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1.
Artículo en Inglés | MEDLINE | ID: mdl-39001805

RESUMEN

The attractive physical properties of two-dimensional (2D) semiconductors in group IVA-VIA have been fully revealed in recent years. Combining them with 2D ambipolar materials to construct van der Waals heterojunctions (vdWHs) can offer tremendous opportunities for designing multifunctional electronic and optoelectronic devices, such as logic switching circuits, half-wave rectifiers, and broad-spectrum photodetectors. Here, an optimized SnSe0.75S0.25 is grown to design a SnSe0.75S0.25/MoTe2 vdWH for logic operation and wide-spectrum photodetection. Benefiting from the excellent gate modulation under the appropriate sulfur substitution and type-II band alignment, the device exhibits reconfigurable antiambipolar and ambipolar transfer behaviors at positive and negative source-drain voltage (Vds), enabling stable XNOR logic operation. It also features a gate-modulated positive and negative rectifying behavior with rectification ratios of 265:1 and 1:196, confirming its potential as half-wave logic rectifiers. Besides, the device can respond from visible to infrared wavelength up to 1400 nm. Under 635 nm illumination, the maximum responsivity of 1.16 A/W and response time of 657/500 µs are achieved at the Vds of -2 V. Furthermore, due to the strong in-plane anisotropic structure of SnSe0.75S0.25-alloyed nanosheet and narrow bandgap of 2H-MoTe2, it shows a broadband polarization-sensitive function with impressive photocurrent anisotropic ratios of 15.6 (635 nm), 7.0 (808 nm), and 3.7 (1310 nm). The direction along the maximum photocurrent can be reconfigurable depending on the wavelengths. These results indicate that our designed alloyed SnSe0.75S0.25/MoTe2 vdWH has reconfigurable logic operation and broadband photodetection capabilities in 2D multifunctional integrated circuits.

2.
mSphere ; : e0043924, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012105

RESUMEN

Companion animals such as cats and dogs harbor diverse microbial communities that can potentially impact human health due to close and frequent contact. To better characterize their total infectomes and assess zoonotic risks, we characterized the overall infectomes of companion animals (cats and dogs) and evaluated their potential zoonotic risks. Meta-transcriptomic analyses were performed on 239 samples from cats and dogs collected across China, identifying 24 viral species, 270 bacterial genera, and two fungal genera. Differences in the overall microbiome and infectome composition were compared across different animal species (cats or dogs), sampling sites (rectal or oropharyngeal), and health status (healthy or diseased). Diversity analyses revealed that viral abundance was generally higher in diseased animals compared to healthy ones, while differences in microbial composition were mainly driven by sampling site, followed by animal species and health status. Disease association analyses validated the pathogenicity of known pathogens and suggested potential pathogenic roles of previously undescribed bacteria and newly discovered viruses. Cross-species transmission analyses identified seven pathogens shared between cats and dogs, such as alphacoronavirus 1, which was detected in both oropharyngeal and rectal swabs albeit with differential pathogenicity. Further analyses showed that some viruses, like alphacoronavirus 1, harbored multiple lineages exhibiting distinct pathogenicity, tissue, or host preferences. Ultimately, a systematic evolutionary screening identified 27 potential zoonotic pathogens in this sample set, with far more bacterial than viral species, implying potential health threats to humans. Overall, our meta-transcriptomic analysis reveals a landscape of actively transcribing microorganisms in major companion animals, highlighting key pathogens, those with the potential for cross-species transmission, and possible zoonotic threats. IMPORTANCE: This study provides a comprehensive characterization of the entire community of infectious microbes (viruses, bacteria, and fungi) in companion animals like cats and dogs, termed the "infectome." By analyzing hundreds of samples from across China, the researchers identified numerous known and novel pathogens, including 27 potential zoonotic agents that could pose health risks to both animals and humans. Notably, some of these zoonotic pathogens were detected even in apparently healthy pets, highlighting the importance of surveillance. The study also revealed key microbial factors associated with respiratory and gastrointestinal diseases in pets, as well as potential cross-species transmission events between cats and dogs. Overall, this work sheds light on the complex microbial landscapes of companion animals and their potential impacts on animal and human health, underscoring the need for monitoring and management of these infectious agents.

