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A new method of harmonic beam coaxial combination (HBCC) from two intra-cavity frequency doubling branches was demonstrated. Firstly, two identical nanosecond (ns) 532â nm green lasers with high power and good beam quality were created. Each green laser was constructed of an intra-cavity frequency doubling branch based on a laser diode (LD) end-pumped acousto-optical (AO) Q-switched 1064â nm Nd:YVO4 laser in a LiB3O5 (LBO) nonlinear crystal. Each branch generated about 45â W green output at a 50â kHz pulse repetition rate (PRR) with diffraction limited beam quality. The first green beam was injected into the LBO crystal in the second branch, and the pulses from the two branches did not exist simultaneously. Then, the HBCC was performed. Consequently, an 83â W combined green output power at 532â nm was obtained with a combination efficiency of 92.2%. The PRR of the HBCC pulse was doubled to be 100â kHz, with a pulse width of about 22â ns, corresponding to a single pulse energy of 0.83â mJ and a peak power of 37.73â kW. The combined beam quality factor was measured to be M x2 = 1.80 in the x direction and M y2 = 1.71 in the y direction, respectively. Moreover, many more beams could also be combined with this method for further scaling the green power.
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Previous research has shown that moral choice depends on language, a phenomenon known as the moral foreign language effect (mFLE). The current study examines the influence of social distance on the mFLE. In Experiment 1, 200 participants were randomly assigned to either close or distant social distance in English or Chinese. In Experiment 2, 188 participants were randomly assigned to either English or Chinese and were presented with eight moral dilemmas, each with five different levels of social distance. After reading the dilemma, participants made a choice on a binary scale (Yes/No) in both Experiments 1 and 2 or on a more sensitive 100-point scale in Experiment 2. The results showed that the mFLE was present in distant social distance but absent in close social distance. Finally, a meta-analysis of the results from both studies confirmed the effect of social distance on the mFLE. These findings demonstrate that social distance might play an important role in moderating the mFLE in moral judgment.
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Juicio , Principios Morales , Humanos , LenguajeRESUMEN
The application of hydrogels in bone repair is limited due to their low mechanical strength. Simulating bone extracellular matrix, methylacrylylated gelatin (GelMA)/methylacrylylated hyaluronic acid (HAMA)/nano-hydroxyapatite(nHap) composite hydrogels were prepared by combining the double network strategy and composite of nHap in this study. The precursor solutions of the composite hydrogels were injectable due to their shear thinning property. The compressive elastic modulus of the composite hydrogel was significantly enhanced, the fracture strength of the composite hydrogel nearly reached 1 MPa, and the composite hydrogel retained its high water content at above 88%. The composite hydrogels possess good compatibility with BMSCS and have the potential to be used as injectable hydrogels for bone defect treatment.
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Thyroid cancer is one of the most common endocrine malignancies. Differentiated thyroid cancer (DTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). DTC generally has a good prognosis. However, tumor dedifferentiation or defect in certain cell death mechanism occurs in a subset of DTC patients, leading to RAI resistance. Therefore, developing novel therapeutic approaches that enhance RAI sensitivity are still warranted. We found that curcumin, an active ingredient in turmeric with anti-cancer properties, rapidly accumulated in the mitochondria of thyroid cancer cells but not normal epithelial cells. Curcumin treatment triggered mitochondrial membrane depolarization, engulfment of mitochondria within autophagosomes and a robust decrease in mitochondrial mass and proteins, indicating that curcumin selectively induced mitophagy in thyroid cancer cells. In addition, curcumin-induced mitophagic cell death and its synergistic cytotoxic effect with radioiodine could be attenuated by autophagy inhibitor, 3-methyladenine (3-MA). Interestingly, the mechanism of mitophagy-inducing potential of curcumin was its unique mitochondria-targeting property, which induced a burst of SDH activity and excessive ROS production. Our data suggest that curcumin induces mitochondrial dysfunction and triggers lethal mitophagy, which synergizes with radioiodine to kill thyroid cancer cells.
