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1.
Int J Psychophysiol ; 204: 112424, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39178992

RESUMEN

Economic decision-making plays a paramount role in both individual and national interests. Individuals have fairness preferences in economic decision-making, but a proposer's moral-related information may affect fairness considerations. In prior ERP studies, researchers have suggested moral identity influences fairness preferences in the Ultimatum Game (UG), but there are discrepancies in the results. Furthermore, whether role models (individuals whom someone else looks to help decide suitable behaviors), who can modulate people's moral standards, can affect fairness concerns in UG is still understudied. To address the questions, we selected the moral-related statements by eliminating those with illegal information and employed the ERP technique to explore whether the interplay of the proposer's role model and moral-related behavior influenced fairness processing in the modified UG and the corresponding neural mechanisms. We mainly found that the aforementioned interaction effect on proposal considerations in UG could be mirrored in both rejection rates and P300 variations. The results demonstrate that the interaction between the proposer's role model and moral behavior can modulate fairness concerns in UG. Our current work provides new avenues for elucidating the time course of the influencing mechanism of fair distributions in complicated social environments.

2.
EBioMedicine ; 107: 105286, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39168091

RESUMEN

BACKGROUND: Genome-wide association studies (GWAS) have revealed many brain disorder-associated SNPs residing in the noncoding genome, rendering it a challenge to decipher the underlying pathogenic mechanisms. METHODS: Here, we present an unsupervised Bayesian framework to identify disease-associated genes by integrating risk SNPs with long-range chromatin interactions (iGOAT), including SNP-SNP interactions extracted from ∼500,000 patients and controls from the UK Biobank, and enhancer-promoter interactions derived from multiple brain cell types at different developmental stages. FINDINGS: The application of iGOAT to three psychiatric disorders and three neurodegenerative/neurological diseases predicted sets of high-risk (HRGs) and low-risk (LRGs) genes for each disorder. The HRGs were enriched in drug targets, and exhibited higher expression during prenatal brain developmental stages than postnatal stages, indicating their potential to affect brain development at an early stage. The HRGs associated with Alzheimer's disease were found to share genetic architecture with schizophrenia, bipolar disorder and major depressive disorder according to gene co-expression module analysis and rare variants analysis. Comparisons of this method to the eQTL-based method, the TWAS-based method, and the gene-level GWAS method indicated that the genes identified by our method are more enriched in known brain disorder-related genes, and exhibited higher precision. Finally, the method predicted 205 risk genes not previously reported to be associated with any brain disorder, of which one top-risk gene, MLH1, was experimentally validated as being schizophrenia-associated. INTERPRETATION: iGOAT can successfully leverage epigenomic data, phenotype-genotype associations, and protein-protein interactions to advance our understanding of brain disorders, thereby facilitating the development of new therapeutic approaches. FUNDING: The work was funded by the National Key Research and Development Program of China (2024YFF1204902), the Natural Science Foundation of China (82371482), Guangzhou Science and Technology Research Plan (2023A03J0659) and Natural Science Foundation of Guangdong (2024A1515011363).

3.
Hum Genet ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39192052

RESUMEN

The development of sequencing technology has promoted discovery of variants in the human genome. Identifying functions of these variants is important for us to link genotype to phenotype, and to diagnose diseases. However, it usually requires researchers to visit multiple databases. Here, we presented a one-stop webserver for variant function annotation tools (VCAT, https://biomed.nscc-gz.cn/zhaolab/VCAT/ ) that is the first one connecting variant to functions via the epigenome, protein, drug and RNA. VCAT is also the first one to make all annotations visualized in interactive charts or molecular structures. VCAT allows users to upload data in VCF format, and download results via a URL. Moreover, VCAT has annotated a huge number (1,262,041,068) of variants collected from dbSNP, 1000 Genomes projects, gnomAD, ICGC, TCGA, and HPRC Pangenome project. For these variants, users are able to searcher their functions, related diseases and drugs from VCAT. In summary, VCAT provides a one-stop webserver to explore the potential functions of human genomic variants including their relationship with diseases and drugs.

