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1.
Proc Natl Acad Sci U S A ; 121(11): e2316553121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437553

RESUMO

Developing cost-effective and high-performance electrocatalysts for oxygen reduction reaction (ORR) is critical for clean energy generation. Here, we propose an approach to the synthesis of iron phthalocyanine nanotubes (FePc NTs) as a highly active and selective electrocatalyst for ORR. The performance is significantly superior to FePc in randomly aggregated and molecularly dispersed states, as well as the commercial Pt/C catalyst. When FePc NTs are anchored on graphene, the resulting architecture shifts the ORR potentials above the redox potentials of Fe2+/3+ sites. This does not obey the redox-mediated mechanism operative on conventional FePc with a Fe2+-N moiety serving as the active sites. Pourbaix analysis shows that the redox of Fe2+/3+ sites couples with HO- ions transfer, forming a HO-Fe3+-N moiety serving as the ORR active sites under the turnover condition. The chemisorption of ORR intermediates is appropriately weakened on the HO-Fe3+-N moiety compared to the Fe2+-N state and thus is intrinsically more ORR active.

2.
Circ Res ; 132(2): 208-222, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36656967

RESUMO

OBJECTIVE: ASPP1 (apoptosis stimulating of p53 protein 1) is critical in regulating cell apoptosis as a cofactor of p53 to promote its transcriptional activity in the nucleus. However, whether cytoplasmic ASPP1 affects p53 nuclear trafficking and its role in cardiac diseases remains unknown. This study aims to explore the mechanism by which ASPP1 modulates p53 nuclear trafficking and the subsequent contribution to cardiac ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: The immunofluorescent staining showed that under normal condition ASPP1 and p53 colocalized in the cytoplasm of neonatal mouse ventricular cardiomyocytes, while they were both upregulated and translocated to the nuclei upon hypoxia/reoxygenation treatment. The nuclear translocation of ASPP1 and p53 was interdependent, as knockdown of either ASPP1 or p53 attenuated nuclear translocation of the other one. Inhibition of importin-ß1 resulted in the cytoplasmic sequestration of both p53 and ASPP1 in neonatal mouse ventricular cardiomyocytes with hypoxia/reoxygenation stimulation. Overexpression of ASPP1 potentiated, whereas knockdown of ASPP1 inhibited the expression of Bax (Bcl2-associated X), PUMA (p53 upregulated modulator of apoptosis), and Noxa, direct apoptosis-associated targets of p53. ASPP1 was also increased in the I/R myocardium. Cardiomyocyte-specific transgenic overexpression of ASPP1 aggravated I/R injury as indicated by increased infarct size and impaired cardiac function. Conversely, knockout of ASPP1 mitigated cardiac I/R injury. The same qualitative data were observed in neonatal mouse ventricular cardiomyocytes exposed to hypoxia/reoxygenation injury. Furthermore, inhibition of p53 significantly blunted the proapoptotic activity and detrimental effects of ASPP1 both in vitro and in vivo. CONCLUSIONS: Binding of ASPP1 to p53 triggers their nuclear cotranslocation via importin-ß1 that eventually exacerbates cardiac I/R injury. The findings imply that interfering the expression of ASPP1 or the interaction between ASPP1 and p53 to block their nuclear trafficking represents an important therapeutic strategy for cardiac I/R injury.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Traumatismo por Reperfusão , Proteína Supressora de Tumor p53 , Animais , Camundongos , Apoptose/fisiologia , Hipóxia/metabolismo , Isquemia/metabolismo , Carioferinas , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Adaptadoras de Transdução de Sinal/genética
3.
Cancer ; 130(S8): 1392-1402, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38271367

