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Cross-individual variability is considered the essence of biology, preventing precise mathematical descriptions of biological motion1-7 like the physics law of motion. Here we report that the cerebellum shapes motor kinematics by encoding dynamic motor frequencies with remarkable numerical precision and cross-individual uniformity. Using in-vivo electrophysiology and optogenetics in mice, we confirmed that deep cerebellar neurons encoded frequencies via populational tuning of neuronal firing probabilities, creating cerebellar oscillations and motions with matched frequencies. The mechanism was consistently presented in self-generated rhythmic and non-rhythmic motions triggered by a vibrational platform, or skilled tongue movements of licking in all tested mice with cross-individual uniformity. The precision and uniformity allowed us to engineer complex motor kinematics with designed frequencies. We further validated the frequency-coding function of the human cerebellum using cerebellar electroencephalography recordings and alternating-current stimulation during voluntary tapping tasks. Our findings reveal a cerebellar algorithm for motor kinematics with precision and uniformity, the mathematical foundation for brain-computer interface for motor control.
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Despite the high mortality rate, sepsis lacks specific and effective treatment options. Conventional antibiotics, such as TIENAM (TIE; imipenem and cilastatin sodium for injection), face challenges owing to the emergence of bacterial resistance, which reduces their effectiveness and causes adverse effects. Addressing resistance and judicious drug use is crucial. Our research revealed that aloin (Alo) significantly boosts survival rates and reduces inflammation and bacterial load in mice with sepsis, demonstrating strong antimicrobial activity. Using a synergistic Alo + TIE regimen in a cecal ligation and puncture (CLP)-induced sepsis model, we observed a remarkable increase in survival rates from 10 % to 75 % within 72 h compared with the CLP group alone. This combination therapy also modulated inflammatory markers interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α, mitigated tissue damage, regulated immune cells by lowering NK, activated CD8+ and CD4+ T cells while increasing peritoneal macrophages, and decreased the bacterial load in the peritoneal cavity. We noted a significant shift in the abdominal cavity microbiota composition post-treatment, with a decrease in harmful bacteria, such as Lachnospiraceae_NK4A136_group, Klebsiella, Bacillus, and Escherichia, and an increase in beneficial bacteria, such as Lactobacillus and Mucispirillum. Our study emphasizes the efficacy of combining Alo with TIE to combat sepsis, and paves the way for further investigations and potential clinical applications aiming to overcome the limitations of TIE and enhance the therapeutic prospects of Alo.
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Despite the high mortality associated with sepsis, effective and targeted treatments remain scarce. The use of conventional antibiotics such as TIENAM (imipenem and cilastatin sodium for injection, TIE) is challenging because of the increasing bacterial resistance, which diminishes their efficacy and leads to adverse effects. Our previous studies demonstrated that ulinastatin (UTI) exerts a therapeutic impact on sepsis by reducing systemic inflammation and modulating immune responses. In this study, we examined the possibility of administering UTI and TIE after inducing sepsis in a mouse model using cecal ligation and puncture (CLP). We assessed the rates of survival, levels of inflammatory cytokines, the extent of tissue damage, populations of immune cells, microbiota in ascites, and important signaling pathways. The combination of UTI and TIE significantly improved survival rates and reduced inflammation and bacterial load in septic mice, indicating potent antimicrobial properties. Notably, the survival rates of UTI+TIE-treated mice increased from 10 % to 75 % within 168 h compared to those of mice that were subjected to CLP. The dual treatment successfully regulated the levels of inflammatory indicators (interleukin [IL]-6, IL-1ß, and tumor necrosis factor [TNF]-α) and immune cell numbers by reducing B cells, natural killer cells, and TNFR2+ Treg cells and increasing CD8+ T cells. Additionally, the combination of UTI and TIE alleviated tissue damage, reduced bacterial load in the peritoneal cavity, and suppressed the NF-κB signaling pathway. Our findings indicate that UTI and TIE combination therapy can significantly enhance sepsis outcomes by reducing inflammation and boosting the immune system. The results offer a promising therapeutic approach for future sepsis treatment.