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Curcumina , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/tratamiento farmacológico , Curcumina/farmacología , Radioisótopos de Yodo , Succinato Deshidrogenasa/metabolismo , Mitofagia , Línea Celular Tumoral , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/tratamiento farmacológico , Mitocondrias/metabolismoRESUMEN
BACKGROUND: Due to dedifferentiation of tumor cells, manifested by a decreased expression of iodide-handling genes in thyrocytes, some thyroid carcinomas lose their capability for radioiodine concentration and gradually develop radioactive iodine (RAI) resistance. This work aimed to investigate the role of tumor microenvironment (TME) in the process of tumor cell dedifferentiation. MATERIALS AND METHODS: Bioinformatic analyses and subsequent immunohistochemistry (IHC) and western blot assays were performed in papillary thyroid carcinoma (PTC) and matched normal tissue. ELISA was used to assess the secretion of cytokines under the stimulation of pharmacological endoplasmic reticulum (ER) stress inducer. RESULTS: Higher levels of pro-inflammatory cytokines, interleukin 6 (IL-6) and (C-X-C motif chemokine ligand 8 (CXCL8), were found in thyroid cancer tissues compared with matched normal tissues. ER stress, induced by stressful environmental stimuli, such as nutrient deprivation and hypoxia, occurred in thyroid tumors. Classic ER stress inducers, thapsigargin (Tg) and tunicamycin (Tm), promoted the expression of IL6 and CXCL8 in thyroid cancer cells at mRNA and protein levels. Of note, rIL-6 and rCXCL8 promoted the dedifferentiation of thyroid cancer cells or even non-transformed cells in an autocrine/paracrine manner, weakening radioiodine uptake ability of thyroid cancer cells. Intriguingly, sorafenib, a multiple kinase inhibitor (MKI), could potently suppress not only ER stress-induced but also basal expressions of IL-6 and CXCL8 in thyroid cancer cells. CONCLUSIONS: The inflammatory TME could regulate cell dedifferentiation, leading to loss of thyroid-specific gene expressions, through reciprocal interaction between thyroid tumor cells and follicular cells. Our study provides a new perspective on the mechanisms of how inflammatory TME affects DTC dedifferentiation.
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Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/patología , Radioisótopos de Yodo , Yoduros , Interleucina-6 , Microambiente TumoralRESUMEN
BACKGROUND: Insecticide resistance continuously poses a threat to agricultural production. Chemosensory protein-mediated resistance is a new mechanism of insecticide resistance discovered in recent years. In-depth research on resistance mediated by chemosensory proteins (CSPs) provides new insight into aid insecticide resistance management. RESULTS: Chemosensory protein 1 in Plutella xylostella (PxCSP1) was overexpressed in the two indoxacarb-resistant field populations and PxCSP1 has a high affinity with indoxacarb. PxCSP1 was upregulated when exposed to indoxacarb and the knockdown of this gene elevated sensitivity to indoxacarb, which demonstrate that PxCSP1 is involved in the indoxacarb resistance. Considering that CSPs may confer resistance in insects via binding or sequestering, we explored the binding mechanism of indoxacarb in PxCSP1-mediated resistance. Using molecular dynamics simulations and site-directed mutation, we found that indoxacarb forms a solid complex with PxCSP1 mainly through van der Waals interactions and electrostatic interactions. Between these, the electrostatic interaction provided by the Lys100 side chain in PxCSP1, and especially the hydrogen bonding between the NZ atom and the O of the carbamoyl carbonyl group of indoxacarb, are the key factors for the high affinity of PxCSP1 to indoxacarb. CONCLUSIONS: The overexpression of PxCPS1 and its high affinity to indoxacarb is partially responsible for indoxacarb resistance in P. xylostella. Modification of indoxacarb's carbamoyl group has the potential to alleviate indoxacarb resistance in P. xylostella. These findings will contribute to solving chemosensory protein-mediated indoxacarb resistance and provide a better understanding of the insecticide resistance mechanism. © 2023 Society of Chemical Industry.
