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1.
Heliyon ; 10(16): e35426, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39253150

RESUMO

Ling Gui Zhu Gan decoction (LGZGD) is a traditional Chinese medicine (TCM) prescription that is widely used in cardiovascular disease clinical prevention and treatment with high efficacy. Recent studies have shown that LGZGD can also be used in hyperlipidemia (HL) intervention, but its pharmacodynamic material basis and its mechanisms remains unclear. This study aimed to reveal the protective effects of LGZGD on HL, elucidate the pharmacodynamic material basis. The hamster HL model was established by high-fat diet. Thereafter, non-targeted metabolomics and quantitative lipidomics were established for screening differential metabolites and pathways. Finally, the mechanisms were elucidated based on network pharmacology to screen for shared targets, which were computational selected by molecular docking. After four weeks of LGZGD administration, the TC, TG, and liver index levels decreased notably and hepatocyte injury was obviously reduced. The Multi-omics identified 62 differential metabolites and 144 differential lipids, respectively. The network pharmacology study predicted 343, 85, and 974 relevant targets from LGZGD components, HL, differential metabolites and lipids, respectively. Eventually, seven core targets were selected by molecular docking. Six key components in LGZGD, including genistein and naringenin, could play a therapeutic role in HL by regulating seven pathways, including HMGCR and PPARA. This comprehensive strategy provides a promising example and approach for further research on TCM for the treatment of lipid metabolic diseases.

2.
ChemSusChem ; : e202401313, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087447

RESUMO

Carbon dots (CDs) still suffer from unclear surface state fluorescence mechanism for fine modulation. Here, redox reactions for cathode and anode within electrochemical method are firstly employed to construct differentiated strategy for surface-state modulation, so as to obtain CDs with controllable emission in separated electrodes simultaneously. The fluorescence peaks of CDs from blue to red centered at 425 nm (mCDs-), 530 nm (mCDs+), 580 nm (oCDs-) and 665 nm (oCDs+) are mainly originated from the different bombardment effects of the ions and reaction tendencies of modifier during the electrolysis process. The phenylenediamine (as modifier) tends to introduce the amino groups on the surface of CDs- while introduced nitrogen atoms into the carbon nucleus skeleton around the anode, thus leading to much larger size and the formation of the graphite N for CDs+. It is the different surface states formed by phenylenediamine and the absorption redshift triggered by graphite N that ensures the tunable emission. The improved electrochemical method is of great significance for finely spectra modulation and efficient synthesis.

3.
J Health Psychol ; : 13591053241273663, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39183626

RESUMO

The current study examined the relationship between mothers' selfie-related behaviors and adolescents' cosmetic surgery consideration, as well as the mediating effects of the adolescents' selfie-related behaviors, body surveillance, and facial dissatisfaction. A total of 541 mother-child dyads with adolescents averaging 16.55 years old, was recruited. The path analysis revealed that mothers' selfie-related behaviors were not directly related to adolescents' consideration of cosmetic surgery, but the link was mediated by the adolescents' selfie-related behaviors, body surveillance, and facial dissatisfaction. Specifically, there was a mediating effect of adolescents' facial dissatisfaction, as well as serial mediating effects of adolescents' selfie-related behaviors and facial dissatisfaction, of adolescents' selfie-related behaviors and body surveillance, and of adolescents' selfie-related behaviors, body surveillance and facial dissatisfaction. Additionally, we did not find a significant gender difference in the model. These findings provide further insights into the association between a mother's selfie activities and adolescent children's cosmetic surgery consideration.

