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1.
Anal Methods ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695127

RESUMO

The CRISPR-Cas system has been found to be extremely sensitive and there is an urgent demand to extend its potential in bioassays. Herein, we developed a novel nanobiosensor to detect the human papillomavirus 16 genes (HPV-16 DNA), which is triggered by CRISPR-Cas12a to amplify the fluorescence signal by metal-enhanced fluorescence (CAMEF). Along with the changing of the fluorescence signal, the aggregation of the substrate of MEF also leads to a change in the color of the mixture solution, enabling dual signal detection with the fluorescence and the naked eye. Furthermore, the designed CAMEF probe was verified to detect the HPV-16 DNA accurately and reliably in biological samples. Triggered by the CRISPR system, the designed CAMEF probe allows quantitative detection of the HPV-16 DNA in the wide range of 10-500 pM. Owing to the MEF, the fluorescence signal of the CAMEF probe was significantly amplified with the detection limit as low as 1 pM. Besides, we can determine the concentration of HPV-16 DNA simply by the naked eye, which also drastically reduces the possibility of false-positive signals. Theoretically, the target ssDNA could be any strand of DNA obtained by designing the crRNA sequence in the CRISPR-Cas system. We believe that the designed CAMEF sensor can present a reliable approach for the accurate detection of low amounts of target ssDNA in complex biological samples.

2.
J Anim Sci ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713167

RESUMO

Follicular fluid meiosis-activating sterol (FF-MAS) is a small molecule compound found in follicular fluid, named for its ability to induce oocyte resumption of meiosis. Granulosa cells (GCs) within the follicle are typically located in a hypoxic environment under physiologic conditions due to limited vascular distribution. Previous research suggests that hypoxia-induced cell cycle arrest and apoptosis in GCs may be crucial triggering factors in porcine follicular atresia. However, the impact of FF-MAS on GCs within follicles has not been explored so far. In this study, we uncovered a novel role of FF-MAS in facilitating GC survival under hypoxic conditions by inhibiting STAT4 expression. We found that STAT4 expression was upregulated in porcine GCs exposed to 1% O2. Both gain and loss of function assays confirmed that STAT4 was required for cell apoptosis under hypoxia conditions, and that the GC apoptosis caused by hypoxia was markedly attenuated following FF-MAS treatment through inhibition of STAT4 expression. Correlation analysis in vivo revealed that GC apoptosis was associated with increased STAT4 expression, while the FF-MAS content in follicular fluid was negatively correlated with STAT4 mRNA levels and cell apoptosis. These findings elucidate a novel role of FF-MAS-mediated protection of GCs by inhibiting STAT4 expression under hypoxia, which might contribute to the mechanistic understanding of follicular development.

3.
Heliyon ; 10(9): e29895, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38694126

RESUMO

While immersive shopping has injected new vitality into China's e-commerce, it has also resulted in consumers' over-reliance on online shopping. Psychological studies have linked online shopping addiction with depression, but business practices challenge this conclusion. This study, grounded in addiction theory, developed a theoretical model, and conducted an online survey with 214 live-streaming shoppers using structural equation modeling for validation. The primary focus was on determining whether consumers truly become addicted to online shopping in the four stages of the addiction model. The study unveils the process of consumers becoming addicted to online shopping. It explores the moderating role of perceived risk in the relationship between utilitarian and hedonic purchases and online shopping addiction. The findings suggest that through tactics such as traffic promotion, traffic trapping, anchor feature utilization, and incorporation of consumer aesthetics, merchants may induce utilitarian and hedonic purchases, leading to addiction to live-streaming shopping among consumers. Furthermore, perceived risk significantly and negatively moderates the relationship between utilitarian purchases and online shopping addiction. Our research indicates that merchants intentionally create external stimuli, enticing consumers to indulge in online shopping, suggesting that online shopping addiction is not merely a simple psychological state but may be influenced by external factors. This study provides novel insights into the phenomenon of online shopping addiction while offering valuable recommendations for consumers seeking to avoid succumbing to its allure.

