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Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.
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Gene co-expression networks may encode hitherto inadequately recognized vulnerabilities for adult gliomas. By identifying evolutionally conserved gene co-expression modules around EGFR (EM) or PDGFRA (PM), we recently proposed an EM/PM classification scheme, which assigns IDH-wildtype glioblastomas (GBM) into the EM subtype committed in neural stem cell compartment, IDH-mutant astrocytomas and oligodendrogliomas into the PM subtype committed in early oligodendrocyte lineage. Here, we report the identification of EM/PM subtype-specific gene co-expression networks and the characterization of hub gene polypyrimidine tract-binding protein 1 (PTBP1) as a genomic alteration-independent vulnerability in IDH-wildtype GBM. Supervised by the EM/PM classification scheme, we applied weighted gene co-expression network analysis to identify subtype-specific global gene co-expression modules. These gene co-expression modules were characterized for their clinical relevance, cellular origin and conserved expression pattern during brain development. Using lentiviral vector-mediated constitutive or inducible knockdown, we characterized the effects of PTBP1 on the survival of IDH-wildtype GBM cells, which was complemented with the analysis of PTBP1-depedent splicing pattern and overexpression of splicing target neuron-specific CDC42 (CDC42-N) isoform. Transcriptomes of adult gliomas can be robustly assigned into 4 large gene co-expression modules that are prognostically relevant and are derived from either malignant cells of the EM/PM subtypes or tumor microenvironment. The EM subtype is associated with a malignant cell-intrinsic gene module involved in pre-mRNA splicing, DNA replication and damage response, and chromosome segregation, and a microenvironment-derived gene module predominantly involved in extracellular matrix organization and infiltrating immune cells. The PM subtype is associated with two malignant cell-intrinsic gene modules predominantly involved in transcriptional regulation and mRNA translation, respectively. Expression levels of these gene modules are independent prognostic factors and malignant cell-intrinsic gene modules are conserved during brain development. Focusing on the EM subtype, we identified PTBP1 as the most significant hub for the malignant cell-intrinsic gene module. PTBP1 is not altered in most glioma genomes. PTBP1 represses the conserved splicing of CDC42-N. PTBP1 knockdown or CDC42-N overexpression disrupts actin cytoskeleton dynamics, causing accumulation of reactive oxygen species and cell apoptosis. PTBP1-mediated repression of CDC42-N splicing represents a potential genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype GBM.
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Glioblastoma , Ribonucleoproteínas Nucleares Heterogéneas , Proteína de Unión al Tracto de Polipirimidina , Proteína de Unión al GTP cdc42 , Proteína de Unión al Tracto de Polipirimidina/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Humanos , Ribonucleoproteínas Nucleares Heterogéneas/genética , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Proteína de Unión al GTP cdc42/genética , Proteína de Unión al GTP cdc42/metabolismo , Línea Celular Tumoral , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Redes Reguladoras de Genes , Regulación Neoplásica de la Expresión Génica , Empalme del ARN , Neuronas/metabolismo , Neuronas/patologíaRESUMEN
OBJECTIVES: Malnutrition and nutritional risk are risk factors for many adverse health outcomes in older adults, but they have rarely been assessed in China. The aim of this study was to evaluate the availability of Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA), a nutritional scale originally developed to predict mortality, in assessing nutritional risks and predicting adverse health outcomes in Chinese community-dwelling older adults. METHODS: This was a population-based longitudinal cohort study (Chinese Longitudinal Healthy Longevity Survey), with a 4-y follow-up of 2063 community-dwelling adults aged 65 y or older. Nutritional risks were assessed via the use of ENIGMA and Geriatric Nutritional Risk Index (GNRI) at baseline (the 2014 wave). Cognitive