4.
Integr Zool ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082860

RESUMO

A possible explanation for ocean acidification-induced changes in fish behavior is a systemic effect on the nervous system. Three biological barriers at the blood-brain interface effectively separate the brain from the body fluids. It is not known whether fish brain regions in contact with these barriers are affected by acidification. Here, we studied structural changes in medaka (Oryzias melastigma) brain regions contacting cerebrospinal fluid (CSF) after short-term (7 days) CO2 exposure. The brain water content decreased significantly and the superficial structure of the pia mater was changed, but there was no obvious damage to the internal structures of the brain after seawater acidification. Seawater acidification also led to an increase in apoptosis and a decrease in the number of proliferative cells in brain areas contacting CSF. These results indicate that the structure of CSF-contacting brain regions in medaka was affected by seawater acidification, and the brain responded to seawater acidification stress by increasing apoptosis and reducing proliferation.

5.
ACS Appl Mater Interfaces ; 16(27): 35190-35199, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38943571

RESUMO

Composites of organic small molecules (OSMs) and single-walled carbon nanotubes (SWCNTs) have drawn great attention as flexible thermoelectric (TE) materials in recent years. Here, we synthesized thieno[2',3':4,5]thieno[3,2-b]thieno[2,3-d]thiophene (TTA) and 2,6-dibromothieno[2',3':4,5]thieno[3,2-b]thieno[2,3-d]thiophene (TTA-2Br) and compounded them with SWCNTs, obtaining thermoelectric TTA/SWCNT and TTA-2Br/SWCNT composites. The introduction of the electron-withdrawing Br group was found to decrease the highest molecular orbital energy level and bandgap (Eg) of TTA-2Br. As a result, the Seebeck coefficient (S) and power factor (PF) of the OSM/SWCNT composite films were significantly improved. Moreover, suitable energy barrier between TTA-2Br and SWCNTs facilitates the energy filtering effect, which further enhances thermoelectric properties of the 40 wt % TTA-2Br/SWCNT composite film with optimum thermoelectric properties (PF = 242.59 ± 9.42 µW m-1 K-2 at room temperature), good thermal stability, and mechanical flexibility. In addition, the thermoelectric generator (TEG) prepared using 40 wt % TTA-2Br/SWCNT composite films and n-type SWCNT films can generate an output power of 102.8 ± 7.4 nW at a temperature difference of 20 °C. This work provides new insights into the preparation of OSM/SWCNT composites with significantly enhanced thermoelectric properties.

6.
J Neurosci ; 44(29)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38755005

RESUMO

Preclinical assessments of pain have often relied upon behavioral measurements and anesthetized neurophysiological recordings. Current technologies enabling large-scale neural recordings, however, have the potential to unveil quantifiable pain signals in conscious animals for preclinical studies. Although pain processing is distributed across many brain regions, the anterior cingulate cortex (ACC) is of particular interest in isolating these signals given its suggested role in the affective ("unpleasant") component of pain. Here, we explored the utility of the ACC toward preclinical pain research using head-mounted miniaturized microscopes to record calcium transients in freely moving male mice expressing genetically encoded calcium indicator 6f (GCaMP6f) under the Thy1 promoter. We verified the expression of GCaMP6f in excitatory neurons and found no intrinsic behavioral differences in this model. Using a multimodal stimulation paradigm across naive, pain, and analgesic conditions, we found that while ACC population activity roughly scaled with stimulus intensity, single-cell representations were highly flexible. We found only low-magnitude increases in population activity after complete Freund's adjuvant (CFA) and insufficient evidence for the existence of a robust nociceptive ensemble in the ACC. However, we found a temporal sharpening of response durations and generalized increases in pairwise neural correlations in the presence of the mechanistically distinct analgesics gabapentin or ibuprofen after (but not before) CFA-induced inflammatory pain. This increase was not explainable by changes in locomotion alone. Taken together, these results highlight challenges in isolating distinct pain signals among flexible representations in the ACC but suggest a neurophysiological hallmark of analgesia after pain that generalizes to at least two analgesics.