3.
World J Gastrointest Oncol ; 16(6): 2404-2418, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38994138

RESUMEN

BACKGROUND: Research on gastrointestinal mucosal adenocarcinoma (GMA) is limited and controversial, and there is no reference tool for predicting postoperative survival. AIM: To investigate the prognosis of GMA and develop predictive model. METHODS: From the Surveillance, Epidemiology, and End Results database, we collected clinical information on patients with GMA. After random sampling, the patients were divided into the discovery (70% of the total, for model training), validation (20%, for model evaluation), and completely blind test cohorts (10%, for further model evaluation). The main assessment metric was the area under the receiver operating characteristic curve (AUC). All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA's prognosis. RESULTS: This model had an AUC of 0.7433 [95% confidence intervals (95%CI): 0.7424-0.7442] in the discovery cohort, 0.7244 (GMA: 0.7234-0.7254) in the validation cohort, and 0.7388 (95%CI: 0.7378-0.7398) in the test cohort. We packaged it into Windows software for doctors' use and uploaded it. Mucinous gastric adenocarcinoma had the worst prognosis, and these were protective factors of GMA: Regional nodes examined [hazard ratio (HR): 0.98, 95%CI: 0.97-0.98, P < 0.001)] and chemotherapy (HR: 0.62, 95%CI: 0.58-0.66, P < 0.001). CONCLUSION: The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively. Combining surgery, chemotherapy, and adequate lymph node dissection during surgery can improve patient outcomes.

4.
Food Chem ; 457: 140028, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38917561

RESUMEN

The gold standard of milk is human milk, not cow milk. The present study expects to explored the comprehensive nutritional value of different kinds of milk and the differences between them through multi-omics analysis and found functional components that are more similar to human milk. This study employed untargeted LC-MS/MS metabolomics, untargeted LC-MS/MS lipidomics, and 4D label-free proteomics analysis techniques. The findings revealed substantial disparities in metabolites, lipids, and proteins among the five types of milk. Notably, pig milk exhibited a remarkable abundance of N-acetylneuraminic acid (Neu5Ac) and specific polar lipids. Yak milk stood out with significantly elevated levels of creatine and lipoprotein lipase (LPL) compared to other species. Buffalo milk boasted the highest concentrations of L-isoleucine, echinocystic acid, and alkaline phosphatase, tissue-nonspecific isozyme (ALPL). The concentrations of iminostilbene and osteopontin (OPN) were higher in cow milk.

5.
Eur J Med Chem ; 274: 116545, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38823263

RESUMEN

Prostate cancer (PCa) is one of the most common tumors in men, with the overexpression of prostate-specific membrane. In this study, we developed four new 68Ga-labeled PSMA-targeting tracers by introducing quinoline, phenylalanine and decanoic acid groups to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Four radiotracers were synthesized with radiochemical purity >95 %, and exhibited high stability in vivo and in vitro. The inhibition constants (Ki) of SDTWS01-04 to PSMA were in the nanomolar range (<10 nM). Micro PET/CT imaging and biodistribution analysis revealed that 68Ga-SDTWS01 enabled clear tumor visualization in PET images at 1.5 h post-injection, with excellent pharmacokinetic properties. Notably, the kidney uptake of 68Ga-SDTWS01 significantly reduced, with higher tumor-to-kidney ratio (0.36 ± 0.02), tumor-to-muscle ratio (24.31 ± 2.10), compared with 68Ga-PSMA-11 (T/K: 0.15 ± 0.01; T/M: 14.97 ± 1.40), suggesting that 68Ga-SDTWS01 is a promising radiotracer for the diagnosis of PCa. Moreover, SDTWS01 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for the treatment of PCa.


