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1.
Cell ; 186(7): 1352-1368.e18, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-37001500

RESUMEN

Resilience enables mental elasticity in individuals when rebounding from adversity. In this study, we identified a microcircuit and relevant molecular adaptations that play a role in natural resilience. We found that activation of parvalbumin (PV) interneurons in the primary auditory cortex (A1) by thalamic inputs from the ipsilateral medial geniculate body (MG) is essential for resilience in mice exposed to chronic social defeat stress. Early attacks during chronic social defeat stress induced short-term hyperpolarizations of MG neurons projecting to the A1 (MGA1 neurons) in resilient mice. In addition, this temporal neural plasticity of MGA1 neurons initiated synaptogenesis onto thalamic PV neurons via presynaptic BDNF-TrkB signaling in subsequent stress responses. Moreover, optogenetic mimicking of the short-term hyperpolarization of MGA1 neurons, rather than merely activating MGA1 neurons, elicited innate resilience mechanisms in response to stress and achieved sustained antidepressant-like effects in multiple animal models, representing a new strategy for targeted neuromodulation.


Asunto(s)
Corteza Auditiva , Ratones , Animales , Corteza Auditiva/metabolismo , Tálamo/fisiología , Neuronas/metabolismo , Cuerpos Geniculados , Interneuronas/fisiología , Parvalbúminas/metabolismo
2.
Apoptosis ; 29(1-2): 243-266, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37670104

RESUMEN

A particular GTPase-activating protein called RACGAP1 is involved in apoptosis, proliferation, invasion, metastasis, and drug resistance in a variety of malignancies. Nevertheless, the role of RACGAP1 in pan-cancer was less studied, and its value of the expression and prognostic of nasopharyngeal carcinoma (NPC) has not been explored. Hence, the goal of this study was to investigate the oncogenic and immunological roles of RACGAP1 in various cancers and its potential value in NPC. We comprehensively analyzed RACGAP1 expression, prognostic value, function, methylation levels, relationship with immune cells, immune infiltration, and immunotherapy response in pan-cancer utilizing multiple databases. The results discovered that RACGAP1 expression was elevated in most cancers and suggested poor prognosis, which could be related to the involvement of RACGAP1 in various cancer-related pathways such as the cell cycle and correlated with RACGAP1 methylation levels, immune cell infiltration and reaction to immunotherapy, and chemoresistance. RACGAP1 could inhibit anti-tumor immunity and immunotherapy responses by fostering immune cell infiltration and cytotoxic T lymphocyte dysfunction. Significantly, we validated that RACGAP1 mRNA and protein were highly expressed in NPC. The Gene Expression Omnibus database revealed that elevated RACGAP1 expression was associated with shorter PFS in patients with NPC, and RACGAP1 potentially influenced cell cycle progression, DNA replication, metabolism, and immune-related pathways, resulting in the recurrence and metastasis of NPC. This study indicated that RACGAP1 could be a potential biomarker in pan-cancer and NPC.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Apoptosis/genética , Proteínas Activadoras de GTPasa/genética , Proteínas Activadoras de GTPasa/metabolismo , Neoplasias Nasofaríngeas/genética
3.
Langmuir ; 40(15): 8170-8179, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38581390

RESUMEN

The performances of flexible piezoresistive sensors based on polymer nanocomposites are significantly affected by the environmental temperature; therefore, comprehensively investigating the temperature-dependent electromechanical response behaviors of conductive polymer nanocomposites is crucial for developing high-precision flexible piezoresistive sensors in a wide-temperature range. Herein, carbon nanotube (CNT)/polydimethylsiloxane (PDMS) composites widely used for flexible piezoresistive sensors were prepared, and then the temperature-dependent electrical, mechanical, and electromechanical properties of the optimized CNT/PDMS composite in the temperature range from -150 to 150 °C were systematically investigated. At a low temperature of -150 °C, the CNT/PDMS composite becomes brittle with a compressive modulus of ∼1.2 MPa and loses its elasticity and reversible sensing capability. At a high temperature (above 90 °C), the CNT/PDMS composite softens, shows a fluid-like mechanical property, and loses its reversible sensing capability. In the temperature range from -60 to 90 °C, the CNT/PDMS composite exhibits good elasticity and reversible sensing behaviors and its modulus, resistivity, and sensing sensitivity decrease with an increasing temperature. At room temperature (30 °C), the CNT/PDMS composite exhibits better mechanical and piezoresistive stability than those at low and high temperatures. Given that environmental temperature changes have significant effects on the sensing performances of conductive polymer composites, the effect of ambient temperature changes must be considered when flexible piezoresistive sensors are designed and fabricated.