Assuntos
Giro do Cíngulo , Animais , Camundongos , Masculino , Giro do Cíngulo/fisiopatologia , Giro do Cíngulo/efeitos dos fármacos , Dor/fisiopatologia , Inflamação , Camundongos Endogâmicos C57BL , Analgesia/métodos , Analgésicos/farmacologia , Adjuvante de Freund/toxicidade , Ibuprofeno/farmacologia
7.
J Neuropathol Exp Neurol ; 83(8): 670-683, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38819094

RESUMO

The common neurodegenerative disorder Alzheimer disease (AD) is characterized by memory dysfunction and cognitive decline in the elderly. Neuropathological features include aggregated ß-amyloid (Aß) accumulation, neuroinflammation, and oxidative stress in the brain. Daphnetin (DAPH), a natural coumarin derivative, has the potential for inhibiting inflammatory and oxidative responses. We explored neuroprotective roles of DAPH treatment in the APP/PS1 transgenic mouse AD model. DAPH ameliorated spatial learning disabilities in Morris water maze tests and reduced Aß deposition, assessed by immunohistochemistry. It also reduced the Aß content in supernatants of neurons from fetal APP/PS1 mice, assessed by cell-based soluble ELISA. Molecular docking and fluorescence resonance energy transfer-based assay results suggested that DAPH could directly inhibit BACE1 activity. Furthermore, in vitro experiments utilizing isolated rat neurons assessing RNA expression profiling, immunofluorescence, TUNEL assay, and Western-blot analysis, suggested the potential of DAPH for regulating BDNF and GM-CSF expression and mitigating Aß1-42-induced cortical injury, synaptic loss, and apoptosis. HO-1 and Nrf2 mRNA and protein expression were also increased in a dose-dependent manner. These results underscore the potential of DAPH as a neuroprotective agent in reversing memory deficits associated with AD and bolster its candidacy as a multitarget natural small-molecule drug for AD patients.


Assuntos
Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Ácido Aspártico Endopeptidases , Modelos Animais de Doenças , Heme Oxigenase-1 , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2 , Neurônios , Fármacos Neuroprotetores , Umbeliferonas , Animais , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Umbeliferonas/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Ratos , Ácido Aspártico Endopeptidases/metabolismo , Camundongos , Fármacos Neuroprotetores/farmacologia , Heme Oxigenase-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Ratos Sprague-Dawley , Masculino , Proteínas de Membrana
8.
Sci Total Environ ; 923: 171477, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38460686

RESUMO

Mapping vegetation formation types in large areas is crucial for ecological and environmental studies. However, this is still challenging to distinguish similar vegetation formation types using existing predictive vegetation mapping methods, based on commonly used environmental variables and remote sensing spectral data, especially when there are not enough training samples. To solve this issue, we proposed a predictive vegetation mapping method by integrating an advanced machine learning algorithm and knowledge in an early coarse-scale vegetation map (VMK). First, we implemented classification using the random forest algorithm by integrating the early vegetation map as an auxiliary feature (VMF). Then, we determined the rationality of classified vegetation types and distinguished the confusing types, respectively, based on the knowledge of the spatial distributions and hierarchies of vegetation. Finally, we replaced each recognized unreasonable vegetation type with its corresponding reasonable vegetation type. We implemented the new method in upstream of the Yellow River based on GaoFen-1 satellite images and other environmental variables (i.e., topographical and climate variables). Results showed that the overall accuracy using the VMK method ranged from 67.7 % to 76.8 %, which was 10.9 % to 13.4 % and 3.2 % to 6.6 %, respectively, higher than that of the method without the early vegetation map (NVM) and the VMF method, based on cross-validation with 20 % to 60 % random training samples. The spatial details of the vegetation map using the VMK method were also more reasonable compared to the NVM and VMF methods. These results indicated that the VMK method can distinctly improve the mapping accuracy at the vegetation formation level by integrating knowledge of existing vegetation maps. The proposed method can largely reduce the requirements on the number of field samples, which is especially important for alpine mountains and arctic region, where collecting training samples is more difficult due to the harsh natural environment.

