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1.
Bioinformatics ; 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39418177

RESUMEN

MOTIVATION: Recent advances in spatial transcriptomics technologies have provided multi-modality data integrating gene expression, spatial context, and histological images. Accurately identifying spatial domains and spatially variable genes is crucial for understanding tissue structures and biological functions. However, effectively combining multi-modality data to identify spatial domains and determining SVGs closely related to these spatial domains remains a challenge. RESULTS: In this study, we propose spatial transcriptomics Multi-modality and Multi-granularity Collaborative Learning (spaMMCL). For detecting spatial domains, spaMMCL mitigates the adverse effects of modality bias by masking portions of gene expression data, integrates gene and image features using a shared graph convolutional network, and employs graph self-supervised learning to deal with noise from feature fusion. Simultaneously, based on the identified spatial domains, spaMMCL integrates various strategies to detect potential SVGs at different granularities, enhancing their reliability and biological significance. Experimental results demonstrate that spaMMCL substantially improves the identification of spatial domains and SVGs. AVAILABILITY AND IMPLEMENTATION: The code and data of spaMMCL are available on Github: Https://github.com/liangxiao-cs/spaMMCL. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

2.
Angew Chem Int Ed Engl ; 63(38): e202407149, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-38949229

RESUMEN

This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer-Villiger oxidation of cyclohexanone, which was developed to produce seven-membered lactones and establish the required stereochemistry at the C14 position (92 % yield, 99 % ee, 500 mg scale). Cis- and trans-tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid-triggered, tunable acyl-Pictet-Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl-Pictet-Spengler cyclization cascade. By strategically using these two reactions and the late-stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids.


Asunto(s)
Alcaloides , Estereoisomerismo , Alcaloides/química , Alcaloides/síntesis química , Ciclización , Estructura Molecular , Oxidación-Reducción
3.
Biochem Biophys Res Commun ; 665: 71-77, 2023 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-37149985

RESUMEN

People of all ages could suffer from sleep disorders, which are increasingly recognized as common manifestations of neurologic disease. Acorus tatarinowii is a herb that has been used in traditional medicine to promote sleep. ß-asarone, as the main component of volatile oil obtained from Acorus tatarinowii, may be the main contributor to the sleeping-promoting efficacy of Acorus tatarinowii. In the study, adult male C57BL/6 mice were administered ß-asarone at 12.5 mg/kg, 25 mg/kg, and 50 mg/kg. Behavioral experiments showed that ß-asarone at 25 mg/kg could significantly improve sleep duration. It was also observed that the proportion of NREM (Non-Rapid Eye Movement) sleep increased considerably after administration of ß-asarone. In the PVN (paraventricular nucleus of hypothalamus) region of the hypothalamus, it was observed that the glutamate content decreased after ß-asarone treatment. At the same time, the expression of VGLUT2 (vesicular glutamate transporters 2) decreased while the expression of GAD65 (glutamic acid decarboxylase 65) and GABARAP (GABA Type A Receptor-Associated Protein) increased in the hypothalamus, suggesting that ß-asarone may suppress arousal by reducing glutamate and promoting transformation of glutamate to the inhibitory neurotransmitter GABA (γ-aminobutyric acid). This study is the first to focus on the association between ß-asarone and sleep, shedding perspectives for pharmacological applications of ß-asarone and providing a new direction for future research.


Asunto(s)
Ácido Glutámico , Núcleo Hipotalámico Paraventricular , Masculino , Ratones , Animales , Ratones Endogámicos C57BL , Sueño , Anisoles/farmacología , Ácido gamma-Aminobutírico
4.
J Nutr ; 153(9): 2561-2570, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37543214

