino , Perfilación de la Expresión Génica , Feromonas/biosíntesis , Transcriptoma , Reproducción , Atractivos Sexuales/biosíntesis , Atractivos Sexuales/metabolismo
5.
Nano Lett ; 23(24): 11999-12005, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38100577

RESUMEN

Redispersion is an effective method for regeneration of sintered metal-supported catalysts. However, the ambiguous mechanistic understanding hinders the delicate controlling of active metals at the atomic level. Herein, the redispersion mechanism of atomically dispersed Pt on CeO2 is revealed and manipulated by in situ techniques combining well-designed model catalysts. Pt nanoparticles (NPs) sintered on CeO2 nano-octahedra under reduction and oxidation conditions, while redispersed on CeO2 nanocubes above ∼500 °C in an oxidizing atmosphere. The dynamic shrinkage and disappearance of Pt NPs on CeO2 (100) facets was directly visualized by in situ TEM. The generated atomically dispersed Pt with the square-planar [PtO4]2+ structure on CeO2 (100) facets was also confirmed by combining Cs-corrected STEM and spectroscopy techniques. The redispersion and atomic control were ascribed to the high mobility of PtO2 at high temperatures and its strong binding with square-planar O4 sites over CeO2 (100). These understandings are important for the regulation of atomically dispersed platinum catalysts.

6.
Horm Metab Res ; 55(10): 692-700, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37385295

RESUMEN

Malnutrition is a risk factor of adverse clinical outcome in patients with cancer. Recent studies suggest that geriatric nutritional risk index (GNRI) could reflect the nutritional status in patients with various clinical conditions. The aim of the systematic review and meta-analysis was to evaluate the association between GNRI and survival of patients with hepatocellular carcinoma (HCC). Observational studies evaluating the association between pretreatment GNRI and survival of patients with HCC were obtained by search of PubMed, Web of Science, Embase, Wanfang, and CNKI databases. A random-effects model was used to pool the results after incorporating the potential influence of heterogeneity. Seven cohort studies including 2636 patients with HCC contributed to the meta-analysis. Pooled results showed that HCC patients with low pretreatment GNRI were associated with poor overall survival [hazard ratio (HR): 1.77, 95% confidence interval (CI): 1.32 to 2.37, p<0.001; I2=66%) and progression-free survival (HR: 1.62, 95% CI: 1.39 to 1.89, p<0.001; I2=0%) as compared to those with normal GNRI. Sensitivity analyses by excluding one study at a time showed similar results (p all<0.05). Subgroup analyses showed that the association between low pretreatment GNRI and poor survival of patients with HCC was not significantly affected by age of the patients, main treatment, cutoff of GNRI, or the follow-up durations. In conclusion, malnutrition indicated by a low pretreatment GNRI may be a risk factor of poor survival of patients with HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Desnutrición , Humanos , Anciano , Evaluación Nutricional , Medición de Riesgo , Pronóstico , Estado Nutricional , Desnutrición/complicaciones , Factores de Riesgo , Evaluación Geriátrica/métodos , Estudios Retrospectivos
7.
Proc Natl Acad Sci U S A ; 117(31): 18459-18469, 2020 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-32694211

RESUMEN

Mdn1 is an essential mechanoenzyme that uses the energy from ATP hydrolysis to physically reshape and remodel, and thus mature, the 60S subunit of the ribosome. This massive (>500 kDa) protein has an N-terminal AAA (ATPase associated with diverse cellular activities) ring, which, like dynein, has six ATPase sites. The AAA ring is followed by large (>2,000 aa) linking domains that include an ∼500-aa disordered (D/E-rich) region, and a C-terminal substrate-binding MIDAS domain. Recent models suggest that intramolecular docking of the MIDAS domain onto the AAA ring is required for Mdn1 to transmit force to its ribosomal substrates, but it is not currently understood what role the linking domains play, or why tethering the MIDAS domain to the AAA ring is required for protein function. Here, we use chemical probes, single-particle electron microscopy, and native mass spectrometry to study the AAA and MIDAS domains separately or in combination. We find that Mdn1 lacking the D/E-rich and MIDAS domains retains ATP and chemical probe binding activities. Free MIDAS domain can bind to the AAA ring of this construct in a stereo-specific bimolecular interaction, and, interestingly, this binding reduces ATPase activity. Whereas intramolecular MIDAS docking appears to require a treatment with a chemical inhibitor or preribosome binding, bimolecular MIDAS docking does not. Hence, tethering the MIDAS domain to the AAA ring serves to prevent, rather than promote, MIDAS docking in the absence of inducing signals.