9.
Angew Chem Int Ed Engl ; 63(16): e202400803, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38414106

RESUMO

Unsymmetric organic semiconductors have many advantages such as good solubility, rich intermolecular interactions for potential various optoelectronic applications. However, their synthesis is more challenging due to intricate structures thus normally suffering tedious synthesis. Herein, we report a trisulfur radical anion (S3⋅-) triggered domino thienannulation strategy for the synthesis of dibenzo[d,d']thieno[2,3-b;4,5-b']dithiophenes (DBTDTs) using readily available 1-halo-2-ethynylbenzenes as starting materials. This domino protocol features no metal catalyst and the formation of six C-S and one C-C bonds in a one-pot reaction. Mechanistic study revealed a unique domino radical anion pathway. Single crystal structure analysis of unsymmetric DBTDT shows that its unique unsymmetric structure endows rich and multiple weak S⋅⋅⋅S interactions between molecules, which enables the large intermolecular transfer integrals of 86 meV and efficient charge transport performance with a carrier mobility of 1.52 cm2 V-1 s-1. This study provides a facile and highly efficient synthetic strategy for more high-performance unsymmetric organic semiconductors.

10.
Br J Nutr ; 131(4): 553-566, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-37699661

RESUMO

Sterol regulatory element-binding protein 2 (SREBP2) is considered to be a major regulator to control cholesterol homoeostasis in mammals. However, the role of SREBP2 in teleost remains poorly understand. Here, we explored the molecular characterisation of SREBP2 and identified SREBP2 as a key modulator for 3-hydroxy-3-methylglutaryl-coenzyme A reductase and 7-dehydrocholesterol reductase, which were rate-limiting enzymes of cholesterol biosynthesis. Moreover, dietary palm oil in vivo or palmitic acid (PA) treatment in vitro elevated cholesterol content through triggering SREBP2-mediated cholesterol biosynthesis in large yellow croaker. Furthermore, our results also found that PA-induced activation of SREBP2 was dependent on the stimulating of endoplasmic reticulum stress (ERS) in croaker myocytes and inhibition of ERS by 4-Phenylbutyric acid alleviated PA-induced SREBP2 activation and cholesterol biosynthesis. In summary, our findings reveal a novel insight for understanding the role of SREBP2 in the regulation of cholesterol metabolism in fish and may deepen the link between dietary fatty acid and cholesterol biosynthesis.


Assuntos
Gorduras Insaturadas na Dieta , Perciformes , Animais , Colesterol/metabolismo , Estresse do Retículo Endoplasmático , Músculos/metabolismo , Óleo de Palmeira/farmacologia , Perciformes/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
11.
Mikrochim Acta ; 191(1): 29, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38095724

RESUMO

A novel nucleic acid aptamer nanoprobes-mediated hairpin allosteric and aptamer-assisted CRISPR system for detection of Streptococcus pneumoniae and Staphylococcus aureus is presented. In this fluorescence assay system, utilizing the hairpin allosteric effect caused by the aptamer binding to the target bacteria, the detection of S. pneumoniae is first achieved through changes in fluorescence due to FRET. Subsequently, a Cas12a protein mixture is added to detect S. aureus. The amplified output signal is triggered by two methods to ensure the sensitivity of the method: the synergistic FRET effect is achieved by the assembly of multi-aptamer through the conjugation of streptavidin-biotin, and the trans-cleavage function of CRISPR/Cas 12a. Under the optimized conditions, the proposed hairpin allosteric aptasensor could achieve high sensitivity (a detection limit of 135 cfu/mL) and broad-concentration quantification (dynamic range of 103-107 cfu/mL) of S. pneumoniae. The aptamer-assisted CRISPR system for S. aureus detection showed good linearity (R2 = 0.996) in the concentration range 102-108 cfu/mL, with a detection limit of 39 cfu/mL. No cross-reactivity with other foodborne pathogenic bacteria was observed in both systems. Taking only 55 min, this method of multiple pathogen detection proved to be promising.


