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Supercapacitor is an important energy storage device widely used in the automobile industry, military production, and communication equipment because of its fast charge-discharge rate, and high power density. Herein, carbon quantum dots modified and Y3+ doped Ni3(NO3)2(OH)4 (NiY@CQDs) nanospheres are prepared by a solvothermal method and used as an electrode material. The electrochemical properties of NiY@CQDs were measured in a three-electrode system. An asymmetric supercapacitor (ASC) cell was assembled with activated carbon (AC) as the anode and NiY@CQDs as the cathode. The electrochemical properties of the ASC device were measured in a two-electrode system. Experimental results show the shape of NiY@CQDs is petal-shaped and the introducing carbon quantum dots and doping Y3+ significantly increases the specific surface area, conductivity, and specific capacitance of Ni3(NO3)2(OH)4. The mass-specific capacitance of NiY@CQDs reaches up to 2944â F g-1 at a current density of 1â A g-1. The asymmetric supercapacitor of NiY@CQDs//AC has a high energy density of 138.65â Wh kg-1 at a power density of 1500â W kg-1, displaying a wide range of application prospects in the energy storage area.
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As one of the most prevalent heritable cardiovascular diseases, dilated cardiomyopathy (DCM) induces cardiac insufficiency and dysfunction. Although genetic mutation has been identified one of the causes of DCM, the usage of genetic biomarkers such as RNAs for DCM early diagnosis is still being overlooked. In addition, the alternation of RNAs could reflect the progression of the diseases, as an indicator for the prognosis of patients. Therefore, it is beneficial to develop genetic based diagnostic tool for DCM. RNAs are often unstable within circulatory system, leading to the infeasibility for clinical application. Recently discovered exosomal miRNAs have the stability that is then need for diagnostic purpose. Hence, fully understanding of the exosomal miRNA within DCM patients is vital for clinical translation. In this study, we employed the next generation sequencing based on the plasma exosomal miRNAs to comprehensively characterize the miRNAs expression in plasma exosomes from DCM patients exhibiting chronic heart failure (CHF) compared to healthy individuals. A complex landscape of differential miRNAs and target genes in DCM with CHF patients were identified. More importantly, we discovered that 92 differentially expressed miRNAs in DCM patients undergoing CHF were correlated with several enriched pathways, including oxytocin signalling pathway, circadian entrainment, hippo signalling pathway-multiple species, ras signalling pathway and morphine addiction. This study reveals the miRNA expression profiles in plasma exosomes in DCM patients with CHF, and further reveal their potential roles in the pathogenesis of it, presenting a new direction for clinical diagnosis and management of DCM patients with CHF.
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Cardiomiopatía Dilatada , Insuficiencia Cardíaca , MicroARNs , Humanos , MicroARNs/metabolismo , Cardiomiopatía Dilatada/diagnóstico , Corazón , Enfermedad CrónicaRESUMEN
Rhizosphere microbes play key roles in plant growth and productivity in agricultural systems. One of the critical issues is revealing the interaction of agricultural management (M) and rhizosphere selection effects (R) on soil microbial communities, root exudates and plant productivity. Through a field management experiment, we found that bacteria were more sensitive to the M × R interaction effect than fungi, and the positive effect of rhizosphere bacterial diversity on plant biomass existed in the bacterial three two-tillage system. In addition, inoculation experiments demonstrated that the nitrogen cycle-related isolate Stenotrophomonas could promote plant growth and alter the activities of extracellular enzymes N-acetyl- d-glucosaminidase and leucine aminopeptidase in rhizosphere soil. Microbe-metabolites network analysis revealed that hubnodes Burkholderia-Caballeronia-Paraburkholderia and Pseudomonas were recruited by specific root metabolites under the M × R interaction effect, and the inoculation of 10 rhizosphere-matched isolates further proved that these microbes could promote the growth of soybean seedlings. Kyoto Encyclopaedia of Genes and Genomes pathway analysis indicated that the growth-promoting mechanisms of these beneficial genera were closely related to metabolic pathways such as amino acid metabolism, melatonin biosynthesis, aerobactin biosynthesis and so on. This study provides field observation and experimental evidence to reveal the close relationship between beneficial rhizosphere microbes and plant productivity under the M × R interaction effect.
