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Insufficient angiogenic stimulation and dysregulated glycolipid metabolism in senescent vascular endothelial cells (VECs) constitute crucial features of vascular aging. Concomitantly, the generation of excess senescence-associated secretory phenotype (SASP) and active immune-inflammatory responses propagates within injured vessels, tissues, and organs. Until now, targeted therapies that efficiently rectify phenotypic abnormalities in senescent VECs have still been lacking. Here, we constructed a Pd/hCeO2-BMS309403@platelet membrane (PCBP) nanoheterostructured capsule system loaded with fatty acid-binding protein 4 (FABP4) inhibitors and modified with platelet membranes and investigated its therapeutic role in aged mice. PCBP showed significant maintenance in aged organs and demonstrated excellent biocompatibility. Through cyclic tail vein administration, PCBP extended the lifespan and steadily ameliorated abnormal phenotypes in aged mice, including SASP production, immune and inflammatory status, and age-related metabolic disorders. In senescent ECs, PCBP mediated the activation of vascular endothelial growth factor (VEGF) signaling and glycolysis and inhibition of FABP4 by inducing the synthesis of hypoxia-inducible factor-1α, thereby reawakening neovascularization and restoring glycolipid metabolic homeostasis. In conclusion, the PCBP nanocapsule system provides a promising avenue for interventions against aging-induced dysfunction.
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Envejecimiento , Nanocápsulas , Animales , Ratones , Envejecimiento/metabolismo , Nanocápsulas/química , Humanos , Ratones Endogámicos C57BL , Glucolípidos/química , Glucolípidos/metabolismo , Senescencia Celular/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , AngiogénesisRESUMEN
Many organisms move directly toward light for prey hunting or navigation, which is called phototaxis. Mimicking this behavior in robots is crucially important in the energy industry and environmental exploration. However, the phototaxis robots with rigid bodies and sensors still face challenges in adapting to unstructured environments, and the soft phototaxis robots often have high requirements for light sources with limited locomotion performance. Here, we report a 3.5 g soft microrobot that can perceive the azimuth angle of light sources and exhibit rapid phototaxis locomotion autonomously enabled by three-dimensional flexible optoelectronics and compliant shape memory alloy (SMA) actuators. The optoelectronics is assembled from a planar patterned flexible circuit with miniature photodetectors, introducing the self-occlusion to light, resulting in high sensing ability (error < 3.5°) compared with the planar counterpart. The actuator produces a straightening motion driven by an SMA wire and is then returned to a curled shape by a prestretched elastomer layer. The actuator exhibits rapid actuation within 0.1 s, a significant degree of deformation (curvature change of â¼87 m-1) and a blocking force of â¼0.4 N, which is 68 times its own weight. Finally, we demonstrated the robot is capable of autonomously crawling toward a moving light source in a hybrid aquatic-terrestrial environment without human intervention. We envision that our microrobot could be widely used in autonomous light tracking applications.
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The bacterial infection and poor osseointegration of Ti implants could significantly compromise their applications in bone repair and replacement. Based on the carrier separation ability of the heterojunction and the redox reaction of pseudocapacitive metal oxides, we report an electrically responsive TiO2-SnO2-RuO2 coating with a multilayered heterostructure on a Ti implant. Owing to the band gap structure of the TiO2-SnO2-RuO2 coating, electron carriers are easily enriched at the coating surface, enabling a response to the endogenous electrical stimulation of the bone. With the formation of SnO2-RuO2 pseudocapacitance on the modified surface, the postcharging mode can significantly change the surface chemical state of the coating due to the redox reaction, enhancing the antibacterial ability and osteogenesis-related gene expression of the human bone marrow mesenchymal stem cells. Owing to the attraction for Ca2+, only the negatively postcharged SnO2@RuO2 can promote apatite deposition. The in vivo experiment reveals that the S-SnO2@RuO2-NP could effectively kill the bacteria colonized on the surface and promote osseointegration with the synostosis bonding interface. Thus, negatively charging the electrically responsive coating of TiO2-SnO2-RuO2 is a good strategy to endow modified Ti implants with excellent antibacterial ability and osseointegration.
