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1.
J Asian Nat Prod Res ; : 1-30, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38920368

RESUMEN

Modifications at different positions on the aloperine molecule were performed to improve its anticancer activity and develop anticancer drugs. The in vitro anticancer activities of 44 synthesized compounds were evaluated. The effect of modification positions on anticancer activity was discussed and a structure-activity relationship analysis was established. A novel series of compounds with modifications at the N12 position showed much higher cytotoxicity than aloperine. Among them, compound 22 displayed promising in vitro anticancer activity against PC9 cells with a median inhibitory concentration (IC50) of 1.43 µM. The mechanism studies indicated that compound 22 induced cell apoptosis and cell cycle arrest in PC9 cells. These results demonstrate the potential of aloperine thiourea derivatives in anticancer activity.

2.
Brain Res Bull ; : 111021, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38942396

RESUMEN

The ability to accurately encode the temporal information of sensory events and hence to make prompt action is fundamental to humans' prompt behavioral decision-making. Here we examined the ability of ensemble coding (averaging multiple inter-intervals in a sound sequence) and subsequent immediate reproduction of target duration at half, equal, or double that of the perceived mean interval in a sensorimotor loop. With magnetoencephalography (MEG), we found that the contingent magnetic variation (CMV) in the central scalp varied as a function of the averaging tasks, with a faster rate for buildup amplitudes and shorter peak latencies in the "half" condition as compared to the "double" condition. ERD (event-related desynchronization) -to-ERS (event-related synchronization) latency was shorter in the "half" condition. A robust beta band (15-23Hz) power suppression and recovery between the final tone and the action of key pressing was found for time reproduction. The beta modulation depth (i.e., the ERD-to-ERS power difference) was larger in motor areas than in primary auditory areas. Moreover, results of phase slope index (PSI) indicated that beta oscillations in the left supplementary motor area (SMA) led those in the right superior temporal gyrus (STG), showing SMA to STG directionality for the processing of sequential (temporal) auditory interval information. Our findings provide the first evidence to show that CMV and beta oscillations predict the coupling between perception and action in time averaging.

3.
Nat Commun ; 15(1): 5407, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926359

RESUMEN

Cycloaddition reactions play a pivotal role in synthetic chemistry for the direct assembly of cyclic architectures. However, hurdles remain for extending the C4 synthon to construct diverse heterocycles via programmable [4+n]-cycloaddition. Here we report an atom-economic and modular intermolecular cycloaddition using furan-fused cyclobutanones (FCBs) as a versatile C4 synthon. In contrast to the well-documented cycloaddition of benzocyclobutenones, this is a complementary version using FCB as a C4 reagent. It involves a C-C bond activation and cycloaddition sequence, including a Rh-catalyzed enantioselective [4 + 2]-cycloaddition with imines and an Au-catalyzed diastereoselective [4 + 4]-cycloaddition with anthranils. The obtained furan-fused lactams, which are pivotal motifs that present in many natural products, bioactive molecules, and materials, are inaccessible or difficult to prepare by other methods. Preliminary antitumor activity study indicates that 6e and 6 f exhibit high anticancer potency against colon cancer cells (HCT-116, IC50 = 0.50 ± 0.05 µM) and esophageal squamous cell carcinoma cells (KYSE-520, IC50 = 0.89 ± 0.13 µM), respectively.


Asunto(s)
Reacción de Cicloadición , Ciclobutanos , Furanos , Catálisis , Ciclobutanos/química , Humanos , Furanos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Estereoisomerismo , Células HCT116
4.
Microbiome ; 12(1): 114, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38915127

RESUMEN

BACKGROUND: Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS. RESULTS: We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells. CONCLUSIONS: Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. Video Abstract.


