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1.
Nature ; 589(7841): 214-219, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33408416

RESUMO

Quantum key distribution (QKD)1,2 has the potential to enable secure communication and information transfer3. In the laboratory, the feasibility of point-to-point QKD is evident from the early proof-of-concept demonstration in the laboratory over 32 centimetres4; this distance was later extended to the 100-kilometre scale5,6 with decoy-state QKD and more recently to the 500-kilometre scale7-10 with measurement-device-independent QKD. Several small-scale QKD networks have also been tested outside the laboratory11-14. However, a global QKD network requires a practically (not just theoretically) secure and reliable QKD network that can be used by a large number of users distributed over a wide area15. Quantum repeaters16,17 could in principle provide a viable option for such a global network, but they cannot be deployed using current technology18. Here we demonstrate an integrated space-to-ground quantum communication network that combines a large-scale fibre network of more than 700 fibre QKD links and two high-speed satellite-to-ground free-space QKD links. Using a trusted relay structure, the fibre network on the ground covers more than 2,000 kilometres, provides practical security against the imperfections of realistic devices, and maintains long-term reliability and stability. The satellite-to-ground QKD achieves an average secret-key rate of 47.8 kilobits per second for a typical satellite pass-more than 40 times higher than achieved previously. Moreover, its channel loss is comparable to that between a geostationary satellite and the ground, making the construction of more versatile and ultralong quantum links via geosynchronous satellites feasible. Finally, by integrating the fibre and free-space QKD links, the QKD network is extended to a remote node more than 2,600 kilometres away, enabling any user in the network to communicate with any other, up to a total distance of 4,600 kilometres.

2.
Nature ; 582(7813): 501-505, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32541968

RESUMO

Quantum key distribution (QKD)1-3 is a theoretically secure way of sharing secret keys between remote users. It has been demonstrated in a laboratory over a coiled optical fibre up to 404 kilometres long4-7. In the field, point-to-point QKD has been achieved from a satellite to a ground station up to 1,200 kilometres away8-10. However, real-world QKD-based cryptography targets physically separated users on the Earth, for which the maximum distance has been about 100 kilometres11,12. The use of trusted relays can extend these distances from across a typical metropolitan area13-16 to intercity17 and even intercontinental distances18. However, relays pose security risks, which can be avoided by using entanglement-based QKD, which has inherent source-independent security19,20. Long-distance entanglement distribution can be realized using quantum repeaters21, but the related technology is still immature for practical implementations22. The obvious alternative for extending the range of quantum communication without compromising its security is satellite-based QKD, but so far satellite-based entanglement distribution has not been efficient23 enough to support QKD. Here we demonstrate entanglement-based QKD between two ground stations separated by 1,120 kilometres at a finite secret-key rate of 0.12 bits per second, without the need for trusted relays. Entangled photon pairs were distributed via two bidirectional downlinks from the Micius satellite to two ground observatories in Delingha and Nanshan in China. The development of a high-efficiency telescope and follow-up optics crucially improved the link efficiency. The generated keys are secure for realistic devices, because our ground receivers were carefully designed to guarantee fair sampling and immunity to all known side channels24,25. Our method not only increases the secure distance on the ground tenfold but also increases the practical security of QKD to an unprecedented level.

3.
Traffic ; 24(1): 20-33, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36412210

RESUMO

AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer disease (AD) by generating the toxic ß-amyloid peptide (Aß). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aß in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aß, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.


Assuntos
Subunidades sigma do Complexo de Proteínas Adaptadoras , Doença de Alzheimer , Camundongos , Humanos , Animais , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Endossomos/metabolismo , Lisossomos/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Complexo 2 de Proteínas Adaptadoras/metabolismo , Subunidades sigma do Complexo de Proteínas Adaptadoras/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
4.
Immunity ; 45(2): 442-56, 2016 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-27521270

RESUMO

Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body.


