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1.
J Colloid Interface Sci ; 677(Pt B): 853-861, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39173517

RESUMEN

Electrocatalytic nitrate reduction reaction presents a promising avenue for environmentally friendly ammonia (NH3) synthesis and wastewater treatment. An essential aspect to consider is the meticulous design of electrocatalysts. This study explores the utilization of a Ni-Co alloy nanosheet-decorated three-dimensional titanium dioxide (3D-TiO2) nanobelts electrodeposited on titanium meshes (NixCoy@TiO2/TM) for efficient electrocatalytic NH3 production. The optimized Ni1Co3@TiO2/TM electrode achieves a significant NH3 yield of 676.3 ± 27.1 umol h-1 cm-2 with an impressive Faradaic efficiency (FE) of 95.1 % ± 2.1 % in a 0.1 M KOH solution containing 0.1 M NO3- at -0.4 V versus the reversible hydrogen electrode. Additionally, the electrode demonstrates exceptional electrochemical activity for NH3 synthesis in simulated wastewater, delivering an outstanding NH3 yield of 751.6 ± 44.3 umol h-1 cm-2 with a FE of 96.8 % ± 0.4 % at the same potential of -0.4 V. Moreover, the electrode exhibits minimal variation in current density, NH3 yields and FEs throughout the 24-h stability test and the 20-cycle test, demonstrating its excellent stability and durability. This study offers a straightforward electrodeposited approach for the development of 3D-nanostructured alloys as catalysts for NH3 electrosynthesis from nitrates at room temperature.

2.
Neural Regen Res ; 20(8): 2420-2432, 2025 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39359098

RESUMEN

JOURNAL/nrgr/04.03/01300535-202508000-00031/figure1/v/2024-09-30T120553Z/r/image-tiff The protein connector enhancer of kinase suppressor of Ras 2 (CNKSR2), present in both the postsynaptic density and cytoplasm of neurons, is a scaffolding protein with several protein-binding domains. Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders, particularly intellectual disability, although the precise mechanism involved has not yet been fully understood. Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane, thereby influencing synaptic signaling and the morphogenesis of dendritic spines. However, the function of CNKSR2 in the cytoplasm remains to be elucidated. In this study, we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2. Through a combination of bioinformatic analysis and cytological experiments, we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome. We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290. Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2. When we downregulated CNKSR2 expression in mouse neuroblastoma cells (Neuro 2A), we observed significant changes in the expression of numerous centrosomal genes. This manipulation also affected centrosome-related functions, including cell size and shape, cell proliferation, and motility. Furthermore, we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder. Our findings establish a connection between CNKSR2 and the centrosome, and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

3.
ACS Appl Mater Interfaces ; 16(37): 49594-49601, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39230599

RESUMEN

Covalent organic framework (COF) film with electrofluorochromic (EFC) and electrochromic (EC) properties has been synthesized by using triphenylamine-based monomers. The film exhibited a high maximum fluorescence contrast of 151 when subjected to a drive voltage of 0.75 V vs the Ag/AgCl electrode, causing the fluorescence to be quenched, which resulted in the EFC process's "fluorescence off" state. The switching times for the fluorescence on and off states were 0.51 and 7.79 s, respectively. Over the same voltage range, the COF film also displayed EC properties, achieving a contrast of 50.23% and a coloration efficiency of 297.4 cm2 C-1 at 532 nm, with switching times of 18.6 s for coloration and 0.7 s for bleaching. Notably, the quenched fluorescence of the COF film could be restored by adding dopamine as a reductant. This phenomenon enabled the implementation of a NAND logic gate using the applied potential as a physical input and dopamine addition as a chemical input. This study demonstrates the successful development of COF films with bifunctional EFC and EC properties, showcasing their potential for use in constructing advanced optoelectronic devices.

4.
Stem Cell Res Ther ; 15(1): 296, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39256886

RESUMEN

BACKGROUND: Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells. METHODS: We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures. RESULTS: We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro. CONCLUSIONS: Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.