4.
Hum Brain Mapp ; 45(12): e26789, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39185719

RESUMEN

Emotion perception interacts with how we think and speak, including our concept of emotions. Body expression is an important way of emotion communication, but it is unknown whether and how its perception is modulated by conceptual knowledge. In this study, we employed representational similarity analysis and conducted three experiments combining semantic similarity, mouse-tracking task, and one-back behavioral task with electroencephalography and functional magnetic resonance imaging techniques, the results of which show that conceptual knowledge predicted the perceptual representation of body expressions. Further, this prediction effect occurred at approximately 170 ms post-stimulus. The neural encoding of body expressions in the fusiform gyrus and lingual gyrus was impacted by emotion concept knowledge. Taken together, our results indicate that conceptual knowledge of emotion categories shapes the configural representation of body expressions in the ventral visual cortex, which offers compelling evidence for the constructed emotion theory.


Asunto(s)
Mapeo Encefálico , Electroencefalografía , Emociones , Imagen por Resonancia Magnética , Humanos , Emociones/fisiología , Masculino , Adulto Joven , Femenino , Adulto , Percepción Social , Formación de Concepto/fisiología
5.
Cogn Emot ; : 1-11, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953160

RESUMEN

Intertemporal decision-making is important for both economy and physical health. Nevertheless, in daily life, individuals tend to prefer immediate and smaller rewards to delayed and larger rewards, which is known as delay discounting (DD). Episodic future thinking (EFT) has been proven to influence DD. However, there is still no inconsistent conclusion on the effect of negative EFT on DD. Considering the perceived controllability of negative EFT may address the issue (Controllability refers to the extent to which progress and result of an event could be controlled by ourselves). In the current study, we manipulated EFT conditions (baseline, neutral EFT, negative-controllable EFT and negative-uncontrollable EFT), delayed time (i.e. 1 week, 1 month, 3 months, 6 months, 1 year and 3 years) and reward magnitude (small, large). We mainly found that when experiencing negative-uncontrollable EFT compared to negative-controllable EFT in the delayed time of 6 months with large rewards, individuals chose more delayed rewards, suggesting that negative-uncontrollable EFT effectively reduced DD under conditions of both large-magnitude reward and longer delayed time. The current study provides new insight for healthy groups on optimising EFT. In that case, individuals are able to gain long-term benefits in financial management and healthcare.

6.
Hypertens Res ; 47(9): 2561-2573, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39014115

RESUMEN

Pregnancy is normally contraindicated in pulmonary arterial hypertension (PAH). Thanks to medical advances, the prognosis for pregnancy in patients with PAH has improved. The aim of our study was to investigate pregnancy conditions and outcomes in patients with mild, moderate and severe PAH. We searched PubMed, Embase, CNKI, Wanfang and Weipu databases for studies published before May 2024. Data from 29 included studies from 1898 references were pooled and analyzed. We calculated the rates for each group as well as the risk ratio (RR) and 95% confidence interval (CI) between pairwise. There was no statistical difference in maternal and neonatal survival between the mild and moderate groups. Maternal survival in the mild, moderate and severe groups was 100.0%, 99.7% and 88.8%, respectively, and neonatal survival was 100.0%, 99.7% and 96.0%, respectively. The incidence of NYHA class III-IV, pregnancy loss, intensive care unit (ICU) admission, fetal growth restriction, and neonatal asphyxia was lowest in patients with mild PAH and highest in patients with severe PAH (P < 0.001). The incidence of vaginal deliveries and term pregnancies was highest in the mild group and lowest in the severe group (P < 0.001). In conclusion, pregnant women with mild PAH can safely deliver a newborn. Given similar survival rates but greater economic and medical burdens, caution is advised in the moderate group. Pregnancy in the severe group is considered contraindicated.


