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The magnetic and electric dipoles of ferroics play a central role in their fascinating properties. In particular, topological configurations have shown promising potential for use in novel electromechanical and electronic devices. Magnetic configurations from simple collinear to complex topological are well-documented. In contrast, many complex topological features in the electric counterpart remain unexplored. Here, we report the first example of three-dimensional electric dipole sinewave topological structure in a PbZrO3-based bulk perovskite, which presents an interesting triple-hysteresis loop macroscopically. This polar configuration consists of two orthogonal sinewave electric dipole modulations decoded from a polar incommensurate phase by advanced diffraction and atomic-resolution imaging techniques. The resulting topology is unraveled to be the competition between the antiferroelectric and ferroelectric states, stabilized by the modulation of the Pb 6s2 lone pair and the antiferrodistortive effect. These findings further reinforce the similarity of the magnetic and electric topologies.
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Circulating cell-free mitochondrial DNA (ccf-mtDNA) is an indicator of cell death, inflammation, and oxidative stress. ccf-mtDNA in pregnancies with placental dysfunction differs from that in healthy pregnancies, and the direction of this difference depends on gestational age and method of mtDNA quantification. Reactive oxygen species (ROS) trigger release of mtDNA, yet it is unknown whether trophoblast cells release mtDNA in response to oxidative stress, a common feature of pregnancies with placental pathology. We hypothesized that oxidative stress would induce cell death and release of mtDNA from trophoblast cells. BeWo cells were treated with antimycin A (10-320 µM) or rotenone (0.2-50 µM) to induce oxidative stress. A multiplex real-time quantitative PCR (qPCR) assay was used to quantify mtDNA and nuclear DNA in membrane-bound, non-membrane-bound, and vesicle-bound forms in cell culture supernatants and cell lysates. Treatment with antimycin A increased ROS (P < 0.0001), induced cell necrosis (P = 0.0004) but not apoptosis (P = 0.6471), and was positively associated with release of membrane-bound and non-membrane-bound mtDNA (P < 0.0001). Antimycin A increased mtDNA content in exosome-like extracellular vesicles (vesicle-bound form; P = 0.0019) and reduced autophagy marker expression (LC3A/B, P = 0.0002; p62, P < 0.001). Rotenone treatment did not influence mtDNA release or cell death (P > 0.05). Oxidative stress induces release of mtDNA into the extracellular space and causes nonapoptotic cell death and a reduction in autophagy markers in BeWo cells, an established in vitro model of human trophoblast cells. Intersection between autophagy and necrosis may mediate the release of mtDNA from the placenta in pregnancies exposed to oxidative stress.NEW & NOTEWORTHY This is the first study to test whether trophoblast cells release mitochondrial (mt)DNA in response to oxidative stress and to identify mechanisms of release and biological forms of mtDNA from this cellular type. This research identifies potential cellular mechanisms that can be used in future investigations to establish the source and biomarker potential of circulating mtDNA in preclinical experimental models and humans.