impairment, functional limitation, and frailty were evaluated using the Chinese version of the Mini-Mental State Examination, Instrumental Activities of Daily Living/Instrumental Activities of Daily Living scale, and Frailty Index, respectively, at baseline and 4-y follow-up (the 2018 wave). Mortality was measured by survival status and duration of exposure to death from baseline to follow-up. The associations of nutritional risks with prevalent/incident cognitive impairment, functional limitation and frailty, and 4-y mortality were estimated using logistic regression and Cox proportional hazards regression models, adjusting for confounders. The discriminatory accuracy of ENIGMA and GNRI for these adverse health outcomes were compared by receiver operating characteristic analyses. RESULTS: According to ENIGMA, 48.6% of the Chinese community-dwelling older adults (age: 86.5±11.3 y) showed moderate and high nutritional risk. Nutritional risks defined by the ENIGMA were significantly associated with increased prevalence and incidence of cognitive impairment, functional limitation, and frailty (odds ratio ranging from 1.79 to 89.6, values ranging from P < 0.001 to 0.048) but were mostly insignificant for that defined by GNRI. With respect to 4-y mortality, nutritional risks as defined by GNRI showed better prediction effects than those defined by ENIGMA. Receiver operating characteristic analyses indicated that nutritional risks defined by ENIGMA had better discriminatory accuracy than those defined by GNRI for prevalent and incident cognitive impairment (C = 0.73 vs 0.64, P < 0.001; C = 0.65 vs 0.59, P = 0.015, respectively), functional limitation (C = 0.74 vs 0.63, P < 0.001 at baseline; C = 0.61 vs 0.56, P = 0.016 at follow-up), frailty (C = 0.85 vs 0.67, P < 0.001 at baseline; C = 0.64 vs 0.55, P < 0.001 at follow-up), and even 4-y mortality (C = 0.68 vs 0.64, P = 0.020). CONCLUSIONS: ENIGMA could serve as a nutritional risk screening tool that has a robust role in predicting cognitive impairment, functional limitation, and frailty in Chinese community-dwelling older adults. It may be recommended for early nutritional risk screening and has the potential to guide early nutritional intervention in communities and primary care settings in China.
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BACKGROUND: Delta-like ligand 3 (DLL3) is highly expressed on the cell surface of small cell lung cancer (SCLC), one of the most lethal malignancies, but minimally or not in normal tissues, making it an attractive target for SCLC. However, none of the DLL3-targeting antibody-drug conjugates (ADCs) have been approved for SCLC therapy yet. We developed DB-1314, the new anti-DLL3 ADC composed of a novel humanized anti-DLL3 monoclonal antibody (DB131401) conjugated with eight molecules of P1021 (topoisomerase I inhibitor), and described its preclinical profiles. METHODS: The binding epitope for DB131401 and Rovalpituzumab was tested by biolayer interferometry. The binding affinity and specificity of DB-1314 to DLL3 and other homologous proteins were respectively measured by surface plasmon resonance and enzyme-linked immunosorbent assay. Internalization, bystander effects, and antibody-dependent cell-mediated cytotoxicity (ADCC) were assessed by respective assay. DLL3 was quantified by antibodies bound per cell assay and immunohistochemistry. In vitro and in vivo growth inhibition studies were evaluated in SCLC cell lines, and cell line/patient-derived xenograft models. The safety profile was measured in cynomolgus monkeys. RESULTS: DB-1314 induces potent, durable, and dose-dependent antitumor effects in cells in vitro and in cell/patient-derived xenograft models in vivo. The killing activity of DB-1314 mechanically arises from P1021-induced DNA damage, whereby P1021 is delivered and released within tumor cells through DLL3-specific binding and efficient internalization. Bystander effects and ADCC also contribute to the antitumor activity of DB-1314. DB-1314 displays favorable pharmacokinetic and toxicokinetic profiles in rats and cynomolgus monkeys; besides, DB-1314 is well-tolerated at a dose of up to 60 mg/kg in monkeys. CONCLUSIONS: These results suggest that DB-1314 may be a candidate ADC targeting DLL3 for the treatment of DLL3-positive SCLC, supporting further evaluation in the clinical setting.