4.
Cardiovasc Diabetol ; 19(1): 130, 2020 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-32847602

RESUMEN

BACKGROUND: Type 2 diabetes is closely related to an increased risk of atrial fibrillation (AF) and atrial flutter (AFL). Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors can attenuate AF/AFL progression remains unclear. METHODS: We searched electronic databases (PubMed, Embase and ClinicalTrials.gov) from their inception to January 2020 for trials evaluating the AF outcomes of SGLT2 inhibitors in patients with type 2 diabetes. The data search and extraction were conducted with a standardized data form and any conflicts were resolved by consensus. Relative risks (RRs) with 95% confidence intervals (CIs) were used for binary variables, and the weighed mean differences (WMDs) with the standard deviation (SDs) were applied for continuous variables. RESULTS: We included data from 16 identified trials consisting of 38,335 patients with type 2 diabetes. Incorporated data demonstrated that compared to placebo, SGLT2 inhibitors significantly reduced AF/AFL (RR: 0.76; 95% CI 0.65-0.90; p = 0.001) and all-cause mortality (RR: 0.91; 95% CI 0.83-0.99; p = 0.03). AF/AFL reductions were not modified by age, body weight, glycated haemoglobin (HbA1c), or systolic blood pressure (SBP) at baseline (all p-interactions > 0.3). SGLT2 inhibitors also significantly reduced heart failure events (RR: 0.73; 95% CI 0.64-0.84; p < 0.00001), HbA1c (WMD: - 0.62%; 95% CI - 0.89 to - 0.34; p < 0.00001), body weight (WMD: - 2.12 kg; 95% CI - 2.91 to - 1.34; p < 0.00001), SBP (WMD: - 3.34 mmHg; 95% CI - 4.12 to - 2.56; p < 0.00001), and diastolic blood pressure (DBP) (WMD: - 1.11 mmHg; 95% CI - 1.62 to - 0.60; p < 0.0001). Of note, cerebrovascular events and myocardial infarction did not increase in patients taking SGLT2 inhibitors. CONCLUSION: SGLT2 inhibitors may confer a specific AF/AFL-reduction benefit in the susceptible type 2 diabetes population, regardless of age, body weight, HbA1c, and systolic blood pressure at baseline. Such an AF/AFL-reduction benefit may be partly attributed to pharmacological effects on reductions in HbA1c, body weight, blood pressure, and the occurrence of heart failure.


Asunto(s)
Fibrilación Atrial/prevención & control , Aleteo Atrial/prevención & control , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Fibrilación Atrial/epidemiología , Aleteo Atrial/epidemiología , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Hemoglobina Glucada/metabolismo , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento
5.
BMC Nephrol ; 20(1): 150, 2019 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-31039758

RESUMEN

BACKGROUND: The serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China. METHODS: We recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR). RESULTS: We found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis. CONCLUSIONS: The present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.