Asunto(s)
Adenocarcinoma , Células Madre Neoplásicas , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/genética , Animales , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Ratones , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/genética , Nitrilos/farmacología , Feniltiohidantoína/farmacología
5.
Int Immunopharmacol ; 140: 112884, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39133959

RESUMEN

Multiple lines of evidence suggest that Retinoic Acid Related Orphan Nuclear Receptor gamma t (RORγt) is a potent therapeutic target for inflammatory bowel disease (IBD). However, systemic blockade of RORγt easily leads to thymic lymphoma and aberrant liver function. Therefore, the development of gut-limited RORγt antagonists may lead to the development of innovative IBD therapeutics that improve safety and retain effectiveness. We discovered SPH7854, a potent and selective RORγt antagonist. The effect of SPH7854 on the differentiation of T helper 1 (Th1)/Th17/regulatory T (Treg) cells was evaluated in mouse and human primary cells. SPH7854 (2-(4-(ethylsulfonyl)phenyl)-N- (6-(2-methyl-2-(pyridin-2-yl) propanoyl)pyridin-3-yl)acetamide) dose-dependently inhibited interleukin-17A (IL-17A) secretion from mouse CD4 + T cells and human peripheral blood mononuclear cells (PBMC). Additionally, SPH7854 strongly suppressed Th17 cell differentiation and considerably promoted Treg cell differentiation while slightly affected Th1 cell differentiation from mouse CD4 + T cells. The pharmacokinetic (PK) studies indicated that SPH7854 was restricted to the gut: the bioavailability and maximal plasma concentration of SPH7854 after oral administration (6 mg/kg) were 1.24 ± 0.33 % and 4.92 ± 11.81 nM, respectively, in rats. Strikingly, oral administration of SPH7854 (5 mg/kg and 15 mg/kg) twice daily significantly alleviated 2, 4, 6-trinitrobenzensulfonic acid (TNBS)-induced colitis in rats. SPH7854, especially at 15 mg/kg, significantly alleviated symptoms and improved macroscopic signs and microscopic structure in rat colitis, with decreased colonic mucosal levels of IL-17A, IL-6, tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1) and myeloperoxidase (MPO). These evidences indicated that blockade of RORγt activity via a gut-limited antagonist may be an effective and safe therapeutic strategy for IBD treatment.


Asunto(s)
Colitis , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Células Th17 , Ácido Trinitrobencenosulfónico , Animales , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/antagonistas & inhibidores , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Humanos , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/inmunología , Masculino , Ratas , Ratones , Células Th17/inmunología , Células Th17/efectos de los fármacos , Ratas Sprague-Dawley , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Interleucina-17/metabolismo , Interleucina-17/antagonistas & inhibidores , Acetamidas/uso terapéutico , Acetamidas/farmacología , Células Cultivadas , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Colon/efectos de los fármacos , Colon/patología , Colon/inmunología , Ratones Endogámicos C57BL
6.
Sensors (Basel) ; 24(15)2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39124102

RESUMEN

The surface quality of milled blade-root grooves in industrial turbine blades significantly influences their mechanical properties. The surface texture reveals the interaction between the tool and the workpiece during the machining process, which plays a key role in determining the surface quality. In addition, there is a significant correlation between acoustic vibration signals and surface texture features. However, current research on surface quality is still relatively limited, and most considers only a single signal. In this paper, 160 sets of industrial field data were collected by multiple sensors to study the surface quality of a blade-root groove. A surface texture feature prediction method based on acoustic vibration signal fusion is proposed to evaluate the surface quality. Fast Fourier transform (FFT) is used to process the signal, and the clean and smooth features are extracted by combining wavelet denoising and multivariate smoothing denoising. At the same time, based on the gray-level co-occurrence matrix, the surface texture image features of different angles of the blade-root groove are extracted to describe the texture features. The fused acoustic vibration signal features are input, and the texture features are output to establish a texture feature prediction model. After predicting the texture features, the surface quality is evaluated by setting a threshold value. The threshold is selected based on all sample data, and the final judgment accuracy is 90%.