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Antibacterianos , Materiales Biocompatibles Revestidos , Oseointegración , Compuestos de Estaño , Titanio , Titanio/química , Titanio/farmacología , Oseointegración/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Compuestos de Estaño/química , Compuestos de Estaño/farmacología , Animales , Compuestos de Rutenio/química , Compuestos de Rutenio/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie , Osteogénesis/efectos de los fármacosRESUMEN
Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.
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Proteínas Adaptadoras de Señalización CARD , Humanos , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas Adaptadoras de Señalización CARD/deficiencia , Femenino , Adulto Joven , Mutación , Neutrófilos/inmunología , Células Th17/inmunología , Candidiasis Mucocutánea Crónica/genética , Candidiasis Mucocutánea Crónica/inmunología , Monocitos/inmunología , CitocinasRESUMEN
BACKGROUND: Although normal acute phase reactants (APRs) play an important role in assessing disease activity of rheumatoid arthritis (RA), some studies pointed out the discordance between disease activity and APR level. Neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs) and lymphocyte-to-monocyte ratios (LMRs) have been reported to be sensitive measures of inflammatory reaction. This study aims to explore the value of these haematological makers in assessment of APR-negative RA patients. METHODS: Out of a cohort of 418 consecutive patients with RA, we enrolled 135 patients with normal APR for this study. We performed ultrasound assessments to evaluate synovitis and bone erosion in the affected joints. Synovitis was evaluated by ultrasound grey scale (GS) and power Doppler (PD) with semi-quantitative scoring (0-3). Demographic, clinical and laboratory data were collected from the patients. Disease Activity Score-28 joints (DAS28), NLR, MLR and PLR were calculated. RESULTS: In RA patients with normal APR, PLR exhibited a positive correlation with ultrasound-detected synovitis and bone erosion, whereas NLR, MLR showed no significant correlation with ultrasonography parameters. The area under the ROC curve (AUC) for identifying synovitis with a GS grade ≥2 based on a PLR cutoff value of ≥159.6 was 0.7868 (sensitivity: 80.95%, specificity: 74.24%). For synovitis with a PD grade ≥2, the AUC was 0.7690, using a PLR cutoff value of ≥166.1 (sensitivity: 68.0%, specificity: 83.87%). CONCLUSIONS: Our findings suggested that PLR might be a reliable and cost-effective marker for identifying moderate-to-severe synovitis in RA patients with normal APR.
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Artritis Reumatoide , Biomarcadores , Linfocitos , Sinovitis , Humanos , Sinovitis/diagnóstico por imagen , Sinovitis/sangre , Sinovitis/diagnóstico , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Adulto , Plaquetas , Proteínas de Fase Aguda/análisis , Anciano , Índice de Severidad de la Enfermedad , Recuento de Plaquetas , Curva ROC , Recuento de Linfocitos , NeutrófilosRESUMEN
In order to understand the role of microorganisms in litter decomposition and the nutrient cycle in volcanic forest ecosystems, the dominant forest species Larix gmelinii in the volcanic lava plateau of the Wudalianchi volcano was considered as the research object. We analyzed the response of bacterial community structure and diversity to litter decomposition for 1 year, with an in situ decomposition experimental design using litter bags and Illumina MiSeq high-throughput sequencing. The results showed that after 365 days, the litter quality residual rate of Larix gmelinii was 77.57%, and the litter N, P, C:N, C:P, and N:P showed significant differences during the decomposition period (p < 0.05). The phyla Cyanobacteria and the genus unclassified_o_Chloroplast were the most dominant groups in early decomposition (January and April). The phyla Proteobacteria, Actinobacteriota, and Acidobacteriota and the genera Massilia, Pseudomonas, and Sphingomona were higher in July and October. The microbial communities showed extremely significant differences during the decomposition period (p < 0.05), with PCoa, RDA, and litter QRR, C:P, and N as the main factors driving litter bacteria succession. Microbial functional prediction analysis showed that Chloroplasts were the major functional group in January and April. Achemoheterotrophy and aerobic chemoheterotrophy showed a significant decrease as litter decomposition progressed.