Asunto(s)
Complicaciones Cardiovasculares del Embarazo , Resultado del Embarazo , Humanos , Embarazo , Femenino , Complicaciones Cardiovasculares del Embarazo/epidemiología , Hipertensión Arterial Pulmonar/epidemiología , China/epidemiología , Recién Nacido , Índice de Severidad de la Enfermedad , Hipertensión Pulmonar/epidemiología , Adulto , Pueblos del Este de Asia
7.
Behav Sci (Basel) ; 14(6)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38920840

RESUMEN

Ensemble coding allows observers to form an average to represent a set of elements. However, it is unclear whether observers can extract an average from a cross-category set. Previous investigations on this issue using low-level stimuli yielded contradictory results. The current study addressed this issue by presenting high-level stimuli (i.e., a crowd of facial expressions) simultaneously (Experiment 1) or sequentially (Experiment 2), and asked participants to complete a member judgment task. The results showed that participants could extract average information from a group of cross-category facial expressions with a short perceptual distance. These findings demonstrate cross-category ensemble coding of high-level stimuli, contributing to the understanding of ensemble coding and providing inspiration for future research.

8.
J Cogn Neurosci ; 36(9): 1864-1878, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38739570

RESUMEN

Intertemporal decision-making is pivotal for human interests and health. Recently, studies instructed participants to make intertemporal choices for both themselves and others, but the specific mechanisms are still debated. To address the issue, in the current study, the cost-unneeded conditions (i.e., "Self Immediately - Self Delay" and "Other Immediately - Other Delay" conditions) and the cost-needed conditions (i.e., "Self Immediately - Other Delay" and "Self Delay - Other Immediately" conditions) were set with the identity of OTHER being a stranger. We manipulated the magnitude of reward (Experiment 1) and disrupted the activation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation (rTMS; Experiment 2). We found that both the behavioral and rTMS manipulations increased smaller but sooner choice probability via reducing self-control function. The reduced self-control function elicited by rTMS affected both self- and other-related intertemporal choices via increasing the choice preference for smaller but sooner reward options, which may help people deeply understand the relationship between self- and other-related intertemporal choices in processing mechanism, especially when the OTHER condition is set as a stranger.


Asunto(s)
Descuento por Demora , Corteza Prefontal Dorsolateral , Conducta Impulsiva , Recompensa , Estimulación Magnética Transcraneal , Humanos , Descuento por Demora/fisiología , Masculino , Femenino , Adulto Joven , Conducta Impulsiva/fisiología , Corteza Prefontal Dorsolateral/fisiología , Adulto , Conducta de Elección/fisiología , Corteza Prefrontal/fisiología
9.
Anal Chim Acta ; 1308: 342659, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38740459

RESUMEN

BACKGROUND: Kanamycin is an antibiotic that can easily cause adverse side effects if used improperly. Due to the extremely low concentrations of kanamycin in food, quantitative detection of kanamycin becomes a challenge. As one of the DNA self-assembly strategies, entropy-driven strand displacement reaction (EDSDR) does not require enzymes or hairpins to participate in the reaction, which greatly reduces the instability of detection results. Therefore, it is a very beneficial attempt to construct a highly sensitive and specific fluorescence detection method based on EDSDR that can detect kanamycin easily and quickly while ensuring that the results are effective and stable. RESULTS: We created an enzyme-free fluorescent aptamer sensor with high specificity and sensitivity for detecting kanamycin in milk by taking advantage of EDSDR and the high specific binding between the target and its aptamer. The specific binding can result in the release of the promoter chain, which then sets off the pre-planned EDSDR cycle. Fluorescent label modification on DNA combined with the fluorescence quenching-recovery mechanism gives the sensor impressive fluorescence response capabilities. The research results showed that within the concentration range of 0.1 nM-50 nM, there was a good relationship between the fluorescence intensity of the solution and the concentration of kanamycin. Specificity experiments and actual sample detection experiments confirmed that the biosensor could achieve highly sensitive and specific detection of trace amounts of kanamycin in food, with a detection limit of 0.053 nM (S/N = 3). SIGNIFICANCE: To our knowledge, this is the first strategy to combine EDSDR with fluorescence to detect kanamycin in food. Accurate results can be obtained in as little as 90 min with no enzymes or hairpins involved in the reaction. Furthermore, our enzyme-free biosensing method is straightforward, highly sensitive, and extremely specific. It has many possible applications, including monitoring antibiotic residues and food safety.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Entropía , Colorantes Fluorescentes , Kanamicina , Leche , Kanamicina/análisis , Kanamicina/química , Aptámeros de Nucleótidos/química , Leche/química , Colorantes Fluorescentes/química , Técnicas Biosensibles/métodos , Espectrometría de Fluorescencia , Límite de Detección , Animales , Antibacterianos/análisis , Antibacterianos/química , Contaminación de Alimentos/análisis
10.
Int J Psychophysiol ; 201: 112360, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38735630

