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1.
Nature ; 623(7987): 531-537, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37853122

RESUMEN

Achieving both high efficiency and long-term stability is the key to the commercialization of perovskite solar cells (PSCs)1,2. However, the diversity of perovskite (ABX3) compositions and phases makes it challenging to fabricate high-quality films3-5. Perovskite formation relies on the reaction between AX and BX2, whereas most conventional methods for film-growth regulation are based solely on the interaction with the BX2 component. Herein, we demonstrate an alternative approach to modulate reaction kinetics by anion-π interaction between AX and hexafluorobenzene (HFB). Notably, these two approaches are independent but work together to establish 'dual-site regulation', which achieves a delicate control over the reaction between AX and BX2 without unwanted intermediates. The resultant formamidinium lead halides (FAPbI3) films exhibit fewer defects, redshifted absorption and high phase purity without detectable nanoscale δ phase. Consequently, we achieved PSCs with power conversion efficiency (PCE) up to 26.07% for a 0.08-cm2 device (25.8% certified) and 24.63% for a 1-cm2 device. The device also kept 94% of its initial PCE after maximum power point (MPP) tracking for 1,258 h under full-spectrum AM 1.5 G sunlight at 50 ± 5 °C. This method expands the range of chemical interactions that occur in perovskite precursors by exploring anion-π interactions and highlights the importance of the AX component as a new and effective working site to improved photovoltaic devices with high quality and phase purity.

2.
Nature ; 614(7948): 456-462, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36792740

RESUMEN

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.


Asunto(s)
Electromiografía , Electrónica Médica , Nanoestructuras , Docilidad , Polímeros , Prótesis e Implantes , Dispositivos Electrónicos Vestibles , Humanos , Nanoestructuras/química , Polímeros/química , Piel , Monitoreo Fisiológico , Electrónica Médica/instrumentación , Electrónica Médica/métodos , Electromiografía/instrumentación
3.
Nature ; 615(7950): 56-61, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36859579

RESUMEN

Correlating atomic configurations-specifically, degree of disorder (DOD)-of an amorphous solid with properties is a long-standing riddle in materials science and condensed matter physics, owing to difficulties in determining precise atomic positions in 3D structures1-5. To this end, 2D systems provide insight to the puzzle by allowing straightforward imaging of all atoms6,7. Direct imaging of amorphous monolayer carbon (AMC) grown by laser-assisted depositions has resolved atomic configurations, supporting the modern crystallite view of vitreous solids over random network theory8. Nevertheless, a causal link between atomic-scale structures and macroscopic properties remains elusive. Here we report facile tuning of DOD and electrical conductivity in AMC films by varying growth temperatures. Specifically, the pyrolysis threshold temperature is the key to growing variable-range-hopping conductive AMC with medium-range order (MRO), whereas increasing the temperature by 25 °C results in AMC losing MRO and becoming electrically insulating, with an increase in sheet resistance of 109 times. Beyond visualizing highly distorted nanocrystallites embedded in a continuous random network, atomic-resolution electron microscopy shows the absence/presence of MRO and temperature-dependent densities of nanocrystallites, two order parameters proposed to fully describe DOD. Numerical calculations establish the conductivity diagram as a function of these two parameters, directly linking microstructures to electrical properties. Our work represents an important step towards understanding the structure-property relationship of amorphous materials at the fundamental level and paves the way to electronic devices using 2D amorphous materials.

4.
Plant J ; 118(6): 1793-1814, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38461478

RESUMEN

Flavan-3-ols are prominent phenolic compounds found abundantly in the young leaves of tea plants. The enzymes involved in flavan-3-ol biosynthesis in tea plants have been extensively investigated. However, the localization and associations of these numerous functional enzymes within cells have been largely neglected. In this study, we aimed to investigate the synthesis of flavan-3-ols in tea plants, particularly focusing on epigallocatechin gallate. Our analysis involving the DESI-MSI method to reveal a distinct distribution pattern of B-ring trihydroxylated flavonoids, primarily concentrated in the outer layer of buds. Subcellular localization showed that CsC4H, CsF3'H, and CsF3'5'H localizes endoplasmic reticulum. Protein-protein interaction studies demonstrated direct associations between CsC4H, CsF3'H, and cytoplasmic enzymes (CHS, CHI, F3H, DFR, FLS, and ANR), highlighting their interactions within the biosynthetic pathway. Notably, CsF3'5'H, the enzyme for B-ring trihydroxylation, did not directly interact with other enzymes. We identified cytochrome b5 isoform C serving as an essential redox partner, ensuring the proper functioning of CsF3'5'H. Our findings suggest the existence of distinct modules governing the synthesis of different B-ring hydroxylation compounds. This study provides valuable insights into the mechanisms underlying flavonoid diversity and efficient synthesis and enhances our understanding of the substantial accumulation of B-ring trihydroxylated flavan-3-ols in tea plants.