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Sepsis, characterized by high mortality rates, causes over 50 % of acute lung injury (ALI) cases, primarily due to the heightened susceptibility of the lungs during this condition. Suppression of the excessive inflammatory response is critical for improving the survival of patients with sepsis; nevertheless, no specific anti-sepsis drugs exist. Huperzine A (HupA) exhibits neuroprotective and anti-inflammatory properties; however, its underlying mechanisms and effects on sepsis-induced ALI have yet to be elucidated. In this study, we demonstrated the potential of HupA for treating sepsis and explored its mechanism of action. To investigate the in vivo impacts of HupA, a murine model of sepsis was induced through cecal ligation and puncture (CLP) in both wild-type (WT) and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. Our results showed that HupA ameliorates sepsis-induced acute lung injury by activating the α7nAChR. We used the CLP sepsis model in wild-type and α7nAChR -/- mice and found that HupA significantly increased the survival rate through α7nAChR, reduced the pro-inflammatory cytokine levels and oxidative stress, ameliorated histopathological lung injury, altered the circulating immune cell composition, regulated gut microbiota, and promoted short-chain fatty acid production through α7nAChR in vivo. Additionally, HupA inhibited Toll-like receptor NF-κB signaling by upregulating the α7nAChR/protein kinase B/glycogen synthase kinase-3 pathways. Our data elucidate HupA's mechanism of action and support a "new use for an old drug" in treating sepsis. Our findings serve as a basis for further in vivo studies of this drug, followed by application to humans. Therefore, the findings have the potential to benefit patients with sepsis.
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Despite the high mortality rate associated with sepsis, no specific drugs are available. Decoy receptor 3 (DcR3) is now considered a valuable biomarker and therapeutic target for managing inflammatory conditions. DcR3-SUMO, an analog of DcR3, has a simple production process and high yield. However, its precise underlying mechanisms in sepsis remain unclear. This study investigated the protective effects of DcR3-SUMO on lipopolysaccharide (LPS)-induced inflammatory cells and septic mice. We evaluated the effects of DcR3 intervention and overexpression on intracellular inflammatory cytokine levels in vitro. DcR3-SUMO significantly reduced cytokine levels within inflammatory cells, and notably increased DcR3 protein and mRNA levels in LPS-induced septic mice, confirming its anti-inflammatory efficacy. Our in vitro and in vivo results demonstrated comparable anti-inflammatory effects between DcR3-SUMO and native DcR3. DcR3-SUMO protein administration in septic mice notably enhanced tissue morphology, decreased sepsis scores, and elevated survival rates. Furthermore, DcR3-SUMO treatment effectively lowered inflammatory cytokine levels in the serum, liver, and lung tissues, and mitigated the extent of tissue damage. AlphaFold3 structural predictions indicated that DcR3-SUMO, similar to DcR3, effectively interacts with the three pro-apoptotic ligands, namely TL1A, LIGHT, and FasL. Collectively, DcR3-SUMO and DcR3 exhibit comparable anti-inflammatory effects, making DcR3-SUMO a promising therapeutic agent for sepsis.
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Citocinas , Lipopolisacáridos , Miembro 6b de Receptores del Factor de Necrosis Tumoral , Sepsis , Animales , Sepsis/metabolismo , Sepsis/tratamiento farmacológico , Miembro 6b de Receptores del Factor de Necrosis Tumoral/metabolismo , Miembro 6b de Receptores del Factor de Necrosis Tumoral/genética , Ratones , Citocinas/metabolismo , Inflamación/metabolismo , Masculino , Humanos , Proteínas Recombinantes de Fusión/farmacología , Antiinflamatorios/farmacología , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Ratones Endogámicos C57BLRESUMEN
INTRODUCTION: Cardiovascular events resulting from volume overload are a primary cause of mortality in hemodialysis patients. Bioelectrical impedance analysis (BIA) is significantly valuable for assessing the volume status of hemodialysis (HD) patients. In this article, we explore the correlation between the volume index measured by BIA and the cardiac function index assessed by echocardiography (ECG) in HD patients. METHODS: Between April and November 2018, we conducted a cross-sectional study involving randomly selected 126 maintenance HD patients. Comprehensive data on medical history and laboratory test results were collected. Subsequently, we investigated the correlation between volume indices measured by BIA and cardiac function parameters by ECG. RESULTS: We discovered a significant correlation between the volume indices measured by BIA and various parameter of cardiac function. The Left Ventricular Hypertrophy (LVH) group exhibited higher levels of the percentage of Extracellular Water (ECW%) and the percentage of Total Body Water (TBW%) compared to the Non-LVH group. Extracellular Water (ECW) and Third Interstitial Fluid Volume (TSFV) were identified as independent risk factors for Left Ventricular Mass (LVM), and both demonstrated a high predictive value for LVM. ECW% emerged as an independent risk factor for the Left Ventricular Mass Index (LVMI), with a high predictive value for LVMI. CONCLUSION: ECW and TSFV were found to be positively associated with cardiac function parameters in HD patients.
