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1.
Food Chem ; 463(Pt 1): 141148, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39243611

RESUMEN

This study investigated the effect of liquid nitrogen ball-milled mechanochemical treatment on multiscale structure and physicochemical properties of starches with typically selected A (rice starch, ReS), B (potato starch, PtS) and C (pea starch, PeS) crystal types. The morphology of starch samples changed from integral granules to irregular fragments, and the interaction between the exposure OH bonds led to a serious agglomeration. As the treatment times extended, the crystalline structure of starch samples was gradually destroyed, and the excessive treatment approached amorphization. Moreover, the thermal stability of starch samples showed the downward tendency; and with amorphization increased, the swelling power (SP), solubility (S), water absorption capacity (WAC), oil absorption capacity (OAC) and hydrolysis rate of starch samples gradually increased. The obtained results provided a theoretical foundation for broadening the application range of ball-milled starches with different crystal types.

2.
Nat Commun ; 15(1): 8108, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284820

RESUMEN

Conventionally, rocking-chair batteries capacity primarily depends on cation shuttling. However, intrinsically high-charge-density metal-ions, such as Al3+, inevitably cause strong Coulombic ion-lattice interactions, resulting in low practical energy density and inferior long-term stability towards rechargeable aluminium batteries (RABs). Herein, we introduce tunable quantum confinement effects and tailor a family of anion/cation co-(de)intercalation superlattice cathodes, achieving high-voltage anion charge compensation, with extra-capacity, in RABs. The optimized superlattice cathode with adjustable van der Waals not only enables facile traditional cation (de)intercalation, but also activates O2- compensation with an extra anion reaction. Furthermore, the constructed cathode delivers high energy-density (466 Wh kg-1 at 107 W kg-1) and one of the best cycle stability (225 mAh g-1 over 3000 cycles at 2.0 A g-1) in RABs. Overall, the anion-involving redox mechanism overcomes the bottlenecks of conventional electrodes, thereby heralding a promising advance in energy-storage-systems.

3.
Front Pharmacol ; 15: 1448319, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268473

RESUMEN

Objective: Addressing the rising prevalence of pain disorders and limitations of current analgesics, our study explores repurposing antihypertensive drugs for pain management, inspired by the link between hypertension and pain. We leverage a drug-target Mendelian Randomization (MR) approach to explore their dual benefits and establish causal connections. Methods: A comprehensive compilation of antihypertensive drug classes was undertaken through British National Formulary, with their target genes identified using the DrugBank database. Relevant single nucleotide polymorphisms (SNPs) associated with these targets were selected from published genomic studies on systolic blood pressure (SBP) as genetic instruments. These SNPs were validated through MR against acute coronary artery disease (CAD) to ensure genes not linked to CAD were excluded from acting as proxies for antihypertensive drugs. An MR analysis of 29 pain-related outcomes was conducted using the FinnGen R10 database employing the selected and validated genetic instruments. We utilized the Inverse Variance Weighted (IVW) method for primary analysis, applying Bonferroni correction to control type I error. IVW's multiplicative random effects (MRE) addressed heterogeneity, and MR-PRESSO managed pleiotropy, ensuring accurate causal inference. Results: Our analysis differentiates strong and suggestive evidence in linking antihypertensive drugs to pain disorder risks. Strong evidence was found for adrenergic neuron blockers increasing migraine without aura risk, loop diuretics reducing panniculitis, and vasodilator antihypertensives lowering limb pain risk. Suggestive evidence suggests alpha-adrenoceptor blockers might increase migraine risk, while beta-adrenoceptor blockers could lower radiculopathy risk. Adrenergic neuron blockers also show a potential protective effect against coxarthrosis (hip osteoarthritis) and increased femgenpain risk (pain and other conditions related to female genital organs and menstrual cycle). Additionally, suggestive links were found between vasodilator antihypertensives and reduced radiculopathy risk, and both alpha-adrenoceptor blockers and renin inhibitors possibly decreasing dorsalgianas risk (unspecified dorsalgia). These findings highlight the intricate effects of antihypertensive drugs on pain disorders, underlining the need for further research. Conclusion: The findings indicate that antihypertensive medications may exert varied effects on pain management, suggesting a repurposing potential for treating specific pain disorders. The results advocate for further research to confirm these associations and to explore underlying mechanisms, to optimize pain management practices.

