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1.
Fish Shellfish Immunol ; 149: 109560, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615702

RESUMO

The JAK (Janus kinase)-STAT (Signal transducer and activator of transcription) is a well-known functional signaling pathway that plays a key role in several important biological activities such as apoptosis, cell proliferation, differentiation, and immunity. However, limited studies have explored the functions of STAT genes in invertebrates. In the present study, the gene sequences of two STAT genes from the Pacific oyster (Crassostrea gigas), termed CgSTAT-Like-1 (CgSTAT-L1) and CgSTAT-Like-2 (CgSTAT-L2), were obtained using polymerase chain reaction (PCR) amplification and cloning. Multiple sequence comparisons revealed that the sequences of crucial domains of these proteins were conserved, and the similarity with the protein sequence of other molluscan STAT is close to 90 %. The phylogenetic analyses indicated that CgSTAT-L1 and CgSTAT-L2 are novel members of the mollusk STAT family. Quantitative real-time PCR results implied that CgSTAT-L1 and CgSTAT-L2 mRNA expression was found in all tissues, and significantly induced after challenge with lipopolysaccharide (LPS), peptidoglycan (PGN), or poly(I:C). After that, dual-luciferase reporter assays denoted that overexpression of CgSTAT-L1 and CgSTAT-L2 significantly activated the NF-κB signaling, and, interestingly, the overexpressed CgSTAT proteins potentiated LPS-induced NF-κB activation. These results contributed a preliminary analysis of the immune-related function of STAT genes in oysters, laying the foundation for deeper understanding of the function of invertebrate STAT genes.

2.
Analyst ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623605

RESUMO

Surface-enhanced Raman spectroscopy (SERS) has emerged as an indispensable analytical tool in biomolecular research, providing unmatched sensitivity critical for the elucidation of biomolecular structures. This review presents a thorough examination of SERS, outlining its fundamental principles, cataloging its varied applications within the biomolecular sphere, and contemplating its future developmental trajectories. We begin with a detailed analysis of SERS's mechanistic principles, emphasizing both the phenomena of surface enhancement and the complexities inherent in Raman scattering spectroscopy. Subsequently, we delve into the pivotal role of SERS in the structural analysis of diverse biomolecules, including proteins, nucleic acids, lipids, carbohydrates, and biochromes. The remarkable capabilities of SERS extend beyond mere detection, offering profound insights into biomolecular configurations and interactions, thereby enriching our comprehension of intricate biological processes. This review also sheds light on the application of SERS in real-time monitoring of various bio-relevant compounds, from enzymes and coenzymes to metal ion-chelate complexes and cellular organelles, thereby providing a holistic view and empowering researchers to unravel the complexities of biological systems. We also address the current challenges faced by SERS, such as enhancing sensitivity and resolution, developing stable and reproducible substrates, and conducting thorough analyses in complex biological matrices. Nonetheless, the continual advancements in nanotechnology and spectroscopy solidify the standing of SERS as a formidable force in biomolecular research. In conclusion, the versatility and robustness of SERS not only deepen our understanding of biomolecular intricacies but also pave the way for significant developments in medical research, therapeutic innovation, and diagnostic approaches.

3.
J Colloid Interface Sci ; 667: 111-118, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38626654

RESUMO

Due to the rapid increase in the number of spent lithium-ion batteries, there has been a growing interest in the recovery of degraded graphite. In this work, a rapid thermal shock (RTS) strategy is proposed to regenerate spent graphite for use in lithium-ion batteries. The results of structural and morphological characterization demonstrate that the graphite is well regenerated by the RTS process. Additionally, an amorphous carbon layer forms and coats onto the surface of the graphite, contributing to excellent rate performance. The regenerated graphite (RG-1000) displays excellent rate performance, with capacities of 413 mAh g-1 at 50 mA g-1 and 102.1 mAh g-1 at 1000 mA g-1, respectively. Furthermore, it demonstrates long-term cycle stability, maintaining a capacity of 80 mAh g-1 at 1000 mA g-1 with a capacity retention of 78.4 % after 600 cycles. This RTS method enables rapid and efficient regeneration of spent graphite anodes for lithium-ion batteries, providing a facile and environmentally friendly strategy for their direct regeneration.

4.
Acta Pharm Sin B ; 14(4): 1878-1891, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572115

RESUMO

Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.