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Environmental factors like COVID-19 can have significant impact on technical efficiency (TE) and total factor productivity (TFP) of health services provided. In this study, focusing on Maternal and Child Health (MCH) hospitals in Hubei Province of China in 2019 to 2021, we aimed to measure their TE and TFP, identify some influential environmental factors, and propose some policy recommendations. Altogether 62 secondary MCH hospitals were selected as the study sample. Four input indicators, 3 output indicators, and 4 environmental indicators were selected to analyze the panel data from 2019 to 2021. Three-stage Data Envelopment Analysis (DEA) and Malmquist Productivity Index (MPI) model were employed to estimate the TE and TFP of these hospitals. During 2019 to 2021, the inputs of the sample hospitals had increased, while the outputs had decreased. The inputs redundancy was negatively associated with birth rate, number of residents, and GDP per capita (P < .05). It was positively associated with number of COVID-19 infections (P < .05). The adjusted TE scores in 2019 to 2021 were 0.822, 0.784, and 0.803, respectively. The TFP declined in 2020 and 2021 compared to 2019, with scores being 0.845 and 0.762. The technical efficiency change (TEC) scores from 2019 to 2021 were 0.926 and 1.063. The technological change (TC) scores from 2019 to 2021 were 0.912 and 0.716. During 2019 to 2021, the operation of sample hospitals had been significantly influenced by environmental factors like COVID-19 pandemic, low birth rate, number of residents, and GDP per capita. The inputs had increased but outputs had decreased, leading to an increase in inputs redundancy and a decline in TE. The TFP showed a downward trend, with TC and SEC being the priority directions for improvement. Some recommendations are made for both hospitals and government to continuously improve the TE and TFP.
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COVID-19 , Eficiencia Organizacional , Humanos , China , COVID-19/epidemiología , SARS-CoV-2 , Femenino , Servicios de Salud Materno-Infantil/estadística & datos numéricos , Servicios de Salud Materno-Infantil/organización & administración , NiñoRESUMEN
Volcanic lava is an excellent model of primary succession, in which basalt-associated microorganisms drive the cycling of different elements such as nitrogen, carbon, and other nutrients. Microbial communities in volcanic soils are of particular interest for study on the emergence and evolution of life within special and extreme conditions. The initial processes of colonization and subsequent rock weathering by microbial communities are still poorly understood. We analyzed the soil bacterial and fungal communities and diversities associated with lava (LBL) and kipuka (BK) sites in Wudalianchi using 16S and ITS rRNA Illumina Miseq sequencing techniques. The results showed that soil physical and chemical properties (pH, MC, TOC, TN, TP, AP, DOC, and DON) significantly differed between LBL and BK. The Shannon, Ace, and Pd indexes of fungi in the two sites showed a significant difference (p < 0.05). The dominant bacterial phyla forming communities at LBL and BK sites were Acidobacteria, Proteobacteria, Actinobacteria, and Basidiomycota, and their differences were driven by Gemmatimonadetes and Verrucomicrobia. The dominant fungal phyla of LBL and BK sites were Ascomycota, Zygomycota, and Rozellomcota, which differed significantly between the two sites. The microbial communities showed extremely significant differences (p < 0.05), with MC, pH, and nitrogen being the main influencing factors according to RDA/CCA and correlation analysis. Microbial functional prediction analysis across the two sites showed that the relative abundance of advantageous functional groups was significantly different (p < 0.05). The combined results drive us to conclude that the volcanic soil differences in the deposits appear to be the main factor shaping the microbial communities in Wudalianchi (WDLC) volcanic ecosystems.
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G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.