RESUMO

Antibody-drug conjugates (ADCs)-a groundbreaking class of agents for targeted oncological therapies-consist of monoclonal antibodies with strong antigenic specificity coupled with highly active cytotoxic agents (also referred to as "payloads"). Over the past 2 decades, breast cancer research has evolved into a focal point for the research and development of ADCs, leading to several recent landmark publications. These advancements are ushering in a transformative era in breast cancer treatment and redefining conventional classifications by introducing a prospective subtype termed "HER2-low." The latest iterations of ADCs have demonstrated enhanced efficacy in disease management through the optimization of various factors, notably the incorporation of the bystander effect. These conjugates are no longer limited to the oncogenic driver human epidermal growth factor receptor 2 (HER2). Other antigens, including human epidermal growth factor receptor 3 (HER3), trophoblast cell surface antigen 2 (Trop-2), zinc transporter ZIP6 (LIV-1), and folate receptor α (FRα), have recently emerged as intriguing tumor cell surface nondriver gene targets for ADCs, each with one or more specific ADCs that showed encouraging results in the breast cancer field. This article reviews recent advances in the application of ADCs in the treatment of HER2-low breast cancer. Additionally, this review explores the underlying factors contributing to the impact of target selection on ADC efficacy to provide new insights for optimizing the clinical application of ADCs in individuals with low HER2 expression in advanced breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Imunoconjugados , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Imunoconjugados/uso terapêutico , Estudos Prospectivos , Anticorpos Monoclonais/uso terapêutico , Oncologia , Antineoplásicos/uso terapêutico
4.
Small ; 20(16): e2307792, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38037483

RESUMO

A high-throughput ion beam sputtering system is used to synthesize compositional gradient superlattice-like (SLL) thin film libraries of Ge-Sb-Te alloys over the entire phase diagram. The optical properties and structural evolution of the Ge-Sb-Te combinatorial SLL thin film are investigated. A systematic screening over the annealing temperature, annealing time, and modulation period has elucidated the critical factors that affect the stability of the metastable phase and optical properties. It is found that amorphous stability and optical constant are highly dependent on the modulation period and chemical composition of the thin film. This data-driven approach offers new perspectives for accelerating the development of new materials with excellent optical and amorphous stability and for exploring their mechanisms, by greatly expanding the dataset of Ge-Sb-Te alloys with SLL structures through high-throughput experiments.

5.
Plant Cell Environ ; 47(8): 2895-2910, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38623040

RESUMO

Phytoplasmic SAP11 effectors alter host plant architecture and flowering time. However, the exact mechanisms have yet to be elucidated. Two SAP11-like effectors, SJP1 and SJP2, from 'Candidatus Phytoplasma ziziphi' induce shoot branching proliferation. Here, the transcription factor ZjTCP7 was identified as a central target of these two effectors to regulate floral transition and shoot branching. Ectopic expression of ZjTCP7 resulted in enhanced bolting and earlier flowering than did the control. Interaction and expression assays demonstrated that ZjTCP7 interacted with the ZjFT-ZjFD module, thereby enhancing the ability of these genes to directly bind to the ZjAP1 promoter. The effectors SJP1 and SJP2 unravelled the florigen activation complex by specifically destabilising ZjTCP7 and ZjFD to delay floral initiation. Moreover, the shoot branching of the ZjTCP7-SRDX transgenic Arabidopsis lines were comparable to those of the SJP1/2 lines, suggesting the involvement of ZjTCP7 in the regulation of shoot branching. ZjTCP7 interacted with the branching repressor ZjBRC1 to enhance suppression of the auxin efflux carrier ZjPIN3 expression. ZjTCP7 also directly bound to and upregulated the auxin biosynthesis gene ZjYUCCA2, thereby promoting auxin accumulation. Our findings confirm that ZjTCP7 serves as a bifunctional regulator destabilised by the effectors SJP1 and SJP2 to modulate plant development.


Assuntos
Arabidopsis , Flores , Phytoplasma , Brotos de Planta , Plantas Geneticamente Modificadas , Phytoplasma/fisiologia , Flores/crescimento & desenvolvimento , Flores/genética , Brotos de Planta/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/microbiologia , Arabidopsis/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Regiões Promotoras Genéticas/genética , Ácidos Indolacéticos/metabolismo
6.
Histopathology ; 84(7): 1199-1211, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38409885

