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1.
Nat Mater ; 23(8): 1055-1062, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38831130

RESUMEN

The coexistence of correlated electron and hole crystals enables the realization of quantum excitonic states, capable of hosting counterflow superfluidity and topological orders with long-range quantum entanglement. Here we report evidence for imbalanced electron-hole crystals in a doped Mott insulator, namely, α-RuCl3, through gate-tunable non-invasive van der Waals doping from graphene. Real-space imaging via scanning tunnelling microscopy reveals two distinct charge orderings at the lower and upper Hubbard band energies, whose origin is attributed to the correlation-driven honeycomb hole crystal composed of hole-rich Ru sites and rotational-symmetry-breaking paired electron crystal composed of electron-rich Ru-Ru bonds, respectively. Moreover, a gate-induced transition of electron-hole crystals is directly visualized, further corroborating their nature as correlation-driven charge crystals. The realization and atom-resolved visualization of imbalanced electron-hole crystals in a doped Mott insulator opens new doors in the search for correlated bosonic states within strongly correlated materials.

2.
Plant Physiol ; 195(4): 2799-2814, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-38743633

RESUMEN

The cultivated apple (Malus domestica Borkh.) is a cross-pollinated perennial fruit tree of great economic importance. Earlier versions of apple reference genomes were unphased, fragmented, and lacked comprehensive insights into the apple's highly heterozygous genome, which impeded advances in genetic studies and breeding programs. In this study, we assembled a haplotype-resolved telomere-to-telomere (T2T) reference genome for the diploid apple cultivar Golden Delicious. Subsequently, we constructed a pangenome based on 12 assemblies from wild and cultivated species to investigate the dynamic changes of functional genes. Our results revealed the gene gain and loss events during apple domestication. Compared with cultivated species, more gene families in wild species were significantly enriched in oxidative phosphorylation, pentose metabolic process, responses to salt, and abscisic acid biosynthesis process. Our analyses also demonstrated a higher prevalence of different types of resistance gene analogs (RGAs) in cultivars than their wild relatives, partially attributed to segmental and tandem duplication events in certain RGAs classes. Structural variations, mainly deletions and insertions, have affected the presence and absence of TIR-NB-ARC-LRR, NB-ARC-LRR, and CC-NB-ARC-LRR genes. Additionally, hybridization/introgression from wild species has also contributed to the expansion of resistance genes in domesticated apples. Our haplotype-resolved T2T genome and pangenome provide important resources for genetic studies of apples, emphasizing the need to study the evolutionary mechanisms of resistance genes in apple breeding.


Asunto(s)
Domesticación , Genoma de Planta , Malus , Telómero , Malus/genética , Genoma de Planta/genética , Telómero/genética , Genes de Plantas , Haplotipos/genética , Resistencia a la Enfermedad/genética
3.
J Am Chem Soc ; 146(1): 833-848, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38113458

RESUMEN

The high-performance Y6-based nonfullerene acceptors (NFAs) feature a C-shaped A-DA'D-A-type molecular architecture with a central electron-deficient thiadiazole (Tz) A' unit. In this work, we designed and synthesized a new A-D-A-type NFA, termed CB16, having a C-shaped ortho-benzodipyrrole-based skeleton of Y6 but with the Tz unit eliminated. When processed with nonhalogenated xylene without using any additives, the binary PM6:CB16 devices display a remarkable power conversion efficiency (PCE) of 18.32% with a high open-circuit voltage (Voc) of 0.92 V, surpassing the performance of the corresponding Y6-based devices. In contrast, similarly synthesized SB16, featuring an S-shaped para-benzodipyrrole-based skeleton, yields a low PCE of 0.15% due to the strong side-chain aggregation of SB16. The C-shaped A-DNBND-A skeleton in CB16 and the Y6-series NFAs constitutes the essential structural foundation for achieving exceptional device performance. The central Tz moiety or other A' units can be employed to finely adjust intermolecular interactions. The single-crystal X-ray structure reveals that ortho-benzodipyrrole-embedded A-DNBND-A plays an important role in the formation of a 3D elliptical network packing for efficient charge transport. Solution structures of the PM6:NFAs detected by small- and wide-angle X-ray scattering (SWAXS) indicate that removing the Tz unit in the C-shaped skeleton could reduce the self-packing of CB16, thereby enhancing the complexing and networking with PM6 in the spin-coating solution and the subsequent device film. Elucidating the structure-property-performance relationships of A-DA'D-A-type NFAs in this work paves the way for the future development of structurally simplified A-D-A-type NFAs.

