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1.
Food Res Int ; 163: 112204, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596136

RESUMO

In order to study the effect of oxidation on the dye-binding behavior of myofibrillar proteins, selected dyes with different charges (positively charged Sarfarin O (SO), neutral bromophenol blue (BPB), and negatively charged Orange G (OG)) were incubated with myofibrils oxidized by the Fenton system with H2O2 (10 mM). Upon oxidation, loss of free thiols, formation of carbonyls, particle size, and hydrophobicity of myofibrillar proteins (MPs) increased. The absolute value of Zeta-potential increased by 14.48 % after oxidation, the myofibrillar proteins shifted to a more acidic isoelectric point (pI) upon oxidation. Oxidation decreased net positive charges of myofibrillar protein and the binding ability of MPs towards OG in the environment with pH less than pI and the affinity of MPs towards SO in the environment with pH more than pI were thus increased. Here we propose a hypothesis that oxidation-induced change in net charges is the driving force affecting the amount of protein-bound dye. This paper aims to examine the effect of oxidation on the net charges of myofibrillar proteins and to provide insight into the mechanism of oxidation-induced changes in protein-bound dyes.


Assuntos
Corantes , Proteínas Musculares , Ponto Isoelétrico , Peróxido de Hidrogênio , Miofibrilas
2.
Food Chem ; 409: 135279, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-36603476

RESUMO

This study aimed to investigate the effect of hydroxyl radical oxidizing system (HROS) and endogenous oxidizing system (EOS, i.e., frozen storage at -20 °C) on protein oxidation, digestive properties, and peptide modification of myofibrillar proteins (MPs) in bighead carp (Hypophthalmichthys nobilis) fillets. The oxidation degree increased with the frozen time and H2O2 concentration as evidenced by carbonyl group generation and sulfhydryl group loss in MPs. The digestibility of protein declined gradually during frozen storage, while it increased after treatment with 5 mM H2O2 compared with no H2O2 intervention. More modification numbers and types were observed in the EOS group than HROS in digested MPs peptides, which might be due to the complexity of the frozen fillet system such as the presence of lipid. The potential conversion of α-aminoadipic semialdehyde (AAS) to α-aminoadipic acids (AAA) was observed in HROS. Additionally, the myosin heavy chain was more susceptible to oxidation among all MPs by EOS oxidation.


Assuntos
Carpas , Cyprinidae , Animais , Radical Hidroxila , Oxirredução , Congelamento
3.
J Funct Biomater ; 14(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36662074

RESUMO

Carbon dots (CDs) are a new category of crystalline, quasi-spherical fluorescence, "zero-dimensional" carbon nanomaterials with a spatial size between 1 nm to 10 nm and have gained widespread attention in recent years. Green CDs are carbon dots synthesised from renewable biomass such as agro-waste, plants or medicinal plants and other organic biomaterials. Plant-mediated synthesis of CDs is a green chemistry approach that connects nanotechnology with the green synthesis of CDs. Notably, CDs made with green technology are economical and far superior to those manufactured with physicochemical methods due to their exclusive benefits, such as being affordable, having high stability, having a simple protocol, and being safer and eco-benign. Green CDs can be synthesized by using ultrasonic strategy, chemical oxidation, carbonization, solvothermal and hydrothermal processes, and microwave irradiation using various plant-based organic resources. CDs made by green technology have diverse applications in biomedical fields such as bioimaging, biosensing and nanomedicine, which are ascribed to their unique properties, including excellent luminescence effect, strong stability and good biocompatibility. This review mainly focuses on green CDs synthesis, characterization techniques, beneficial properties of plant resource-based green CDs and their biomedical applications. This review article also looks at the research gaps and future research directions for the continuous deepening of the exploration of green CDs.

4.
Food Chem ; 411: 135515, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36693300

RESUMO

The objective of this study was to elucidate the influence of oxidative modifications of myofibrillar proteins (MPs) on their surface properties. Oxidative modifications (deamination, formation of disulfide bonds and Schiff bases), particle size, net surface charge, and binding ability of volatiles (2-enthylfuran, 1-octen-3-ol, hexanal, and octanal) of oxidized MPs was measured. Molecular docking of volatiles with actomyosin was performed using Qvina-W program and the specific oxidative modifications (monoxidation and deamination) of MPs were determined using LC-MS/MS. Results showed that oxidation of Cys (forming sulfinic, sulfonic, sulfenic acid, and disulfide bonds), monoxidation of Ala, Lys, Glu, and Asn, and deamination of Lys changed the surface properties of oxidized MPs including enhanced surface hydrophobicity and decreased affinity to volatile compounds and water. Overall, this study gives evidence of how protein oxidation affects the properties of MPs and therefore deteriorates fish meat quality.