Assuntos
Sangue/imunologia , Movimento Celular , Tecido Linfoide/imunologia , Espectrometria de Massas/métodos , Especificidade de Órgãos , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/fisiologia , Animais , Biodiversidade , Biomarcadores/metabolismo , Diferenciação Celular , Linhagem da Célula , Células Cultivadas , Citocinas/metabolismo , Humanos , Ativação Linfocitária , Camundongos , Receptores de Retorno de Linfócitos/metabolismo , Transcriptoma
5.
J Pathol ; 263(1): 74-88, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38411274

RESUMO

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Proteínas de Transporte , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteínas dos Microfilamentos , Sirtuínas , Humanos , Acetilação , Actinas/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Histona Acetiltransferases/metabolismo , Metástase Linfática , Sirtuínas/metabolismo
6.
Proc Natl Acad Sci U S A ; 119(31): e2201607119, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35878043

RESUMO

Nonradical Fenton-like catalysis offers opportunities to overcome the low efficiency and secondary pollution limitations of existing advanced oxidation decontamination technologies, but realizing this on transition metal spinel oxide catalysts remains challenging due to insufficient understanding of their catalytic mechanisms. Here, we explore the origins of catalytic selectivity of Fe-Mn spinel oxide and identify electron delocalization of the surface metal active site as the key driver of its nonradical catalysis. Through fine-tuning the crystal geometry to trigger Fe-Mn superexchange interaction at the spinel octahedra, ZnFeMnO4 with high-degree electron delocalization of the Mn-O unit was created to enable near 100% nonradical activation of peroxymonosulfate (PMS) at unprecedented utilization efficiency. The resulting surface-bound PMS* complex can efficiently oxidize electron-rich pollutants with extraordinary degradation activity, selectivity, and good environmental robustness to favor water decontamination applications. Our work provides a molecule-level understanding of the catalytic selectivity and bimetallic interactions of Fe-Mn spinel oxides, which may guide the design of low-cost spinel oxides for more selective and efficient decontamination applications.


Assuntos
Elétrons , Óxidos , Catálise , Óxido de Magnésio/química , Óxidos/química , Peróxidos/química
7.
J Am Chem Soc ; 146(12): 8206-8215, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38412246

RESUMO

Spin-crossover (SCO) materials exhibit remarkable potential as bistable switches in molecular devices. However, the spin transition temperatures (Tc) of known compounds are unable to cover the entire ambient temperature spectrum, largely limiting their practical utility. This study reports an exemplary two-dimensional SCO solid solution system, [FeIII(H0.5LCl)2-2x(H0.5LF)2x]·H2O (H0.5LX = 5-X-2-hydroxybenzylidene-hydrazinecarbothioamide, X = F or Cl, x = 0 to 1), in which the adjacent layers are adhered via hydrogen bonding. Notably, the Tc of this system can be fine-tuned across 90 K (227-316 K) in a linear manner by modulating the fraction x of the LF ligand. Elevating x results in strengthened hydrogen bonding between adjacent layers, which leads to enhanced intermolecular interactions between adjacent SCO molecules. Single-crystal diffraction analysis and periodic density functional theory calculations revealed that such a special kind of alteration in interlayer interactions strengthens the FeIIIN2O2S2 ligand field and corresponding SCO energy barrier, consequently resulting in increased Tc. This work provides a new pathway for tuning the Tc of SCO materials through delicate manipulation of molecular interactions, which could expand the application of bistable molecular solids to a much wider temperature regime.

8.
BMC Plant Biol ; 24(1): 493, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831288

RESUMO

Drought is one of the natural stresses that greatly impact plants. Castor bean (Ricinus communis L.) is an oil crop with high economic value. Drought is one of the factors limiting castor bean growth. The drought resistance mechanisms of castor bean have become a research focus. In this study, we used castor germinating embryos as experimental materials, and screened genes related to drought resistance through physiological measurements, proteomics and metabolomics joint analysis; castor drought-related genes were subjected to transient silencing expression analysis in castor leaves to validate their drought-resistant functions, and heterologous overexpression and backward complementary expression in Arabidopsis thaliana, and analysed the mechanism of the genes' response to the participation of Arabidopsis thaliana in drought-resistance.Three drought tolerance-related genes, RcECP 63, RcDDX 31 and RcA/HD1, were obtained by screening and analysis, and transient silencing of expression in castor leaves further verified that these three genes corresponded to drought stress, and heterologous overexpression and back-complementary expression of the three genes in Arabidopsis thaliana revealed that the function of these three genes in drought stress response.In this study, three drought tolerance related genes, RcECP 63, RcDDX 31 and RcA/HD1, were screened and analysed for gene function, which were found to be responsive to drought stress and to function in drought stress, laying the foundation for the study of drought tolerance mechanism in castor bean.


