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Increasing grain yield is a major goal of breeders due to the rising global demand for food. We previously reported that the miR397-LACCASE (OsLAC) module regulates brassinosteroid (BR) signaling and grain yield in rice (Oryza sativa). However, the precise roles of laccase enzymes in the BR pathway remain unclear. Here, we report that OsLAC controls grain yield by preventing the turnover of TRANSTHYRETIN-LIKE (OsTTL), a negative regulator of BR signaling. Overexpressing OsTTL decreased BR sensitivity in rice, while loss-of-function of OsTTL led to enhanced BR signaling and increased grain yield. OsLAC directly binds to OsTTL and regulates its phosphorylation-mediated turnover. The phosphorylation site Ser226 of OsTTL is essential for its ubiquitination and degradation. Overexpressing the dephosphorylation-mimic form of OsTTL (OsTTLS226A) resulted in more severe defects than did overexpressing OsTTL. These findings provide insight into the role of an ancient laccase in BR signaling and suggest that the OsLAC-OsTTL module could serve as a target for improving grain yield.
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Regulación de la Expresión Génica de las Plantas , Lacasa , MicroARNs , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Oryza/crecimiento & desarrollo , Oryza/enzimología , Lacasa/metabolismo , Lacasa/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , MicroARNs/genética , MicroARNs/metabolismo , Fosforilación , Grano Comestible/crecimiento & desarrollo , Grano Comestible/genética , Grano Comestible/metabolismo , Transducción de Señal , Plantas Modificadas Genéticamente , Brasinoesteroides/metabolismoRESUMEN
The precise timing of flowering plays a pivotal role in ensuring successful plant reproduction and seed production. This process is intricately governed by complex genetic networks that integrate internal and external signals. This study delved into the regulatory function of microRNA397 (miR397) and its target gene LACCASE-15 (OsLAC15) in modulating flowering traits in rice (Oryza sativa). Overexpression of miR397 led to earlier heading dates, decreased number of leaves on the main stem, and accelerated differentiation of the spikelet meristem. Conversely, overexpression of OsLAC15 resulted in delayed flowering and prolonged vegetative growth. Through biochemical and physiological assays, we uncovered that miR397-OsLAC15 had a profound impact on carbohydrate accumulation and photosynthetic assimilation, consequently enhancing the photosynthetic intensity in miR397-overexpressing rice plants. Notably, we identified that OsLAC15 is at least partially localized within the peroxisome organelle, where it regulates the photorespiration pathway. Moreover, we observed that a high CO2 concentration could rescue the late flowering phenotype in OsLAC15-overexpressing plants. These findings shed valuable insights into the regulatory mechanisms of miR397-OsLAC15 in rice flowering and provided potential strategies for developing crop varieties with early flowering and high-yield traits through genetic breeding.
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Oryza , Oryza/metabolismo , Flores/fisiología , Fitomejoramiento , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Reproducción , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Mesendodermal specification and cardiac differentiation are key issues for developmental biology and heart regeneration medicine. Previously, we demonstrated that FAM122A, a highly conserved housekeeping gene, is an endogenous inhibitor of protein phosphatase 2A (PP2A) and participates in multifaceted physiological and pathological processes. However, the in vivo function of FAM122A is largely unknown. In this study, we observed that Fam122 deletion resulted in embryonic lethality with severe defects of cardiovascular developments and significantly attenuated cardiac functions in conditional cardiac-specific knockout mice. More importantly, Fam122a deficiency impaired mesendodermal specification and cardiac differentiation from mouse embryonic stem cells but showed no influence on pluripotent identity. Mechanical investigation revealed that the impaired differentiation potential was caused by the dysregulation of histone modification and Wnt and Hippo signaling pathways through modulation of PP2A activity. These findings suggest that FAM122A is a novel and critical regulator in mesendodermal specification and cardiac differentiation. This research not only significantly extends our understanding of the regulatory network of mesendodermal/cardiac differentiation but also proposes the potential significance of FAM122A in cardiac regeneration.