Asunto(s)
Complemento C3/análisis , Glomerulonefritis por IGA/diagnóstico , Inmunoglobulina A/sangre , Proteinuria/sangre , Adulto , Factores de Edad , Análisis de Varianza , Biomarcadores/sangre , Estudios de Cohortes , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Puntaje de Propensión , Curva ROC , Análisis de Regresión , Factores Sexuales
6.
J Sep Sci ; 40(1): 81-92, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27731929

RESUMEN

There is a recognized challenge in analyzing traditional Chinese medicine formulas because of their complex chemical compositions. The application of modern analytical techniques such as high-performance liquid chromatography coupled with a tandem mass spectrometry has improved the characterization of various compounds from traditional Chinese medicine formulas significantly. This study aims to conduct a bibliometric analysis to recognize the overall trend of high-performance liquid chromatography coupled with tandem mass spectrometry approaches in the analysis of traditional Chinese medicine formulas, its significance and possible underlying interactions between individual herbs in these formulas. Electronic databases were searched systematically, and the identified studies were collected and analyzed using Microsoft Access 2010, Graph Pad 5.0 software and Ucinet software package. 338 publications between 1997 and 2015 were identified, and analyzed in terms of annual growth and accumulated publications, top journals, forms of traditional Chinese medicine preparations and highly studied formulas and single herbs, as well as social network analysis of single herbs. There is a significant increase trend in using high-performance liquid chromatography coupled with tandem mass spectrometry related techniques in analysis of commonly used forms of traditional Chinese medicine formulas in the last 3 years. Stringent quality control is of great significance for the modernization and globalization of traditional Chinese medicine, and this bibliometric analysis provided the first and comprehensive summary within this field.


Asunto(s)
Bibliometría , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/análisis , Espectrometría de Masas en Tándem , Espectrometría de Masas , Medicina Tradicional China/tendencias
7.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(9): 1064-8, 2014 Sep.
Artículo en Zh | MEDLINE | ID: mdl-25335329

RESUMEN

OBJECTIVE: To study the effect of Shugan Jiangu Recipe (SJR) on bone mineral density (BMD) and serum bone metabolic biochemical markers in postmenopausal breast cancer patients with osteopenia. METHODS: Totally 38 patients of postmenopausal women with breast cancer, who received aromatase inhibitors (AIs), were assigned to the treatment group (21 cases) and the control group (17 cases) by using random digit table. All patients took Caltrate D Tablet (containing Ca 600 mg and Vit D3 125 IU), one tablet daily. Patients in the treatment group took SJR, 6 g each time, twice daily for 6 successive months. The bone mineral density (BMD) level was detected before treatment and at months 6 after treatment. Levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), and C-terminal telopeptide of type II collagen (CTX-II) were detected by enzyme linked immunosorbent assay (ELISA). The drug safety was also assessed. RESULTS: Compared with before treatment, BMD of L2-4 and femur neck obviously increased in the treatment group at month 6 after treatment (P < 0.01), serum BALP and TRAP decreased (P < 0.05). Compared with before treatment, BMD of L2-4 and femur neck obviously decreased in the control group at month 6 after treatment (P < 0.05), serum BALP and TRAP increased (P < 0.01). Compared with the control group, lumbar and femur neck BMD obviously increased, serum levels of BGP and BALP obviously decreased, and serum levels of CTX-II and TRAP obviously increased in the treatment group at month 6 after treatment (P < 0.01). No serious adverse event occurred during the treatment period. Bone fracture occurred in one case of the control group (5.8%). CONCLUSION: SJR could attenuate bone loss of postmenopausal women with breast cancer who received AIs, increase BMD and improve abnormal bone metabolism.


Asunto(s)
Inhibidores de la Aromatasa/efectos adversos , Densidad Ósea/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Osteoporosis Posmenopáusica/prevención & control , Fosfatasa Ácida/sangre , Anciano , Fosfatasa Alcalina/sangre , Huesos/efectos de los fármacos , Huesos/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Colágeno Tipo II/sangre , Femenino , Humanos , Isoenzimas/sangre , Persona de Mediana Edad , Osteocalcina/sangre , Osteoporosis Posmenopáusica/inducido químicamente , Fragmentos de Péptidos/sangre , Fosfatasa Ácida Tartratorresistente
8.
ACS Appl Mater Interfaces ; 15(2): 3476-3485, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36621816