4.
Diagnostics (Basel) ; 14(7)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38611671

RESUMO

(1) Background: Transsphenoidal pituitary surgery can be conducted via microscopic or endoscopic approaches, and there has been a growing preference for the latter in recent years. However, the occurrence of rare complications such as postoperative sinusitis remains inadequately documented in the existing literature. (2) Methods: To address this gap, we conducted a comprehensive retrospective analysis of medical records spanning from 2018 to 2023, focusing on patients who underwent transsphenoidal surgery for pituitary neuroendocrine tumors (formerly called pituitary adenoma). Our study encompassed detailed evaluations of pituitary function and MRI imaging pre- and postsurgery, supplemented by transnasal endoscopic follow-up assessments at the otolaryngology outpatient department. Risk factors for sinusitis were compared using univariate and multivariate logistic regression analyses. (3) Results: Out of the 203 patients included in our analysis, a subset of 17 individuals developed isolated sphenoid sinusitis within three months postoperation. Further scrutiny of the data revealed significant associations between certain factors and the occurrence of postoperative sphenoid sinusitis. Specifically, the classification of the primary tumor emerged as a notable risk factor, with patients exhibiting nonfunctioning pituitary neuroendocrine tumors with 3.71 times the odds of developing sinusitis compared to other tumor types. Additionally, postoperative cortisol levels demonstrated a significant inverse relationship, with lower cortisol levels correlating with an increased risk of sphenoid sinusitis postsurgery. (4) Conclusions: In conclusion, our findings underscore the importance of considering tumor classification and postoperative cortisol levels as potential predictors of postoperative sinusitis in patients undergoing transsphenoidal endoscopic pituitary surgery. These insights offer valuable guidance for clinicians in identifying at-risk individuals and implementing tailored preventive and management strategies to mitigate the occurrence and impact of sinusitis complications in this patient population.

5.
Anal Chem ; 96(18): 7101-7110, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38663376

RESUMO

While DNA amplifier-built nanobiosensors featuring a DNA polymerase-free catalytic hairpin assembly (CHA) reaction have shown promise in fluorescence imaging assays within live biosystems, challenges persist due to unsatisfactory precision stemming from premature activation, insufficient sensitivity arising from low reaction kinetics, and poor biostability caused by endonuclease degradation. In this research, we aim to tackle these issues. One aspect involves inserting an analyte-binding unit with a photoinduced cleavage bond to enable a light-powered notion. By utilizing 808 nm near-infrared (NIR) light-excited upconversion luminescence as the ultraviolet source, we achieve entirely a controllable sensing event during the biodelivery phase. Another aspect refers to confining the CHA reaction within the finite space of a DNA self-assembled nanocage. Besides the accelerated kinetics (up to 10-fold enhancement) resulting from the nucleic acid restriction behavior, the DNA nanocage further provides a 3D rigid skeleton to reinforce enzymatic resistance. After selecting a short noncoding microRNA (miRNA-21) as the modeled low-abundance sensing analyte, we have verified that the innovative NIR light-powered and DNA nanocage-confined CHA nanobiosensor possesses remarkably high sensitivity and specificity. More importantly, our sensing system demonstrates a robust imaging capability for this cancer-related universal biomarker in live cells and tumor-bearing mouse bodies, showcasing its potential applications in disease analysis.


Assuntos
Técnicas Biossensoriais , DNA , Raios Infravermelhos , MicroRNAs , MicroRNAs/análise , Humanos , Técnicas Biossensoriais/métodos , Animais , DNA/química , Camundongos , Imagem Óptica , Nanoestruturas/química
6.
Plant Dis ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679591