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Células Madre Embrionarias , Procesamiento Proteico-Postraduccional , Animales , Ratones , Diferenciación Celular/fisiología , Células Madre Embrionarias/metabolismo , Células Madre Embrionarias de Ratones/metabolismoRESUMEN
Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.
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Proteínas de la Membrana , Células-Madre Neurales , Humanos , Proteínas de la Membrana/genética , Hipoxia de la Célula , Hipoxia/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Autofagia , Células-Madre Neurales/metabolismo , Proliferación Celular , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismoRESUMEN
An effective and straightforward Ag(I)-mediated annulation of 2-(2-enynyl)quinolines and N'-(2-alkynylbenzylidene)hydrazides was developed, forging various synthetically challenging 17bH-isoquinolino[2'',1'':1',6']pyridazino[4',5':3,4]pyrrolo[1,2-a]quinolines, including different nitrogen-containing fused rings, in moderate to excellent yields. This one-pot cycloaddition strategy features exclusive regioselectivity, high atom economy, and broad substrate scope under mild conditions. The practicality and reliability of this cycloaddition reaction was demonstrated by a successful scale-up synthesis.
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BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.
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Adenocarcinoma Mucinoso , Neoplasias del Apéndice , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Estudios Retrospectivos , Masculino , Femenino , Neoplasias del Apéndice/terapia , Neoplasias del Apéndice/mortalidad , Neoplasias del Apéndice/patología , Persona de Mediana Edad , Adulto , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Anciano , Terapia Combinada , Resultado del Tratamiento , Tasa de Supervivencia , Clasificación del Tumor , Perforación Intestinal/etiología , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/mortalidadRESUMEN
Herein, we describe an innovative approach to the asymmetric electrochemical α-alkylation of aldehydes facilitated by a newly designed bifunctional chiral electrocatalyst. The highly efficient bifunctional chiral electrocatalyst combines a chiral aminocatalyst with a redox mediator. It plays a dual role as a redox mediator for electrooxidation, while simultaneously providing remarkable asymmetric induction for the stereoselective α-alkylation of aldehydes. Additionally, this novel catalyst exhibits enhanced catalytic activity and excellent stereoselective control comparable to conventional catalytic systems. As a result, this strategy provides a new avenue for versatile asymmetric electrochemistry. The electrooxidation of diverse phenols enables the C-H/C-H oxidative α-alkylation of aldehydes in a highly chemo- and stereoselective fashion. Detailed mechanistic studies by control experiments and cyclic voltammetry analysis demonstrate possible reaction pathways and the origin of enantio-induction.
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Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.
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Ferroptosis , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Imagen Óptica , Lisosomas/química , Apoptosis/fisiología , Concentración de Iones de HidrógenoRESUMEN
Optical waveguides prepared by femtosecond laser direct writing have birefringent properties, which can affect polarization encoding and entanglement on chips. Here, we first propose a shape-stress dual compensation fabrication scheme to decrease birefringence. Ultralow birefringent waveguides (1 × 10-9) were obtained by controlling the cross sectional shape of the main waveguide and adjusting the position of the auxiliary lines. In addition, we prepared polarization-independent directional coupler and demonstrated the evolution of polarization-independent waveguide array with different polarized light. In the future, ultralow birefringent waveguides will be widely applied in polarization encoding and entangled quantum photonic integrated circuits.
