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ConspectusNeurotechnology has seen dramatic improvements in the last three decades. The major focus in the field has been to design electrical communication platforms with high spatial resolution, stability, and translatability for understanding and affecting neural pathways. The deployment of nanomaterials in bioelectronics has enhanced the capabilities of conventional approaches employing microelectrode arrays (MEAs) for electrical interfaces, allowing the construction of miniaturized, high-performance neuroelectronics (Garg, R.; et al. ACS Appl. Nano Mater. 2023, 6, 8495). While these advancements in the electrical neuronal interface have revolutionized neurotechnology both in scale and breadth, an in-depth understanding of neurons' interactions is challenging due to the complexity of the environments where the cells and tissues are laid. The activity of large, three-dimensional neuronal systems has proven difficult to accurately monitor and modulate, and chemical cell-cell communication is often completely neglected. Recent breakthroughs in nanotechnology have provided opportunities to use new nonelectric modes of communication with neurons and to significantly enhance electrical signal interface capabilities. The enhanced electrochemical activity and optical activity of nanomaterials owing to their nonbulk electronic properties and surface nanostructuring have seen extensive utilization. Nanomaterials' enhanced optical activity enables remote neural state modulation, whereas the defect-rich surfaces provide an enormous number of available electrocatalytic sites for neurochemical detection and electrochemical modulation of cell microenvironments through Faradaic processes. Such unique properties can allow multimodal neural interrogation toward generating closed-loop interfaces with access to more complete neural state descriptors. In this Account, we will review recent advances and our efforts spearheaded toward utilizing nanostructured electrodes for enhanced bidirectional interfaces with neurons, the application of unique hybrid nanomaterials for remote nongenetic optical stimulation of neurons, tunable nanomaterials for highly sensitive and selective neurotransmitter detection, and the utilization of nanomaterials as electrocatalysts toward electrochemically modulating cellular activity. We highlight applications of these technologies across cell types through nanomaterial engineering with a focus on multifunctional graphene nanostructures applied though several modes of neural modulation but also an exploration of broad material classes for maximizing the potency of closed-loop bioelectronics.
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Nanoestructuras , Neuronas , Nanoestructuras/química , Neuronas/fisiología , Humanos , Microelectrodos , Animales , Nanotecnología/métodosRESUMEN
Chemoresistance remains a major challenge in the current treatment of acute myeloid leukemia (AML). The bone marrow microenvironment (BMM) plays a complex role in protecting leukemia cells from chemotherapeutics, and the mechanisms involved are not fully understood. Antileukemia drugs kill AML cells directly but also damage the BMM. Here, we determined antileukemia drugs induce DNA damage in bone marrow stromal cells (BMSCs), resulting in resistance of AML cell lines to adriamycin and idarubicin killing. Damaged BMSCs induced an inflammatory microenvironment through NF-κB; suppressing NF-κB with small molecule inhibitor Bay11-7082 attenuated the prosurvival effects of BMSCs on AML cell lines. Furthermore, we used an ex vivo functional screen of 507 chemokines and cytokines to identify 44 proteins secreted from damaged BMSCs. Fibroblast growth factor-10 (FGF10) was most strongly associated with chemoresistance in AML cell lines. Additionally, expression of FGF10 and its receptors, FGFR1 and FGFR2, was increased in AML patients after chemotherapy. FGFR1 and FGFR2 were also widely expressed by AML cell lines. FGF10-induced FGFR2 activation in AML cell lines operates by increasing P38 MAPK, AKT, ERK1/2, and STAT3 phosphorylation. FGFR2 inhibition with small molecules or gene silencing of FGFR2 inhibited proliferation and reverses drug resistance of AML cells by inhibiting P38 MAPK, AKT, and ERK1/2 signaling pathways. Finally, release of FGF10 was mediated by ß-catenin signaling in damaged BMSCs. Our data indicate FGF10-FGFR2 signaling acts as an effector of damaged BMSC-mediated chemoresistance in AML cells, and FGFR2 inhibition can reverse stromal protection and AML cell chemoresistance in the BMM.