RESUMO

AIMS: Intracranial germ cell tumour (IGCT) is a type of rare central nervous system tumour that mainly occurs in children and adolescents, with great variation in its incidence rate and molecular characteristics in patients from different populations. The genetic alterations of IGCT in the Chinese population are still unknown. METHODS AND RESULTS: In this study, 47 patients were enrolled and their tumour specimens were analysed by whole-exome sequencing (WES). We found that KIT was the most significantly mutated gene (15/47, 32%), which mainly occurred in the germinoma group (13/20, 65%), and less frequently in NGGCT (2/27, 7%). Copy number variations (CNVs) of FGF6 and TFE3 only appeared in NGGCT patients (P = 0.003 and 0.032, respectively), while CNVs of CXCR4, RAC2, PDGFA, and FEV only appeared in germinoma patients (P = 0.004 of CXCR4 and P = 0.027 for the last three genes). Compared with a previous Japanese cohort, the somatic mutation rates of RELN and SYNE1 were higher in the Chinese. Prognostic analysis showed that the NF1 mutation was associated with shorter overall survival and progression-free survival in IGCT patients. Clonal evolution analysis revealed an early branched evolutionary pattern in two IGCT patients who underwent changes in the histological subtype or degree of differentiation during disease surveillance. CONCLUSION: This study indicated that Chinese IGCT patients may have distinct genetic characteristics and identified several possible genetic alterations that have the potential to become prognostic biomarkers of NGGCT patients.


Assuntos
Neoplasias Encefálicas , Sequenciamento do Exoma , Neoplasias Embrionárias de Células Germinativas , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , Povo Asiático/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , China/epidemiologia , Variações do Número de Cópias de DNA , População do Leste Asiático , Mutação , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Proteína Reelina
7.
Opt Lett ; 49(12): 3300-3303, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875605

RESUMO

Optical path length (OPL) noise resulting from stray light significantly constrains interferometry displacement measurements in the low-frequency band. This paper presents an analytical model considering the presence of stray light in heterodyne laser interferometers. Due to the cyclic nonlinear coupling effect, there will be some special OPLs of stray light, minimizing the frequency-mixing impact to zero. Consequently, we propose a noise suppression scheme that locks the OPL of stray light at the zero coupling point. Therefore, we significantly enhanced the interference displacement measurement noise within the low-frequency band. Experimental results show that the interferometer achieves a displacement noise level lower than 6 pm/Hz1/2 covering 1 mHz.

8.
Chemphyschem ; 25(6): e202400081, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38303551

RESUMO

Identifying a universal activity descriptor for metal oxides, akin to the d-band center for transition metals, remains a significant challenge in catalyst design, largely due to the intricate electronic structures of metal oxides. This review highlights a major advancement in formulating the number of excess electrons (NEE) as an activity descriptor for oxygen evolution reaction (OER) on reducible metal oxide surfaces. We elaborate on the quantitative relationship between NEE and the adsorption properties of OER intermediates, and unveil the decisive role of the octet rule on the OER performance of these oxides. This insight provides a robust theoretical basis for designing effective OER catalysts. Moreover, we discuss critical experimental evidence supporting this theory and summarize recent advances in employing NEE as a guiding principle for developing highly efficient OER catalysts experimentally.

9.
Anesthesiology ; 140(4): 765-785, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38118180

RESUMO

BACKGROUND: The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain. METHODS: Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents. RESULTS: The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling. CONCLUSIONS: Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice.


Assuntos
Analgesia , Neoplasias Ósseas , Dor do Câncer , Ratos , Masculino , Feminino , Camundongos , Animais , Dor do Câncer/tratamento farmacológico , Receptores Proteína Tirosina Quinases , Ratos Sprague-Dawley , Fator de Crescimento Neural/metabolismo , Camundongos Endogâmicos C57BL , Dor , Neoplasias Ósseas/complicações , Corno Dorsal da Medula Espinal , Receptores Opioides
10.
Eur Radiol ; 34(1): 402-410, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37552255

