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1.
Int J Mol Sci ; 25(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38612874

RESUMO

The Hippo pathway plays crucial roles in governing various biological processes during tumorigenesis and metastasis. Within this pathway, upstream signaling stimuli activate a core kinase cascade, involving MST1/2 and LATS1/2, that subsequently phosphorylates and inhibits the transcriptional co-activators YAP and its paralog TAZ. This inhibition modulates the transcriptional regulation of downstream target genes, impacting cell proliferation, migration, and death. Despite the acknowledged significance of protein kinases in the Hippo pathway, the regulatory influence of protein phosphatases remains largely unexplored. In this study, we conducted the first gain-of-functional screen for protein tyrosine phosphatases (PTPs) regulating the Hippo pathway. Utilizing a LATS kinase biosensor (LATS-BS), a YAP/TAZ activity reporter (STBS-Luc), and a comprehensive PTP library, we identified numerous novel PTPs that play regulatory roles in the Hippo pathway. Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer biology and potential therapeutic strategies.


Assuntos
Neoplasias , Monoéster Fosfórico Hidrolases , Via de Sinalização Hippo , Genes Reguladores , Transdução de Sinais , Fatores de Transcrição
2.
Virus Res ; 345: 199378, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38643857

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to human health globally. It is crucial to develop a vaccine to reduce the effect of the virus on public health, economy, and society and regulate the transmission of SARS-CoV-2. Influenza B virus (IBV) can be used as a vector that does not rely on the current circulating influenza A strains. In this study, we constructed an IBV-based vector vaccine by inserting a receptor-binding domain (RBD) into a non-structural protein 1 (NS1)-truncated gene (rIBV-NS110-RBD). Subsequently, we assessed its safety, immunogenicity, and protective efficacy against SARS-CoV-2 in mice, and observed that it was safe in a mouse model. Intranasal administration of a recombinant rIBV-NS110-RBD vaccine induced high levels of SARS-CoV-2-specific IgA and IgG antibodies and T cell-mediated immunity in mice. Administering two doses of the intranasal rIBV-NS110-RBD vaccine significantly reduced the viral load and lung damage in mice. This novel IBV-based vaccine offers a novel approach for controlling the SARS-CoV-2 pandemic.

3.
Carbohydr Polym ; 332: 121919, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431397

RESUMO

The differences in the gelling properties of soy protein isolate (SPI) and soy protein isolate amyloid fibrils (SAFs) as well as the role of cellulose nanocrystals (CNC) in regulating their gel behaviors were investigated in this study. The binding of CNC to ß-conglycinin (7S), glycinin (11S), and SAFs was predominantly driven by non-covalent interactions. CNC addition reduced the particle size, turbidity, subunit segments, and crystallinity of SPI and SAFs, promoted the conversion of α-helix to ß-sheet, improved the thermal stability, exposed more tyrosine and tryptophan residues, and enhanced the intermolecular interactions. A more regular and ordered lamellar network structure was formed in the SAFs-CNC composite gel, which could be conducive to the improvement of gel quality. This study would provide theoretical reference for the understanding of the regulatory mechanism of protein amyloid fibrils gelation as well as the high-value utilization of SAFs-CNC complex as a functional protein-based material or food ingredient in food field.


Assuntos
Celulose , Nanopartículas , Celulose/química , Proteínas de Soja/química , Amiloide/química , Tamanho da Partícula
4.
Food Chem ; 447: 138975, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38489882

RESUMO

Here, the influence and potential mechanism by which cellulose nanocrystals (CNC) collaborated with Ca2+ enhancing the heat-induced gelation of pea protein isolate (PPI) were investigated. It was found that the combination of 0.45% CNC and 15 mM Ca2+ synergistically increased the gel strength (from 14.18 to 65.42 g) and viscoelasticity of PPI while decreased the water holding capacity. The improved particle size, turbidity, and thermostability as well as the reduced solubility, crystallinity, and gel porosity were observed in CNC/CaCl2 composite system. CNC fragments bind to specific amino acids in 11S legumin and 7S vicilin mainly through hydrogen bonding and van der Waals forces. Moreover, changes in the protein secondary structure and enhancement of the molecular interaction induced by CNC and Ca2+ could favor the robust gel network. The results will provide a new perspective on the functional regulation of pea protein and the creation of pea protein gel-based food.