RESUMEN

BACKGROUND: In early life, sialic acid (SA) plays a crucial role in neurodevelopment and neuronal function. However, it remains unclear whether and how SA supplementation in early life promotes behavioral response to stress in adolescence. OBJECTIVES: This study aimed to examine the effects and mechanisms of SA on the antistress capability under challenging situations. METHODS: In this study, C57BL/6 mice were daily supplemented with 1 µL SA solution/g body weight at the dose of 10 mg/kg/d from postnatal day (PND) 5-45. The antistress behaviors, including open field, elevated plus maze, forced swimming test, and tail suspension test, were performed at PND 46, PND 48, PND 50, and PND 52 to detect the antistress ability of SA, respectively. RESULTS: Our results showed that SA-treated mice were more active in facing challenging situations. The fiber photometry experiment showed that SA promoted the excitatory neuronal response in the medial prefrontal cortex (mPFC), which was extensively interconnected to stress. Besides, electrophysiological results revealed SA enhanced synaptic transmission rather than neuronal excitability of mPFC excitatory neurons. It was also supported by the increasing spine density of mPFC excitatory neurons. At the molecular amount, the SA elevated the transmitter release-related proteins of mPFC, including Synapsin 1 and vesicular glutamate transporter 1 (VGlut 1). Furthermore, SA supplementation enhanced synaptic transmission mainly by altering the kinetics of synaptic transmission. CONCLUSIONS: The SA supplementation enhanced the response capability to stress under challenging situations, and the enhanced synaptic transmission of mPFC excitatory neurons may be the neurological basis of active response under challenging situations. In general, our findings suggested that SA supplementation in early life can promote stress resistance in adolescence.


Asunto(s)
Ácido N-Acetilneuramínico , Transmisión Sináptica , Ratones , Animales , Ácido N-Acetilneuramínico/farmacología , Ratones Endogámicos C57BL , Transmisión Sináptica/fisiología , Neuronas/fisiología , Corteza Prefrontal/fisiología
5.
Molecules ; 28(12)2023 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-37375254

RESUMEN

We provide a method to regulate intramolecular charge transfer (ICT) through distorting fragment dipole moments based on molecular planarity and intuitively investigate the physical mechanisms of one-photon absorption (OPA), two-photon absorption (TPA), and electron circular dichroism (ECD) properties of the multichain 1,3,5 triazine derivatives o-Br-TRZ, m-Br-TRZ, and p-Br-TRZ containing three bromobiphenyl units. As the position of the C-Br bond on the branch chain becomes farther away, the molecular planarity is weakened, with the position of charge transfer (CT) on the branch chain of bromobiphenyl changing. The excitation energy of the excited states decreases, which leads to the redshift of the OPA spectrum of 1,3,5-triazine derivatives. The decrease in molecular plane results in a change in the magnitude and direction of the molecular dipole moment on the bromobiphenyl branch chain, which weakens the intramolecular electrostatic interaction of bromobiphenyl branch chain 1,3,5-triazine derivatives and weakens the charge transfer excitation of the second step transition in TPA, leading to an increase in the enhanced absorption cross-section. Furthermore, molecular planarity can also induce and regulate chiral optical activity through changing the direction of the transition magnetic dipole moment. Our visualization method helps to reveal the physical mechanism of TPA cross-sections generated via third-order nonlinear optical materials in photoinduced CT, which is of great significance for the design of large TPA molecules.

6.
Bioinformatics ; 36(22-23): 5481-5491, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33367525

RESUMEN

MOTIVATION: Protein kinases have been the focus of drug discovery research for many years because they play a causal role in many human diseases. Understanding the binding profile of kinase inhibitors is a prerequisite for drug discovery, and traditional methods of predicting kinase inhibitors are time-consuming and inefficient. Calculation-based predictive methods provide a relatively low-cost and high-efficiency approach to the rapid development and effective understanding of the binding profile of kinase inhibitors. Particularly, the continuous improvement of network pharmacology methods provides unprecedented opportunities for drug discovery, network-based computational methods could be employed to aggregate the effective information from heterogeneous sources, which have become a new way for predicting the binding profile of kinase inhibitors. RESULTS: In this study, we proposed a network-based influence deep diffusion model, named IDDkin, for enhancing the prediction of kinase inhibitors. IDDkin uses deep graph convolutional networks, graph attention networks and adaptive weighting methods to diffuse the effective information of heterogeneous networks. The updated kinase and compound representations are used to predict potential compound-kinase pairs. The experimental results show that the performance of IDDkin is superior to the comparison methods, including the state-of-the-art kinase inhibitor prediction method and the classic model widely used in relationship prediction. In experiments conducted to verify its generalizability and in case studies, the IDDkin model also shows excellent performance. All of these results demonstrate the powerful predictive ability of the IDDkin model in the field of kinase inhibitors. AVAILABILITY AND IMPLEMENTATION: Source code and data can be downloaded from https://github.com/CS-BIO/IDDkin. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