RESUMEN

Economic decision-making is pivotal to both human private interests and the national economy. People pursue fairness in economic decision-making, but a proposer's moral identity can influence fairness processing. Previous ERP studies have revealed that moral identity has an effect on fairness considerations in the Ultimatum Game (UG), but the findings are inconsistent. To address the issue, we revised the moral-related sentences and used the ERP technique to measure the corresponding neural mechanism. We have observed that the fairness effect in UG can be mirrored in both MFN and P300 changes, whereas the moral identity effect on fairness in UG can be reflected by MFN but not P300 changes. These findings indicate that the moral identity of the proposer can modulate fairness processing in UG. The current study opens new avenues for clarifying the temporal course of the relationship between the proposer's moral identity and fairness in economic decision-making, which is beneficial for understanding the influencing mechanism of fairness processing and fair allocations in complex social contexts.


Asunto(s)
Toma de Decisiones , Potenciales Evocados , Juegos Experimentales , Principios Morales , Humanos , Masculino , Adulto Joven , Femenino , Toma de Decisiones/fisiología , Adulto , Potenciales Evocados/fisiología , Electroencefalografía , Encéfalo/fisiología
11.
Am J Clin Oncol ; 47(9): 412-418, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38764405

RESUMEN

OBJECTIVES: Studies investigating preoperative 5-fraction radiation therapy (RT) for soft tissue sarcoma (STS) are limited. We performed a meta-analysis to determine the efficacy and safety of this treatment paradigm. METHODS: This study-level meta-analysis was conducted using Bayesian methods. Statistical estimation for risk of outcome rates was conducted by posterior mean and 95% highest posterior density (HPD) intervals. Studies with 2-year local control (LC) and description of major wound complications (MWC) per the CAN-NCIC-SR2 study were included and served as the primary endpoints. Secondary endpoints included rates of acute and late toxicity. A total of 10 studies were identified and 7 met the inclusion criteria. Subgroup analyses were performed for ≥30 Gy vs <30 Gy. RESULTS: A total of 209 patients from 7 studies were included. Five studies used ≥30 Gy (n=144), and 2 studies <30 Gy (n=64). Median follow-up was 29 months (range: 21 to 57 mo). Primary tumor location was lower extremity in 68% and upper extremity in 22%. Most tumors were intermediate or high grade (95%, 160/169), and 50% (79/158) were >10 cm. The two-year LC for the entire cohort was 96.9%, and the rate of MWC was 30.6%. There was a trend toward improved LC with ≥ 30 Gy (95% HPD: 0.95 to 0.99 vs 0.84 to 0.99). There was no difference in MWC (95% HPD: 0.18 to 0.42 vs 0.17 to 0.55) or late toxicity between the groups. CONCLUSIONS: Preoperative 5-fraction RT for STS demonstrates excellent 2-year LC with MWC and toxicity similar to standard fractionation preoperative RT. Multi-institutional trials with a universal RT protocol are warranted.


Asunto(s)
Fraccionamiento de la Dosis de Radiación , Sarcoma , Humanos , Teorema de Bayes , Cuidados Preoperatorios , Sarcoma/radioterapia , Sarcoma/cirugía , Sarcoma/patología
12.
Cancer Lett ; 596: 216846, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38582397

RESUMEN

Cancer cells employ the unfolded protein response (UPR) or induce autophagy, especially selective removal of certain ER domains via reticulophagy (termed ER-phagy), to mitigate endoplasmic reticulum (ER) stress for ER homeostasis when encountering microenvironmental stress. N6-methyladenosine (m6A) is one of the most abundant epitranscriptional modifications and plays important roles in various biological processes. However, the molecular mechanism of m6A modification in the ER stress response is poorly understood. In this study, we first found that ER stress could dramatically elevate m6A methylation levels through XBP1s-dependent transcriptional upregulation of METTL3/METTL14 in breast cancer (BC) cells. Further MeRIP sequencing and relevant validation results confirmed that ER stress caused m6A methylation enrichment on target genes for ER-phagy. Mechanistically, METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and p62, thus enhancing their mRNA stability. Of note, we further confirmed that the chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase m6A methylation for ER-phagy. Furthermore, the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice. Thus, our data built a novel bridge on the crosstalk between ER stress, m6A methylation and ER-phagy. Most importantly, our work provides novel evidence of METTL3 and METTL14 as potential therapeutic targets for PTX sensitization in breast cancer.