5.
Sci Total Environ ; 867: 161433, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36623668

RESUMO

This research is one main objective to assess combined toxicity of trace metal mixtures in aquatic biota in coastal sediments. Coastal sediments around the world are a major reservoir of trace metals from industrial wastewater discharge. Our case study site, Daya Bay in southern China, was selected because it has been under severe man-made impacts. Diffusive gradients in thin films (DGT) technique has proven to be a good method for measuring the bioavailability of trace metals. The bioavailability and distribution of trace metals in surface sediments were investigated along with their possible biological risks. The average bioavailable (DGT-labile) concentrations (µg/L) were 0.44 (V), 0.51 (Cr), 52.49 (Mn), 0.10 (Co), 1.36 (Ni), 0.74 (Cu), 14.53 (Zn), 0.97 (As), 0.14 (Se), 6.73 (Mo), 0.17 (Cd), 0.27 (Sb), 0.10 (W), and 1.32 (Pb). Nonmetric multidimensional scaling (NMS) is a robust multivariate ordination method that makes no assumptions about the distribution of the underlying data. NMS was used to explore that DGT-labile concentrations of trace metals were influenced by sediment properties. NMS results indicated that most DGT- labile trace metals influenced by sediment properties. Risk assessment of single trace metal toxicity revealed that risk quotient (RQ) values for Mn, Cu, Zn and Pb significantly exceeded 1, demonstrating that the toxic effects of these trace metals should be not ignored. The probabilistic ecological risk assessment for integral toxicity of one mixture of 14 trace metals revealed that Daya Bay surface sediments had a low probability (9.04 %) of adverse effects on aquatic biota.

6.
Biomaterials ; 294: 121995, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36641813

RESUMO

Nanocarriers have become an effective strategy to overcome epithelial absorption barriers. During the absorption process, the endocytosis mechanisms, cell internalization pathways, and transport efficiency of nanocarriers are greatly impacted by their physical properties. To understand the relationship between physical properties of nanocarriers and their abilities overcoming multiple absorption barriers, nanocarriers with variable physical properties were prepared via self-assembly of hydrolyzed α-lactalbumin peptide fragments. The impacts of size, shape, and rigidity of nanocarriers on epithelial cells endocytosis mechanisms, internalization pathways, transport efficiency, and bioavailability were studied systematically. The results showed that nanospheres were mainly internalized via clathrin-mediated endocytosis, which was then locked in lysosomes and degraded enzymatically in cytoplasm. While macropinocytosis was the primary pathway of nanotubes and transported to the endoplasmic reticulum and Golgi apparatus, resulting in a high drug concentration and sustained release in cytoplasm. Besides, nanotubes can overcome the multi-drug resistance by inhibiting the P-glycoprotein efflux. Furthermore, nanotubes can open intercellular tight-junctions instantaneously and reversibly, which promotes transport into blood circulation. The aqueous solubility of hydrophobic bioactive mangiferin (Mgf) was improved by nanocarriers. Most importantly, the bioavailability of Mgf was the highest for cross-linked short nanotube (CSNT) which outperformed free Mgf and other formulations by in vivo pharmacokinetic studies. Finally, Mgf-loaded CSNT showed an excellent therapeutic efficiency in vivo for the intervention of streptozotocin-induced diabetes. These results indicate that cross-linked α-lactalbumin nanotubes could be an effective nanocarrier delivery system for improving the epithelium cellular absorption and bioavailability of hydrophobic bioactive compounds.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36607153

RESUMO

OBJECTIVE: The aim of the study was to evaluate the long-term efficacy and quality of life concerning SSLF using conventional instruments for Chinese women with symptomatic stage 2 and 3 apical prolapse. METHOD: This single-arm prospective cohort study was conducted at our hospital between October 2011 and December 2018. Eligible participants were followed up over 3 years after surgery. The primary surgical outcome was composite surgical failure. Secondary outcomes included satisfactory rate, quality of life (QoL) scores and long-term complications. RESULTS: Fifty-nine patients were enrolled (mean age, 57.1 years), of whom 55 (93.22%) completed 3-year follow-up. At year 3, the composite failure rate was 21.34% (95%CI 9.30% -31.79%), and satisfactory rate was 81.40% (95%CI 66.09% -91.08%). Right thigh pain and de novo dyspareunia occurred in 1.8% and 14.6% patients after year 1, but at year 3 there was none. 5.5% patients had lower urinary tract symptoms. Improvement in urinary symptoms and prolapse symptoms was found, but sexual function showed no significant change. CONCLUSIONS: Compared with results at year 1, complication rates of SSLF decreased at year 3. The composite failure rate was relatively low and satisfactory rate relatively high at year.3. Prolapse and urinary symptoms improved significantly after surgery.

