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2.
Front Mol Neurosci ; 17: 1387481, 2024.
Article in English | MEDLINE | ID: mdl-38840778

ABSTRACT

Background: Central sensitization is one of the pivotal pathological mechanisms in chronic migraine (CM). Silent information regulator 1 (SIRT1) was shown to be involved in CM, but its specific mechanism is unclear. Reactive oxygen species (ROS) are increasingly regarded as important signaling molecules in several models of pain. However, studies about the role of ROS in the central sensitization of CM model are rare. We thus explored the specific process of SIRT1 involvement in the central sensitization of CM, focusing on the ROS pathway. Methods: Inflammatory soup was repeatedly administered to male Sprague-Dawley rats to establish a CM model. The SIRT1 expression level in trigeminal nucleus caudalis (TNC) tissues was assessed by qRT-PCR and Western blotting analysis. The levels of ROS were detected by a Tissue Reactive Oxygen Detection Kit, DHE staining, and the fluorescence signal intensity of 8-OHdG. A ROS scavenger (tempol), a SIRT1 activator (SRT1720), a SIRT1 inhibitor (EX527), and a mitochondrial fission inhibitor (Mdivi-1) were used to investigate the specific molecular mechanisms involved. NMDAR2B, CGRP, ERK, and mitochondrial fission-related protein were evaluated by Western blotting, and the CGRP level in frozen sections of the TNC was detected via immunofluorescence staining. Results: After repeated inflammatory soup infusion and successful establishment of the CM rat model, SIRT1 expression was found to be significantly reduced, accompanied by elevated ROS levels. Treatment with Tempol, SRT1720, or Mdivi-1 alleviated allodynia and reduced the increase in NMDAR2B phosphorylation and CGRP and ERK phosphorylation in the CM rat. In contrast, EX527 had the opposite effect in CM rat. SRT1720 and EX527 decreased and increased ROS levels, respectively, in CM rats, and tempol reversed the aggravating effect of EX527 in CM rats. Furthermore, the regulatory effect of SIRT1 on ROS may include the involvement of the mitochondrial fission protein DRP1. Conclusion: The results indicate the importance of SIRT1 in CM may be due to its role in regulating the production of ROS, which are involved in modulating central sensitization in CM. These findings could lead to new ideas for CM treatment with the use of SIRT1 agonists and antioxidants.

3.
Mol Biol Evol ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829799

ABSTRACT

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric R. norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited lower brown adipose tissue (BAT) activity and higher metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.

4.
bioRxiv ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38826261

ABSTRACT

The Human BioMolecular Atlas Program (HuBMAP) aims to construct a reference 3D structural, cellular, and molecular atlas of the healthy adult human body. The HuBMAP Data Portal (https://portal.hubmapconsortium.org) serves experimental datasets and supports data processing, search, filtering, and visualization. The Human Reference Atlas (HRA) Portal (https://humanatlas.io) provides open access to atlas data, code, procedures, and instructional materials. Experts from more than 20 consortia are collaborating to construct the HRA's Common Coordinate Framework (CCF), knowledge graphs, and tools that describe the multiscale structure of the human body (from organs and tissues down to cells, genes, and biomarkers) and to use the HRA to understand changes that occur at each of these levels with aging, disease, and other perturbations. The 6th release of the HRA v2.0 covers 36 organs with 4,499 unique anatomical structures, 1,195 cell types, and 2,089 biomarkers (e.g., genes, proteins, lipids) linked to ontologies. In addition, three workflows were developed to map new experimental data into the HRA's CCF. This paper describes the HRA user stories, terminology, data formats, ontology validation, unified analysis workflows, user interfaces, instructional materials, application programming interface (APIs), flexible hybrid cloud infrastructure, and demonstrates first atlas usage applications and previews.