4.
Br J Cancer ; 130(8): 1286-1294, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38388856

RESUMEN

BACKGROUND: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke. METHODS: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes. RESULTS: We found that among Chinese individuals diagnosed with lung cancer who never smoke, females were diagnosed with lung cancer younger than males in the Taiwan Cancer Registry (n = 29,832) (Δ years = -2.2 (95% confidence interval (CI):-2.5, -1.9), in Shanghai (n = 1049) (Δ years = -1.6 (95% CI:-2.9, -0.3), and in Sutter Health and Kaiser Permanente Hawai'i in the US (n = 82) (Δ years = -11.3 (95% CI: -17.7, -4.9). While there was a suggestion of similar patterns in African American and non-Hispanic White individuals. the estimated differences were not consistent across studies and were not statistically significant. CONCLUSIONS: We found evidence of sex differences for age at lung cancer diagnosis among individuals who never smoke.


Asunto(s)
Etnicidad , Neoplasias Pulmonares , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Humo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/patología , China , Blanco
5.
Biochem Biophys Res Commun ; 702: 149633, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38341921

RESUMEN

Ribosomal protein 25 (RPS25) has been related to male fertility diseases in humans. However, the role of RPS25 in spermatogenesis has yet to be well understood. RpS25 is evolutionarily highly conserved from flies to humans through sequence alignment and phylogenetic tree construction. In this study, we found that RpS25 plays a critical role in Drosophila spermatogenesis and its knockdown leads to male sterility. Examination of each stage of spermatogenesis from RpS25-knockdown flies showed that RpS25 was not required for initial germline cell divisions, but was required for spermatid elongation and individualization. In RpS25-knockdown testes, the average length of cyst elongation was shortened, the spermatid nuclei bundling was disrupted, and the assembly of individualization complex from actin cones failed, resulting in the failure of mature sperm production. Our data revealed an essential role of RpS25 during Drosophila spermatogenesis through regulating spermatid elongation and individualization.


Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Humanos , Masculino , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Filogenia , Semen/metabolismo , Espermátides/metabolismo , Espermatogénesis/genética , Espermatozoides/metabolismo , Testículo/metabolismo
6.
Small ; : e2400458, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38607289

RESUMEN

1D nanowire networks, sharing similarities of structure, information transfer, and computation with biological neural networks, have emerged as a promising platform for neuromorphic systems. Based on brain-like structures of 1D nanowire networks, neuromorphic synaptic devices can overcome the von Neumann bottleneck, achieving intelligent high-efficient sensing and computing function with high information processing rates and low power consumption. Here, high-temperature neuromorphic synaptic devices based on SiC@NiO core-shell nanowire networks optoelectronic memristors (NNOMs) are developed. Experimental results demonstrate that NNOMs attain synaptic short/long-term plasticity and modulation plasticity under both electrical and optical stimulation, and exhibit advanced functions such as short/long-term memory and "learning-forgetting-relearning" under optical stimulation at both room temperature and 200 °C. Based on the advanced functions under light stimulus, the constructed 5 × 3 optoelectronic synaptic array devices exhibit a stable visual memory function up to 200 °C, which can be utilized to develop artificial visual systems. Additionally, when exposed to multiple electronic or optical stimuli, the NNOMs effectively replicate the principles of Pavlovian classical conditioning, achieving visual heterologous synaptic functionality and refining neural networks. Overall, with abundant synaptic characteristics and high-temperature thermal stability, these neuromorphic synaptic devices offer a promising route for advancing neuromorphic computing and visual systems.