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Structural dynamics and conformational transitions are crucial for the activities of enzymes. As one of the most widely used industrial biocatalysts, lipase could be activated by the water-oil interfaces. The interface activations were believed to be dominated by the close-to-open transitions of the lid subdomains. However, the detailed mechanism and the roles of structure transitions are still under debate. In this study, the dynamic structures and conformational transitions of Burkholderia cepacia lipase (LipA) were investigated by combining all-atom molecular dynamics simulations, enhanced sampling simulation, and spectrophotometric assay experiments. The conformational transitions between the lid-open and lid-closed states of LipA in aqueous solution are directly observed by the computational simulation methods. The interactions between the hydrophobic residues on the two lid-subdomains are the driven forces for the LipA closing. Meanwhile, the hydrophobic environment provided by the oil interfaces would separate the interactions between the lid-subdomains and promote the structure opening of LipA. Moreover, our studies demonstrate the opening of the lids structure is insufficient to initiate the interfacial activation, providing explanations for the inability of interfacial activation of many lipases with lid structures.
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Burkholderia cepacia , Agua , Agua/química , Lipasa/química , Burkholderia cepacia/metabolismo , Simulación de Dinámica Molecular , Conformación ProteicaRESUMEN
A new positive-sense single-stranded RNA (+ssRNA) mycovirus, Verticillium dahliae magoulivirus 1 (VdMoV1), was isolated from two strains (2-19 and XLZ70) of Verticillium dahliae. The complete genome of VdMoV1 is 2303 nucleotides (nt) in length and has a large open reading frame (nt positions from 61 to 1938) encoding an RNA-dependent RNA polymerase (RdRp). A multiple sequence alignment indicated that the central region of the RdRp encoded by VdMoV1 contains eight typical viral RdRp motifs. BLASTp analysis demonstrated that VdMoV1 has the highest sequence identity (86.88%) to Bremia lactucae associated ourmia-like virus 2 (BlaOLV2). Phylogenetic analysis revealed that VdMoV1 is a new member of the genus Magoulivirus. As far as we know, VdMoV1 is the first reported member of the family Botourmiaviridae infecting V. dahliae.
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Virus ARN Monocatenarios Positivos , Verticillium , Genoma Viral , Sistemas de Lectura Abierta , Filogenia , Enfermedades de las Plantas/virología , ARN Viral/genética , ARN Polimerasa Dependiente del ARN/genética , Verticillium/virología , Virus ARN Monocatenarios Positivos/aislamiento & purificaciónRESUMEN
AIMS: Hearing impairment (HI) is prevalent among middle-aged and older adults, but few studies have examined its mental health consequences in China. This study investigated the association of HI with depressive symptoms and whether family financial support moderated the association among adults aged 45 in China. METHODS: Data were obtained from three waves of the China Health and Retirement Longitudinal Study (2011, 2013 and 2015). Hearing impairment was defined as a self-reported hearing problem in one or both ears. Depressive symptoms were measured with CESD-10. Associations between HI and depressive symptoms were modeled using fixed-effect models. RESULTS: People with self-reported hearing loss were more likely than those without hearing loss to have depressive symptoms, with an odds ratio of 1.25 [1.07-1.47]. The association remained significant after adjusting for socio-demographic characteristics, lifestyle behaviors, and health conditions. Family financial support moderated this association. Among those with HI, adults with a higher level of family financial support tend to have better performance on symptoms of depression. CONCLUSIONS: HI was positively associated with depressive symptoms among adults aged ≥45 in China, and family financial support played a buffering role in the relationship between HI and depressive symptoms.
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Depresión , Pérdida Auditiva , Anciano , China/epidemiología , Depresión/psicología , Apoyo Financiero , Pérdida Auditiva/epidemiología , Pérdida Auditiva/psicología , Humanos , Estudios Longitudinales , Persona de Mediana EdadRESUMEN
It is of great significance to construct specially designed gold nanocrystals (AuNCs) with precisely controllable size and morphology to achieve an excellent physicochemical performance. In this work, sea urchin-shaped AuNCs with tunable plasmonic property were successfully synthesized by the hybridized double-strand poly adenine (dsPolyA) DNA-directed self-assembly technique. Hybridized dsPolyA as the directing template had suitable rigidity and upright conformation, which benefited the controllable formation of these anisotropic multi-branched AuNCs with the assistance of surfactant. The effects of essential conditions influencing the synthesis and precise morphology control were investigated in detail. COMSOL simulation was used to evaluate their electromagnetic field distribution according to their morphologies, and the result suggested that sea urchin-shaped AuNCs had abundant 'hot spots' for surface-enhanced Raman scattering (SERS) detection due to their regular nanoprotuberance structure. Finally, sea urchin-shaped AuNCs with excellent SERS and catalytic performance were applied for the quantitative analysis of food colorant and catalytic degradation of potential pollutants. The SERS enhancement factor of sea urchin-shaped AuNCs was up to 5.27 × 106, and the catalytic degradation rate for 4-NP by these AuNCs was up to -0.13min-1.