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Antimicina A , DNA Mitocondrial , Espaço Extracelular , Estresse Oxidativo , Espécies Reativas de Oxigênio , Trofoblastos , Humanos , Trofoblastos/metabolismo , Trofoblastos/efeitos dos fármacos , Trofoblastos/patologia , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Feminino , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Espaço Extracelular/metabolismo , Antimicina A/farmacologia , Rotenona/farmacologia , Placenta/metabolismo , Placenta/efeitos dos fármacos , Placenta/patologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Necrose , Linhagem Celular , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacosRESUMO
The indigenous microbial milieu within tumorous tissues exerts a pivotal influence on the genesis and advancement of gastric cancer (GC). This investigation scrutinizes the functions and molecular mechanisms attributed to Prevotella intermedia in the malignant evolution of GC. Isolation of P. intermedia from paired GC tissues was undertaken. Quantification of P. intermedia abundance in 102 tissues was accomplished using quantitative real-time PCR (qRT-PCR). Assessment of the biological effects of P. intermedia on GC cells was observed using culture medium supernatant. Furthermore, the protein profile of GC cells treated with tumor-derived P. intermedia was examined through label-free protein analysis. The functionality of perilipin 3 (PLIN3) was subsequently confirmed using shRNA. Our investigation revealed that the relative abundance of P. intermedia in tumor tissues significantly surpassed that of corresponding healthy tissues. The abundance of P. intermedia exhibited correlations with tumor differentiation (p = 0.006), perineural invasion (p = 0.004), omentum majus invasion (p = 0.040), and the survival duration of GC patients (p = 0.042). The supernatant derived from tumor-associated P. intermedia bolstered the proliferation, clone formation, migration, and invasion of GC cells. After indirect co-cultivation with tumor-derived P. intermedia, dysregulation of 34 proteins, including PLIN3, was discerned in GC cells. Knockdown of PLIN3 mitigated the malignancy instigated by P. intermedia in GC cells. Our findings posit that P. intermedia from the tumor microenvironment plays a substantial role in the malignant progression of GC via the modulation of PLIN3 expression. Moreover, the relative abundance of P. intermedia might serve as a potential biomarker for the diagnosis and prognosis of GC.
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Neoplasias Gástricas , Humanos , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Perilipina-3 , Prevotella intermedia , Prognóstico , Neoplasias Gástricas/patologia , Microambiente TumoralRESUMO
Rare-earth (RE)-based frustrated magnets are fertile playgrounds for discovering exotic quantum phenomena and exploring adiabatic demagnetization refrigeration applications. Here, we report the synthesis, structure, and magnetic properties of a family of rare-earth cyanurates RE5(C3N3O3)(OH)12 (RE = Gd-Lu) with an acentric space group P6Ì 2m. Magnetic susceptibility χ(T) and isothermal magnetization M(H) measurements manifest that RE5(C3N3O3)(OH)12 (RE = Gd, Dy-Yb) compounds exhibit no magnetic ordering down to 2 K, while Tb5(C3N3O3)(OH)12 shows long-range magnetic ordering around 3.6 K. Among them, magnetically frustrated spin-7/2 Gd5(C3N3O3)(OH)12 shows long-range magnetic ordering around 1.25 K and a large magnetocaloric effect with a maximum magnetic entropy change ΔSm of up to 58.1 J kg-1 K-1 at ΔH = 7 T at liquid-helium temperature regimes.
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OBJECTIVE: Existing approaches to fairness evaluation often overlook systematic differences in the social determinants of health, like demographics and socioeconomics, among comparison groups, potentially leading to inaccurate or even contradictory conclusions. This study aims to evaluate racial disparities in predicting mortality among patients with chronic diseases using a fairness detection method that considers systematic differences. METHODS: We created five datasets from Mass General Brigham's electronic health records (EHR), each focusing on a different chronic condition: congestive heart failure (CHF), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), chronic liver disease (CLD), and dementia. For each dataset, we developed separate machine learning models to predict 1-year mortality and examined racial disparities by comparing prediction performances between Black and White individuals. We compared racial fairness evaluation between the overall Black and White individuals versus their counterparts who were Black and matched White individuals identified by propensity score matching, where the systematic differences were mitigated. RESULTS: We identified significant differences between Black and White individuals in age, gender, marital status, education level, smoking status, health insurance type, body mass index, and Charlson comorbidity index (p-value < 0.001). When examining matched Black and White subpopulations identified through propensity score matching, significant differences between particular covariates existed. We observed weaker significance levels in the CHF cohort for insurance type (p = 0.043), in the CKD cohort for insurance type (p = 0.005) and education level (p = 0.016), and in the dementia cohort for body mass index (p = 0.041); with no significant differences for other covariates. When examining mortality prediction models across the five study cohorts, we conducted a comparison of fairness evaluations before and after mitigating systematic differences. We revealed significant differences in the CHF cohort with p-values of 0.021 and 0.001 in terms of F1 measure and Sensitivity for the AdaBoost model, and p-values of 0.014 and 0.003 in terms of F1 measure and Sensitivity for the MLP model, respectively. DISCUSSION AND CONCLUSION: This study contributes to research on fairness assessment by focusing on the examination of systematic disparities and underscores the potential for revealing racial bias in machine learning models used in clinical settings.