5.
Toxicol Sci ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38603619

RESUMO

Organophosphate esters (OPEs), used as flame retardants and plasticizers, are present ubiquitously in the environment. Previous studies suggest that exposure to OPEs is detrimental to female fertility in humans. However, no experimental information is available on the effects of OPE mixtures on ovarian granulosa cells, which play essential roles in female reproduction. We used high-content imaging to investigate the effects of environmentally relevant OPE mixtures on KGN human granulosa cell phenotypes. Perturbations to steroidogenesis were assessed using ELISA and qRT-PCR. A high-throughput transcriptomic approach, TempO-Seq™, was used to identify transcriptional changes in a targeted panel of genes. Effects on lipid homeostasis were explored using a cholesterol assay and global lipidomic profiling. OPE mixtures altered multiple phenotypic features of KGN cells, with triaryl OPEs in the mixture showing higher potencies than other mixture components. The mixtures increased basal production of steroid hormones; this was mediated by significant changes in the expression of critical transcripts involved in steroidogenesis. Further, the total-OPE mixture disrupted cholesterol homeostasis and the composition of intracellular lipid droplets. Exposure to complex mixtures of OPEs, similar to those found in house dust, may adversely affect female reproductive health by altering a multitude of phenotypic and functional endpoints in granulosa cells. This study provides novel insights into the mechanisms of actions underlying the toxicity induced by OPEs and highlights the need to examine the effects of human relevant chemical mixtures.

6.
J Colloid Interface Sci ; 666: 346-354, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38603877

RESUMO

The unique electronic and crystal structures of rare earth metals (RE) offer promising opportunities for enhancing the hydrogen evolution reaction (HER) properties of materials. In this work, a series of RE (Sm, Nd, Pr and Ho)-doped Rh@NSPC (NSPC stands for N, S co-doped porous carbon nanosheets) with sizes less than 2 nm are prepared, utilizing a simple, rapid and solvent-free joule-heat pyrolysis method for the first time. The optimized Sm-Rh@NSPC achieves HER performance. The high-catalytic performance and stability of Sm-Rh@NSPC are attributed to the synergistic electronic interactions between Sm and Rh clusters, leading to an increase in the electron cloud density of Rh, which promotes the adsorption of H+, the dissociation of Rh-H bonds and the release of H2. Notably, the overpotential of the Sm-Rh@NSPC catalyst is a mere 18.1 mV at current density of 10 mAcm-2, with a Tafel slope of only 15.2 mV dec-1. Furthermore, it exhibits stable operation in a 1.0 M KOH electrolyte at 10 mA cm-2 for more than 100 h. This study provides new insights into the synthesis of composite RE hybrid cluster nanocatalysts and their RE-enhanced electrocatalytic performance. It also introduces fresh perspectives for the development of efficient electrocatalysts.

7.
Am J Surg Pathol ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38595297

RESUMO

A recent study described a rare subtype of tuberous sclerosis complex (TSC)-mutated renal cell carcinoma primarily characterized by Xanthomatous giant cell morphology. Only 2 cases in young individuals have been reported so far, making the correct diagnosis challenging from a pathological perspective. It remains unknown whether this tumor represents an independent subtype or belongs to other TSC-mutated tumors. We conducted a clinicopathologic evaluation and immunohistochemical profiling of 5 cases of Xanthomatous Giant Cell Renal Cell Carcinoma (XGC RCC) with confirmed TSC2 mutations through targeted DNA sequencing. In addition, we analyzed transcriptomic profiles using RNA-seq for the following samples: XGC RCC, Low-grade Oncocytic tumors (LOT), High-grade Oncocytic tumors/Eosinophilic Vacuolar Tumors (HOT/EVT), Eosinophilic Solid and Cystic Renal Cell Carcinomas (ESC RCC), Chromophobe cell Renal Cell Carcinomas (ChRCC), Renal Oncocytomas (RO), clear cell Renal Cell Carcinomas (ccRCC), and normal renal tissues. There were 2 female and 3 male patients, aged 22 to 58 years, who underwent radical nephrectomy for tumor removal. The tumor sizes ranged from 4.7 to 9.5 cm in diameter. These tumors exhibited ill-defined boundaries, showed an expansive growth pattern, and featured distinctive tumor giant cells with abundant eosinophilic to Xanthomatous cytoplasm and prominent nucleoli. All tumors had low Ki-67 proliferation indices (<1%) and demonstrated immune reactivity for CD10, PAX8, CK20, CathepsinK, and GPNMB. Next-generation sequencing confirmed TSC2 mutations in all cases. RNA sequencing-based clustering indicated a close similarity between the tumor and ESC RCC. One patient (1/5) died of an accident 63 months later, while the remaining patients (4/5) were alive without tumor recurrences or metastases at the time of analysis, with a mean follow-up duration of 43.4 months. Our research supports the concept that Xanthomatous giant cell renal cell carcinoma (XGC RCC) shares clinicopathological and molecular characteristics with ESC RCC and shows a relatively positive prognosis, providing further support for a close morphologic spectrum between the two. We propose considering XGC RCC as a distinct subtype of ESC RCC.