RESUMEN

Pressure sensing is highly demanding in wearable devices, robotics, and artificial intelligence, whereas it is still a big challenge to develop a pressure sensor with an excellent linear response in a broad detection range. Herein, a flexible and porous carbon nanotube (CNT)/carbon black (CB)/carbonyl iron powder (CIP)/silicone composite is proposed by a simple strategy of mixing, curing, and washing. Due to the porous structure induced by the sacrifice of sugar particles, an excellent linear response (R2 = 0.999) is achieved for the composite sensor by manipulating the contributions of contact resistance and tunnel resistance to the sensing performance via the alternation of CB and CNT contents. Moreover, the porous structure donates the composite sensor a low compressive modulus at a low pressure level, while the CIPs introduced lead to a high compressive modulus at a high pressure level with the assistance of an external magnetic field. As a result, the sensor produced has a wide linear response range of 80 Pa to 220 kPa, much wider than most of the linear response pressure sensors reported previously. The wide detection range is demonstrated by cyclic pressure tests in the frequency range of 0.1-5 Hz, durability tests, and monitoring human or robot motions including breathing, walking, lifting, and boxing, etc. Taking the advantages of low cost, high sensitivity, and excellent linear response in a wide pressure range, the current composite sensor is promising for precise monitoring of human motions and delicate controlling of robots.


Asunto(s)
Nanotubos de Carbono , Dispositivos Electrónicos Vestibles , Humanos , Inteligencia Artificial , Nanotubos de Carbono/química , Porosidad , Presión
9.
Neuron ; 111(18): 2847-2862.e10, 2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37402372

RESUMEN

Alzheimer's disease (AD) is caused by a complex interaction between genetic and environmental factors. However, how the role of peripheral organ changes in response to environmental stimuli during aging in AD pathogenesis remains unknown. Hepatic soluble epoxide hydrolase (sEH) activity increases with age. Hepatic sEH manipulation bidirectionally attenuates brain amyloid-ß (Aß) burden, tauopathy, and cognitive deficits in AD mouse models. Moreover, hepatic sEH manipulation bidirectionally regulates the plasma level of 14,15-epoxyeicosatrienoic acid (-EET), which rapidly crosses the blood-brain barrier and modulates brain Aß metabolism through multiple pathways. A balance between the brain levels of 14,15-EET and Aß is essential for preventing Aß deposition. In AD models, 14,15-EET infusion mimicked the neuroprotective effects of hepatic sEH ablation at biological and behavioral levels. These results highlight the liver's key role in AD pathology, and targeting the liver-brain axis in response to environmental stimuli may constitute a promising therapeutic approach for AD prevention.


Asunto(s)
Enfermedad de Alzheimer , Animales , Ratones , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Epóxido Hidrolasas/genética , Epóxido Hidrolasas/metabolismo , Hígado/metabolismo , Hígado/patología
10.
ACS Appl Mater Interfaces ; 14(5): 7311-7320, 2022 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-35078316

RESUMEN

Development of lightweight structural materials from fast-growing bamboos is of great significance to building a sustainable society. However, previously developed structural bamboos by delignification combined with densification would easily fail under large external loading after exposure to water due to structure collapse, severely limiting their practical applications. Here, we demonstrate an ultrastrong and exceptional environmentally stable bamboo composite consisting of a graphene oxide (GO)/bamboo core and hierarchical SiO2 protection layer. The GO/bamboo composite exhibits ultrahigh tensile strength (641.6 MPa), superb flexural strength (428.4 MPa), and excellent toughness (17.5 MJ/m3), which are increased by about 480, 250, and 360% compared with natural bamboo, respectively. As a result, the specific tensile strength of the GO/bamboo composite is up to 513.3 MPa·cm3/g due to its low density (1.25 g/cm3), outperforming engineering structural materials such as aluminum alloys, steels, and titanium alloys. These large improvements benefit from the well-preserved bamboo scaffold and the strong hydrogen bonds between bamboo fibers and GO nanosheets. On the other hand, the SiO2@GO/bamboo composite shows superhydrophobicity due to the construction of hierarchical SiO2 layers, which endows it with outstanding water resistance. Moreover, the bamboo composite shows an ultralow coefficient of thermal expansion (≈2.3 × 10-6 K-1), indicating its excellent dimensional stability. Considering the ultrahigh mechanical performance and outstanding environmental stability, the developed lightweight SiO2@GO/bamboo composite is hopeful to be a green and sustainable structural material for practical engineering applications.