8.
Food Chem ; 404(Pt A): 134556, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36444012

RESUMO

Whey protein (WP) is ubiquitously applied in food products, but its sensitivity to food processing conditions has limited its application. Herein, we chose propylene glycol alginate (PGA) to combine with WP to enhance its stability. The ideal ratio of WP/PGA for coacervation was 3:1, and the soluble complex and insoluble complex were formed at pH 5.2 (pHc) and pH 4.4 (pHφ1) at this ratio, respectively. The UV absorption spectra, fluorescence spectra, and XRD results revealed that the interaction between PGA and WP changed the tertiary conformation of WP. The FTIR and molecular docking results suggested electrostatic interactions, hydrogen bonding and hydrophobic interactions were all involved in the formation of WP-PGA complexes, and the thermal stability of WP was improved based on the DSC results. These findings supported PGA to keep dairy products stable and transparent at the isoelectric point and WP-PGA complexes could be applied in encapsulating bioactive substances.


Assuntos
Alginatos , Simulação de Acoplamento Molecular , Proteínas do Soro do Leite
9.
Am J Hosp Palliat Care ; : 10499091221148141, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36546313

RESUMO

Little has been published on the meaning of food to palliative care patients with anorexia. Our study aims to investigate the meaning of food in palliative patients with anorexia. Fifteen patients with anorexia were recruited from the Palliative Care Unit of an acute hospital in Singapore from August 2018 to August 2021. A phenomenological methodology was employed to study the lived experience of anorexia and the meaning of food to palliative care patients. Our study findings revealed that food has social, physical, and emotional meaning in palliative care patients with anorexia. The social meaning of food was the predominant theme. Food was viewed as an important tool to bond and connect with their loved ones. It was perceived to be more important than the food itself and the taste of food was enhanced through social interactions. Food intake was related to physical strength and health status. Patients regarded eating as a way to improve their health status. Emotionally, eating was associated with positive feelings like enjoyment and freedom. Half of our participants felt that anorexia contributed to their low mood. Therefore, unlike the traditional focus of modifying the taste and quality of food in patients with anorexia, the authors recommended a focused assessment and management of the social aspect of anorexia on individual. This is important to mitigate the negative impact of anorexia, thus improving the quality of life and increasing their dignity towards the end of their lives.

10.
Pharmaceuticals (Basel) ; 15(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36558996

RESUMO

We extracted, purified, and characterized three neutral and three acidic polysaccharides from the roots, stems, and leaves of Aralia continentalis Kitigawa. The results of the analysis of monosaccharide composition indicated that the polysaccharides from the roots and stems were more similar to each other than they were to the polysaccharides from the leaves. The in vitro antioxidant results demonstrated that the acidic polysaccharides had stronger antioxidant activity than the neutral fractions. Therefore, we investigated the primary purified acidic polysaccharide fractions (WACP(R)-A-c, WACP(S)-A-c, and WACP(L)-A-d) by NMR and enzymatic analysis. The structural analytical results indicated that WACP(R)-A-c contained homogalacturonan (HG); WACP(S)-A-c contained HG and rhamnogalacturonan II (RG-II), and WACP(L)-A-d contained HG, RG-II, and rhamnogalacturonan I (RG-I) domains. Our findings offer insights into the screening of natural polysaccharide-based antioxidants and provide a theoretical basis for the application of A. continentalis.