7.
Brain Behav ; 14(8): e3570, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39192611

RESUMEN

INTRODUCTION: Subjective cognitive decline (SCD) refers to individuals' perceived decline in memory and/or other cognitive abilities relative to their previous level of performance. Sensory decline is one of the main manifestations of decline in older adults with SCD. The efficient integration of visual and auditory information, known as audiovisual integration, is a crucial perceptual process. This study aims to evaluate audiovisual integration in older adults with SCD. METHODS: We adopted the audiovisual detection task, the Colavita task, and the Sound-Induced Flash Illusion (SIFI) task to evaluate the audiovisual integration by examining both redundant and illusory effects. Older adults diagnosed with SCD (N = 50, mean age = 67.8 years) and a control group of non-SCD older adults (N = 51, mean age = 66.5 years) were recruited. All participants took part in the three aforementioned experiments. RESULTS: The outcomes showed that a redundant effect occurred in both SCD and non-SCD older adults, with SCD older adults gaining more benefits in audiovisual detection task. Moreover, an equivalent amount of the visual dominance effect was observed among both SCD and non-SCD older adults in Colavita task. In addition, older adults with SCD perceived an equal fission illusion but a bigger fusion illusion compared with non-SCD older adults in SIFI task. CONCLUSIONS: Overall, older adults with SCD exhibit increased audiovisual redundant effects and stronger fusion illusion susceptibility compared to non-SCD older adults. Besides, visual dominance was observed in both groups via the Colavita task, with no significant difference between non-SCD and SCD older adults. These findings implied that audiovisual integration might offer a potential way for the identification of SCD.


Asunto(s)
Percepción Auditiva , Disfunción Cognitiva , Ilusiones , Percepción Visual , Humanos , Anciano , Femenino , Masculino , Disfunción Cognitiva/fisiopatología , Percepción Auditiva/fisiología , Ilusiones/fisiología , Percepción Visual/fisiología , Persona de Mediana Edad
8.
J Cosmet Dermatol ; 23(11): 3508-3516, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39037908

RESUMEN

BACKGROUND: Poly L-lactic acid (PLLA) can stimulate fibrous tissue regeneration to exert a filling effect. However, severe inflammatory reactions and unsatisfactory effects remain a concern. OBJECTIVE: Herein, we describe the mechanism of action, efficacy, and safety of PLLA microspheres in suspension (PLLA-b-PEG/HA) for facial contouring and soft tissue augmentation. METHODS: PLLA-b-PEG/HA, ssynthesized by copolymerization with ethylene glycol, were suspended in hyaluronic acid (HA). Physiological verification was performed using scanning electron microscopy and X-ray computed tomography. PLLA-b-PEG/HA were subcutaneously injected into the dorsal region of 4-month-old rabbits. Ultrasound assessed volumetric capacity at 3 days and 1, 2, 4, and 12 weeks. The inflammatory response, collagen production, and HA degradation were evaluated. A retrospective case series of 10 patients who received PLLA-b-PEG/HA injections was conducted to assess long-term efficacy and safety. RESULTS: PLLA-b-PEG exhibited a spherical structure with a smooth surface (20-45 µm diameter). In rabbits, implant site volume increased within 4 weeks, gradually decreasing thereafter. Fibrous capsules, microvessel density, and new collagen fiber formation progressively increased at 4, 12, and 26 weeks after injection. Clinical data demonstrated significant improvements in face contouring at months 3 and 12 after injection. All patients showed improved internal contours based on the Global Aesthetic Improvement Scale. After 12 months, 90% of the patients retained good shaping and support effects with minimal adverse reactions. CONCLUSIONS: PLLA-b-PEG/HA demonstrated superior biocompatibility and facial regeneration potential, with outstanding dual collagen-stimulating properties. The clinical efficacy and safety of PLLA-b-PEG/HA have been validated and established as a promising therapeutic option.