RESUMO

OBJECTIVES: To evaluate the prognostic value of radiomics features based on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) images in patients with cardiac amyloidosis (CA). METHODS: This retrospective study included 120 CA patients undergoing CMR at three institutions. Radiomics features were extracted from global and three different segments (base, mid-ventricular, and apex) of left ventricular (LV) on short-axis LGE images. Primary endpoint was all-cause mortality. The predictive performance of the radiomics features and semi-quantitative and quantitative LGE parameters were compared by ROC. The AUC was used to observe whether Rad-score had an incremental value for clinical stage. The Kaplan-Meier curve was used to further stratify the risk of CA patients. RESULTS: During a median follow-up of 12.9 months, 30% (40/120) patients died. There was no significant difference in the predictive performance of the radiomics model in different LV sections in the validation set (AUCs of the global, basal, middle, and apical radiomics model were 0.75, 0.77, 0.76, and 0.77, respectively; all p > 0.05). The predictive performance of the Rad-score of the base-LV was better than that of the LGE total enhancement mass (AUC:0.77 vs. 0.54, p < 0.001) and LGE extent (AUC: 0.77 vs. 0.53, p = 0.004). Rad-score combined with Mayo stage had better predictive performance than Mayo stage alone (AUC: 0.86 vs. 0.81, p = 0.03). Rad-score (≥ 0.66) contributed to the risk stratification of all-cause mortality in CA. CONCLUSIONS: Compared to quantitative LGE parameters, radiomics can better predict all-cause mortality in CA, while the combination of radiomics and Mayo stage could provide higher predictive accuracy. CLINICAL RELEVANCE STATEMENT: Radiomics analysis provides incremental value and improved risk stratification for all-cause mortality in patients with cardiac amyloidosis. KEY POINTS: • Radiomics in LV-base was superior to LGE semi-quantitative and quantitative parameters for predicting all-cause mortality in CA. • Rad-score combined with Mayo stage had better predictive performance than Mayo stage alone or radiomics alone. • Rad-score ≥ 0.66 was associated with a significantly increased risk of all-cause mortality in CA patients.


Assuntos
Amiloidose , Gadolínio , Humanos , Gadolínio/farmacologia , Meios de Contraste/farmacologia , Estudos Retrospectivos , Radiômica , Amiloidose/diagnóstico por imagem , Prognóstico , Valor Preditivo dos Testes , Imagem Cinética por Ressonância Magnética/métodos , Função Ventricular Esquerda
11.
J Org Chem ; 89(9): 6353-6363, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38625867

RESUMO

An efficient formylation of pyrrolo[2,1-a]isoquinoline derivatives has been reached by the use of TBHP (tBuOOH) and Et3N as the mediator. In this strategy, CHO and CDO can be readily incorporated into heteroarenes by the utilization of CHCl3 and CDCl3 as the carbonyl sources. Interestingly, a solvent-controlled chemoselectivity was observed. The use of PhCl as a solvent resulted in dearomatization and peroxidation of pyrrolo[2,1-a]isoquinolines, delivering functionalized peroxides in 53-64% yields.

12.
J Org Chem ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38920085

RESUMO

An efficient oxidative chlorination of pyrrolo[2,1-a]isoquinolines has been established using HCl (aq) as the chlorine source and DMSO as the terminal oxidant in HFIP at ambient temperature. A variety of chlorinated pyrrolo[2,1-a]isoquinoline derivatives have been prepared readily in 23 to 99% yields. This chlorination strategy can be expanded to the functionalization of other electron-rich heteroarenes including substituted pyrroles, indoles, and naphthols.

13.
Inorg Chem ; 63(27): 12624-12634, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38910548

RESUMO

Four Ag(I) complexes with mefenamato and nitrogen heterocyclic ligands, [Ag(2-apy)(mef)]2 (1), [Ag(3-apy)(mef)] (2), [Ag2(tmpyz)(mef)2] (3), and {[Ag(4,4'-bipy)(mef)]2(CH3CN)1.5(H2O)2}n (4), (mef = mefenamato, 2-apy = 2-aminopyridine, 3-apy = 3-aminopyridine, tmpyz = 2,3,5,6-tetramethylpyrazine, 4,4'-bipy = 4,4'-bipyridine), were synthesized and characterized. The interactions of these complexes with BSA were investigated by fluorescence spectroscopy, which indicated that these complexes quench the fluorescence of BSA by a static mechanism. The fluorescence data also indicated that the complexes showed good affinity for BSA, and one binding site on BSA was suitable for the complexes. The in vitro cytotoxicity of the four complexes against human cancer cell lines (MCF-7, HepG-2, A549, and MDA-MB-468) and one normal cell line (HTR-8) was evaluated by the MTT assay. Complex 1 displayed high cytotoxic activity against A549 cells. Further studies revealed that complex 1 could enhance the intracellular levels of ROS (reactive oxygen species) in A549 cells, cause cell cycle arrest in the G0/G1 phase, and induce apoptosis in A549 cells in a dose-dependent manner.