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Aprendizado de Máquina , Humanos , Masculino , Feminino , Doença Crônica , Idoso , Pessoa de Meia-Idade , Racismo , População Branca/estatística & dados numéricos , Registros Eletrônicos de Saúde , Doença Pulmonar Obstrutiva Crônica/mortalidade , Negro ou Afro-Americano/estatística & dados numéricos , Insuficiência Cardíaca/mortalidadeRESUMO
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line medications for acute migraine attacks. However, the response exhibits considerable variability among individuals. Thus, this study aimed to explore a machine learning model based on the percentage of amplitude oscillations (PerAF) and gray matter volume (GMV) to predict the response to NSAIDs in migraine treatment. METHODS: Propensity score matching was adopted to match patients having migraine with response and nonresponse to NSAIDs, ensuring consistency in clinical characteristics and migraine-related features. Multimodal magnetic resonance imaging was employed to extract PerAF and GMV, followed by feature selection using the least absolute shrinkage and selection operator regression and recursive feature elimination algorithms. Multiple predictive models were constructed and the final model with the smallest predictive residuals was chosen. The model performance was evaluated using the area under the receiver operating characteristic (ROCAUC) curve, area under the precision-recall curve (PRAUC), balance accuracy (BACC), sensitivity, F1 score, positive predictive value (PPV), and negative predictive value (NPV). External validation was performed using a public database. Then, correlation analysis was performed between the neuroimaging predictors and clinical features in migraine. RESULTS: One hundred eighteen patients with migraine (59 responders and 59 non-responders) were enrolled. Six features (PerAF of left insula and left transverse temporal gyrus; and GMV of right superior frontal gyrus, left postcentral gyrus, right postcentral gyrus, and left precuneus) were observed. The random forest model with the lowest predictive residuals was selected and model metrics (ROCAUC, PRAUC, BACC, sensitivity, F1 score, PPV, and NPV) in the training and testing groups were 0.982, 0.983, 0.927, 0.976, 0.930, 0.889, and 0.973; and 0.711, 0.648, 0.639, 0.667,0.649, 0.632, and 0.647, respectively. The model metrics of external validation were 0.631, 0.651, 0.611, 0.808, 0.656, 0.553, and 0.706. Additionally, a significant positive correlation was found between the GMV of the left precuneus and attack time in non-responders. CONCLUSIONS: Our findings suggest the potential of multimodal neuroimaging features in predicting the efficacy of NSAIDs in migraine treatment and provide novel insights into the neural mechanisms underlying migraine and its optimized treatment strategy.
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Anti-Inflamatórios não Esteroides , Substância Cinzenta , Imageamento por Ressonância Magnética , Transtornos de Enxaqueca , Neuroimagem , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/diagnóstico por imagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Adulto , Masculino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/efeitos dos fármacos , Substância Cinzenta/patologia , Neuroimagem/métodos , Aprendizado de Máquina , Pessoa de Meia-Idade , BiomarcadoresRESUMO
Heat-activated second harmonic generation (SHG) switching materials are gaining interest for their ability to switch between SHG on and off states, offering potential in optoelectronic applications. The novel nonlinear optical (NLO) switch, (C5H6NO)+(CH3SO3)- (4-hydroxypyridinium methylsulfonate, 4HPMS), is a near-room-temperature thermal driven material with a strong SHG response (3.3 × KDP), making it one of the most potent heat-stimulated NLO switches. It offers excellent contrast of 13 and a high laser-induced damage threshold (2.5 × KDP), with reversibility > 5â cycles. At 73 °C, 4HPMS transitions from the noncentrosymmetric Pna21 room temperature phase (RTP) to the centrosymmetric P21/c phase, caused by the rotation of the (C5H6NO)+ and (CH3SO3)- due to partially thermal breaking of intermolecular hydrogen bonds. The reverse phase change exhibits a large 50 °C thermal hysteresis. Density functional theory (DFT) calculations show that (C5H6NO)+ primarily dictates both the SHG coefficient (dij) and birefringence (âµn(Zeiss) = 0.216 vs âµn(cal.) = 0.202 at 546â nm; Δn(Immersion) = 0.210 vs âµn(cal.) = 0.198 at 589.3â nm), while the band gap (Eg) is influenced synergistically by (C5H6NO)+ and (CH3SO3)-. Additionally, 4HPMS-RTP also exhibits mechanochromism upon grinding as well as an aggregation-enhanced emission in a mixture of acetone and water.