4.
Cell Commun Signal ; 22(1): 401, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148095

RESUMEN

TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.


Asunto(s)
Linfoma de Células B Grandes Difuso , Proteína p53 Supresora de Tumor , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Humanos , Proteína p53 Supresora de Tumor/genética , Pronóstico , Mutación Missense/genética , Mutación/genética , Microambiente Tumoral/genética , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad
5.
J Med Virol ; 96(8): e29873, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39165041

RESUMEN

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Células T de Memoria , Reinfección , SARS-CoV-2 , Humanos , Adolescente , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Masculino , Reinfección/inmunología , Reinfección/virología , Femenino , Células T de Memoria/inmunología , Estudios Prospectivos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Formación de Anticuerpos , Glicoproteína de la Espiga del Coronavirus/inmunología , Memoria Inmunológica , Niño , Linfocitos T/inmunología
6.
Artículo en Inglés | MEDLINE | ID: mdl-39141451

RESUMEN

Recent advancements in non-invasive blood glucose detection have seen progress in both photoplethysmogram and multiple near-infrared methods. While the former shows better predictability of baseline glucose levels, it lacks sensitivity to daily fluctuations. Near-infrared methods respond well to short-term changes but face challenges due to individual and environmental factors. To address this, we developed a novel fingertip blood glucose detection system combining both methods. Using multiple light sensors and a lightweight deep learning model, our system achieved promising results in oral glucose tolerance tests. A total of 10 participants were involved in the study, each providing approximately 700 data segments of about 10 seconds each. With a root mean squared error of 0.242 mmol/L and 100% accuracy in zone A of the Parkes error grid, our approach demonstrates the potential of multiple near-infrared sensors for non-invasive glucose detection.

7.
Anal Methods ; 16(31): 5357-5371, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39045721

RESUMEN

Hapten immunoassays have found extensive application across various domains such as disease diagnostics, environmental monitoring, as well as the evaluation of food and pharmaceutical safety. These techniques traditionally rely on competitive assay formats and often face challenges with sensitivity and specificity. This review focuses on the emergent noncompetitive immunoassay technologies that promise to transcend these limitations through innovative approaches. Noncompetitive immunoassays, leveraging novel elements such as anti-idiotype antibodies, anti-immunocomplex (IC) antibodies, and the strategic use of nanomaterial-enhanced signal detection, are setting new benchmarks for analytical performance. These advancements not only enhance the detection capabilities but also significantly improve specificity inherent in traditional methods. Moreover, the integration of novel materials and binding reagents in these assays offers substantial improvements in assay dynamics, providing faster, more accurate, and reliable results. This review consolidates the latest methodologies and their applications, underlining the transformative impact of noncompetitive technologies in the sensitive detection of haptens across various fields.


Asunto(s)
Haptenos , Haptenos/inmunología , Haptenos/química , Inmunoensayo/métodos , Humanos , Animales , Anticuerpos Antiidiotipos/inmunología , Nanoestructuras/química
8.
Anal Chem ; 96(33): 13410-13420, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38967251

RESUMEN

As one of the most common cancers, accurate, rapid, and simple histopathological diagnosis is very important for breast cancer. Raman imaging is a powerful technique for label-free analysis of tissue composition and histopathology, but it suffers from slow speed when applied to large-area tissue sections. In this study, we propose a dual-modal Raman imaging method that combines Raman mapping data with microscopy bright-field images to achieve virtual staining of breast cancer tissue sections. We validate our method on various breast tissue sections with different morphologies and biomarker expressions and compare it with the golden standard of histopathological methods. The results demonstrate that our method can effectively distinguish various types and components of tissues, and provide staining images comparable to stained tissue sections. Moreover, our method can improve imaging speed by up to 65 times compared to general spontaneous Raman imaging methods. It is simple, fast, and suitable for clinical applications.