7.
J Transl Med ; 22(1): 571, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38879493

RESUMEN

BACKGROUND: No reliable clinical tools exist to predict acute kidney injury (AKI) progression. We aim to explore a scoring system for predicting the composite outcome of progression to severe AKI or death within seven days among early AKI patients after cardiac surgery. METHODS: In this study, we used two independent cohorts, and patients who experienced mild/moderate AKI within 48 h after cardiac surgery were enrolled. Eventually, 3188 patients from the MIMIC-IV database were used as the derivation cohort, while 499 patients from the Zhongshan cohort were used as external validation. The primary outcome was defined by the composite outcome of progression to severe AKI or death within seven days after enrollment. The variables identified by LASSO regression analysis were entered into logistic regression models and were used to construct the risk score. RESULTS: The composite outcome accounted for 3.7% (n = 119) and 7.6% (n = 38) of the derivation and validation cohorts, respectively. Six predictors were assembled into a risk score (AKI-Pro score), including female, baseline eGFR, aortic surgery, modified furosemide responsiveness index (mFRI), SOFA, and AKI stage. And we stratified the risk score into four groups: low, moderate, high, and very high risk. The risk score displayed satisfied predictive discrimination and calibration in the derivation and validation cohort. The AKI-Pro score discriminated the composite outcome better than CRATE score, Cleveland score, AKICS score, Simplified renal index, and SRI risk score (all P < 0.05). CONCLUSIONS: The AKI-Pro score is a new clinical tool that could assist clinicians to identify early AKI patients at high risk for AKI progression or death.


Asunto(s)
Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Progresión de la Enfermedad , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Femenino , Masculino , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Persona de Mediana Edad , Anciano , Factores de Riesgo , Estudios de Cohortes , Índice de Severidad de la Enfermedad , Curva ROC , Medición de Riesgo , Pronóstico
8.
Genet Med ; 26(10): 101201, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38953292

RESUMEN

PURPOSE: This study compared Lynch syndrome universal tumor screening (UTS) across multiple health systems (some of which had 2 or more distinct UTS programs) to understand multilevel factors that may affect the successful implementation of complex programs. METHODS: Data from 66 stakeholder interviews were used to conduct multivalue coincidence analysis and identify key factors that consistently make a difference in whether UTS programs were implemented and optimized at the system level. RESULTS: The selected coincidence analysis model revealed combinations of conditions that distinguish 4 optimized UTS programs, 10 nonoptimized programs, and 4 systems with no program. Fully optimized UTS programs had both a maintenance champion and a positive inner setting. Two independent paths were unique to nonoptimized programs: (1) positive attitudes and a mixed inner setting or (2) limited planning and engaging among stakeholders. Negative views about UTS evidence or lack of knowledge about UTS led to a lack of planning and engaging, which subsequently prevented program implementation. CONCLUSION: The model improved our understanding of program implementation in health care systems and informed the creation of a toolkit to guide UTS implementation, optimization, and changes. Our findings and toolkit may serve as a use case to increase the successful implementation of other complex precision health programs.

9.
New Phytol ; 242(3): 1098-1112, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38515249

RESUMEN

The potential for totipotency exists in all plant cells; however, the underlying mechanisms remain largely unknown. Earlier findings have revealed that the overexpression of LEAFY COTYLEDON 2 (LEC2) can directly trigger the formation of somatic embryos on the cotyledons of Arabidopsis. Furthermore, cotyledon cells that overexpress LEC2 accumulate significant lipid reserves typically found in seeds. The precise mechanisms and functions governing lipid accumulation in this process remain unexplored. In this study, we demonstrate that WRINKLED1 (WRI1), the key regulator of lipid biosynthesis, is essential for somatic embryo formation, suggesting that WRI1-mediated lipid biosynthesis plays a crucial role in the transition from vegetative to embryonic development. Our findings indicate a direct interaction between WRI1 and LEC2, which enhances the enrichment of LEC2 at downstream target genes and stimulates their induction. Besides, our data suggest that WRI1 forms a complex with LEC1, LEC2, and FUSCA3 (FUS3) to facilitate the accumulation of auxin and lipid for the somatic embryo induction, through strengthening the activation of YUCCA4 (YUC4) and OLEOSIN3 (OLE3) genes. Our results uncover a regulatory module controlled by WRI1, crucial for somatic embryogenesis. These findings provide valuable insights into our understanding of plant cell totipotency.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos , Lípidos , Semillas/genética , Factores de Transcripción/metabolismo
10.
J Med Virol ; 96(1): e29348, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38180275