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Resistencia a Antineoplásicos , Leucemia Mieloide Aguda , Células Madre Mesenquimatosas , Humanos , Células de la Médula Ósea/metabolismo , Daño del ADN , Factor 10 de Crecimiento de Fibroblastos/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Células Madre Mesenquimatosas/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Células del Estroma/metabolismo , Microambiente Tumoral , Comunicación ParacrinaRESUMEN
BACKGROUND: Advanced hepatocellular carcinoma (HCC) can be treated with sorafenib, which is the primary choice for targeted therapy. Nevertheless, the effectiveness of sorafenib is greatly restricted due to resistance. Research has shown that exosomes and circular RNAs play a vital role in the cancer's malignant advancement. However, the significance of exosomal circular RNAs in the development of resistance to sorafenib in HCC remains uncertain. METHODS: Ultracentrifugation was utilized to isolate exosomes (Exo-SR) from the sorafenib-resistant HCC cells' culture medium. Transcriptome sequencing and differential expression gene analysis were used to identify the targets of Exo-SR action in HCC cells. To identify the targets of Exo-SR action in HCC cells, transcriptome sequencing and analysis of differential expression genes were employed. To evaluate the impact of exosomal circUPF2 on resistance to sorafenib in HCC, experiments involving gain-of-function and loss-of-function were conducted. RNA pull-down assays and mass spectrometry analysis were performed to identify the RNA-binding proteins interacting with circUPF2. RNA immunoprecipitation (RIP), RNA pull-down, electrophoretic mobility shift assay (EMSA), immunofluorescence (IF) -fluorescence in situ hybridization (FISH), and rescue assays were used to validate the interactions among circUPF2, IGF2BP2 and SLC7A11. Finally, a tumor xenograft assay was used to examine the biological functions and underlying mechanisms of Exo-SR and circUPF2 in vivo. RESULTS: A novel exosomal circRNA, circUPF2, was identified and revealed to be significantly enriched in Exo-SR. Exosomes with enriched circUPF2 enhanced sorafenib resistance by promoting SLC7A11 expression and suppressing ferroptosis in HCC cells. Mechanistically, circUPF2 acts as a framework to enhance the creation of the circUPF2-IGF2BP2-SLC7A11 ternary complex contributing to the stabilization of SLC7A11 mRNA. Consequently, exosomal circUPF2 promotes SLC7A11 expression and enhances the function of system Xc- in HCC cells, leading to decreased sensitivity to ferroptosis and resistance to sorafenib. CONCLUSIONS: The resistance to sorafenib in HCC is facilitated by the exosomal circUPF2, which promotes the formation of the circUPF2-IGF2BP2-SLC7A11 ternary complex and increases the stability of SLC7A11 mRNA. Focusing on exosomal circUPF2 could potentially be an innovative approach for HCC treatment.