Assuntos
Nanopartículas , Proteínas de Ervilha , Celulose/química , Cálcio , Géis/química , Água/química , Nanopartículas/química
5.
Micromachines (Basel) ; 15(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38542583

RESUMO

Laser-based additive manufacturing has garnered significant attention in recent years as a promising 3D-printing method for fabricating metallic components. However, the surface roughness of additive manufactured components has been considered a challenge to achieving high performance. At present, the average surface roughness (Sa) of AM parts can reach high levels, greater than 50 µm, and a maximum distance between the high peaks and the low valleys of more than 300 µm, which requires post machining. Therefore, laser polishing is increasingly being utilized as a method of surface treatment for metal alloys, wherein the rapid remelting and resolidification during the process significantly alter both the surface quality and subsurface material properties. In this paper, the surface roughness, microstructures, microhardness, and wear resistance of the as-received, continuous wave laser polishing (CWLP), and pulsed laser polishing (PLP) processed samples were investigated systematically. The results revealed that the surface roughness (Sa) of the as-received sample was 6.29 µm, which was reduced to 0.94 µm and 0.84 µm by CWLP and PLP processing, respectively. It was also found that a hardened layer, about 200 µm, was produced on the Ti6Al4V alloy surface after laser polishing, which can improve the mechanical properties of the component. The microhardness of the laser-polished samples was increased to about 482 HV with an improvement of about 25.2% compared with the as-received Ti6Al4V alloy. Moreover, the coefficient of friction (COF) was slightly reduced by both CWLP and LPL processing, and the wear rate of the surface layer was improved to 0.790 mm3/(N∙m) and 0.714 mm3/(N∙m), respectively, under dry fraction conditions.

6.
Enzyme Microb Technol ; 177: 110438, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38518554

RESUMO

Klebsiella pneumoniae can use glucose or glycerol as carbon sources to produce 1,3-propanediol or 2,3-butanediol, respectively. In the metabolism of Klebsiella pneumoniae, hydrogenase-3 is responsible for H2 production from formic acid, but it is not directly related to the synthesis pathways for 1,3-propanediol and 2,3-butanediol. In the first part of this research, hycEFG, which encodes subunits of the enzyme hydrogenase-3, was knocked out, so K. pneumoniae ΔhycEFG lost the ability to produce H2 during cultivation using glycerol as a carbon source. As a consequence, the concentration of 1,3-propanediol increased and the substrate (glycerol) conversion ratio reached 0.587 mol/mol. Then, K. pneumoniae ΔldhAΔhycEFG was constructed to erase lactic acid synthesis which led to the further increase of 1,3-propanediol concentration. A substrate (glycerol) conversion ratio of 0.628 mol/mol in batch conditions was achieved, which was higher compared to the wild type strain (0.545 mol/mol). Furthermore, since adhE encodes an alcohol dehydrogenase that catalyzes ethanol production from acetaldehyde, K. pneumoniae ΔldhAΔadhEΔhycEFG was constructed to prevent ethanol production. Contrary to expectations, this did not lead to a further increase, but to a decrease in 1,3-propanediol production. In the second part of this research, glucose was used as the carbon source to produce 2,3-butanediol. Knocking out hycEFG had distinct positive effect on 2,3-butanediol production. Especially in K. pneumoniae ΔldhAΔadhEΔhycEFG, a substrate (glucose) conversion ratio of 0.730 mol/mol was reached, which is higher compared to wild type strain (0.504 mol/mol). This work suggests that the inactivation of hydrogenase-3 may have a global effect on the metabolic regulation of K. pneumoniae, leading to the improvement of the production of two industrially important bulk chemicals, 1,3-propanediol and 2,3-butanediol.