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Insecticidas , Mariposas Nocturnas , Animales , Mariposas Nocturnas/genética , Insecticidas/farmacología , Oxazinas/farmacología , Resistencia a los Insecticidas/genéticaRESUMEN
BACKGROUND: In recent years, the design of food-grade Pickering emulsion delivery systems has become an effective strategy for improving the low bioavailability of bioactive substances. Protein-based Pickering emulsions have received extensive attention because of a high biocompatibility and loading capacity. The bioavailability of active substances is mainly evaluated by simulating in vitro gastrointestinal digestion. As a model organism for antioxidation and anti-aging, Caenorhabditis elegans can provide additional biological information for the in vivo utilization of active substances. RESULTS: After the introduction of caffeic acid, the average particle size and Zeta potential of the casein-caffeic acid covalent complex nanoparticles (CCP) were 171.11 nm and - 37.73 mV, respectively. The three-phase contact angle was also increased to 89.8°. By using CCP to stabilize Pickering emulsion (CCE), the retention quantity of the embedded curcumin increased by 2.19-fold after 28 days. In the simulated gastric digestion, curcumin degradation in CCE was reduced by 61.84%, released slowly in the intestinal environment, and the final bioaccessibility was increased by 1.90-fold. In C. elegans, CCE significantly reduced ROS accumulation, increased SOD activity by 2.01-fold and CAT activity by 2.30-fold, decreased MDA content by 36.76%, prolonging the lifespan of nematodes by 13.33% under H2 O2 stimulation and improving bioavailability in vivo. CONCLUSION: The results indictae that CCP-stabilized Pickering emulsion can efficiently implement the physiological activities of bioactive compounds in vitro digestion and C. elegans, and thus it can be regarded as a reliable delivery system for food and medicine. © 2023 Society of Chemical Industry.
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Curcumina , Nanopartículas , Animales , Curcumina/química , Emulsiones/química , Caseínas/metabolismo , Disponibilidad Biológica , Caenorhabditis elegans/metabolismo , Nanopartículas/química , Tamaño de la PartículaRESUMEN
The Kleier model and Carrier-mediated theory are effective for molecularly designing pesticides with phloem mobility. However, the single Kleier model or Carrier-mediated theory cannot achieve a reliable explanation of the phloem mobility of all exogenous substances. A detailed investigation of the two models and the scope of their applications can provide a more accurate and highly efficient basis for the guidance of the design and development of phloem-mobile pesticides. In the present paper, a strategy using active ingredient-amino acid conjugates as mode compounds is developed based on Carrier-mediated theory. An N-alkylated amino acid is used to improve the pesticide's physicochemical properties following the Kleier model, thus allowing the conjugates to fall on the predicted and more accessible transportation region of phloem. Moreover, the influence of this movement on phloem is inspected by the Kleier model and Carrier-mediated theory. To verify this strategy, a series of N-alkylated phenazine-1-carboxylic acid-glycine compounds (PCA-Gly) were designed and synthesized. The results related to the castor bean seeds (R. communis L.) indicated that all the target compounds (4a−4f) had phloem mobility. The capacity for phloem mobility shows that N-alkylated glycine containing small substituents can significantly improve PCA phloem mobility, such as 4c(i-C3H7-N) > 4a(CH3-N) ≈ 4b(C2H5-N) > 4d (t-C4H9-N) > PCA-Gly > 4e(C6H5-N) > 4f(CH2COOH-N), with an oil−water partition coefficient between 1.2~2.5. In particular, compounds 4a(CH3-N), 4b(C2H5-N), and 4c(i-C3H7-N) present better phloem mobility, with the average concentrations in phloem sap of 14.62 µΜ, 13.98 µΜ, and 17.63 µΜ in the first 5 h, which are 8 to 10 times higher than PCA-Gly (1.71 µΜ). The results reveal that the Kleier model and Carrier-mediated theory play a guiding role in the design of phloem-mobile pesticides. However, the single Kleier model or Carrier-mediated theory are not entirely accurate. Still, there is a synergism between Carrier-mediated theory and the Kleier model for promoting the phloem transport of exogenous compounds. Therefore, we suggest the introduction of endogenous plant compounds as a promoiety to improve the phloem mobility of pesticides through Carrier-mediated theory. It is necessary to consider the improvement of physicochemical properties according to the Kleier model, which can contribute to a scientific theory for developing phloem-mobile pesticides.