5.
Medicine (Baltimore) ; 103(23): e38425, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847732

ABSTRACT

BACKGROUND: Not all the breast lesions were mass-like, some were non-mass-like at ultrasonography. In these lesions, conventional ultrasonography had a high sensitivity but a low specificity. Sonoelastography can evaluate tissue stiffness to differentiate malignant masses from benign ones. Then what about the non-mass lesions? The aim of this study was to evaluate the current accuracy of sonoelastography in the breast non-mass lesions and compare the results with those of the American College of Radiology breast Imaging-Reporting and Data System (BI-RADS). METHODS: An independent literature search of English medical databases, including PubMed, Web of Science, Embase & MEDLINE (Embase.com) and Cochrane Library, was performed by 2 researchers. The accuracy of sonoelastography was calculated and compared with those of BI-RADS. RESULTS: Fourteen relevant studies including 1058 breast non-mass lesions were included. Sonoelastography showed a pooled sensitivity of 0.74 (95% CI: 0.70-0.78), specificity of 0.89 (95% CI: 0.85-0.91), diagnostic odds ratio (DOR) of 25.22 (95% CI: 17.71-35.92), and an area under the curve of 0.9042. Eight articles included both sonoelastography and BI-RADS. The pooled sensitivity, specificity, DOR and AUC were 0.69 versus 0.91 (P < .01), 0.90 versus 0.68 (P < .01), 19.65 versus 29.34 (P > .05), and 0.8685 versus 0.9327 (P > .05), respectively. CONCLUSIONS: Sonoelastography has a higher specificity and a lower sensitivity for differential diagnosis between malignant and benign breast non-mass lesions compared with BI-RADS, although there were no differences in AUC between them.


Subject(s)
Elasticity Imaging Techniques , Ultrasonography, Mammary , Humans , Elasticity Imaging Techniques/methods , Female , Ultrasonography, Mammary/methods , Breast Neoplasms/diagnostic imaging , Sensitivity and Specificity , Diagnosis, Differential , Breast/diagnostic imaging , Breast/pathology , Breast Diseases/diagnostic imaging
6.
Insect Sci ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728615

ABSTRACT

Wing dimorphism is regarded as an important phenotypic plasticity involved in the migration and reproduction of aphids. However, the signal transduction and regulatory mechanism of wing dimorphism in aphids are still unclear. Herein, the optimal environmental conditions were first explored for inducing winged offspring of green peach aphid, and the short photoperiod was the most important environmental cue to regulate wing dimorphism. Compared to 16 L:8 D photoperiod, the proportion of winged offspring increased to 90% under 8 L:16 D photoperiod. Subsequently, 5 differentially expressed microRNAs (miRNAs) in aphids treated with long and short photoperiods were identified using small RNA sequencing, and a novel miR-3040 was identified as a vital miRNA involved in photoperiod-mediated wing dimorphism. More specifically, the inhibition of miR-3040 expression could reduce the proportion of winged offspring induced by short photoperiod, whereas its activation increased the proportion of winged offspring under long photoperiod. Meanwhile, the expression level of miR-3040 in winged aphids was about 2.5 times that of wingless aphids, and the activation or inhibition of miR-3040 expression could cause wing deformity, revealing the dual-role regulator of miR-3040 in wing dimorphism and wing development. In summary, the current study identified the key environmental cue for wing dimorphism in green peach aphid, and the first to demonstrate the dual-role regulator of miR-3040 in photoperiod-mediated wing dimorphism and wing development.

8.
J Cosmet Dermatol ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726847

ABSTRACT

BACKGROUND: Botulinum neurotoxin injections are the most frequently performed cosmetic procedures, but conventional blind injection for glabellar wrinkles remains to have some limitations. AIMS: We intend to directly inject botulinum neurotoxin into the glabella complex guided by real time ultrasound. We aim to propose a more efficient and safer botulinum neurotoxin injection strategy for glabellar wrinkles. METHODS: A total of 40 subjects with moderate to severe glabellar lines were enrolled in this study to receive botulinum neurotoxin injection, either through ultrasound-guided real time injection or conventional blind injection. Facial Wrinkle Scale (ranging from 0 = none to 3 = severe) and inter-brow distance (from 3D scanned face images) were used to evaluate the glabellar wrinkles improvement. Paired t test and two-sample t test were performed to analyze the within-group and between-group differences. RESULTS: The wrinkle score reduction was significant (p < 0.0001) immediately after the injection in ultrasound-guided injection group, but not in blind injection group (p = 0.163). Ultrasound-guided injection also showed a higher performance of wrinkle score reduction and more effective inter-brow distance increase over blind injection at Day 0 (p < 0.0001), Day 1 (p < 0.0001), Day 21 (p < 0.01) and Day 35 (p < 0.01) after initial treatment. CONCLUSIONS: The results of the study confirmed that botulinum neurotoxin injection for glabellar wrinkles under ultrasound guidance achieves quicker onset of action and better final outcomes compared to conventional blind injection.