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In this study, the effects of dietary lipopolysaccharide (LPS) on Litopenaeus vannamei were investigated to determine whether LPS could play a role as a potential immunostimulant in shrimp. L. vannamei with an initial body weight of 0.30 ± 0.02 g were fed a diet containing LPS at doses of 0, 0.2, 1, 5, 25 or 125 mg kg-1 for eight weeks (groups LPS0, LPS0.2, LPS1, LPS5, LPS25 and LPS125, respectively). After eight weeks of feeding, the growth performance, immunity and transcriptome response of L. vannamei were analysed. Only dietary LPS at 0.2 and 1 mg kg-1 resulted in a significant increase in the growth of L. vannamei (P < 0.05). According to the weight gain rate (WGR) and specific growth rate (SGR), the optimum dietary LPS level was 2.462 and 2.455 mg kg-1, respectively. When compared with the control group, the survival rate (SR) of L. vannamei in the LPS0.2 group was significantly increased after white spot syndrome virus (WSSV) infection and the SR of L. vannamei in the LPS1 group was significantly increased after Vibrio parahaemolyticus infection (both P < 0.05). Compared with the LPS0 group, immune enzyme activity in the serum of L. vannamei could be significantly increased and the content of maleic dialdehyde (MDA) significantly decreased by dietary LPS. Transcriptome analysis of the haemocytes of L. vannamei identified 399 up-regulated differentially expressed genes (DEGs) and 5000 down-regulated DEGs in the LPS0.2 compared to the control group. Most of the DEGs were significantly enriched in the following pathways: phosphatidylinositol signalling, Wnt signalling, Jak-STAT signalling and inositol phosphate metabolism. In conclusion, this study revealed that diets supplemented with low-dose LPS had positive effects on the growth and immunity of L. vannamei.
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Penaeidae , Virus del Síndrome de la Mancha Blanca 1 , Animales , Lipopolisacáridos/farmacología , Inmunidad Innata/genética , Alimentación Animal/análisis , Dieta/veterinaria , Perfilación de la Expresión Génica , Virus del Síndrome de la Mancha Blanca 1/genéticaRESUMEN
Doxorubicin (DOX), is a high efficiency anthracycline antitumor drug. However, the clinical application of DOX is limited mainly by dose-related adverse drug reactions. Currently, the therapeutic effects of Atorvastatin (ATO) on DOX-induced hepatotoxicity were studied in vivo. The results indicated that DOX impaired hepatic function, as measured by an increased levels of liver weight index and serum concentrations of aspartate transaminase and alanine transaminase, as well as alteration of hepatic histology. In addition, DOX increased the serum levles of triglyceride (TG) and nonestesterified fatty acid. ATO prevented these changes. Mechanical analysis revealed that ATO restored the changes of malondialdehyde, reactive oxygen radical species, glutathione peroxidase and manganese superoxide dismutase. Additionally, ATO inhibited the increased expression levels of nuclear factor-kappa B and interleukin 1ß, hence suppressing inflammation. Meanwhile, ATO inhibited cell apoptosis by dramatically decreasing the Bax/Bcl-2 ratio. In addition, ATO mitigated the lipidtoxicity by inhibiting the adipolysis of TG and accelerating hepatic lipid metabolism. Taken together, the results suggest ATO has therapeutic effect on DOX-induced hepatotoxicity via inhibition of oxidative damage, inflammatory and apoptosis. In addition, ATO attenuates DOX-induced hyperlipidemia via modulation of lipid metabolism.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Ratas , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Atorvastatina/farmacología , Doxorrubicina/toxicidad , Estrés Oxidativo , Antiinflamatorios/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , ApoptosisRESUMEN
Extracellular vesicles (EVs) are nano-sized, natural, cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve as natural carriers for therapeutic agents and drugs, and have many advantages over conventional nanocarriers, including their low immunogenicity, good biocompatibility, natural blood-brain barrier penetration, and capacity for gene delivery. This review first introduces the classification of EVs and then discusses several currently popular methods for isolating and purifying EVs, EVs-mediated drug delivery, and the functionalization of EVs as carriers. Thereby, it provides new avenues for the development of EVs-based therapeutic strategies in different fields of medicine. Finally, it highlights some challenges and future perspectives with regard to the clinical application of EVs.