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As an important characterization method, pair distribution function (PDF) has been extensively used in structural analysis of nanomaterials, providing key insights into the degree of crystallinity, atomic structure, local disorder etc. The collection of scattering signals with good statistics is necessary for a reliable structural analysis. However, current conventional electron diffraction experiments using PDF (ePDF) are limited in their ability to acquire continuous diffraction rings for large nanoparticles. Herein, a new method - tilt-ePDF - is proposed to improve the data quality and compatibility of ePDF by a combination of electron diffraction and specimen tilting. In the present work, a tilt-series of electron diffraction patterns was collected from gold nanoparticles with three different sizes and a standard sample polycrystalline aluminium film for ePDF analysis. The results show that tilt-ePDF can not only enhance the continuity of diffraction rings, but can also improve the signal-to-noise ratio in the high scattering angle range. As a result, compared with conventional ePDF data, tilt-ePDF data provide structure parameters with a better accuracy and lower residual factors in the refinement against the crystal structure. This method provides a new way of utilizing ePDF to obtain accurate local structure information from nanoparticles.
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Ductile inorganic thermoelectric (TE) materials open a new approach to develop high-performance flexible TE devices. N-type Ag2(S,Se,Te) and p-type AgCu(Se,S,Te) pseudoternary solid solutions are two typical categories of ductile inorganic TE materials reported so far. Comparing with the Ag2(S,Se,Te) pseudoternary solid solutions, the phase composition, crystal structure, and physical properties of AgCu(Se,S,Te) pseudoternary solid solutions are more complex, but their relationships are still ambiguous now. In this work, via systematically investigating the phase composition, crystal structure, mechanical, and TE properties of about 60 AgCu(Se,S,Te) pseudoternary solid solutions, the comprehensive composition-structure-property phase diagrams of the AgCuSe-AgCuS-AgCuTe pseudoternary system is constructed. By mapping the complex phases, the "ductile-brittle" and "n-p" transition boundaries are determined and the composition ranges with high TE performance and inherent ductility are illustrated. On this basis, high performance p-type ductile TE materials are obtained, with a maximum zT of 0.81 at 340 K. Finally, flexible in-plane TE devices are prepared by using the AgCu(Se,S,Te)-based ductile TE materials, showing high output performance that is superior to those of organic and inorganic-organic hybrid flexible devices.
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BACKGROUND: Age is known to be the biggest risk factor for Alzheimer's disease (AD), and Mexican Americans (MAs), who are one of the fastest-aging populations in the United States, are at a uniquely elevated risk. Mitochondrial stress and dysfunction are key players in the progression of AD and are also known to be impacted by lifestyle and environmental exposures/stressors. OBJECTIVE: This study aimed to identify population-specific differences in indicators of mitochondrial stress and dysfunction associated with AD risk that are detectable in the blood. METHODS: Examining blood from both non-Hispanic white (NHW) and MA participants (Nâ=â527, MA nâ=â284, NHW nâ=â243), mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) copy numbers were assessed through quantitative PCR. Data was stratified by population and sample type, and multiple linear regression analyses were performed to identify factors that may influence this phenotype of mitochondrial dysfunction. RESULTS: In the MA cohort, there was a significant relationship between cellular mtDNA:nDNA ratio and body mass index, CDR sum of boxes score, the APOEÉ2/É3 genotype, and education. Further, there was a significant relationship between cell-free mtDNA copy number and both education and CDR sum score. In the NHW cohort, there was a significant relationship between cellular mtDNA:nDNA ratio and both age and CDR sum score. Age was associated with cell-free mtDNA in the NHW cohort. CONCLUSIONS: This evidence supports the existence of population-based differences in the factors that are predictive of this blood-based phenotype of mitochondrial dysfunction, which may be indicative of cognitive decline and AD risk.