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Ecocardiografía , Impedancia Eléctrica , Hipertrofia Ventricular Izquierda , Fallo Renal Crónico , Diálisis Renal , Humanos , Diálisis Renal/efectos adversos , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Ecocardiografía/métodos , Anciano , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/etiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/fisiopatología , Agua Corporal , AdultoRESUMEN
The use of adsorbents for direct air capture (DAC) of CO2 is regarded as a promising and essential carbon dioxide removal technology to help meet the goals outlined by the 2015 Paris Agreement. A class of adsorbents that has gained significant attention for this application is ultramicroporous metal organic frameworks (MOFs). However, the necessary data needed to facilitate process scale evaluation of these materials is not currently available. Here, we investigate TIFSIX-3-Ni, a previously reported ultramicroporous MOF for DAC, and measure several physicochemical and equilibrium adsorption properties. We report its crystal structure, textural properties, thermal stability, specific heat capacity, CO2, N2, and H2O equilibrium adsorption isotherms at multiple temperatures, and Ar and O2 isotherms at a single temperature. For CO2, N2, and H2O, we also report isotherm model fitting parameters and calculate heats of adsorption. We assess the manufacturability and process stability of TIFSIX-3-Ni by investigating the impact of batch reproducibility, binderless pelletization, humidity, and adsorption-desorption cycling (50 cycles) on its crystal structure, textural properties, and CO2 adsorption. For pelletized TIFSIX-3-Ni, we also report its skeletal, pellet, and bed density, total pore volume, and pellet porosity. Overall, our data enable initial process modeling and optimization studies to evaluate TIFSIX-3-Ni for DAC at the process scale. They also highlight the possibility to pelletize TIFSIX-3-Ni and the limited stability of the MOF under humid and oxidative conditions as well as upon multiple adsorption-desorption cycles.
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Bacteria-mediated cancer therapeutic strategies have attracted increasing interest due to their intrinsic tumor tropism. However, bacteria-based drugs face several challenges including the large size of bacteria and dense extracellular matrix, limiting their intratumoral delivery efficiency. In this study, we find that hyperbaric oxygen (HBO), a noninvasive therapeutic method, can effectively deplete the dense extracellular matrix and thus enhance the bacterial accumulation within tumors. Inspired by this finding, we modify Escherichia coli Nissle 1917 (EcN) with cypate molecules to yield EcN-cypate for photothermal therapy, which can subsequently induce immunogenic cell death (ICD). Importantly, HBO treatment significantly increases the intratumoral accumulation of EcN-cypate and facilitates the intratumoral infiltration of immune cells to realize desirable tumor eradication through photothermal therapy and ICD-induced immunotherapy. Our work provides a facile and noninvasive strategy to enhance the intratumoral delivery efficiency of natural/engineered bacteria, and may promote the clinical translation of bacteria-mediated synergistic cancer therapy.
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Escherichia coli , Oxigenoterapia Hiperbárica , Inmunoterapia , Terapia Fototérmica , Oxigenoterapia Hiperbárica/métodos , Animales , Inmunoterapia/métodos , Ratones , Terapia Fototérmica/métodos , Línea Celular Tumoral , Humanos , Muerte Celular Inmunogénica/efectos de los fármacos , Neoplasias/terapia , Neoplasias/inmunología , Femenino , Ratones Endogámicos BALB C , Matriz Extracelular/metabolismoRESUMEN
Essential tremor (ET) is the most prevalent movement disorder, characterized primarily by action tremor, an involuntary rhythmic movement with a specific frequency. However, the neuronal mechanism underlying the coding of tremor frequency remains unexplored. Here, we used in vivo electrophysiology, optogenetics, and simultaneous motion tracking in the Grid2dupE3 mouse model to investigate whether and how neuronal activity in the olivocerebellum determines the frequency of essential tremor. We report that tremor frequency was encoded by the temporal coherence of population neuronal firing within the olivocerebellums of these mice, leading to frequency-dependent cerebellar oscillations and tremors. This mechanism was precise and generalizable, enabling us to use optogenetic stimulation of the deep cerebellar nuclei to induce frequency-specific tremors in wild-type mice or alter tremor frequencies in tremor mice. In patients with ET, we showed that deep brain stimulation of the thalamus suppressed tremor symptoms but did not eliminate cerebellar oscillations measured by electroencephalgraphy, indicating that tremor-related oscillations in the cerebellum do not require the reciprocal interactions with the thalamus. Frequency-disrupting transcranial alternating current stimulation of the cerebellum could suppress tremor amplitudes, confirming the frequency modulatory role of the cerebellum in patients with ET. These findings offer a neurodynamic basis for the frequency-dependent stimulation of the cerebellum to treat essential tremor.