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Ciclina D1 , Proteínas de Unión al ADN , G-Cuádruplex , Factores de Transcripción , Humanos , Proteínas que Contienen Bromodominio , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Dedos de Zinc/genéticaRESUMEN
Effective neuroprotective agents are required to prevent neurological damage caused by reactive oxygen species (ROS) generated by cerebral ischemia-reperfusion injury (CIRI) following an acute ischemic stroke. Herein, it is aimed to develop the neuroprotective agents of cerium oxide loaded with platinum clusters engineered modifications (Ptn-CeO2). The density functional theory calculations show that Ptn-CeO2 could effectively scavenge ROS, including hydroxyl radicals (·OH) and superoxide anions (·O2 -). In addition, Ptn-CeO2 exhibits the superoxide dismutase- and catalase-like enzyme activities, which is capable of scavenging hydrogen peroxide (H2O2). The in vitro studies show that Ptn-CeO2 could adjust the restoration of the mitochondrial metabolism to ROS homeostasis, rebalance cytokines, and feature high biocompatibility. The studies in mice CIRI demonstrate that Ptn-CeO2 could also restore cytokine levels, reduce cysteine aspartate-specific protease (cleaved Caspase 3) levels, and induce the polarization of microglia to M2-type macrophages, thus inhibiting the inflammatory responses. As a result, Ptn-CeO2 inhibits the reperfusion-induced neuronal apoptosis, relieves the infarct volume, reduces the neurological severity score, and improves cognitive function. Overall, these findings suggest that the prominent neuroprotective effect of the engineered Ptn-CeO2 has a significant neuroprotective effect and provides a potential therapeutic alternative for CIRI.
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Cerio , Fármacos Neuroprotectores , Platino (Metal) , Daño por Reperfusión , Cerio/química , Cerio/farmacología , Animales , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Ratones , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/uso terapéutico , Platino (Metal)/química , Platino (Metal)/farmacología , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Masculino , Especies Reactivas de Oxígeno/metabolismo , Homeostasis/efectos de los fármacos , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacosRESUMEN
OBJECTIVES: To explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival. METHODS: This is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival. RESULTS: A total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34-5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23-24.10; p 0.026 and HR, 5.09; 95% CI, 1.95-13.26; p 0.001). DISCUSSION: Presence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.
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Autoanticuerpos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Meningitis Criptocócica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Cryptococcus gattii/inmunología , Cryptococcus neoformans/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Meningitis Criptocócica/mortalidad , Meningitis Criptocócica/inmunología , Meningitis Criptocócica/diagnóstico , Pronóstico , Estudios Retrospectivos , Estudios SeroepidemiológicosRESUMEN
Ulcerative colitis (UC) is a chronic inflammatory bowel disease mainly involving the colon and rectum, which features recurrent mucosal inflammation. The excessive production of reactive oxygen species (ROS) is a trigger for pathological changes such as cell apoptosis and disordered immune microenvironments, which are crucial for the progression of UC and can be a promising therapeutic target. Nowadays, the development of targeted therapeutic strategies for UC is still in its infancy. Thus, developing effective therapies based on ROS scavenging and elucidating their molecular pathways are urgently needed. Herein, a biomimetic nanoformulation (Pd@M) with cubic palladium (Pd) as the core and macrophage-derived extracellular vesicles (MEVs) as the shell is synthesized for the treatment of UC. These Pd@M nanoformulations exhibit multienzyme-like activities for effective ROS scavenging, excellent targeting ability as well as good biocompatibility. It is verified that Pd@M can regulate the polarization state of macrophages by inhibiting glycolysis, and decrease neutrophil infiltration and recruitment. In this way, the colonic inflammatory and immune microenvironment is remodeled, and apoptosis is prevented, ultimately improving colonic mucosal barrier function and alleviating colitis in the mouse model. This finding provides a promising alternative option for the treatment of UC patients.
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Colitis Ulcerosa , Vesículas Extracelulares , Animales , Ratones , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Paladio/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Macrófagos/metabolismo , Vesículas Extracelulares/metabolismo , HomeostasisRESUMEN
To meet the demand of flexible access for high-precision synchronization frequency, we demonstrate multi-node stable radio frequency (RF) dissemination over a long-distance optical fiber. Stable radio frequency signals can be extracted at any node along the optical fiber, not just at the endpoint. The differential mixing structure (DMS) is employed to avoid the frequency harmonic leakage and enhance the precision. The phase-locked loop (PLL) provides frequency reference for the DMS while improving the signal to noise ratio (SNR) of dissemination signal. We measure the frequency instability of multi-node stable frequency dissemination system (MFDS) at different locations along the 2,000 km optical fiber. The measured short-term instability with average time of 1 s are 1.90 × 10-14 @ 500 km, 2.81 × 10-14 @ 1,000 km, 3.46 × 10-14 @ 1,500 km, and 3.84 × 10-14 @ 2,000 km respectively. The long-term instability with average time of 10,000 s are basically the same at any position of the optical fiber, which is about (6.24 ± 0.05) × 10-17. The resulting instability is sufficient for the propagation of precision active hydrogen masers.