7.
Molecules ; 27(19)2022 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-36235063

RESUMEN

Many novel physical properties of twisted bilayer graphene have been discovered and studied successively, but the physical mechanism of the chiral modulation of BLG by a twisted angle lacks theoretical research. In this work, the density functional theory, the wavefunction analysis of the excited state, and the quantum theory of atoms in molecules are used to calculate and analyze the anti-symmetric chiral characteristics of zigzag-edge twisted bilayer graphene quantum dots based on periodic complementary twisted angles. The analysis of the partial density of states shows that Moiré superlattices can effectively adjust the contribution of the atomic basis function of the fragment to the transition dipole moment. The topological analysis of electron density indicates that the Moiré superlattices structure can enhance the localization of the system, increasing the electron density of the Moiré central ring, reducing the electron surge capacity in general and inducing the reversed helical properties of the top and underlying graphene, which can be used as the origin of the chiral discrimination; it also reveals the mole in the superlattice chiral physical mechanism. On this basis, we will also study the nonlinear optical properties of twisted bilayer graphene based on a twisted angle.

8.
FASEB J ; 34(11): 14371-14388, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32949431

RESUMEN

As a reversible scar repair reaction, liver fibrosis can be blocked or even reversed by proper intervention during its formation. Our work suggests that acid-sensitive ion channel 1a (ASIC1a) participates in liver fibrosis and presents a novel mechanism involving m6 A modification and miR-350/SPRY2. We demonstrated that the expression of ASIC1a was significantly increased in liver tissue of patients with liver fibrosis and animal models of liver fibrosis, as well as PDGF-BB-induced activated HSC-T6. After downregulating the expression of ASIC1a, the degree of liver fibrosis is reduced and HSC activation was inhibited, the level of m6 A modification and miR-350 expression were also reduced. The results of dual luciferase reporter assay showed that miR-350 can bind to the target gene SPRY2 and inhibit its expression. We also found that METTL3 can regulate the extent of m6 A modification of pri-miR-350 by binding to DGCR8. In addition, silencing or blocking the expression of ASIC1a can reduce the expression of PI3K/AKT and ERK signaling pathway-related proteins in activated HSCs. Taken together, we demonstrated that ASIC1a regulates the processing of miR-350 through METTL3-dependent m6 A modification, and mature miR-350 targets SPRY2 and further promotes liver fibrosis through the PI3K/KT and ERK pathways.


Asunto(s)
Canales Iónicos Sensibles al Ácido/metabolismo , Adenosina/análogos & derivados , Cirrosis Hepática/metabolismo , Proteínas de la Membrana/genética , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Canales Iónicos Sensibles al Ácido/genética , Adenosina/metabolismo , Animales , Línea Celular , Células Cultivadas , Humanos , Hígado/metabolismo , Cirrosis Hepática/genética , Sistema de Señalización de MAP Quinasas , Masculino , Proteínas de la Membrana/metabolismo , Metiltransferasas/metabolismo , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas de Unión al ARN/metabolismo
9.
Chemistry ; 26(46): 10439-10443, 2020 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-32500532

RESUMEN

The Eburnamine-Vincamine alkaloids have been studied intensively over the past six decades for their outstandingly potent vasorelaxation activity. Stereocontrolled assembly of the C20/C21 adjacent chiral centers has been a formidable challenge in the synthesis of this family. Herein, we report a concise stereoselective total synthesis of two trans-ring-fused non-natural analogues, (-)-20-epi-Vincamine and (-)-20-epi-Eburnamonine, that features the following key steps: a) a continuous-flow oxidation/lactam alcoholysis cascade producing the symmetrical dihydro-ß-carboline diester precursors, and b) a highly stereoselective Ir/f-Binaphane-catalyzed hydrogenation/lactamization cascade leading to the privileged trans-(20R, 21S) lactam ester scaffold with high-level enantio- and diastereocontrol.