RESUMEN

Ground glass hepatocytes (GGHs) have been associated with hepatocellular carcinoma (HCC) recurrence and poor prognosis. We previously demonstrated that pre-S expression in some GGHs is resistant to current hepatitis B virus (HBV) antiviral therapies. This study aimed to investigate whether integrated HBV DNA (iDNA) is the primary HBV DNA species responsible for sustained pre-S expression in GGH after effective antiviral therapy. We characterized 10 sets of micro-dissected, formalin-fixed-paraffin-embedded, and frozen GGH, HCC, and adjacent hepatitis B surface antigen-negative stained tissues for iDNA, pre-S deletions, and the quantity of covalently closed circular DNA. Eight patients had detectable pre-S deletions, and nine had detectable iDNA. Interestingly, eight patients had integrations within the TERT and CCNE1 genes, which are known recurrent integration sites associated with HCC. Furthermore, we observed a recurrent integration in the ABCC13 gene. Additionally, we identified variations in the type and quantity of pre-S deletions within individual sets of tissues by junction-specific PacBio long-read sequencing. The data from long-read sequencing indicate that some pre-S deletions were acquired following the integration events. Our findings demonstrate that iDNA exists in GGH and can be responsible for sustained pre-S expression in GGH after effective antiviral therapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Virus de la Hepatitis B/genética , ADN Viral/genética , Neoplasias Hepáticas/genética , Hepatocitos , Mutación , Antivirales/uso terapéutico
11.
Int J Neuropsychopharmacol ; 27(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38135278

RESUMEN

BACKGROUND: Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that projects throughout the central nervous system, including the noradrenergic locus coeruleus (LC). Our previous study suggested that MCH/MCH receptor 1 (MCHR1) in the LC may be involved in the regulation of depression. The present study investigated whether the role of MCH/MCHR1 in the LC in depression-like behaviors is associated with the regulation of norepinephrine. METHOD: Chronic unpredictable stress (CUS) and an acute intra-LC microinjection of MCH induced depression-like behaviors in rats. The MCHR1 antagonist SNAP-94847 was also microinjected in the LC in rats that were suffering CUS or treated with MCH. The sucrose preference, forced swim, and locomotor tests were used for behavioral evaluation. Immunofluorescence staining, enzyme-linked immunosorbent assay, western blot, and high-performance liquid chromatography with electrochemical detection were used to explore the mechanism of MCH/MCHR1 in the regulation of depression-like behaviors. RESULTS: CUS induced an abnormal elevation of MCH levels and downregulated MCHR1 in the LC, which was highly correlated with the formation of depression-like behaviors. SNAP-94847 exerted antidepressant effects in CUS-exposed rats by normalizing tyrosine hydroxylase, dopamine ß hydroxylase, and norepinephrine in the LC. An acute microinjection of MCH induced depression-like behaviors through its action on MCHR1. MCHR1 antagonism in the LC significantly reversed the MCH-induced downregulation of norepinephrine production by normalizing MCHR1-medicated cAMP-PKA signaling. CONCLUSIONS: Our study confirmed that the MCH/MCHR1 system in the LC may be involved in depression-like behaviors by downregulating norepinephrine production. These results improve our understanding of the pathogenesis of depression that is related to the MCH/MCHR1 system in the LC.


Asunto(s)
Hormonas Hipotalámicas , Locus Coeruleus , Ratas , Animales , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Norepinefrina , Hormonas Hipotalámicas/metabolismo , Hormonas Hipofisarias/farmacología , Melaninas/farmacología
12.
Phys Rev Lett ; 132(24): 246902, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38949373

RESUMEN

We show that excitonic resonances and interexciton transitions can enhance the probability of spontaneous parametric down-conversion, a second-order optical response that generates entangled photon pairs. We benchmark our ab initio many-body calculations using experimental polar plots of second harmonic generation in NbOI_{2}, clearly demonstrating the relevance of excitons in the nonlinear response. A strong double-exciton resonance in 2D NbOCl_{2} leads to giant enhancement in the second order susceptibility. Our work paves the way for the realization of efficient ultrathin quantum light sources.