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Inmunoconjugados , Neoplasias Pulmonares , Proteínas de la Membrana , Carcinoma Pulmonar de Células Pequeñas , Inhibidores de Topoisomerasa I , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Humanos , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa I/uso terapéutico , Línea Celular Tumoral , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/antagonistas & inhibidores , Macaca fascicularis , Ensayos Antitumor por Modelo de Xenoinjerto , Ratas , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Ratones , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , BenzodiazepinonasRESUMEN
Magnoflorine (Mag), a natural alkaloid component originating from the Ranunculaceae Juss. Family, has a various of pharmacological activities. This study aimed to investigate the therapeutic effects and potential mechanism of Mag on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) based on comprehensive approaches. Therapeutic effects of Mag on 3% DSS-induced UC mice were analyzed. UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway of Mag on DSS-induced UC. Furthermore, the predicted mRNA and protein levels of JAK2/STAT3 signaling pathway in colon tissue were verified and assessed by qRT-PCR and Western Blotting, respectively. Therapeutic effects of Mag on UC mice were presented in down-regulation serum biochemical indices, alleviating histological damage of colon tissue. Serum untargeted metabolomics analysis showed that the potential mechanism of Mag on UC is mainly associated with the regulation of six biomarkers and 11 pathways, which may be responsible for the therapeutic efficacy of UC. The "component-metabolites-targets" interactive network indicated that Mag exerts its anti-UC effect by regulating PTGS1 and PTGS2, thereby regulating arachidonic acid. Moreover, the results of qRT-PCR showed that Mag could substantially decrease the relative mRNA expression level of Hub genes. In addition, it was found that Mag could inhibit the relative mRNA and protein expression of JAK2/STAT3 signaling pathway. The present results highlighted the role of Mag ameliorated colon injury in DSS-induced UC mice by inhibiting the JAK2/STAT3 signaling pathway. These results suggest that Mag may be an effective agent for the treatment of UC.
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Ferroptosis is a form of iron-dependent regulatory cell death that is related to the pathogenesis and progression of various cardiovascular diseases, such as arrhythmia, diabetic cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure. This makes it a promising therapeutic target for cardiovascular diseases. It is interesting that a significant number of cardiovascular disease treatment drugs derived from phytochemicals have been shown to target ferroptosis, thus producing cardioprotective effects. This study offers a concise overview of the initiation and control mechanisms of ferroptosis. It discusses the core regulatory factors of ferroptosis as potential new therapeutic targets for various cardiovascular diseases, elucidating how ferroptosis influences the progression of cardiovascular diseases. In addition, this review systematically summarizes the regulatory effects of phytochemicals on ferroptosis, emphasizing their potential mechanisms and clinical applications in treating cardiovascular diseases. This study provides a reference for further elucidating the molecular mechanisms of phytochemicals in treating cardiovascular diseases. This may accelerate their application in the treatment of cardiovascular diseases and is worth further research in this field.
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Ferro-rotational (FR) materials, renowned for their distinctive material functionalities, present challenges in the growth of homo-FR crystals (i.e., single FR domain). This study explores a cost-effective approach to growing homo-FR helimagnetic RbFe(SO4)2 (RFSO) crystals by lowering the crystal growth temperature below the TFR threshold using the high-pressure hydrothermal method. Through polarized neutron diffraction experiments, it is observed that nearly 86% of RFSO crystals consist of a homo-FR domain. Notably, RFSO displays remarkable stability in the FR phase, with an exceptionally high TFR of ≈573 K. Furthermore, RFSO exhibits a chiral helical magnetic structure with switchable ferroelectric polarization below 4 K. Importantly, external electric fields can induce a single magnetic domain state and manipulate its magnetic chirality. The findings suggest that the search for new FR magnets with outstanding material properties should consider magnetic sulfates as promising candidates.