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Doença de Alzheimer , Doenças Mitocondriais , Humanos , DNA Mitocondrial/genética , Doença de Alzheimer/genética , Mitocôndrias/genética , EnvelhecimentoRESUMO
Driving under the influence (DUI) of alcohol or cannabis poses public health risks. Little is known about DUI of Delta-8 THC, a newer cannabis product. Using 2022 survey data among 189 U.S. adults ages 18-25 (58.73% male, 59.26% non-Hispanic White), multivariable logistic regression examined substance-specific (alcohol, cannabis, Delta-8) DUI perceived likelihood and risk in relation to past-year DUI among those with past-year use of each. Overall, 72.49% reported past-year alcohol use, 50.53% cannabis, and 22.46% Delta-8. Among those reporting past-year use of each respective substance, 33.58% reported DUI of alcohol, 32.63% cannabis, and 57.14% Delta-8. On average, participants had the same DUI perceived likelihood ("somewhat unlikely") across substances and perceived alcohol DUI as riskiest. Higher alcohol DUI perceived likelihood and lower perceived risk were associated with alcohol-related DUI. Greater cannabis-related perceived likelihood (but not risk) was associated with cannabis-related DUI. Neither Delta-8 DUI perceived likelihood nor risk were associated with Delta-8 DUI. In sum, perceived DUI likelihood for alcohol, cannabis, or Delta-8 tended to be similar. Among those with past-year use of each, the proportion of DUI was highest for Delta-8. Interventions should target DUI-related perceived likelihood and promote protective behavioral strategies that reduce substance-specific DUI risk.
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OBJECTIVE: Despite protective behavioral strategies (PBS) being an important part of alcohol prevention programs, utilization of PBS is sub-optimal, and research is needed to determine factors associated with use and non-use of PBS. The present study examined daily-level associations between situational familiarity (i.e., familiarity with locations and people) and the use of alcohol-related PBS among adolescents and young adults. METHOD: Participants (analysis N = 564, 55.1% females, 45.2% White, Non-Hispanic, ages 15 to 25, mean = 21.07 years [SD = 2.79]) were part of a longitudinal ecological momentary assessment burst study on cognitions and alcohol use. Mixed effects Poisson models were used to analyze data for engagement in PBS (i.e., serious harm reduction, stopping/limiting, and manner of drinking PBS). RESULTS: Within-person results indicated when participants had elevated (i.e., higher than their own average) familiarity with their location, they were less likely to use serious harm reduction PBS (Rate ratio [RR] = 0.94, p < 0.001) and stopping/limiting PBS (RR = 0.95, p < 0.001). Results showed that on drinking days with elevated familiarity with people, individuals were more likely to use serious harm reduction PBS (RR = 1.03, p = 0.01). There were no significant daily-level associations between familiarity with people or location and manner of drinking PBS. CONCLUSION: The study suggests PBS use, particularly for serious harm reduction and stopping/limiting strategies, varies among adolescents and young adults based on familiarity with location and people. Alcohol prevention interventions, including just-in-time interventions, should consider how to promote PBS use particularly in familiar locations and with less familiar people.