Assuntos
Arabidopsis , Secas , Ricinus communis , Sementes , Ricinus communis/genética , Ricinus communis/fisiologia , Sementes/genética , Sementes/fisiologia , Sementes/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/fisiologia , Genes de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , Resistência à Seca
9.
New Phytol ; 242(1): 278-288, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37984873

RESUMO

Mimicry is the phenomenon in which one species (the mimic) closely resembles another (the model), enhancing its own fitness by deceiving a third party into interacting with it as if it were the model. In plants, mimicry is used primarily to gain fitness by withholding rewards from mutualists or deterring herbivores cost-effectively. While extensive work has been documented on putative defence mimicry, limited investigation has been conducted in the field of chemical mimicry. In this study, we used field experiments, chemical analyses, behavioural assays, and electrophysiology, to test the hypothesis that the birthwort Aristolochia delavayi employs chemical mimicry by releasing leaf scent that closely resembles stink bug defensive compounds and repels vertebrate herbivores. We show that A. delavayi leaf scent is chemically and functionally similar to the generalized defensive volatiles of stink bugs and that the scent effectively deters vertebrate herbivores, likely through the activation of TRPA1 channels via (E)-2-alkenal compounds. This study provides an unequivocal example of chemical mimicry in plants, revealing intricate dynamics between plants and vertebrate herbivores. Our study underscores the potency of chemical volatiles in countering vertebrate herbivory, urging further research to uncover their potentially underestimated importance.


Assuntos
Aristolochia , Heterópteros , Animais , Herbivoria , Aristolochia/química , Aristolochia/fisiologia , Heterópteros/fisiologia , Vertebrados , Plantas
10.
J Hum Genet ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866925

RESUMO

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.

11.
Plant Physiol ; 191(1): 463-478, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36342216

RESUMO

Integuments form important protective cell layers surrounding the developing ovules in gymno- and angiosperms. Although several genes have been shown to influence the development of integuments, the transcriptional regulatory mechanism is still poorly understood. In this work, we report that the Class II KNOTTED1-LIKE HOMEOBOX (KNOX II) transcription factors KNOTTED1-LIKE HOMEBOX GENE 3 (KNAT3) and KNAT4 regulate integument development in Arabidopsis (Arabidopsis thaliana). KNAT3 and KNAT4 were co-expressed in inflorescences and especially in young developing ovules. The loss-of-function double mutant knat3 knat4 showed an infertility phenotype, in which both inner and outer integuments of the ovule are arrested at an early stage and form an amorphous structure as in the bell1 (bel1) mutant. The expression of chimeric KNAT3- and KNAT4-EAR motif repression domain (SRDX repressors) resulted in severe seed abortion. Protein-protein interaction assays demonstrated that KNAT3 and KNAT4 interact with each other and also with INNER NO OUTER (INO), a key transcription factor required for the outer integument formation. Transcriptome analysis showed that the expression of genes related with integument development is influenced in the knat3 knat4 mutant. The knat3 knat4 mutant also had a lower indole-3-acetic acid (IAA) content, and some auxin signaling pathway genes were downregulated. Moreover, transactivation analysis indicated that KNAT3/4 and INO activate the auxin signaling gene IAA INDUCIBLE 14 (IAA14). Taken together, our study identified KNAT3 and KNAT4 as key factors in integument development in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Óvulo Vegetal , Ácidos Indolacéticos/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas Nucleares/metabolismo
12.
Opt Express ; 32(7): 12601-12608, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571078