Asunto(s)
Ácido Elágico , Encefalomielitis Autoinmune Experimental , Microbioma Gastrointestinal , Esclerosis Múltiple , Propionatos , Ácido Elágico/farmacología , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/microbiología , Propionatos/metabolismo , Ratones , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/microbiología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Femenino , Autoinmunidad/efectos de los fármacos , Disbiosis/microbiología , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/inmunología , Humanos , Administración Oral
5.
Angew Chem Int Ed Engl ; : e202401557, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775225

RESUMEN

A regio- and stereoselective stepwise (4+2) annulation of N-propargylamides and α,ß-unsaturated imines/ketones has been accomplished with synergetic catalysis by a combination of a gold-complex and a chiral quinine-derived squaramide (QN-SQA), leading to highly functionalized chiral tetrahydropyridines/dihydropyrans in good to high yields with generally excellent enantioselectivity. Mechanistic studies and DFT calculations indicate that the in situ formed alkylgold species is the key intermediate in this transformation, and the amide group served as a traceless directing group in this highly selective transformation. This method complements the enantioselective (4+2) annulation of allene reagents, providing the formal internal C-C π-bond cycloaddition products, which is challenging and remains elusive.

6.
Int J Biol Macromol ; 269(Pt 2): 131964, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692525

RESUMEN

This study aims to identify FDA-approved drugs that can target the kappa-opioid receptor (KOR) for the treatment of demyelinating diseases. Demyelinating diseases are characterized by myelin sheath destruction or formation that results in severe neurological dysfunction. Remission of this disease is largely dependent on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLGs) in demyelinating lesions. KOR is an important regulatory protein and drug target for the treatment of demyelinating diseases. However, no drug targeting KOR has been developed due to the long clinical trials for drug discovery. Here, a structure-based virtual screening was applied to identify drugs targeting KOR among 1843 drugs of FDA-approved drug libraries, and famotidine was screen out by its high affinity cooperation with KOR as well as the clinical safety. We discovered that famotidine directly promoted OPC maturation and remyelination using the complementary in vitro and in vivo models. Administration of famotidine was not only effectively enhanced CNS myelinogenesis, but also promoted remyelination. Mechanically speaking, famotidine promoted myelinogenesis or remyelination through KOR/STAT3 signaling pathway. In general, our study provided evidence of new clinical applicability of famotidine for the treatment of demyelinating diseases for which there is currently no effective therapy.


Asunto(s)
Diferenciación Celular , Famotidina , Receptores Opioides kappa , Remielinización , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Humanos , Ratones , Diferenciación Celular/efectos de los fármacos , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/metabolismo , Famotidina/farmacología , Vaina de Mielina/metabolismo , Vaina de Mielina/efectos de los fármacos , Células Precursoras de Oligodendrocitos/efectos de los fármacos , Células Precursoras de Oligodendrocitos/metabolismo , Células Precursoras de Oligodendrocitos/citología , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , Oligodendroglía/citología , Receptores Opioides kappa/metabolismo , Remielinización/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Femenino , Ratones Endogámicos C57BL , Células HEK293
7.
Org Lett ; 26(22): 4793-4796, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38796778

RESUMEN

Triflimide catalysis of the [3 + 2]-cycloaddition of 3-indolymethanols with vinyldiazoacetates provides general access to ß-tetrahydrocyclopenta[b]indol-substituted α-diazoesters. Initiated by addition of the in situ generated vinylogous iminium electrophile from 3-indolymethanol to the vinylogous position of the vinyldiazo compound and completed by intramolecular cyclization from the vinyldiazonium ion intermediate, this transformation occurs in good yields and excellent diastereoselectivity with a broad substrate scope under mild conditions. The resulting α-diazoesters undergo Rh2(OAc)4-catalyzed substrate-dependent 1,2-migration to form multisubstituted carbazoles in high yields.