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Oro/química , Nanopartículas del Metal/química , Oligonucleótidos/química , Espectrometría Raman/métodos , Catálisis , Nanopartículas del Metal/ultraestructura , Nanotecnología/métodos , Propiedades de SuperficieRESUMEN
BACKGROUND: Hearing loss is highly prevalent and associated with reduced well-being in older adults. But little is known about the role of social factors in the association of hearing difficulty and its health consequences. This study aims to examine the association between self-reported hearing loss and health-related quality of life (HRQoL, consisted of physical and mental component summary, PCS and MCS), and to investigate whether social engagement mediates this association. METHOD: Data on 4035 older adults aged 60 years or above from a cross-sectional nationally representative database in China were obtained to address this study. HRQoL was measured by the Short Form 12 Health Survey (SF-12). Hearing loss was defined by a dichotomized measure of self-reported hearing difficulty, which has been proved to be sensitive and displayed moderate associations with audiometric assessment in elderly population. Social engagement was measured by the Index of Social Engagement Scale. Bootstrap test was applied to test for the significance of the mediating role of social engagement. RESULTS: Self-reported hearing loss was found negatively associated with HRQoL in older adults, and hearing loss was much more related to reduced mental well-being. Social engagement played a partial mediating role in the association of hearing loss and HRQoL. Social engagement account for 4.14% of the variance in the change of PCS scores and 13.72% for MCS, respectively. CONCLUSION: The study lends support to the hypothesis that hearing loss is associated with aging well beings, and the use of hearing aid or proper social engagement intervention may improve the quality of life among the elderly.
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Pérdida Auditiva , Calidad de Vida , Anciano , China/epidemiología , Estudios Transversales , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/epidemiología , Humanos , Autoinforme , Participación SocialRESUMEN
BACKGROUND: Hearing loss, a highly prevalent sensory impairment affecting older adults, is a risk factor for cognition decline. However, there were very limited studies on this association in low-resource countries. This study aimed to assess the association between self-reported hearing loss and cognitive decline, and whether engagement in leisure activities moderated this association among older adults in China. METHODS: Data were obtained from two waves of the nationally representative survey of China Longitudinal Healthy Longevity Survey (CLHLS) between 2011/12-2014. Eight thousand eight hundred forty-four individuals aged 65 years old or above with a dichotomized measure of self-reported hearing status were included. Modified Mini-Mental Examination (MMSE) was used to measure global cognition. Fixed-effects models were used to estimate whether leisure activity engagement moderated the association of self-perceived hearing loss with global cognitive change in the overall sample and sex subsamples. RESULTS: Self-reported hearing loss was associated with cognitive impairment, with an odds ratio of 2.48 [1.22, 5.06]. Sex difference in the association of hearing loss and cognitive impairment was not found. Self-reported hearing loss was associated with cognitive decline, with 8% increase in risk compared with those with normal hearing. Frequent engagement in leisure activities moderated the association between hearing loss and cognitive decline for the whole and male samples. CONCLUSION: Hearing loss was associated with cognitive decline, and leisure activities engagement moderated the association among males rather than females.