Asunto(s)
ATPasas Asociadas con Actividades Celulares Diversas/química , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimología , ATPasas Asociadas con Actividades Celulares Diversas/genética , Adenosina Trifosfato/metabolismo , Regulación Alostérica , Sitios de Unión , Dominios Proteicos , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
8.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36675132

RESUMEN

Insects use a powerful and complex olfactory recognition system to sense odor molecules in the external environment to guide behavior. A large family of odorant receptors (ORs) mediates the detection of pheromone compounds. Anoplophora glabripennis is a destructive pest that harms broad-leaved tree species. Although olfactory sensation is an important factor affecting the information exchange of A. glabripennis, little is known about the key ORs involved. Here, we identified ninety-eight AglaORs in the Agla2.0 genome and found that the AglaOR gene family had expanded with structural and functional diversity. RT-qPCR was used to analyze the expression of AglaORs in sex tissues and in adults at different developmental stages. Twenty-three AglaORs with antennal-biased expression were identified. Among these, eleven were male-biased and two were female-biased and were more significantly expressed in the sexual maturation stage than in the post-mating stage, suggesting that these genes play a role in sexual communication. Relatively, two female-biased AglaORs were overexpressed in females seeking spawning grounds after mating, indicating that these genes might be involved in the recognition of host plant volatiles that may regulate the selection of spawning grounds. Our study provides a theoretical basis for further studies into the molecular mechanism of A. glabripennis olfaction.


Asunto(s)
Escarabajos , Receptores Odorantes , Animales , Femenino , Masculino , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Escarabajos/metabolismo , Olfato , Plantas/metabolismo , Comunicación , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Antenas de Artrópodos/metabolismo
9.
Angew Chem Int Ed Engl ; 62(49): e202310062, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-37702304

RESUMEN

Knowing the structure of catalytically active species/phases and providing methods for their purposeful generation are two prerequisites for the design of catalysts with desired performance. Herein, we introduce a simple method for precise preparation of supported/bulk catalysts. It utilizes the ability of metal oxides to dissolve and to simultaneously precipitate during their treatment in an aqueous ammonia solution. Applying this method for a conventional VOx -Al2 O3 catalyst, the concentration of coordinatively unsaturated Al sites was tuned simply by changing the pH value of the solution. These sites affect the strength of V-O-Al bonds of isolated VOx species and thus the reducibility of the latter. This method is also applicable for controlling the reducibility of bulk catalysts as demonstrated for a CeO2 -ZrO2 -Al2 O3 system. The application potential of the developed catalysts was confirmed in the oxidative dehydrogenation of ethylbenzene to styrene with CO2 and in the non-oxidative propane dehydrogenation to propene. Our approach is extendable to the preparation of any metal oxide catalysts dissolvable in an ammonia solution.

10.
J Struct Biol ; 211(3): 107572, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32652237

RESUMEN

McrBC is a conserved modification-dependent restriction system that in Escherichia coli specifically targets foreign DNA containing methylated cytosines. Crystallographic data show that the N-terminal domain of Escherichia coli McrB binds substrates via a base flipping mechanism. This region is poorly conserved among the plethora of McrB homologs, suggesting that other species may use alternative binding strategies and/or recognize different targets. Here we present the crystal structure of the N-terminal domain from Stayphlothermus marinus McrB (Sm3-180) at 1.92 Å, which adopts a PUA-like EVE fold that is closely related to the YTH and ASCH RNA binding domains. Unlike most PUA-like domains, Sm3-180 binds DNA and can associate with different modified substrates. We find the canonical 'aromatic cage' binding pocket that confers specificity for methylated bases in other EVE/YTH domains is degenerate and occluded in Sm3-180, which may contribute to its promiscuity in target recognition. Further structural comparison between different PUA-like domains identifies motifs and conformational variations that correlate with the preference for binding either DNA or RNA. Together these data have important implications for PUA-like domain specificity and suggest a broader biological versatility for the McrBC family than previously described.