Asunto(s)
Radioisótopos de Galio , Glutamato Carboxipeptidasa II , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Radioisótopos de Galio/química , Humanos , Masculino , Animales , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/tratamiento farmacológico , Glutamato Carboxipeptidasa II/metabolismo , Glutamato Carboxipeptidasa II/antagonistas & inhibidores , Distribución Tisular , Ratones , Radiofármacos/síntesis química , Radiofármacos/química , Radiofármacos/farmacología , Antígenos de Superficie/metabolismo , Estructura Molecular , Línea Celular Tumoral
6.
Environ Sci Technol ; 58(28): 12498-12508, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38900106

RESUMEN

Appropriate mixed carbon sources have great potential to enhance denitrification efficiency and reduce operational costs in municipal wastewater treatment plants (WWTPs). However, traditional methods struggle to efficiently select the optimal mixture due to the variety of compositions. Herein, we developed a machine learning-assisted high-throughput method enabling WWTPs to rapidly identify and optimize mixed carbon sources. Taking a local WWTP as an example, a mixed carbon source denitrification data set was established via a high-throughput method and employed to train a machine learning model. The composition of carbon sources and the types of inoculated sludge served as input variables. The XGBoost algorithm was employed to predict the total nitrogen removal rate and microbial growth, thereby aiding in the assessment of the denitrification potential. The predicted carbon sources exhibited an enhanced denitrification potential over single carbon sources in both kinetic experiments and long-term reactor operations. Model feature analysis shows that the cumulative effect and interaction among individual carbon sources in a mixture significantly enhance the overall denitrification potential. Metagenomic analysis reveals that the mixed carbon sources increased the diversity and complexity of denitrifying bacterial ecological networks in WWTPs. This work offers an efficient method for WWTPs to optimize mixed carbon source compositions and provides new insights into the mechanism behind enhanced denitrification under a supply of multiple carbon sources.


Asunto(s)
Carbono , Desnitrificación , Aprendizaje Automático , Aguas Residuales/química , Nitrógeno , Eliminación de Residuos Líquidos/métodos , Aguas del Alcantarillado/microbiología
7.
Aging Cell ; : e14187, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716507

RESUMEN

Behavioral changes or neuropsychiatric symptoms (NPSs) are common features in dementia and are associated with accelerated cognitive impairment and earlier deaths. However, how NPSs are intertwined with cognitive decline remains elusive. In this study, we identify that the basolateral amygdala (BLA) is a key brain region that is associated with mood disorders and memory decline in the AD course. During the process from pre- to post-onset in AD, the dysfunction of parvalbumin (PV) interneurons and pyramidal neurons in the amygdala leads to hyperactivity of pyramidal neurons in the basal state and insensitivity to external stimuli. We further demonstrate that serotonin (5-HT) receptors in distinct neurons synergistically regulate the BLA microcircuit of AD rather than 5-HT levels, in which both restrained inhibitory inputs by excessive 5-HT1AR signaling in PV interneurons and depolarized pyramidal neurons via upregulated 5-HT2AR contribute to aberrant neuronal hyperactivity. Downregulation of these two 5-HT receptors simultaneously enables neurons to resist ß-amyloid peptides (Aß) neurotoxicity and ameliorates the mood and cognitive defects. Therefore, our study reveals a crucial role of 5-HT receptors for regulating neuronal homeostasis in AD pathogenesis, and this would provide early intervention and potential targets for AD cognitive decline.

8.
Cancer Genet ; 286-287: 1-10, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38810361

RESUMEN

Colon cancer (CC) is a common malignancy over the world and its morbidity and mortality significantly went up in China in recent years. Molecular functions in cancers have gradually been the pivot subject in cancer research. Neuroepithelial cell transforming 1 (NET1) was reported to contribute to prostate cancer and gastric cancer. Our study figured out that NET1 was overexpressed in CC cells. Then, loss-of-function assays revealed that NET1 facilitated CC cell proliferation and repressed CC cell apoptosis. Next, miR-338-3p was confirmed to target NET1. After that, we verified that circ_0017552 which originates from NET1 could positively modulate NET1 expression. Besides, circ_0017552 was a sponge of miR-338-3p. Rescue assays' results demonstrated that circ_0017552 could regulate CC cell proliferation and apoptosis through up-regulation of NET1. A transcription factor named Sp1 (SP1) was found to be present in circ_0017552. SP1 induced transcription of circ_0017552 to facilitate CC cell proliferation and inhibit CC cell apoptosis. In a word, SP1-induced circ_0017552 regulated CC cell proliferation and apoptosis through miR-338-3p/NET1 axis.