RESUMO

Cucumber green mottle mosaic virus (CGMMV) was first discovered on cucumber in the United Kingdom in 1935 (Ainsworth, 1935), and has spread worldwide except to Antarctica (Jones, 2021). Given its extensive damage, it is considered an important pathogen on global cucurbit plants and fruit crops. In China, CGMMV was first reported on pumpkin in Guangxi Province in 2003 (Qin et al., 2005), and occurred on 34 plants species across 23 provinces (Liu et al., 2016). Cynanchum rostellatum is a member of the family Apocynaceae. In July 2021, leaves of C. rostellatum exhibiting virus-like symptoms (yellowing, severe crinkling, deformation) were observed and collected in Liaoning Province, China. Aphids were also observed on the leaves and stems (Fig. S1) of the plants and were collected. Total RNA was extracted from diseased leaves following the CTAB method, followed by the depletion of ribosomal RNAs (rRNA) with TIANSeq rRNA Depletion Kit (Tiangen, China). The RNAs were, then processed into a DNBSEQ LncRNA-Seq library, and sequenced on the MGISEQ-2000 platform at BGI Genomics (Wuhan, China). A total of 106.98 M clean reads were obtained after data filtering using SOAPnuke software (BGI, China). The clean reads were assembled into contigs using CLC Genomics Workbench 11 (Qiagen, USA) and Trinity v2.0.6 (Haas et al., 2013). A contig (4,760 reads, average coverage:73.76) of 6,391 nucleotides was found to share the highest sequence identity (99.83%) with CGMMV isolate GDLZ (MK933286), irrespective of other virus-like contigs related to Polerovirus and Totivirus. Based on the genome of GDLZ isolate, seven specific primers (Table S1) were designed to amplify the full viral genomic sequences using a PrimeScriptTM One-Step RT-PCR Kit. Seven expected amplicons were obtained, cloned, and sequenced. The complete genome was determined to be 6,423 nucleotides (GenBank accession number OR854819) in length and designated as LNMJ isolate. LNMJ shared 96.8%-99.7% nucleotide sequence identities with CGMMV isolates from China. Phylogenetic analysis based on the complete genome sequences showed that LNMJ clustered together with CGMMV isolates hn (GenBank accession number KC851866), GDLZ (GenBank accession number MK933286), and JD8 (GenBank accession number KM873784) from China. The specific primers LM-TJ-3F/3R were designed to determine the virus-symptom association for LNMJ, and all twelve symptomatic C. rostellatum plants collected from fields tested positive for LNMJ. Two out of six randomly selected aphids from the diseased plants also tested positive. To further prove its infectivity, LNMJ was inoculated mechanically onto ten healthy Nicotiana benthamiana plants, and the results indicated a high infection rate of 80% (8/10), at 30 days post-inoculation despite no distinct symptoms observed. To our knowledge, this is the first report of the natural infection of C. rostellatum plants with CGMMV. C. rostellatum is a widespread herb in China (Wei et al., 2019) and more surveys are needed to determine the distribution of CGMMV. The habitats of C. rostellatum span diverse agroecological zones, and thus our study underscores the potential spillover of CGMMV to neighboring crops as a significant risk.

7.
Anal Methods ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683672

RESUMO

Cortisol is a vital glucocorticoid hormone reflecting stress levels and related disease processes. In this study, we report an aptamer-functionalized plasmonic nano-urchin (α-FeOOH@Au-aptamer)-aided cortisol-capturing and surface-enhanced Raman spectroscopy (SERS) analysis approach. The designed α-FeOOH@Au-aptamer exhibits a well-patterned plasma structure, which combines the good SERS enhancement ability of reduced nanogaps between the Au plasma and the hot spot-favored structure of anisotropic tips from α-FeOOH urchins, with the high affinity of the aptamer towards cortisol molecules. The α-FeOOH@Au-aptamer achieved reporter-free SERS quantification for cortisol with good sensitivity (limit of detection <0.28 µmol L-1), robust salt (1.0 mol per L NaCl) and protein (5.0 mg per mL bovine serum protein) tolerance, favorable reproducibility, as well as good reusability. We further demonstrated the good cortisol-capturing ability and SERS efficacy of the α-FeOOH@Au-aptamer profiling in the serum and urine samples. Our approach provides an alternative tool for cortisol analysis and a reference strategy for report-free SERS detection of small molecules.