Asunto(s)
Neoplasias de la Mama , Espectrometría Raman , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Humanos , Espectrometría Raman/métodos , Femenino , Coloración y Etiquetado
9.
J Alzheimers Dis ; 100(s1): S115-S129, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39058442

RESUMEN

Background: The prevalence of Alzheimer's disease (AD) is increasing, therefore, identifying biomarkers to predict those vulnerable to AD is imperative. Type 2 diabetes (T2D) serves as an independent risk factor for AD. Early prediction of T2D patients who may be more susceptible to AD, so as to achieve early intervention, is of great significance to reduce the prevalence of AD. Objective: To establish periphery biomarkers that could predict conversion of T2D into pre-AD-like cognitive decline. Methods: A follow-up study was carried out from 159 T2D patients at baseline. The correlations of cognitive states (by MMSE score) with multi-periphery biomarkers, including APOE genotype, plasma amyloid-ß level, platelet GSK-3ß activity, and olfactory score were analyzed by logistic regression. ROC curve was used for establishing the prediction model. Additionally, MRI acquired from 38 T2D patients for analyzing the correlation among cognitive function, biomarkers and brain structure. Results: Compared with the patients who maintained normal cognitive functions during the follow-up period, the patients who developed MCI showed worse olfactory function, higher platelet GSK-3ß activity, and higher plasma Aß42/Aß40 ratio. We conducted a predictive model which T2D patients had more chance of suffering from pre-AD-like cognitive decline. The MRI data revealed MMSE scores were positively correlated with brain structures. However, platelet GSK-3ß activity was negatively correlated with brain structures. Conclusions: Elevated platelet GSK-3ß activity and plasma Aß42/Aß40 ratio with reduced olfactory function are correlated with pre-AD-like cognitive decline in T2D patients, which used for predicting which T2D patients will convert into pre-AD-like cognitive decline in very early stage.


Asunto(s)
Péptidos beta-Amiloides , Biomarcadores , Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/psicología , Masculino , Femenino , Disfunción Cognitiva/sangre , Estudios de Seguimiento , Péptidos beta-Amiloides/sangre , Biomarcadores/sangre , Anciano , Persona de Mediana Edad , Enfermedad de Alzheimer/sangre , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Imagen por Resonancia Magnética , Progresión de la Enfermedad , Apolipoproteínas E/genética , Plaquetas/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/metabolismo , Fragmentos de Péptidos/sangre
10.
Artículo en Inglés | MEDLINE | ID: mdl-38990453

RESUMEN

BACKGROUND: The potential value of detecting epithelial-mesenchymal transition (EMT) CTCs in early breast cancer, especially during the neoadjuvant therapy period, requires further investigation. We analyzed dynamic CTC phenotype status, to improve recurrence risk stratification for patients with stage III breast cancers. METHODS: We enrolled 45 patients with stage III breast cancers from 2 clinical trials undergoing neoadjuvant chemotherapy and utilized the CanPatrol CTC enrichment technique pre- and post-chemotherapy to identify CTC phenotypes, including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs, in peripheral blood samples. Kaplan-Meier analyses were conducted to explore the prognostic value of dynamic change of CTC count and the proportion of CTCs with different phenotypes. Then, redefine the risk stratification based on CTC status and clinicopathological risk in combination. RESULTS: Increased proportion of M + CTCs was a high-risk CTC status that was associated with decreased DFS (HR, 3.584; 95% CI, 1.057-12.15). In a combined analysis with clinicopathological risk, patients with high-risk tumors had an elevated risk of recurrence compared to patients with low-risk tumors (HR, 4.482; 95% CI, 1.246-16.12). The recurrence risk could be effectively stratified by newly defined risk stratification criteria, with 5-year DFS of 100.0%, 77.3%, and 50.0%, respectively, for low-risk, mid-risk, and high-risk patients (P = 0.0077). Finally, in the ROC analysis, the redefined risk stratification demonstrated higher predictive significance with an AUC of 0.7727, compared to CTC status alone (AUC of 0.6751) or clinicopathological risk alone (AUC of 0.6858). CONCLUSION: The proportion of M + CTCs increased after neoadjuvant chemotherapy indicating a higher risk of tumor recurrence. Combining CTC status with clinicopathological risk has potential to redefine the risk stratification of stage III breast cancers and provide improved predictions of relapse.