8.
J Agric Food Chem ; 72(14): 8269-8283, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38557049

RESUMO

Many species of the Urticaceae family are important cultivated fiber plants that are known for their economic and industrial values. However, their secondary metabolite profiles and associated biosynthetic mechanisms have not been well-studied. Using Laportea bulbifera as a model, we conducted widely targeted metabolomics, which revealed 523 secondary metabolites, including a unique accumulation of flavonol glycosides in bulblet. Through full-length transcriptomic and RNA-seq analyses, the related genes in the flavonoid biosynthesis pathway were identified. Finally, weighted gene correlation network analysis and functional characterization revealed four LbUGTs, including LbUGT78AE1, LbUGT72CT1, LbUGT71BX1, and LbUGT71BX2, can catalyze the glycosylation of flavonol aglycones (kaempferol, myricetin, gossypetin, and quercetagetin) using UDP-Gal and UDP-Glu as the sugar donors. LbUGT78AE1 and LbUGT72CT1 showed substrate promiscuity, whereas LbUGT71BX1 and LbUGT71BX2 exhibited different substrate and sugar donor selectivity. These results provide a genetic resource for studying Laportea in the Urticaceae family, as well as key enzymes responsible for the metabolism of valuable flavonoid glycosides.


Assuntos
Glicosídeos , Urticaceae , Glicosídeos/química , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Flavonoides , Flavonóis , Plantas/metabolismo , Difosfato de Uridina , Perfilação da Expressão Gênica , Urticaceae/metabolismo , Açúcares
9.
Am J Surg Pathol ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501656

RESUMO

ABSTRACT: Renal hemangioblastoma (HB) is a rare subset of HBs arising outside of the central nervous system (CNS), with its molecular drivers remaining entirely unknown. There were no significant alterations detected in previous studies, including von Hippel-Lindau gene alterations, which are commonly associated with CNS-HB. This study aimed to determine the real molecular identity of renal HB and better understand its relationship with CNS-HB. A cohort of 10 renal HBs was submitted for next-generation sequencing technology. As a control, 5 classic CNS-HBs were similarly analyzed. Based on the molecular results, glycoprotein nonmetastatic B (GPNMB) immunohistochemistry was further performed in the cases of renal HB and CNS-HB. Mutational analysis demonstrated that all 10 renal HBs harbored somatic mutations in tuberous sclerosis complex 1 (TSC1, 5 cases), TSC2 (3 cases), and mammalian target of rapamycin (2 cases), with the majority classified as pathogenic or likely pathogenic. The CNS-HB cohort uniformly demonstrated somatic mutations in the von Hippel-Lindau gene. GPNMB was strong and diffuse in all 10 renal HBs and completely negative in CNS-HBs, reinforcing the molecular findings. Our study reveals a specific molecular hallmark in renal HB, characterized by recurrent TSC/mammalian target of rapamycin mutations, which defines it as a unique entity distinct from CNS-HB. This molecular finding potentially expands the therapeutic options for patients with renal HB. GPNMB can be considered for inclusion in immunohistochemical panels to improve renal HB identification.