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Improving the productivity and relative efficiency of traditional Chinese medicine (TCM) hospitals is pivotal for hospital managers and policymakers to optimize the utilization of TCM resources in China. This study aimed to measure the productivity and relative efficiency of public tertiary TCM hospitals in Hubei Province. The input and output indicators data were extracted from the Health Commission of Hubei Province (HCHP) from 2019 to 2021. The Bootstrap-Malmquist-DEA model was employed to measure the productivity and relative efficiency of the hospitals. The statistical significance was set at P < .05. The numbers of total diagnostic patients and discharged patients declined by 23.44% and 28.34% from 2019 to 2020, and then increased by 25.76% and 20.44% respectively from 2020 to 2021. The average bias-corrected technical efficiency (TE) scores of the TCM hospitals from 2019 to 2021 were 0.8391, 0.8048, and 0.8559, indicating good efficiency. The average total factor productivity (TFP) in 2020 and 2021 decreased compared to that in 2019, with scores of 0.7479 and 0.8996, respectively. Between 2019 and 2020, the TFP changes among 19 out of 21 (90.48%) TCM hospitals and the technological changes (TC) among 20 out of 21 (95.24%) were less than 1.0000 (P < .05). The TFP changes of 17 out of 21 (80.95%) TCM hospitals and the TC of 20 out of 21 (95.24%) were less than 1.0000 (P < .05) between 2019 and 2021. COVID-19 might have constrained the provision of healthcare services by the public tertiary TCM hospitals in Hubei Province. Priority should be given to the utilization of healthcare resources, performance evaluation, information system strengthening, and internal hospital management to boost technical efficiency. TCM hospitals need to focus further on technology innovation to improve their technological progress.
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Eficiencia Organizacional , Administración Hospitalaria , Humanos , Medicina Tradicional China , Hospitales Públicos , ChinaRESUMEN
Brain-computer interfaces (BCIs) have attracted considerable attention in motor and language rehabilitation. Most devices use cap-based non-invasive, headband-based commercial products or microneedle-based invasive approaches, which are constrained for inconvenience, limited applications, inflammation risks and even irreversible damage to soft tissues. Here, we propose in-ear visual and auditory BCIs based on in-ear bioelectronics, named as SpiralE, which can adaptively expand and spiral along the auditory meatus under electrothermal actuation to ensure conformal contact. Participants achieve offline accuracies of 95% in 9-target steady state visual evoked potential (SSVEP) BCI classification and type target phrases successfully in a calibration-free 40-target online SSVEP speller experiment. Interestingly, in-ear SSVEPs exhibit significant 2nd harmonic tendencies, indicating that in-ear sensing may be complementary for studying harmonic spatial distributions in SSVEP studies. Moreover, natural speech auditory classification accuracy can reach 84% in cocktail party experiments. The SpiralE provides innovative concepts for designing 3D flexible bioelectronics and assists the development of biomedical engineering and neural monitoring.
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Interfaces Cerebro-Computador , Humanos , Potenciales Evocados Visuales , Electroencefalografía , Calibración , Lenguaje , Estimulación Luminosa , AlgoritmosRESUMEN
As ubiquitously expressed transcripts in eukaryotes, circular RNAs (circRNAs) are covalently closed and lack a 5'-cap and 3'-polyadenylation (poly (A)) tail. Initially, circRNAs were considered non-coding RNA (ncRNA), and their roles as sponging molecules to adsorb microRNAs have been extensively reported. However, in recent years, accumulating evidence has demonstrated that circRNAs could encode functional polypeptides through the initiation of translation mediated by internal ribosomal entry sites (IRESs) or N6-methyladenosine (m6A). In this review, we collectively discuss the biogenesis, cognate mRNA products, regulatory mechanisms, aberrant expression and biological phenotypes or clinical relevance of all currently reported, cancer-relevant protein-coding circRNAs. Overall, we provide a comprehensive overview of circRNA-encoded proteins and their physiological and pathological functions.