7.
Heliyon ; 10(6): e28232, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38524583

RESUMO

Luteolin, a naturally occurring pharmaceutical compound with significant antitumor properties, faces challenges in clinical applications due to its low solubility in water and limited bioavailability. To address these issues, a one-step synthesis method was employed to encapsulate luteolin within ZIF-8. The successful preparation of luteolin@ ZIF-8 nanoparticles was confirmed through various analytical techniques, including fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), laser size distribution analysis, X-ray diffraction (XRD), and release curve assessment. Results indicate that the formulated luteolin@ ZIF-8 nanoparticles exhibited high drug loading (1360 mg/g) and demonstrated selective drug release in acidic microenvironments. Furthermore, the encapsulation of luteolin increased the size of ZIF-8 from 168.4 ± 0.2 nm to 384.7 ± 1.4 nm, but did not change its crystalline structure significantly. Notably, the results of in vitro anti-cervical and prostate cancers experiments revealed that luteolin@ ZIF-8 had better efficacy in inhibiting the proliferation and migration of HeLa and PC3 cells than free luteolin. The antitumor activity of luteolin@ ZIF-8 was sustained for 72 h, with a particularly pronounced inhibitory effect on HeLa cells as compared to PC3 cells. This study underscores the effective enhancement of luteolin's antitumor activity through encapsulation in ZIF-8, offering substantial implications for improving its clinical applications.

8.
J Am Chem Soc ; 146(12): 7963-7970, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38483110

RESUMO

Cellulose serves as a sustainable biomaterial for a wide range of applications in biotechnology and materials science. While chemical and enzymatic glycan assembly methods have been developed to access modest quantities of synthetic cellulose for structure-property studies, chemical polymerization strategies for scalable and well-controlled syntheses of cellulose remain underdeveloped. Here, we report the synthesis of precision cellulose via living cationic ring-opening polymerization (CROP) of glucose 1,2,4-orthopivalates. In the presence of dibutyl phosphate as an initiator and triflic acid as a catalyst, precision cellulose with well-controlled molecular weights, defined chain-end groups, and excellent regio- and stereospecificity was readily prepared. We further demonstrated the utility of this method through the synthesis of precision native d-cellulose and rare precision l-cellulose.


Assuntos
Celulose , Glucose , Celulose/química , Polimerização , Glucose/química , Polissacarídeos , Cátions
9.
ACS Cent Sci ; 10(2): 358-366, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38435533

RESUMO

Encapsulating enzymes within metal-organic frameworks has enhanced their structural stability and interface tunability for catalysis. However, the small apertures of the frameworks restrict their effectiveness to small organic molecules. Herein, we present a green strategy directed by visible linker micelles for the aqueous synthesis of MAF-6 that enables enzymes for the catalytic asymmetric synthesis of chiral molecules. Due to the large pore aperture (7.6 Å), double the aperture size of benchmark ZIF-8 (3.4 Å), MAF-6 allows encapsulated enzyme BCL to access larger substrates and do so faster. Through the optimization of surfactants' effect during synthesis, BCL@MAF-6-SDS (SDS = sodium dodecyl sulfate) displayed a catalytic efficiency (Kcat/Km) that was 420 times greater than that of BCL@ZIF-8. This biocomposite efficiently catalyzed the synthesis of drug precursor molecules with 94-99% enantioselectivity and nearly quantitative yields. These findings represent a deeper understanding of de novo synthetic encapsulation of enzyme in MOFs, thereby unfolding the great potential of enzyme@MAF catalysts for asymmetric synthesis of organics and pharmaceuticals.

10.
STAR Protoc ; 5(1): 102872, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38319785

RESUMO

Autophagy supports cell survival under different stress conditions, where ATG8-family proteins are required for autophagosome biogenesis/maturation and selective autophagy. Here, we present a protocol for studying ATG8-family protein phosphorylation using Phos-tag gel, a modified SDS-PAGE system, when the related phosphorylation site information and/or specific phospho-antibody are unavailable. We describe steps for generating GST-ATG8 proteins in bacteria, purifying S protein-Flag-SBP protein (SFB)-tagged kinasefrom cells, preparing gel, and an in vitro kinase assay. We then detail procedures for western blotting and image processing. For complete details on the use and execution of this protocol, please refer to Seo et al.1.


Assuntos
Autofagia , Piridinas , Família da Proteína 8 Relacionada à Autofagia/genética , Família da Proteína 8 Relacionada à Autofagia/metabolismo , Fosforilação
11.
BMC Musculoskelet Disord ; 25(1): 160, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378509

RESUMO

BACKGROUND: The safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years. METHODS: Data were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis. RESULTS: The final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24-123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616). CONCLUSION: The two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up.


Assuntos
Antibacterianos , Infecções Relacionadas à Prótese , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Infecções Relacionadas à Prótese/etiologia , Resultado do Tratamento , Reinfecção/complicações , Reinfecção/tratamento farmacológico , Reoperação/métodos
12.
Inorg Chem ; 63(5): 2647-2654, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38262040

RESUMO

The increasing demands in optoelectronic applications have driven the advancement of organic-inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4 (Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4 (Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2- polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d-d electron transition of Mn2+ with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV-1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyair s-1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4 and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm-1, which provides a potential visualization tool for X-ray radiography.