Asunto(s)
Camellia sinensis , Catequina , Citocromos b5 , Flavonoides , Proteínas de Plantas , Flavonoides/metabolismo , Flavonoides/biosíntesis , Camellia sinensis/metabolismo , Camellia sinensis/genética , Catequina/metabolismo , Catequina/análogos & derivados , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Citocromos b5/metabolismo , Citocromos b5/genética , Hojas de la Planta/metabolismo , Hidroxilación , Retículo Endoplásmico/metabolismo
5.
Mol Ther ; 32(2): 469-489, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38098230

RESUMEN

Macrophages play a crucial role in shaping the immune state within the tumor microenvironment (TME) and are often influenced by tumors to hinder antitumor immunity. However, the underlying mechanisms are still elusive. Here, we observed abnormal expression of complement 5a receptor (C5aR) in human ovarian cancer (OC), and identified high levels of C5aR expression on tumor-associated macrophages (TAMs), which led to the polarization of TAMs toward an immunosuppressive phenotype. C5aR knockout or inhibitor treatment restored TAM antitumor response and attenuated tumor progression. Mechanistically, C5aR deficiency reprogrammed macrophages from a protumor state to an antitumor state, associating with the upregulation of immune response and stimulation pathways, which in turn resulted in the enhanced antitumor response of cytotoxic T cells in a manner dependent on chemokine (C-X-C motif) ligand 9 (CXCL9). The pharmacological inhibition of C5aR also improved the efficacy of immune checkpoint blockade therapy. In patients, C5aR expression associated with CXCL9 production and infiltration of CD8+ T cells, and a high C5aR level predicted poor clinical outcomes and worse benefits from anti-PD-1 therapy. Thus, our study sheds light on the mechanisms underlying the modulation of TAM antitumor immune response by the C5a-C5aR axis and highlights the potential of targeting C5aR for clinical applications.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias , Humanos , Quimiocina CXCL9/genética , Inmunidad , Neoplasias/patología , Receptor de Anafilatoxina C5a/genética , Microambiente Tumoral , Macrófagos Asociados a Tumores/metabolismo , Femenino
6.
BMC Plant Biol ; 24(1): 807, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39187785

RESUMEN

Cadmium (Cd) is a biologically non-essential heavy metal, a major soil pollutant, and extremely harmful to plants. The phytohormone methyl jasmonate (MeJA) plays an important role in plant heavy-metal resistance. However, the understanding of the effects of MeJA supply level on alleviating Cd toxicity in plants is limited. Here, we investigated how MeJA regulated the development of physiological processes and cell wall modification in Cosmos bipinnatus. We found that low concentrations of MeJA increased the dry weight of seedlings under 120 µM Cd stress by reducing the transport of Cd from roots to shoots. Moreover, a threshold concentration of exogenous MeJA increased the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in plant roots, the concentration of Cd in the root cell wall, and the contents of pectin and hemicellulose 1 polysaccharides, through converting Cd into pectin-bound forms. These results suggested that MeJA mitigated Cd toxicity by modulating root cell wall polysaccharide and functional group composition, especially through pectin polysaccharides binding to Cd, with effects on Cd transport capacity, specific chemical forms of Cd, and homeostatic antioxidant systems in C. bipinnatus.


Asunto(s)
Acetatos , Cadmio , Ciclopentanos , Oxilipinas , Reguladores del Crecimiento de las Plantas , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Acetatos/farmacología , Cadmio/toxicidad , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Contaminantes del Suelo/toxicidad , Pared Celular/metabolismo , Pared Celular/efectos de los fármacos , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Antioxidantes/metabolismo , Superóxido Dismutasa/metabolismo
7.
J Transl Med ; 22(1): 615, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961500