8.
Nano Lett ; 24(17): 5277-5283, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38624178

RESUMO

As tactile force sensing has become increasingly significant in the field of machine haptics, achieving multidimensional force sensing remains a challenge. We propose a 3D flexible force sensor that consists of an axisymmetric hemispherical protrusion and four equally sized quarter-circle electrodes. By simulating the device using a force and electrical field model, it has been found that the magnitude and direction of the force can be expressed through the voltage relationship of the four electrodes when the magnitude of the shear force remains constant and its direction varies within 0-360°. The experimental results show that a resolution of 15° can be achieved in the range 0-90°. Additionally, we installed the sensor on a robotic hand, enabling it to perceive the magnitude and direction of touch and grasp actions. Based on this, the designed 3D flexible tactile force sensor provides valuable insights for multidimensional force detection and applications.

9.
J Mater Chem B ; 12(18): 4361-4374, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38639047

RESUMO

Repair of large bone defects is one of the clinical problems that have not yet been fully solved. The dynamic balance of bone tissue is regulated by many biological, chemical and physical environmental factors. Simulating the microenvironment of bone tissue in the physiological state through biomimetic materials is an important development direction of tissue engineering in recent years. With the deepening of research, it has been found that when bone tissue is damaged, its surrounding magnetoelectric microenvironment is subsequently destroyed, and providing a magnetoelectric microenvironment in the biomimetic state will be beneficial to promote bone repair. This review describes the piezoelectric effect of natural bone tissue with magnetoelectric stimulation for bone regeneration, provides a detailed account of the historical development of magnetoelectric composites and the current magnetoelectric composites that are most commonly utilized in the field of tissue engineering. Besides, the hypothesized mechanistic pathways through which magnetoelectric composite materials promote bone regeneration are critically examined, including the enhancement of osteogenesis, promotion of cell adhesion and angiogenesis, modulation of bone immunity, and promotion of nerve regeneration.


Assuntos
Regeneração Óssea , Engenharia Tecidual , Humanos , Animais , Osteogênese/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia
10.
Sci Adv ; 10(17): eadn0947, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669338

RESUMO

Organic electrosynthesis in aqueous media is presently hampered by the poor solubility of many organic reactants and thus low purity of liquid products in electrolytes. Using the electrooxidation of benzyl alcohol (BA) as a model reaction, we present a "sandwich-type" organic-solid-water (OSW) system, consisting of BA organic phase, KOH aqueous electrolyte, and porous anodes with Janus-like superwettability. The system allows independent diffusion of BA molecules from the organic phase to electrocatalytic active sites, enabling efficient electrooxidation of high-concentration BA to benzaldehyde (97% Faradaic efficiency at ~180 mA cm-2) with substantially reduced ohmic loss compared to conventional solid-liquid systems. The confined organic-water boundary within the electrode channels suppresses the interdiffusion of molecules and ions into the counterphase, thus preventing the hydration and overoxidation of benzaldehyde during long-term electrocatalysis. As a result, the direct production of high-purity benzaldehyde (91.7%) is achieved in a flow cell, showcasing the effectiveness of electrocatalysis over OSW interfaces for the one-step synthesis of high-purity organic compounds.

11.
Angew Chem Int Ed Engl ; 63(19): e202400122, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38494445

RESUMO

Electrochemical acetylene reduction (EAR) employing Cu catalysts represents an environmentally friendly and cost-effective method for ethylene production and purification. However, Cu-based catalysts encounter product selectivity issues stemming from carbon-carbon coupling and other side reactions. We explored the use of secondary metals to modify Cu-based catalysts and identified Cd decoration as particular effective. Cd decoration demonstrated a high ethylene Faradaic efficiency (FE) of 98.38 % with well-inhibited carbon-carbon coupling reactions (0.06 % for butadiene FE at -0.5 V versus reversible hydrogen electrode) in a 5 vol % acetylene gas feed. Notably, ethylene selectivity of 99.99 % was achieved in the crude ethylene feed during prolonged stability tests. Theoretical calculations revealed that Cd metal accelerates the water dissociation on neighboring Cu surfaces allowing more H* to participate in the acetylene semi-hydrogenation, while increasing the energy barrier for carbon-carbon coupling, thereby contributing to a high ethylene semi-hydrogenation efficiency and significant inhibition of carbon-carbon coupling. This study provides a paradigm for a deeper understanding of secondary metals in regulating the product selectivity of EAR electrocatalysts.