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Carcinoma Hepatocelular , Resistencia a Antineoplásicos , Exosomas , Ferroptosis , Neoplasias Hepáticas , ARN Circular , Proteínas de Unión al ARN , Sorafenib , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Humanos , Exosomas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Sorafenib/farmacología , ARN Circular/genética , ARN Circular/metabolismo , Ferroptosis/efectos de los fármacos , Línea Celular Tumoral , Animales , Ratones , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Ratones Desnudos , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos BALB CRESUMEN
Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient. Compared to those in neat and depleted plasma, the plasma proteins identified by our assay exhibited distinct biological profiles, as validated in several public datasets. A pilot investigation of the proteomic profile of a hepatocellular carcinoma (HCC) cohort identified 15 promising protein features, highlighting the diagnostic value of the plasma proteome in distinguishing individuals with and without HCC. Furthermore, this assay can be easily integrated with all current downstream protein profiling methods and potentially extended to other biofluids. In conclusion, we established a robust and efficient plasma proteomic assay with unprecedented identification depth, paving the way for the translation of plasma proteomics into clinical applications.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Zeolitas , Humanos , Carcinoma Hepatocelular/diagnóstico , Proteoma , Proteómica/métodos , Neoplasias Hepáticas/diagnóstico , Biomarcadores/análisis , Proteínas Sanguíneas/análisisRESUMEN
BACKGROUND: To evaluate the efficacy, effectiveness and safety of fermented Ophiocordyceps sinensis mycelium (FOSM) products for preventing contrast-associated acute kidney injury (CA-AKI). METHODS: Randomized controlled trials were searched from four Chinese and four English electronic databases and three clinical trial registries up to July 2023. Methodological quality was assessed by using the Cochrane risk-of-bias tool 2.0. Risk difference (RD) or risk ratio (RR) and mean difference (MD) were calculated along with the 95% confidence intervals (CIs). RESULTS: Fourteen trials testing three types of FOSM products (Bailing, Zhiling, and Jinshuibao capsules) involving 1271 participants injected contrast agents were included. For the risk of bias, all trials were rated as some concerns. Compared with routine preventive procedure (RPP) (saline hydration and alprostadil), FOSM products plus RPP showed beneficial effects in reducing the incidence of CA-AKI (14.62% and 5.35%, respectively; RD -0.06, 95% CI -0.09 to -0.03). Subgroup analysis showed that Bailing/Jinshuibao plus RPP demonstrated lower incidence of CA-AKI compared to RPP. However, there was no statistically significant difference between Zhiling with RPP and RPP in the incidence of CA-AKI. Additionally, only when FOSM products were taken before injection of the contrast, it was superior to RPP in reducing the incidence of CA-AKI. There was no statistical difference in adverse events between these two groups. CONCLUSIONS: Low certainty evidence suggests that preventive oral use of FOSM products as an adjuvant agent was safe and might decrease the incidence of CA-AKI. However, high-quality placebo-controlled trials are needed to confirm its benefit.
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Lesión Renal Aguda , Productos Biológicos , Cordyceps , Humanos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/prevención & control , Adyuvantes Farmacéuticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Productos Biológicos/uso terapéuticoRESUMEN
BACKGROUND & AIMS: Copper (Cu) is an essential trace element whose serum levels have been reported to act as an effective indicator of the efficacy of radiotherapy. However, little is known about the role of Cu in radiotherapy. In this study we aimed to determine this role and investigate the precise mechanism by which Cu or Cu-related proteins regulate the radiosensitivity of hepatocellular carcinoma (HCC). METHODS: The expression and function of Cu and copper metabolism MURR1 domain 10 (COMMD10) were assessed via a Cu detection assay, immunostaining, real-time PCR, western blot, a radiation clonogenic assay and a 5-ethynyl-2'-deoxyuridine assay. Ferroptosis was determined by detecting glutathione, lipid peroxidation, malondialdehyde and ferrous ion (Fe) levels. The in vivo effects of Cu and COMMD10 were examined with Cu/Cu chelator treatment or lentivirus modification of COMMD10 expression in radiated mouse models. RESULTS: We identified a novel role of Cu in promoting the radioresistance of HCC cells. Ionizing radiation (IR) induced a reduction of COMMD10, which increased intracellular Cu and led to radioresistance of HCC. COMMD10 enhanced ferroptosis and radiosensitivity in vitro and in vivo. Mechanistically, low expression of COMMD10 induced by IR inhibited the ubiquitin degradation of HIF1α (by inducing Cu accumulation) and simultaneously impaired its combination with HIF1α, promoting HIF1α nuclear translocation and the transcription of ceruloplasmin (CP) and SLC7A11, which jointly inhibited ferroptosis in HCC cells. In addition, elevated CP promoted HIF1α expression by reducing Fe, forming a positive feedback loop. CONCLUSIONS: COMMD10 inhibits the HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe homeostasis in HCC. This work provides new targets and treatment strategies for overcoming radioresistance in HCC. LAY SUMMARY: Radiotherapy benefits patients with unresectable or advanced hepatocellular carcinoma (HCC), but its effectiveness is hampered by radioresistance. Herein, we uncovered a novel role for copper in promoting the radioresistance of HCCs. This work has revealed new targets and potential treatment strategies that could be used to sensitize HCC to radiotherapy.