11.
Neuropharmacology ; 206: 108947, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35026286

RESUMEN

Extracting relevant information and transforming it into appropriate behavior, is a fundamental brain function, and requires the coordination between the sensory and cognitive systems, however, the underlying mechanisms of interplay between sensory and cognition systems remain largely unknown. Here, we developed a mouse model for mimicking human auditory mismatch negativity (MMN), a well-characterized translational biomarker for schizophrenia, and an index of early auditory information processing. We found that a subanesthetic dose of ketamine decreased the amplitude of MMN in adult mice. Using pharmacological and chemogenetic approaches, we identified an auditory cortex-entorhinal cortex-hippocampus neural circuit loop that is required for the generation of MMN. In addition, we found that inhibition of dCA1→MEC circuit impaired the auditory related fear discrimination. Moreover, we found that ketamine induced MMN deficiency by inhibition of long-range GABAergic projection from the CA1 region of the dorsal hippocampus to the medial entorhinal cortex. These results provided circuit insights for ketamine effects and early auditory information processing. As the entorhinal cortex is the interface between the neocortex and hippocampus, and the hippocampus is critical for the formation, consolidation, and retrieval of episodic memories and other cognition, our results provide a neural mechanism for the interplay between the sensory and cognition systems.


Asunto(s)
Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Corteza Entorrinal/fisiología , Potenciales Evocados Auditivos/fisiología , Antagonistas de Aminoácidos Excitadores/farmacología , Hipocampo/fisiología , Ketamina/farmacología , Red Nerviosa/fisiología , Animales , Corteza Auditiva/efectos de los fármacos , Percepción Auditiva/efectos de los fármacos , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/fisiología , Discriminación en Psicología/efectos de los fármacos , Discriminación en Psicología/fisiología , Corteza Entorrinal/efectos de los fármacos , Potenciales Evocados Auditivos/efectos de los fármacos , Miedo/fisiología , Hipocampo/efectos de los fármacos , Ratones , Red Nerviosa/efectos de los fármacos
12.
ACS Appl Mater Interfaces ; 14(18): 21474-21485, 2022 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-35486453

RESUMEN

Multiresponsive and high-performance flexible actuators with a simple configuration, high mechanical strength, and low-power consumption are highly desirable for soft robotics. Here, a novel mechanically robust and multiresponsive Ti3C2Tx MXene-based actuator with high actuation performance via dual-mechanism synergistic effect driven by the hygroexpansion of bacterial cellulose (BC) layer and the thermal expansion of biaxially oriented polypropylene (BOPP) layer is developed. The actuator is flexible and shows an ultrahigh tensile strength of 195 MPa. Unlike the conventional bimorph-structured actuators based on a single-mechanism, the actuator developed provides a favorable architecture for dual-mechanism synergism, resulting in exceptionally reversible actuation performance under electricity and near-infrared (NIR) light stimuli. Typically, the developed actuator can produce the largest bending angle (∼400°) at the lowest voltage (≤4 V) compared with that reported previously for single mechanism soft actuators. Furthermore, the actuator also can be driven by a NIR light at a 2 m distance, displaying an excellent long-distance photoresponsive property. Finally, various intriguing applications are demonstrated to show the great potential of the actuator for soft robotics.

