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1.
FASEB J ; 36(9): e22488, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35929441

RESUMEN

DCBLD2 is a neuropilin-like transmembrane protein that is up-regulated during arterial remodeling in humans, rats, and mice. Activation of PDGFR-ß via PDGF triggers receptor phosphorylation and endocytosis. Subsequent activation of downstream signals leads to the stimulation of phenotypic conversion of VSMCs and arterial wall proliferation, which are common pathological changes in vascular remodeling diseases such as atherosclerosis, hypertension, and restenosis after angioplasty. In this study, we hypothesized that DCBLD2 regulates neointimal hyperplasia through the regulation of PDGFR-ß endocytosis of vascular smooth muscle cells (VSMCs) through Caveolin-1 (Cav-1). Compared with wild-type (WT) mice or control littermate mice, the germline or VSMC conditional deletion of the Dcbld2 gene resulted in a significant increase in the thickness of the tunica media in the carotid artery ligation. To elucidate the underlying molecular mechanisms, VSMCs were isolated from the aorta of WT or Dcbld2-/- mice and were stimulated with PDGF. Western blotting assays demonstrated that Dcbld2 deletion increased the PDGF signaling pathway. Biotin labeling test and membrane-cytosol separation test showed that after DCBLD2 was knocked down or knocked out, the level of PDGFR-ß on the cell membrane was significantly reduced, while the amount of PDGFR-ß in the cytoplasm increased. Co-immunoprecipitation experiments showed that after DCBLD2 gene knock-out, the binding of PDGFR-ß and Cav-1 in the cytoplasm significantly increased. Double immunofluorescence staining showed that PDGFR-ß accumulated Cav-1/lysosomes earlier than for control cells, which indicated that DCBLD2 gene knock-down or deletion accelerated the endocytosis of PDGF-induced PDGFR-ß in VSMCs. In order to confirm that DCBLD2 affects the relationship between Cav-1 and PDGFR-ß, proteins extracted from VSMCs cultured in vitro were derived from WT and Dcbld2-/- mice, whereas co-immunoprecipitation suggested that the combination of DCBLD2 and Cav-1 reduced the bond between Cav-1 and PDGFR-ß, and DCBLD2 knock-out was able to enhance the interaction between Cav-1 and PDGFR-ß. Therefore, the current results suggest that DCBLD2 may inhibit the caveolae-dependent endocytosis of PDGFR-ß by anchoring the receptor on the cell membrane. Based on its ability to regulate the activity of PDGFR-ß, DCBLD2 may be a novel therapeutic target for the treatment of cardiovascular diseases.


Asunto(s)
Caveolina 1 , Músculo Liso Vascular , Animales , Caveolina 1/genética , Caveolina 1/metabolismo , Proliferación Celular , Células Cultivadas , Endocitosis , Humanos , Hiperplasia/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Ratas , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo
2.
Chem Biodivers ; 19(4): e202100902, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35199932

RESUMEN

Two olean-27-carboxylic acid-type triterpenoids (1 and 2) were isolated from Saxifraga umbellulata (Saxifragaceae), representing the first case in the chemical discoveries of genus Saxifraga. Compound 1 was determined to be a new compound named 'Saxifragic acid' based on the comprehensive spectroscopic and X-ray crystallographic analyses. Compound 2 (deacetylated saxifragic acid) is a known compound reported before, but its absolute configuration through X-ray crystallographic analyses was first described here. In addition, their cytotoxicity against five digestive human cancer cell lines (BGC-823, GBC-SD, CCC-9810, HT-29, and HepG2) and hepatoprotective activity against CCl4 -induced L-o2 cell injury in vitro were evaluated. Interestingly, UPLC-QTOFMS analysis showed that these two compounds could be used as chemical markers to discriminate between S. umbellulata and S. tangutica, both of which are used for the treatment of hepatobiliary diseases in traditional Tibetan medicine.