Assuntos
Antineoplásicos , Complexos de Coordenação , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Mefenâmico , Prata , Humanos , Prata/química , Prata/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ligantes , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Ácido Mefenâmico/farmacologia , Ácido Mefenâmico/química , Apoptose/efeitos dos fármacos , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/síntese química , Proliferação de Células/efeitos dos fármacos , Nitrogênio/química , Estrutura Molecular , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Linhagem Celular Tumoral
14.
Arch Virol ; 169(2): 22, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38193974

RESUMO

African swine fever (ASF) is an infectious disease caused by ASF virus (ASFV), which is characterized by high infectivity, rapid onset of disease, and a high mortality rate. Outbreaks of ASFV have caused great economic losses to the global pig industry, and there is a need to develop safe and effective vaccines. In this study, two recombinant pseudorabies virus (PRV) strains, rGXGG-2016-ΔgI/ΔgE-EP364R and rGXGG-2016-ΔgI/ΔgE-B119L, expressing the EP364R and B119L protein, respectively, of ASFV, were constructed by homologous recombination technology. Western blotting and immunofluorescence analysis showed that these foreign proteins were expressed in cells infected with the recombinant strains. The strains showed good genetic stability and proliferative characteristics for 20 passages in BHK-21 cells. Both of these strains were immunogenic in mice, inducing the production of specific antibodies against the expressed ASFV proteins while providing protection against lethal challenge with PRV. Thus, the recombinant strains rGXGG-2016-ΔgI/ΔgE-EP364R and rGXGG-2016-ΔgI/ΔgE-B119L could be used as candidate vaccines for both ASFV and PRV. In addition, our study identifies two potential target genes for the development of safe and efficient ASFV vaccines, provides a reference for the construction of bivalent ASFV and PRV vaccines, and demonstrates the feasibility of developing a live ASFV vector vaccine.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Herpesvirus Suídeo 1 , Animais , Camundongos , Suínos , Vírus da Febre Suína Africana/genética , Herpesvirus Suídeo 1/genética , Febre Suína Africana/prevenção & controle , Vacinas Atenuadas , Imunidade
15.
Environ Sci Technol ; 58(15): 6814-6824, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38581381

RESUMO

Identifying persistent, mobile, and toxic (PMT) substances from synthetic chemicals is critical for chemical management and ecological risk assessment. Inspired by the triazine analogues (e.g., atrazine and melamine) in the original European Union's list of PMT substances, the occurrence and compositions of alkylamine triazines (AATs) in the estuarine sediments of main rivers along the eastern coast of China were comprehensively explored by an integrated strategy of target, suspect, and nontarget screening analysis. A total of 44 AATs were identified, of which 23 were confirmed by comparison with authentic standards. Among the remaining tentatively identified analogues, 18 were emerging pollutants not previously reported in the environment. Tri- and di-AATs were the dominant analogues, and varied geographic distributions of AATs were apparent in the investigated regions. Toxic unit calculations indicated that there were acute and chronic risks to algae from AATs on a large geographical scale, with the antifouling biocide cybutryne as a key driver. The assessment of physicochemical properties further revealed that more than half of the AATs could be categorized as potential PMT and very persistent and very mobile substances at the screening level. These results highlight that AATs are a class of PMT substances posing high ecological impacts on the aquatic environment and therefore require more attention.


Assuntos
Atrazina , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Rios/química , Triazinas/análise , Atrazina/análise , China , Monitoramento Ambiental
16.
Bioorg Chem ; 149: 107487, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38805910