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When legged robots perform complex tasks in unstructured environments, falls are inevitable due to unknown external disturbances. However, current research mainly focuses on the locomotion control of legged robots without falling. This paper proposes a comprehensive decision-making and control framework to address the falling over of quadruped robots. First, a capturability-based fall prediction algorithm is derived for planar single-contact and 3D multi-contact locomotion with a predefined gait sequence. For safe fall control, a novel contact-implicit trajectory optimization method is proposed to generate both state and input trajectories and contact mode sequences. Specifically, incorporating uncertainty into the system and terrain models enables mitigating the non-smoothness of contact dynamics while improving the robustness of the resulting trajectories. Furthermore, a model-free deep reinforcement learning-based approach is presented to achieve fall recovery after the robot completes a fall. Experimental results demonstrate that the proposed fall prediction algorithm accurately predicts robot falls with up to 95% accuracy approximately 395ms in advance. Compared to classical locomotion controllers, which often struggle to maintain balance under significant pushes or terrain perturbations, the presented framework can autonomously switch to the fall controller approximately 0.06s after the perturbation, effectively preventing falls or achieving recovery with a threefold reduction in touchdown impact velocity. These findings highlight the effectiveness of the proposed framework in enhancing the stability and safety of legged robots in unstructured environments.
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Band structure of a semiconducting film critically determines the charge separation and transport efficiency. In antimony selenosulfide (Sb2(S,Se)3) solar cells, the hydrothermal method has achieved control of band gap width of Sb2(S,Se)3 thin film through tuning the atomic ratio of S/Se, resulting in an efficiency breakthrough towards 10 %. However, the obtained band structure exhibits an unfavorable gradient distribution in terms of carrier transport, which seriously impedes the device efficiency improvement. To solve this problem, here we develop a strategy by intentionally regulating hydrothermal temperature to control the chemical reaction kinetics between S and Se sources with Sb source. This approach enables the control over vertical distribution of S/Se atomic ratio in Sb2(S,Se)3 films, forming a favorable band structure which is conducive to carrier transport. Meanwhile, the adjusted element distribution not only ensures the uniformity of grain structure, but also increases the Se content of the films and suppress sulfur vacancy defects. Ultimately, the device delivers a high efficiency of 10.55 %, which is among the highest reported efficiency of Sb2(S,Se)3 solar cells. This study provides an effective strategy towards manipulating the element distribution in mixed-anion compound films prepared by solution-based method to optimize their optical and electrical properties.
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Zinc(II) ions (Zn2g) play crucial roles in the growth, propagation, and metabolism of animals, plants, and humans. Abnormal concentrations of Zn2+ in the environment and living organisms pose potential risks to environmental protection and human health. Therefore, it is imperative to develop rapid, reliable and in-situ detection methods for Zn2+ in both environmental and biological contexts. Furthermore, effective analytical methods are required for diagnosing diseases and understanding physiological metabolic mechanisms associated with Zn2+ concentration levels. Organic small-molecule fluorescent probes offer advantages such as fast, reliable, convenient, non-destructive detection capabilities and have significant application potential in Zn2+ detection and bioimaging; thus garnering extensive attention. Over the past two years alone, various organic small-molecule probes for Zn2+ based on different detection mechanisms and fluorophores have been rapidly developed. However, these probes still exhibit several limitations that need further resolution. In light of this context, we provide a comprehensive summary of the detection mechanisms, performance characteristics, and application scope of Zn2+ fluorescence probes since year 2022 while highlighting their advantages. We also propose solutions to address existing issues with these probes and outline future directions for their advancement. This review aims to serve as a valuable reference source offering insights into the development of advanced organic small-molecule-based fluorescence probes specifically designed for detecting Zn2+.
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Previous studies have verified that celastrol (Cel) protects against rheumatoid arthritis (RA) by inhibiting the NLRP3 inflammasome signaling pathway, but the molecular mechanism by which Cel regulates NLRP3 has not been clarified. This study explored the specific mechanisms of Cel in vitro and in vivo. A type II collagen-induced arthritis (CIA) mouse model was used to study the antiarthritic activity of Cel; analysis of paw swelling, determination of the arthritis score, and pathological examinations were performed. The antiproliferative and antimigratory effects of Cel on TNF-α induced fibroblast-like synoviocytes (FLSs) were tested. Proinflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB/NLRP3 pathway components was determined by western blotting and immunofluorescence staining in vitro and in vivo. The putative binding sites between Cel and Hsp90 were predicted through molecular docking, and the binding interactions were determined using the Octet RED96 system and coimmunoprecipitation. Cel decreased arthritis severity and reduced TNF-α-induced FLSs migration and proliferation. Additionally, Cel inhibited NF-κB/NLRP3 signaling pathway activation, reactive oxygen species (ROS) production, and proinflammatory cytokine secretion. Furthermore, Cel interacted directly with Hsp90 and blocked the interaction between Hsp90 and NLRP3 in FLSs. Our findings revealed that Cel regulates NLRP3 inflammasome signaling pathways both in vivo and in vitro. These effects are induced through FLSs inhibition of the proliferation and migration by blocking the interaction between Hsp90 and NLRP3.