8.
Biosensors (Basel) ; 14(5)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38785717

RESUMEN

Real-time monitoring of physiological indicators inside the body is pivotal for contemporary diagnostics and treatments. Implantable electrodes can not only track specific biomarkers but also facilitate therapeutic interventions. By modifying biometric components, implantable electrodes enable in situ metabolite detection in living tissues, notably beneficial in invasive glucose monitoring, which effectively alleviates the self-blood-glucose-managing burden for patients. However, the development of implantable electrochemical electrodes, especially multi-channel sensing devices, still faces challenges: (1) The complexity of direct preparation hinders functionalized or multi-parameter sensing on a small scale. (2) The fine structure of individual electrodes results in low spatial resolution for sensor functionalization. (3) There is limited conductivity due to simple device structures and weakly conductive electrode materials (such as silicon or polymers). To address these challenges, we developed multiple-channel electrochemical microneedle electrode arrays (MCEMEAs) via a separated functionalization and assembly process. Two-dimensional microneedle (2dMN)-based and one-dimensional microneedle (1dMN)-based electrodes were prepared by laser patterning, which were then modified as sensing electrodes by electrochemical deposition and glucose oxidase decoration to achieve separated functionalization and reduce mutual interference. The electrodes were then assembled into 2dMN- and 1dMN-based multi-channel electrochemical arrays (MCEAs), respectively, to avoid damaging functionalized coatings. In vitro and in vivo results demonstrated that the as-prepared MCEAs exhibit excellent transdermal capability, detection sensitivity, selectivity, and reproducibility, which was capable of real-time, in situ glucose concentration monitoring.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Electrodos , Animales , Glucosa Oxidasa , Ratas , Humanos , Glucemia/análisis , Agujas
9.
J Chem Inf Model ; 64(10): 4348-4358, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38709146

RESUMEN

Developing new pharmaceuticals is a costly and time-consuming endeavor fraught with significant safety risks. A critical aspect of drug research and disease therapy is discerning the existence of interactions between drugs and proteins. The evolution of deep learning (DL) in computer science has been remarkably aided in this regard in recent years. Yet, two challenges remain: (i) balancing the extraction of profound, local cohesive characteristics while warding off gradient disappearance and (ii) globally representing and understanding the interactions between the drug and target local attributes, which is vital for delivering molecular level insights indispensable to drug development. In response to these challenges, we propose a DL network structure, MolLoG, primarily comprising two modules: local feature encoders (LFE) and global interactive learning (GIL). Within the LFE module, graph convolution networks and leap blocks capture the local features of drug and protein molecules, respectively. The GIL module enables the efficient amalgamation of feature information, facilitating the global learning of feature structural semantics and procuring multihead attention weights for abstract features stemming from two modalities, providing biologically pertinent explanations for black-box results. Finally, predictive outcomes are achieved by decoding the unified representation via a multilayer perceptron. Our experimental analysis reveals that MolLoG outperforms several cutting-edge baselines across four data sets, delivering superior overall performance and providing satisfactory results when elucidating various facets of drug-target interaction predictions.


Asunto(s)
Aprendizaje Profundo , Proteínas , Proteínas/metabolismo , Proteínas/química , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/metabolismo , Descubrimiento de Drogas/métodos , Modelos Moleculares
10.
Nat Commun ; 15(1): 4574, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811537

RESUMEN

Heterocyclic rings are important structural scaffolds encountered in both natural and synthetic compounds, and their biological activity often depends on these motifs. They are predominantly accessible via cycloaddition reactions, realized by either thermal, photochemical, or catalytic means. Various starting materials are utilized for this purpose, and, among them, diazo compounds are often encountered, especially vinyldiazo compounds that give access to donor-acceptor cyclopropenes which engage in [2+n] cycloaddition reactions. Herein, we describe the development of photochemical processes that produce diverse heterocyclic scaffolds from multisubstituted oximidovinyldiazo compounds. High chemoselectivity, good functional group tolerance, and excellent scalability characterize this methodology, thus predisposing it for broader applications. Experimental and computational studies reveal that under light irradiation these diazo reagents selectively transform into cyclopropenes which engage in cycloaddition reactions with various dipoles, while under thermal conditions the formation of pyrazole from vinyldiazo compounds is favored.

12.
Neurol Neuroimmunol Neuroinflamm ; 11(3): e200221, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38579189

RESUMEN

BACKGROUND AND OBJECTIVES: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population. METHODS: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls. RESULTS: Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10-8, OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 (p = 4.36 × 10-7; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 (p = 1.28 × 10-8; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQß1-126H (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R (p = 3.40 × 10-8; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02. DISCUSSION: Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Cadenas beta de HLA-DQ , Helicasa Inducida por Interferón IFIH1 , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/genética , Estudio de Asociación del Genoma Completo , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase II/genética , Antígenos HLA-A/genética , Cadenas beta de HLA-DQ/genética , Helicasa Inducida por Interferón IFIH1/genética
13.
World J Clin Cases ; 12(12): 2065-2073, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38680258