13.
Exp Eye Res ; 239: 109784, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199261

RESUMEN

Transient receptor potential vanilloid (TRPV) channels are members of the TRP channel superfamily, which are ion channels that sense mechanical and osmotic stimuli and participate in Ca2+ signalling across the cell membrane. TRPV channels play important roles in maintaining the normal functions of an organism, and defects or abnormalities in TRPV channel function cause a range of diseases, including cardiovascular, neurological and urological disorders. Glaucoma is a group of chronic progressive optic nerve diseases with pathological changes that can occur in the tissues of the anterior and posterior segments of the eye, including the ciliary body, trabecular meshwork, Schlemm's canal, and retina. TRPV channels are expressed in these tissues and play various roles in glaucoma. In this article, we review various aspects of the pathogenesis of glaucoma, the structure and function of TRPV channels, the relationship between TRPV channels and systemic diseases, and the relationship between TRPV channels and ocular diseases, especially glaucoma, and we suggest future research directions. This information will help to further our understanding of TRPV channels and provide new ideas and targets for the treatment of glaucoma and optic nerve damage.


Asunto(s)
Glaucoma , Traumatismos del Nervio Óptico , Humanos , Esclerótica/patología , Retina/patología , Malla Trabecular/metabolismo , Traumatismos del Nervio Óptico/metabolismo , Nervio Óptico/patología
14.
Exp Eye Res ; 241: 109853, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38453038

RESUMEN

High myopia is a risk factor for primary open angle glaucoma (POAG). The pathological mechanism of high myopia induced POAG occurrence is not fully understood. In this study, we successfully established the guinea pig model of ocular hypertension with high myopia, and demonstrated the susceptibility of high myopia for the occurrence of microbead-induced glaucoma compared with non-myopia group and the effect of YAP/TGF-ß signaling pathway in TM pathogenesis induced by high myopia. Moreover, we performed stretching treatment on primary trabecular meshwork (TM) cells to simulate the mechanical environment of high myopia. It was found that stretching treatment disrupted the cytoskeleton, decreased phagocytic function, enhanced ECM remodeling, and promoted cell apoptosis. The experiments of mechanics-induced human TM cell lines appeared the similar trend. Mechanically, the differential expressed genes of TM cells caused by stretch treatment enriched YAP/TGF-ß signaling pathway. To inhibit YAP/TGF-ß signaling pathway effectively reversed mechanics-induced TM damage. Together, this study enriches mechanistic insights of high myopia induced POAG susceptibility and provides a potential target for the prevention of POAG with high myopia.


Asunto(s)
Glaucoma de Ángulo Abierto , Hipertensión Ocular , Humanos , Animales , Cobayas , Factor de Crecimiento Transformador beta/metabolismo , Malla Trabecular/metabolismo , Glaucoma de Ángulo Abierto/prevención & control , Glaucoma de Ángulo Abierto/genética , Hipertensión Ocular/metabolismo , Factores de Riesgo , Células Cultivadas
15.
Ann Hematol ; 103(8): 2917-2930, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38671297

RESUMEN

The molecular pathogenesis of extranodal NK/T-cell lymphoma (NKTCL) remains obscured despite the next-generation sequencing (NGS) studies explored on ever larger cohorts in the last decade. We addressed the highly variable mutation frequencies reported among previous studies with comprehensive amplicon coverage and enhanced sequencing depth to achieve higher genomic resolution for novel genetic discovery and comparative mutational profiling of the oncogenesis of NKTCL. Targeted exome sequencing was conducted to interrogate 415 cancer-related genes in a cohort of 36 patients with NKTCL, and a total of 548 single nucleotide variants (SNVs) and 600 Copy number variances (CNVs) were identified. Recurrent amplification of the MCL1 (67%) and PIM1 (56%) genes was detected in a dominant majority of patients in our cohort. Functional mapping of genetic aberrations revealed that an enrichment of mutations in the JAK-STAT signaling pathway, including the cytokine receptor LIFR (copy number loss) upstream of JAK3, STAT3 (activating SNVs), and downstream effectors of MYC, PIM1 and MCL1 (copy number gains). RNA in situ hybridization showed the significant consistence of MCL1 RNA level and copy number of MCL1 gene. We further correlated molecular and clinical parameters with overall survival (OS) of these patients. When correlations were analyzed by univariate followed by multivariate modelling, only copy number loss of LIFR gene and stage (III-IV) were independent prognostic factors of reduced OS. Our findings identified that novel loss of LIFR gene significantly correlated with the adverse clinical outcome of NKTCL patients and provided therapeutic opportunities for this disease through manipulating LIFR.