Asunto(s)
Proteínas Arqueales/química , Proteínas Arqueales/metabolismo , Desulfurococcaceae/química , Proteínas de Unión al ARN/química , Proteínas Arqueales/genética , Sitios de Unión , Cristalografía por Rayos X , ADN de Archaea/química , ADN de Archaea/metabolismo , Modelos Moleculares , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Dominios Proteicos , Pliegue de Proteína , Factores de Empalme de ARN/química , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo
11.
Angew Chem Int Ed Engl ; 58(13): 4232-4237, 2019 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-30650222

RESUMEN

Controllable synthesis of well-defined supported intermetallic catalysts is desirable because of their unique properties in physical chemistry. To accurately pinpoint the evolution of such materials at an atomic-scale, especially clarification of the initial state under a particular chemical environment, will facilitate rational design and optimal synthesis of such catalysts. The dynamic formation of a ZnO-supported PdZn catalyst is presented, whereby detailed analyses of in situ transmission electron microscopy, electron energy-loss spectroscopy, and in situ X-ray diffraction are combined to form a nanoscale understanding of PdZn phase transitions under realistic catalytic conditions. Remarkably, introduction of atoms (H and Zn in sequence) into the Pd matrix was initially observed. The resultant PdHx is an intermediate phase in the intermetallic formation process. The evolution of PdHx in the PdZn catalyst initializes at the PdHx /ZnO interfaces, and proceeds along the PdHx ⟨111⟩ direction.

12.
J Am Chem Soc ; 140(36): 11241-11251, 2018 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-30016862

RESUMEN

The mechanism on interfacial synergistic catalysis for supported metal catalysts has long been explored and investigated in several important heterogeneous catalytic processes (e.g., water-gas shift (WGS) reaction). The modulation of metal-support interactions imposes a substantial influence on activity and selectivity of catalytic reaction, as a result of the geometric/electronic structure of interfacial sites. Although great efforts have validated the key role of interfacial sites in WGS over metal catalysts supported on reducible oxides, direct evidence at the atomic level is lacking and the mechanism of interfacial synergistic catalysis is still ambiguous. Herein, Ni nanoparticles supported on TiO2- x (denoted as Ni@TiO2- x) were fabricated via a structure topotactic transformation of NiTi-layered double hydroxide (NiTi-LDHs) precursor, which showed excellent catalytic performance for WGS reaction. In situ microscopy was carried out to reveal the partially encapsulated structure of Ni@TiO2- x catalyst. A combination study including in situ and operando EXAFS, in situ DRIFTS spectra combined with TPSR measurements substantiates a new redox mechanism based on interfacial synergistic catalysis. Notably, interfacial Ni species (electron-enriched Niδ- site) participates in the dissociation of H2O molecule to generate H2, accompanied by the oxidation of Niδ--O v-Ti3+ (O v: oxygen vacancy) to Niδ+-O-Ti4+ structure. Density functional theory calculations further verify that the interfacial sites of Ni@TiO2- x catalyst serve as the optimal active site with the lowest activation energy barrier (∼0.35 eV) for water dissociation. This work provides a fundamental understanding on interfacial synergistic catalysis toward WGS reaction, which is constructive for the rational design and fabrication of high activity heterogeneous catalysts.

13.
Chemistry ; 24(22): 5748-5753, 2018 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-29473659

RESUMEN

Detection of hypochlorous acid (HClO) in the living system may help to uncover its essential biological functions. However, current imaging agents suffer from poor water solubility that limit their live-tissue applications. Here, a water-soluble probe (NNH) is devised through innovative hydrazone modification of 1,8-naphthalimide at 3' position. NNH was successfully applied to tracking endogenous HClO in both cultured macrophages and a liver injury model in mice. NNH demonstrated remarkably increased water solubility and multiple desirable features including two-photon absorbance, anti-bleaching capability, rapid cellular uptake, and low cytotoxicity. NNH is the first hydrazone-based probe for real-time imaging of HClO in live tissue.