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Disfunción Cognitiva , Pérdida Auditiva , Anciano , Pueblo Asiatico , China/epidemiología , Cognición , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Femenino , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/epidemiología , Humanos , Actividades Recreativas , MasculinoRESUMEN
BACKGROUND/AIMS: Increasing evidences indicated the important roles of alternative splicing in the progression and prognosis of bladder urothelial carcinoma (BLCA). However, most previous research has focused on one or several alternative splicing events, without a comprehensive evaluation of the prognostic value of splicing events in BLCA. In this study, we aimed to determine risk scores for predicting prognosis of BLCA patients based on splicing events. METHODS: RNA-sequencing data and clinical information of BLCA patients were downloaded from The Cancer Genome Atlas, and data of splicing events were obtained from the SpliceSeq database. Univariate and multivariate Cox regression analyses were employed to identify survival-associated alternative spicing events (SASEs) and to calculate risk scores. Protein-protein interaction analysis of genes of the SASEs was performed using STRING, a database of known and predicted protein-protein interactions, and pathway enrichment analysis of the genes was implemented using the Database for Annotation, Visualization and Integrated Discovery (version 6.8). Receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to evaluate the clinical significance of genes from the SASEs for building a risk score in BLCA. Correlation between splicing events of splicing factors and non-splicing factors were analyzed with Pearson correlation coefficient. A potential regulatory network was then built using Cytoscape 3.5. RESULTS: In total, 39,508 alternative splicing events in 317 patients with BLCA were analyzed, including 4,632 SASEs. The area under the curve of the ROC of risk score (all) was 0.748 for predicting survival status of BLCA patients. Low- and high-risk score groups classified using the median "risk score (all)" value displayed remarkably different survival time (Low vs. High = 3304.841±239.758 vs 1198.614±152.460 days). The potential regulatory network with SASEs of splicing factors and other genes was constructed, which might be part of the biological mechanisms associated with prognosis of BLCA patients. CONCLUSIONS: In this study, prognostic signatures constructed using splicing events could be used for predicting the prognosis of BLCA patients.
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Empalme Alternativo , Redes Reguladoras de Genes , ARN Mensajero/genética , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Estudios de Cohortes , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Children who suffer from parental migration have been manifested to exhibit physical and mental impairments at higher rates. This current study aims to explore unintentional injury disparity among schooling left-behind children, migrant children and residential children in China, and to examine the risk factors of unintentional injury among the three types of children based on a multi-level system framework. This study will fill the gaps of this topic for China and contribute to the world literature in the context of countries with frequent population migration. METHODS: Data for 4479 children aged 6-16 of a representative population sample were obtained from a survey conducted in China in 2017. Child's unintentional injury in this survey was measured based on the definition and classification of ICD-10. Descriptive analysis, multivariable logistic regression and zero-inflated negative binomial regression were employed in this study. RESULTS: Left-behind children showed higher prevalence of total unintentional injury than migrant and residential children, as well as in 14 specific unintentional injuries. There was a statistical difference between left-behind and residential children's unintentional injuries, but no significant difference was found between migrant and residential children. Results also indicated that both individual and environmental factors constructed as a multi-level system were associated with children's unintentional injuries. CONCLUSIONS: Family migration may have contributed to the increased unintentional injury risks among children. Left-behind children were more vulnerable to suffer from unintentional injuries than migrant and residential children, and specific attentions should be paid to unique group of children, especially the left-behind children. Given the importance and serious consequences of children's unintentional injuries, the findings may provide implications for necessary intervention.
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Trastornos Mentales/epidemiología , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Migrantes/estadística & datos numéricos , Heridas y Lesiones/epidemiología , Adolescente , Niño , China/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Reliable quantification by surface enhanced Raman scattering (SERS) highly depends on the development of a reproducible substrate with excellent anti-interference capability. In this work, an intrinsic internal standard (IS) SERS substrate based on a diblock copolymer, polystyrene-block-poly-4-vinylpyridine (PS-b-P4VP), as a template was developed by a modified block copolymer lithography (BCL) technique of reserving the diblock copolymer template. This substrate generated a stable vibration peak at 1066 cm-1 attributed to poly(4-vinylpyridine) (P4VP) which could be used as an intrinsic IS for precise SERS quantification. A series of characterization results showed that the diblock copolymer template endowed this substrate with homogeneous distribution of Au nanoparticles, excellent stability and reproducibility. A minor relative standard deviation (RSDs) of SERS responses at 1066 cm-1 was measured and calculated to be 4.3% from ten different substrates in the same batch, which suggested good substrate-to-substrate reproducibility of this substrate. Finally, this intrinsic IS substrate was successfully applied for the rapid quantification of a trace banned dye, chrysoidine, in food samples with complicated matrices by SERS. It was proved that chrysoidine could be found and quantified to be 0.50 and 0.41 mg L-1 in a positive dried bean curd stick and chilli powder sample respectively with good recoveries by this substrate coupled with SERS. The development of intrinsic IS substrates would benefit rapid and accurate quantification of trace targets in complex samples coupled with SERS analysis.