Asunto(s)
Saxifragaceae , Triterpenos , Ácidos Carboxílicos , Humanos , Estructura Molecular , Saxifragaceae/química , Triterpenos/farmacología
3.
Angew Chem Int Ed Engl ; 61(34): e202207319, 2022 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-35703374

RESUMEN

Synthetic messenger RNA (mRNA) switches are powerful synthetic biological tools that can sense cellular molecules to manipulate cell fate. However, their performances are limited by high output signal noise due to leaky output protein expression. Here, we designed a readout control module that disables protein leakage from generating signal. Aptamer array on the switch guides the inactive output protein to self-assemble into functional assemblies that generate output signal. Leaky protein expression fails to saturate the array, thus produces marginal signal. In this study, we demonstrated that switches with this module exhibit substantially lower signal noise and, consequently, higher input sensitivity and wider output range. Such switches are applicable for different types of input molecules and output proteins. The work here demonstrates a new type of spatially guided protein self-assembly, affording novel synthetic mRNA switches that promise accurate cell manipulation for biomedical applications.


Asunto(s)
Oligonucleótidos , Biología Sintética , ARN Mensajero/genética
4.
Biomed Eng Online ; 19(1): 52, 2020 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-32552718

RESUMEN

BACKGROUND: Colorectal cancer is the third leading cause of cancer-related deaths worldwide. Sonodynamic therapy (SDT) is an emerging cancer therapy, and in contrast to photodynamic therapy, could non-invasively reach deep-seated tissues and locally activates a sonosensitizer preferentially accumulated in the tumor area to produce cytotoxicity effects. In comparison with traditional treatments, SDT may serve as an alternative strategy for human colon cancer treatment. Here, we investigated the sonodynamic effect using sinoporphyrin sodium (DVDMS) as a novel sonosensitizer on human colon cancer cells in vitro. RESULTS: The absorption spectra of DVDMS revealed maximum absorption at 363 nm wavelength and emission peak at 635 nm. Confocal microscopy images revealed the DVDMS was primarily localized in the cytoplasm, while no evident signal was detected within the nuclei. Flow cytometry analysis showed rapid intracellular uptake of DVDMS by two types of human colon cancer cells (HCT116 and RKO). Cell viability of HCT116 was tolerant with the concentration of DVDMS up to 20 µg/mL, while the case of RKO was 5 µg/mL. In comparison with the control group, the SDT-treated groups of these two types of human colon cancer cells showed significant increase in cellular apoptosis and necrosis ratio. Increased intracellular reactive oxygen species (ROS) production was detected, indicating the involvement of ROS in mediating SDT effects. CONCLUSION: DVDMS results an effective sonosensitizer for the ultrasound-mediated cancer cell killing, and its anticancer effect seems to rely on its ability to produce ROS under ultrasound exposure.


Asunto(s)
Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Porfirinas/farmacología , Terapia por Ultrasonido/métodos , Apoptosis/efectos de los fármacos , Transporte Biológico , Células HCT116 , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Necrosis/inducido químicamente , Porfirinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
5.
Cell Chem Biol ; 31(1): 150-162.e7, 2024 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-38035883

RESUMEN

Accurately characterizing cell types within complex cell structures provides invaluable information for comprehending the cellular status during biological processes. In this study, we have developed an miRNA-switch cocktail platform capable of reporting and tracking the activities of multiple miRNAs (microRNAs) at the single-cell level, while minimizing disruption to the cell culture. Drawing on the principles of traditional miRNA-sensing mRNA switches, our platform incorporates subcellular tags and employs intelligent engineering to segment three subcellular regions using two fluorescent proteins. These designs enable the quantification of multiple miRNAs within the same cell. Through our experiments, we have demonstrated the platform's ability to track marker miRNA levels during cell differentiation and provide spatial information of heterogeneity on outlier cells exhibiting extreme miRNA levels. Importantly, this platform offers real-time and in situ miRNA reporting, allowing for multidimensional evaluation of cell profile and paving the way for a comprehensive understanding of cellular events during biological processes.


Asunto(s)
MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Diferenciación Celular , Perfilación de la Expresión Génica/métodos
6.
Chem Commun (Camb) ; 60(41): 5427-5430, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38685869

RESUMEN

Synthetic mRNA circuits commonly sense input to produce binary output signals for cell separation. Based on virus-origin cap-independent translation initiation machinery and RBP-aptamer interaction, we designed smart synthetic mRNA-based circuits that sense single input molecules to bidirectionally tune output signals in an orthogonal manner, enabling high-resolution separation of cell populations.