Asunto(s)
Neoplasias de la Mama , Estrés del Retículo Endoplásmico , Metiltransferasas , Paclitaxel , Proteína 1 de Unión a la X-Box , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Paclitaxel/farmacología , Proteína 1 de Unión a la X-Box/genética , Proteína 1 de Unión a la X-Box/metabolismo , Animales , Metiltransferasas/genética , Metiltransferasas/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/farmacología , Autofagia/efectos de los fármacos , Metilación , Ratones Desnudos , Respuesta de Proteína Desplegada/efectos de los fármacos , Células MCF-7 , Antineoplásicos Fitogénicos/farmacología
13.
BMC Genomics ; 25(1): 352, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594623

RESUMEN

BACKGROUND: Posterior capsular opacification (PCO) is the main reason affecting the long-term postoperative result of cataract patient, and it is well accepted that fibrotic PCO is driven by transforming growth factor beta (TGFß) signaling. Ferroptosis, closely related to various ocular diseases, but has not been explored in PCO. METHODS: RNA sequencing (RNA-seq) was performed on both TGF-ß2 treated and untreated primary lens epithelial cells (pLECs). Differentially expressed genes (DEGs) associated with ferroptosis were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to investigate their biological function. Additionally, protein-to-protein interactions among selected ferroptosis-related genes by PPI network and the top 10 genes with the highest score (MCC algorithm) were selected as the hub genes. The top 20 genes with significant fold change values were validated using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our analysis revealed 1253 DEGs between TGF-ß2 treated and untreated pLECs, uncovering 38 ferroptosis-related genes between two groups. Among these 38 ferroptosis-related genes,the most prominent GO enrichment analysis process involved in the response to oxidative stress (BPs), apical part of cell (CCs),antioxidant activity (MFs). KEGG were mainly concentrated in fluid shear stress and atherosclerosis, IL-17 and TNF signaling pathways, and validation of top 20 genes with significant fold change value were consistent with RNA-seq. CONCLUSIONS: Our RNA-Seq data identified 38 ferroptosis-related genes in TGF-ß2 treated and untreated pLECs, which is the first observation of ferroptosis related genes in primary human lens epithelial cells under TGF-ß2 stimulation.


Asunto(s)
Opacificación Capsular , Ferroptosis , Humanos , Factor de Crecimiento Transformador beta2/genética , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta2/farmacología , Transcriptoma , Transición Epitelial-Mesenquimal/genética , Ferroptosis/genética , Western Blotting , Opacificación Capsular/genética , Opacificación Capsular/metabolismo , Células Epiteliales/metabolismo
14.
Biodes Res ; 6: 0030, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550916

RESUMEN

In the biotechnological industry, multicopy gene integration represents an effective strategy to maintain a high-level production of recombinant proteins and to assemble multigene biochemical pathways. In this study, we developed copper-induced in vivo gene amplification in budding yeast for multicopy gene expressions. To make copper as an effective selection pressure, we first constructed a copper-sensitive yeast strain by deleting the CUP1 gene encoding a small metallothionein-like protein for copper resistance. Subsequently, the reporter gene fused with a proline-glutamate-serine-threonine-destabilized CUP1 was integrated at the δ sites of retrotransposon (Ty) elements to counter the copper toxicity at 100 µM Cu2+. We further demonstrated the feasibility of modulating chromosomal rearrangements for increased protein expression under higher copper concentrations. In addition, we also demonstrated a simplified design of integrating the expression cassette at the CUP1 locus to achieve tandem duplication under high concentrations of copper. Taken together, we envision that this method of copper-induced in vivo gene amplification would serve as a robust and useful method for protein overproduction and metabolic engineering applications in budding yeast.