10.
J Phys Chem A ; 123(37): 8071-8081, 2019 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-31461280

RESUMEN

The chiral source and its mechanism in the molecular system are of great significance in many fields. In this work, we proposed visualized methods to investigate the physical mechanism of a chiral molecule, where the electric and magnetic interactions are visualized with the transitional electric dipole moment, the transitional magnetic dipole moment, and the transitional electric quadrupole moment, and their tensor product. This will also serve as an effective means of visualizing the interaction of light with matter. The relationship between the molecular Raman optical activity (ROA) response and molecular structure was analyzed in an intuitive way. The relationship between chromophore chirality and molecular vibration mode are revealed via interaction between the transition electric dipole moment and the transition magnetic dipole moment. The molecular chirality is derived from the anisotropy of the molecular transition electric dipole moment and the transition magnetic dipole moment. The anisotropic dipole moment localized molecular chromophore is the source of the vibration mode in which the ROA responds to the reverse.

11.
Bioinformatics ; 33(2): 184-191, 2017 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-27634948

RESUMEN

MOTIVATION: Many forms of variations exist in the human genome including single nucleotide polymorphism, small insert/deletion (DEL) (indel) and structural variation (SV). Somatically acquired SV may regulate the expression of tumor-related genes and result in cell proliferation and uncontrolled growth, eventually inducing tumor formation. Virus integration with host genome sequence is a type of SV that causes the related gene instability and normal cells to transform into tumor cells. Cancer SVs and viral integration sites must be discovered in a genome-wide scale for clarifying the mechanism of tumor occurrence and development. RESULTS: In this paper, we propose a new tool called seeksv to detect somatic SVs and viral integration events. Seeksv simultaneously uses split read signal, discordant paired-end read signal, read depth signal and the fragment with two ends unmapped. Seeksv can detect DEL, insertion, inversion and inter-chromosome transfer at single-nucleotide resolution. Different types of sequencing data, such as single-end sequencing data or paired-end sequencing data can accommodate to detect SV. Seeksv develops a rescue model for SV with breakpoints located in sequence homology regions. Results on simulated and real data from the 1000 Genomes Project and esophageal squamous cell carcinoma samples show that seeksv has higher efficiency and precision compared with other similar software in detecting SVs. For the discovery of hepatitis B virus integration sites from probe capture data, the verified experiments show that more than 90% viral integration sequences detected by seeksv are true. AVAILABILITY AND IMPLEMENTATION: seeksv is implemented in C ++ and can be downloaded from https://github.com/qkl871118/seeksv CONTACT: : dragonbw@163.comSupplementary information: Supplementary data are available at Bioinformatics online.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Variación Estructural del Genoma , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Integración Viral , Carcinoma de Células Escamosas de Esófago , Genoma Humano , Humanos
12.
Neurol Neurochir Pol ; 52(1): 25-28, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28964406

RESUMEN

OBJECTIVE: Pericallosal artery aneurysms are not common clinically. The microsurgery and endovascular therapy are surgically challenging operations. The objective of the study is to summarize their clinical symptoms and optimal treatment strategies of pericallosal artery aneurysms. METHODS: Nine cases of pericallosal artery aneurysms detected by digital subtraction angiography (DSA) were reviewed. The clinical manifestation, brain imaging characteristics, and optimal treatment methods were summarized. RESULTS: Patients with spontaneous aneurysm had good clinical outcomes after endovascular coiling or microsurgical clipping treatment. There were no any neurological function deficits in five patients. One patient suffered from permanent neurological function deficits. Patients with traumatic aneurysm pericallosal had relatively poor outcomes, including two patients showing disturbed consciousness and the paralysis of the lower limbs with slow recovery, and one patient was dead after the surgery. CONCLUSION: Spontaneous subarachnoid hemorrhage and interhemispheric fissure hematoma suggest spontaneously pericallosal aneurysm, while traumatic corpus callosum hematoma as well the accompanying embryo of intraventricular hemorrhage suggest traumatic pericallosal aneurysm. Endovascular embolization is the primary surgical treatment for pericallosal aneurysm, while patients with pericallosal aneurysm are not suitable for surgical treatment. Microsurgical clipping treatment may be a choice. However, both of these treatment strategies have high risk.