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IgNAR exhibits significant promise in the fields of cancer and anti-virus biotherapies. Notably, the variable regions of IgNAR (VNAR) possess comparable antigen binding affinity with much smaller molecular weight (â¼12 kDa) compared to IgNAR. Antigen specific VNAR screening is a changeling work, which limits its application in medicine and therapy fields. Though phage display is a powerful tool for VNAR screening, it has a lot of drawbacks, such as small library coverage, low expression levels, unstable target protein, complicating and time-consuming procedures. Here we report VANR screening with next generation sequencing (NGS) could effectively overcome the limitations of phage display, and we successfully identified approximately 3000 BAFF-specific VNARs in Chiloscyllium plagiosum vaccinated with the BAFF antigen. The results of modelling and molecular dynamics simulation and ELISA assay demonstrated that one out of the top five abundant specific VNARs exhibited higher binding affinity to the BAFF antigen than those obtained through phage display screening. Our data indicates NGS would be an alternative way for VNAR screening with plenty of advantages.
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Secuenciación de Nucleótidos de Alto Rendimiento , Tiburones , Tiburones/inmunología , Tiburones/genética , Animales , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Proteínas de Peces/química , Antígenos/inmunología , Antígenos/genética , Enfermedades de los Peces/inmunologíaRESUMEN
OBJECTIVES: The aim of this study is to investigate the safety and efficacy of excimer laser coronary angioplasty (ELCA) combined with drug-coated balloons (DCBs) in the treatment of in-stent restenosis (ISR), and to explore whether the contrast injection technique would improve the neointimal tissue ablation of ELCA. METHODS: We studied patients diagnosed with ISR between January 2019 and October 2022 at two medical centers. These patients underwent DCB angioplasty guided by optical coherence tomography (OCT). Based on whether ELCA was performed before DCB treatment, patients were categorized into two groups: the ELCA + DCB group and the DCB group. All patients underwent clinical follow-up 1 year after the procedure. The primary endpoint was the 1-year rate of target lesion revascularization (TLR), which was defined as any repeat percutaneous intervention or bypass surgery on the target vessel conducted to address restenosis or other complications related to the target lesion. The secondary endpoints including immediate luminal gain (ΔMLA, defined as the difference in minimum lumen area before and after the intervention). RESULTS: A total of 85 lesions in 75 patients were included. The mean age of the study population was 64.2 ± 12.0 years, with 81.3% male. Baseline clinical characteristics were well-balanced, and procedural success was 100% in both groups. The ELCA + DCB group (n = 24) exhibited a greater ΔMLA compared to the DCB group (n = 61) (3.57 ± 0.79 mm² vs. 2.50 ± 1.06 mm², [95% confidence interval, CI: 0.57-1.69], p < 0.001), The reduction in 1-year TLR was more frequently observed in patients from the ELCA + DCB group compared to the DCB group (hazard ratio 0.33 [95% CI: 0.11-0.99]; log-rank p = 0.048). The exploratory analysis showed that ELCA with contrast infusion is associated with greater acute lumen gain compared to ELCA with saline infusion (p < 0.001). CONCLUSIONS: The combination of ELCA and DCB is a safe and effective treatment strategy for in-stent stenosis. Additionally, compared with saline injection, ELCA with contrast injection is associated with greater acute lumen gain. However, the optimal contrast agent concentration and long-term outcome of the contrast injection technique need confirmation through larger sample sizes and prospective studies.