11.
Foods ; 11(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36359963

RESUMO

The effect of salted duck egg white powder (SDEWP) as a source of salt at different salt equivalent (SE) levels (0-2.5% SE) on gel qualities and texture properties of threadfin bream surimi was investigated. SDEWP possessed a high protein (64.59%) and salt (34.86%) concentration. The breaking force of surimi gel increased by the amount of SDEWP (p < 0.05). The addition of SDEWP up to 1.5% SE into the surimi gel has significantly increased the deformation (13.8%) and decreased the expressible moisture content (38.5%). Hardness, gumminess, and chewiness were augmented as higher levels of SDEWP were added, whereas cohesiveness decreased when the SDEWP above 1.5% SE was used. The incorporation of SDEWP had no significant effect on the springiness (p < 0.05). Less proteolytic degradation was observed in the surimi gel fortified with SDEWP. A higher amount of added SDEWP enhanced the whiteness of the surimi gel (p < 0.05). A denser and more ordered gel network was attained when SDEWP with 1.5% SE was added. SDEWP could be exploited as a source for salt and non-fish proteins in threadfin bream surimi, in which SDEWP containing 1.5% SE could significantly improve the quality of surimi gel.

12.
Foods ; 11(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36360074

RESUMO

Phenolic compounds from cashew (Anacardium occidentale L.) leaves were extracted using ethanol with the aid of ultrasonication. Three independent variables, including ultrasound amplitude, time, and ethanol concentration, were used for response surface methodology (RSM) along with the central composite design (CCD). Under the optimized condition (70% amplitude; 40 min; 80% ethanol), the extraction yield and total phenolic contents were 24.50% and 431.16 mg GAE/g dry extract, respectively. Cashew leaf extract (CLE) had the lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Shewanella sp. than P. aeruginosa. The release of K+ and Mg2+ ions from damaged cell membranes with a coincidental decrease of TTC dehydrogenase activity were augmented when treated with CLE. In addition, scanning electron microscopic (SEM) image revealed deformations and perforation of cell walls of bacteria treated with CLE. The dominant compounds in CLE were amentoflavone, quercetin, and its glycosides. Based on microbial challenge test, the growth of P. aeruginosa and Shewanella sp. inoculated in tilapia slices were inhibited by CLE at 400 and 600 ppm within 15 days of refrigerated storage.

13.
Small ; : e2205260, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36424174

RESUMO

Thrombotic diseases have a high rate of mortality and disability, and pose a serious threat to global public health. Currently, most thrombolytic drugs especially protein drugs have a short blood-circulation time, resulting in low thrombolytic efficiency. Therefore, a platelet membrane (Pm) cloaked nanotube (NT-RGD/Pm) biomimetic delivery system with enhanced thrombolytic efficiency is designed. Nanotubes (NT) with an excellent clot-penetration properties are used to load a protein thrombolytic drug urokinase (Uk). Platelet-targeting arginine glycine-aspartic peptide (RGD) is grafted onto the surface of the nanotubes (NT-RGD) prior to cloaking. Multiple particle tracking (MPT) technique and confocal laser scanning microscope (CLSM) analysis are applied and the results show that the nanotubes possess a strong penetration and diffusion capacity in thrombus clots. After the Pm cloaking on NT-RGD/Uk, it shows a thrombus microenvironmental responsive release property and the half-life of Uk is six times longer than that of free Uk. Most importantly, NT-RGD-Uk/Pm exhibits a 60% thrombolytic efficiency in the FeCl3 -induced thrombosis mouse model, and it is able to significantly reduce the bleeding side effects of Uk. This Pm-cloaked nanotube system is an effective and promising platform for the controlled and targeted delivery of drugs for the thrombus treatment.

14.
Small ; : e2203647, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36446641

RESUMO

The previously published report by Wang et al. provides universal equations for evaluating the net CO2 emission via photothermal/thermal CO2 hydrogenation reactions in batch and flow reactors, respectively. However, it remains to be discussed whether the original feed amount or feed rate of H2 should be changed accordingly when the CO2 reduction rate is selected as the variable to investigate the net CO2 emission rate of the system. If not, the reaction would not be in accordance with the stoichiometric ratio, which is inconsistent with reality, bringing about the optimistic scenario in the assessment of CO2 footprint. This work has taken the potential relationship between the original feed amount or feed rate of H2 and CO2 conversion rate into account. The effects of CO2 conversion rate on the net CO2 emission rate in the photothermal catalytic system are re-examined, the obtained trends exhibit more challenging preconditions to achieve net-zero carbon emission than those in the work by Wang et al. The quantitative results indicate that green hydrogen source is indeed vital for carbon neutrality in photothermal CO2 catalysis. Here, the viewpoints will be worth considering and be seen as complementary to the proposed carbon emission assessment equations.