Asunto(s)
Arterias , Aneurisma Roto , Embolización Terapéutica , Humanos , Aneurisma Intracraneal , Resultado del Tratamiento
13.
ACS Nano ; 18(8): 6413-6423, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38349943

RESUMEN

Aqueous zinc-ion batteries emerge as a promising energy storage system with merits of high security, abundance, and being environmentally benign. But the low operating voltages of aqueous electrolytes restrict their energy densities. Previous reports have mostly focused on modifying the electrolytes to enlarge the operating voltages of aqueous zinc-ion batteries. However, either extra-expensive salts or potential safety hazards of organic additives are considered to be adverse for practical large-scale applications. Here, a proof-of-concept to enlarge the operating voltage of an aqueous zinc-ion battery by incorporating a well-designed semiconductor photocathode is proposed, which produces a photovoltage (Vph) across the semiconductor/liquid junction (SCLJ) interface to elevate the output voltage of zinc-ion battery under irradiation. The operating voltage of an aqueous zinc-ion battery can be markedly raised from 1.78 (thermodynamic limit) to 2.4 V when a BiOI nanoflake array photocathode with good surface modification is introduced, achieving a round-trip efficiency of 114.3% and a 34.8% increase of energy density compared to the theoretical value. The successive ionic layer adsorption and reaction modified surface effectively passivates surface trap defects of the BiOI photocathode and thus enlarges its Vph from 60 to 240 mV under irradiation. This study provides a design to enlarge the output voltages of aqueous zinc-ion batteries and other energy storage systems, providing insight into widening the voltage window, which is that the operating voltages are determined by photocathode under irradiation and not restricted by the electrochemical stability window of dilute aqueous electrolytes.

14.
ACS Appl Mater Interfaces ; 16(34): 44689-44696, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39137323

RESUMEN

Carbonate-based electrolytes show distinct advantages in high-voltage cathodes but generate nonuniform and mechanically fragile solid-electrolyte interphase (SEI) in lithium (Li) metal batteries. Herein, we propose a LiF-rich SEI incorporating an in situ polymerized poly(hexamethylene diisocyanate)-based gel polymer electrolyte (GPE) to improve the homogeneity and mechanical stability of SEI. Fluoroethylene carbonate (FEC) as a fluorine-based additive for building LiF-rich SEI on Li metal electrodes. With this strategy, the assembled Li symmetric batteries cycled stably for 700 h, and the formation of byproducts on the Li electrode surface was significantly inhibited. The Li/LiFePO4 battery delivered significant capacity retention (91% retention after 800 cycles) at 1 C. With high-voltage LiNi0.8Co0.1Mn0.1O2 (NCM811) as cathode, the Li/GPE-FEC/NCM811 cell delivered a discharge capacity of 168.9 mAh g-1 with a capacity retention of 82% after 300 cycles at 0.5 C. From the above, the work could assist the rapid development of high-energy-density rechargeable Li metal batteries toward remarkable performance.

15.
J Neuroimmune Pharmacol ; 19(1): 31, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38886223

RESUMEN

Neuroinflammation is a key factor in cognitive dysfunction and neurodegenerative diseases such as Alzheimer's disease (AD), so inhibiting neuroinflammation is considered as a potential treatment for AD. Epigallocatechin-3-gallate (EGCG), a polyhydroxyphenol of green tea, has been found to exhibit anti-oxidative, anti-inflammatory and neuroprotective effects. The aim of this study was to investigate the inhibitory effect of EGCG on inflammation and its mechanism. In this study, BV2 cells were simultaneously exposed to lipopolysaccharides (LPS) and the amyloid-ß oligomer (AßO) to induce inflammatory microenvironments. Inflammatory cytokines and NLRP3 inflammasome-related molecules were detected by RT-PCR and Western Blot. The results show that EGCG inhibits LPS/AßO-induced inflammation in BV2 cells through regulating IL-1ß, IL-6, and TNF-α. Meanwhile, EGCG reduces the activation of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and levels of intracellular ROS in BV2 cells treated with LPS/AßO by affecting the mitochondrial membrane potential (MMP). Further research found that EGCG inhibited MMP through regulating thioredoxin-interacting protein (TXNIP) in LPS/AßO-induced neuroinflammation. In conclusion, EGCG may alleviate LPS/AßO-induced microglial neuroinflammation by suppressing the ROS/ TXNIP/ NLRP3 pathway. It may provide a potential mechanism underlying the anti-inflammatory properties of EGCG for alleviating AD.