Asunto(s)
Ácido Hipocloroso/análisis , Animales , Línea Celular , Hidrazonas/química , Ratones , Microscopía Fluorescente/métodos , Imagen Molecular , Naftalimidas/química , Fotones , Espectrometría de Fluorescencia/métodos , Agua
14.
Mol Pharm ; 11(7): 2022-9, 2014 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-24533867

RESUMEN

Development of new, antimetastatic drugs from natural products has been substantially constrained by the lack of a reliable in vitro screening system. Such a system should ideally mimic the native, three-dimensional (3D) tumor microenvironment involving different cell types and allow quantitative analysis of cell behavior critical for metastasis. These requirements are largely unmet in the current model systems, leading to poor predictability of the in vitro collected data for in vivo trials, as well as prevailing inconsistency among different in vitro tests. In the present study, we report application of a 3D, microfluidic device for validation of the antimetastatic effects of 12 natural compounds. This system supports co-culture of endothelial and cancer cells in their native 3D morphology as in the tumor microenvironment and provides real-time monitoring of the cells treated with each compound. We found that three compounds, namely sanguinarine, nitidine, and resveratrol, exhibited significant antimetastatic or antiangiogenic effects. Each compound was further examined for its respective activity with separate conventional biological assays, and the outcomes were in agreement with the findings collected from the microfluidic system. In summary, we recommend use of this biomimetic model system as a new engineering tool for high-throughput evaluation of more diverse natural compounds with varying anticancer potentials.


Asunto(s)
Antineoplásicos/farmacología , Productos Biológicos/farmacología , Biomimética/métodos , Microfluídica/métodos , Benzofenantridinas/farmacología , Línea Celular Tumoral , Técnicas de Cocultivo/métodos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Células Endoteliales/efectos de los fármacos , Humanos , Isoquinolinas/farmacología , Dispositivos Laboratorio en un Chip/métodos , Modelos Biológicos , Resveratrol , Estilbenos/farmacología , Microambiente Tumoral/efectos de los fármacos
15.
Adv Mater ; 36(6): e2304655, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37567583

RESUMEN

Hair loss affects over 50 million people worldwide with limited therapeutic options. Despite evidence highlighting the vital role of local immune cells in regulating the life cycle of hair follicles (HFs), accurate regulation of immunocytes to directly promote hair growth remains unachieved. Here, inspired by the physiological feedback in the skin immunity to suppress microbe-triggered inflammation, an oligosaccharide biomaterial with "unmasked" specific activity is developed to recruit regulatory T (Treg ) cells around HFs, leading to accelerated hair growth in mice. By processing the glucomannan polysaccharide via controllable enzymatic cleavage, a series of oligosaccharide fractions with more specific chemokine-inducing functions is obtained. Notably, a hexasaccharide-based fraction (OG6) stimulates macrophages to selectively express Treg -chemoattractant C-C Motif Chemokine Ligand 5 (CCL5) through a mannose receptor-mediated endocytosis and NOD1/2-dependent signaling, as evidenced by molecular docking, inhibition assays, and a Foxp3-reporter mouse model. Intradermal delivery of OG6 to the depilated mouse skin promotes Treg mobilization around HFs and stimulates de novo regeneration of robust hairs. This study demonstrates that unmasking precise immunomodulatory functions in oligosaccharides from their parental polysaccharide can potentially solve the long-lasting dilemma with polysaccharide biomaterials that are widely renowned for versatile activities yet high heterogeneity, opening new avenues to designing glycan-based therapeutic tools with improved specificity and safety.


Asunto(s)
Cabello , Linfocitos T Reguladores , Humanos , Ratones , Animales , Linfocitos T Reguladores/metabolismo , Simulación del Acoplamiento Molecular , Quimiocinas/metabolismo , Oligosacáridos/metabolismo , Polisacáridos
16.
J Agric Food Chem ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39083594

RESUMEN

Anoplophora glabripennis is a critical global quarantine pest. Recently, its distribution has been extended to colder and higher-latitude regions. The adaptation to low temperatures is vital for the successful colonization of insects in new environments. However, the metabolic pathways of A. glabripennis larvae under cold stress remain undefined. This study analyzed the larval hemolymph under different low-temperature treatments using LC-MS/MS. The results showed that differential metabolites associated with sugar and lipid metabolism are pivotal in the larval chill coma process. Under low-temperature treatments, the glycerol content increased significantly compared with the control group. Cold stress significantly induced the expression of AglaGK2 and AglaGPDHs. After undergoing RNAi treatment for 48 h, larvae exposed to -20 °C for 1 h showed reduced recovery when injected with ds-AglaGK2 and ds-AglaGPDH1 compared to the control group, indicating that glycerol biosynthesis plays a role in the low-temperature adaptation of A. glabripennis larvae. Our results provide a theoretical basis for clarifying the molecular mechanism of A. glabripennis larvae in response to environmental stresses.