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Angioplastia Coronaria con Balón , Reestenosis Coronaria , Láseres de Excímeros , Humanos , Masculino , Persona de Mediana Edad , Femenino , Reestenosis Coronaria/terapia , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/etiología , Anciano , Láseres de Excímeros/uso terapéutico , Angioplastia Coronaria con Balón/instrumentación , Resultado del Tratamiento , Estudios Retrospectivos , Stents Liberadores de Fármacos , Tomografía de Coherencia Óptica , Terapia Combinada , Angioplastia de Balón Asistida por LáserRESUMEN
CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a ß-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4-ß-catenin transcription complex through competitive to ß-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/ß-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing ß-catenin signaling may serve as a potential therapeutic candidate.
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Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Células Madre Neoplásicas , ARN Circular , Factor de Transcripción SOX9 , Neoplasias Gástricas , Factor de Transcripción 4 , beta Catenina , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Humanos , Factor de Transcripción SOX9/metabolismo , Factor de Transcripción SOX9/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , beta Catenina/metabolismo , beta Catenina/genética , ARN Circular/genética , ARN Circular/metabolismo , Factor de Transcripción 4/genética , Factor de Transcripción 4/metabolismo , Animales , Ratones , Línea Celular Tumoral , Ratones Desnudos , Masculino , Femenino , Resistencia a Antineoplásicos/genética , Ratones Endogámicos BALB C , Persona de Mediana EdadRESUMEN
PURPOSE: The gut microbiota might be closely related to central retinal artery occlusion (CRAO), but the causality has not been well defined. Two-sample Mendelian randomization (MR) study was used to reveal the potential causal effect between the gut microbiota and CRAO. METHODS: Data for gut microbiota were obtained from the genome-wide association studies of the Dutch Microbiome Project (DMP) (n = 7738) and the MiBioGen consortium (n = 18,340), and data on CRAO were obtained from samples of FinnGen project (546 cases and 344,569 controls). Causalities of exposures and outcomes were explored mainly using the inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median (WM), simple mode, weighted mode, and MR Pleiotropy RESidual Sum and Outlier were simultaneously applied to validate the final results. RESULTS: We identified three microbial pathways (two risk factors/one protective factor) and seven microbial taxa (two risk factors/five protective factors) associated with CRAO in the DMP study. Based on the data from the MiBioGen consortium, we identified seven microbial taxa (two risk factors/five protective factors) associated with CRAO, including the Eubacterium genus, which was consistently identified as a risk factor in both the DMP and the MiBioGen consortium MR analyses. CONCLUSION: Our study implicates the potential causal effects of specific microbial taxa and pathways on CRAO, potentially providing new insights into the prevention and treatment of CRAO through specific gut microbial taxa and pathway. Since our conclusion is a hypothesis derived from secondary genome-wide association studies (GWAS) data analysis, further research is needed for confirmation.
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A novel biomass-based magnetic nanoparticle (Fe3O4-P-CMC/PAMAM) was synthesized by crosslinking carboxymethyl chitosan (CMC) and poly(amidoamine) (PAMAM), followed by phosphorylation with the incorporation of magnetic ferric oxide nanoparticles. The characterization results verified the successful functionalization and structural integrity of the adsorbents with a surface area of ca. 43 m2/g. Batch adsorption experiments revealed that the adsorbent exhibited a maximum adsorption capacity of 1513.47 mg·g-1 for U(VI) at pH 5.5 and 298.15 K, with Fe3O4-P-CMC/G1.5-2 showing the highest affinity among the series. The adsorption kinetics adhered to a pseudo-second-order model (R2 = 0.99, qe,exp = 463.81 mg·g-1, k2 = 2.15×10-2 g·mg-1·min-1), indicating a chemically driven process. Thermodynamic analysis suggested that the adsorption was endothermic and spontaneous (ΔH° = 14.71 kJ·mol-1, ΔG° = -50.63 kJ·mol-1, 298. 15 K), with increasing adsorption capacity at higher temperatures. The adsorbent demonstrated significant selectivity for U(VI) in the presence of competing cations, with Fe3O4-P-CMC/G1.5-2 showing a high selectivity coefficient. The performed desorption and reusability tests indicated that the adsorbent could be effectively regenerated using 1M HCl, maintaining its adsorption capacity after five cycles. XPS analysis highlighted the role of phosphonate and amino groups in the complexation with uranyl ions, and validated the existence of bimodal U4f peaks at 380.1 eV and 390.1 eV belonging to U 4f7/2 and U 4f5/2. The results of this study underscore the promise of the developed adsorbent as an effective and selective material for the treatment of uranium-contaminated wastewater.