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Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/radioterapia , Línea Celular Tumoral , Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Cobre/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Hierro/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , Ratones , Tolerancia a Radiación/genéticaRESUMEN
We report here, and rationalize, a synergistic effect between a non-noble metal oxide catalyst (CuO) and high-frequency ultrasound (HFUS) on glucose oxidation. While CuO and HFUS are able to independently oxidize glucose to gluconic acid, the combination of CuO with HFUS led to a dramatic change of the reaction selectivity, with glucuronic acid being formed as the major product. By means of density functional theory (DFT) calculations, we show that, under ultrasonic irradiation of water at 550 kHz, the surface lattice oxygen of a CuO catalyst traps H· radicals stemming from the sonolysis of water, making the ring-opening of glucose energetically unfavorable and leaving a high coverage of ·OH radical on the CuO surface, which selectively oxidizes glucose to glucuronic acid. This work also points toward a path to optimize the size of the catalyst particle for an ultrasonic frequency that minimizes the damage to the catalyst, resulting in its successful reuse.
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Copper (Cu), a crucial trace element in physiological processes, has garnered significant interest for its involvement in cancer progression and potential therapeutic applications. The regulation of cellular copper levels is essential for maintaining copper homeostasis, as imbalances can lead to toxicity and cell death. The development of drugs that target copper homeostasis has emerged as a promising strategy for anticancer treatment, with a particular focus on copper chelators, copper ionophores, and novel copper complexes. Recent research has also investigated the potential of copper complexes in cancer therapy.
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Antineoplásicos , Complejos de Coordinación , Cobre , Neoplasias , Cobre/química , Cobre/farmacología , Humanos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Quelantes/química , Quelantes/farmacología , Quelantes/síntesis química , Animales , Estructura MolecularRESUMEN
BACKGROUND: Multiple countries have conducted surveys on the level of life space mobility for community-dwelling elderly through the Life-Space Assessment, the results vary greatly, from 41.7 to 88.6. However, there is no meta-analysis on the current situation of community-dwelling elderly life space mobility. OBJECTIVE: To systematically assess the global level of life space mobility for community-dwelling elderly, to identify potential covariates such as geographical regions, survey years, gender, and age that contribute to the heterogeneity between the studies, and to identify the dynamic trend based on survey years. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Two reviewers searched the following 8 electronic bibliographic databases from inception until May 28, 2023: PubMed, The Cochrane Library, Web of Science, Embase, Chinese Biomedical Database, China Knowledge Resource Integrated Database, WanFang, and Weipu Database. REVIEW METHODS: This review was conducted using the Stata 14.1 and R 4.3.1. The Cochrane's Q statistical and I2 index were used to test for heterogenicity and assess the degree of heterogenicity, respectively. Studies were appraised using the Agency for Healthcare Research and Quality tool, the Newcastle-Ottawa Scale for the quality of cross-sectional studies, cohort studies, respectively. RESULTS: A total of 29 studies were selected from databases and reference lists. The pooled score of Life-Space Assessment was 66.84 (95% CI: 63.30-70.39) and the prevalence of restricted life space was 42% (95% CI: 0.27-0.57). The geographical regions, survey years, gender were found to be a significant covariate of the pooled score of life space mobility estimate in the subgroup analysis. The mean score of Life-Space Assessment gradually achieved stability after 2017. CONCLUSIONS: The life space mobility of community-dwelling elderly in the global is at a moderate level, with 42% of them experiencing restricted life space. South America, females and earlier survey years have a lower level of life space mobility. In the future, the government should identify vulnerable groups for targeted intervention to promote the level of LSM in the community-dwelling elderly. REGISTRATION: PROSPERO [CRD42023443054].