13.
Angew Chem Int Ed Engl ; 63(9): e202314583, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38196289

RESUMO

Biointerfacing nanomaterials with cell membranes has been successful in the functionalization of nanoparticles or nanovesicles, but microbubble functionalization remains challenging due to the unique conformation of the lipid monolayer structure at the gas-liquid interface that provides insufficient surfactant activity. Here, we describe a strategy to rationally regulate the surfactant activity of platelet membrane vesicles by adjusting the ratio of proteins to lipids through fusion with synthetic phospholipids (i.e., liposomes). A "platesome" with the optimized protein-to-lipid ratio can be assembled at the gas-liquid interface in the same manner as pulmonary surfactants to stabilize a microsized gas bubble. Platesome microbubbles (PMBs) inherited 61.4 % of the platelet membrane vesicle proteins and maintained the active conformation of integrin αIIbß3 without the talin 1 for fibrin binding. We demonstrated that the PMBs had good stability, long circulation, and superior functionality both in vitro and in vivo. Moreover, by molecular ultrasound imaging, the PMBs provide up to 11.8 dB of ultrasound signal-to-noise ratio enhancement for discriminating between acute and chronic thrombi. This surface tension regulating strategy may provide a paradigm for biointerfacing microbubbles with cell membranes, offering a potential new approach for the construction of molecular ultrasound contrast agents for the diagnosis of different diseases.


Assuntos
Surfactantes Pulmonares , Trombose , Humanos , Tensoativos , Microbolhas , Fosfolipídeos , Lipoproteínas , Meios de Contraste/química
14.
Talanta ; 269: 125481, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039669

RESUMO

Terahertz (THz) fingerprint metasensing is an effective method to identify chemical substances in a rapid and non-destructive way. Currently, two main principles are used in THz metasensing: the change of the real part of permittivity causing the dip resonance frequency deviation, and the fingerprint peak of the imaginary part of permittivity causing the dip resonance splitting (absorption induced transparency, AIT). Most previous work investigated AIT detection for only single chemical substance. The suitable AIT metasensor structure are still required for simultaneously measurement of multiple and mixture chemical substances. In this manuscript, we proposed the N-order concentric rings metasensor for specific recognition multiple and mixed chemical substances based on AIT fingerprint enhancement. The structure has broadband multiple plasmonic resonance dips which are generated by near field dipole resonances. The equivalent circuit model was built to realize the reconfigurable function. Then, 5-order concentric rings structure was designed and fabricated for simultaneously specific recognition of four chemical substances (α-lactose, benzoic acid, vitamin B2 and 2, 5-dichloroanline). The influence of the real and imaginary part of the chemical substances' permittivity on AIT effect had discussed in details. Simulation results indicated that the frequency-deviation of the resonance dip can be stabilized and will not be changed when the concentration of chemical substances is over 20 mg/mL. As shifted plasmonic resonance peaks match the chemical substances' imaginary part of permittivity fingerprint spectra, the perfect AIT effect can be realized. The metasensor can simultaneously and non-destructively conduct a specific detection of α-lactose, benzoic acid, vitamin B2 and 2,5-dichloroanline, and their mixture. The limit of detections of α-lactose, benzoic acid, vitamin B2 and 2,5-dichloroanline are 8.61 mg/mL, 6.96 mg/mL, 7.54 mg/mL and 8.35 mg/mL, respectively. Also, the sensitivity of the metasensor can reach 0.00211, 0.00208, 0.00211 and 0.00219 (unit: 1/mg/mL), respectively. By utilizing one-way analysis of variance method, the possibility of recognition error for each chemical substance is lower than 0.001. Our metasensor provides a novel and accurate platform for THz fingerprint sensing.