RESUMO

Silicon avalanche photodiode (APD) single-photon detectors in space are continuously affected by radiation, which gradually degrades their dark count performance. From August 2016 to June 2023, we conducted approximately seven years (2507 days) of in-orbit monitoring of the dark count performance of APD single-photon detectors on the Micius Quantum Science Experimental Satellite. The results showed that due to radiation effects, the dark count growth rate was approximately 6.79 cps/day @ -24 °C and 0.37 cps/day @ -55 °C, with a significant suppression effect on radiation-induced dark counts at lower operating temperature. Based on the proposed radiation damage induced dark count annealing model, simulations were conducted for the in-orbit dark counts of the detector, the simulation results are consistent with in-orbit test data. In May 2022, four of these detectors underwent a cumulative 5.7 hours high-temperature annealing test at 76 °C, dark count rate shows no measurable changes, consistent with annealing model. As of now, these ten APD single-photon detectors on the Micius Quantum Science Experimental Satellite have been in operation for approximately 2507 days and are still functioning properly, providing valuable experience for the future long-term space applications of silicon APD single-photon detectors.

13.
Cytokine ; 179: 156618, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38663252

RESUMO

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.


Assuntos
Quimiocina CXCL11 , Quimiocina CXCL9 , Derrame Pleural , Receptores CXCR3 , Tuberculose Pleural , Humanos , Quimiocina CXCL9/metabolismo , Quimiocina CXCL11/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Derrame Pleural/metabolismo , Derrame Pleural/diagnóstico , Receptores CXCR3/metabolismo , Tuberculose Pleural/diagnóstico , Tuberculose Pleural/metabolismo , Adulto , Ligantes , Método Duplo-Cego , Células THP-1 , Biomarcadores/metabolismo , Macrófagos/metabolismo , Estudos Prospectivos , Idoso , Curva ROC
14.
Microb Pathog ; 187: 106535, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176463

RESUMO

Tuberculosis remains a threat to public health. The only approved vaccine, Bacillus Calmette-Guérin (BCG), is administered intradermally and provides limited protection, and its effect on innate immunity via the respiratory route has not been fully elucidated. A mouse model with genetically depleted TREM1 and seven-color flow cytometry staining were used to characterize the comprehensive immune response induced by respiratory BCG, through evaluating organ bacterial loads, lung histopathology, and lung immunohistochemistry. During respiratory BCG infection, the murine lungs displayed effective bacterial clearance. Notably, marked differences in neutrophils were observed between thymus and bone marrow cells, characterized by a significant increase in the expression of the triggering receptor expressed on myeloid cells 1 (TREM1). Subsequently, upon depletion of TREM1, a reduction in pulmonary neutrophils was observed, which further exacerbated bacterial loads and resulted in worsened pathology following respiratory BCG infection. In summary, up-regulated expression of TREM1 in rapidly increasing circulating neutrophil by pulmonary BCG is required for an efficient host response to BCG infection, and suggests the important role of TREM1 in neutrophil-related pulmonary bacteria clearance and pathology.


Assuntos
Bacillus , Mycobacterium bovis , Animais , Camundongos , Vacina BCG , Pulmão/patologia , Neutrófilos , Receptor Gatilho 1 Expresso em Células Mieloides
15.
FASEB J ; 37(12): e23304, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37971426

RESUMO

The phosphatase and tensin congeners (Pten) gene affects cell growth, cell proliferation, and rearrangement of connections, and it is closely related to cellular senescence, but it remains unclear the role of muscle-Pten gene in exercise against age-related deterioration in skeletal muscle and mortality induced by a high-salt diet (HSD). In here, overexpression and knockdown of muscle Pten gene were constructed by building MhcGAL4 /PtenUAS-overexpression and MhcGAL4 /PtenUAS-RNAi system in flies, and flies were given exercise training and a HSD for 2 weeks. The results showed that muscle Pten knockdown significantly reduced the climbing speed, climbing endurance, GPX activity, and the expression of Pten, Sirt1, PGC-1α genes, and it significantly increased the expression of Akt and ROS level, and impaired myofibril and mitochondria of aged skeletal muscle. Pten knockdown prevented exercise from countering the HSD-induced age-related deterioration of skeletal muscle. Pten overexpression has the opposite effect on skeletal muscle aging when compared to it knockdown, and it promoted exercise against HSD-induced age-related deterioration of skeletal muscle. Pten overexpression significantly increased lifespan, but its knockdown significantly decreased lifespan of flies. Thus, current results confirmed that differential expression of muscle Pten gene played an important role in regulating skeletal muscle aging and lifespan, and it also affected the adaptability of aging skeletal muscle to physical exercise since it determined the activity of muscle Pten/Akt pathway and Pten/Sirt1/PGC-1α pathway.