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Cerebelo , Temblor Esencial , Neuronas , Núcleo Olivar , Temblor Esencial/fisiopatología , Animales , Humanos , Núcleo Olivar/fisiopatología , Cerebelo/fisiopatología , Ratones , Masculino , Optogenética , Femenino , Estimulación Encefálica Profunda , Persona de Mediana Edad , Electroencefalografía , AncianoRESUMEN
Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies. IMPORTANCE: Sepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.
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Ciego , Modelos Animales de Enfermedad , Miembro 6b de Receptores del Factor de Necrosis Tumoral , Sepsis , Animales , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Ratones , Miembro 6b de Receptores del Factor de Necrosis Tumoral/genética , Miembro 6b de Receptores del Factor de Necrosis Tumoral/metabolismo , Ciego/cirugía , Humanos , Ligadura , Punciones , Masculino , Ratones Endogámicos C57BL , Microbioma Gastrointestinal , Citocinas/metabolismo , Lipopolisacáridos , Apoptosis/efectos de los fármacos , InflamaciónRESUMEN
Sensors designed based on the trans-cleavage activity of CRISPR/Cas12a systems have opened up a new era in the field of biosensing. The current design of CRISPR/Cas12-based sensors in the "on-off-on" mode mainly focuses on programming the activator strand (AS) to indirectly switch the trans-cleavage activity of Cas12a in response to target information. However, this design usually requires the help of additional auxiliary probes to keep the activator strand in an initially "blocked" state. The length design and dosage of the auxiliary probe need to be strictly optimized to ensure the lowest background and the best signal-to-noise ratio. This will inevitably increase the experiment complexity. To solve this problem, we propose using AS after the "RESET" effect to directly regulate the Cas12a enzymatic activity. Initially, the activator strand was rationally designed to be embedded in a hairpin structure to deprive its ability to activate the CRISPR/Cas12a system. When the target is present, target-mediated strand displacement causes the conformation change in the AS, the hairpin structure is opened, and the CRISPR/Cas12a system is reactivated; the switchable structure of AS can be used to regulate the degree of activation of Cas12a according to the target concentration. Due to the advantages of low background and stability, the CRISPR/Cas12a-based strategy can not only image endogenous biomarkers (miR-21) in living cells but also enable long-term and accurate imaging analysis of the process of exogenous virus invasion of cells. Release and replication of virus genome in host cells are indispensable hallmark events of cell infection by virus; sensitive monitoring of them is of great significance to revealing virus infection mechanism and defending against viral diseases.
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Técnicas Biosensibles , Sistemas CRISPR-Cas , MicroARNs , Sistemas CRISPR-Cas/genética , Técnicas Biosensibles/métodos , Humanos , MicroARNs/análisis , MicroARNs/metabolismo , Regulación Alostérica , Proteínas Asociadas a CRISPR/metabolismo , Endodesoxirribonucleasas/metabolismo , Endodesoxirribonucleasas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Células HEK293RESUMEN
Developing a polymer-based photocrosslinked 3D printable scaffolds comprised of gelatin methacryloyl (G) and hyaluronic acid methacryloyl (H) incorporated with two molecular weights of polyethylene glycol diacrylate (P) of various concentrations that enables rabbit adipose-derived stem cells (rADSCs) to survive, grow, and differentiate into smooth muscle cells (SMCs). Then, the chemical modification and physicochemical properties of the PGH bioinks were evaluated. The cell viability was assessed via MTT, CCK-8 assay and visualized employing Live/Dead assay. In addition, the morphology and nucleus count of differentiated SMCs were investigated by adopting TRAP (tartrate-resistant acid phosphatase) staining, and quantitative RT-PCR analysis was applied to detect gene expression using two different SMC-specific gene markers α-SMA and SM-MHC. The SMC-specific protein markers namely α-SMA and SM-MHC were applied to investigate SMC differentiation ability by implementing Immunocytofluorescence staining (ICC) and western blotting. Moreover, the disk, square, and tubular cellular models of PGH7 (GelMA/HAMA=2/1) + PEGDA-8000 Da, 3% w/v) hybrid bioink were printed using an extrusion bioprinting and cell viability of rADSCs was also analysed within 3D printed square construct practising Live/Dead assay. The results elicited the overall viability of SMCs, conserving its phenotype in biocompatible PGH7 hybrid bioink revealing its great potential to regenerate SMCs associated organs repair.