10.
Food Chem ; 448: 139126, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38555693

RESUMO

Uncontrolled antibacterial, insufficient barrier and low strength are the bottlenecks of food packaging applications. Herein, Ta4C3Tx nanosheet as a template was used to prepare Ta4C3Tx immobilized silver nanoparticles (Ta4C3Tx-AgNPs), which was compounded with nanocellulose to obtain high-strength and high barrier controllable bactericidal nanocellulose-based bioplastic packaging (CTa-Ag). The results indicated that due to the hydrogen bonding between nanocellulose and Ta4C3Tx, the bridging effect of QCS (quaternized chitosan) and the filling of Ta4C3Tx-AgNPs, the CTa-Ag had tightly stacked microstructure, which endowed them with excellent mechanical properties (4.0 GPa), ultra-low oxygen permeability (0.009 cm3/m2·d·atm) and stable photothermal conversion efficiency. Importantly, the packaging exhibits the ability to control the release of antibacterial active ingredients. Moreover, the synergistic effects of controllable release of nano active factors, photothermal and photocatalysis in CTa-Ag gave it long-lasting antibacterial properties. This study brings new insights into the design and manufacture of multifunctional, controllable and long-lasting antibacterial bioplastic food packaging.

11.
J Glob Health ; 14: 04048, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38483439

RESUMO

Background: Although tummy time is recommended as a form of physical activity for non-movable infants worldwide, little is known regarding the current status of tummy time practices among Chinese infants. Early childhood education (ECE) institutions provide children with rich learning experiences; however, tummy time practices among infants in these ECE institutions were unclear. This study aimed to investigate the status of tummy time among infants within the context of ECE institutions. Methods: We conducted a cross-sectional survey with primary caregivers of infants aged 0-11 months across 31 provinces of China from 1 March to 30 April 2023. To recruit participants, we collaborated with Gymboree Play & Music, an ECE institution with over 500 centres in nearly 200 cities in urban China. Our survey instrument was developed based on the World Health Organization (WHO) guidelines and literature to collect data on infants' tummy time practices, caregivers' tummy time knowledge and information sources. We used self-administered questionnaires through WeChat, in which participants scanned a quick response (QR) code to complete the questionnaire. Results: We included 1040 infants and their primary caregivers, with 504 infants aged 0-5 and 536 infants aged 6-11 months old. Less than half of infants (48.2%) started tummy time in the neonatal period, with 20.5% starting within two weeks after birth. Only 27.2% of infants engaged in at least 30 minutes of tummy time during the last 24 hours, with infants aged 0-5 months significantly lower than those aged 6-11 months (21.6 vs 32.5%, P < 0.0001). No significant difference was found between attending ECE class and non-attending ECE class groups for the proportion of infants with tummy time ≥30 minutes per day (28.9 vs 23.4%, P = 0.0625); however, infants aged 0-5 months in the attending group engaged in longer duration of tummy time than those in the non-attending group (P = 0.0005). The compliance with the tummy time guidelines in infants receiving long-nurturing care was significantly higher than those receiving short-nurturing care (30.4 vs 22.1%, P = 0.0036). Only 42.7% of caregivers knew that at least 30 minutes daily tummy time was necessary for infant, and more primary caregivers in the attending group knew that, compared to the non-attending group (45.3 vs 36.8%, P = 0.0098). Conclusions: The current status of infants' tummy time practices and caregivers' knowledge are generally suboptimal within the context of ECE institutions in urban China. Longer nurturing time contributes to higher compliance with tummy time guidelines. Effectively promoting tummy time practices through multiple channels in China is crucial.


Assuntos
Povo Asiático , Exercício Físico , Criança , Lactente , Recém-Nascido , Humanos , Pré-Escolar , Estudos Transversais , China , Cidades
12.
Comput Struct Biotechnol J ; 23: 1106-1116, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38495554

RESUMO

Flavonoid glycosides are widespread in plants, and are of great interest owing to their diverse biological activities and effectiveness in preventing chronic diseases. Periploca forrestii, a renowned medicinal plant of the Apocynaceae family, contains diverse flavonoid glycosides and is clinically used to treat rheumatoid arthritis and traumatic injuries. However, the mechanisms underlying the biosynthesis of these flavonoid glycosides have not yet been elucidated. In this study, we used widely targeted metabolomics and full-length transcriptome sequencing to identify flavonoid diversity and biosynthetic genes in P. forrestii. A total of 120 flavonoid glycosides, including 21 C-, 96 O-, and 3 C/O-glycosides, were identified and annotated. Based on 24,123 full-length coding sequences, 99 uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) were identified and classified into 14 groups. Biochemical assays revealed that four UGTs exhibited O-glycosyltransferase activity toward apigenin and luteolin. Among them, PfUGT74B4 and PfUGT92A8 were highly promiscuous and exhibited multisite O-glycosylation or consecutive glycosylation activities toward various flavonoid aglycones. These four glycosyltransferases may significantly contribute to the diversity of flavonoid glycosides in P. forrestii. Our findings provide a valuable genetic resource for further studies on P. forrestii and insights into the metabolic engineering of bioactive flavonoid glycosides.