15.
Anal Chim Acta ; 1288: 342172, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38220303

RESUMEN

BACKGROUND: MicroRNAs play an important role in regulating cell function and gene expression. Early prevention and clinical diagnosis of diseases have high requirements for high-sensitivity detection of microRNAs. Due to the limitations of tedious operation and large sample size, miRNA with small molecular weight and low expression abundance cannot be accurately detected in traditional miRNA detection. To improve the sensitivity and accuracy of detection, we established a novel biosensor based on nucleic acid circuit of signal amplification, which converted miRNA recognition into a fluorescence signal for amplification. RESULTS: We designed a biosensor based on an exponential amplification reaction with cascaded HCR and DNAzyme nucleic acid circuit (named E-NOF biosensor) by amplicon sub-fragments to trigger the construction of fluorescence nano-orbitals (NOF), which could be used to detect miRNA ultrasensitively. By modifying two fluorophores (Cy3 and Cy5) on the chain of constructing nano-orbitals, when the amplicon triggered the construction of nano-orbitals, fluorescence resonance energy transfer (FRET) occurred between Cy3 and Cy5, and then two fluorescence signals with different trends could be observed. Therefore, through the ratio of the two signals, we could quantitatively and quickly detect the miRNA from 1 fM to 100 nM, and the E-NOF biosensor detection limit was as low as 0.129 fM. Furthermore, the HCR nucleic acid circuit cascaded with DNAzyme could enrich the fluorophores on the nano-orbitals and significantly enhance the fluorescence signal by accelerating the reaction rate. SIGNIFICANCE: According to our understanding, the E-NOF biosensor is the first strategy to cascade EXPAR with HCR and DNAzyme nucleic acid circuit for miRNA-1246 detection. Accurate results can be obtained in only 120 min. Compared with the traditional HCR system, the sensitivity of the new E-NOF biosensor is increased by 1 × 109 times. Furthermore, the biosensor can also detect biomarkers in human serum samples. It has great potential in miRNA detection and identification.


Asunto(s)
Técnicas Biosensibles , Carbocianinas , ADN Catalítico , MicroARNs , Humanos , MicroARNs/genética , Límite de Detección , Hibridación de Ácido Nucleico , Colorantes Fluorescentes , Técnicas Biosensibles/métodos
16.
J Am Soc Mass Spectrom ; 35(2): 357-364, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38252030

RESUMEN

A novel tridentate-cyclometalating Pt(IV) complex, namely, Pt(IV)(C∧N∧C)(Cl)2(DMSO), is initially synthesized through a series of reactions using Pt(II) complexes. The optoelectronic properties of Pt(IV)(C∧N∧C)(Cl)2(DMSO) are fully studied by adequate characterizations.

17.
Biosens Bioelectron ; 250: 116058, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38281368

RESUMEN

The rapid and accurate detection of fungal pathogens is of utmost importance in the fields of healthcare, food safety, and environmental monitoring. In this study, we implemented a cascaded amplifying circuit in Saccharomyces cerevisiae to improve the G protein-coupled receptor (GPCR) mediated fungal detection. The GPCR signaling pathway was coupled with the galactose-regulated (GAL) system and a positive feedback loop was implemented to enhance the performance of yeast biosensor. We systematically compared four generations of biosensors for detecting the mating pheromone of Candida albicans, and the best biosensor exhibited the limit of detection (LOD) as low as 0.25 pM and the limit of quantification (LOQ) of 1 pM after 2 h incubation. Subsequently, we developed a betaxanthin-based colorimetric module for the easy visualization of signal outputs, and the resulting biosensors can give reliable naked-eye readouts. In summary, we demonstrated that cascaded amplifying circuits could substantially improve the engineered yeast biosensors with a better sensitivity and signal output magnitude, which will pave the way for their real-world applications in public health.


Asunto(s)
Técnicas Biosensibles , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Técnicas Biosensibles/métodos , Transducción de Señal , Receptores Acoplados a Proteínas G/metabolismo , Feromonas/metabolismo
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(6): 1676-1683, 2023 Dec.
Artículo en Chino | MEDLINE | ID: mdl-38071045

RESUMEN

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia(AML). METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate, objective remission rate(ORR) and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML (unfit AML) and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months, P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION: VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.