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Research indicates general willingness to drink (i.e., "How willing are you to drink tonight?") fluctuates day-to-day and is associated with daily-level drinking. However, it is unknown whether willingness to engage in specific alcohol-related behaviors is associated with actual engagement in those behaviors above and beyond general willingness to drink at the daily level. The present study examined whether daily-level willingness to engage in specific behaviors (i.e., pre-gaming, blacking out, hooking up) predicted engaging in those respective behaviors on drinking days above and beyond one's general willingness to drink. Participants included adolescents and young adults who were part of a longitudinal ecological momentary assessment (EMA) study on cognitions and alcohol use. Participants (N = 675; 43 % male) who reported drinking on weekend days (i.e., Friday and Saturday [N = 3,727 days]), were included. The study involved a 3-week EMA burst design with bursts occurring quarterly over 12 months. Multilevel logistic regressions indicated on drinking days when participants reported being more willing than their own average to pre-game (OR = 1.77, p <.001), black out (OR = 1.46, p <.05), or drink before hooking up (OR = 1.68, p <.001), they were more likely to pregame, black out, and hook up, respectively, whereas general willingness to drink was not associated with any outcomes at the daily level.Results suggest willingness to engage in specific behaviors may be essential to target in prevention programming in comparison to general willingness to drink when aiming to reduce specific risk behaviors.
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Consumo de Bebidas Alcoólicas , Assunção de Riscos , Humanos , Masculino , Adolescente , Adulto Jovem , Feminino , Estudos Longitudinais , Cognição , Avaliação Momentânea EcológicaRESUMO
OBJECTIVE: This study examined daily associations between alcohol use, cannabis use, and simultaneous alcohol and cannabis/marijuana (SAM) use with the likelihood of hooking up (uncommitted sexual encounter that may or may not include intercourse). METHOD: We used a longitudinal measurement burst ecological momentary assessment (EMA) design with 3-week EMA bursts with daily measurements repeated quarterly across 12 months. 1,009 (57 % female, Mean age = 20.00 [SD = 3.21]) Texan adolescents and young adults ages 15-25 participated in the study. Mixed effects logistic regression models were estimated using maximum likelihood estimation to evaluate the associations between substance use and hooking up. RESULTS: Within-person results indicated that participants were more likely to hook up on days with alcohol use and on days with cannabis use, but not on days with SAM use. Participants were also more likely to hook up on drinking days with higher-than-usual alcohol use. Between-person results indicated that participants who used alcohol more often or cannabis more often on average were more likely to hook up, and participants who tended to drink more on drinking days were more likely to hook up. CONCLUSIONS: Given the significant daily-level associations between alcohol and cannabis use and hooking up behavior, public health initiatives should focus on developing interventions to reduce alcohol and cannabis use and promote safer hooking up behavior among adolescents and young adults.
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Avaliação Momentânea Ecológica , Uso da Maconha , Humanos , Adolescente , Feminino , Masculino , Adulto Jovem , Adulto , Uso da Maconha/epidemiologia , Uso da Maconha/psicologia , Estudos Longitudinais , Estados Unidos/epidemiologia , Comportamento Sexual/estatística & dados numéricos , Comportamento Sexual/psicologia , Consumo de Álcool por Menores/estatística & dados numéricos , Consumo de Álcool por Menores/psicologia , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Texas/epidemiologiaRESUMO
Diffuse large B-cell lymphoma (DLBCL), a cancer of B cells, has been one of the most challenging and complicated diseases because of its considerable variation in clinical behavior, response to therapy, and prognosis. Radiomic features from medical images, such as PET images, have become one of the most valuable features for disease classification or prognosis prediction using learning-based methods. In this paper, a new flexible ensemble deep learning model is proposed for the prognosis prediction of the DLBCL in 18F-FDG PET images. This study proposes the multi-R-signature construction through selected pre-trained deep learning models for predicting progression-free survival (PFS) and overall survival (OS). The proposed method is trained and validated on two datasets from different imaging centers. Through analyzing and comparing the results, the prediction models, including Age, Ann abor stage, Bulky disease, SUVmax, TMTV, and multi-R-signature, achieve the almost best PFS prediction performance (C-index: 0.770, 95% CI: 0.705-0.834, with feature adding fusion method and C-index: 0.764, 95% CI: 0.695-0.832, with feature concatenate fusion method) and OS prediction (C-index: 0.770 (0.692-0.848) and 0.771 (0.694-0.849)) on the validation dataset. The developed multiparametric model could achieve accurate survival risk stratification of DLBCL patients. The outcomes of this study will be helpful for the early identification of high-risk DLBCL patients with refractory relapses and for guiding individualized treatment strategies.