Asunto(s)
Técnicas Cosméticas , Rellenos Dérmicos , Ácido Hialurónico , Microesferas , Poliésteres , Rejuvenecimiento , Animales , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/química , Ácido Hialurónico/efectos adversos , Conejos , Femenino , Humanos , Poliésteres/química , Poliésteres/administración & dosificación , Técnicas Cosméticas/efectos adversos , Persona de Mediana Edad , Rellenos Dérmicos/administración & dosificación , Rellenos Dérmicos/química , Rellenos Dérmicos/efectos adversos , Adulto , Estudios Retrospectivos , Cara , Envejecimiento de la Piel/efectos de los fármacos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Polietilenglicoles/efectos adversos , Masculino , Inyecciones Subcutáneas , Colágeno , Resultado del Tratamiento , Lactatos
9.
Artículo en Chino | MEDLINE | ID: mdl-38973037

RESUMEN

Objective:To analyze the surgical efficacy and safety of tympanoplasty with and without mastoidectomy for the treatment of active simple chronic suppurative otitis media(CSOM), and to investigate whether mastoidectomy can be avoided in tympanoplasty for active CSOM. Methods:The clinical data of 55 patients(55 ears) with active CSOM were retrospectively analyzed. Based on the development of the mastoid process and the upper tympanic chamber, patients who met the criteria for wall-up mastoidectomy were classified as group A (30 patients), and underwent tympanoplasty combined with wall-up mastoidectomy. Patients who did not meet the criteria for wall-up mastoidectomy were classified as group B(25 cases), and underwent tympanoplasty with the opening of the middle and upper tympanic chambers and sinus drainage after partial removal of the shield plate bone. The survival rate of tympanic membrane grafts, hearing before and after surgery, and complications such as reperforation were compared between the two groups at 3 months postoperatively. Results:The overall postoperative tympanic membrane survival rate of patients with active CSOM was 96.4%(53/55), including 96.7% in group A; 96.0% in group B. There was no significant difference in the tympanic membrane survival rate between the two groups(P>0.05). The postoperative mean air-bone gap(ABG) was significantly reduced in both groups compared with the preoperative period, but there was no significant difference in ABG gain between the two groups(P>0.05). No patients experienced serious adverse conditions such as peripheral facial paralysis, cerebrospinal fluid leakage, or sensorineural deafness after surgery. Conclusion:Microscopic tympanoplasty with patency of the middle and upper tympanic chambers and tympanic sinus drainage can be used to treat active simple chronic otitis media with satisfactory tympanic membrane viability and hearing improvement efficacy. This approach reduces patient trauma, prevents complications such as skin depressions in the mastoid area due to abrasion of the mastoid bone, and shortens the waiting time before surgery.


Asunto(s)
Mastoidectomía , Otitis Media Supurativa , Timpanoplastia , Humanos , Otitis Media Supurativa/cirugía , Timpanoplastia/métodos , Estudios Retrospectivos , Mastoidectomía/métodos , Masculino , Femenino , Resultado del Tratamiento , Enfermedad Crónica , Persona de Mediana Edad , Adulto , Membrana Timpánica/cirugía , Apófisis Mastoides/cirugía
10.
Biomimetics (Basel) ; 9(7)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39056870

RESUMEN

The minimum connected dominating set problem is a combinatorial optimization problem with a wide range of applications in many fields. We propose an efficient local search algorithm to solve this problem. In this work, first, we adopt a new initial solution construction method based on three simplification rules. This method can reduce the size of the original graph and thus obtain a high-quality initial solution. Second, we propose an approach based on a two-level configuration checking strategy and a tabu strategy to reduce the cycling problem. Third, we introduce a perturbation strategy and a vertex weighting strategy to help the algorithm be able to jump out of the local optimum effectively. Fourth, we combine the scoring functions Cscore and Mscore with the aforementioned strategies to propose effective methods for selecting vertices. These methods assist the algorithm in selecting vertices that are suitable for addition to or removal from the current candidate solution. Finally, we verify the performance advantages of the local search algorithm by comparing it with existing optimal heuristic algorithms on two sets of instances. The experimental results show that the algorithm exhibits better performance on two sets of classical instances.