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Vida Independiente , Femenino , Humanos , Anciano , Estudios Transversales , Estudios de Cohortes , Prevalencia , ChinaRESUMEN
OBJECTIVE: The fragility index (FI), which is the minimum number of changes in status from "event" to "non-event" resulting in a loss of statistical significance, serves as a significant supplementary indicator for clinical physicians in interpreting clinical trial results and aids in understanding the outcomes of randomized controlled trials (RCTs). In this systematic literature survey, we evaluated the FI for RCTs evaluating Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS), and explored potential associations between study characteristics and the robustness of RCTs. METHODS: A comprehensive search was conducted in four databases in Chinese and four databases in English from their inception to January 1, 2023. RCTs encompassed 1:1 ratio into two parallel arms and reported at least one binary outcome that demonstrated statistical significance were included. FI was calculated by the iterative reduction of a target outcome event in the treatment group and concomitant subtraction of a non-target event from that group, until positive significance (defined as P < 0.05 by Fisher's exact test) is lost. The lower the FI (minimum 1) of a trial outcome, the more fragile the positive result of the outcome was. Linear regression models were adopted to explore influence factors of the value of FI. RESULTS: A total of 30 trials from 2 4118 potentially relevant citations were finally included. The median FI of total trials included was 1.5 (interquartile range [IQR], 1-5), and half of the trials (n = 15) had a FI equal to 1. In 12 trials (40%), the total number of participants lost to follow-up surpassed the respective FI. The study also identified that increased FI was significantly associated with no TCM syndrome differentiation for inclusion criteria of the patients, larger total sample size, low risk of bias, and larger numbers of events. CONCLUSIONS: The majority of CHM IBS RCTs with positive results were found to be fragile. Ensuring adequate sample size, scientifically rigorous study design, proper control of confounding factors, and a quality control calibration for consistency of TCM diagnostic results among clinicians should be addressed to increase the robustness of the RCTs. We recommend reporting the FI as one of the components of sensitivity analysis in future RCTs to facilitate the assessment of the fragility of trials.
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Medicamentos Herbarios Chinos , Síndrome del Colon Irritable , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome del Colon Irritable/tratamiento farmacológico , Humanos , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Serological tests for Epstein-Barr virus (EBV) antibodies have been widely conducted for the screening of nasopharyngeal carcinoma (NPC) in endemic areas. Further risk stratification of NPC can be achieved through plasma lipoprotein and metabolic profiles. A total of 297 NPC patients and 149 EBV-positive participants are enrolled from the NCT03919552 and NCT05682703 cohorts for plasma nuclear magnetic resonance (NMR) metabolomic analysis. Small, dense very low density lipoprotein particles (VLDL-5) and large, buoyant low density lipoprotein particles (LDL-1) are found to be closely associated with nasopharyngeal carcinogenesis. Herein, an NMR-based risk score (NRS), which combines lipoprotein subfractions and metabolic biomarkers relevant to NPC, is developed and well validated within a multicenter cohort. Combining the median cutoff value of the NRS (N50) with that of the serological test for EBV antibodies, the risk stratification model achieves a satisfactory performance in which the area under the curve (AUC) is 0.841 (95% confidence interval: 0.811-0.871), and the positive predictive value (PPV) reaches 70.08% in the combined cohort. These findings not only suggest that VLDL-5 and LDL-1 particles can serve as novel risk factors for NPC but also indicate that the NRS has significant potential in personalized risk prediction for NPC.