13.
ACS Appl Mater Interfaces ; 14(11): 13778-13789, 2022 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-35259871

RESUMEN

Herein, a multifunctional polyurethane (PU) composite foam with a hierarchical structure is fabricated by dip-coating a carbon nanotube/shear-thickening gel (CNT/STG) and spray-coating nano-SiO2/STG on PU foam. The prepared nano-SiO2/CNT/STG@PU (SCS@PU) composite foam is lightweight, highly compressive, electrically conductive, superhydrophobic, and impact-energy absorptive. As a result, it possesses an excellent sensing ability to compression with a stable response up to 80% strain, an outstanding linearity of R2 > 0.99, and a wide response frequency of 0.01 to 1 Hz; it can also be used for effectively detecting impact force and sensing various human motions. Moreover, the superhydrophobicity with a water contact angle up to 154° of SCS@PU composite foam endows it with an excellent resistance to hazardous liquids (strong acid and alkali) to ensure its service reliability under harsh circumstances. In particular, the SCS@PU exhibits an outstanding anti-impact capability with an impact force attenuation rate of SCS@PU as high as 81%. Finally, its applications as soft body armors are demonstrated in protecting a wearer wearing a helmet with the SCS@PU as liner and using the SCS@PU as a smart kneecap against impact. On consideration of its excellent strain-sensing ability, superhydrophobicity, and outstanding anti-impact capability, the multifunctional SCS@PU composite foam developed is promising for personal safety protection.

14.
World J Gastroenterol ; 28(1): 123-139, 2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-35125823

RESUMEN

BACKGROUND: Hepatic stellate cell (HSC) hyperactivation is a central link in liver fibrosis development. HSCs perform aerobic glycolysis to provide energy for their activation. Focal adhesion kinase (FAK) promotes aerobic glycolysis in cancer cells or fibroblasts, while FAK-related non-kinase (FRNK) inhibits FAK phosphorylation and biological functions. AIM: To elucidate the effect of FRNK on liver fibrosis at the level of aerobic glycolytic metabolism in HSCs. METHODS: Mouse liver fibrosis models were established by administering CCl4, and the effect of FRNK on the degree of liver fibrosis in the model was evaluated. Transforming growth factor-ß1 was used to activate LX-2 cells. Tyrosine phosphorylation at position 397 (pY397-FAK) was detected to identify activated FAK, and the expression of the glycolysis-related proteins monocarboxylate transporter 1 (MCT-1) and enolase1 (ENO1) was assessed. Bioinformatics analysis was performed to predict putative binding sites for c-myc in the ENO1 promoter region, which were validated with chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: The pY397-FAK level was increased in human fibrotic liver tissue. FRNK knockout promoted liver fibrosis in mouse models. It also increased the activation, migration, proliferation and aerobic glycolysis of primary hepatic stellate cells (pHSCs) but inhibited pHSC apoptosis. Nevertheless, opposite trends for these phenomena were observed after exogenous FRNK treatment in LX-2 cells. Mechanistically, the FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis, which was inhibited by exogenous FRNK. CONCLUSION: FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway, thereby improving liver fibrosis. FRNK might be a potential target for liver fibrosis treatment.


Asunto(s)
Células Estrelladas Hepáticas , Cirrosis Hepática , Animales , Adhesión Celular , Células Cultivadas , Quinasa 1 de Adhesión Focal , Proteína-Tirosina Quinasas de Adhesión Focal , Glucólisis , Células Estrelladas Hepáticas/metabolismo , Ratones , Fosfopiruvato Hidratasa , Proteínas Proto-Oncogénicas c-myc , Proteínas ras
15.
ACS Appl Mater Interfaces ; 13(27): 32084-32093, 2021 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-34189902

RESUMEN

Transparent e-skin that can fully mimic human skin with J-shaped mechanical-behavior and tactile sensing attributes have not yet been reported. In this work, the skin-like hydrogel composite with J-shaped mechanical behavior and highly transparent, tactile, soft but strong, flexible, and stretchable attributes is developed as structural strain sensing element for e-skin. Piezo-resistive polyacrylamide (PAAm) hydrogel is used as supporting matrix to endow high transparency, softness, flexibility, stretch-ability and strain sensing capability desired for e-skin. Ultrahigh molecular weight polyethylene (UHMWPE) fiber with a wavy configuration is designed as reinforcement filler to provide the tunable strain-limiting effect. As a result, the as-prepared UHMWPE fiber/PAAm composite e-skin presents unique "J-shape" stress-strain behavior akin to human skin. And the PAAm composite can switch from supersoft to highly stiff in the designed strain range up to 100% with a prominent tensile strength of 48.3 MPa, which enables it to have the high stretch-ability and excellent load-bearing ability, simultaneously. Moreover, finite element model is developed to clarify the stress distribution and damage evolution for the UHMWPE fiber/PAAm composite during the tensile process. The PAAm composite exhibits not only an excellent strain sensing performance with a long-term reliability up to 5000 loading-unloading cycles but also an extraordinary softness and mechanical strength with a low initial modulus of 6.7 kPa, which is matchable with soft human epidermis. Finally, the e-skin is used for demonstrations in monitoring various human activities and protecting structural integrity in designed strain ranges. The strategy for reinforcing piezo-resistive hydrogel with wavy-shaped UHMWPE fibers proposed here is promising for the development of transparent, flexible, soft but strong e-skin with a tunable strain-limiting effect akin to human skin.