Asunto(s)
Linfoma Extranodal de Células NK-T , Mutación , Humanos , Linfoma Extranodal de Células NK-T/genética , Linfoma Extranodal de Células NK-T/terapia , Linfoma Extranodal de Células NK-T/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Pronóstico , Variaciones en el Número de Copia de ADN
16.
Inorg Chem ; 63(2): 1328-1336, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38166367

RESUMEN

Designing friction materials with high electron storage capacity, high work function, low cost, and high stability is an important method to improve the output performance of a triboelectric nanogenerator (TENG). Here, we report two kinds of friction materials based on Keggin-type polyoxometalates (POMs)-modified graphite carbon nitride (g-C3N4), namely, g-C3N4@PMo12 and g-C3N4@PW12, and form TENG with commercial indium tin oxide/poly(ethylene terephthalate) (ITO/PET) electrodes. The performance test shows that the g-C3N4@PMo12 TENG device exhibits a high output voltage of about 78 V, a current of about 657 nA, and a transfer charge of about 15 nC, which is more than 3 times higher than that of unmodified TENG. This performance improvement is attributed to the fact that POM loaded on the surface of g-C3N4 can be used as a shallow electron trap to increase the electron storage capacity through electron interaction and to increase the charge density on the surface of the material by increasing the work function of the composite. This work not only broadens the choices of TENG friction materials but also offers a practical means of enhancing TENG's output performance.

17.
J Chem Inf Model ; 64(10): 4373-4384, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38743013

RESUMEN

Artificial intelligence-based methods for predicting drug-target interactions (DTIs) aim to explore reliable drug candidate targets rapidly and cost-effectively to accelerate the drug development process. However, current methods are often limited by the topological regularities of drug molecules, making them difficult to generalize to a broader chemical space. Additionally, the use of similarity to measure DTI network links often introduces noise, leading to false DTI relationships and affecting the prediction accuracy. To address these issues, this study proposes an Adaptive Iterative Graph Optimization (AIGO)-DTI prediction framework. This framework integrates atomic cluster information and enhances molecular features through the design of functional group prompts and graph encoders, optimizing the construction of DTI association networks. Furthermore, the optimization of graph structure is transformed into a node similarity learning problem, utilizing multihead similarity metric functions to iteratively update the network structure to improve the quality of DTI information. Experimental results demonstrate the outstanding performance of AIGO-DTI on multiple public data sets and label reversal data sets. Case studies, molecular docking, and existing research validate its effectiveness and reliability. Overall, the method proposed in this study can construct comprehensive and reliable DTI association network information, providing new graphing and optimization strategies for DTI prediction, which contribute to efficient drug development and reduce target discovery costs.


Asunto(s)
Algoritmos , Simulación del Acoplamiento Molecular , Inteligencia Artificial , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/metabolismo , Descubrimiento de Drogas/métodos
18.
J Appl Microbiol ; 135(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38192042

RESUMEN

AIM: This study aimed to investigate the positive effect of natto powder on obese rats fed with a high-fat diet (HFD). METHODS AND RESULTS: Sprague-Dawley rats were fed with a HFD for 8 weeks continuously and gavaged with natto powder, respectively, for 8 weeks starting from the ninth week. The results showed that natto powder significantly reduced the body weight of rats and maintained the balance of cholesterol metabolism in the body by inhibiting the activity of liver X receptors (LXR) target genes, increasing the active expression of cholesterol 7 alpha-hydroxylase, and reducing the active expression of sterol-regulatory element-binding protein and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Furthermore, natto powder increased the relative abundance of potentially beneficial microbiota in gut and decreased the relative abundance of obesity-related harmful bacteria, and also increased the Bacteroidetes/Firmicutes ratio and improved the composition of gut microbiota. CONCLUSIONS: Natto powder maintains the balance of cholesterol metabolism by inhibiting the LXR pathway and regulating the gut microbiota.