11.
J Asian Nat Prod Res ; : 1-11, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39082687

RESUMEN

Four new lycoctonine-type C19-diterpenoid alkaloids kamaonensines H-K (1-4) have been isolated from the whole plants of Delphinium kamaonense, together with 12 known compounds (5-16). Interestingly, kamaonensines 1-3 contained a rare nitrone (immine N-oxide) moiety, respectively. Their structures were established by spectroscopic analyses. The active evaluation of compounds (1-16) by LPS induced RAW 264.7 macrophages showed that compounds 4 and 8 displayed strong anti-inflammatory activities. While compounds 11 and 12 also showed strong cytotoxicities by the RAW 264.7 cell viability assay.

12.
Nat Commun ; 15(1): 4717, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830914

RESUMEN

Materials with field-tunable polarization are of broad interest to condensed matter sciences and solid-state device technologies. Here, using hydrogen (H) donor doping, we modify the room temperature metallic phase of a perovskite nickelate NdNiO3 into an insulating phase with both metastable dipolar polarization and space-charge polarization. We then demonstrate transient negative differential capacitance in thin film capacitors. The space-charge polarization caused by long-range movement and trapping of protons dominates when the electric field exceeds the threshold value. First-principles calculations suggest the polarization originates from the polar structure created by H doping. We find that polarization decays within ~1 second which is an interesting temporal regime for neuromorphic computing hardware design, and we implement the transient characteristics in a neural network to demonstrate unsupervised learning. These discoveries open new avenues for designing ferroelectric materials and electrets using light-ion doping.

13.
Ann Hematol ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38886191

RESUMEN

Diffuse large B-cell lymphoma (DLBCL), accounts for 30-40% of newly diagnosed lymphomas, has an overall cure rate of approximately 60%. Despite previous reports suggesting a negative prognostic association between CCND3 mutations and Burkitt lymphoma, their prognostic implications in DLBCL remain controversial. To investigate this, we evaluated CCND3 mutation status in 2059 DLBCL patient samples from four database (integrated cohort) and additional 167 DLBCL patient samples in our center (JSPH cohort). The mutation was identified in 5.5% (113/2059) of the cases in the integrated cohort, with 86% (97/113) found in exon 5. Furthermore, P284, R271, I290 and Q276 are described as CCND3 mutation hotspots. CCND3 mutation was associated with decreased overall survival (OS) in the integrated cohort (P = 0.0407). Further subgroup analysis revealed that patients diagnosed as EZB subtype DLBCL by LymphGen algorithm with CCND3 mutations had poorer OS than patients diagnosed as EZB subtype without CCND3 mutations (P = 0.0140). Using the next-generation sequencing (NGS) in the JSPH cohort, it was found that both cell cycle and DNA replication pathways were highly upregulated in patients with CCND3 mutations. Our results suggest that CCND3 mutations can serve as a novel prognostic factor in DLBCL pathogenesis. Consequently, the development of personalized therapeutic strategies for DLBCL patients with CCND3 mutations might enhance their prognosis.