RESUMEN

OBJECTIVE: To explore the correlation between asthma risk and genetic variants affecting the expression or function of lipid-lowering drug targets. METHODS: We conducted Mendelian randomization (MR) analyses using variants in several genes associated with lipid-lowering medication targets: HMGCR (statin target), PCSK9 (alirocumab target), NPC1L1 (ezetimibe target), APOB (mipomersen target), ANGPTL3 (evinacumab target), PPARA (fenofibrate target), and APOC3 (volanesorsen target), as well as LDLR and LPL. Our objective was to investigate the relationship between lipid-lowering drugs and asthma through MR. Finally, we assessed the efficacy and stability of the MR analysis using the MR Egger and inverse variance weighted (IVW) methods. RESULTS: The elevated triglyceride (TG) levels associated with the APOC3, and LPL targets were found to increase asthma risk. Conversely, higher LDL-C levels driven by LDLR were found to decrease asthma risk. Additionally, LDL-C levels (driven by APOB, NPC1L1 and HMGCR targets) and TG levels (driven by the LPL target) were associated with improved lung function (FEV1/FVC). LDL-C levels driven by PCSK9 were associated with decreased lung function (FEV1/FVC). CONCLUSION: In conclusion, our findings suggest a likely causal relationship between asthma and lipid-lowering drugs. Moreover, there is compelling evidence indicating that lipid-lowering therapies could play a crucial role in the future management of asthma.


Asunto(s)
Asma , Hipolipemiantes , Análisis de la Aleatorización Mendeliana , Humanos , Asma/genética , Asma/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Hipolipemiantes/farmacología , Proproteína Convertasa 9/genética , Estudios de Asociación Genética , Pulmón/efectos de los fármacos , Pulmón/patología , Lipoproteína Lipasa/genética , Triglicéridos/sangre , Receptores de LDL/genética , Hidroximetilglutaril-CoA Reductasas/genética , Proteína 3 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina/genética , Apolipoproteína C-III/genética , Apolipoproteínas B/genética , Pruebas de Función Respiratoria , LDL-Colesterol/sangre , Proteínas de Transporte de Membrana , PPAR alfa
8.
Clin Proteomics ; 21(1): 29, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594611

RESUMEN

BACKGROUND: Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. METHOD: Patients with ACP (n = 15) or Rathke's cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples. RESULTS: The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP. CONCLUSIONS: This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.

9.
Neuroendocrinology ; 114(6): 577-588, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38368872

RESUMEN

INTRODUCTION: Acromegaly patients, in addition to the most prominent physical and endocrine changes, also exhibit a higher risk of cognitive dysfunction. However, the reasons and mechanisms underlying cognitive impairments in acromegaly patients remain unknown. METHODS: Acromegalic rats were induced by subcutaneous injection of tumor cells, with continuous monitoring of the body weight and hormones to confirm the occurrence of acromegaly. Behavioral assessments, including open field test, novel object recognition test, and Barnes maze test, were conducted to evaluate the animals' cognitive function. Western blotting, immunohistochemistry, and immunofluorescence techniques were employed to examine changes in the hippocampal tau protein, Aß, and associated signaling pathways. RESULTS: The tumor cells secreting growth hormone increased the secretion of growth hormone, resulting in changes in body size and endocrine functions, thus causing acromegaly. The acromegaly model showed deficiencies in working memory and spatial memory. Hyperphosphorylation of tau protein was observed in the hippocampus of the acromegaly model, but no Aß deposition was observed. The acromegaly model exhibits hippocampal growth hormone (GH) resistance, decreased expression of GH receptors, and subsequently reduced expression activity of the PI3K-Akt-GSK3ß signaling pathway, which is responsible for the hyperphosphorylation of tau protein. CONCLUSION: The prolonged elevation of GH and insulin-like growth factor 1 caused by acromegaly may lead to abnormalities in the SD rat's PI3K-Akt-GSK3ß signaling pathway, subsequently resulting in hyperphosphorylation of the hippocampal tau protein and cognitive impairment.