RESUMO

The peel of Trichosanthes kirilowii Maxim, is considered one of the primary sources for Trichosanthis pericarpium in traditional Chinese medicine, exhibiting lipid-lowering properties. The impact on hyperlipidemia mice of the crude polysaccharide from the peel of T. Kirilowii (TRP) was investigated in this study. The findings revealed that TRP exhibited a significant improvement in hepatic lipid deposition. Moreover, it significantly decreased serum levels of TC, TG, and LDL-C, while concurrently increasing HDL-C. 16S rRNA amplicon sequencing technique revealed that TRP group exhibited an increased relative abundance of Actinobacteria, a down-regulated relative abundance of Ruminiclostridium, and an up-regulated relative abundance of Ileibacterium. Therefore, TRP might play a role in anti-hyperlipidemia through regulation of the intestinal milieu and enhancement of microbial equilibrium. Consequently, targeted fractionation of TRP resulted in the isolation of a homogeneous acidic polysaccharide termed TRP-1. The TRP-1 polysaccharide, with an average molecular weight of 1.00 × 104 Da, and was primarily composed of Rha, GlcA, GalA, Glc, Gal and Ara. TRP-1 possessed a backbone consisting of alternating connections between â†’ 6)-α-Galp-(1 â†’ 4)-α-Rhap-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ units and branched chain containing â†’ 6)-α-Glcp-(1→, 2,4)-ß-Glcp-(1, and â†’ 4)-α-GlapA-(1→. Both TRP and TRP-1 exhibited significant disruption of cholesterol micelles, highlighting their potential as lipid-lowering agents that effectively inhibit cholesterol absorption pathways.


Assuntos
Colesterol , Microbioma Gastrointestinal , Hiperlipidemias , Polissacarídeos , Trichosanthes , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Trichosanthes/química , Camundongos , Hiperlipidemias/tratamento farmacológico , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Colesterol/metabolismo , Colesterol/sangue , Hipolipemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/isolamento & purificação , Masculino , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga
17.
BMC Med Imaging ; 24(1): 45, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360550

RESUMO

BACKGROUND: Tumor mutational burden (TMB) is one of the most significant predictive biomarkers of immunotherapy efficacy in non-small cell lung cancer (NSCLC). Radiomics allows high-throughput extraction and analysis of advanced and quantitative medical imaging features. This study develops and validates a radiomic model for predicting TMB level and the response to immunotherapy based on CT features in NSCLC. METHOD: Pre-operative chest CT images of 127 patients with NSCLC were retrospectively studied. The 3D-Slicer software was used to outline the region of interest and extract features from the CT images. Radiomics prediction model was constructed by LASSO and multiple logistic regression in a training dataset. The model was validated by receiver operating characteristic (ROC) curves and calibration curves using external datasets. Decision curve analysis was used to assess the value of the model for clinical application. RESULTS: A total of 1037 radiomic features were extracted from the CT images of NSCLC patients from TCGA. LASSO regression selected three radiomics features (Flatness, Autocorrelation and Minimum), which were associated with TMB level in NSCLC. A TMB prediction model consisting of 3 radiomic features was constructed by multiple logistic regression. The area under the curve (AUC) value in the TCGA training dataset was 0.816 (95% CI: 0.7109-0.9203) for predicting TMB level in NSCLC. The AUC value in external validation dataset I was 0.775 (95% CI: 0.5528-0.9972) for predicting TMB level in NSCLC, and the AUC value in external validation dataset II was 0.762 (95% CI: 0.5669-0.9569) for predicting the efficacy of immunotherapy in NSCLC. CONCLUSION: The model based on CT radiomic features helps to achieve cost effective improvement in TMB classification and precise immunotherapy treatment of NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Radiômica , Tomografia Computadorizada por Raios X/métodos , Biomarcadores Tumorais , Imunoterapia
18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 193-203, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38686715

RESUMO

Objective To understand the differences in the demand,preference,and tendency for elderly care services between urban and rural areas in the Pearl River Delta (PRD),and to provide reference for the planning and balanced allocation of elderly care resources in urban and rural areas. Methods Using the multi-stage stratified random sampling method,we selected 7 community health service centers in 2 prefecture-level cities in the PRD and conducted a questionnaire survey on the elderly care service demand,preference,and tendency among 1919 regular residents aged 60 years and above who attended the centers. Results A total of 641 urban elderly residents (33.4%) and 1278 rural elderly residents (66.6%) were surveyed in the PRD.The urban and rural elderly residents showed differences in the child number (χ2=43.379,P<0.001),willingness to purchase socialized elderly care services (χ2=104.141,P<0.001),and attitudes to the concept of raising child to avoid elderly hardship (χ2=65.632,P<0.001).The proportion (71.8%) of rural elderly residents who prefer family-based elderly care was higher than that (57.1%) of urban elderly residents (χ2=41.373,P<0.001).The proportion (62.2%) of urban elderly residents clearly expressing their willingness to choose institutions for elderly care was higher than that (44.0%) of rural elderly residents (χ2=57.007,P<0.001).Compared with family-based elderly care,the willingness to choose institutional or community-based in-house elderly care was low among the urban elderly residents with surplus monthly household income or balanced income and expenditure;urban males,those with college education background or above,and those who purchased socialized elderly care services tended to prefer community-based in-house elderly care.In rural areas,the elderly residents who had local household registry were prone to choose institutional or community-based in-house elderly care,while those who had more than one child and those who were satisfied with the current living conditions were less willing to choose community-based in-house elderly care. Conclusions It is suggested that the urban-rural differences in the elderly care service demand,preference and tendency should be fully considered in the planning and allocation of urban and rural elderly care resources.Efforts remain to be made to develop diversified social elderly care services tailored to the characteristics of urban and rural areas.