Asunto(s)
Microbioma Gastrointestinal , Alimentos de Soja , Ratas , Animales , Ratones , Polvos/farmacología , Receptores X del Hígado , Ratas Sprague-Dawley , Obesidad/microbiología , Dieta Alta en Grasa , Colesterol/metabolismo , Ratones Endogámicos C57BL
19.
BMC Cardiovasc Disord ; 24(1): 414, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39123133

RESUMEN

BACKGROUND: The development of acute kidney injury (AKI) post-cardiac surgery significantly increases patient morbidity and healthcare costs. Prior researches have established Syndecan-1 (SDC-1) as a potential biomarker for endothelial injury and subsequent acute kidney injury development. This study assessed whether postoperative SDC-1 levels could further predict AKI requiring kidney replacement therapy (AKI-KRT) and AKI progression. METHODS: In this prospective study, 122 adult cardiac surgery patients, who underwent valve or coronary artery bypass grafting (CABG) or a combination thereof and developed AKI within 48 h post-operation from May to September 2021, were monitored for the progression to stage 2-3 AKI or the need for KRT. We analyzed the predictive value of postoperative serum SDC-1 levels in relation to multiple endpoints. RESULTS: In the study population, 110 patients (90.2%) underwent cardiopulmonary bypass, of which thirty received CABG or combined surgery. Fifteen patients (12.3%) required KRT, and thirty-eight (31.1%) developed progressive AKI, underscoring the severe AKI incidence. Multivariate logistic regression indicated that elevated SDC-1 levels were independent risk factors for progressive AKI (OR = 1.006) and AKI-KRT (OR = 1.011). The AUROC for SDC-1 levels in predicting AKI-KRT and AKI progression was 0.892 and 0.73, respectively, outperforming the inflammatory cytokines. Linear regression revealed a positive correlation between SDC-1 levels and both hospital (ß = 0.014, p = 0.022) and ICU stays (ß = 0.013, p < 0.001). CONCLUSION: Elevated postoperative SDC-1 levels significantly predict AKI progression and AKI-KRT in patients following cardiac surgery. The study's findings support incorporating SDC-1 level monitoring into post-surgical care to improve early detection and intervention for severe AKI.


Asunto(s)
Lesión Renal Aguda , Biomarcadores , Procedimientos Quirúrgicos Cardíacos , Progresión de la Enfermedad , Valor Predictivo de las Pruebas , Terapia de Reemplazo Renal , Sindecano-1 , Humanos , Sindecano-1/sangre , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , Factores de Riesgo , Medición de Riesgo , Resultado del Tratamiento , Factores de Tiempo , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Regulación hacia Arriba
20.
Support Care Cancer ; 32(8): 516, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014258

RESUMEN

PURPOSE: Dyadic communication positively affects marital relationships, good relationships help restore body image, and this study explores the relationship between dyadic communication and body image of breast cancer patients. METHODS: Cross-sectional correlation design with convenience sampling was used to recruit participants from two outpatient medical centers. Demographic information, medical records, and two questionnaires, dyadic communicative resilience scale (DCRS) and body image scale (BIS), were administered. Participants comprised women with breast cancer and their partners. Multiple regression analysis was performed to control related factors to understand the association between the DCRS of the women with breast cancer and their partners and the women's body image. Analysis of variance (ANOVA) was performed to analyze between three categories of couple's communication status (consistent and good, consistent and poor, and inconsistent) and body image of women with breast cancer. RESULTS: Data were obtained from 162 women with breast cancer and 90 partners. The study found (1) significant correlation between the women's perception of their communication and body image, (2) humor in partner's perception of their communication was significantly associated with women's body image, and (3) dyadic communication that both patients and partners were consistent and good in the domain of keeping pre-cancer routines and attractiveness was associated with women's body image. CONCLUSION: The correlation between dyadic communication and the body image of women with breast cancer is significant. Improving communication specific on keeping pre-cancer routines and attractiveness between women with breast cancer and their partners could enhance the women's body image.


Asunto(s)
Imagen Corporal , Neoplasias de la Mama , Comunicación , Humanos , Femenino , Neoplasias de la Mama/psicología , Imagen Corporal/psicología , Estudios Transversales , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Esposos/psicología , Relaciones Interpersonales , Masculino , Anciano , Análisis de Regresión , Análisis de Varianza , Resiliencia Psicológica
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