9.
J Nurs Scholarsh ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691056

ABSTRACT

BACKGROUND: Cancer screening is a pivotal method for reducing mortality from disease, but the screening coverage is still lower than expected. Telehealth interventions demonstrated significant benefits in cancer care, yet there is currently no consensus on their impact on facilitating cancer screening or on the most effective remote technology. DESIGN: A network meta-analysis was conducted to detect the impact of telehealth interventions on cancer screening and to identify the most effective teletechnologies. METHODS: Six English databases were searched from inception until July 2023 to yield relevant randomized controlled trials (RCTs). Two individual authors completed the literature selection, data extraction, and methodological evaluations using the Cochrane Risk of Bias tool. Traditional pairwise analysis and network meta-analysis were performed to identify the overall effects and compare different teletechnologies. RESULTS: Thirty-four eligible RCTs involving 131,644 participants were enrolled. Overall, telehealth interventions showed statistically significant effects on the improvement of cancer screening. Subgroup analyses revealed that telehealth interventions were most effective for breast and cervical cancer screening, and rural populations also experienced benefits, but there was no improvement in screening for older adults. The network meta-analysis indicated that mobile applications, video plus telephone, and text message plus telephone were associated with more obvious improvements in screening than other teletechnologies. CONCLUSION: Our study identified that telehealth interventions were effective for the completion of cancer screening and clarified the exact impact of telehealth on different cancer types, ages, and rural populations. Mobile applications, video plus telephone, and text message plus telephone are the three forms of teletechnologies most likely to improve cancer screening. More well-designed RCTs involving direct comparisons of different teletechnologies are needed in the future. CLINICAL RELEVANCE: Telehealth interventions should be encouraged to facilitate cancer screening, and the selection of the optimal teletechnology based on the characteristics of the population is also necessary.

10.
Eur J Nutr ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703226

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is a clinical syndrome characterized by multiple metabolic disorders and is a serious global health problem. The coffee effect, acting as one of the most prevalent beverages on metabolic syndrome, is debatable. METHODS: We included patients from the National Health and Nutrition Examination Survey 2003-2018 and used a comprehensive evaluation called the MetS z-score to assess the severity of metabolic syndrome. The relationship between coffee, decaffeinated coffee, tea, and MetS z-scores was explored using a weighted linear regression. We also divided the participants into metabolic and non-metabolic syndrome groups according to the NCEP/ATP III criteria for the subgroup analysis. RESULTS: A total of 14,504 participants were included in this study. The results demonstrated that drinking more than three cups of coffee daily was significantly linked to lower MetS z-scores (p < 0.001). Daily coffee consumption was also associated with lower BMI (p = 0.02), systolic blood pressure (p < 0.001), Homeostatic Model Assessment for Insulin Resistance (p < 0.001), and triglycerides (p < 0.001), while it was positively correlated with HDL-C (p = 0.001). Participants who consumed more than three cups of coffee daily had a lower MetS z-score in the MetS (p < 0.001) and non-MetS (p = 0.04) groups. CONCLUSION: This research indicates that coffee consumption is linked to MetS severity. However, decaffeinated coffee and tea intake were unrelated to MetS severity.

11.
Vaccine ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38714448

ABSTRACT

Inactivated vaccines lack the capability to serologically differentiate between infected and vaccinated animals, thereby impeding the effective eradication of pathogen. Conversely, vaccines based on virus-like particles (VLPs) emulate natural viruses in both size and antigenic structure, presenting a promising alternative to overcome these limitations. As the complexity of swine infectious diseases increases, the increase of vaccine types and doses may intensify the stress response. This exacerbation can lead to diminished productivity, failure of immunization, and elevated costs. Given the critical dynamics of co-infection and the clinically indistinguishable symptoms associated with foot-and-mouth disease virus (FMDV) and senecavirus A (SVA), there is a dire need for an efficacious intervention. To address these challenges, we developed a combined vaccine composed of three distinct VLPs, specifically designed to target SVA and FMDV serotypes O and A. Our research demonstrates that this trivalent VLP vaccine induces antigen-specific and robust serum antibody responses, comparable to those produced by the respective monovalent vaccines. Moreover, the immune sera from the combined VLP vaccine strongly neutralized FMDV type A and O, and SVA, with neutralization titers comparable to those of the individual vaccines, indicating a high level of immunogenic compatibility among the three VLP components. Importantly, the combined VLPs vaccines-immunized sera conferred efficient protection against single or mixed infections with FMDV type A and O, and SVA viruses in pigs. In contrast, individual vaccines could only protect pigs against homologous virus infections and not against heterologous challenges. This study presents a novel combined vaccines candidate against FMD and SVA, and provides new insights for the development of combination vaccines for other viral swine diseases.