Asunto(s)
Péptidos beta-Amiloides , Proteínas Portadoras , Catequina , Lipopolisacáridos , Proteína con Dominio Pirina 3 de la Familia NLR , Enfermedades Neuroinflamatorias , Especies Reactivas de Oxígeno , Transducción de Señal , Catequina/análogos & derivados , Catequina/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Lipopolisacáridos/toxicidad , Animales , Péptidos beta-Amiloides/toxicidad , Ratones , Especies Reactivas de Oxígeno/metabolismo , Proteínas Portadoras/metabolismo , Transducción de Señal/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Línea Celular , Tiorredoxinas/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo
16.
Adv Sci (Weinh) ; 11(32): e2403870, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38899831

RESUMEN

Guided nanowires grown on polymer surfaces facilitate their seamless integration as flexible devices without post-growth processing steps. However, this is challenging due to the inability of polymer films to provide the required lattice-matching effect. In this work, this challenge is addressed by replicating highly aligned nanogrooves from a compact disc (CD) onto a casted flexible polydimethylsiloxane (PDMS) surface. Leveraging the replicated nanogrooves, copper hexadecafluorophthalocyanine (F16CuPc) and various metal phthalocyanines are guided into large-area, self-aligned nanowires. Subsequently, by employing specifically designed shadow masks during electrode deposition, these nanowires are seamlessly integrated as either a monolithic flexible photodetector with a large sensing area or on-chip flexible photodetector arrays. The resulting flexible photodetectors exhibit millisecond and long-term stable response to UV-vis-NIR light. Notably, they demonstrate exceptional bending stability, retaining stable and sensitive photoresponse even at a curvature radius as low as 0.5 cm and after enduring 1000 bending cycles. Furthermore, the photodetector array showcases consistent sensitivity and response speed across the entire array. This work not only proves the viability of guided nanowire growth on flexible polymer surfaces by replicating CD nanogrooves but also underscores the potential for large-scale monolithic integration of guided nanowires as flexible devices.

17.
Toxicology ; 502: 153717, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38160928

RESUMEN

Lead (Pb) is an environmental neurotoxic metal. Chronic Pb exposure causes behavioral changes in humans and rodents, such as dysfunctional learning and memory. Nevertheless, it is not clear whether Pb exposure disrupts the neural circuit. Thus, here we aim at investigating the effects the chronic Pb exposure on neural-behavioral and neural circuits in mice from prenatal to postnatal day (PND) 63. Pregnant mice and their male offspring were treated with Pb (150 ppm) until postnatal day 63. In this study, several behavior tests and Golgi-Cox staining methods were used to assess spatial memory ability and synaptogenesis. Virus-based tracing systems and immunohistochemistry assays were used to test the relevance of chronic Pb exposure with disrupted neural circuits. The behavioral experiments and Golgi-Cox staining results showed that Pb exposure impaired spatial memory and spine density in mice. The virus tracing results revealed that the Entorhinal cortex (EC) neurons could be directly projected to Cornuammonis 1 (CA1) and Dentate gyrus (DG), forming a critical circuit inhibited, in either a direct or indirect way, by Pb invasion. In addition, excitatory neural input from EC(labeled with CaMKII)to CA1 and DG was significantly attenuated by Pb exposure. In conclusion, our data indicated that Pb significantly impaired the excitatory connections from EC to the hippocampus (CA1 and DG), providing a novel neuro-circuitry basis for Pb neurotoxicity.