RESUMEN

BACKGROUND: Human immunodeficiency virus (HIV)-associated dementia (HAD) is a subcortical form of dementia characterized by memory deficits and psychomotor slowing. However, HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease (CJD), particularly in patients with acquired immune deficiency syndrome (AIDS). CASE SUMMARY: We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure. The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins. His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern. Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination. Initially, symptomatic treatment and administration of amantadine were pursued for presumed CJD, but the patient's condition continued to deteriorate. By contrast, the patient's condition improved following anti-HIV therapy. This individual is also the only patient with this prognosis to have survived over 4 years. Thus, the diagnosis was revised to HAD. CONCLUSION: In the diagnostic process of rapidly progressive dementia, it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty. The 14-3-3 protein should not be regarded as the definitive marker for CJD. Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision, especially in AIDS patients with potential CJD. Ultimately, a trial of diagnostic treatment may be considered when additional testing is not feasible.

14.
J Health Psychol ; : 13591053241248940, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38686932

RESUMEN

This study investigated whether emotion regulation mediates or modulates the relationship of SLEs with sleep quality and potential sex differences. A total of 1447 Chinese university students completed the Adolescent Self-Rating Life Events Checklist, the Pittsburgh Sleep Quality Index, and the Emotion Regulation Questionnaire. The results indicated that both cognitive reappraisal and expressive suppression significantly mediated and moderated the negative association between SLEs and sleep quality. Additionally, sex differences were found for the mediating role of cognitive reappraisal and for the modulating roles of cognitive reappraisal and expressive suppression in the relationship between SLEs and sleep quality. Although the present cross-sectional data does not allow us to test any causal relationships, these results help clarify the underlying emotion-regulation process between SLEs and sleep in university students and highlight the importance of considering sex differences in emotion regulation.

15.
Int Immunopharmacol ; 131: 111861, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38484665

RESUMEN

Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.


Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Histona Desacetilasa 6 , Leucemia Mieloide Aguda , Animales , Humanos , Ratones , Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Glutatión/metabolismo , Histona Desacetilasa 6/antagonistas & inhibidores , Leucemia Mieloide Aguda/metabolismo , Hígado/patología , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos
16.
Gen Psychiatr ; 37(2): e101281, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481577

RESUMEN

Background: The alexithymia trait is of high clinical interest. The Perth Alexithymia Questionnaire (PAQ) was recently developed to enable detailed facet-level and valence-specific assessments of alexithymia. Aims: In this paper, we introduce the first Chinese version of the PAQ and examine its psychometric properties and clinical applications. Methods: In Study 1, the PAQ was administered to 990 Chinese participants. We examined its factor structure, internal consistency, test-retest reliability, as well as convergent, concurrent and discriminant validity. In Study 2, four groups, including a major depressive disorder (MDD) group (n=50), a matched healthy control group for MDD (n=50), a subclinical depression group (n=50) and a matched healthy control group for subclinical depression (n=50), were recruited. Group comparisons were conducted to assess the clinical relevance of the PAQ. Results: In Study 1, the intended five-factor structure of the PAQ was found to fit the data well. The PAQ showed good internal consistency and test-retest reliability, as well as good convergent, concurrent and discriminant validity. In Study 2, the PAQ was able to successfully distinguish the MDD group and the subclinical depression group from their matched healthy controls. Conclusions: The Chinese version of the PAQ is a valid and reliable instrument for comprehensively assessing alexithymia in the general population and adults with clinical/subclinical depression.