11.
Environ Sci Pollut Res Int ; 31(25): 36778-36795, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38753239

RESUMEN

Nuclear reactors will face the problem of decommissioning at the end of their operating life due to the high radioactivity of reactor components and environmental safety considerations. The Heavy Water Research Reactor (HWRR) is the first large-scale research reactor to be decommissioned in China. The second phase of HWRR decommissioning involves the main components in the reactor block, so the radiation source terms and the radioactive waste level need to be evaluated before demolition and disposal. Based on the operating history, three-dimensional geometry, materials, and other information of the HWRR, the activity of radionuclides in the main components of HWRR is calculated and analyzed, and the MCNP/ORIGEN coupling scheme is utilized for theoretical analysis. The theoretical results indicate that 14C, 54Mn, 55Fe, 60Co, 63Ni, and 152Eu are the main radioactive nuclides. The total activity of radioactive nuclides was 2.36E + 15 Bq at the end of 2007, 4.27E + 13 Bq at the end of 2021, and 1.83E + 13 Bq at the end of 2025. Furthermore, local sampling and radiometric analyses based on the HPGe gamma-ray spectrometer are also performed to verify the theoretical results, the ratio of theoretical activity values to the measured activity of the experimental sample is within 2.5 times, so the theoretical results are conservative. According to the classification standards for radioactive waste, the inner shell, outer shell, cooling water tank, sand layer, and heavy concrete shielding layer are all low-level waste. These results and conclusions can serve as a reference for the second phase decommissioning of the HWRR and the subsequent disposal of radioactive waste.


Asunto(s)
Residuos Radiactivos , China , Reactores Nucleares , Monitoreo de Radiación
12.
J Colloid Interface Sci ; 668: 264-271, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38678882

RESUMEN

Electricity-driven nitrate (NO3-) to ammonia (NH3) conversion presents a unique opportunity to simultaneously eliminate nitrate from sewage while capturing ammonia. However, the Faradaic efficiency and ammonia yield in this eight-electron process remain unsatisfactory, underscoring the critical need for more effective electrocatalysts. In this study, a RuCo alloy nanosheets electrodeposited on pinewood-derived three-dimensional porous carbon (RuCo@TDC) is introduced as a highly-efficient electrocatalyst for the nitrate reduction reaction. The RuCo@TDC catalyst exhibits superior electrocatalytic performance, achieving the highest NH3 yield of 2.02 ± 0.11 mmol h-1 cm-2 at -0.6 V versus the reversible hydrogen electrode (vs. RHE) and the highest Faradaic efficiency of 95.7 ± 0.8 % at -0.2 V vs. RHE in an electrolyte mixture of 0.1 M KOH and 0.1 M KNO3. Furthermore, the Zn-NO3- battery using RuCo@TDC as the cathode provides a maximum power density of 2.46 mW cm-2 and a satisfactory NH3 yield of 1110 µg h-1 cm-2.

13.
Nat Genet ; 56(3): 442-457, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38361033

RESUMEN

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Multiómica , Proteómica , Reprogramación Metabólica , Diciclohexilcarbodiimida , Progresión de la Enfermedad , Pronóstico
14.
bioRxiv ; 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37808692

RESUMEN

Developing therapeutic strategies against COVID-19 has gained widespread interest given the likelihood that new viral variants will continue to emerge. Here we describe one potential therapeutic strategy which involves targeting members of the glutaminase family of mitochondrial metabolic enzymes (GLS and GLS2), which catalyze the first step in glutamine metabolism, the hydrolysis of glutamine to glutamate. We show three examples where GLS expression increases during coronavirus infection of host cells, and another in which GLS2 is upregulated. The viruses hijack the metabolic machinery responsible for glutamine metabolism to generate the building blocks for biosynthetic processes and satisfy the bioenergetic requirements demanded by the 'glutamine addiction' of virus-infected host cells. We demonstrate how genetic silencing of glutaminase enzymes reduces coronavirus infection and that newer members of two classes of small molecule allosteric inhibitors targeting these enzymes, designated as SU1, a pan-GLS/GLS2 inhibitor, and UP4, which is specific for GLS, block viral replication in mammalian epithelial cells. Overall, these findings highlight the importance of glutamine metabolism for coronavirus replication in human cells and show that glutaminase inhibitors can block coronavirus infection and thereby may represent a novel class of anti-viral drug candidates. Teaser: Inhibitors targeting glutaminase enzymes block coronavirus replication and may represent a new class of anti-viral drugs.