12.
Adv Sci (Weinh) ; 11(17): e2304763, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38429890

RESUMO

Innovative functional electrical stimulation has demonstrated effectiveness in enhancing daily walking and rehabilitating stroke patients with foot drop. However, its lack of precision in stimulating timing, individual adaptivity, and bilateral symmetry, resulted in diminished clinical efficacy. Therefore, a closed-loop wearable device network of intrinsically controlled functional electrical stimulation (CI-FES) system is proposed, which utilizes the personal surface myoelectricity, derived from the intrinsic neuro signal, as the switch to activate/deactivate the stimulation on the affected side. Simultaneously, it decodes the myoelectricity signal of the patient's healthy side to adjust the stimulation intensity, forming an intrinsically controlled loop with the inertial measurement units. With CI-FES assistance, patients' walking ability significantly improved, evidenced by the shift in ankle joint angle mean and variance from 105.53° and 28.84 to 102.81° and 17.71, and the oxyhemoglobin concentration tested by the functional near-infrared spectroscopy. In long-term CI-FES-assisted clinical testing, the discriminability in machine learning classification between patients and healthy individuals gradually decreased from 100% to 92.5%, suggesting a remarkable recovery tendency, further substantiated by performance on the functional movement scales. The developed CI-FES system is crucial for contralateral-hemiplegic stroke recovery, paving the way for future closed-loop stimulation systems in stroke rehabilitation is anticipated.


Assuntos
Terapia por Estimulação Elétrica , Reabilitação do Acidente Vascular Cerebral , Dispositivos Eletrônicos Vestíveis , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Reabilitação do Acidente Vascular Cerebral/instrumentação , Masculino , Pessoa de Meia-Idade , Feminino , Terapia por Estimulação Elétrica/métodos , Terapia por Estimulação Elétrica/instrumentação , Idoso , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Caminhada/fisiologia , Adulto , Desenho de Equipamento , Espectroscopia de Luz Próxima ao Infravermelho/métodos
13.
Elife ; 132024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38390967

RESUMO

Deciphering patterns of connectivity between neurons in the brain is a critical step toward understanding brain function. Imaging-based neuroanatomical tracing identifies area-to-area or sparse neuron-to-neuron connectivity patterns, but with limited throughput. Barcode-based connectomics maps large numbers of single-neuron projections, but remains a challenge for jointly analyzing single-cell transcriptomics. Here, we established a rAAV2-retro barcode-based multiplexed tracing method that simultaneously characterizes the projectome and transcriptome at the single neuron level. We uncovered dedicated and collateral projection patterns of ventromedial prefrontal cortex (vmPFC) neurons to five downstream targets and found that projection-defined vmPFC neurons are molecularly heterogeneous. We identified transcriptional signatures of projection-specific vmPFC neurons, and verified Pou3f1 as a marker gene enriched in neurons projecting to the lateral hypothalamus, denoting a distinct subset with collateral projections to both dorsomedial striatum and lateral hypothalamus. In summary, we have developed a new multiplexed technique whose paired connectome and gene expression data can help reveal organizational principles that form neural circuits and process information.