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Sistemas de Liberación de Medicamentos , Vesículas Extracelulares , Sistemas de Liberación de Medicamentos/métodos , Vesículas Extracelulares/metabolismo , Proteínas , Transporte BiológicoRESUMEN
BACKGROUND: Anlotinib has demonstrated encouraging clinical outcomes in the treatment of lung cancer, soft tissue sarcoma and thyroid carcinoma. Several clinical studies have shown a relationship between anlotinib treatment and the occurrence of hyperlipidemia. The fundamental mechanisms, however, are still largely unclear. Here, the effect of anlotinib on lipid metabolism in an animal model and human cancer cells was evaluated and the role of lipid metabolism in the antitumor efficacy of anlotinib was investigated. METHODS: The C57BL/6 J mouse model as well as A549 and H460 human lung cancer cell lines were used to examine the impact of anlotinib on lipid metabolism both in vivo and in vitro. Levels of triglycerides, high-density lipoprotein, low-density lipoprotein (LDL), and total cholesterol in serum or cell samples were determined using assay kits. The expression levels of crucial genes and proteins involved in lipid metabolism were measured by quantitative RT-PCR and Western blotting. Furthermore, exogenous LDL and knockdown of low-density lipoprotein receptor (LDLR) were used in H460 cells to investigate the relevance of lipid metabolism in the anticancer efficacy of anlotinib. RESULTS: Anlotinib caused hyperlipidemia in C57BL/6 J mice, possibly by downregulating hepatic LDLR-mediated uptake of LDL cholesterol. AMP-activated protein kinase and mammalian target of rapamycin inhibition may also be involved. Additionally, anlotinib enhanced sterol response element binding protein 1/2 nuclear accumulation as well as upregulated LDLR expression in A549 and H460 cells, which may be attributable to intracellular lipid accumulation. Knockdown of LDLR reduced intracellular cholesterol content, but interestingly, anlotinib significantly improved intracellular cholesterol accumulation in LDLR-knockdown cells. Both exogenous LDL and LDLR knockdown decreased the sensitivity of cells to anlotinib. CONCLUSIONS: Anlotinib modulates host lipid metabolism through multiple pathways. Anlotinib also exerts a significant impact on lipid metabolism in cancer cells by regulating key transcription factors and metabolic enzymes. In addition, these findings suggest lipid metabolism is implicated in anlotinib sensitivity.
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Metabolismo de los Lípidos , Neoplasias Pulmonares , Ratones , Animales , Humanos , Ratones Endogámicos C57BL , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , LDL-Colesterol , MamíferosRESUMEN
The uncertainty of lidar measured atmospheric temperature T or line-of-sight (LOS) wind V is inversely proportional to the signal-to-noise ratio (SNR) of the received photocounts. We term the proportionality constant, which depicts the efficacy of the measurement method, the single-photon (or unity SNR) measurement uncertainty for T and/or V measurement. In this study, we use the single-photon measurement uncertainty as the figure of merit to compare and understand the practical differences between Cabannes scattering (CS), Rayleigh inversion (RI), rotational Raman (RR), and laser induced fluorescence (LIF) lidars for atmospheric temperature and wind measurements, and to optimize the choice and receiver design of a lidar system for a potential application.
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The intine, the inner layer of the pollen wall, is essential for the normal development and germination of pollen. However, the composition and developmental regulation of the intine in rice (Oryza sativa) remain largely unknown. Here, we identify a microRNA, OsmiR528, which regulates the formation of the pollen intine and thus male fertility in rice. The mir528 knockout mutant aborted pollen development at the late binucleate pollen stage, significantly decreasing the seed-setting rate. We further demonstrated that OsmiR528 affects pollen development by directly targeting the uclacyanin gene OsUCL23 (encoding a member of the plant-specific blue copper protein family of phytocyanins) and regulating intine deposition. OsUCL23 overexpression phenocopied the mir528 mutant. The OsUCL23 protein localized in the prevacuolar compartments (PVCs) and multivesicular bodies (MVBs). We further revealed that OsUCL23 interacts with a member of the proton-dependent oligopeptide transport (POT) family of transporters to regulate various metabolic components, especially flavonoids. We propose a model in which OsmiR528 regulates pollen intine formation by directly targeting OsUCL23 and in which OsUCL23 interacts with the POT protein on the PVCs and MVBs to regulate the production of metabolites during pollen development. The study thus reveals the functions of OsmiR528 and an uclacyanin during pollen development.