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Fabaceae , Plaguicidas , Aminoácidos/química , Fabaceae/metabolismo , Glicina/farmacología , Plaguicidas/análisis , Fenazinas , Floema/química , Ricinus/metabolismoRESUMEN
The low-temperature poly-Si oxide (LTPO) backplane is realized by monolithically integrating low-temperature poly-Si (LTPS) and amorphous oxide semiconductor (AOS) thin-film transistors (TFTs) in the same display backplane. The LTPO-enabled dynamic refreshing rate can significantly reduce the display's power consumption. However, the essential hydrogenation of LTPS would seriously deteriorate AOS TFTs by increasing the population of channel defects and carriers. Hydrogen (H) diffusion barriers were comparatively investigated to reduce the H content in amorphous indium-gallium-zinc oxide (a-IGZO). Moreover, the intrinsic H-resistance of a-IGZO was impressively enhanced by plasma treatments, such as fluorine and nitrous oxide. Enabled by the suppressed H conflict, a novel AOS/LTPS integration structure was tested by directly stacking the H-resistant a-IGZO on poly-Si TFT, dubbed metal-oxide-on-Si (MOOS). The noticeably shrunken layout footprint could support much higher resolution and pixel density for next-generation displays, especially AR and VR displays. Compared to the conventional LTPO circuits, the more compact MOOS circuits exhibited similar characteristics.
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BACKGROUND: The genetic backgrounds and occurrence patterns of weedy rice (WR, Oryza sativa) are highly diverse, and so are the challenges facing its control among countries. WR control is difficult because it is similar to cultivated rice and manual removal is one of the few options for control. Understanding the ecology of WR will aid efforts to break its life cycle and establish long-term management strategies under both irrigated and rainfed systems. RESULTS: Nicaraguan WR (NWR) plants were genetically closer to the AUS and Indica pools in terms of to genetic distance. A map of admixture coefficients suggested a pattern of long-distance dispersal and spread of NWR across Nicaragua, which has likely been facilitated by commercial activities and sharing of harvesting equipment between border cities or important trading ports and inland regions. Moreover, the NWR plants from the soil seedbank in irrigated regions showed different habitats and lower grain number per panicle compared with plants spread by seed-mediated contamination. In addition, grain indexes showed that length-to-width ratio was a better indicator than awn length for distinguishing between NWR and Nicaraguan Indica cultivars. CONCLUSION: Analysis of the population structure and habitats of NWR revealed five clusters derived from seed-mediated contamination in rainfed upland regions, plants from the soil seedbank in irrigated double-cropping regions, and pollen-mediated contamination across both regions. Field weed management before harvesting and seed purification based on the length-to-width ratio can be conducted to improve the efficiency of long-term control of WR in Nicaragua. © 2022 Society of Chemical Industry.
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Oryza , Grano Comestible , Oryza/genética , Malezas/genética , Semillas/genética , SueloRESUMEN
Objectives: Social function is an important indicator for physical and psychological health of older adults. However, there is a lack of a standardized questionnaire for measuring social function of older adults. This study developed a questionnaire to assess Chinese older adults' social function. Methods: We used three samples (N = 2,257 aged ≥60 years) to test the reliability and validity of the questionnaire. Results: Based on exploratory and confirmatory factor analyses with two samples, the final version of Social Function Questionnaire for Chinese Older Adults (SFQCOA) contained three dimensions with 12 items: social support, social adaptation, and social engagement. Criterion validity test with the third sample showed that SFQCOA was positively related to the healthy indices and negatively related to the unhealthy indices. Conclusion: The validity and reliability of the questionnaire reach the requirements of psychometric standards, suggesting it is an effective tool for measuring social function of older adults.