Asunto(s)
Leucemia Mieloide Aguda , Nucleofosmina , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Recurrencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
19.
Curr Med Sci ; 43(6): 1151-1161, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38057538

RESUMEN

OBJECTIVE: Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia. However, their efficacy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains unclear. METHODS: Clinical data of R/R AML patients who received a CDCAG regimen (chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor) from July 1, 2018 to October 31, 2021 at our center were retrospectively assessed, and the safety and efficacy of the CDCAG regimen were evaluated. Patients were followed up until November 30, 2021, with a median follow-up of 21.6 months (95% CI: 10.0-33.2 months). RESULTS: A total of 67 patients were enrolled. Two patients died within 3 weeks after the initiation, and therefore only 65 patients underwent the assement for clinical response and survival. It was found that 56.9% patients achieved complete remission with a median overall survival (OS) of 9.6 months. The median OS of responders was 25.9 months, while that of non-responders was 5.0 months (P<0.0001). Patients with gene mutations had a superior overall response rate (ORR) (80.4% vs. 45.5%, P=0.043) compared to those without gene mutations. The presence of DNA methyltransferase 3 A (DNMT3A), ten-eleven translocation-2 (TET2), and isocitrate dehydrogenase 1/2 (IDH1/2) mutations did not affect the response rate (88.2% vs. 68.9%, P=0.220) and reflected a better OS (not attained vs. 9.0 months, P=0.05). The most common non-hematologic adverse events were pulmonary infection (73.1%), followed by febrile neutropenia (23.9%) and sepsis (19.4%). CONCLUSIONS: The CDCAG regimen was effective and well-tolerated in R/R AML patients, increasing the potential for allogeneic hematopoietic stem cell transplantation. Moreover, patients with DNMT3A, TET2, and IDH1/2 mutations might benefit from this regimen.


Asunto(s)
Citarabina , Leucemia Mieloide Aguda , Humanos , Citarabina/uso terapéutico , Estudios Retrospectivos , Decitabina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Aclarubicina/uso terapéutico , Resultado del Tratamiento , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética
20.
Zhongguo Zhong Yao Za Zhi ; 48(22): 6030-6038, 2023 Nov.
Artículo en Chino | MEDLINE | ID: mdl-38114209

RESUMEN

This study aimed to explore the correlation between rhizosphere soil microorganisms of wild Arnebia euchroma and the content of medicinal components to provide guidance for the selection of the ecological planting base. The total DNA of rhizosphere soil microorganisms of wild A. euchroma was extracted, and the microbial community structure of rhizosphere soil microorganisms was analyzed by IlluminaMiseq high-throughput sequencing technology. The content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin in medicinal materials was determined by high-performance liquid chromatography(HPLC). The physicochemical pro-perties of rhizosphere soil of wild A. euchroma in main producing areas were determined, and the correlation of soil microbial abundance with index component content and soil physicochemical properties was analyzed by SPSS software. The results showed that the species composition of rhizosphere fungi and bacteria in A. euchroma from different habitats was similar at the phylum and genus levels, but their relative abundance, richness index(Chao1), and community diversity(Simpson) index were different. Correlation analysis showed that the content of available phosphorus in soil was positively correlated with the content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin, and the abundance of five fungal genera such as Solicoccozyma and six bacterial genera such as Pseudo-nocardia and Bradyrhizobium was positively correlated with the content of medicinal components in medicinal materials. The abundance of Bradyrhizobium was significantly positively correlated with the content of ß,ß'-dimethylacrylalkanin. The abundance of fungi such as Archaeorhizomyces was significantly positively correlated with the content of available phosphorus in rhizosphere soil, and Bradyrhizobium was significantly negatively correlated with soil pH. Therefore, the abundance of fungi and bacteria in the rhizosphere of A. euchroma has a certain correlation with the medicinal components and the physicochemical properties of the rhizosphere soil, which can provide a scientific basis for the selection of ecological planting bases in the later stage.


Asunto(s)
Boraginaceae , Rizosfera , Microbiología del Suelo , Bacterias/genética , Fósforo , Suelo
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