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Metaloproteínas/genética , MicroARNs/metabolismo , Oryza/fisiología , Proteínas de Plantas/genética , Polen/metabolismo , Regulación de la Expresión Génica de las Plantas , Microscopía Electrónica de Transmisión , Plantas Modificadas Genéticamente , Polen/ultraestructuraRESUMEN
Insulin-induced gene 2 (INSIG2) functions as a blocker of cholesterol biosynthesis and has been shown to be involved in colon and pancreatic cancer pathogenesis. Cholesterol is a risk factor for breast cancer pathophysiology; however, the underlying mechanisms are not well-defined. Hence, our goal was to determine the role of INISG2 in breast cancer. INSIG2 mRNA and protein expression was correlated to metastatic potential of breast cancer cell lines. Knockdown of INSIG2 inhibited epithelial-to-mesenchymal transition. Conversely, overexpression of INSIG2 induced epithelial-to-mesenchymal transition. Knockdown of INSIG2 did not affect cell proliferation but resulted in altered metabolism in vitro and attenuated experimental metastasis in vivo. Analysis of breast cancer tissue microarrays revealed significantly higher INSIG2 protein expression in breast cancer tissues. INSIG2 protein expression was correlated to hormone receptor status, with significantly higher expression in patients with triple-negative and human epidermal growth factor receptor 2 molecular subtypes of invasive breast cancer. Analysis of The Cancer Genome Atlas, however, revealed significantly lower INSIG2 mRNA expression in triple-negative breast cancer patients. Higher INSIG2 mRNA expression was correlated to poor survival probability. Asian patients with high INSIG2 mRNA expression had significantly lower survival probability compared with Asian patients with low/medium INSIG2 mRNA expression. These results reveal a yet undefined role of INSIG2 in breast cancer, potentially more relevant for breast cancer patients in Asia.
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Neoplasias de la Mama/patología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , Metástasis de la Neoplasia/genética , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Transición Epitelial-Mesenquimal/genética , Femenino , Xenoinjertos , Humanos , Ratones , Ratones Desnudos , Metástasis de la Neoplasia/patologíaRESUMEN
In this study, a hybrid method for high-quality rapid drilling of transparent hard materials which combines femtosecond laser (fs-laser) Bessel beam modifying materials and selective wet etching is presented. Using this method, micro-holes with no taper of different sizes (from 10 to 35 µm) and shapes (square, triangle, circular, and pentagram) are fabricated. Bessel beams of different lengths can be generated flexibly by loading different computer-generated holograms (CGHs) into the spatial light modulator (SLM) and the maximum length of light interacting with materials can reach 320 µm, leading to a reduction of the laser scanning time by two orders of magnitude. Moreover, a set of three-dimensional multi-layer submicron through-holes in crystal materials is also realized, with an aspect ratio of more than 1000 for each hole. These results indicate that this method has broad application potential in chip packaging, aviation manufacturing, single particle catalysis, and other fields.