Asunto(s)
Acromegalia , Disfunción Cognitiva , Modelos Animales de Enfermedad , Hipocampo , Proteínas tau , Animales , Masculino , Ratas , Acromegalia/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/etiología , Hormona del Crecimiento/metabolismo , Hipocampo/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Aprendizaje por Laberinto/fisiología , Fosforilación , Ratas Sprague-Dawley , Transducción de Señal/fisiología , Proteínas tau/metabolismo
10.
Fish Shellfish Immunol ; 153: 109821, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39117129

RESUMEN

Polymeric immunoglobulin receptor (pIgR) is an important immune factor in the mucosal immune system of fish, which plays a key role in mediating the secretion and transport of immunoglobulin into mucus. In this study, the full-length cDNA sequence of Megalobrama amblycephala pIgR gene was firstly cloned and the immune response to Aeromonas hydrophila was detected. After being challenged by Aeromonas hydrophila at 3 d, significantly pathological features were observed in intestine, head kidney, spleen, liver and gill of Megalobrama amblycephala. The content of lysozyme (Lys) and the activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) increased significantly at 1 d and reached the peak at 3 d, and the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in serum reached the peak at 5 d and 7 d after infection, respectively. The expression level of IL-1ß gene reached the peak at 3 d in intestine, 5 d in gill and spleen, 7 d in head kidney and liver of Megalobrama amblycephala after infected by Aeromonas hydrophila, respectively. The TNF-α gene expression reached the peak at 3 d in intestine and gill, 5 d in head kidney and spleen, 7 d in liver after infection, respectively. The experimental results showed that the infection of Aeromonas hydrophila caused the pathological changes of immune-related tissues and triggered the inflammation responses. The full-length cDNA sequence of Megalobrama amblycephala pIgR was 1828 bp, and its open reading frame (ORF) was 1023 bp, encoding 340 amino acids. The pIgR of Megalobrama amblycephala has a signal peptide sequence, followed by extracellular region, transmembrane region and intracellular region. The extracellular region includes two Ig-like domains (ILDs), and its tertiary structure is twisted "L". The phylogenetic tree was constructed using the adjacency method, and the pIgR genes of Megalobrama amblycephala and cyprinidae fish were clustered into a single branch. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of pIgR gene in different tissues of Megalobrama amblycephala. The expression level of pIgR gene was the highest in liver, followed by intestine, head kidney, skin, middle kidney and spleen, lower in heart, gill and brain, and the lowest in muscle. After being infected by Aeromonas hydrophila, the expression level of Megalobrama amblycephala pIgR gene in intestine, head kidney, spleen, liver and gill showed a trend of increasing first and then decreasing within 28 d. The pIgR gene expression reached the peak in mucosal immune-related tissues (gill and intestine) was earlier than that in systemic immune-related tissues (head kidney and spleen), and the relative expression level of pIgR gene at peak in intestine (12.3 fold) was higher than that in head kidney (3.73 fold) and spleen (7.84 fold). These results suggested that Megalobrama amblycephala pIgR might play an important role in the mucosal immune system to against Aeromonas hydrophila infection.

11.
BMC Neurol ; 24(1): 198, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867178

RESUMEN

BACKGROUND: At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear. OBJECTIVE: To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD. METHODS: We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction. RESULTS: Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients' ipsilateral MCA-PI were less than 0.614, and another one's MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009). CONCLUSIONS: A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.


Asunto(s)
Infarto Cerebral , Revascularización Cerebral , Enfermedad de Moyamoya , Complicaciones Posoperatorias , Ultrasonografía Doppler Transcraneal , Humanos , Enfermedad de Moyamoya/cirugía , Enfermedad de Moyamoya/diagnóstico por imagen , Masculino , Femenino , Adulto , Infarto Cerebral/etiología , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/epidemiología , Estudios Retrospectivos , Revascularización Cerebral/efectos adversos , Revascularización Cerebral/métodos , Ultrasonografía Doppler Transcraneal/métodos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/cirugía , Flujo Pulsátil/fisiología , Adulto Joven , Factores de Riesgo
12.
Nature ; 555(7694): 83-88, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29466334