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MicroARNs , ARN Circular , Humanos , ARN Circular/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero , Carcinogénesis/genética , Transformación Celular NeoplásicaRESUMEN
Droplet-based triboelectric nanogenerators (D-TENGs) have recently gained much attention due to their great potential in harvesting energy. However, the output performance of conventional single-electrode droplet-based TENGs is limited owing to low induced electrification efficiency. The asymmetric distribution of electric fields on both sides of the electrode edge enhances the electrostatic induction process and improves the output performance of D-TENG. Herein, an induced electrification-enhanced droplet-based triboelectric nanogenerator (IED-TENG) is developed to effectively enhance the output performance by simultaneously optimizing the electrode structure and the dynamics of the water droplet. One droplet falling from a height of 30 cm results in a -70 V output voltage and -6 µA short-circuit current, which is 70 times and 20 times the full-inductive-electrode mode, respectively. The working principle and the relationship between electric signal and droplet dynamics are analyzed in detail. Moreover, the peak output voltage can reach -110 V, and the peak current can get -140 µA by using the power generation of multiple water droplets. The present protocol provides an easy and reproducibility strategy in energy harvesting and sensing areas.
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Herbicide pollution is a main form of water pollution. As a result of additional harms to other non-target organisms, it threatens the function and structure of ecosystems. Previous researches mainly focused on the assessment of the toxicity and ecological effect of herbicides on monotrophic organisms. Responses of mixotrophs as an important component of functional groups are rarely understood in contaminated waters, although their metabolic plasticity and unique ecological functions in ecosystem stability are a major concern. This work aimed to investigate the trophic plasticity of mixotrophic organisms in atrazine-contaminated waters, and a primarily heterotrophic Ochromonas was used as the tested organism. Results showed that the herbicide atrazine significantly inhibited the photochemical activity and impaired the photosynthetic machine of Ochromonas, and photosynthesis activated by light was sensitive to atrazine. However, phagotrophy was unaffected by atrazine and closely correlated with growth rate, indicating that heterotrophy helped population maintenance during herbicide exposure. Mixotrophic Ochromonas upregulated the gene expression level involved in photosynthesis, energy synthesis, and antioxidation to adapt to increasing atrazine after long-term exposure. Compared with bacterivory, herbivory increased atrazine tolerance of photosynthesis under mixotrophic status. This study systematically illustrated the mechanism by which mixotrophic Ochromonas respond to the herbicide atrazine at population, photochemical activity, morphology, and gene expression levels and demonstrated the potential effect of atrazine on the metabolic flexibility and ecological niches of mixotrophs. These findings will provide important theoretical reference for governance and management decision-making in contaminated environments.
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Atrazina , Herbicidas , Ochromonas , Atrazina/toxicidad , Atrazina/metabolismo , Herbicidas/toxicidad , Herbicidas/metabolismo , Ecosistema , Fotoquímica , Fotosíntesis , Ochromonas/fisiología , Expresión GénicaRESUMEN
Deltamethrin (DM) is a widely used pesticide and has been generally detected in aquatic systems. To systematically investigate the toxic effects, zebrafish embryos were treated with various concentrations of DM for 120 h. The LC50 was determined to be 102 µg L-1. Lethal concentrations of DM induced severe morphological defects in the surviving individuals. Under non-lethal concentrations, DM suppressed the development of neurons in the larvae, which was associated with the reduction in locomotor activity. DM exposure induced cardiovascular toxicity, including suppressed growth of blood vessels and enhanced heart rates. DM also disrupted the development of bones in the larvae. Moreover, liver degeneration, apoptosis and oxidative stress were observed in the larvae treated with DM. Correspondingly, the transcriptional levels of the genes related to the toxic effects were altered by DM. In conclusion, the results obtained in this study provided evidence that DM showed multiple toxic effects on aquatic organisms.