15.
Mikrochim Acta ; 191(1): 52, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38147136

RESUMO

Coconut cadang-cadang viroid (CCCVd) is an infectious single-stranded RNA (ssRNA) pathogen, which leads directly to the death of a large number of coconut palm trees and heavy economic loss to coconut farmers. Herein, a novel electrochemical impedance RNA genosensor is presented based on highly stable gold nanoparticles (AuNPs) decorated phosphorene (BP) nanohybrid with graphene (Gr) for highly sensitive, low-cost, and label-free detection of CCCVd. BP-AuNPs are environmentally friendly prepared by ultrasonic-assisted liquid-phase exfoliation of black phosphorus, accompanying direct reduction of chloroauric acid. Gr/BP-AuNPs are facilely prepared by the in situ growth of AuNPs onto the BP surface and its nanohybrid with Gr to improve environmental stability of BP. Gr/BP-AuNP-based RNA genosensor is fabricated by immobilizing the thiol-functionalized single-stranded DNA (ssDNA) oligonucleotide probe onto the surface of Gr/BP-AuNP-modified glassy carbon electrode via gold-thiol interactions, which served as an electrochemical genosensing platform for the label-free impedance detection of CCCVd by hybridization between the functionalized ssDNA probe and the complementary CCCVd ssRNA sequence in a wide linear range from 1.0 × 10-11 to 1.0 × 10-7 M with a low limit of detection of 2.8 × 10-12 M. This work supplies an experimental support and theoretical direction for the fabrication of RNA biosensors based on graphene-like materials and potential application for a specific diagnosis of plant RNA viral disease in Arecaceae planting industry.


Assuntos
Grafite , Nanopartículas Metálicas , Ouro , DNA de Cadeia Simples , Compostos de Sulfidrila
16.
Adv Healthc Mater ; : e2302566, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37931140

RESUMO

Effectively controlling bacterial infection, reducing the inflammation and promoting vascular regeneration are all essential strategies for wound repair. Nanozyme technology has potential applications in the treatment of infections because its non-antibiotic dependent, topical and noninvasive nature. In wound management, copper-based nanozymes have emerged as viable alternatives to antibiotics. In this study, an ultrasmall cupric enzyme with high enzymatic activity is synthesized and added to a nontoxic, self-healing, injectable cationic guar gum (CG) hydrogel network. The nanozyme exhibits remarkable antioxidant properties under neutral conditions, effectively scavenging reactive nitrogen and oxygen species (RNOS). Under acidic conditions, Cu NDs have peroxide (POD) enzyme-like activity, which allows them to eliminate hydrogen peroxides and produce free radicals locally. Antibacterial experiments show that they can kill bacteria and remove biofilms. It reveals that low concentrations of Cu ND/CG decrease the expression of the inflammatory factors in cells and tissues, effectively controlling inflammatory responses. Cu ND/CG hydrogels also inhibit HIF-1α and promote VEGF expression in the wound with the ability to promote vascular regeneration. In vivo safety assessments reveal a favorable biosafety profile. Cu ND/CG hydrogels offer a promising solution for treating acute and infected wounds, highlighting the potential of innovative nanomaterials in wound healing.

17.
Autophagy ; : 1-3, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37937799

RESUMO

As a key regulator of development, organ size, tissue homeostasis and cancer, the Hippo pathway is tightly regulated by various growth-related signaling events. Among them, energy stress activates the Hippo pathway to inhibit its downstream effector YAP1. Our recent work reported a YAP1-independent role of the Hippo pathway in promoting macroautophagy/autophagy and cell survival in response to energy stress, a process mediated by Hippo kinase MAP4K2. MAP4K2 interacts with and phosphorylates MAP1LC3A/LC3A at S87, which in turn drives autophagosome-lysosome fusion via the RAB3GAP-RAB18 axis. Energy stress activates MAP4K2 by reducing its association with the Hippo phosphatase complex STRIPAK component STRN4. Moreover, MAP4K2 is highly expressed in head and neck cancer, while MAP4K2 and its mediated autophagy are required for head and neck cancer development. Taken together, our study not only reveals a noncanonical role of the Hippo pathway in energy stress response, but also suggests Hippo kinase MAP4K2 as a potential therapeutic target for head and neck cancer treatment.Abbreviation: AMPK: 5'-AMP-activated protein kinase; Atg8: autophagy related 8; LATS1: large tumor suppressor 1; LIR: microtubule-associated protein 1 light chain 3-interacting region; MAP1LC3A/LC3A: microtubule-associated protein 1 light chain 3 alpha; MAP4K2: mitogen-activated protein kinase kinase kinase kinase 2; PPP2/PP2A: protein phosphatase 2; RAB3GAP: RAB3 GTPase activating protein; RAB18: RAB18, member RAS oncogene family; SLMAP: sarcolemma associated protein; STK3/MST2: serine/threonine kinase 3; STK4/MST1: serine/threonine kinase 4; STRIPAK: striatin-interacting phosphatase and kinase; STRN4: striatin, calmodulin binding protein 4; SQSTM1/p62: sequestosome 1; TEAD: TEA domain family member; ULK1: unc-51 like kinase 1; WWTR1/TAZ: WW domain containing transcription regulator 1; YAP1: yes-associated protein 1.