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Three-dimensional (3D) printing technology has great potential for constructing structurally and functionally complex scaffold materials for tissue engineering. Bio-inks are a critical part of 3D printing for this purpose. In this study, based on dynamic hydrazone-crosslinked hyaluronic acid (HA-HYD) and photocrosslinked gelatin methacrylate (GelMA), a double-network (DN) hydrogel with significantly enhanced mechanical strength, self-healing, and shear-thinning properties was developed as a printable hydrogel bio-ink for extrusion-based 3D printing. Owing to shear thinning, the DN hydrogel bio-inks could be extruded to form uniform filaments, which were printed layer by layer to fabricate the scaffolds. The self-healing performance of the filaments and photocrosslinking of GelMA worked together to obtain an integrated and stable printed structure with high mechanical strength. The in vitro cytocompatibility assay showed that the DN hydrogel printed scaffolds supported the survival and proliferation of bone marrow mesenchymal stem cells. GelMA/HA-HYD DN hydrogel bio-inks with printability, good structural integrity, and biocompatibility are promising materials for 3D printing of tissue engineering scaffolds.
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Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-aged women. In this study, a rat model of PCOS was established by subcutaneous injection of dehydroepiandrosterone (DHEA). NOX4 was highly expressed in PCOS rat ovaries, while its specific role in PCOS remains unclear. Lentivirus-mediated shRNA targeting NOX4 inhibited oxidative stress by reducing ROS, 4-HNE and MDA levels, and increasing SOD and GPX activities in rat ovaries. NOX4 deficiency increased Bcl-2 levels and decreased Bax, cleaved caspase-3 and cleaved caspase-9 levels and DHEA-induced cell apoptosis in rat ovaries. Similar to the in vivo results, NOX4 silencing inhibited oxidative stress and cell apoptosis in DHEA-treated rat granulosa cells. Moreover, NOX4 silencing promoted Nrf-2 translocation, and the expression of Nrf-2 and HO-1 both in vivo and in vitro. Thus, NOX4 deficiency may ameliorate PCOS in rats by reducing oxidative stress and cell apoptosis via activating the Nrf-2/HO-1 signal pathway.
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Síndrome del Ovario Poliquístico , Adulto , Animales , Apoptosis , Deshidroepiandrosterona/efectos adversos , Femenino , Humanos , NADP/metabolismo , NADPH Oxidasa 4/genética , NADPH Oxidasa 4/metabolismo , Estrés Oxidativo , Síndrome del Ovario Poliquístico/metabolismo , Ratas , Transducción de Señal/genéticaRESUMEN
Oedaleus decorus asiaticus (Bey-Bienko) is a destructive pest in grasslands and adjacent farmland in northern China, Mongolia, and other countries in Asia. It has been supposed that this insect pest can migrate a long distance and then induce huge damages, however, the migration mechanism is still unrevealed. The current study uses insect light trap data from Yanqing (Beijing), together with regional meteorological data to determine how air flow contributes to the long-distance migration of O. decorus asiaticus. Our results indicate that sinking airflow is the main factor leading to the insects' forced landing, and the prevailing northwest wind was associated with O. decorus asiaticus taking off in the northwest and moving southward with the airflow from July to September. Meanwhile, the insects have a strong migratory ability, flying along the airflow for several nights. Thus, when the airflow from the northwest met the northward-moving warm current from the southwest, a large number of insects were dropped due to sinking airflow, resulting in a large outbreak. Our simulations suggest that the source of the grasshoppers involved in these outbreaks during early 2000s in northern China probably is in Mongolia, and all evidence indicates that there are two important immigrant routes for O. decorus asiaticus migration from Mongolia to Beijing. These findings improves our understanding of the factors guiding O. decorus asiaticus migration, providing valuable information to reduce outbreaks in China that have origins from outside the country.
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Capsaicin (CAP) is a well-known anti-cancer agent. Recently, we reported capsaicin-induced apoptosis in anaplastic thyroid cancer (ATC) cells. It is well accepted that the generation of cancer stem cells (CSCs) is responsible for the dedifferentiation of ATC, the most lethal subtype of thyroid cancer with highly dedifferentiation status. Whether CAP inhibited the ATC growth through targeting CSCs needed further investigation. In the present study, CAP was found to induce autophagy in ATC cells through TRPV1 activation and subsequent calcium influx. Meanwhile, CAP dose-dependently decreased the sphere formation capacity of ATC cells. The stemness-inhibitory effect of CAP was further by extreme limiting dilution analysis (ELDA). CAP significantly decreased the protein level of OCT4A in both 8505C and FRO cells. Furthermore, CAP-induced OCT4A degradation was reversed by autophagy inhibitors 3-MA and chloroquine, BAPTA-AM and capsazepine, but not proteasome inhibitor MG132. Collectively, our study firstly showed CAP suppressed the stemness of ATC cells partially via calcium-dependent autophagic degradation of OCT4A. Our study lent credence to the feasible application of capsaicin in limiting ATC stemness.