Asunto(s)
Separación Celular , ARN Mensajero , Humanos , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Separación Celular/métodos , ARN Mensajero/genética , ARN Mensajero/metabolismo
7.
Front Oncol ; 13: 1080237, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36776308

RESUMEN

Background: Thioredoxin-1 (TXN), a redox balance factor, plays an essential role in oxidative stress and has been shown to act as a potential contributor to various cancers. This study evaluated the role of TXN in lung cancer by bioinformatics analyses. Materials and methods: Genes differentially expressed in lung cancer and oxidative stress related genes were obtained from The Cancer Genome Atlas, Gene Expression Omnibus and GeneCards databases. Following identification of TXN as an optimal differentially expressed gene by bioinformatics, the prognostic value of TXN in lung cancer was evaluated by univariate/multivariate Cox regression and Kaplan-Meier survival analyses, with validation by receiver operation characteristic curve analysis. The association between TXN expression and lung cancer was verified by immunohistochemical analysis of the Human Protein Atlas database, as well as by western blotting and qPCR. Cell proliferation was determined by cell counting kit-8 after changing TXN expression using lentiviral transfection. Results: Twenty differentially expressed oxidative stress genes were identified. Differential expression analysis identified five genes (CASP3, CAT, TXN, GSR, and HSPA4) and Kaplan-Meier survival analysis identified four genes (IL-6, CYCS, TXN, and BCL2) that differed significantly in lung cancer and normal lung tissue, indicating that TXN was an optimal differentially expressed gene. Multivariate Cox regression analysis showed that T stage (T3/T4), N stage (N2/N3), curative effect (progressive diseases) and high TXN expression were associated with poor survival, although high TXN expression was poorly predictive of overall survival. TXN was highly expressed in lung cancer tissues and cells. Knockdown of TXN suppressed cell proliferation, while overexpression of TXN enhanced cell proliferation. Conclusion: High expression of TXN plays an important role in lung cancer development and prognosis. Because it is a prospective prognostic factor, targeting TXN may have clinical benefits in the treatment of lung cancer.

8.
Ultrason Sonochem ; 94: 106346, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36870921

RESUMEN

Recently, emerging evidence has demonstrated that cavitation actually creates important bidirectional channels on biological barriers for both intratumoral drug delivery and extratumoral biomarker release. To promote the barrier-breaking effects of cavitation for both therapy and diagnosis, we first reviewed recent technical advances of ultrasound and its contrast agents (microbubbles, nanodroplets, and gas-stabilizing nanoparticles) and then reported the newly-revealed cavitation physical details. In particular, we summarized five types of cellular responses of cavitation in breaking the plasma membrane (membrane retraction, sonoporation, endocytosis/exocytosis, blebbing and apoptosis) and compared the vascular cavitation effects of three different types of ultrasound contrast agents in breaking the blood-tumor barrier and tumor microenvironment. Moreover, we highlighted the current achievements of the barrier-breaking effects of cavitation in mediating drug delivery and biomarker release. We emphasized that the precise induction of a specific cavitation effect for barrier-breaking was still challenged by the complex combination of multiple acoustic and non-acoustic cavitation parameters. Therefore, we provided the cutting-edge in-situ cavitation imaging and feedback control methods and suggested the development of an international cavitation quantification standard for the clinical guidance of cavitation-mediated barrier-breaking effects.


Asunto(s)
Medios de Contraste , Ultrasonido , Ultrasonido/métodos , Sistemas de Liberación de Medicamentos , Acústica , Ultrasonografía , Microburbujas
9.
Int J Pharm ; 645: 123359, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37652279