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An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method was developed to elucidate the impurity profiles of paclitaxel and paclitaxel injections from different Chinese pharmaceutical companies. The fragmentation patterns for paclitaxel and the related impurities were analyzed and summarized. To remove the interference from auxiliary materials, such as hydrogenated castor oil, paclitaxel was dissolved in ethanol for acid, base, peroxide, and light induced forced degradation analysis, which could produce all the impurities exist in the paclitaxel injection. A total of 10 impurities were characterized, such as cephalomannine (1), 7-epi-10-deacetylpaclitaxel (2), 7-epipaclitaxel (3), baccatin â ¢ (4), ethyl ester side chain (5), 7-epi-baccatin â ¢ (6), 10-deacetylpaclitaxel (7), paclitaxel isomer(C3-C11 bridge) (8), paclitaxel isomer (9), and N-benzoyl-(2R,3S)-3-phenylisoserine (10), respectively. Among them, compounds 1-3 could be introduced during manufacture processing. In the forced degradation studies, while acid induced degradation products included 3-7, base induced degradation could produce 2-7 and 10; while 7 is the main compound produced by hydrogen peroxide treatment, 4 compounds (3-5 and 7) were produced by high temperature environment and 5 compounds (2-5 and 9 which is the first reported) from intensity light exposure. Furthermore, 8 was the main impurity came from intensity light exposed paclitaxel powder. The results from this study provide an important reference in processing, optimization, quality control and evaluation of paclitaxel.
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Contaminación de Medicamentos , Paclitaxel/análisis , Alcaloides , China , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Inyecciones , Espectrometría de Masas en Tándem , TaxoidesRESUMEN
BACKGROUND: Cognitive impairment is one of the major diseases facing the aging population. The progressive decline of cognitive function can lead to declining health or even the loss of life, work, and social ability. Exercise and behavioral stimulation can increase neurotransmitters in the brain and improve overall health and cognitive function. Reactivity training can mobilize neuromuscular function and induce changes in brain plasticity, which may effectively improve cognitive dysfunction and delay the occurrence and development of Alzheimer disease; however, the evidence supporting its effectiveness is still limited. OBJECTIVE: This study aims to explore the effectiveness and reliability of visual-motor reaction training in improving cognitive function, thereby promoting the application of novel nonpharmacological therapies. METHODS: This study is a single-center, open-label, controlled clinical trial. A total of 78 participants will be recruited for the study, including an equal number of athletes, ordinary healthy college students, and ordinary older adults in the community. Participants will receive 2 weeks of visual-motor response training. The primary outcome of this study is to assess differences in functional magnetic resonance imaging (fMRI) at 2 weeks. The secondary outcomes were the following: acousto-optic response time, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Mini Mental State Examination (MMSE), Activity of Daily Living (ADL) Scale, Subjective Cognitive Decline Questionnaire-9 (SCD-Q9), a 10-word memory test, and safety. RESULTS: The study was approved by the Shanghai Clinical Research Ethics Committee on January 2, 2024 (SECCR/2023-162-01). As of September 11, 2024, we have completed the recruitment of all 3 groups of volunteers. We expect to complete data collection and analysis by February 2025. CONCLUSIONS: The purpose of this study is to compare improvements in brain perceptual motor functions and cognitive levels across different populations through response ability training and to explore the efficacy and safety of exercise-based nonpharmacological therapies in improving cognitive function. Other potential benefits include understanding the functional differences and perceptual characteristics of the brain's perceptual-motor system between athletes and the general population and exploring the adaptability of the brain in acquiring skills during competitive sports training. This could provide an evidence base for early sports talent development and broader youth development. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400079602; https://tinyurl.com/23fbbndw. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56424.