13.
Huan Jing Ke Xue ; 45(2): 1026-1037, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471940

RESUMO

Quantifying the risk of soil heavy metal sources can identify the main pollution sources. It can provide a scientific basis for reducing the ecological and human health risks of soil heavy metals. Taking the shallow soil in a Pb-Zn mine watershed in northern Guangxi as a research object, ecological and human health risk assessments were conducted using potential ecological risk assessment (RI) and human health risk assessment (HRA), and the source apportionment of soil heavy metals was completed using the absolute principal component-multiple linear regression receptor (APCS-MLR) model and random forest (RF) model. Then, a combined risk assessment model, consisting of RI, HRA, and APCS-MLR, was used to quantify the risk of soil heavy metal sources. The results showed that the contents of Pb, Zn, Cu, and Cd exceeded the environmental screening values for agricultural land with mean values of 342.77, 693.34, 61.27, and 3.08 mg·kg-1, respectively, and there was a certain degree of contamination. Pb, Cr, and As were the main health risk impact factors, with higher health risks for children than for adults. Three sources were identified: mining activities (Source Ⅰ), soil parent material sources and original formation (Source Ⅱ), and unknown sources. Pb, Zn, Cu, and Cd were mainly derived from Source Ⅰ, and Cr and As were controlled by unknown sources and Source Ⅱ. The source risk assessment results of soil heavy metals indicated that the potential ecological risk and non-carcinogenic risk were mainly from Source Ⅰ and Source Ⅱ, and carcinogenic risk was mainly from unknown sources. The unknown sources had a high proportion in source apportionment and risk assessment, and should be further researched to provide scientific basis for soil heavy metal control. The combined risk assessment model based on source analysis, focusing on the risk characteristics of different sources, can accurately identify high-risk pollution sources. It is a more reasonable and reliable risk assessment method.


Assuntos
Metais Pesados , Poluentes do Solo , Adulto , Criança , Humanos , Solo , Monitoramento Ambiental , Cádmio , Chumbo , Poluentes do Solo/análise , China , Medição de Risco , Metais Pesados/análise
14.
Int J Surg ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38506734

RESUMO

BACKGROUND: Addressing segmental bone defects remains a complex task in orthopedics, and recent advancements have led to the development of novel drugs to enhance the bone regeneration. However, long-term oral administration can lead to malnutrition and poor patient compliance. Scaffolds loaded with medication are extensively employed to facilitate the restoration of bone defects. METHODS: Inspired by the local use of total flavonoids of Rhizoma Drynariae (TFRD) in the treatment of fracture, a novel 3D-printed HA/CMCS/PDA/TFRD scaffold with anti-infection, biodegradable and induced angiogenesis was designed, and to explore its preclinical value in segmental bone defect of tibia. RESULTS: The scaffold exhibited good degradation and drug release performance. In vitro, the scaffold extract promoted osteogenesis by enhancing bone-related gene/protein expression and mineral deposition in BMSCs. It also stimulated endothelial cell migration and promoted angiogenesis through the upregulation of specific genes and proteins associated with cell migration and tube formation. This may be attributed to the activation of the PI3k/AKT/HIF-1α pathway, facilitating the processes of osteogenesis and angiogenesis. Furthermore, the HA/CMCS/PDA/TFRD scaffold was demonstrated to alleviate infection, enhance angiogenesis, promote bone regeneration, and increase the maximum failure force of new formed bone in a rat model of segmental bone defects. CONCLUSION: Porous scaffolds loaded with TFRD can reduce infection, be biodegradable, and induce angiogenesis, presenting a novel approach for addressing tibial segmental bone defects.