RESUMEN

This study employed superficial ultrasound exposure of good ocular safety and a drug-loaded hydrogel of long residence time to enable transscleral delivery. First, we designed an acoustic adaptor to limit the ultrasound exposure depth to 1.59 mm to protect the posterior eye segments. Then, we optimized the alginate/polyacrylamide ratio (3:7) of a dual-crosslinked hydrogel to enable ultrasound-triggered release of model drug (70-kDa fluorescein isothiocyanate-conjugated dextran). Using fluorescence imaging to quantify the drug release, we showed that the developed method resulted in enhanced transscleral delivery in both ex vivo porcine scleras (2.6-fold) and in vivo rabbit scleras (2.2-fold). We also demonstrated that the method increased the drug penetration depth to the whole thickness of the sclera. In particular, the drug release efficiency increased with increasing ultrasound exposure time (1 and 3 min) and intensity (8, 19, 36, and 61 mW/cm2). Using scanning electron microscopy, we revealed that ultrasound exposure resulted in rougher surfaces and microscale rupture of the hydrogel. Moreover, Masson staining of scleral slices showed that the integrity of the top scleral fibers was disturbed by ultrasound exposure, and this disturbance recovered 3 days later. Our work demonstrates that the developed method holds great potential for mediating ocular drug delivery.


Asunto(s)
Hidrogeles , Segmento Posterior del Ojo , Animales , Conejos , Porcinos , Permeabilidad , Esclerótica , Ultrasonografía , Sistemas de Liberación de Medicamentos/métodos
10.
Turk Neurosurg ; 33(5): 722-730, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35023138

RESUMEN

AIM: To evaluate the relationship between Golgi phosphoprotein 3 (GOLPH3) and vasculogenic mimicry (VM) in glioblastoma cells. MATERIAL AND METHODS: Glioma tissues from 40 glioma patients with different pathological grades were collected. GOLPH3 and VM were evaluated by immunostaining in glioma tissues. Then, the correlation between GOLPH3 and VM were analyzed clinically. Additionally, a GOLPH3-downregulation lentivirus was constructed and transfected into the human primary glioblastoma cell line, U-87 MG. Afterwards, apoptosis, migration and invasion were assessed to determine the effects of downregulation GOLPH3. Then, E-cadherin and matrix metalloproteinase 2 (MMP2) were detected for assessment of the epithelial mesenchymal transition (EMT). RESULTS: GOLPH3 and VM were found to be positively correlated following clinical analysis (p < 0.01, r=0.788). Furthermore, GOLPH3 downregulation suppressed the migration and invasion of U87 MG cells (p < 0.05), followed by upregulation of E-cadherin and downregulation of MMP2. CONCLUSION: Collectively, our results demonstrate that GOLPH3 promoted VM in glioblastoma cells and that the corresponding mechanism was associated with the EMT. Our finding suggests that GOLPH3 may represent a promising therapeutic target for mitigating the recurrence and invasion of gliomas.


Asunto(s)
Glioblastoma , Glioma , Humanos , Glioblastoma/patología , Metaloproteinasa 2 de la Matriz , Transición Epitelial-Mesenquimal , Línea Celular Tumoral , Movimiento Celular , Glioma/patología , Cadherinas/metabolismo , Neovascularización Patológica , Proteínas de la Membrana
11.
ACS Synth Biol ; 12(9): 2516-2523, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37652441

RESUMEN

Synthetic mRNA circuits manipulate cell fate by controlling output protein expression via cell-specific input molecule detection. Most current circuits either repress or enhance output production upon input binding. Such binary input-output mechanisms restrict the fine-tuning of protein expression to control complex cellular events. Here we designed mRNA circuits using enhancer/repressor modules that were independently controlled by different input molecules, resulting in bidirectional output regulation; the maximal enhancement over maximal repression was 57 fold. The circuit either enhances or represses protein production in different cells based on the difference in the expression of two microRNAs. This study examined novel bidirectional circuit designs capable of fine-tuning protein production by sensing multiple input molecules. It also broadened the scope of cell manipulation by synthetic mRNA circuits, facilitating the development of mRNA circuits for precise cell manipulation and providing cell-based solutions to biomedical problems.