RESUMEN

Skin-like electronics that can adhere seamlessly to human skin or within the body are highly desirable for applications such as health monitoring, medical treatment, medical implants and biological studies, and for technologies that include human-machine interfaces, soft robotics and augmented reality. Rendering such electronics soft and stretchable-like human skin-would make them more comfortable to wear, and, through increased contact area, would greatly enhance the fidelity of signals acquired from the skin. Structural engineering of rigid inorganic and organic devices has enabled circuit-level stretchability, but this requires sophisticated fabrication techniques and usually suffers from reduced densities of devices within an array. We reasoned that the desired parameters, such as higher mechanical deformability and robustness, improved skin compatibility and higher device density, could be provided by using intrinsically stretchable polymer materials instead. However, the production of intrinsically stretchable materials and devices is still largely in its infancy: such materials have been reported, but functional, intrinsically stretchable electronics have yet to be demonstrated owing to the lack of a scalable fabrication technology. Here we describe a fabrication process that enables high yield and uniformity from a variety of intrinsically stretchable electronic polymers. We demonstrate an intrinsically stretchable polymer transistor array with an unprecedented device density of 347 transistors per square centimetre. The transistors have an average charge-carrier mobility comparable to that of amorphous silicon, varying only slightly (within one order of magnitude) when subjected to 100 per cent strain for 1,000 cycles, without current-voltage hysteresis. Our transistor arrays thus constitute intrinsically stretchable skin electronics, and include an active matrix for sensory arrays, as well as analogue and digital circuit elements. Our process offers a general platform for incorporating other intrinsically stretchable polymer materials, enabling the fabrication of next-generation stretchable skin electronic devices.


Asunto(s)
Electrónica/instrumentación , Docilidad , Piel , Transistores Electrónicos , Dispositivos Electrónicos Vestibles , Humanos , Polímeros/química , Silicio/química
13.
Mol Ther ; 31(5): 1313-1331, 2023 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-36739479

RESUMEN

Astrocyte-microglial interaction plays a crucial role in brain injury-associated neuroinflammation. Our previous data illustrated that astrocytes secrete microRNA, leading to anti-inflammatory effects on microglia. Long non-coding RNAs participate in neuroinflammation regulation after traumatic brain injury. However, the effect of astrocytes on microglial phenotype via long non-coding RNAs and the underlying molecular mechanisms remain elusive. We used long non-coding RNA sequencing on murine astrocytes and found that exosomal long non-coding RNA 4933431K23Rik attenuated traumatic brain injury-induced microglial activation in vitro and in vivo and ameliorated cognitive function deficiency. Furthermore, microRNA and messenger RNA sequencing together with binding prediction illustrated that exosomal long non-coding RNA 4933431K23Rik up-regulates E2F7 and TFAP2C expression by sponging miR-10a-5p. Additionally, E2F7 and TFAP2C, as transcription factors, regulated microglial Smad7 expression. Using Cx3cr1-Smad7 overexpression of adeno-associated virus, microglia specifically overexpressed Smad7 in the attenuation of neuroinflammation, resulting in less cognitive deficiency after traumatic brain injury. Mechanically, overexpressed Smad7 physically binds to IκBα and inhibits its ubiquitination, preventing NF-κB signaling activation. The Smad7 activator asiaticoside alleviates neuroinflammation and protects neuronal function in traumatic brain injury mice. This study revealed that an exosomal long non-coding RNA from astrocytes attenuates microglial activation after traumatic brain injury by up-regulating Smad7, providing a potential therapeutic target.


Asunto(s)
Lesiones Traumáticas del Encéfalo , MicroARNs , ARN Largo no Codificante , Ratones , Animales , Microglía/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Astrocitos/metabolismo , Enfermedades Neuroinflamatorias , MicroARNs/metabolismo , Lesiones Traumáticas del Encéfalo/genética , Lesiones Traumáticas del Encéfalo/metabolismo , Fenotipo , Ratones Endogámicos C57BL
14.
Int J Med Sci ; 21(1): 123-136, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38164349

RESUMEN

CREB3 subfamily belongs to the bZIP transcription factor family and comprises five members. Normally they are located on the endoplasmic reticulum (ER) membranes and proteolytically activated through RIP (regulated intramembrane proteolysis) on Golgi apparatus to liberate the N-terminus to serve as transcription factors. CREB3L1 acting as one of them transcriptionally regulates the expressions of target genes and exhibits distinct functions from the other members of CREB3 family in eukaryotes. Physiologically, CREB3L1 involves in the regulation of bone morphogenesis, neurogenesis, neuroendocrine, secretory cell differentiation, and angiogenesis. Pathologically, CREB3L1 implicates in the modulation of osteogenesis imperfecta, low grade fibro myxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), glioma, breast cancer, thyroid cancer, and tissue fibrosis. This review summarizes the upstream and downstream regulatory network of CREB3L1 and thoroughly presents our current understanding of CREB3L1 research progress in both physiological and pathological conditions with special focus on the novel findings of CREB3L1 in cancers.