15.
Environ Res ; 251(Pt 2): 118688, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38493855

RESUMO

The widespread usage of quaternary ammonium compounds (QACs) as disinfectants during the COVID-19 pandemic poses significant environmental risks, such as toxicity to organisms and the emergence of superbugs. In this study, different inorganic salts (NaCl, KCl, CaCl2, MgCl2) were used to induce endophytes LSE01 isolated from hyperaccumulating plants. After five generations of cultivation under 80 g/L NaCl, the minimum inhibitory concentration (MIC) of LSE01 to QACs increased by about 3-fold, while its degradation extent increased from 8% to 84% for C12BDMA-Cl and 5%-89% for C14BDMA-Cl. Transmission electron microscopy (TEM) and three-dimensional fluorescence spectra indicated that the cells induced by high concentration of salt caused plasmolysis and secreted more bound extracellular polymeric substances (B-EPS); these changes are likely to be an important reason for the observed increased resistance and enhanced degradation extent of LSE01 to QACs. Our findings suggest that salt-induction could be an effective way to enhance the resistance and removal of toxic organic pollutants by functional microorganisms.

16.
Elife ; 132024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38450720

RESUMO

Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions. Due to the diversity of synapses in different brain areas, circuits and neurons, although many synaptic CAMs, such as Neurexins (NRXNs), Neuroligins (NLGNs), Synaptic cell adhesion molecules (SynCAMs), Leucine-rich-repeat transmembrane neuronal proteins (LRRTMs), and SLIT and NTRK-like protein (SLITRKs) have been identified as synaptogenic molecules, how these molecules determine specific synapse formation and whether other molecules driving synapse formation remain undiscovered are unclear. Here, to provide a tool for synapse labeling and synaptic CAMs screening by artificial synapse formation (ASF) assay, we generated synaptotagmin-1-tdTomato (Syt1-tdTomato) transgenic mice by inserting the tdTomato-fused synaptotagmin-1 coding sequence into the genome of C57BL/6J mice. In the brain of Syt1-tdTomato transgenic mice, the tdTomato-fused synaptotagmin-1 (SYT1-tdTomato) signals were widely observed in different areas and overlapped with synapsin-1, a widely-used synaptic marker. In the olfactory bulb, the SYT1-tdTomato signals are highly enriched in the glomerulus. In the cultured hippocampal neurons, the SYT1-tdTomato signals showed colocalization with several synaptic markers. Compared to the wild-type (WT) mouse neurons, cultured hippocampal neurons from Syt1-tdTomato transgenic mice presented normal synaptic neurotransmission. In ASF assays, neurons from Syt1-tdTomato transgenic mice could form synaptic connections with HEK293T cells expressing NLGN2, LRRTM2, and SLITRK2 without immunostaining. Therefore, our work suggested that the Syt1-tdTomato transgenic mice with the ability to label synapses by tdTomato, and it will be a convenient tool for screening synaptogenic molecules.


Assuntos
Moléculas de Adesão Celular , 60598 , Sinapses , Humanos , Camundongos , Animais , Camundongos Transgênicos , Células HEK293 , Camundongos Endogâmicos C57BL , Moléculas de Adesão Celular/metabolismo , Sinapses/fisiologia , Sinaptotagminas/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo
17.
Epidemiol Infect ; 152: e44, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477024

RESUMO

Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children's Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1-4 years exhibited higher risk of PTB and TB meningitis, and children aged 5-12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.


Assuntos
Tuberculose Meníngea , Tuberculose Pulmonar , Humanos , Criança , Feminino , Pré-Escolar , Tuberculose Meníngea/epidemiologia , Pequim/epidemiologia , Estudos Retrospectivos , Tuberculose Pulmonar/epidemiologia , China/epidemiologia
18.
Ecotoxicol Environ Saf ; 274: 116236, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38503101