9.
Environ Sci Pollut Res Int ; 31(24): 35853-35863, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38743334

RESUMEN

Phenolic root exudates (PREs) secreted by wetland plants facilitate the accumulation of iron in the rhizosphere, potentially providing the essential active iron required for the generation of enzymes that degrade polycyclic aromatic hydrocarbon, thereby enhancing their biodegradation. However, the underlying mechanisms involved are yet to be elucidated. This study focuses on phenanthrene (PHE), a typical polycyclic aromatic hydrocarbon pollutant, utilizing representative PREs from wetland plants, including p-hydroxybenzoic, p-coumaric, caffeic, and ferulic acids. Using hydroponic experiments, 16S rRNA sequencing, and multiple characterization techniques, we aimed to elucidate the interaction mechanism between the accelerated degradation of PHE and the formation of rhizosphere biofilm/iron plaque influenced by PREs. Although all four types of PREs altered the biofilm composition and promoted the formation of iron plaque on the root surface, only caffeic acid, possessing a similar structure to the intermediate metabolite of PHE (catechol), could accelerate the PHE degradation rate. Caffeic acid, notable for its catechol structure, plays a significant role in enhancing PHE degradation through two main mechanisms: (a) it directly boosts PHE co-metabolism by fostering the growth of PHE-degrading bacteria, specifically Burkholderiaceae, and by facilitating the production of the key metabolic enzyme catechol 1,2-dioxygenase (C12O) and (b) it indirectly supports PHE biodegradation by promoting iron plaque formation on root surfaces, thereby enriching free iron for efficient microbial synthesis of C12O, a crucial factor in PHE decomposition.


Asunto(s)
Biodegradación Ambiental , Biopelículas , Hierro , Fenantrenos , Raíces de Plantas , Rizosfera , Fenantrenos/metabolismo , Hierro/metabolismo , Fenoles/metabolismo , Humedales
10.
FASEB J ; 38(10): e23664, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38775797

RESUMEN

Adipogenesis, a pivotal cellular process involving the differentiation of mesenchymal stem cells (MSCs) to mature adipocytes, plays a significant role in various physiological functions. Dysregulation of adipogenesis is implicated in conditions such as obesity. However, the complete molecular understanding of adipogenesis remains elusive. This study aimed to uncover the novel role of lamina-associated polypeptide 2 alpha (LAP2α) in human adipose-derived stem cells (hASCs) adipogenesis and its impact on high-fat diet (HFD)-induced obesity and associated metabolic disturbances. LAP2α expression was assessed during the adipogenic differentiation of hASCs using RT-qPCR and western blotting. The functional role of LAP2α in adipogenesis was explored both in vitro and in vivo through loss- and gain-of-function studies. Moreover, mice with HFD-induced obesity received lentivirus injection to assess the effect of LAP2α knockdown on fat accumulation. Molecular mechanisms underlying LAP2α in adipogenic differentiation were investigated using RT-qPCR, Western blotting, immunofluorescence staining, and Oil Red O staining. LAP2α expression was upregulated during hASCs adipogenic differentiation. LAP2α knockdown hindered adipogenesis, while LAP2α overexpression promoted adipogenic differentiation. Notably, LAP2α deficiency resisted HFD-induced obesity, improved glucose intolerance, mitigated insulin resistance, and prevented fatty liver development. Mechanistically, LAP2α knockdown attenuated signal transducer and activator of transcription 3 (STAT3) activation by reducing the protein level of phosphorylated STAT3. A STAT3 activator (Colivelin) counteracted the negative impact of LAP2α deficiency on hASCs adipogenic differentiation. Taken together, our current study established LAP2α as a crucial regulator of hASCs adipogenic differentiation, unveiling a new therapeutic target for obesity prevention.