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Hidrogeles , Andamios del Tejido , Animales , Conejos , Andamios del Tejido/química , Hidrogeles/química , Gelatina/química , Músculo Liso , Fenotipo , Células Madre , Impresión Tridimensional , Ingeniería de Tejidos/métodosRESUMEN
In recent years, the CRISPR/Cas12a-based sensing strategy has shown significant potential for specific target detection due to its rapid and sensitive characteristics. However, the "always active" biosensors are often insufficient to manipulate nucleic acid sensing with high spatiotemporal control. It remains crucial to develop nucleic acid sensing devices that can be activated at the desired time and space by a remotely applied stimulus. Here, we integrated photoactivation with the CRISPR/Cas12a system for DNA and RNA detection, aiming to provide high spatiotemporal control for nucleic acid sensing. By rationally designing the target recognition sequence, this photoactivation CRISPR/Cas12a system could recognize HPV16 and survivin, respectively. We combined the lateral flow assay strip test with the CRISPR/Cas12a system to realize the visualization of nucleic acid cleavage signals, displaying potential instant test application capabilities. Additionally, we also successfully realized the temporary control of its fluorescent sensing activity for survivin by photoactivation in vivo, allowing rapid detection of target nucleic acids and avoiding the risk of contamination from premature leaks during storage. Our strategy suggests that the CRISPR/Cas12a platform can be triggered by photoactivation to sense various targets, expanding the technical toolbox for precise biological and medical analysis. This study represents a significant advancement in nucleic acid sensing and has potential applications in disease diagnosis and treatment.
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Técnicas Biosensibles , Ácidos Nucleicos , Sistemas CRISPR-Cas/genética , Survivin/genética , Biomarcadores , Pruebas en el Punto de AtenciónRESUMEN
Lung adenocarcinoma (LUAD) is one of the sole causes of death in lung cancer patients. This study combined with single-cell RNA-seq analysis to identify tumor stem-related prognostic models to predict the prognosis of lung adenocarcinoma, chemotherapy agents, and immunotherapy efficacy. mRNA expression-based stemness index (mRNAsi) was determined by One Class Linear Regression (OCLR). Differentially expressed genes (DEGs) were detected by limma package. Single-cell RNA-seq analysis in GSE123902 dataset was performed using Seurat package. Weighted Co-Expression Network Analysis (WGCNA) was built by rms package. Cell differentiation ability was determined by CytoTRACE. Cell communication analysis was performed by CellCall and CellChat package. Prognosis model was constructed by 10 machine learning and 101 combinations. Drug predictive analysis was conducted by pRRophetic package. Immune microenvironment landscape was determined by ESTIMATE, MCP-Counter, ssGSEA analysis. Tumor samples have higher mRNAsi, and the high mRNAsi group presents a worse prognosis. Turquoise module was highly correlated with mRNAsi in TCGA-LUAD dataset. scRNA analysis showed that 22 epithelial cell clusters were obtained, and higher CSCs malignant epithelial cells have more complex cellular communication with other cells and presented dedifferentiation phenomenon. Cellular senescence and Hippo signaling pathway are the major difference pathways between high- and low CSCs malignant epithelial cells. The pseudo-temporal analysis shows that cluster1, 2, high CSC epithelial cells, are concentrated at the end of the differentiation trajectory. Finally, 13 genes were obtained by intersecting genes in turquoise module, Top200 genes in hdWGCNA, DEGs in high- and low- mRNAsi group as well as DEGs in tumor samples vs. normal group. Among 101 prognostic models, average c-index (0.71) was highest in CoxBoost + RSF model. The high-risk group samples had immunosuppressive status, higher tumor malignancy and low benefit from immunotherapy. This work found that malignant tumors and malignant epithelial cells have high CSC characteristics, and identified a model that could predict the prognosis, immune microenvironment, and immunotherapy of LUAD, based on CSC-related genes. These results provided reference value for the clinical diagnosis and treatment of LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Pronóstico , Análisis de Expresión Génica de una Sola Célula , Adenocarcinoma del Pulmón/genética , Células Epiteliales , Neoplasias Pulmonares/genética , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Predicting suicide is a pressing issue among older adults; however, predicting its risk is difficult. Capitalizing on the recent development of machine learning, considerable progress has been made in predicting complex behavior such as suicide. As depression remained the strongest risk for suicide, we aimed to apply deep learning algorithms to identify suicidality in a group with late-life depression (LLD). METHODS: We enrolled 83 patients with LLD, 35 of which were non-suicidal and 48 were suicidal, including 26 with only suicidal ideation and 22 with past suicide attempts, for resting-state functional magnetic resonance imaging (MRI). Cross-sample entropy (CSE) analysis was conducted to examine the complexity of MRI signals among brain regions. Three-dimensional (3D) convolutional neural networks (CNNs) were used, and the classification accuracy in each brain region was averaged to predict suicidality after sixfold cross-validation. RESULTS: We found brain regions with a mean accuracy above 75% to predict suicidality located mostly in default mode, fronto-parietal, and cingulo-opercular resting-state networks. The models with right amygdala and left caudate provided the most reliable accuracy in all cross-validation folds, indicating their neurobiological importance in late-life suicide. CONCLUSION: Combining CSE analysis and the 3D CNN, several brain regions were found to be associated with suicidality.
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Ideación Suicida , Suicidio , Humanos , Anciano , Depresión/diagnóstico por imagen , Intento de Suicidio , Imagen por Resonancia Magnética , Entropía , Redes Neurales de la ComputaciónRESUMEN
The existence of a delicate redox balance in tumors usually leads to cancer treatment failure. Breaking redox homeostasis by amplifying oxidative stress and reducing glutathione (GSH) can accelerate cancer cell death. Herein, we construct a ferroptosis-reinforced nanocatalyst (denoted as HBGL) to amplify intracellular oxidative stress via dual H2O2 production-assisted chemodynamic therapy (CDT). Specifically, a long-circulating liposome is employed to deliver hemin (a natural iron-containing substrate for Fenton reaction and ferroptosis), ß-lapachone (a DNA topoisomerase inhibitor with H2O2 generation capacity for chemotherapy), and glucose oxidase (which can consume glucose for starvation therapy and generate H2O2). HBGL can achieve rapid, continuous, and massive H2O2 and â¢OH production and GSH depletion in cancer cells, resulting in increased intracellular oxidative stress. Additionally, hemin can reinforce the ferroptosis-inducing ability of HBGL, which is reflected in the downregulation of glutathione peroxidase-4 and the accumulation of lipid peroxide. Notably, HBGL can disrupt endo/lysosomes and impair mitochondrial function in cancer cells. HBGL exhibits effective tumor-killing ability without eliciting obvious side effects, indicating its clinical translation potential for synergistic starvation therapy, chemotherapy, ferroptosis therapy, and CDT. Overall, this nanocatalytic liposome may be a promising candidate for achieving potentiated cancer treatment.