Asunto(s)
Fibrosarcoma , Humanos , Fibrosarcoma/genética , Fibrosarcoma/metabolismo , Fibrosarcoma/patología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Biomarcadores de Tumor/genética , Proteínas del Tejido Nervioso , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética
15.
J Sep Sci ; 47(13): e2400308, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38982562

RESUMEN

Jiawei Huoxiang Zhengqi Pill (JHZP) is a commonly used Chinese patent medicine for the clinical treatment of headache, dizziness, chest tightness as well as abdominal distension, and pain caused by wind-cold flu. In this study, a comprehensive strategy combining ultra-high performance liquid chromatography with diode array detector (UHPLC-DAD) fingerprinting and multi-component quantitative analysis was established and validated for quality evaluation of JHZP. A total of 49 characteristic common peaks were selected in a chromatographic fingerprinting study to assess the similarity of 15 batches of JHZP. Furthermore, 109 compounds were identified or preliminarily identified from JHZP by coupling with an advanced hybrid linear ion trap-Orbitrap mass spectrometer. For quantification, the optimized ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was employed for the simultaneous determination of 13 target compounds within 12 min. The sensitivity, precision, reproducibility, and accuracy of the method were satisfactory. This validated UPLC-MS/MS method was successfully applied to analyzing 15 batches of JHZP. The proposed comprehensive strategy combining UHPLC-DAD fingerprinting and multi-component UPLC-MS/MS analysis proved to be highly efficient, accurate, and reliable for the quality evaluation of JHZP, which can be considered as a reference for the overall quality evaluation of other Chinese herbal formulations.


Asunto(s)
Medicamentos Herbarios Chinos , Control de Calidad , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/química
16.
Arch Toxicol ; 98(2): 395-408, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38103071

RESUMEN

Artificial light at night (ALAN) pollution has been regarded as a global environmental concern. More than 80% of the global population is exposed to light pollution. Exacerbating this issue, artificially lit outdoor areas are growing by 2.2% per year, while continuously lit areas have brightened by 2.2% each year due to rapid population growth and expanding urbanization. Furthermore, the increasing prevalence of night shift work and smart device usage contributes to the inescapable influence of ALAN. Studies have shown that ALAN can disrupt endogenous biological clocks, resulting in a disturbance of the circadian rhythm, which ultimately affects various physiological functions. Up until now, scholars have studied various disease mechanisms caused by ALAN that may be related to the response of the circadian system to light. This review outlines the molecular mechanisms by which ALAN causes circadian rhythm abnormalities in sleep disorders, endocrine diseases, cardiovascular disease, cancer, immune impairment, depression, anxiety and cognitive impairments.


Asunto(s)
Contaminación Lumínica , Horario de Trabajo por Turnos , Iluminación/efectos adversos , Ritmo Circadiano/fisiología , Contaminación Ambiental
17.
Neurosurg Rev ; 47(1): 384, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39085721

RESUMEN

"Low-lying" posterior communicating artery (PCoA) aneurysms require great attention in surgical clipping due to their distinct anatomical characteristics. In this study, we propose an easy method to immediately recognize "low-lying" PCoA aneurysms in neurosurgical practice. A total of 89 cases with "low-lying" PCoA aneurysms were retrospectively analyzed. All patients underwent preoperative digital subtraction angiography (DSA) examinations and microsurgical clipping. Cases were classified into the "low-lying" and regular groups based on intraoperative findings. The distance- and angle-relevant parameters that reflected the relative location of the aneurysms and tortuosity of the internal carotid artery were measured using 3D-DSA images. The data were sequentially integrated into a mathematical analysis to obtain the prediction model. Finally, we proposed a novel mathematical formula to preoperatively predict the existence of "low-lying" PCoA aneurysms with great accuracy. Neurosurgeons might benefit from this model, which enables them to directly identify "low-lying" PCoA aneurysms and make appropriate surgical decisions accordingly.


Asunto(s)
Angiografía de Substracción Digital , Aneurisma Intracraneal , Procedimientos Neuroquirúrgicos , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Adulto , Angiografía de Substracción Digital/métodos , Procedimientos Neuroquirúrgicos/métodos , Estudios Retrospectivos , Anciano , Angiografía Cerebral/métodos , Modelos Teóricos , Arteria Carótida Interna/cirugía , Arteria Carótida Interna/diagnóstico por imagen
18.
J Ultrasound Med ; 43(7): 1265-1277, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38558301