Assuntos
Neuritos , Neurônios , Neurônios/metabolismo , Encéfalo , Córtex Pré-Frontal , Vias Neurais/fisiologia
14.
Cell Rep ; 43(2): 113756, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38358886

RESUMO

Short-term memory (STM) maintains information during a short delay period. How long-range and local connections interact to support STM encoding remains elusive. Here, we tackle the problem focusing on long-range projections from the medial prefrontal cortex (mPFC) to the anterior agranular insular cortex (aAIC) in head-fixed mice performing an olfactory delayed-response task. Optogenetic and electrophysiological experiments reveal the behavioral importance of the two regions in encoding STM information. Spike-correlogram analysis reveals strong local and cross-region functional coupling (FC) between memory neurons encoding the same information. Optogenetic suppression of mPFC-aAIC projections during the delay period reduces behavioral performance, the proportion of memory neurons, and memory-specific FC within the aAIC, whereas optogenetic excitation enhances all of them. mPFC-aAIC projections also bidirectionally modulate the efficacy of STM-information transfer, measured by the contribution of FC spiking pairs to the memory-coding ability of following neurons. Thus, prefrontal projections modulate insular neurons' functional connectivity and memory-coding ability to support STM.


Assuntos
Córtex Insular , Memória de Curto Prazo , Animais , Camundongos , Citoplasma , Neurônios , Optogenética
15.
Science ; 383(6682): eadj9198, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38300992

RESUMO

Mapping single-neuron projections is essential for understanding brain-wide connectivity and diverse functions of the hippocampus (HIP). Here, we reconstructed 10,100 single-neuron projectomes of mouse HIP and classified 43 projectome subtypes with distinct projection patterns. The number of projection targets and axon-tip distribution depended on the soma location along HIP longitudinal and transverse axes. Many projectome subtypes were enriched in specific HIP subdomains defined by spatial transcriptomic profiles. Furthermore, we delineated comprehensive wiring diagrams for HIP neurons projecting exclusively within the HIP formation (HPF) and for those projecting to both intra- and extra-HPF targets. Bihemispheric projecting neurons generally projected to one pair of homologous targets with ipsilateral preference. These organization principles of single-neuron projectomes provide a structural basis for understanding the function of HIP neurons.


Assuntos
Axônios , Mapeamento Encefálico , Hipocampo , Neurônios , Animais , Camundongos , Axônios/fisiologia , Axônios/ultraestrutura , Hipocampo/ultraestrutura , Neurônios/classificação , Neurônios/ultraestrutura , Análise de Célula Única/métodos , Rede Nervosa , Masculino , Camundongos Endogâmicos C57BL
16.
Arch Virol ; 169(3): 56, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386128

RESUMO

A new cytorhabdovirus, tentatively named "chelidonium yellow mottle associated virus" (CheYMaV), was identified in Chelidonium majus with yellow mottle symptoms by high-throughput sequencing and RT-PCR. Its genome is 12,121 nucleotides in length and contains eight open reading frames (ORFs) in the order 3'-N-P'-P-P3-M-G-P6-L-5'. Amino acid sequence comparisons between the putative proteins of CheYMaV and the corresponding proteins of other cytorhabdoviruses showed that it shares the highest sequence similarity with Trifolium pratense virus A (TpVA, MH982250) and Glehnia littoralis virus 1 (GllV1, BK014304), but with sequence identity values below the species demarcation threshold for cytorhabdoviruses (< 80%). Phylogenetic analysis showed that CheYMaV is most closely related to TpVA and GllV1. CheYMaV should therefore be considered a new member of the genus Cytorhabdovirus. This is the first report of a cytorhabdovirus identified in Chelidonium majus.


Assuntos
Chelidonium majus , Besouros , Filogenia , China , Sequência de Aminoácidos
17.
Nat Cell Biol ; 26(1): 86-99, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38172614

RESUMO

The Hippo pathway has important roles in organ development, tissue homeostasis and tumour growth. Its downstream effector TAZ is a transcriptional coactivator that promotes target gene expression through the formation of biomolecular condensates. However, the mechanisms that regulate the biophysical properties of TAZ condensates to enable Hippo signalling are not well understood. Here using chemical crosslinking combined with an unbiased proteomics approach, we show that FUS associates with TAZ condensates and exerts a chaperone-like effect to maintain their proper liquidity and robust transcriptional activity. Mechanistically, the low complexity sequence domain of FUS targets the coiled-coil domain of TAZ in a phosphorylation-regulated manner, which ensures the liquidity and dynamicity of TAZ condensates. In cells lacking FUS, TAZ condensates transition into gel-like or solid-like assembles with immobilized TAZ, which leads to reduced expression of target genes and inhibition of pro-tumorigenic activity. Thus, our findings identify a chaperone-like function of FUS in Hippo regulation and demonstrate that appropriate biophysical properties of transcriptional condensates are essential for gene activation.