12.
Neuroscientist ; : 10738584241252576, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712859

ABSTRACT

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with onset in childhood. The molecular mechanisms underlying ASD have not yet been elucidated completely. Evidence has emerged to support a link between microglial dysfunction and the etiology of ASD. This review summarizes current research on microglial dysfunction in neuroinflammation and synaptic pruning, which are associated with altered transcriptomes and autophagy in ASD. Dysbiosis of gut microbiota in ASD and its correlation with microglial dysfunction are also addressed.

13.
Front Pharmacol ; 15: 1343582, 2024.
Article in English | MEDLINE | ID: mdl-38803434

ABSTRACT

Background: Evidence indicates that the addition of ezetimibe to statin therapy reduces cardiovascular events. However, the impact of ezetimibe-statin combination therapy on coronary plaque regression, plaque stabilization, and diameter stenosis remains a matter of controversy. Methods: We performed electronic searches in PubMed, Web of Knowledge, and the Cochrane Central Register of Controlled Trials to identify eligible trials assessing the effects of ezetimibe-statin combination therapy versus statin monotherapy reporting at least one outcome among total atheroma volume (TAV), minimum fibrous cap thickness (FCT), lumen volume (LV), and lumen area (LA) derived from intravascular imaging modalities of intravascular ultrasound (IVUS) and optical coherence tomography (OCT). We used the random-effects model and performed trial sequential analysis (TSA) during this meta-analysis. Results: Eleven articles with a total of 926 individuals (460 in the dual-lipid-lowering therapy group and 466 in the statin monotherapy group) were included in the final meta-analysis. Compared to statin monotherapy, ezetimibe-statin combination therapy was associated with significantly decreased TAV [WMD = -3.17, 95% CI (-5.42 to -0.92), and p = 0.006], with no effect on the LV of the coronary artery [WMD = -0.52, 95% CI (-2.24 to 1.21), and p = 0.56], the LA of the coronary artery [WMD = 0.16, 95% CI (-0.10-0.42), and p = 0.22], or minimum FCT thickness [WMD = 19.11, 95%CI (-12.76-50.97)]. Conclusion: In patients with coronary artery disease, ezetimibe-statin combination therapy resulted in a significant regression in TAV compared to statin monotherapy, whereas no overall improvements of minimum FCT or lumenal stenosis were observed.

14.
Proc Natl Acad Sci U S A ; 121(23): e2322359121, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38805286

ABSTRACT

Rearranged during transfection (RET) rearrangement oncoprotein-mediated Ras/MAPK signaling cascade is constitutively activated in cancers. Here, we demonstrate a unique signal niche. The niche is a ternary complex based on the chimeric RET liquid-liquid phase separation. The complex comprises the rearranged kinase (RET fusion); the adaptor (GRB2), and the effector (SHC1). Together, they orchestrate the Ras/MAPK signal cascade, which is dependent on tyrosine kinase. CCDC6-RET fusion undergoes LLPS requiring its kinase domain and its fusion partner. The CCDC6-RET fusion LLPS promotes the autophosphorylation of RET fusion, with enhanced kinase activity, which is necessary for the formation of the signaling niche. Within the signal niche, the interactions among the constituent components are reinforced, and the signal transduction efficiency is amplified. The specific RET fusion-related signal niche elucidates the mechanism of the constitutive activation of the Ras/MAPK signaling pathway. Beyond just focusing on RET fusion itself, exploration of the ternary complex potentially unveils a promising avenue for devising therapeutic strategies aimed at treating RET fusion-driven diseases.