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Infecciones por Virus de Epstein-Barr , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/diagnóstico , Femenino , Persona de Mediana Edad , Estudios de Cohortes , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/virología , Adulto , Medición de Riesgo/métodos , Herpesvirus Humano 4/inmunología , Lipoproteínas VLDL/sangre , Lipoproteínas LDL/sangreRESUMEN
Carbon electrodes are ideal for electrochemistry with molecular catalysts, exhibiting facile charge transfer and good stability. Yet for solar-driven catalysis with semiconductor light absorbers, stable semiconductor/carbon interfaces can be difficult to achieve, and carbon's high optical extinction means it can only be used in ultrathin layers. Here, we demonstrate a plasma-enhanced chemical vapor deposition process that achieves well-controlled deposition of out-of-plane "fuzzy" graphene (FG) on thermally oxidized Si substrates. The resulting Si|FG interfaces possess a silicon oxycarbide (SiOC) interfacial layer, implying covalent bonding between Si and the FG film that is consistent with the mechanical robustness observed from the films. The FG layer is uniform and tunable in thickness and optical transparency by deposition time. Using p-type Si|FG substrates, noncovalent immobilization of cobalt phthalocyanine (CoPc) molecular catalysts was employed for the photoelectrochemical reduction of CO2 in aqueous solution. The Si|FG|CoPc photocathodes exhibited good catalytic activity, yielding a current density of â¼1 mA/cm2, Faradaic efficiency for CO of â¼70% (balance H2), and stable photocurrent for at least 30 h at -1.5 V vs Ag/AgCl under 1-sun illumination. The results suggest that plasma-deposited FG is a robust carbon electrode for molecular catalysts and suitable for further development of aqueous-stable Si photocathodes for CO2 reduction.
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PURPOSE: The efficacy of induction chemotherapy (IC) as a primary treatment for advanced nasopharyngeal carcinoma (NPC) remains a topic of debate, with a lack of dependable biomarkers for predicting its efficacy. This study seeks to establish a predictive classifier using plasma metabolomics profiles. PATIENTS AND METHODS: A total of 166 NPC patients enrolled in the clinical trial NCT05682703 who were undergoing IC were included in the study. Plasma lipoprotein profiles were obtained using 1H-nuclear magnetic resonance before and after IC treatment. An artificial intelligence-assisted radiomics method was developed to effectively evaluate its efficacy. Metabolic biomarkers were identified through a machine learning approach based on a discovery cohort and subsequently validated in a validation cohort that mimicked the most unfavorable real-world scenario. RESULTS: Our research findings indicate that the effectiveness of IC varies among individual patients, with a correlation observed between efficacy and changes in metabolite profiles. Using machine learning techniques, it was determined that the extreme gradient boosting model exhibited notable efficacy, attaining an area under the curve (AUC) value of 0.792 (95% CI, 0.668-0.913). In the validation cohort, the model exhibited strong stability and generalizability, with an AUC of 0.786 (95% CI, 0.533-0.922). CONCLUSIONS: In this study, we found that dysregulation of plasma lipoprotein may result in resistance to IC in NPC patients. The prediction model constructed based on the plasma metabolites' profile has good predictive capabilities and potential for real-world generalization. This discovery has implications for the development of treatment strategies and may offer insight into potential targets for enhancing the effectiveness of IC.
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Biomarcadores de Tumor , Quimioterapia de Inducción , Metaboloma , Metabolómica , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/patología , Masculino , Persona de Mediana Edad , Adulto , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Metabolómica/métodos , Biomarcadores de Tumor/sangre , Aprendizaje Automático , Resultado del Tratamiento , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , PronósticoRESUMEN
Seamless integration of the body and electronics toward the understanding, quantification, and control of disease states remains one of the grand scientific challenges of this era. As such, research efforts have been dedicated to developing bioelectronic devices for chemical, mechanical, and electrical sensing, and cellular and tissue functionality modulation. The technologies developed to achieve these capabilities cross a wide range of materials and scale (and dimensionality), e.g., from micrometer to centimeters (from 2-dimensional (2D) to 3-dimensional (3D) assemblies). The integration into multimodal systems which allow greater insight and control into intrinsically multifaceted biological systems requires careful design and selection. This snapshot review will highlight the state-of-the-art in cellular recording and modulation as well as the material considerations for the design and manufacturing of devices integrating their capabilities.