Asunto(s)
MicroARNs , Diferenciación Celular , ARN Mensajero/genética
12.
Ultrason Sonochem ; 101: 106685, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37976565

RESUMEN

As a non-viral transfection method, ultrasound and microbubble-induced sonoporation can achieve spatially targeted gene delivery with synergistic immunostimulatory effects. Here, we report for the first time the application of sonoporation for improving DNA vaccination performance. This study developed a new microbubble design with nanoscale DNA/PEI complexes loaded onto cationic microbubbles to attain significant increases in DNA-loading capacity (0.25 pg per microbubble) and in vitro transfection efficiency. Using live-cell imaging, we revealed the membrane perforation and cellular delivery characteristics of sonoporation. Using luciferase reporter gene for in vivo transfection, we showed that sonoporation increased the transfection efficiency by 40.9-fold when compared with intramuscular injection. Moreover, we comprehensively optimized the sonoporation protocol and further increased the transfection efficiency by 43.6-fold. Immunofluorescent staining results showed that sonoporation effectively activated the MHC-II+ immune cells. Using a hepatitis B DNA vaccine, sonoporation induced significantly higher serum antibody levels when compared with intramuscular injection, and the antibodies sustained for 56 weeks. In addition, we recorded the longest reported expression period (400 days) of the sonoporation-delivered gene. Whole genome resequencing confirmed that the gene with stable expression existed in an extrachromosomal state without integration. Our results demonstrated the potential of sonoporation for efficient and safe DNA vaccination.


Asunto(s)
Microburbujas , Vacunas de ADN , Plásmidos/genética , Vacunas de ADN/genética , ADN/genética , Vacunación
13.
iScience ; 26(4): 106471, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37096034

RESUMEN

Ground-level ozone threatens rice production, which provides staple food for more than half of the world's population. Improving the adaptability of rice crops to ozone pollution is essential to ending global hunger. Rice panicles not only affect grain yield and grain quality but also the adaptability of plants to environmental changes, but the effects of ozone on rice panicles are not well understood. Through an open top chamber experiment, we investigated the effects of long-term and short-term ozone on the traits of rice panicles, finding that both long-term and short-term ozone significantly reduced the number of panicle branches and spikelets in rice, and especially the fertility of spikelets in hybrid cultivar. The reduction in spikelet quantity and fertility because of ozone exposure is caused by changes in secondary branches and attached spikelet. These results suggest the potential for effective adaptation to ozone by altering breeding targets and developing growth stage-specific agricultural techniques.

14.
Int J Pharm ; 617: 121595, 2022 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-35189315

RESUMEN

Skin disruptions of micrometer- or submillimeter-diameter generated by microneedle or laser ablation can be used for intradermal vaccination. Here, we report a new skin-disruption method that uses highly-focused ultrasound to controllably perforate murine skin. We showed that programming of ultrasound parameters varied skin perforation area from 0.078 ± 0.045 mm2 to 1.295 ± 0.279 mm2. The skin perforation area increased with increasing ultrasound pressure and exposure time, and decreased with increasing ultrasound frequency and incidence angle. Moreover, successful perforation can be monitored using ultrasound pulse-echo imaging. We found that ultrasound perforation elevated local skin expression of heat shock protein 70 and effectively attracted MHC II-positive immune cells after intradermal delivery of Hepatitis B surface antigen (HBsAg). We demonstrated that the antigen dose delivered by ultrasound perforation can be effectively modulated via programmable perforation arrays (comprised of 1 × 2, 1 × 3, 1 × 5 or 3 × 3 areas of exposure). Using a 1 × 3 perforation array for vaccination, the measured mean optical density (OD) value of serum anti-HBsAg IgG was slightly higher than that of intradermal injection. The addition of an adjuvant of recombinant cholera toxin B further increased OD values of anti-HBsAg IgG. This ultrasound perforation method holds great promise for monitorable and programmable intradermal vaccination.