17.
Cell Rep ; 43(7): 114425, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38970789

RESUMEN

Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host's energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight.


Asunto(s)
Dieta Alta en Grasa , Metabolismo Energético , Obesidad , Animales , Obesidad/metabolismo , Obesidad/terapia , Ratones , Proteína Desacopladora 1/metabolismo , Ingeniería de Tejidos/métodos , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Humanos , Peso Corporal , Ratones Obesos
18.
Pest Manag Sci ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38979967

RESUMEN

BACKGROUND: Monochamus saltuarius is a destructive trunk-borer of pine forest and an effective dispersal vector for pinewood nematode (PWN), a causative agent of pine wilt disease (PWD), which leads to major ecological disasters. Cold winter temperatures determine insect survival and distribution. However, little is known about the cold tolerance and potential physiological mechanisms of M. saltuarius. RESULTS: We demonstrated that dead Pinus koraiensis trunks do not provide larvae with insulation. The M. saltuarius larvae are freeze-tolerant species. Unlike most other freeze-tolerant insects, they can actively freeze extracellular fluid at higher subzero temperatures by increasing their supercooling points. The main energy sources for larvae overwintering are glycogen and the mid-late switch to lipid. The water balance showed a decrease in free and an increase in bound water of small magnitude. Cold stress promoted lipid peroxidation, thus activating the antioxidant system to prevent cold-induced oxidative damage. We found eight main pathways linked to cold stress and 39 important metabolites, ten of which are cryoprotectants, including maltose, UDP-glucose, d-fructose 6P, galactinol, dulcitol, inositol, sorbitol, l-methionine, sarcosine, and d-proline. The M. saltuarius larvae engage in a dual respiration process involving both anaerobic and aerobic pathways when their bodily fluids freeze. Cysteine and methionine metabolism, as well as alanine, aspartate, and glutamate metabolism, are the most important pathways linked to antioxidation and energy production. CONCLUSIONS: The implications of our findings may help strengthen and supplement the management strategies for monitoring, quarantine, and control of this pest, thereby contributing to controlling the further spread of PWD. © 2024 Society of Chemical Industry.

19.
Bioact Mater ; 37: 315-330, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38694764

RESUMEN

Cancer vaccination holds great promise for cancer treatment, but its effectiveness is hindered by suboptimal activation of CD8+ cytotoxic T lymphocytes, which are potent effectors to mediate anti-tumor immune responses. A possible solution is to switch antigen-presenting cells to present tumor antigens via the major histocompatibility complex class I (MHC-I) to CD8+ T cells - a process known as cross-presentation. To achieve this goal, we develop a three-dimensional (3D) scaffold vaccine to promote antigen cross-presentation by persisted toll-like receptor-2 (TLR2) activation after one injection. This vaccine comprises polysaccharide frameworks that "hook" TLR2 agonist (acGM) via tunable hydrophobic interactions and forms a 3D macroporous scaffold via click chemistry upon subcutaneous injection. Its retention-and-release of acGM enables sustained TLR2 activation in abundantly recruited dendritic cells in situ, inducing intracellular production of reactive oxygen species (ROS) in optimal kinetics that crucially promotes efficient antigen cross-presentation. The scaffold loaded with model antigen ovalbumin (OVA) or tumor specific antigen can generate potent immune responses against lung metastasis in B16-OVA-innoculated wild-type mice or spontaneous colorectal cancer in transgenic ApcMin/+ mice, respectively. Notably, it requires neither additional adjuvants nor external stimulation to function and can be adjusted to accommodate different antigens. The developed scaffold vaccine may represent a new, competent tool for next-generation personalized cancer vaccination.

20.
Research (Wash D C) ; 6: 0043, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36930759

RESUMEN

Chemical electron microscopy (CEM), a toolbox that comprises imaging and spectroscopy techniques, provides dynamic morphological, structural, chemical, and electronic information about an object in chemical environment under conditions of observable performance. CEM has experienced a revolutionary improvement in the past years and is becoming an effective characterization method for revealing the mechanism of chemical reactions, such as catalysis. Here, we mainly address the concept of CEM for heterogeneous catalysis in the gas phase and what CEM could uniquely contribute to catalysis, and illustrate what we can know better with CEM and the challenges and future development of CEM.

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