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Exosomes contribute substantially to the communication between tumor cells and normal cells. Benefiting from the stable structure, circular RNAs (circRNAs) are believed to serve an important function in exosome-mediated intercellular communication. Here, we focused on circRNAs enriched in starvation-stressed hepatocytic exosomes and further investigated their function and mechanism in hepatocellular carcinoma (HCC) progression. Differentially expressed circRNAs in exosomes were identified by RNA sequencing, and circTGFBR2 was identified and chosen for further study. The molecular mechanism of circTGFBR2 in HCC was demonstrated by RNA pulldown, RIP, dual-luciferase reporter assays, rescue experiments and tumor xenograft assay both in vitro and vivo. We confirmed exosomes with enriched circTGFBR2 led to an upregulated resistance of HCC cells to starvation stress. Mechanistically, circTGFBR2 delivered into HCC cells via exosomes serves as a competing endogenous RNA by binding miR-205-5p to facilitate ATG5 expression and enhance autophagy in HCC cells, resulting in resistance to starvation. Thus, we revealed that circTGFBR2 is a novel tumor promoter circRNA in hepatocytic exosomes and promotes HCC progression by enhancing ATG5-mediated protective autophagy via the circTGFBR2/miR-205-5p/ATG5 axis, which may be a potential therapeutic target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , ARN Circular/genética , ARN Circular/metabolismo , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Autofagia/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteína 5 Relacionada con la Autofagia/genética , Proteína 5 Relacionada con la Autofagia/metabolismoRESUMEN
People make fast and reasonable predictions about the physical behavior of everyday objects. To do so, people may use principled mental shortcuts, such as object simplification, similar to models developed by engineers for real-time physical simulations. We hypothesize that people use simplified object approximations for tracking and action (the body representation), as opposed to fine-grained forms for visual recognition (the shape representation). We used three classic psychophysical tasks (causality perception, time-to-collision, and change detection) in novel settings that dissociate body and shape. People's behavior across tasks indicates that they rely on coarse bodies for physical reasoning, which lies between convex hulls and fine-grained shapes. Our empirical and computational findings shed light on basic representations people use to understand everyday dynamics, and how these representations differ from those used for recognition. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Hydrogels are promising materials for soft and implantable strain sensors owing to their large compliance (E<100 kPa) and significant extensibility (εmax >500%) compared to other polymer networks. Further, hydrogels can be functionalized to seamlessly integrate with many types of tissues. However, most current methods attempt to imbue additional electronic functionality to structural hydrogel materials by incorporating fillers with orthogonal properties such as electronic or mixed ionic conduction. Although composite strategies may improve performance or facilitate heterogeneous integration with downstream hardware, composites complicate the path for regulatory approval and may compromise the otherwise compelling properties of the underlying structural material. Here we report hydrogel strain sensors composed of genipin-crosslinked gelatin and dopamine-functionalized poly(ethylene glycol) for in vivo monitoring of cardiac function. By measuring their impedance only in their resistive regime (>10 kHz), hysteresis is reduced and the resulting gauge factor is increased by ~50x to 1.02±0.05 and 1.46±0.05 from approximately 0.03-0.05 for PEG-Dopa and genipin-crosslinked gelatin respectively. Adhesion and in vivo biocompatibility are studied to support implementation of strain sensors for monitoring cardiac output in porcine models. Impedance-based strain sensing in the kilohertz regime simplifies the piezoresistive behavior of these materials and expands the range of hydrogel-based strain sensors.