14.
Adv Mater ; 36(30): e2404172, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38734973

RESUMEN

Aqueous aluminum ion batteries (AAIBs) hold significant potential for grid-scale energy storage owing to their intrinsic safety, high theoretical capacity, and abundance of aluminum. However, the strong electrostatic interactions and delayed charge compensation between high-charge-density aluminum ions and the fixed lattice in conventional cathodes impede the development of high-performance AAIBs. To address this issue, this work introduces, for the first time, high-entropy Prussian blue analogs (HEPBAs) as cathodes in AAIBs with unique lattice tolerance and efficient multipath electron transfer. Benefiting from the intrinsic long-range disorder and robust lattice strain field, HEPBAs enable the manifestation of the lattice respiration effect and minimize lattice volume changes, thereby achieving one of the best long-term stabilities (91.2% capacity retention after 10 000 cycles at 5.0 A g-1) in AAIBs. Additionally, the interaction between the diverse metal atoms generates a broadened d-band and reduced degeneracy compared with conventional Prussian blue and its analogs (PBAs), which enhances the electron transfer efficiency with one of the best rate performance (79.2 mAh g-1 at 5.0 A g-1) in AAIBs. Furthermore, exceptional element selectivity in HEPBAs with unique cocktail effect can facile tune electrochemical behavior. Overall, the newly developed HEPBAs with a high-entropy effect exhibit promising solutions for advancing AAIBs and multivalent-ion batteries.

15.
Leukemia ; 38(7): 1541-1552, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38750139

RESUMEN

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.


Asunto(s)
Biomarcadores de Tumor , ADN Tumoral Circulante , Linfoma de Células B Grandes Difuso , Mutación , Humanos , Linfoma de Células B Grandes Difuso/líquido cefalorraquídeo , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/líquido cefalorraquídeo , Biomarcadores de Tumor/genética , Anciano , Adulto , ADN Tumoral Circulante/líquido cefalorraquídeo , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Pronóstico , Anciano de 80 o más Años , Adulto Joven , Estudios Prospectivos
16.
iScience ; 27(4): 109550, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38595796

RESUMEN

During the evolution of large models, performance evaluation is necessary for assessing their capabilities. However, current model evaluations mainly rely on specific tasks and datasets, lacking a united framework for assessing the multidimensional intelligence of large models. In this perspective, we advocate for a comprehensive framework of cognitive science-inspired artificial general intelligence (AGI) tests, including crystallized, fluid, social, and embodied intelligence. The AGI tests consist of well-designed cognitive tests adopted from human intelligence tests, and then naturally encapsulates into an immersive virtual community. We propose increasing the complexity of AGI testing tasks commensurate with advancements in large models and emphasizing the necessity for the interpretation of test results to avoid false negatives and false positives. We believe that cognitive science-inspired AGI tests will effectively guide the targeted improvement of large models in specific dimensions of intelligence and accelerate the integration of large models into human society.

17.
Cancer Lett ; 591: 216877, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38615930

RESUMEN

Mantle cell lymphoma (MCL) is an incurable and aggressive subtype of non-Hodgkin B-cell lymphoma. Increased lipid uptake, storage, and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. However, no data has been explored for the roles of lipid metabolism reprogramming in MCL. Here, we identified aberrant lipid metabolism reprogramming and PRMT5 as a key regulator of cholesterol and fatty acid metabolism reprogramming in MCL patients. High PRMT5 expression predicts adverse outcome prognosis in 105 patients with MCL and GEO database (GSE93291). PRMT5 deficiency resulted in proliferation defects and cell death by CRISPR/Cas9 editing. Moreover, PRMT5 inhibitors including SH3765 and EPZ015666 worked through blocking SREBP1/2 and FASN expression in MCL. Furthermore, PRMT5 was significantly associated with MYC expression in 105 MCL samples and the GEO database (GSE93291). CRISPR MYC knockout indicated PRMT5 can promote MCL outgrowth by inducing SREBP1/2 and FASN expression through the MYC pathway.


Asunto(s)
Proliferación Celular , Acido Graso Sintasa Tipo I , Metabolismo de los Lípidos , Linfoma de Células del Manto , Proteína-Arginina N-Metiltransferasas , Proteínas Proto-Oncogénicas c-myc , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/metabolismo , Linfoma de Células del Manto/patología , Humanos , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Acido Graso Sintasa Tipo I/metabolismo , Acido Graso Sintasa Tipo I/genética , Línea Celular Tumoral , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Regulación Neoplásica de la Expresión Génica , Animales , Ratones , Masculino , Pronóstico , Femenino , Colesterol/metabolismo , Sistemas CRISPR-Cas , Reprogramación Metabólica
18.
Nat Mater ; 23(6): 790-795, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38561519