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Aprendizado Profundo , Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Prognóstico , Tomografia por Emissão de Pósitrons/métodos , Pessoa de Meia-Idade , Feminino , Masculino , Idoso , Adulto , Interpretação de Imagem Assistida por Computador/métodosRESUMO
We report chemical vapor deposition (CVD) synthesis of two quasi-one-dimensional (quasi-1D) polymorphs of BiSCl, denoted by y-BiSCl and r-BiSCl. The length of the CVD samples can reach about 0.4 mm. Such quasi-1D samples of the two polymorphs can be readily separated into individual pieces for either characterization or application. The two polymorphs can be clearly differentiated by Raman spectroscopy. First-principles calculations and group analysis are used to assign each Raman peak to the corresponding vibrational mode. Ultraviolet-visible measurements on solution grown thin-film samples reveal that the two polymorphs exhibit significantly different band gaps of 2.08 eV (y-BiSCl) and 1.81 eV (r-BiSCl). First-principles calculation further shows that the interatomic chain binding energy is 18.1 meV/Å2, confirming that the van der Waals stacking determines the difference in their band gaps. Our findings highlight the possibility of realizing the desired functionalities in quasi-1D materials by controlling stacking orientation.
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BACKGROUND: Thymocyte selection-associated HMG-BOX (TOX) belongs to a family of transcription factors containing a highly conserved region of the high mobility group box (HMG-Box). A growing body of research has shown that TOX is involved in the occurrence and development of tumors and promotes T-cell exhaustion. We assessed the role of TOX with The Cancer Genome Atlas (TCGA) Pancancer Data. METHODS: TOX expression was examined with RNA-seq data from the TCGA and Genotype-Tissue Expression (GTEx) databases. The genetic alteration status and protein level of TOX were analyzed using databases, including the Human Protein Atlas (HPA), GeneCards, and STRING. The prognostic significance was estimated with survival data from the TCGA. Moreover, R software was used for enrichment analysis of TOX. The relationship between TOX and immune cell infiltration was assessed with the Tumor Immune Estimation Resource (TIMER) 2.0 database and the "CIBERSORT" method. The correlation between TOX and immune checkpoints was further explored. Immunohistochemical analysis was used to further verify the difference in TOX expression between cancerous and paracancerous tissues, and cell viability was evaluated using a CCK-8 assay. RESULTS: In most cancer types in the TCGA cohort, differential TOX expression was observed. The genetic alteration status and protein level of TOX were examined, and the prognosis of cancers was associated with TOX expression. Moreover, TOX levels were closely related to different immune-related pathways, immune cell infiltration and immune checkpoints. Additionally, significant differences in TOX expression between several cancerous and paracancerous tissues were validated. Furthermore, TOX clearly impacted the viability of cancer cells. CONCLUSIONS: TOX, a potential biomarker for cancer, may be involved in the regulation of the immune microenvironment and can be used for new targeted drugs.
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Diabetic kidney disease (DKD) is a devastating kidney disease and lacks effective therapeutic interventions. The present study was aimed to determine whether reconstituted high-density lipoprotein (rHDL) ameliorated renal injury in eNOS-/- dbdb mice, a mouse model of DKD. Three groups of mice, wild type C57BLKS/J (non-diabetes), eNOS-/- dbdb (diabetes), and eNOS-/- dbdb treated with rHDL (diabetes+rHDL) with both males and females were used. The rHDL nanoparticles were administered to eNOS-/- dbdb mice at Week 16 at 5 µg/g body weight in ~100 µL of saline solution twice per week for 4 weeks via retroorbital injection. We found that rHDL treatment significantly blunted progression of albuminuria and GFR decline observed in DKD mice. Histological examinations showed that the rHDLs significantly alleviated glomerular injury and renal fibrosis, and inhibited podocyte loss. Western blots and immunohistochemical examinations showed that increased protein abundances of fibronectin and collagen IV in the renal cortex of eNOS-/- dbdb mice were significantly reduced by the rHDLs. Taken together, the present study suggests a renoprotective effect of rHDLs on DKD.