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Understanding the communication of individual neurons necessitates precise control of neural activity. Photothermal modulation is a remote and non-genetic technique to control neural activity with high spatiotemporal resolution. The local heat release by photothermally active nanomaterial will change the membrane properties of the interfaced neurons during light illumination. Recently, it is demonstrated that the two-dimensional Ti3 C2 Tx MXene is an outstanding candidate to photothermally excite neurons with low incident energy. However, the safety of using Ti3 C2 Tx for neural modulation is unknown. Here, the biosafety of Ti3 C2 Tx -based photothermal modulation is thoroughly investigated, including assessments of plasma membrane integrity, mitochondrial stress, and oxidative stress. It is demonstrated that culturing neurons on 25 µg cm-2 Ti3 C2 Tx films and illuminating them with laser pulses (635 nm) with different incident energies (2-10 µJ per pulse) and different pulse frequencies (1 pulse, 1 Hz, and 10 Hz) neither damage the cell membrane, induce cellular stress, nor generate oxidative stress. The threshold energy to cause damage (i.e., 14 µJ per pulse) exceeded the incident energy for neural excitation (<10 µJ per pulse). This multi-assay safety evaluation provides crucial insights for guiding the establishment of light conditions and protocols in the clinical translation of photothermal modulation.
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The roles of cerebral structures distal to isolated thalamic infarcts in cognitive deficits remain unclear. We aimed to identify the in vivo microstructural characteristics of remote gray matter (GM) and thalamic pathways and elucidate their roles across cognitive domains. Patients with isolated ischemic thalamic stroke and healthy controls underwent neuropsychological assessment and magnetic resonance imaging. Neurite orientation dispersion and density imaging (NODDI) was modeled to derive the intracellular volume fraction (VFic) and orientation dispersion index. Fiber density (FD) was determined by constrained spherical deconvolution, and tensor-derived fractional anisotropy (FA) was calculated. Voxel-wise GM analysis and thalamic pathway tractography were performed. Twenty-six patients and 26 healthy controls were included. Patients exhibited reduced VFic in remote GM regions, including ipsilesional insular and temporal subregions. The microstructural metrics VFic, FD, and FA within ipsilesional thalamic pathways decreased (false discovery rate [FDR]-p < 0.05). Noteworthy associations emerged as VFic within insular cortices (ρ = -0.791 to -0.630; FDR-p < 0.05) and FD in tracts connecting the thalamus and insula (ρ = 0.830 to 0.971; FDR-p < 0.001) were closely associated with executive function. The VFic in Brodmann area 52 (ρ = -0.839; FDR-p = 0.005) and FA within its thalamic pathway (ρ = -0.799; FDR-p = 0.003) correlated with total auditory memory scores. In conclusion, NODDI revealed neurite loss in remote normal-appearing GM regions and ipsilesional thalamic pathways in thalamic stroke. Reduced cortical dendritic density and axonal density of thalamocortical tracts in specific subregions were associated with improved cognitive functions. Subacute microstructural alterations beyond focal thalamic infarcts might reflect beneficial remodeling indicating post-stroke plasticity.
RESUMEN
Implantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant host. Previous exogenous oxygenation strategies have been bulky and had limited oxygen production or regulation. Here, we show an electrocatalytic approach that enables bioelectronic control of oxygen generation in complex cellular environments to sustain engineered cell viability and therapy under hypoxic stress and at high cell densities. We find that nanostructured sputtered iridium oxide serves as an ideal catalyst for oxygen evolution reaction at neutral pH. We demonstrate that this approach exhibits a lower oxygenation onset and selective oxygen production without evolution of toxic byproducts. We show that this electrocatalytic on site oxygenator can sustain high cell loadings (>60k cells/mm3) in hypoxic conditions in vitro and in vivo. Our results showcase that exogenous oxygen production devices can be readily integrated into bioelectronic platforms, enabling high cell loadings in smaller devices with broad applicability.