Assuntos
Aptâmeros de Nucleotídeos , Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus/genética , Aptâmeros de Nucleotídeos/genética , Streptococcus pneumoniae/genética , Bactérias
12.
Chem Sci ; 14(45): 13254-13264, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38023496

RESUMO

Annularly 1,3-localized singlet diradicals are energetic and homolytic intermediates, but commonly too short-lived for widespread utilization. Herein, we describe a direct observation of a long-lived and seven-membered singlet diradical, oxepine-3,6-dione-2,7-diyl (OXPID), via spectroscopic experiments and also theoretical evidence from computational studies, which is generated via photo-induced ring-expansion of 2,3-diaryl-1,4-naphthoquinone epoxide (DNQO). The photo-generated OXPID reverts to the thermally stable σ-bonded DNQO with t1/2 in the µs level, thus constituting a novel class of T-type molecular photoswitches with high light-energy conversion efficiency (η = 7.8-33%). Meanwhile, the OXPID is equilibrated to a seven-membered cyclic 1,3-dipole as an electronic tautomer that can be captured by ring-strained dipolarophiles with an ultrafast cycloaddition rate (k2CA up to 109 M-1 s-1). The T-type photoswitchable DNQO is then exploited to be a highly selective and recyclable photoclick reagent, enabling spatiotemporal-resolved bioorthogonal ligation on living cell membranes via a tailored DNQO-Cy3 probe.

13.
PeerJ ; 11: e15948, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719108

RESUMO

Cyanotis arachnoidea C. B. Clarke is a traditional Chinese medicinal herb that has a limited clinical use in the treatment of diabetes mellitus (DM) in minority areas of Guizhou in China. However, few prior reports are available on the quality control of Cyanotis arachnoidea, and its quality markers and hypoglycemic mechanism are still unclear. The purpose of this study is to explore the quality markers (Q-markers) of Cyanotis arachnoidea and predict its hypoglycemic mechanism. In this study, ultra-high-performance liquid chromatography (UHPLC) fingerprint combined with chemical pattern recognition were performed, and four differential components were screened out as quality markers, including 20-Hydroxyecdysone, 3-O-acetyl-20-hydroxyecdysone, Ajugasterone C, and 2-O-acetyl-20-hydroxyecdysone. Network pharmacology analysis revealed 107 therapeutic target genes of Cyanotis arachnoidea in DM treatment, and the key targets were Akt1, TNF, IL-6, MAPK3, and JUN. The hypoglycemic mode of action of Cyanotis arachnoidea may be mediated by tumor necrosis factor (TNF) signaling, cancer, insulin resistance, and JAK-STAT pathways. Molecular docking analysis disclosed that the foregoing quality markers effectively bound their key target genes. An in vitro experiment conducted on pancreatic islet ß-cells indicated that the forenamed active components of Cyanotis arachnoidea had hypoglycemic efficacy by promoting PI3K/Akt and inhibiting MAPK signaling. UHPLC also accurately quantified the quality markers. The identification and analysis of quality markers for Cyanotis arachnoidea is expected to provide references for the establishment of a quality control evaluation system and clarify the material basis and hypoglycemic mechanisms of this traditional Chinese medicine (TCM).


Assuntos
Commelinaceae , Ecdisterona , Ecdisterona/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Hipoglicemiantes/farmacologia
14.
Molecules ; 28(18)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37764295

RESUMO

Although numerous thermoelectric (TE) composites of organic materials and single-walled carbon nanotubes (SWCNTs) have been developed in the past decade, most of the research has been related to polymers without much on organic small molecules (OSMs). In this work, benzothieno[3,2-b]benzofuran (BTBF) and its derivatives (BTBF-Br and BTBF-2Br) were synthesized and their TE composites with SWCNTs were prepared. It is found that the highest molecular orbital level and band gap (Eg) of BTBF, BTBF-Br, and BTBF-2Br gradually decrease upon the introduction of electron-withdrawing Br group on BTBF. These changes significantly improve the Seebeck coefficient and power factor (PF) of OSM/SWCNT composites. An appropriate energy barrier between BTBF-2Br and SWCNTs promotes the energy filtering effect, which further contributes to the enhancement of composites' thermoelectric properties. The composites of SWCNTs and BTBF-2Br with the smallest Eg (4.192 eV) afford the best thermoelectric performance with the room temperature power factor of 169.70 ± 3.46 µW m-1 K-2 in addition to good mechanical flexibility and thermal stability. This study provides a feasible strategy for the preparation of OSM/SWCNT composites with improved thermoelectric properties.