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Eleven undescribed cembrane-type diterpenoids, named litoamentenes A-K (1-11), were isolated from the soft coral Litophyton amentaceum collected from the South China Sea. Their structures were elucidated by extensive analysis of spectroscopic data, comparison with the literature data, single crystal X-ray diffraction, quantum chemical calculations and TDDFT-ECD calculations. This is the first systematic investigation of L. amentaceum. In particular, compounds 1-3 are cembrane-type norditerpenoids that lack isopropyl side chains. Compound 6 is a cembrane-type norditerpenoid without a methyl group at C-4, the first natural product identified with this carbon skeleton. Compounds 6, 9 and 10 showed modest cytotoxicity against several human cancer cell lines with IC50 values ranging from 3.99 to 14.56 µM.
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Antozoos , Diterpenos , Ensayos de Selección de Medicamentos Antitumorales , Antozoos/química , Diterpenos/química , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , Animales , Humanos , Estructura Molecular , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , China , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Modelos MolecularesRESUMEN
By virtue of its narrow pulse width and high peak power, the femtosecond pulsed laser can achieve high-precision material modification, material additive or subtractive, and other forms of processing. With additional good material adaptability and process compatibility, femtosecond laser-induced application has achieved significant progress in flexible electronics in recent years. These advancements in the femtosecond laser fabrication of flexible electronic devices are comprehensively summarized here. This review first briefly introduces the physical mechanism and characteristics of the femtosecond laser fabrication of various electronic microdevices. It then focuses on effective methods of improving processing efficiency, resolution, and size. It further highlights the typical progress of applications, including flexible energy storage devices, nanogenerators, flexible sensors, and detectors, etc. Finally, it discusses the development tendency of ultrashort pulse laser processing. This review should facilitate the precision manufacturing of flexible electronics using a femtosecond laser.
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Suppression of threading dislocations (TDs) in thin germanium (Ge) layers grown on silicon (Si) substrates has been critical for realizing high-performance Si-based optoelectronic and electronic devices. An advanced growth strategy is desired to minimize the TD density within a thin Ge buffer layer in Ge-on-Si systems. In this work, we investigate the impact of P dopants in 500-nm thin Ge layers, with doping concentrations from 1 to 50 × 1018 cm-3. The introduction of P dopants has efficiently promoted TD reduction, whose potential mechanism has been explored by comparing it to the well-established Sb-doped Ge-on-Si system. P and Sb dopants reveal different defect-suppression mechanisms in Ge-on-Si samples, inspiring a novel co-doping technique by exploiting the advantages of both dopants. The surface TDD of the Ge buffer has been further reduced by the co-doping technique to the order of 107 cm-2 with a thin Ge layer (of only 500 nm), which could provide a high-quality platform for high-performance Si-based semiconductor devices.
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The nature of semantic representation has long been a key question in linguistic research. The Embodied Cognition theory challenges the traditional view of language representation, stating that semantic information stems from the sensory-motor cortex, which is activated automatically during semantic processing. However, most of the evidence comes from monolingual studies; it remains unclear whether second-language (L2) comprehension involves different semantic representations or mirrors the pattern seen in first-language (L1) processing. Therefore, the present study investigated the role of the sensory-motor system in language processing via making Electroencephalography (EEG) recordings during the processing of L1 and L2 action verbs. The results showed that L1 (Chinese) action verbs generated higher mu-event-related desynchronization (ERD) than L1 abstract verbs in the early processing stage (250 ms after verb presentation), and the same phenomenon was also observed for L2 (English). The results also indicated that language modulated the processing of action verbs, with L1 action verbs eliciting stronger ERD than L2 action verbs. These results demonstrate that the sensory-motor cortex plays a crucial role in comprehending both L1 and L2 action verbs.