Asunto(s)
Resinas Acrílicas/química , Materiales Biomiméticos/química , Hidrogeles/química , Piel , Humanos , Resistencia a la Tracción
16.
ACS Appl Mater Interfaces ; 13(40): 48009-48019, 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34596376

RESUMEN

Pressure sensors usually suffer from a trade-off between sensitivity and the linear sensing range, which may be improved by manipulating the geometric microstructure of active sensing materials via the molding strategy, standard photolithography technique, and so on. However, these conventional microengineering techniques require specialized equipment, which are extremely complicated, high-cost, and time-consuming to manufacture. Herein, a mold-free, scalable, low-cost, and environment-friendly one-step thermofoaming strategy is proposed to fabricate surface morphology-tunable microdome-patterned composites (MPCs). The microstructured pressure sensor is then prepared by coating the MPCs with highly conductive graphene. Remarkably, the as-prepared pressure sensor presents a better overall sensing performance compared to the previous pressure sensors prepared using complicated microengineering methods. Moreover, an electromechanical response model and finite-element analysis are used to clarify the sensing mechanisms of the present microstructured pressure sensor. Furthermore, several successful application demonstrations are conducted under various pressure levels. Considering the advantages of the one-step fabrication strategy over conventional surface microengineering techniques and the high performance of the microstructured pressure sensor, the present pressure sensor has promising potential applications in health monitoring, tactile sensation, wearable devices, etc.

17.
ACS Appl Mater Interfaces ; 13(1): 1431-1440, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33356105

RESUMEN

It is highly desirable to develop green and renewable structural materials from biomaterials to replace synthetic materials involved from civil engineering to aerospace industries. Herein, we put forward a facile but effective top-down strategy to convert natural bamboo into bamboo steel. The fabrication process of bamboo steel involves the removal of lignin and hemicellulose, freeze-drying followed by epoxy infiltration, and densification combined with in situ solidification. The prepared bamboo steel is a super-strong composite material with a high specific tensile strength (302 MPa g-1 cm3), which is higher than that (227 MPa g-1 cm3) of conventional high specific strength steel. The bamboo steel demonstrates a high tensile strength of 407.6 MPa, a record flexural strength of 513.8 MPa, and a high toughness of 14.08 MJ/m3, which is improved by 360, 290, and 380% over those of natural bamboo, respectively. Particularly, the mechanical properties of the bamboo steel are the highest among the biofiber-reinforced polymer composites reported previously. The well-preserved bamboo scaffolds assure the integrity of bamboo fibers, while the densification under high pressure results in a high-fiber volume fraction with an improved hydrogen bonding among the adjacent bamboo fibers, and the epoxy resin impregnated enhances the stress transfer because of its chemical crosslinking with cellulose molecules. These endow the bamboo steel with superior mechanical performance. Furthermore, the bamboo steel demonstrates an excellent thermal insulating capability with a low thermal conductivity (about 0.29 W/mK). In addition, the bamboo steel shows a low coefficient of thermal expansion (about 6.3 × 10-6 K-1) and a very high-dimensional stability to moisture attack. The strategy of fabricating high-performance bamboo steel with green and abundant natural bamboo as raw materials is highly attractive for the sustainable development of structural engineering materials.