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Cognición , Plasticidad Neuronal , Humanos , Cognición/fisiología , Plasticidad Neuronal/fisiología , Masculino , Femenino , Adulto , Anciano , Persona de Mediana Edad , Adulto Joven , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/terapia , Imagen por Resonancia MagnéticaRESUMEN
Adsorption is one of the most effective methods for ecotoxic antibiotics removal, while developing high-performance adsorbents with excellent adsorption capacity is indispensable. As the unavoidable by-product of wastewater, sewage sludge has dual properties of pollution and resources. In this study, dyeing sludge waste was converted to biochar by KOH activation and pyrolysis, and used as an efficient adsorbent for aqueous antibiotics removal. The optimized dyeing sludge-derived biochar (KSC-8) has excellent specific surface area (1178.4 m2/g) and the adsorption capacity for tetracycline (TC) could reach up to 1081.3 mg/g, which is four and five times higher than those without activation, respectively. The PSO (pseudo-second-order) kinetic model and the Langmuir isotherm model fitted better to the experimental data. The obtained KSC-8 has stabilized adsorption capacity for long-term fixed-bed experiments, and maintained 86.35% TC removal efficiency after five adsorption-regeneration cycles. The adsorption mechanism involves electrostatic attraction, hydrogen bonding, π-π interactions and pore filling. This work is a green and eco-friendly way as converting the waste to treat waste in aiming of simultaneous removal of antibiotics and resource recovery of dyeing sludge.
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Antibacterianos , Contaminantes Químicos del Agua , Aguas del Alcantarillado , Colorantes , Agua , Tetraciclina , Carbón Orgánico , Adsorción , Cinética , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: The co-infection of human immunodeficiency virus type 1 (HIV-1) and tuberculosis poses a lethal threat. Currently, our understanding of the altered immune responses and diverse immune cell subpopulations triggered by dual pathogen infections remains inadequate. METHODS: We utilized single-cell RNA sequencing data from the Gene Expression Omnibus database and the China National GeneBank Nucleotide Sequence Archive to study peripheral blood mononuclear cells from individuals infected with HIV-1 and those co-infected with Mycobacterium tuberculosis (Mtb)/HIV. We investigated cellular components, signaling pathways, biological functions, developmental trajectories, and gene regulatory networks among different cells to determine cellular heterogeneity in the progression of Mtb/HIV co-infection. RESULTS: We constructed a single-cell global transcriptional landscape of Mtb/HIV co-infection, revealing heterogeneity among various cell subpopulations. CD4+ T_RACK1_STAT1 subpopulation may participate in the JAK-STAT signaling pathway through RACK1-mediated transcriptional regulation of STAT1, potentially mediating the immune response in patients. Targeting CD8+ T_RACK1_TIGIT subpopulation via RACK1 may help restore the effector capacity of CD8+ T cells. Additionally, Mono_HSP90AA1 and Mono_APOBEC3A subpopulations were positioned at the endpoints of monocyte differentiation trajectories in different patients, suggesting their significant roles in distinct types of immune responses. CTL_GNLY and NK_HSPA1A subpopulations were specifically enriched in three distinct HIV-infected patient groups, indicating their crucial roles in the immune cytotoxicity associated with Mtb/HIV co-infection. CONCLUSION: The immune system disruptions caused by HIV-1 infection are further exacerbated by co-infection with Mtb. This compounded effect leads to significant heterogeneity in immune cell subpopulations among co-infected individuals, promoting immune system dysfunction.
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Coinfección , Infecciones por VIH , VIH-1 , Mycobacterium tuberculosis , Tuberculosis , Humanos , Infecciones por VIH/inmunología , Mycobacterium tuberculosis/inmunología , Coinfección/inmunología , Tuberculosis/inmunología , VIH-1/inmunología , Leucocitos Mononucleares/inmunología , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT1/genética , Linfocitos T CD8-positivos/inmunología , Transducción de Señal , Receptores de Cinasa C Activada/genética , Receptores de Cinasa C Activada/metabolismo , Linfocitos T CD4-Positivos/inmunología , Análisis de la Célula IndividualRESUMEN
The management of oral squamous cell carcinoma (OSCC) poses significant challenges, leading to organ impairment and ineffective treatment of deep-seated tumors, adversely affecting patient prognosis. A cascade nanoreactor that integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT) for comprehensive multimodal OSCC treatment is introduced. Utilizing iron oxide and mesoporous silica, the FMMSH drug delivery system, encapsulating the photosensitizer prodrug δ-aminolevulinic acid (δ-ALA), is developed. Triphenylphosphine (TPP) modification facilitates mitochondrial targeting, while tumor cell membrane (TCM) coating provides homotypic targeting. The dual-targeting δ-ALA@FMMSH-TPP-TCM demonstrate efficacy in eradicating both superficial and deep tumors through synergistic PDT/CDT. Esterase overexpression in OSCC cells triggers δ-ALA release, and excessive hydrogen peroxide in tumor mitochondria undergoes Fenton chemistry for CDT. The synergistic interaction of PDT and CDT increases cytotoxic ROS levels, intensifying oxidative stress and enhancing apoptotic mechanisms, ultimately leading to tumor cell death. PDT/CDT-induced apoptosis generates δ-ALA-containing apoptotic bodies, enhancing antitumor efficacy in deep tumor cells. The anatomical accessibility of oral cancer emphasizes the potential of intratumoral injection for precise and localized treatment delivery, ensuring focused therapeutic agent delivery to maximize efficacy while minimizing side effects. Thus, δ-ALA@FMMSH-TPP-TCM, tailored for intratumoral injection, emerges as a transformative modality in OSCC treatment.