Assuntos
Condicionamento Físico Animal , Sirtuína 1 , Animais , Sirtuína 1/metabolismo , Drosophila/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Condicionamento Físico Animal/fisiologia , Músculo Esquelético/metabolismo , Dieta , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
16.
Langmuir ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38975927

RESUMO

Lightweight and robust aerogels with multifunctionality are highly desirable to meet the technological demands of current society. Herein, we designed lightweight, elastic, and superhydrophobic multifunctional organic-inorganic fibrous hybrid aerogels which were assembled with organic aramid nanofibers and inorganic hierarchical porous carbon fibers. Thanks to the organic-inorganic fiber hybridization strategy, the optimal aerogels possessed remarkable compressibility and elasticity. Benefiting from the microscopic hierarchical porous structure of carbon fibers and the macroscopic macroporous lamellar structure of aerogels, the optimal aerogels exhibited superb lightweight property, conspicuous electromagnetic microwave absorption ability, and outstanding oily wastewater purification capacity. As for electromagnetic microwave absorption, it achieved a strong reflection loss of -41.8 dB, and the effective absorption bandwidth reached 6.86 GHz. Besides, the oil adsorption capacity for trichloromethane reached as high as 93.167 g g-1 with a capacity retention of 95.6% after 5 cycles. Meanwhile, it could act as a gravity-driven separation membrane to continuously separate trichloromethane from a trichloromethane-water mixture with a high flux of 7867.37 L·m-2·h-1, even for surfactant-stabilized water-in-n-heptane emulsions of 3794.94 L·m-2·h-1. Such a strategy might shed some light on the construction of multifunctional aerogels toward broader applications.

17.
Reprod Biomed Online ; 48(1): 103585, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38016376

RESUMO

RESEARCH QUESTION: What are the proteomic and phosphoproteomic differences between the endometrium of women with recurrent pregnancy loss (RPL) and the endometrium of healthy control women during the proliferative and secretory phases of the menstrual cycle? DESIGN: In total, 54 endometrial samples were collected during the proliferative and secretory phases from women with RPL (n = 28) and healthy controls (n = 26). Comprehensive proteomic and phosphoproteomic analyses were conducted using label-free liquid chromatography-tandem mass spectrometry (n = 44), and verified through Western blotting (n = 10). Three comparison groups were established: total RPL endometrium versus total control endometrium; RPL proliferative endometrium versus control proliferative endometrium; and RPL secretory endometrium versus control secretory endometrium. RESULTS: Differentially expressed proteins and differentially phosphorylated proteins were identified in the three comparison groups. Combining pathway enrichment, network analysis and soft clustering analysis, the insulin/cyclic nucleotide signalling pathway and AMPK/mTOR signalling pathway were identified as the major contributors to the aberration of RPL endometrium. Western blotting verified altered expression of four proteins: cAMP-dependent protein kinase type I-ß regulatory subunit, adenylate cyclase type 3, 5'-AMP-activated protein kinase catalytic subunit α-2 and phosphatidate phosphatase LPIN2. CONCLUSIONS: This exploratory study provides insights into the differentiated protein expression and phosphorylation profiles of the endometrium of women with RPL in both the proliferative and sectretory phases of the menstrual cycle. The results highlight potential proteins associated with the pathogenesis of RPL that may serve as potential indicators for RPL. The findings contribute to the identification of potential targets for RPL treatment as well as its pathogenesis.