18.
ACS Appl Bio Mater ; 3(12): 8748-8756, 2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-35019646

RESUMEN

Bamboo, one of the most abundant biomaterials, has been used as a building material since ancient times; however, its application in functional materials has been rarely explored. Herein, a highly robust and conductive carbonized bamboo aerogel (CBA) is obtained from the natural bamboo through a simple three-step process of pulp oxidization, freeze-drying, and carbonization. The CBA obtained shows not only a low density of 0.02 g/cm3 but also a high conductivity of 6.42 S/m and remarkable elasticity with a maximum recoverable compressive strain of 60% due to its unique three-dimensional (3D) network randomly stacked with the hybrid structure of carbonized bamboo fibers and films. After encapsulation with silicone resin, the CBA/silicone composite prepared exhibits excellent flexibility and stretchability with a low Young's modulus (0.09 MPa) and a large failure strain (275%). Importantly, the CBA/silicone composite also offers remarkable strain-sensing performance with a maximum gauge factor of 30.6, a short responsive time of 50 ms, and a stable response to cyclic loading over 1000 cycles, which is comparable to those of the piezoresistive composites based on expensive nanomaterials. Moreover, the CBA/silicone composite demonstrates the capability as a wearable strain sensor for human motion recognition comprising finger bending, breathing, and throat movement. Considering the green and sustainable nature of bamboo as a raw material, combined with the excellent piezoresistive performance, low production cost, and simple preparation process, the flexible strain sensors with CBA/silicone composite as a sensing element are promising in wearable electronic devices, personalized healthcare, and artificial intelligence systems.

19.
ACS Appl Mater Interfaces ; 12(27): 30871-30881, 2020 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-32520521

RESUMEN

Flexible vibration sensors can not only capture broad classes of physiologically relevant information, including mechano-vibration signatures of body processes and precision kinematics of core-body motions, but also detect environmental seismic waves, providing early warning to wearers in time. Spider is one of the most vibration-sensitive creatures because of its hairlike sensilla and lyriform slit structure. Here, a spider-inspired ultrasensitive flexible vibration sensor is designed and fabricated for multifunctional sensing. The vibration sensitivity of the flexible sensor is increased over 2 orders of magnitude from 0.006 to 0.5 mV/g, and the strain sensitivity is hugely enhanced from 0.08 to 150 compared to a plain sensor counterpart. It is shown that the synergistic effect of cilium arrays and cracks is the key for achieving the greatly enhanced vibration and strain sensitivity. The dynamic sensitivity of 0.5 mV/g outperforms the corresponding commercial vibration sensors. The flexible sensor is demonstrated to be generally feasible for detecting vibration signals caused by walk, tumble, and explosion as well as capturing human body motions, indicating its great potential for applications in human health-monitoring devices, posture control in robotics, early earthquake warning, and so forth.

20.
ACS Appl Mater Interfaces ; 12(7): 8674-8680, 2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-31986011

RESUMEN

Nowadays, the integration of easy production, simple structure, high sensitivity, and multifunctionality is the developing tendency for flexible sensors. Herein we report a facile manufacture of a highly flexible, sensitive, and multifunctional dual-mode sensor with an ultrasimple structure by directly attaching magnetic iron rubber (IR) onto the surface of carbon aerogel (CA) derived from melamine foam. The dual-mode CA/IR sensor exhibits high sensitivities of 5.6 kPa-1 and 1.6·10-3 Oe-1, respectively, toward pressure and magnetic field in a wide frequency ranging from 0.1 to 10 Hz, which are higher than those of the existing flexible pressure/magnetism sensors. The multifunctionality of the dual-mode CA/IR sensor is demonstrated by monitoring blood pulse, human breath, balloon volume, and thoracic volume via pressure and magnetism sensing or their combination. Due to its simple structure and high sensitivities, the dual-mode sensor is employed as the building block to create a direction-recognizable sensor for identifying the directions of pressure and magnetic field for the awareness of surrounding barriers that are of practical importance in sophisticated situations such as autonomous artificial intelligence, autodriving and robotics, and so on.

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