15.
Huan Jing Ke Xue ; 43(11): 4876-4887, 2022 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-36437060

RESUMO

China is one of the largest rice producers in the world, and rice production plays an important role in food security. Currently, arsenic pollution in paddy soils is one of most serious soil pollutions in China. Since paddy soils are maintained in a flooding anoxic condition for long periods, the rate and extent of arsenic transformation processes governed by microbial activities are stronger than that of chemical processes. Thus, understanding the key processes and relating mechanisms of microbial arsenic fixation in paddy soils will provide a theoretical basis for controlling arsenic pollution in paddy soils. In this study, based on a comprehensive analysis of arsenic migration in paddy soils and relating influencing factors, two important pathways relating to As(Ⅲ) fixation through microbial activities were illustrated:microbial CFe(Ⅱ) oxidation coupled with As(Ⅲ) fixation (indirect process) and direct fixation through microbial As(Ⅲ) oxidation (direct process). Additionally, the influences of speciation and the distribution of nitrogen in paddy soils to the processes of microbial arsenic fixations were discussed and by extension, the expressions of key genes and metabolic mechanisms relating to microbial arsenic fixation and nitrogen transformation. Finally, the recent advances in microbial remediation used to control arsenic pollution in paddy soils were summarized, and relating future perspectives targeting microbial remediation were proposed.


Assuntos
Arsênio , Solo , Nitrogênio , Inundações , Clima
16.
Sensors (Basel) ; 22(22)2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36433362

RESUMO

Magnetic coupling resonance wireless power transfer can efficiently provide energy to intracranial implants under safety constraints, and is the main way to power fully implantable brain-computer interface systems. However, the existing maximum efficiency tracking wireless power transfer system is aimed at optimizing the overall system efficiency, but the efficiency of the secondary side is not optimized. Moreover, the parameters of the transmitter and the receiver change nonlinearly in the power control process, and the efficiency tracking mainly depends on wireless communication. The heat dissipation caused by the unoptimized receiver efficiency and the wireless communication delay in power control will inevitably affect neural activity and even cause damage, thus affecting the results of neuroscience research. Here, a linear-power-regulated wireless power transfer method is proposed to realize the linear change of the received power regulation and optimize the receiver efficiency, and a miniaturized linear-power-regulated wireless power transfer system is developed. With the received power control, the efficiency of the receiver is increased to more than 80%, which can significantly reduce the heating of fully implantable microsystems. The linear change of the received power regulation makes the reflected impedance in the transmitter change linearly, which will help to reduce the dependence on wireless communication and improve biological safety in received power control applications.


Assuntos
Temperatura Alta , Tecnologia sem Fio , Próteses e Implantes , Impedância Elétrica , Regulação da Temperatura Corporal
17.
Proc Natl Acad Sci U S A ; 119(44): e2209565119, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36306331

RESUMO

Efferent neurons are believed to play essential roles in maintaining auditory function. The lateral olivocochlear (LOC) neurons-which project from the brainstem to the inner ear, where they release multiple transmitters including peptides, catecholamines, and acetylcholine-are the most numerous yet least understood elements of efferent control of the cochlea. Using in vitro calcium imaging and patch-clamp recordings, we found that LOC neurons in juvenile and young adult mice exhibited extremely slow waves of activity (∼0.1 Hz). These seconds-long bursts of Na+ spikes were driven by an intrinsic oscillator dependent on L-type Ca2+ channels and were not observed in prehearing mice, suggesting an age-dependent mechanism underlying the intrinsic oscillator. Using optogenetic approaches, we identified both ascending (T-stellate cells of the cochlear nucleus) and descending (auditory cortex) sources of synaptic excitation, as well as the synaptic receptors used for such excitation. Additionally, we identified potent inhibition originating in the glycinergic medial nucleus of trapezoid body (MNTB). Conductance-clamp experiments revealed an unusual mechanism of electrical signaling in LOC neurons, in which synaptic excitation and inhibition served to switch on and off the intrinsically generated spike burst mechanism, allowing for prolonged periods of activity or silence controlled by brief synaptic events. Protracted bursts of action potentials may be essential for effective exocytosis of the diverse transmitters released by LOC fibers in the cochlea.