Asunto(s)
Adipogénesis , Dieta Alta en Grasa , Células Madre Mesenquimatosas , Obesidad , Humanos , Dieta Alta en Grasa/efectos adversos , Obesidad/metabolismo , Obesidad/genética , Obesidad/etiología , Animales , Ratones , Células Madre Mesenquimatosas/metabolismo , Masculino , Diferenciación Celular , Ratones Endogámicos C57BL , Tejido Adiposo/metabolismo , Tejido Adiposo/citología , Adipocitos/metabolismo , Células Cultivadas , Técnicas de Silenciamiento del Gen , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Proteínas de Unión al ADN , Proteínas de la Membrana
11.
PLoS One ; 19(5): e0304258, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38781178

RESUMEN

Corydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo.


Asunto(s)
Alcaloides , Corydalis , Metabolómica , Raíces de Plantas , Corydalis/genética , Corydalis/metabolismo , Metabolómica/métodos , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Alcaloides/biosíntesis , Alcaloides/metabolismo , Transcriptoma , Bencilisoquinolinas/metabolismo , Regulación de la Expresión Génica de las Plantas , Vías Biosintéticas/genética , Perfilación de la Expresión Génica , Alcaloides de Berberina/metabolismo , Metaboloma
12.
J Genet Eng Biotechnol ; 22(2): 100372, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38797546

RESUMEN

The myostatin (MSTN) gene exhibits significant nucleotide sequence variations in sheep, impacting growth characteristics and muscular traits of the body. However, its influence on specific growth traits in some sheep remains to be further elucidated. This study utilized single nucleotide polymorphism sequence analysis to investigate the role of the MSTN gene in meat production performance across four sheep breeds: Charolais sheep, Australian White sheep, crossbreeds of Australian White and Small-tailed Han, and crossbreeds of Charolais and Small-tailed Han. At a SNP locus of the MSTN gene, the C2361T site was identified, with three genotypes detected: CC, CT, and TT, among which CC predominated. Gene substitution effect analysis revealed that replacing C with T could elevate the phenotypic value. Comparative analysis of data from different genotypes within the same breed highlighted the superiority of CC and TT genotypes in phenotypic values, underscoring the significance of specific genotypes in influencing key traits. Contrasting the performance of different genotypes across breeds, Charolais sheep and Charolais Han hybrids demonstrated superiority across multiple indicators, offering valuable insights for breeding new sheep varieties. Analysis of gender effects on growth characteristics indicated that ewes exhibited significantly wider chest, waist, and hip widths compared to rams, while rams displayed better skeletal growth and muscle development. Additionally, the MSTN gene also exerted certain effects on lamb growth characteristics, with the CC genotype closely associated with weight. These findings not only contribute crucial insights for sheep breeding but also pave the way for future research exploring the interaction of this gene with others.

13.
Nat Neurosci ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816530

RESUMEN

Neurogenetic disorders, such as neurofibromatosis type 1 (NF1), can cause cognitive and motor impairments, traditionally attributed to intrinsic neuronal defects such as disruption of synaptic function. Activity-regulated oligodendroglial plasticity also contributes to cognitive and motor functions by tuning neural circuit dynamics. However, the relevance of oligodendroglial plasticity to neurological dysfunction in NF1 is unclear. Here we explore the contribution of oligodendrocyte progenitor cells (OPCs) to pathological features of the NF1 syndrome in mice. Both male and female littermates (4-24 weeks of age) were used equally in this study. We demonstrate that mice with global or OPC-specific Nf1 heterozygosity exhibit defects in activity-dependent oligodendrogenesis and harbor focal OPC hyperdensities with disrupted homeostatic OPC territorial boundaries. These OPC hyperdensities develop in a cell-intrinsic Nf1 mutation-specific manner due to differential PI3K/AKT activation. OPC-specific Nf1 loss impairs oligodendroglial differentiation and abrogates the normal oligodendroglial response to neuronal activity, leading to impaired motor learning performance. Collectively, these findings show that Nf1 mutation delays oligodendroglial development and disrupts activity-dependent OPC function essential for normal motor learning in mice.

14.
Environ Sci Technol ; 58(15): 6552-6563, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38571383

RESUMEN

Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.