Asunto(s)
Vacunas contra Hepatitis B , Vacunación , Adyuvantes Inmunológicos , Animales , Antígenos de Superficie de la Hepatitis B , Inyecciones Intradérmicas/métodos , Ratones , Vacunación/métodos
15.
Mol Clin Oncol ; 16(4): 83, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35251634

RESUMEN

The association between endoplasmic reticulum stress (ERS) and apoptosis has been extensively studied. Cyclic adenosine monophosphate responsive element binding protein 3 like 1 (CREB3L1) has an important role in the development of glioma. In the present study, the potential association between ERS-induced apoptosis and CREB3L1 and its clinical implications were investigated. From a total of 30 cases, brain gliomas with different pathological grades surgically resected at the Department of Neurosurgery of the Affiliated Hospital of Guizhou Medical University (Guiyang, China) between January 2018 and January 2019 were collected. The expression of CREB3L1 and ERS-related proteins in gliomas with different degrees of malignancy was detected by immunohistochemistry. Furthermore, U87-MG glioma cells were cultured in vitro and treated with different concentrations of ERS inducer thapsigargin (TG). The Cell Counting Kit-8 (CCK-8) assay was performed to detect changes in cell activity at different incubation times and drug concentrations. Cell apoptosis was detected by Annexin Ⅴ-FITC/propidium iodide double staining and the protein expression levels of CREB3L1 and ERS were detected by western blot analysis. Immunohistochemical analysis suggested that the expression levels of CREB3L1, glucose-regulated protein, 78 kDa (GRP78) and C/EBP-homologous protein (CHOP) in World Health Organization (WHO) grade I glioma were higher than those in WHO grade Ⅱ-Ⅳ (all P<0.01). The results of the CCK-8 assay suggested that the activity of U87-MG glioma cells was significantly decreased after treatment with TG (all P<0.05), and this effect was time- and drug concentration-dependent. Flow cytometric analysis indicated that the apoptotic rate of the cells was increased, which was significant when the concentration of TG was 0.1 µmol/l (P<0.01). Furthermore, the protein expression of CREB3L1, GRP78 and CHOP in glioma cells treated with TG was increased (P<0.05). However, the expression level of Bcl-2 decreased (P<0.05). In conclusion, ERS may reduce the cell proliferative activity and promote apoptosis through mediating CREB3L1 expression. CREB3L1 may be a novel potential target for glioma therapy.

16.
Foods ; 11(21)2022 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-36359939

RESUMEN

Rice production affects the food security and socioeconomic status of over half the world's population. Rice-producing countries, however, are facing population growth, reduction in rice planting area, and global change. Understanding the trends of rice production and major determinants is key to regulating rice production. We thus analyzed the trends of rice production and related determinants in China from 2001 to 2021, revealing that the annual rice production (TRP) has risen steadily (r = 0.929, p < 0.0001) in recent 20 years. TRP in 2021 was 19.9% higher than that in 2001, which was primarily achieved by the increment of middle rice production (MRP). MRP increased by 46.2% from 2000 to 2018, and grain yield per unit area (GPA) was the largest in middle rice. The enhancement of GPAs is significantly correlated with the consumption of agricultural resources and the number of released rice cultivars, but variations exist. TRP and GPA vary in different provinces; Hunan (25 ± 2 megatons) and Xinjiang (8364 ± 806 kg/hectare) show the largest values, respectively. TRP could be further increased by 13.8% by improving MRP. The results suggest that rice production in China has a large potential to be further improved through regulations.

17.
Carbohydr Polym ; 293: 119727, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35798423

RESUMEN

Multifunctional hydrogels show potential applications in actuators and wearable sensors. However, it is still a challenge to develop a photothermal responsive conductive hydrogel with high transparency, mechanical properties, broad sensing range, and low-temperature resistance. In this work, a transparent, photothermal responsive, and highly stretchable alginate-based hydrogels was feasibly constructed by adding two-dimensional non-layered molybdenum dioxide nanosheets (2D-MoO2) to sodium alginate/polyacrylamide mixture and then soaking into the calcium chloride solution. The introduction of 2D-MoO2 renders the hydrogels excellent photothermal properties and controllable photomechanical deformation under near-infrared irradiation, while maintaining high transparency (~60 %).The calcium ions give the hydrogel excellent mechanics, conductivity, and freezing tolerance concurrently. The transparent hydrogel-based sensor shows wide sensing range (0-1800 %) and cycling stability in detecting deformations and real-time human motions even in harsh environments. Therefore, this work provides a new route for generating transparent multifunctional hydrogels towards the applications of remote actuation and strain sensing.