15.
Biomed Res Int ; 2023: 6435776, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37475819

RESUMO

Objectives: A series of laboratory parameters were screened to identify the proper serum markers that could be used to predict breast cancer recurrence at an early stage. Methods: A case-control retrospective study on 224 patients without postoperative recurrence and 43 patients with postoperative recurrence of breast cancer was performed. The edgeR software package was used to identify the test indicators expressed differently between the two groups. Univariate analysis was used to screen for diagnostic marker that could predict postoperative recurrence of breast cancer. In addition, the differential test indicators at different time points from surgery to recurrence were collected in patients with postoperative recurrence of breast cancer as a verification database. Results: We screened out three test indicators (TBA, GSP, and URBC) for differential expression, which were all expressed downregulated in the postoperative recurrence group of breast cancer. Univariate analysis suggested that only the difference in GSP levels between the two groups was statistically significant (P = 0.001). ROC curve analysis showed that the area under the curve of GSP was 0.662, while the area under the curve of GSP+AFP+CEA+CA125+CA153+age was increased to 0.828. In addition, serum GSP levels were significantly reduced after recurrence compared with before recurrence in breast cancer patients (P < 0.01). Conclusions: In summary, GSP could be used for early diagnosis of breast cancer recurrence after surgery, and the predicted value of combining GSP, tumor markers, and age was better than that of individual indicators.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Antígeno Carcinoembrionário , Frutosamina , Recidiva Local de Neoplasia/patologia , Biomarcadores Tumorais/metabolismo
16.
PLoS One ; 18(6): e0287328, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37319180

RESUMO

Both the number of dust explosion accidents and the resulting number of casualties have increased dramatically in recent years. To reduce this risk of dust explosions, we use the functional resonance analysis method (FRAM) to analyze the cause of the dust explosion accident at the Kunshan factory and propose barrier measures to prevent such accidents. The functional units that changed in the production system during the accident and how these functional units coupled to eventually cause the dust explosion were examined and explained. In addition, barrier measures were developed for functional units that changed during production and emergency systems defined to block the propagation of changes between functions and prevent resonance. Through case study, the identification of key functional parameters in both triggering the initial explosion and in then allowing its spread are key to define barriers to prevent a recurrence of such an event. FRAM uses system function coupling instead of traditional linear causality to explain the accident process, and develops barrier measures for changing function units, providing a novel thinking strategy and method for the analysis of accidents and their prevention.


Assuntos
Traumatismos por Explosões , Queimaduras , Humanos , Explosões/prevenção & controle , Poeira , Acidentes de Trabalho , Alumínio
17.
Chem Sci ; 14(13): 3630-3641, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37006673

RESUMO

Photo-click chemistry has emerged as a powerful tool for revolutionizing bioconjugation technologies in pharmacological and various biomimetic applications. However, enriching the photo-click reactions to expand the bioconjugation toolkit remains challenging, especially when focusing on spatiotemporal control endowed by light activation. Herein, we describe a photo-induced defluorination acyl fluoride exchange (photo-DAFEx) as a novel type of photo-click reaction that is mediated through acyl fluorides produced by the photo-defluorination of m-trifluoromethylaniline to covalently conjugate with primary/secondary amines and thiols in an aqueous environment. (TD)-DFT calculations, together with experimental discovery, indicate that the m-NH2PhF2C(sp3)-F bond in the excited triplet state is cleaved by water molecules, which is key to inducing defluorination. Intriguingly, the benzoyl amide linkages built by this photo-click reaction exhibited a satisfactory fluorogenic performance, which allowed visualization of its formation in situ. Accordingly, this photo-controlled covalent strategy was exploited not only for the decoration of small molecules, peptide cyclization and functionalization of proteins in vitro, but also for designing photo-affinity probes targeting endogenous carbonic anhydrase II (hCA-II) in living cells.