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Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Apoptosis , Autofagia , Capsaicina/farmacología , Línea Celular Tumoral , Humanos , Lisosomas , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patologíaRESUMEN
Anaplastic thyroid cancer (ATC) is a rare but highly lethal disease. ATCs are resistant to standard therapies and are extremely difficult to manage. The stepwise cell dedifferentiation results in the impairment of the iodine-metabolizing machinery and the infeasibility of radioiodine treatment in ATC. Hence, reinducing iodine-metabolizing gene expression to restore radioiodine avidity is considered as a promising strategy to fight against ATC. In the present study, capsaicin (CAP), a natural potent transient receptor potential vanilloid type 1 (TRPV1) agonist, was discovered to reinduce ATC cell differentiation and to increase the expression of thyroid transcription factors (TTFs including TTF-1, TTF-2, and PAX8) and iodine-metabolizing proteins, including thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase, and sodium iodine symporter (NIS), in two ATC cell lines, 8505C and FRO. Strikingly, CAP treatment promoted NIS glycosylation and its membrane trafficking, resulting in a significant enhancement of radioiodine uptake of ATC cells in vitro. Mechanistically, CAP-activated TRPV1 channel and subsequently triggered Ca2+ influx, cyclic adenosine monophosphate (cAMP) generation, and cAMP-responsive element-binding protein (CREB) signal activation. Next, CREB recognized and bound to the promoter of SLC5A5 to facilitate its transcription. Moreover, the TRPV1 antagonist CPZ, the calcium chelator BAPTA, and the PKA inhibitor H-89 effectively alleviated the redifferentiation exerted by CAP, demonstrating that CAP might improve radioiodine avidity through the activation of the TRPV1âCa2+/cAMP/PKA/CREB signaling pathway. In addition, our study indicated that CAP might trigger a novel cascade to redifferentiate ATC cells and provide unprecedented opportunities for radioiodine therapy in ATC, bypassing canonical TSHâTSHR pathway.
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Yodo , Simportadores , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Capsaicina/farmacología , Línea Celular Tumoral , Humanos , Yodo/metabolismo , Radioisótopos de Yodo/metabolismo , Radioisótopos de Yodo/uso terapéutico , Receptores de Tirotropina/metabolismo , Sodio/metabolismo , Simportadores/genética , Simportadores/metabolismo , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/metabolismo , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Tirotropina/metabolismoRESUMEN
Curcumin, a polyphenolic compound, is a well-known anticancer agent, although its poor bioavailability remains a big concern. Recent studies suggest that autophagy-targeted therapy may be a useful adjunct treatment for patients with thyroid cancer. Curcumin acts as an autophagy inducer on many cancer cells. However, little is known about the exact role of curcumin on thyroid cancer cells. In the present study, curcumin significantly inhibited the growth of thyroid cancer cells. Autophagy was markedly induced by curcumin treatment as evidenced by an increase in LC3-II conversion, beclin-1 accumulation, p62 degradation as well as the increased formation of acidic vesicular organelles (AVOs). 3-MA, an autophagy inhibitor, partially rescued thyroid cancer cells from curcumin-induced cell death. Additionally, curcumin was found to exert selective cytotoxicity on thyroid cancer cells but not normal epithelial cells and acted as an autophagy inducer through activation of MAPK while inhibition of mTOR pathways. Hyperactivation of the AKT/mTOR axis was observed in the majority of PTC samples we tested, and thyroid cancer cell lines along with cancer tissue specimens sustained a low basal autophagic activity. Taken together, our results provide new evidence that inducing autophagic cell death may serve as a potential anti-cancer strategy to handle thyroid cancer.