Assuntos
População Rural , População Urbana , Humanos , Idoso , China , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos e Questionários , Serviços de Saúde para Idosos/estatística & dados numéricos , Idoso de 80 Anos ou mais , Necessidades e Demandas de Serviços de Saúde
19.
Angew Chem Int Ed Engl ; 63(19): e202402274, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38415322

RESUMO

The high theoretical energy density (1274 Wh kg-1) and high safety enable the all-solid-state Na-S batteries with great promise for stationary energy storage system. However, the uncontrollable solid-liquid-solid multiphase conversion and its associated sluggish polysulfides redox kinetics pose a great challenge in tunning the sulfur speciation pathway for practical Na-S electrochemistry. Herein, we propose a new design methodology for matrix featuring separated bi-catalytic sites that control the multi-step polysulfide transformation in tandem and direct quasi-solid reversible sulfur conversion during battery cycling. It is revealed that the N, P heteroatom hotspots are more favorable for catalyzing the long-chain polysulfides reduction, while PtNi nanocrystals manipulate the direct and full Na2S4 to Na2S low-kinetic conversion during discharging. The electrodeposited Na2S on strongly coupled PtNi and N, P-codoped carbon host is extremely electroreactive and can be readily recovered back to S8 without passivation of active species during battery recharging, which delivers a true tandem electrocatalytic quasi-solid sulfur conversion mechanism. Accordingly, stable cycling of the all-solid-state soft-package Na-S pouch cells with an attractive specific capacity of 876 mAh gS -1 and a high energy of 608 Wh kgcathode -1 (172 Wh kg-1, based on the total mass of cathode and anode) at 60 °C are demonstrated.

20.
J Proteome Res ; 22(6): 1712-1722, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37159428

RESUMO

Tendinopathy is a disease with surging prevalence. Lacking understanding of molecular mechanisms impedes the development of therapeutic approaches and agents. Lysine lactylation (Kla) is a newly discovered post-translational modification related to glycolysis. It has long been noted that manipulation of glycolysis metabolism could affect tendon cell function, tendon homeostasis, and healing process of tendon. However, protein lactylation sites in tendinopathy remain unexplored. Here, we conducted the first proteome-wide Kla analysis in tendon samples harvested from patients with rotator cuff tendinopathy (RCT), which identified 872 Kla sites across 284 proteins. Compared with normal counterparts, 136 Kla sites on 77 proteins were identified as upregulated in the pathological tendon, while 56 sites on 32 proteins were downregulated. Function enrichment analysis demonstrated that the majority of proteins with upregulated Kla levels functioned in organization of the tendon matrix and cholesterol metabolism, accompanied by lower expression levels which meant impaired cholesterol metabolism and degeneration of the tendon matrix, indicating potential cross-talk between protein lactylation and expression levels. At last, by western blotting and immunofluorescence, we verified the correlation between high lactylation and the downregulation of matrix and cholesterol-related proteins including BGN, MYL3, TPM3, and APOC3. ProteomeXchange: PXD033146.


Assuntos
Manguito Rotador , Tendinopatia , Humanos , Manguito Rotador/metabolismo , Manguito Rotador/patologia , Proteínas/metabolismo , Tendões/metabolismo , Tendões/patologia , Lisina/metabolismo , Tendinopatia/genética , Tendinopatia/metabolismo , Tendinopatia/patologia
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