Asunto(s)
Hidrogeles , Dispositivos Electrónicos Vestibles , Alginatos , Conductividad Eléctrica , Humanos , Movimiento (Física)
18.
Mol Ther Nucleic Acids ; 30: 300-310, 2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36320322

RESUMEN

Synthetic mRNAs are rising rapidly as alternative therapeutic agents for delivery of proteins. However, the practical use of synthetic mRNAs has been restricted by their low cellular stability as well as poor protein production efficiency. The key roles of poly(A) tail on mRNA biology inspire us to explore the optimization of tail sequence to overcome the aforementioned limitations. Here, the systematic substitution of non-A nucleotides in the tails revealed that cytidine-containing tails can substantially enhance the protein production rate and duration of synthetic mRNAs both in vitro and in vivo. Such C-containing tails shield synthetic mRNAs from deadenylase CCR4-NOT transcription complex, as the catalytic CNOT proteins, especially CNOT6L and CNOT7, have lower efficiency in trimming of cytidine. Consistently, these enhancement effects of C-containing tails were observed on all synthetic mRNAs tested and were independent of transfection reagents and cell types. As the C-containing tails can be used along with other mRNA enhancement technologies to synergically boost protein production, we believe that these tails can be broadly used on synthetic mRNAs to directly promote their clinical applications.

19.
Artículo en Inglés | MEDLINE | ID: mdl-35966744

RESUMEN

Background. In the past, moxibustion has been widely used to treat endocrine system disorders, but evidence of its effectiveness is scarce at this point. The aim of this multicenter, randomized, controlled trial is to evaluate the efficacy and safety of treating menopausal obesity with moxibustion. Methods/Design. There are six centers taking part in this randomized, controlled, parallel trial. A total of 216 patients with menopausal obesity will be randomly divided into two equal groups: the "moxibustion for harmonization of Yin and Yang" group and the gentle moxibustion group. A 12-week study period with moxibustion will be preceded by a 1-week baseline, followed by a 12-week follow-up. We will conduct an interim analysis to determine whether or not the treatment is efficacious and safe after 216 participants have completed a 12-week treatment period. Evaluations will be conducted at weeks 0, 4, 8, 12, 18, and 24. The main outcome is waist circumference (WC), and the rate of WC reduction will be compared to the baseline. An intention-to-treat analysis will be performed with a two-sided P value of <0.05 considered significant. Participants who withdraw from the trial will be analyzed according to the intention-to-treat formula (ITT). Discussion. These results will be used to support selecting the right moxibustion prescription and guiding the improvement of clinical efficacy. This trial will provide convincing evidence of moxibustion's effectiveness and safety in the treatment of obesity by "moxibustion for harmonization of Yin and Yang," which will be conducive to the promotion and clinical application of the theory of "moxibustion for harmonization of Yin and Yang." Trial Registration. This trial is registered with Clinical Trials.gov: NCT04943705 (registered on June 27, 2021).

20.
Int J Biol Macromol ; 222(Pt A): 487-496, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36174853

RESUMEN

Ionic conductive hydrogels prepared from various biological macromolecules are ideal materials for the manufacture of human motion sensors from the perspective of resource regeneration and environmental sustainability. However, it is still challenging to prepare hydrogels with both high toughness and self-healing ability. In this study, lignin-based ß-CD-PVA (LCP) self-healing conductive hydrogels with high tensile properties were prepared by one-step method using alkali lignin as a plasticizer. Compared with PVA hydrogel, the maximum storage modulus and elongation were increased by 2.5 and 20.0 times, respectively. Uniform distribution of lignin can increase the fluidity and distance of polymer molecular chains, thus improving the viscoelastic and tensile properties of the LCP self-healing hydrogel. LCP hydrogels can maintain self-healing ability in both high (45 °C) and low temperature (0 °C) environments, and the self-healing ability is not affected by pH. Moreover, it also has good conductivity, anti-bacterial, thermostability, and anti-UV property, which has a good application prospect in the field of 3D printing and wearable electronic devices, which expands the efficient utilization of lignin in biorefinery.


Asunto(s)
Hidrogeles , Dispositivos Electrónicos Vestibles , Humanos , Hidrogeles/farmacología , Hidrogeles/química , Lignina , Conductividad Eléctrica , Antibacterianos
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