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Ferroptosis , Neoplasias , Humanos , Peróxido de Hidrógeno , Hemina , Liposomas , Estrés Oxidativo , Glutatión , Neoplasias/tratamiento farmacológico , Línea Celular Tumoral , Microambiente TumoralRESUMEN
OBJECTIVES: To evaluate the clinical and non-contrast computed tomography (CT) features of patients with benign pulmonary subsolid nodules (SSNs) with a solid component ≤ 5 mm and their development trends via follow-up CT. METHODS: We retrospectively collected 436 data from patients who had SSNs with a solid component ≤ 5 mm, including 69 with absorbable benign SSNs (AB-SSNs), 70 with nonabsorbable benign SSNs (NB-SSNs), and 297 with malignant SSNs (M-SSNs). Models 1, 2, and 3 for distinguishing the different types of SSNs were then developed and validated. RESULTS: Patients with AB-SSNs were younger and exhibited respiratory symptoms more frequently than those with M-SSNs. The frequency of nodules detected during follow-up CT was in the following order: AB-SSNs > NB-SSNs > M-SSNs. NB-SSNs were smaller than M-SSNs, and ill-defined margins were more frequent in AB-SSNs than in NB-SSNs and M-SSNs. Benign SSNs exhibited irregular shape, target sign, and lower CT values more frequently compared to M-SSNs, whereas the latter demonstrated bubble lucency more commonly compared to the former. Furthermore, AB-SSNs showed more thickened interlobular septa and satellite lesions than M-SSNs and M-SSNs had more pleural retraction than AB-SSNs (all p < 0.017). The three models had AUCs ranging 0.748-0.920 and 0.790-0.912 in the training and external validation cohorts, respectively. A follow-up CT showed nodule progression in four benign SSNs. CONCLUSIONS: The three SSN types have different clinical and imaging characteristics, with some benign SSNs progressing to resemble malignancy. CRITICAL RELEVANCE STATEMENT: A good understanding of the imaging features and development trends of benign SSNs may help reduce unnecessary follow-up or interventions. This retrospective study explores the CT characteristics of benign SSNs with a solid component ≤ 5 mm by comparing AB-SSNs, NB-SSNs, and M-SSNs and delineates their development trends via follow-up CT. KEY POINTS: 1. Different subsolid nodule types exhibit distinct clinical and imaging features. 2. A miniscule number of benign subsolid nodules can progress to resemble malignancy. 3. Knowing the clinical and imaging features and development trends of benign subsolid nodules can improve management.
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A new study examines how Helicoverpa armigera females detect chemicals released by conspecific eggs in order to avoid laying more eggs on the same substrate. This work opens new avenues for basic research inquiries and offers a potential strategy for controlling insect pests.
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Neurobiología , Oviposición , Femenino , Animales , Helicoverpa armigera , InsectosRESUMEN
BACKGROUND: Late-life depression (LLD) is associated with risk of dementia, yet intervention of LLD provides an opportunity to attenuate subsequent cognitive decline. Omega-3 polyunsaturated fatty acids (PUFAs) supplement is a potential intervention due to their beneficial effect in depressive symptoms and cognitive function. To explore the underlying neural mechanism, we used resting-state functional MRI (rs-fMRI) before and after omega-3 PUFAs supplement in older adults with LLD. METHODS: A 52-week double-blind randomized controlled trial was conducted. We used multi-scale sample entropy to analyze rs-fMRI data. Comprehensive cognitive tests and inflammatory markers were collected to correlate with brain entropy changes. RESULTS: A total of 20 patients completed the trial with 11 under omega-3 PUFAs and nine under placebo. While no significant global cognitive improvement was observed, a marginal enhancement in processing speed was noted in the omega-3 PUFAs group. Importantly, participants receiving omega-3 PUFAs exhibited decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. The brain entropy changes of the PCG in the omega-3 PUFAs group correlated with improvement of language function and attenuation of interleukin-6 levels. LIMITATIONS: Sample size is small with only marginal clinical effect. CONCLUSION: These findings suggest that omega-3 PUFAs supplement may mitigate cognitive decline in LLD through anti-inflammatory mechanisms and modulation of brain entropy. Larger clinical trials are warranted to validate the potential therapeutic implications of omega-3 PUFAs for deterring cognitive decline in patients with late-life depression.
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Depresión , Ácidos Grasos Omega-3 , Humanos , Anciano , Entropía , Ácidos Grasos Omega-3/uso terapéutico , Encéfalo/diagnóstico por imagen , Método Doble Ciego , CogniciónRESUMEN
Electrocardiograms (ECGs) have the inherent property of being intrinsic and dynamic and are shown to be unique among individuals, making them promising as a biometric trait. Although many ECG biometric recognition approaches have demonstrated accurate recognition results in small enrollment sets, they can suffer from performance degradation when many subjects are enrolled. This study proposes an ECG biometric identification system based on locality-sensitive hashing (LSH) that can accommodate a large number of registrants while maintaining satisfactory identification accuracy. By incorporating the concept of LSH, the identity of an unknown subject can be recognized without performing vector comparisons for all registered subjects. Moreover, a kernel density estimator-based method is used to exclude unregistered subjects. The ECGs of 285 subjects from the PTB dataset were used to evaluate the proposed scheme's performance. Experimental results demonstrated an IR and EER of 99% and 4%, respectively, when Nen/Nid = 15/3.