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Ácido Aminolevulínico , Mitocondrias , Neoplasias de la Boca , Fotoquimioterapia , Fármacos Fotosensibilizantes , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Fotoquimioterapia/métodos , Humanos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Animales , Línea Celular Tumoral , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Ácido Aminolevulínico/química , Ácido Aminolevulínico/farmacología , Ratones , Dióxido de Silicio/química , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Sistemas de Liberación de Medicamentos/métodos , Ratones DesnudosRESUMEN
The H2A.Z variant histone 1 (H2AZ1) is aberrantly expressed in various tumors, correlating with an unfavorable prognosis. However, its role in hepatocellular carcinoma (HCC) remains unclear. We aimed to elucidate the pathways affected by H2AZ1 and identify promising therapeutic targets for HCC. Following bioinformatic analysis of gene expression and clinical data from The Cancer Genome Atlas and Gene Expression Omnibus database, we found 6,344 dysregulated genes related to H2AZ1 overexpression in HCC tissues (P < 0.05). We performed weighted gene co-expression network analysis to identify the gene module most related to H2AZ1. The H2AZ1-based index was further developed using Cox regression analysis, which revealed that the poor prognosis in the high H2AZ1-based index group could be attributed to elevated tumor stemness (P < 0.05). Moreover, the clinical model showed good prognostic potential (AUC > 0.7). We found that H2AZ1 knockdown led to reduced superoxide dismutase (SOD) activity, elevated malondialdehyde (MDA) levels, and increased apoptosis rate in tumor cells (P < 0.001). Thus, we developed an H2AZ1-based index model with the potential to predict the prognosis of patients with HCC. Our findings provide initial evidence that H2AZ1 overexpression plays a pivotal role in HCC initiation and progression.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Cognición , Histonas , Neoplasias Hepáticas/genética , PronósticoRESUMEN
BACKGROUND: The substrate employed in surface-enhanced Raman spectroscopy (SERS) constitutes an essential element in the cancer detection methodology. In this research, we introduce a three-dimensional (3D) structured SERS substrate that integrates a porous membrane with silver nanoparticles to enhance SERS spectral signals through the utilization of the aggregation effect of silver nanoparticles. This enhancement is crucial because accurate detection results strongly depend on the intensity of specific peaks in Raman spectroscopy. A highly sensitive SERS substrate can significantly improve the accuracy of detection results. RESULTS: We collected 66 plasma samples from individuals with kidney cancer and control individuals, including both bladder cancer patients and healthy individuals. Then, we utilized substrates with and without porous membranes to acquire the SERS spectra of the samples, enabling us to evaluate the enhancement effect of our SERS substrate. The spectral analysis demonstrated enhanced peak intensities in the experimental group (with porous substrate) compared to the control group (without porous substrate). The uniformity and reproducibility of the SERS substrate are also significantly enhanced, which is very helpful for improving the accuracy of detection results. Additionally, the Principal Component Analysis-Linear Discriminant Analysis algorithm (PCA-LDA) was employed to classify the SERS spectra of both groups. In the experimental group, the classification accuracy was 98.5 % for kidney cancer, and 83.3 % for kidney and bladder cancer. Compared to the control group, it improved by 3 % and 12.6 % respectively. SIGNIFICANT: This indicates that our 3D structured SERS substrate combined with multivariate statistical algorithms PCA-LDA can not only improve the accuracy of SERS detection technology in single cancer detection, but also has great potential in multiple cancer detection. This 3D structured SERS substrate is expected to become a new auxiliary means for cancer detection.