RESUMO

Ambient ultraviolet radiation (UVB) from solar and artificial light presents serious environmental risks to aquatic ecosystems. The Pacific oyster, Crassostrea gigas, perceives changes in the external environment primarily through its mantle tissue, which contains many nerve fibers and tentacles. Changes within the mantles can typically illustrate the injury of ambient UVB. In this study, a comprehensive analysis of phenotypic, behavioral, and physiological changes demonstrated that extreme UVB radiation (10 W/m²) directly suppressed the behavioral activities of C. gigas. Conversely, under ambient UVB radiation (5 W/m²), various physiological processes exhibited significant alterations in C. gigas, despite the behavior remaining relatively unaffected. Using mathematical model analysis, the integrated analysis of the full-length transcriptome, proteome, and metabolome showed that ambient UVB significantly affected the metabolic processes (saccharide, lipid, and protein metabolism) and cellular biology processes (autophagy, apoptosis, oxidative stress) of the C. gigas mantle. Subsequently, using Procrustes analysis and Pearson correlation analysis, the association between multi-omics data and physiological changes, as well as their biomarkers, revealed the effect of UVB on three crucial biological processes: activation of autophagy signaling (key factors: Ca2+, LC3B, BECN1, caspase-7), response to oxidative stress (reactive oxygen species, heat shock 70, cytochrome c oxidase), and recalibration of energy metabolism (saccharide, succinic acid, translation initiation factor IF-2). These findings offer a fresh perspective on the integration of multi-data from non-model animals in ambient UVB risk assessment.


Assuntos
Crassostrea , Animais , Crassostrea/metabolismo , Raios Ultravioleta/efeitos adversos , Ecossistema , Resposta ao Choque Térmico , Transcriptoma
19.
Angew Chem Int Ed Engl ; : e202401957, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526332

RESUMO

Here, we build a tunable multipolar conjugated polymer framework platform via pore wall chemistry to probe the role of electronic structure engineering in improving the Li+ conduction by theoretical studies. Guided by theoretical prediction, we develop a new cyano-vinylene-linked multipolar polymer framework namely CNF-COF, acting as efficient ion sieves to modify polymer electrolytes for long-lifespan all-solid-state (ASS) Li metal batteries. The cyano and fluorine groups dual-decoration in CNF-COF favorably regulates the electronic structure via multipolar donor-acceptor electronic effects to afford proper energy band structure and abundant electron-rich sites for enhanced anti-oxidative ability, facilitated ion-pair dissociation and suppressed anion movements. Thus, the CNF-COF incorporation into poly (ethylene oxide) (PEO) electrolytes not only renders selective rapid Li+ conduction but also facilitates the Li dendrite suppression. Specifically, the constructed composite electrolyte with an ultralow CNF-COF content of only 0.5 wt% is endowed with a high ionic conductivity of 0.634 mS cm-1 at 60 °C and a large Li+ transference number of 0.81. As such, the Li symmetric cell delivers stable Li plating/stripping over 1400 h. Impressively, t he assembled ASS Li battery under 60 °C allows for stable cycling over 2000 cycles at 1 C and over 1000 cycles even at 2 C.

20.
Br J Cancer ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461171

RESUMO

BACKGROUND: Tumor cells continue to evolve the metastatic potential in response to signals provided by the external microenvironment during metastasis. Platelets closely interact with tumor cells during hematogenous metastasis and facilitate tumor development. However, the molecular mechanisms underlying this process are not fully understood. METHODS: RNA-sequencing was performed to screen differentially expressed genes mediated by platelets. The effects of platelet and CD39 on tumor metastasis were determined by experimental metastasis models with WT, NCG and CD39-/- mice. RESULTS: RNA-sequencing results showed that platelets significantly up-regulated CD39 expression in tumor cells. CD39 is a novel immune checkpoint molecule and a key driver of immunosuppression. Our data provided evidence that the expression of CD39 was enhanced by platelets in a platelet-tumor cell contact dependent manner. Although the role of CD39 expressed by immune cells is well established, the effect of CD39 expressed by tumor cells on tumor cell behavior, anti-tumor immunity and tumor metastasis is unclear. We found that CD39 promoted tumor cell invasion, but had no effect on proliferation and migration. Notably, we showed that the ability of platelets to prime tumor cells for metastasis depends on CD39 in the experimental tumor metastasis model. CD39 silencing resulted in fewer experimental metastasis formation, and this anti-metastasis effect was significantly reduced in platelet-depleted mice. Furthermore, overexpression of CD39 in tumor cells promoted metastasis. In order to eliminate the effect of CD39 expressed in cells other than tumor cells, we detected tumor metastasis in CD39-/- mice and obtained similar results. Moreover, overexpression of CD39 in tumor cells inhibited antitumor immunity. Finally, the data from human samples also supported our findings. CONCLUSIONS: Our study shows that direct contact with platelets induces CD39 expression in tumor cells, leading to immune suppression and promotion of metastasis.

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