Assuntos
Proteínas Serina-Treonina Quinases , Transativadores , Transativadores/genética , Transativadores/metabolismo , Ativação Transcricional , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Linhagem Celular Tumoral
19.
Anal Chem ; 96(5): 2142-2151, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38258616

RESUMO

While three-dimensional (3D) DNA walking amplifiers hold considerable promise in the construction of advanced DNA-based fluorescent biosensors for bioimaging, they encounter certain difficulties such as inadequate sensitivity, premature activation, the need for exogenous propelling forces, and low reaction rates. In this contribution, a variety of profitable solutions have been explored. First, a catalytic hairpin assembly (CHA)-achieved nonenzymatic isothermal nucleic acid amplification is integrated to enhance sensitivity. Subsequently, one DNA component is simply functionalized with a photocleavage-bond to conduct a photoresponsive manner, whereby the target recognition occurs only when the biosensor is exposed to an external ultraviolet light source, overcoming premature activation during biodelivery. Furthermore, a special self-propelling walking mechanism is implemented by reducing biothiols to MnO2 nanosheets, thereby propelling forces that are self-supplied to a Mn2+-reliant DNAzyme. By carrying the biosensing system with a DNA molecular framework to induce a unique concentration localization effect, the nucleic acid contact reaction rate is notably elevated by 6 times. Following these, an ultrasensitive in vitro detection performance with a limit of detection down to 2.89 fM is verified for a cancer-correlated microRNA biomarker (miRNA-21). Of particular importance, our multiple concepts combined 3D DNA walking amplifier that enables highly efficient fluorescence bioimaging in live cells and even bodies, exhibiting a favorable application prospect in disease analysis.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , MicroRNAs , DNA Catalítico/química , Compostos de Manganês , Óxidos , DNA/química , MicroRNAs/análise , Técnicas Biossensoriais/métodos , Limite de Detecção
20.
Int Immunopharmacol ; 128: 111544, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266445

RESUMO

The dysregulation of B cell maturation and putrescine metabolism has been implicated in various diseases. However, the causal relationship between them and the underlying mechanisms remain unclear. In this study, we investigated the impact of exogenous putrescine on B cell differentiation in the intestinal microenvironment. Our results demonstrated that administration of exogenous putrescine significantly impaired the proportion of germinal center B (GC B) cells in Peyer's patches (PPs) and lamina propria. Through integration of bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq), we identified putrescine-mediated changes in gene drivers, including those involved in the B cell receptor (BCR) signaling pathway and fatty acid oxidation. Furthermore, putrescine drinking disrupted T-B cell interactions and increased reactive oxygen species (ROS) production in B cells. In vitro activation of B cells confirmed the direct suppression of putrescine on GC B cells differentiation and ROS production. Additionally, we explored the Pearson correlations between putrescine biosynthesis activity and B cell infiltration in pan-cancers, revealing negative correlations in colon adenocarcinoma, stomach adenocarcinoma, and lung adenocarcinoma, but positive correlations in liver hepatocellular carcinoma, and breast invasive carcinoma. Our findings provided novel insights into the suppressive effects of elevated enteric putrescine on intestinal B cells differentiation and highlighted the complex and distinctive immunoregulatory role of putrescine in different microenvironments. These findings expand our understanding of the role of polyamines in B cell immunometabolism and related diseases.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Putrescina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adenocarcinoma/metabolismo , Nódulos Linfáticos Agregados/metabolismo , Neoplasias do Colo/metabolismo , Centro Germinativo , Diferenciação Celular , Microambiente Tumoral
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