15.
Folia Neuropathol ; 61(2): 217-223, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37587896

RESUMEN

Parkinson's disease occurs due to loss of dopaminergic neurons, which alters the behavioural changes. The present study evaluates the effect of exercise on neurodegeneration against Parkinson's disease (PD) rat model and postulates its effect on novel molecular pathway. Rotenone was administered at 1 mg/kg s.c. every 48 h for 18 days for the in-duction of PD and exercise was given to rats for a period of 2 weeks after the confirmation of PD. Moreover, PD rats also received CGS 21680 (adenosine A2A receptor agonist, 0.5 mg/kg, i.p.) with exercise for a period of 2 weeks after confirmation of PD. The effect of exercise was assessed for motor and cognitive function in PD rats. The level of inflammatory cytokines and neurotransmitters was estimated in brain tissue of PD rats. Data of investigation reveal that exercise attenuates cognitive and motor function in PD rats, the exercise + CGS 21680 group shows reverse in the behavioural changes compared to exercise-treated PD rats. The level of inflammatory cytokines and neurochemical level ameliorated in the exercise-treated group compared to the PD group of rats, which is reversed in the exercise + CGS 21680 group. In conclusion, exercise protects neurodegeneration in PD rats by reducing aggregation of a-synuclein and activity of adenosine 2A receptor.


Asunto(s)
Enfermedad de Parkinson , Animales , Ratas , Fenetilaminas , Adenosina , Citocinas
16.
Chem Commun (Camb) ; 59(59): 9017-9028, 2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37409494

RESUMEN

Electrochemical CO2 reduction into value-added chemicals represents an attractive and promising approach to capitalize on the abundant CO2 present in the atmosphere. This reaction, however, is hampered by low energy efficiency and selectivity owing to competition from hydrogen evolution reaction and multiple-electron transfer processes. Therefore, there is a pressing need to develop efficient yet cost-effective electrocatalysts to facilitate practical applications. Sn-based electrocatalysts have gained increasing attention in this active field due to their outstanding merits such as abundance, non-toxicity, and environmental friendliness. This review provides a comprehensive overview of recent advances in Sn-based catalysts for the CO2 reduction reaction (CO2RR), beginning with a brief introduction to the CO2RR mechanism. Subsequently, the CO2RR performance of various Sn-based catalysts with different structures is discussed. The article concludes by addressing the existing challenges and offering personal perspectives on the future prospects in this exciting research area.

17.
Biosens Bioelectron ; 234: 115294, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37126877

RESUMEN

In order to achieve the simultaneous extraction and detection of tetracycline (TC) in milk, the amino-functionalized Fe-based metal-organic frameworks (NH2-MIL-88B) was synthesized via a solvothermal method with Fe3+ and 2-aminoterephthalic acid (NH2-BDC) as precursor. Thanks to the unique structure of NH2-MIL-88B, it could be used to highly effective extract of TC in milk. More interestedly, the introduced -NH2 could react with -OH from TC by a hydrogen-bonding interaction to cause the electronic interactions that enhances the peroxidase-like activity of NH2-MIL-88B, which result in the enhancement of Fenton reaction by the transfer of the electron between TC and NH2-MIL-88B. Under the optimal testing conditions, the linear absorbance response is well correlated with the TC concentration range of 50-1000 nM, which can reach a low LOD of 46.75 nM. Besides, the sensor exhibits excellent selectivity to TC, and the proposed strategy can also be applied to milk with good recovery (83.33-107.00%). Finally, the NH2-MIL-88B and cellulose acetate (CA) are combined to form nanozyme hybrid membranes through the non-solvent induced phase separation method, which can be used to prepare point-of-care testing (POCT) for rapid and in-situ detection of TC.