RESUMEN

OBJECTIVE: To evaluate corpus callosum (CC) size in fetuses with malformations of cortical development (MCD) and to explore the diagnostic value of three CC length (CCL) ratios in identifying cortical abnormalities. METHODS: This is a single-center retrospective study in singleton fetuses at 20-37 weeks of gestation between April 2017 and August 2022. The midsagittal plane of the fetal brain was obtained and evaluated for the following variables: length, height, area of the corpus callosum, and relevant markers, including the ratios of corpus callosum length to internal cranial occipitofrontal dimension (CCL/ICOFD), corpus callosum length to femur length (CCL/FL), and corpus callosum length to cerebellar vermian diameter (CCL/VD). Intra-class correlation coefficient (ICC) was used to evaluate measurement consistency. The accuracy of biometric measurements in prediction of MCD was assessed using the area under the receiver-operating-characteristics curves (AUC). RESULTS: Fetuses with MCD had a significantly decreased CCL, height (genu and splenium), and area as compared with those of normal fetuses (P < .05), but there was no significant difference in body height (P = .326). The CCL/ICOFD, CCL/FL, and CCL/VD ratios were significantly decreased in fetuses with MCD when compared with controls (P < .05). The CCL/ICOFD ratio offered the highest predictive accuracy for MCD, yielding an AUC of 0.856 (95% CI: 0.774-0.938, P < .001), followed by CCL/FL ratio (AUC, 0.780 (95% CI: 0.657-0.904), P < .001), CCL/VD ratio (AUC, 0.677 (95% CI: 0.559-0.795), P < .01). CONCLUSION: The corpus callosum biometric parameters in fetuses with MCD are reduced. The CCL/ICOFD ratio derived from sonographic measurements is considered a promising tool for the prenatal detection of cortical malformations. External validation of these findings and prospective studies are warranted.


Asunto(s)
Cuerpo Calloso , Ultrasonografía Prenatal , Humanos , Femenino , Embarazo , Ultrasonografía Prenatal/métodos , Estudios Retrospectivos , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/embriología , Adulto , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Malformaciones del Desarrollo Cortical/embriología , Reproducibilidad de los Resultados
19.
Ecotoxicol Environ Saf ; 275: 116275, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38564858

RESUMEN

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 µM) and Zn (800 µM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 µM + 200 µM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 µM + 800 µM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.


Asunto(s)
Género Iris , Metales Pesados , Contaminantes del Suelo , Cadmio/toxicidad , Cadmio/análisis , Zinc/toxicidad , Desarrollo de la Planta , Contaminantes del Suelo/toxicidad
20.
Ecotoxicol Environ Saf ; 270: 115922, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38171106

RESUMEN

Bisphenol A (BPA), an environmental endocrine disruptor (EDC), has been implicated in impairing intestinal and male reproductive dysfunction. The efficacy of gut microbiota modulation for BPA-exposed testicular dysfunction has yet to be verified through research. Therefore, this study explored the potential of mixed probiotics in restoring spermatogenesis damage through the gut-testis axis under BPA exposure. We selected two probiotics strains (Lactobacillus rhamnosus and Lactobacillus plantarum) with BPA removal properties in vitro and the BPA-exposed male mice model was established. The probiotics mixture effectively reduced BPA residue in the gut, serum, and testis in mice. Through 16 S rDNA-seq and metabolomics sequencing, we uncovered that vitamin D metabolism and bile acid levels in the gut was abolished under BPA exposure. This perturbation was linked to an increased abundance of Faecalibaculum and decreased abundance of Lachnospiraceae_NK4A136_group and Ligilactobacillus. The probiotics mixture restored this balance, enhancing intestinal barrier function and reducing oxidative stress. This improvement was accompanied by a restored balance of short-chain fatty acids (SCFAs). Remarkably, the probiotics ameliorated testicular dysfunction by repairing structures of seminiferous tubules and reversing arrested spermiogenesis. Further, the probiotics mixture enhanced testosterone-driven increases in spermatogonial stem cells and all stages of sperm cells. Testicular transcriptome profiling linked these improvements to fatty acid degradation and peroxisome pathways. These findings suggest a significant interplay between spermatogenesis and gut microbiota, demonstrating that probiotic intake could be a viable strategy for combating male subfertility issues caused by BPA exposure.


Asunto(s)
Microbioma Gastrointestinal , Fenoles , Probióticos , Masculino , Ratones , Animales , Semen , Espermatogénesis , Compuestos de Bencidrilo/toxicidad , Probióticos/farmacología
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