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Nefropatias Diabéticas , Lipoproteínas HDL , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III , Animais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Camundongos , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Lipoproteínas HDL/farmacologia , Feminino , Camundongos Knockout , Rim/patologia , Rim/metabolismo , Rim/efeitos dos fármacos , Albuminúria , Fibronectinas/metabolismo , Fibronectinas/genética , Fibrose , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológicoRESUMO
Circulating cell-free mitochondrial DNA (ccf-mtDNA) is an indicator of cell death, inflammation, and oxidative stress. ccf-mtDNA differs in pregnancies with placental dysfunction from healthy pregnancies and the direction of this difference depends on gestational age and method of mtDNA quantification. Reactive oxygen species (ROS) trigger release of mtDNA from non-placental cells; yet it is unknown whether trophoblast cells release mtDNA in response to oxidative stress, a common feature of pregnancies with placental pathology. We hypothesized that oxidative stress would induce cell death and release of mtDNA from trophoblast cells. BeWo cells were treated with antimycin A (10-320 µM) or rotenone (0.2-50 µM) to induce oxidative stress. A multiplex real-time quantitative PCR (qPCR) assay was used to quantify mtDNA and nuclear DNA in membrane bound, non-membrane bound, and vesicular-bound forms in cell culture supernatants and cell lysates. Treatment with antimycin A increased ROS (p<0.0001), induced cell necrosis (p=0.0004) but not apoptosis (p=0.6471) and was positively associated with release of membrane-bound and non-membrane bound mtDNA (p<0.0001). Antimycin A increased mtDNA content in exosome-like extracellular vesicles (vesicular-bound form; p=0.0019) and reduced autophagy marker expression (LC3A/B, p=0.0002; p62, p<0.001). Rotenone treatment did not influence mtDNA release or cell death (p>0.05). Oxidative stress induces release of mtDNA into the extracellular space and causes non-apoptotic cell death and a reduction in autophagy markers in BeWo cells, an established in vitro model of human trophoblast cells. Intersection between autophagy and necrosis may mediate the release of mtDNA from the placenta in pregnancies exposed to oxidative stress. NEW & NOTEWORTHY: This is the first study to test whether trophoblast cells release mitochondrial DNA in response to oxidative stress and to identify mechanisms of release and biological forms of mtDNA from this cellular type. This research identifies potential cellular mechanisms that can be used in future investigations to establish the source and biomarker potential of circulating mitochondrial DNA in preclinical experimental models and humans.
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Materials for radiation detection are critically important and urgently demanded in diverse fields, starting from fundamental scientific research to medical diagnostics, homeland security, and environmental monitoring. Low-dimensional halides (LDHs) exhibiting efficient self-trapped exciton (STE) emission with high photoluminescence quantum yield (PLQY) have recently shown a great potential as scintillators. However, an overlooked issue of exciton-exciton interaction in LDHs under ionizing radiation hinders the broadening of its radiation detection applications. Here, we demonstrate an exceptional enhancement of exciton-harvesting efficiency in zero-dimensional (0D) Cs3Cu2I5:Tl halide single crystals by forming strongly localized Tl-bound excitons. Because of the suppression of non-radiative exciton-exciton interaction, an excellent α/ß pulse-shape-discrimination (PSD) figure-of-merit (FoM) factor of 2.64, a superior rejection ratio of 10-9, and a high scintillation yield of 26 000 photons MeV-1 under 5.49 MeV α-ray are achieved in Cs3Cu2I5:Tl single crystals, outperforming the commercial ZnS:Ag/PVT composites for charged particle detection applications. Furthermore, a radiation detector prototype based on Cs3Cu2I5:Tl single crystal demonstrates the capability of identifying radioactive 220Rn gas for environmental radiation monitoring applications. We believe that the exciton-harvesting strategy proposed here can greatly boost the applications of LDHs materials.