Assuntos
Aborto Habitual , Insulina , Gravidez , Humanos , Feminino , Fosforilação , Proteômica/métodos , Endométrio/metabolismo , Aborto Habitual/patologia , Serina-Treonina Quinases TOR/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-38366741

RESUMO

BACKGROUND: Pre-existing health conditions increase the risk of obstetric complications during pregnancy and birth. However, the prevalence and recent changes in the frequency of pre-existing health conditions in the childbearing population remain unknown. OBJECTIVES: To estimate the temporal changes in the prevalence of pre-existing health conditions among pregnant women in British Columbia, Canada. METHODS: We carried out a population-based cross-sectional study of 825,203 deliveries in BC between 2000 and 2019 and examined 17 categories of physical and psychiatric health conditions recorded within 5 years before childbirth. We also undertook age-period-cohort analyses to evaluate temporal changes in pre-existing health conditions. RESULTS: The prevalence of any pre-existing health condition was 26.2% (n = 216,214) with overall trends remaining stable during the study period. Between 2000 and 2019, the prevalence rates of anxiety (5.6%-9.6%), bipolar (1.6%-3.4%), psychosis (0.7%-0.8%), and eating disorders (0.2%-0.3%) increased. The prevalence of hypertension increased sharply from 0.06% in 2000 to 0.3% in 2019. Diabetes mellitus and stroke rates increased, as did the prevalence of systemic lupus, multiple sclerosis, and chronic kidney disease. Advanced maternal age was strongly associated with both psychiatric and circulatory/metabolic conditions. A strong birth cohort effect was evident, with rates of psychiatric conditions increasing among women born after 1985. CONCLUSIONS: In British Columbia, Canada, 1 in 4 mothers had a pre-existing health condition 5 years prior to pregnancy. These findings underscore the need for multi-disciplinary care for women with pre-existing health conditions to improve maternal, foetal, and infant health.

19.
Infection ; 52(3): 1063-1072, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38265608

RESUMO

BACKGROUND AND PURPOSE: The need for dose adjustment of caspofungin in patients with hepatic impairment is controversial, especially for those with Child-Pugh B or C cirrhosis. The purpose of this study was to investigate the safety and efficacy of standard-dose caspofungin administration in Child-Pugh B and C cirrhotic patients in a real-world clinical setting. PATIENTS AND METHODS: The electronic medical records of 258 cirrhotic patients, including 67 Child-Pugh B patients and 191 Child-Pugh C patients, who were treated with standard-dose of caspofungin at the Second Affiliated Hospital of Chongqing Medical University, China, from March 2018 to June 2023 were reviewed retrospectively. The white blood cells (WBC), hepatic, renal and coagulation function results before administration and post administration on days 7, 14 and 21 were collected, and the efficacy was assessed in all patients at the end of caspofungin therapy. RESULTS: Favorable responses were achieved in 137 (53.1%) patients while 34 (13.2%) patients died. We observed that some patients experienced an increase of prothrombin time (PT) or international normalized ratio (INR), or a decrease of WBC, but no exacerbation of hepatic or renal dysfunction were identified and no patient required dose interruption or adjustment because of an adverse drug reaction during treatment with caspofungin. CONCLUSIONS: Standard-dose of caspofungin can be safely and effectively used in patients with Child-Pugh B or C cirrhosis, and we appealed to re-assess the most suitable dosing regimen in this population to avoid a potential subtherapeutic exposure.


Assuntos
Antifúngicos , Caspofungina , Cirrose Hepática , Humanos , Caspofungina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/complicações , Estudos Retrospectivos , Idoso , Antifúngicos/uso terapêutico , Antifúngicos/efeitos adversos , Antifúngicos/administração & dosagem , Resultado do Tratamento , Adulto , China
20.
Inorg Chem ; 63(5): 2647-2654, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38262040

RESUMO

The increasing demands in optoelectronic applications have driven the advancement of organic-inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4 (Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4 (Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2- polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d-d electron transition of Mn2+ with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV-1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyair s-1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4 and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm-1, which provides a potential visualization tool for X-ray radiography.

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