Asunto(s)
Desinfectantes , Desinfección , Desinfección/métodos , Matriz Extracelular de Sustancias Poliméricas , Desinfectantes/farmacología , Cloro/farmacología , Cinética
15.
J Exp Med ; 221(5)2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38597926

RESUMEN

The cognitive side effects of cancer treatment are common, but no targeted therapy exists yet to treat or prevent such neurological sequelae. We explore the role of hormones as mediators between cancer therapy and cognitive impairment, discussing potential future directions.


Asunto(s)
Disfunción Cognitiva , Neoplasias , Humanos , Neoplasias/terapia , Fatiga Mental , Progresión de la Enfermedad
16.
Eur J Nucl Med Mol Imaging ; 51(9): 2819-2832, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38683349

RESUMEN

PURPOSE: A series of new 68Ga-labeled tracers based on [68Ga]Ga-PSMA-617 were developed to augment the tumor-to-kidney ratio and reduce the activity accumulation in bladder, ultimately minimize radiation toxicity to the urinary system. METHODS: We introduced quinoline group, phenylalanine and decanoic acid into different tracers to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Their binding affinity onto LNCaP cells was determined through in vitro saturation assays and competition binding assays. In vivo metabolic study, PET imaging and biodistribution experiment were performed in LNCaP tumor-bearing B-NSG male mice. The most promising tracer was selected for first-in-human study. RESULTS: Four radiotracers were synthesized with radiochemical purity (RCP) > 95% and molar activity in a range of 20.0-25.5 GBq/µmol. The binding affinities (Ki) of TWS01, TWS02 to PSMA were in the low nanomolar range (< 10 nM), while TWS03 and TWS04 exhibited binding affinities with Ki > 20 nM (59.42 nM for TWS03 and 37.14 nM for TWS04). All radiotracers exhibited high stability in vivo except [68Ga]Ga-TWS03. Micro PET/CT imaging and biodistribution analysis revealed that [68Ga]Ga-TWS02 enabled clear tumor visualization in PET images at 1.5 h post-injection, with higher tumor-to-kidney ratio (T/K, 0.93) and tumor-to-muscle ratio (T/M, 107.62) compared with [68Ga]Ga-PSMA-617 (T/K: 0.39, T/M: 15.01) and [68Ga]Ga-PSMA-11 (T/K: 0.15, T/M: 24.00). In first-in-human study, [68Ga]Ga-TWS02 effectively detected PCa-associated lesions including primary and metastatic lesions, with lower accumulation in urinary system, suggesting that [68Ga]Ga-TWS02 might be applied in the detection of bladder invasion, with minimized radiation toxicity to the urinary system. CONCLUSION: Introduction of quinoline group, phenylalanine and decanoic acid into different tracers can modulate the binding affinity and pharmacokinetics of PSMA in vivo. [68Ga]Ga-TWS02 showed high binding affinity to PSMA, excellent pharmacokinetic properties and clear imaging of PCa-associated lesions, making it a promising radiotracer for the clinical diagnosis of PCa. Moreover, TWS02 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for PCa treatment without significant side effects. TRIAL REGISTRATION: The clinical evaluation of this study was registered On October 30, 2021 at https://www.chictr.org.cn/ (No: ChiCTR2100052545).


Asunto(s)
Glutamato Carboxipeptidasa II , Tomografía de Emisión de Positrones , Humanos , Masculino , Ratones , Animales , Distribución Tisular , Línea Celular Tumoral , Glutamato Carboxipeptidasa II/metabolismo , Tomografía de Emisión de Positrones/métodos , Trazadores Radiactivos , Radioisótopos de Galio/farmacocinética , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/radioterapia , Antígenos de Superficie/metabolismo , Radiofármacos/farmacocinética , Radiofármacos/química , Radioquímica , Dipéptidos/farmacocinética , Dipéptidos/química , Compuestos Heterocíclicos con 1 Anillo/química , Compuestos Heterocíclicos con 1 Anillo/farmacocinética , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos
17.
Cancer Discov ; 14(4): 669-673, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38571430

RESUMEN

SUMMARY: The field of cancer neuroscience has begun to define the contributions of nerves to cancer initiation and progression; here, we highlight the future directions of basic and translational cancer neuroscience for malignancies arising outside of the central nervous system.