Subject(s)
GRB2 Adaptor Protein , MAP Kinase Signaling System , Oncogene Proteins, Fusion , Proto-Oncogene Proteins c-ret , Src Homology 2 Domain-Containing, Transforming Protein 1 , ras Proteins , Src Homology 2 Domain-Containing, Transforming Protein 1/metabolism , Src Homology 2 Domain-Containing, Transforming Protein 1/genetics , Humans , GRB2 Adaptor Protein/metabolism , GRB2 Adaptor Protein/genetics , ras Proteins/metabolism , ras Proteins/genetics , Proto-Oncogene Proteins c-ret/metabolism , Proto-Oncogene Proteins c-ret/genetics , Oncogene Proteins, Fusion/metabolism , Oncogene Proteins, Fusion/genetics , Signal Transduction , Phosphorylation
15.
Sci Rep ; 14(1): 10791, 2024 05 11.
Article in English | MEDLINE | ID: mdl-38734751

ABSTRACT

Sweet corn is highly susceptible to the deleterious effects of low temperatures during the initial stages of growth and development. Employing a 56K chip, high-throughput single-nucleotide polymorphism (SNP) sequencing was conducted on 100 sweet corn inbred lines. Subsequently, six germination indicators-germination rate, germination index, germination time, relative germination rate, relative germination index, and relative germination time-were utilized for genome-wide association analysis. Candidate genes were identified via comparative analysis of homologous genes in Arabidopsis and rice, and their functions were validated using quantitative real-time polymerase chain reaction (qRT-PCR). The results revealed 35,430 high-quality SNPs, 16 of which were significantly correlated. Within 50 kb upstream and downstream of the identified SNPs, 46 associated genes were identified, of which six were confirmed as candidate genes. Their expression patterns indicated that Zm11ΒHSDL5 and Zm2OGO likely play negative and positive regulatory roles, respectively, in the low-temperature germination of sweet corn. Thus, we determined that these two genes are responsible for regulating the low-temperature germination of sweet corn. This study contributes valuable theoretical support for improving sweet corn breeding and may aid in the creation of specific germplasm resources geared toward enhancing low-temperature tolerance in sweet corn.


Subject(s)
Cold Temperature , Genome-Wide Association Study , Germination , Polymorphism, Single Nucleotide , Zea mays , Germination/genetics , Zea mays/genetics , Zea mays/growth & development , Gene Expression Regulation, Plant , Quantitative Trait Loci
16.
Talanta ; 276: 126226, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38754187

ABSTRACT

Lysozyme (LYZ) plays a crucial role in the body's immune defense system. Monitoring LYZ levels can provide valuable insights into the diagnosis and severity assessment of various diseases. Traditionally, antibody-based sandwich assays are employed for LYZ detection, but they are often time-consuming and operationally complicated. In this research, a novel sandwich FRET biosensor was developed, which enables rapid detection of LYZ based on peptide-functionalized gold nanoparticles (pAuNPs) and FAM-labeled aptamer (Apt-FAM). Initially, a mixture of Apt-FAM and pAuNPs resulted in partial quenching of the Apt-FAM fluorescence emission through an inner filter effect (IFE), with negligible energy transfer because of the electrostatic repulsion between the negatively charged pAuNPs and Apt-FAM. The introduction of LYZ into the mixture drove the specific binding of Apt-FAM and pAuNPs to LYZ, facilitating the formation of a pAuNPs-LYZ-aptamer sandwich structure. The formation of this complex drew the pAuNPs and Apt-FAM into close enough proximity to enable FRET to occur, which in turn effectively quenched the fluorescence emission of FAM. The decrease in FAM fluorescence intensity was correlated with the increasing concentration of LYZ. Thus, a sandwich FRET biosensor was successfully developed for LYZ detection with a linear detection range of 0-1.75 µM and a detection limit of 85 nM. Additionally, the biosensor allowed visual detection of LYZ in a 96-well microplate, with a rapid response time of just 15 s. This study introduces a innovative sandwich FRET biosensor that combines aptamer and peptide recognition elements, offering a fast and antibody-free method for protein detection.