Asunto(s)
Técnicas Biosensibles , Compuestos Heterocíclicos , Compuestos Férricos , Colorimetría , Antibacterianos , Tetraciclina
18.
Life Sci ; 325: 121774, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37172817

RESUMEN

AIMS: Lipid metabolism in macrophages plays a key role in atherosclerosis development. Excessive low-density lipoprotein taken by macrophages leads to foam cell formation. In this study, we aimed to investigate the effect of astaxanthin on foam cells, and using mass spectrometry-based proteomic approaches to identified the protein expression changes of foam cells. MAIN METHODS: The foam cell model was build, then treated with astaxanthin, and tested the content of TC and FC. And proteomics analysis was used in macrophage, macrophage-derived foam cells and macrophage-derived foam cells treated with AST. Then bioinformatic analyses were performed to annotate the functions and associated pathways of the differential proteins. Finally, western blot analysis further confirmed the differential expression of these proteins. KEY FINDINGS: Total cholesterol (TC) while free cholesterol (FC) increased in foam cells treated with astaxanthin. The proteomics data set presents a global view of the critical pathways involved in lipid metabolism included PI3K/CDC42 and PI3K/RAC1/TGF-ß1 pathways. These pathways significantly increased cholesterol efflux from foam cells and further improved foam cell-induced inflammation. SIGNIFICANCE: The present finding provide new insights into the mechanism of astaxanthin regulate lipid metabolism in macrophage foam cells.


Asunto(s)
Aterosclerosis , Células Espumosas , Humanos , Células Espumosas/metabolismo , Proteómica , Colesterol/metabolismo , Lipoproteínas LDL/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Proteínas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo
19.
Opt Express ; 31(5): 8797-8804, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36859987

RESUMEN

Polarization-sensitive narrowband photodetection at near-infrared (NIR) has attracted significant interest in optical communication, environmental monitoring, and intelligent recognition system. However, the current narrowband spectroscopy heavily relies on the extra filter or bulk spectrometer, which deviates from the miniaturization of on-chip integration. Recently, topological phenomena, such as the optical Tamm state (OTS), provided a new solution for developing functional photodetection, and we experimentally realized the device based on 2D material (graphene) for the first time to the best of our knowledge. Here, we demonstrate polarization-sensitive narrowband infrared photodetection in OTS coupled graphene devices, which are designed with the aid of the finite-difference time-domain (FDTD) method. The devices show narrowband response at NIR wavelengths empowered by the tunable Tamm state. The full width at half maximum (FWHM) of the response peak reaches ∼100 nm, and it can potentially be improved to ultra-narrow of about 10 nm by increasing the periods of dielectric distributed Bragg reflector (DBR). The responsivity and response time of the device reaches 187 mA/W and ∼290 µs at 1550 nm, respectively. Furthermore, the prominent anisotropic features and high dichroic ratios of ∼4.6 at 1300 nm and ∼2.5 at 1500 nm are achieved by integrating gold metasurfaces.

20.
Adv Mater ; 35(12): e2210157, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36732915

RESUMEN

Hot-carrier devices are promising alternatives for enabling path breaking photoelectric conversion. However, existing hot-carrier devices suffer from low efficiencies, particularly in the infrared region, and ambiguous physical mechanisms. In this work, the competitive interfacial transfer mechanisms of detrapped holes and hot electrons in hot-carrier devices are discovered. Through photocurrent polarity research and optical-pump-THz-probe (OPTP) spectroscopy, it is verified that detrapped hole transfer (DHT) and hot-electron transfer (HET) dominate the low- and high-density excitation responses, respectively. The photocurrent ratio assigned to DHT and HET increases from 6.6% to over 1133.3% as the illumination intensity decreases. DHT induces severe degeneration of the external quantum efficiency (EQE), especially at low illumination intensities. The EQE of a hot-electron device can theoretically increase by over two orders of magnitude at 10 mW cm-2 through DHT elimination. The OPTP results show that competitive transfer arises from the carrier oscillation type and carrier-density-related Coulomb screening. The screening intensity determines the excitation weight and hot-electron cooling scenes and thereby the transfer dynamics.

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