RESUMEN

In a solid, the electronic subsystem can exhibit incipient order with lower point group symmetry than the crystal lattice. Ultrafast external fields that couple exclusively to electronic order parameters have rarely been investigated, however, despite their potential importance in inducing exotic effects. Here we show that when inversion symmetry is broken by the antiferromagnetic order in Cr2O3, transmitting a linearly polarized light pulse through the crystal gives rise to an in-plane rotational symmetry-breaking (from C3 to C1) via optical rectification. Using interferometric time-resolved second harmonic generation, we show that the ultrafast timescale of the symmetry reduction is indicative of a purely electronic response; the underlying spin and crystal structures remain unaffected. The symmetry-broken state exhibits a dipole moment, and its polar axis can be controlled with the incident light. Our results establish a coherent nonlinear optical protocol by which to break electronic symmetries and produce unconventional electronic effects in solids.

19.
Clin. transl. oncol. (Print) ; 26(3): 720-731, mar. 2024.
Artículo en Inglés | IBECS | ID: ibc-230801

RESUMEN

Purpose The International Extranodal Lymphoma Study Group (IELSG) score is widely used in clinical practice to stratify the risk of primary central nervous system lymphoma (PCNSL) patients. Our study aims to confirm and improve the IELSG score in PCNSL patients based on Chinese populations. Materials and methods A total of 79 PCNSL patients were retrospectively analyzed. All patients treated with high-dose methotrexate (HD-MTX)-based therapy collected clinical data. The receiver-operating characteristic (ROC) curve was used to determine the optimal cut-off values for the factors in IELSG score. Progression of disease (POD) at the most landmark time point was determine by Epanechnikov kernel and the area under the ROC curve (AUROC). Kaplan–Meier and multivariable regression methods were used to analyze survival data. Nomogram was generated for calculating the weight of each selected factor. Results The traditional IELSG score had no significant difference on OS and PFS except ECOG ≥ 2 and could not stratify the risk groups in PCNSL. The improved IELSG scoring system was established, which incorporated age ≥ 54 years, ECOG ≥ 2, deep brain structure, elevated CSF protein, and LDH/ULN > 0.75. On the other hand, POD18 was identified as a new powerful prognostic factor for PCNSL. In multivariate analysis, POD18 and the improved IELSG scoring system were independent prognostic factors for OS. Nomogram including the two significant variables showed the best performance (C-index = 0.828). Conclusions In this study, the IELSG score was improved and a new prognostic indicator POD18 was incorporated to construct a nomogram prognostic model, thereby further improving the predictive ability of the model (AU)


Asunto(s)
Humanos , Persona de Mediana Edad , Linfoma Compuesto/tratamiento farmacológico , Linfoma Compuesto/metabolismo , Metotrexato/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Encéfalo/metabolismo , Pronóstico
20.
Small ; 20(29): e2312086, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38412409

RESUMEN

Rechargeable aqueous aluminum batteries (AABs) are promising energy storage technologies owing to their high safety and ultra-high energy-to-price ratio. However, either the strong electrostatic forces between high-charge-density Al3+ and host lattice, or sluggish large carrier-ion diffusion toward the conventional inorganic cathodes generates inferior cycling stability and low rate-capacity. To overcome these inherent confinements, a series of promising redox-active organic materials (ROMs) are investigated and a π-conjugated structure ROMs with synergistic C═O and C═N groups is optimized as the new cathode in AABs. Benefiting from the joint utilization of multi-redox centers and rich π-π intermolecular interactions, the optimized ROMs with unique ion coordination storage mechanism facilely accommodate complex active ions with mitigated coulombic repulsion and robust lattice structure, which is further validated via theoretical simulations. Thus, the cathode achieves enhanced rate performance (153.9 mAh g-1 at 2.0 A g-1) and one of the best long-term stabilities (125.7 mAh g-1 after 4,000 cycles at 1.0 A g-1) in AABs. Via molecular exploitation, this work paves the new direction toward high-performance cathode materials in aqueous multivalent-ion battery systems.

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