Assuntos
Núcleo Coclear , Corpo Trapezoide , Camundongos , Animais , Núcleo Coclear/fisiologia , Cóclea/fisiologia , Corpo Trapezoide/fisiologia , Neurônios/fisiologia , Potenciais de Ação/fisiologia
18.
Food Res Int ; 161: 111880, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36192913

RESUMO

Silver carp is a type of Asian carp that poses a threat to the United States. Unfortunately, producing Asian carp surimi in the US has been unsuccessful due to the high cost. Thus, exporting Asian carp to China and other Asian countries in the form of frozen deboned fish mince (without washing) would be a new way to create commercial value. This study was to explore the effects of compound cryoprotectants CC (sucrose, sorbitol, and sodium tripolyphosphate) and CC + SD (salted egg white) on unwashed silver carp mince during frozen storage. In the presence of CC, unwashed mince exerted benefits on gel property and water holding property. CC was able to retard protein oxidation as indicated by the retarded carbonyl content and lower loss in sulfhydryl content. Based on indicators of content of salt-soluble protein, α-helix, myosin heavy chain and intrinsic fluorescence intensity, CC addition inhibited protein aggregation by protecting the protein structure. The inclusion of SD did not show a cryoprotective effect or synergistic antioxidant effect with sucrose-sorbitol, but SD improved the gel strength within 4 weeks of freezing. Thus, CC can provide cryoprotective protection during frozen storage of silver carp mince. CC + SD provides a reference for long-distance transport and off-site production of frozen silver carp mince.


Assuntos
Carpas , Crioprotetores , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Crioprotetores/química , Crioprotetores/farmacologia , Produtos Pesqueiros/análise , Congelamento , Cadeias Pesadas de Miosina , Estresse Oxidativo , Agregados Proteicos , Proteínas , Sorbitol , Sacarose , Água
19.
Nano Lett ; 22(21): 8445-8454, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36255126

RESUMO

Receptor oligomerization is a highly complex molecular process that modulates divergent cell signaling. However, there is a lack of molecular tools for systematically interrogating how receptor oligomerization governs the signaling response. Here, we developed a DNA origami-templated aptamer nanoarray (DOTA) that enables precise programming of the oligomerization of receptor tyrosine kinases (RTK) with defined valency, distribution, and stoichiometry at the ligand-receptor interface. The DOTA allows for advanced receptor manipulations by arraying either monomeric aptamer ligands (mALs) that oligamerize receptor monomers to elicit artificial signaling or dimeric aptamer ligands (dALs) that preorganize the receptor dimer to recapitulate natural activation. We demonstrated that the multivalency and nanoscale spacing of receptor oligomerization coordinately influence the activation level of receptor tyrosine kinase signaling. Furthermore, we illustrated that DOTA-modulated receptor oligomerization could function as a signaling switch to promote the transition from epithelia to mesenchymal-like cells, demonstrating robust control over cellular behaviors. Together, we present a versatile all-in-one DNA nanoplatform for the systematical investigation and regulation of receptor-mediated cellular response.


Assuntos
DNA , Receptores Proteína Tirosina Quinases , Ligantes , Receptores Proteína Tirosina Quinases/genética , Oligonucleotídeos , Transdução de Sinais
20.
Neuroimage Clin ; 36: 103229, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36252555

RESUMO

BACKGROUND: Small vessel disease (SVD) is highly prevalent in the elderly and associated with an increased risk of dementia and stroke. SVD may have disturbed cerebrospinal fluid (CSF) flow, which can compromise waste clearance and accelerate disease progression. METHODS: We retrospectively included 146 SVD patients from a prospectively collected dataset, with one- or two-year follow-up data in 61 patients. The coupling strength between the global blood-oxygen-level-dependent (gBOLD) signal and CSF inflow was used to reflect CSF dynamics. We performed regression analyses to investigate the association between the gBOLD-CSF coupling index and the severity of SVD and vascular risk factors. Longitudinal analysis was carried out to investigate causal relationships. RESULTS: Patients with severe SVD had significantly decreased gBOLD-CSF coupling (ß = -0.180, p = 0.032). Dilation of perivascular spaces in the basal ganglia area (ß = -0.172, p = 0.033) and diabetes (ß = -0.204, p = 0.014) were associated with reduced gBOLD-CSF coupling. In longitudinal analyses, diabetes was associated with faster decline in gBOLD-CSF coupling (ß = 0.20, p = 0.039), while perivascular space (PVS) dilation in the centrum semiovale showed a opposite relationship (ß = -0.20, p = 0.041). The gBOLD-CSF coupling could not predict SVD progression. CONCLUSION: Altered CSF flow is associated with the severity of SVD.

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