18.
Sci Rep ; 13(1): 5984, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37045929

RESUMO

Taking NVP-BEZ235 (BEZ235) as an example to screen drug response-related genes (DRRGs) and explore their potential value in triple-negative breast cancer (TNBC). Through high-throughput technique, multidimensional transcriptome expression data (mRNA, miRNA and lncRNA) of BEZ235-treated and -untreated MDA-MB-468 cell lines were obtained. Combined with transcriptome data of the MDA-MB-468 cells and TCGA-TNBC tissues, differential gene expression analysis and WGCNA were performed to identify DRRGs associated with tumor trait by simulating the drug response microenvironment (DRM) of BEZ235-treated patients. Based on DRRGs, we constructed a ceRNA network and verified the expression levels of three key molecules by RT-qPCR, which not only demonstrated the successful construction of a BEZ235-treated cell line model but also explained the antitumor mechanism of BEZ235. Four molecular subtypes related to the DRM with survival difference were proposed using cluster analysis, namely glycolysis subtype, proliferation depression subtype, immune-suppressed subtype, and immune-activated subtype. A novel prognostic signature consisting of four DRRGs was established by Lasso-Cox analysis, which exhibited outstanding performance in predicting overall survival compared with several excellent reported signatures. The high- and low-risk groups were characterized by enrichment of metabolism-related pathways and immune-related pathways, respectively. Of note, the low-risk group had a better response to immune checkpoint blockade. Besides, pRRophetic analysis found that patients in the low-risk group were more sensitive to methotrexate and cisplation, whereas more resistant to BEZ235, docetaxel and paclitaxel. In conclusion, the DRRGs exemplified by BEZ235 are potential biomarkers for TNBC molecular typing, prognosis prediction and targeted therapy. The novel DRRGs-guided strategy for predicting the subtype, survival and therapy efficacy, might be also applied to more cancers and drugs other than TNBC and BEZ235.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Docetaxel/uso terapêutico , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Microambiente Tumoral
19.
Front Public Health ; 11: 1084005, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36875399

RESUMO

Background: Osteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed. Methods: The study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses. Results: After screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80-34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58-21.87%) and 38.05% (95% CI, 37.22-38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people. Conclusions: This study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Idoso , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Fumar , Estudos de Coortes , Estudos Transversais , Prevalência , China
20.
Psych J ; 12(4): 479-490, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36916767

RESUMO

Duration perception can be heavily distorted owing to repetitive exposure to a relatively long or short sensory event, often causing a duration aftereffect. Here, we used a novel procedure to show that adaptations to both single and average durations produced the duration aftereffect. Participants completed a duration reproduction task (Experiment 1) or a duration category rating task (Experiment 2) after long-term adaptations to a stimulus of medium duration and to stimuli of averagely medium duration. We found that adaptations to both single and average durations resulted in duration aftereffects. The simultaneously recorded functional magnetic resonance imaging (fMRI) data revealed that the reduction in neural activity due to long-term adaptation to single duration was observed in the right supramarginal gyrus (SMG) of the parietal lobe, while adaptation to average duration resulted in fMRI adaptations in the left postcentral gyrus (PCG) and middle cingulate gyrus (MCG). At the individual level, the magnitude of the behavioral aftereffect was positively correlated with the magnitude of fMRI adaptation in the right SMG after adaptation to single duration, while there were no significantly positive correlations between the behavioral aftereffect and fMRI adaptations in the left PCG and MCG. These results suggest that there are different neural mechanisms for aftereffects caused by adaptations to single and average durations.

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