Asunto(s)
Neoplasias , Neurociencias , Humanos , Sistema Nervioso Central , Predicción , Proteómica
18.
Adv Mater ; 36(28): e2313721, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38669677

RESUMEN

Germanium-based monochalcogenides (i.e., GeS and GeSe) with desirable properties are promising candidates for the development of next-generation optoelectronic devices. However, they are still stuck with challenges, such as relatively fixed electronic band structure, unconfigurable optoelectronic characteristics, and difficulty in achieving free-standing growth. Herein, it is demonstrated that two-dimensional (2D) free-standing GeS1-xSex (0 ≤ x ≤ 1) nanoplates can be grown by low-pressure rapid physical vapor deposition (LPRPVD), fulfilling a continuously composition-tunable optical bandgap and electronic band structure. By leveraging the synergistic effect of composition-dependent modulation and free-standing growth, GeS1-xSex-based optoelectronic devices exhibit significantly configurable hole mobility from 6.22 × 10-4 to 1.24 cm2V-1s⁻1 and tunable responsivity from 8.6 to 311 A W-1 (635 nm), as x varies from 0 to 1. Furthermore, the polarimetric sensitivity can be tailored from 4.3 (GeS0.29Se0.71) to 1.8 (GeSe) benefiting from alloy engineering. Finally, the tailored imaging capability is also demonstrated to show the application potential of GeS1-xSex alloy nanoplates. This work broadens the functionality of conventional binary materials and motivates the development of tailored polarimetric optoelectronic devices.

19.
Front Neurol ; 15: 1367801, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38566851

RESUMEN

Objective: To explore the construction and application in the practice of green channel in No. 971 Naval Hospital of PLA (No. 971 Hospital mode) for the treatment of acute ischemic stroke (AIS). Methods: This retrospective study involved a cohort of 694 suspected stroke patients from December 2022 to November 2023 undergoing emergency treatment for stroke at our institution. Among them, 483 patients were treated with standard green channel (the control group), and 211 patients adopted the No. 971 Hospital mode for treatment (the study group). The biggest difference between the two groups was that the treatment process started before admission. We compared the effectiveness of the emergency treatment between the two groups and the thrombolysis treatment. Results: Compared with control group, the accuracy rate of determining stroke and the rate of thrombolysis were significantly higher (p = 0.002, 0.039) and the door to doctor arrival time (DAT) and the door to CT scan time (DCT) of the study group was significantly shorter (all p < 0.001). There were 49 patients (10.1%) and 33 patients (15.6%) from the control group and study group receiving thrombolysis, respectively. The DAT, DCT, imaging to needle time (INT), and door to needle time (DNT) of patients receiving thrombolysis in the study group were significantly shorter than that in the control group (all p < 0.01). The NIHSS in the study group after the thrombolysis was lower than that in the control group (p = 0.042). Conclusion: No. 971 Hospital model can effectively shorten DAT, DCT, INT, and DNT, and improve the effectiveness of thrombolysis and prognoses of AIS patients.

20.
Food Chem X ; 22: 101263, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38465331

RESUMEN

The milk proteins from samples of 13 different animals were identified utilizing 4D-Label-Free proteomics technology, leading to the identification of a substantial number of proteins. Among the various samples, Chinese people (CHP) milk proteins exhibited the highest count, with 1149 distinct proteins. Simultaneously, we identified common proteins present in these animal milk. It's notable presence in goat milk contributes to enhancing infant infection resistance, showcasing the beneficial role of lactoperoxidase. Galectin-3 binding protein (Gal-3BP) and tetraspanin in human milk are significantly higher than those in other animals, which determine the prominent antiviral effect of human milk and the important processes related to cell transduction. Furthermore, human milk, camel milk, goat milk and sheep milk proved to be rich sources of milk fat globule membrane (MFGM) proteins. The insights obtained from this study can serve as a foundational framework for exploring the role of different animal milk proteins in disease treatment and the composition of infant formula.

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