17.
J Clin Invest ; 134(10)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38747285

ABSTRACT

Transforming growth factor ß (TGF-ß) signaling is a core pathway of fibrosis, but the molecular regulation of the activation of latent TGF-ß remains incompletely understood. Here, we demonstrate a crucial role of WNT5A/JNK/ROCK signaling that rapidly coordinates the activation of latent TGF-ß in fibrotic diseases. WNT5A was identified as a predominant noncanonical WNT ligand in fibrotic diseases such as systemic sclerosis, sclerodermatous chronic graft-versus-host disease, and idiopathic pulmonary fibrosis, stimulating fibroblast-to-myofibroblast transition and tissue fibrosis by activation of latent TGF-ß. The activation of latent TGF-ß requires rapid JNK- and ROCK-dependent cytoskeletal rearrangements and integrin αV (ITGAV). Conditional ablation of WNT5A or its downstream targets prevented activation of latent TGF-ß, rebalanced TGF-ß signaling, and ameliorated experimental fibrosis. We thus uncovered what we believe to be a novel mechanism for the aberrant activation of latent TGF-ß in fibrotic diseases and provided evidence for targeting WNT5A/JNK/ROCK signaling in fibrotic diseases as a new therapeutic approach.


Subject(s)
Fibroblasts , Fibrosis , Transforming Growth Factor beta , Wnt-5a Protein , rho-Associated Kinases , Wnt-5a Protein/metabolism , Wnt-5a Protein/genetics , Animals , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/genetics , Mice , Humans , Fibroblasts/metabolism , Fibroblasts/pathology , rho-Associated Kinases/metabolism , rho-Associated Kinases/genetics , Scleroderma, Systemic/pathology , Scleroderma, Systemic/metabolism , Scleroderma, Systemic/genetics , Mice, Knockout , Wnt Proteins/metabolism , Wnt Proteins/genetics , MAP Kinase Signaling System , Myofibroblasts/metabolism , Myofibroblasts/pathology , Signal Transduction , Idiopathic Pulmonary Fibrosis/pathology , Idiopathic Pulmonary Fibrosis/metabolism , Idiopathic Pulmonary Fibrosis/genetics
18.
Phytochemistry ; 224: 114140, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38750709

ABSTRACT

Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 µM, with inhibition ratios ranging from 5.1% to 14.3%.

19.
Adv Sci (Weinh) ; : e2309992, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38774946

ABSTRACT

Radiotherapy demonstrates a synergistic effect with immunotherapy by inducing a transformation of "immune cold" tumors into "immune hot" tumors in triple negative breast cancer (TNBC). Nevertheless, the effectiveness of immunotherapy is constrained by low expression of tumor-exposed antigens, inadequate inflammation, and insufficient tumor infiltrating lymphocyte (TILs). To address this predicament, novel lutecium-based rare earth nanoparticles (RENPs) are synthesized with the aim of amplifying radiation effect and tumor immune response. The nanoprobe is characterized by neodymium-based down-conversion fluorescence, demonstrating robust photostability, biocompatibility, and targetability. The conjugation of RENPs with a CXCR4 targeted drug enables precise delineation of breast tumors using a near-infrared imaging system and improves radiation efficacy via lutetium-based radio-sensitizer in vivo. Furthermore, the study shows a notable enhancement of immune response through the induction of immunogenic cell death and recruitment of TILs, resulting in the inhibition of tumor progression both in vitro and in vivo models following the administration of nanoparticles. Hence, the novel multifunctional nanoprobes incorporating various lanthanide elements offer the potential for imaging-guided tumor delineation, radio-sensitization, and immune activation post-radiation, thus presenting an efficient radio-immunotherapeutic approach for TNBC.

20.
Anal Bioanal Chem ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780654

ABSTRACT

Wax printing is the most widely used method for fabricating microfluidic paper-based analytical devices (µPADs), but it still suffers from disadvantages like discontinuation of wax printers and need for additional equipment for heating treatment. To address these issues, this work initially describes a new class of wax printing approach for high-precision, batch fabrication of µPADs using a household 3D printer. It only involves a one patterning step of printing polyethylene wax into rice paper body. Under optimized parameters, a fabrication resolution, namely the minimum hydrophilic channel width, down to ~189 ± 30 µm could be achieved. In addition, the analytical applicability of such polyethylene wax-patterned µPADs was demonstrated well with enhanced colorimetric detection of dopamine as a model analyte by combining metal-organic framework (MOF) based nanoenzymes (ZIF-67) with a smartphone (for portable quantitative readout). The developed nanosensor could linearly detect dopamine over a concentration range from 10 to 1000 µM, with a detection limit of ca. 2.75 µM (3σ). The recovery results for analyzing several real samples (i.e., pig feed, chicken feed, pork and human serum) were between 91.82 and 102.79%, further validating its good detection accuracy for potential practical applications in food safety and medical diagnosis.

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