18.
Adv Sci (Weinh) ; 10(34): e2304116, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37870207

RESUMO

The integration of metasurfaces and optical waveguides is gradually attracting the attention of researchers because it allows for more efficient manipulation and guidance of light. However, most of the existing studies focus on passive devices, which lack dynamic modulation. This work utilizes the meta-waveguides with liquid crystal(LC) to modulate the on-chip spectrum, which is the first experimentally verified, to the authors' knowledge. By applying a voltage, the refractive index of the liquid crystal surrounding the meta-waveguides can be tuned, resulting in a blue shift of the spectrum. The simulation shows that the 18.4 dB switching ratio can be achieved at 1550 nm. The meta-waveguides are prepared using electron beam lithography (EBL), and the improved transmittance of the spectrum in the short wavelength is experimentally verified, which is consistent with the simulation trend. At 1551.64 nm wavelength, the device achieves a switching ratio of ≈16 dB with an active area of 8 µm × 0.4 µm. Based on this device, an optoelectronic computing architecture for the Hadamard matrix product and a novel wavelength selection switch are proposed. This work offers a promising avenue for on-chip dynamic modulation in integrated photonics, which has the advantage of a compact active area, fast response time, and low energy consumption compared to conventional thermal-light modulation.

19.
Micromachines (Basel) ; 14(9)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37763928

RESUMO

Laser polishing is an emerging efficient technique to remove surface asperity without polluting the environment. However, the insufficient understanding of the mechanism of laser polishing has limited its practical application in industry. In this study, a dual-beam laser polishing experiment was carried out to reduce the roughness of a primary Ti6Al4V sample, and the polishing mechanism was well studied using simulation analysis. The results showed that the surface roughness of the sample was efficiently reduced from an initial 10.96 µm to 1.421 µm using dual-beam laser processing. The simulation analysis regarding the evolution of material surface morphology and the flow behavior of the molten pool during laser the polishing process revealed that the capillary force attributed to surface tension was the main driving force for flattening the large curvature surface of the molten pool at the initial stage, whereas the thermocapillary force influenced from temperature gradient played the key role of eliminating the secondary roughness at the edge of the molten pool during the continuous wave laser polishing process. However, the effect of thermocapillary force can be ignored during the second processing stage in dual-beam laser polishing. The simulation result is well in agreement with the experimental result, indicating the accuracy of the mechanism for the dual-beam laser polishing process. In summary, this work reveals the effect of capillary force and thermocapillary force on molten pool flows during the dual-beam laser polishing processes. Moreover, it is also proved that the dual-beam laser polishing process can further reduce the surface roughness of a sample and obtain a smoother surface.

20.
Mol Cell ; 83(17): 3155-3170.e8, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37595580

RESUMO

The Hippo pathway is known for its crucial involvement in development, regeneration, organ size control, and cancer. While energy stress is known to activate the Hippo pathway and inhibit its effector YAP, the precise role of the Hippo pathway in energy stress response remains unclear. Here, we report a YAP-independent function of the Hippo pathway in facilitating autophagy and cell survival in response to energy stress, a process mediated by its upstream components MAP4K2 and STRIPAK. Mechanistically, energy stress disrupts the MAP4K2-STRIPAK association, leading to the activation of MAP4K2. Subsequently, MAP4K2 phosphorylates ATG8-family member LC3, thereby facilitating autophagic flux. MAP4K2 is highly expressed in head and neck cancer, and its mediated autophagy is required for head and neck tumor growth in mice. Altogether, our study unveils a noncanonical role of the Hippo pathway in energy stress response, shedding light on this key growth-related pathway in tissue homeostasis and cancer.


Assuntos
Autofagia , Via de Sinalização Hippo , Animais , Camundongos , Sobrevivência Celular , Tamanho do Órgão
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