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This study aimed to evaluate the efficacy and safety of transarterial infusion of programmed cell death receptor-1 (PD-1) antibody therapy in advanced or metastatic acral and mucosal melanomas. Eleven patients with acral or mucosal melanoma were referred to the department of Internal Medicine-Oncology in Huazhong University of Science and Technology Union Shenzhen Hospital from January 2019 to August 2020. These patients received transarterial infusions of PD-1 antibody and intravenous infusions of albumin-bound paclitaxel. The median duration of follow-up was 8 months. The patients were treated with transarterial infusion of PD-1 antibody and intravenous infusion of albumin-bound paclitaxel. in study, We collected and recorded immunotherapy-related adverse events. The results showed that the response rate (RR) and the disease control rate (DCR) of the patients (seven with acral melanoma, four with mucosal melanoma) were 54.5 % and 90.9 %, respectively. No grade 3-4 adverse events or major complications were observed during the study. The median progression-free survival was 10 months. The transarterial infusion of PD-1 antibody has remission and control effects on acral and mucosal melanomas, which is important for the clinical care of these patients.
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Melanoma , Neoplasias Cutáneas , Paclitaxel Unido a Albúmina/uso terapéutico , Humanos , Inmunoterapia , Supervivencia sin Progresión , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: The aim of this study was to investigate the associations of osteosarcopenic obesity (OSO) and its components with complete blood cell count-derived inflammation indices. METHODS: In this cross-sectional study, data of 648 participants aged ≥60 years (men/women: 232/416, mean age: 67.21 ± 6.40 years) were collected from January 2018 to December 2020. Areal bone mineral density and body fat percentage were used to define osteopenia/osteoporosis and obesity, respectively. The criteria of the 2019 Asian Working Group for Sarcopenia were used to diagnose sarcopenia. Based on the number of these conditions, participants were divided into four groups: OSO/0, OSO/1, OSO/2, and OSO/3. Logistic regression analysis was conducted to identify associations between blood cell count-derived inflammation indices and the number of disorders with abnormal body composition. RESULTS: Systemic inflammation response index (SIRI), white blood cells, neutrophil-to-lymphocyte ratio (NLR), aggregate inflammation systemic index (AISI), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) showed statistically significant differences among the four groups (P < 0.05). Unlike in the OSO/0 group, in all other groups, AISI, SIRI, PLR, and NLR were significantly associated with increased likelihood of having multiple disorders with abnormal body composition after adjustment for confounders (P < 0.0001 for all). However, LMR showed an inverse correlation with the number of these conditions (P < 0.05). CONCLUSION: Higher SIRI, AISI, NLR, and PLR values and lower LMR values are closely associated with OSO and its individual components-osteoporosis, sarcopenia, and obesity-in older adults, suggesting that the value of these indices in the evaluation of OSO warrants further investigation.
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Osteoporosis , Sarcopenia , Anciano , Recuento de Células Sanguíneas , China/epidemiología , Estudios Transversales , Femenino , Humanos , Inflamación/diagnóstico , Inflamación/epidemiología , Masculino , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/epidemiología , Osteoporosis/complicaciones , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Sarcopenia/diagnóstico , Sarcopenia/epidemiologíaRESUMEN
N6-Methyladenosine (m6A) RNA methylation plays important roles during development in different species. However, knowledge of m6A RNA methylation in monocots remains limited. In this study, we reported that OsFIP and OsMTA2 are the components of m6A RNA methyltransferase complex in rice and uncovered a previously unknown function of m6A RNA methylation in regulation of plant sporogenesis. Importantly, OsFIP is essential for rice male gametogenesis. Knocking out of OsFIP results in early degeneration of microspores at the vacuolated pollen stage and simultaneously causes abnormal meiosis in prophase I. We further analyzed the profile of rice m6A modification during sporogenesis in both WT and OsFIP loss-of-function plants, and identified a rice panicle specific m6A modification motif "UGWAMH". Interestingly, we found that OsFIP directly mediates the m6A methylation of a set of threonine protease and NTPase mRNAs and is essential for their expression and/or splicing, which in turn regulates the progress of sporogenesis. Our findings revealed for the first time that OsFIP plays an indispensable role in plant early sporogenesis. This study also provides evidence for the different functions of the m6A RNA methyltransferase complex between rice and Arabidopsis.