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Antineoplásicos/farmacología , Muerte Celular Autofágica/efectos de los fármacos , Curcumina/farmacología , Neoplasias de la Tiroides/tratamiento farmacológico , Adenina/análogos & derivados , Adenina/farmacología , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that poses a great threat to women's health. MiR-1224-5p is downregulated in the follicular fluid of patients with PCOS, but its role remains largely unknown. In this study, mice were treated with dehydroepiandrosterone (DHEA) to establish an in vivo model of PCOS. We found that enhanced activation of NLRP3 inflammasome was accompanied by downregulation of miR-1224-5p in ovarian tissue of PCOS mice. The effect of miR-1224-5p was further explored in TNF-α-treated human granulosa-like tumor (KGN) cells. Upregulation of miR-1224-5p suppressed TNF-α-induced secretion of DHEA and testosterone. MiR-1224-5p attenuated TNF-α-induced inflammation by inhibiting NLRP3 inflammasome activation, IL-1ß synthesis, and nuclear factor kappa B (NF-κB) p65 nuclear translocation. Notably, miR-1224-5p decreased the expression of Forkhead box O 1 (FOXO1) and its downstream gene thioredoxin interaction protein (TXNIP). Luciferase reporter assay confirmed FOXO1 as a target of miR-1224-5p. Upregulation of FOXO1 abolished miR-1224-5p-induced activation of NLRP3 inflammasome, demonstrating that miR-1224-5p might inhibit NLRP3 inflammasome activation through regulating FOXO1. This study provided novel insights into the pathogenesis of PCOS and suggested that miR-1224-5p might be a promising target for treating PCOS.
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Proteína Forkhead Box O1/metabolismo , MicroARNs/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Síndrome del Ovario Poliquístico , Animales , Modelos Animales de Enfermedad , Femenino , Proteína Forkhead Box O1/genética , Humanos , Inflamasomas/genética , Ratones , MicroARNs/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Ovario/metabolismo , Ovario/patología , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patologíaRESUMEN
INTRODUCTION: This paper presented qualitative and quantitative data collected on the research capacity of global health institutions in China and aimed to provide a landscaping review of the development of global health as a new discipline in the largest emerging economy of the world. METHODS: Mixed methods were used and they included a bibliometric analysis, a standardised survey and indepth interviews with top officials of 11 selected global health research and educational institutions in mainland China. RESULTS: The bibliometric analysis revealed that each institution had its own focus areas, some with a balanced focus among chronic illness, infectious disease and health systems, while others only focused on one of these areas. Interviews of key staff from each institution showed common themes: recognition that the current research capacity in global health is relatively weak, optimism towards the future, as well as an emphasis on mutual beneficial networking with other countries. Specific obstacles raised and the solutions applied by each institution were listed and discussed. CONCLUSION: Global health institutions in China are going through a transition from learning and following established protocols to taking a more leading role in setting up China's own footprint in this area. Gaps still remain, both in comparison with international institutions, as well as between the leading Chinese institutions and those that have just started. More investment needs to be made, from both public and private domains, to improve the overall capacity as well as the mutual learning and communication within the academic community in China.
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Países en Desarrollo , Salud Global , China , Programas de Gobierno , Humanos , PobrezaRESUMEN
Owing to its unique physiochemical properties similar to the extracellular matrix (ECM), three-dimensional (3D) crosslinked hydrogels are widely studied materials for tissue engineering. In this study, to mimic the ECM microenvironment, a two-step covalent cross-linking with hyaluronic acid and gelatin was performed to form an interpenetrating polymer network structure. Gelatin as the first network greatly improved the mechanical strength of the hydrogels, while a hyaluronic acid network as the second network improved the tenacity and biological activity. Compared with a single network hydrogel, the interpenetrating hydrogel system can further regulate the mechanical properties of the hydrogel by adjusting the ratio of the two components, thereby changing the proliferation, activity, and direction of cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs). Not only that, with two culture methods for BMSCs on the surface and 3D wrapped in the double cross-linked hydrogels, they exhibited their potential to induce BMSCs to cartilage differentiation under the condition of 3D encapsulation of BMSCs and contact with BMSCs on its surface. As a scaffold material for cartilage tissue engineering, this double cross-linked hydrogel demonstrated its high feasibility and applicability in delivering BMSCs in vivo and repairing defects.