Asunto(s)
Hipocampo , Plomo , Embarazo , Femenino , Humanos , Ratones , Animales , Masculino , Plomo/toxicidad , Sistema Nervioso , Memoria Espacial , Neuronas
18.
Artículo en Inglés | MEDLINE | ID: mdl-39401295

RESUMEN

Integrating the dual functionalities of a photodetector and photonic synapse into a single device is challenging due to their conflicting requirements for photocurrent decay rates. This study addresses this issue by seamlessly depositing transparent indium tin oxide (ITO) electrodes onto self-oriented copper hexadecafluoro-phthalocyanine (F16CuPc) nanowires growing horizontally along hot-stamped periodic nanogrooves on a transparent flexible polyimide plastic film. This in-situ-fabricated device achieves bending-stable dual functionalities through wavelength regulation while maintaining high transparency and flexibility. Upon exposure to 450-850 nm light, the device exhibits a rapid and sensitive photoresponse with excellent bending stability, making it ideal for optical sensing in both visible and near-infrared spectra. More importantly, the device exhibits a bending-stable excitation postsynaptic current when exposed to light spikes below 405 nm. This enables the successful emulation of various biological synaptic functionalities, including paired-pulse facilitation, spike-number-dependent plasticity, spike-duration-dependent plasticity, spike-rating-dependent plasticity, configurable plasticity between short-term plasticity and long-term plasticity, and memory learning capabilities. Utilizing this device in an artificial neural network achieves a recognition rate of 95% after 57 training epochs. Its ability to switch between photodetection and synaptic modes by adjusting the light wavelength marks a significant advancement in the field of multifunctional flexible electronics based on nanowire arrays.

19.
Nat Commun ; 15(1): 1672, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395923

RESUMEN

The practical applications of solar-driven water splitting pivot on significant advances that enable scalable production of robust photoactive films. Here, we propose a proof-of-concept for fabricating robust photoactive films by a particle-implanting technique (PiP) which embeds semiconductor photoabsorbers in the liquid metal. The strong semiconductor/metal interaction enables resulting films efficient collection of photogenerated charges and superior photoactivity. A photoanode of liquid-metal embraced BiVO4 can stably operate over 120 h and retain ~ 70% of activity when scaled from 1 to 64 cm2. Furthermore, a Z-scheme photocatalyst film of liquid-metal embraced BiVO4 and Rh-doped SrTiO3 particles can drive overall water splitting under visible light, delivering an activity 2.9 times higher than that of the control film with gold support and a 110 h stability. These results demonstrate the advantages of the PiP technique in constructing robust and efficient photoactive films for artificial photosynthesis.

20.
IEEE/ACM Trans Comput Biol Bioinform ; 20(3): 2254-2265, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37022218

RESUMEN

Clustering cells into subgroups plays a critical role in single cell-based analyses, which facilitates to reveal cell heterogeneity and diversity. Due to the ever-increasing scRNA-seq data and low RNA capture rate, it has become challenging to cluster high-dimensional and sparse scRNA-seq data. In this study, we propose a single-cell Multi-Constraint deep soft K-means Clustering(scMCKC) framework. Based on zero-inflated negative binomial (ZINB) model-based autoencoder, scMCKC constructs a novel cell-level compactness constraint by considering association between similar cell, to emphasize the compactness between clusters. Besides, scMCKC utilizes pairwise constraint encoded by prior information to guide clustering. Meanwhile, a weighted soft K-means algorithm is leveraged to determine the cell populations, which assigns the label based on affinity between data and clustering center. Experiments on eleven scRNA-seq datasets demonstrate that scMCKC is superior to the state-of-the-art methods and notably improves cluster performance. Moreover, we validate the robustness on human kidney dataset, which demonstrates that scMCKC exhibits comprehensively excellent performance on clustering analysis. The ablation study on eleven datasets proves that the novel cell-level compactness constraint is conductive to the clustering results.


Asunto(s)
Algoritmos , Análisis de Expresión Génica de una Sola Célula , Humanos , Análisis de Secuencia de ARN/métodos , RNA-Seq/métodos , Análisis por Conglomerados , Análisis de la Célula Individual/métodos , Perfilación de la Expresión Génica/métodos
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