17.
Exp Ther Med ; 27(4): 165, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38476898

RESUMEN

Cell adhesion molecule close homolog of L1 (CHL1) is implicated in tumorigenesis of various malignancies. However, its role and underlying molecular mechanisms in colorectal cancer (CRC) remain unclear. The present study aimed to evaluate the specific biological functions and mechanisms of CHL1, in order to provide a theoretical basis for the use of CHL1 as a biological target in CRC. CHL1 expression was originally determined in CRC cell lines. Subsequently, CHL1 overexpression was induced by plasmid transfection in HT29 and SW480 cells, and cell proliferation, migration and invasion were evaluated using the Cell Counting Kit-8, clone formation, organoids formation and Transwell assays. Immunofluorescence and western blotting were performed to assess the protein expression of E-cadherin or N-cadherin. Differentially expressed genes (DEGs) were further evaluated using RNA-sequencing (RNA-seq) in HT29 and SW480 cells following CHL1 overexpression and functional enrichment analysis. Western blotting was performed to validate the expression of proteins related to the nuclear factor κB (NF-κB) signaling pathway. The TNMplot online database revealed the significant downregulation of CHL1 in CRC tissues. The results indicated that exogenous CHL1 overexpression significantly inhibited the proliferative, organoid-forming, migratory and invasive abilities of HT29 and SW480 cells, and increased E-cadherin protein expression. Additionally, CHL1 overexpression reduced xenograft tumor growth in vivo. RNA-seq and functional analysis revealed that DEGs in CHL1 overexpressing cells were mainly enriched in the NF-κB signaling pathway. The expression of p-p65 and p-p65/p65 ratio were significantly reduced in HT29 and SW480 cells, following CHL1 overexpression. Additionally, the inhibitory effects of CHL1 overexpression on CRC cell proliferation, organoid formation, migration and invasion were partially counteracted following the overexpression of p65 expression. Overall, the present study demonstrates that CHL1 inhibits CRC cell growth, migration and invasion through the inactivation of the NF-κB signaling pathway.

18.
Org Lett ; 26(3): 664-669, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38226908

RESUMEN

A visible-light-driven iron-catalyzed C(sp3)-H amination of diphenylmethane derivatives with 1,2,3,4-tetrazoles under mild conditions has been developed. The reaction proceeds with photosensitizer-free conditions and features satisfactory to good yields. Mechanistic studies revealed that the reaction proceeded via an iron-nitrene intermediate, and H atom abstraction was the rate-determining step. Computational studies showed that the denitrogenation of 1,2,3,4-tetrazole depends on the conversion of the sextet ground state of 1,2,3,4-tetrazole-bounding iron species to the quartet spin state under visible-light irradiation.

19.
Org Biomol Chem ; 22(6): 1141-1145, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38214226

RESUMEN

A strategy for direct synthesis of phenanthrenyl triflates from 1-biphenylyl-2-diazo-2-aryl ketones and triflic anhydride is described. The reaction of 1-biphenylyl-2-diazo-2-aryl ketones with triflic anhydride proceeded smoothly in the presence of 2,6-di-tert-butylpyridine under mild conditions to produce phenanthrenyl triflates in high to excellent yields. The phenanthrenyl triflate products were demonstrated to be utilized as coupling partners in various coupling reactions. The proposed mechanism involves an intramolecular Friedel-Crafts reaction of a vinyl cation intermediate formed in situ.

20.
J Clin Psychol ; 80(7): 1473-1489, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38236207

RESUMEN

OBJECTIVE: Alterations of empathy have been observed in patients with various mental disorders. The Perth Empathy Scale (PES) was recently developed to measure a multidimensional construct of empathy across positive and negative emotions. However, its psychometric properties and clinical applications have not been examined in the Chinese context. METHODS: The Chinese version of the PES was developed and administered to a large Chinese sample (n = 1090). Factor structure, internal consistency, test-retest reliability, and convergent, discriminant, as well as concurrent validity were examined. Moreover, 50 patients with major depressive disorder (MDD) and 50 healthy controls were recruited to explore the clinical utility of the PES. RESULTS: Confirmatory factor analyses supported a theoretically congruent three-factor structure of empathy, namely Cognitive Empathy, Negative Affective Empathy and Positive Affective Empathy. The PES showed good to excellent internal consistency reliability, good convergent and discriminant validity, acceptable concurrent validity, and moderate to high test-retest reliability. Patients with MDD had significantly lower PES scores compared to healthy controls. Linear discriminant function comprised of the three factors correctly differentiated 71% of participants, which further verified the clinical utility of the PES. CONCLUSIONS: Our findings indicated that the Chinese version of the PES is a reliable and valid instrument to measure cognitive and affective empathy across negative and positive emotions, and could therefore be used in both research and clinical practice.


Asunto(s)
Trastorno Depresivo Mayor , Empatía , Psicometría , Humanos , Masculino , Femenino , Adulto , Psicometría/instrumentación , Psicometría/normas , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto Joven , China , Comparación Transcultural , Adolescente , Análisis Factorial
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