RESUMEN
Evaluation of microvascular networks was impeded until recently by the need of histological tissue sectioning, which precluded 3D analyses. Using light-sheet microscopy, we investigated microvascular network characteristics in the peri-infarct cortex of mice 3-56 days after transient middle cerebral artery occlusion. In animal subgroups, the sphingosine-1-phosphate analog FTY720 (Fingolimod) was administered starting 24 hours post-ischemia. Light-sheet microscopy revealed a striking pattern of microvascular changes in the peri-infarct cortex, that is, a loss of microvessels, which was most prominent after 7 days and followed by the reappearance of microvessels over 56 days which revealed an increased branching point density and shortened branches. Using a novel AI-based image analysis algorithm we found that the length density of microvessels expressing the arterial specification marker α-smooth muscle actin markedly increased in the peri-infarct cortex already at 7 days post-ischemia. The length and branch density of small microvessels, but not of intermediate or large microvessels increased above pre-ischemic levels within 14-56 days. FTY720 increased the length and branch density of small microvessels. This study demonstrates long-term alterations of microvascular architecture post-ischemia indicative of increased collateralization most notably of small microvessels. Light-sheet microscopy will greatly advance the assessment of microvascular responses to restorative stroke therapies.
RESUMEN
Endovascular treatment (EVT) using stents has become the primary option for severe cerebrovascular stenosis. However, considerable challenges remain to be addressed, such as in-stent restenosis (ISR) and late thrombosis. Many modified stents have been developed to inhibit the hyperproliferation of vascular smooth muscle cells (SMCs) and protect vascular endothelial cells (VECs), thereby reducing such complications. Some modified stents, such as those infused with rapamycin, have improved in preventing acute thrombosis. However, ISR and late thrombosis, which are long-term complications, remain unavoidable. Panax notoginseng saponin (PNS), a traditional Chinese medicine consisting of various compounds, is beneficial in promoting the proliferation and migration of VECs and inhibiting the proliferation of SMCs. Herein, a 3D-printed polycaprolactone (PCL) stent loaded with PNS (PNS-PCL stent) was developed based on a previous study. In vitro studies confirmed that PNS promotes the migration and proliferation of VECs, which were damaged, by increasing the expression levels of microRNA-126, p-AKT, and endothelial nitric oxide synthase. In vivo, the PNS-PCL stents maintained the patency of the carotid artery in rabbits for up to three months, outperforming the PCL stents. The PNS-PCL stents may present a new solution for the EVT of cerebrovascular atherosclerotic stenosis in the future.
RESUMEN
Joint attention is an indispensable tool for daily communication. Abnormalities in joint attention may be a key reason underlying social impairment in schizophrenia spectrum disorders. In this study, we aimed to explore the attentional orientation mechanism related to schizotypal traits in a social situation. Here, we employed a Posner cueing paradigm with social attentional cues. Subjects needed to detect the location of a target that is cued by gaze and head orientation. The power in the theta frequency band was used to examine the attentional process in the schizophrenia spectrum. There were four main findings. First, a significant association was found between schizotypal traits and attention orientation in response to invalid gaze cues. Second, individuals with schizotypal traits exhibited significant activation of neural oscillations and synchrony in the theta band, which correlated with their schizotypal tendencies. Third, neural oscillations and synchrony demonstrated a synergistic effect during social tasks, particularly when processing gaze cues. Finally, the relationship between schizotypal traits and attention orientation was mediated by neural oscillations and synchrony in the theta frequency band. These findings deepen our understanding of the impact of theta activity in schizotypal traits on joint attention and offer new insights for future intervention strategies.
Asunto(s)
Atención , Señales (Psicología) , Esquizofrenia , Ritmo Teta , Humanos , Masculino , Femenino , Ritmo Teta/fisiología , Atención/fisiología , Adulto Joven , Esquizofrenia/fisiopatología , Adulto , Electroencefalografía , Trastorno de la Personalidad Esquizotípica/fisiopatología , Psicología del EsquizofrénicoRESUMEN
Klebsiella pneumoniae can enter a viable but nonculturable (VBNC) state to survive in unfavorable environments. Our research found that high-, medium-, and low-alcohol-producing K. pneumoniae strains are associated with nonalcoholic fatty liver disease. However, the presence of the three Kpn strains has not been reported in the VBNC state or during resuscitation. In this study, the effects of different strains, salt concentrations, oxygen concentrations, temperatures, and nutrients in K. pneumoniae VBNC state were evaluated. The results showed that high-alcohol-producing K. pneumoniae induced a slower VBNC state than medium-alcohol-producing K. pneumoniae, and low-alcohol-producing K. pneumoniae. A high-salt concentration and micro-oxygen environment accelerated the loss of culturability. Simultaneously, both real-time quantitative PCR and droplet digital PCR were developed to compare the quantitative comparison of three Kpn strain VBNC states by counting single-copy gene numbers. At 22°C or 37°C, the number of culturable cells decreased significantly from about 108 to 105-106 CFU/mL. In addition, imipenem, ciprofloxacin, polymyxin, and phiW14 inhibited cell resuscitation but could not kill VBNC-state cells. These results revealed that the different environments evaluated play different roles in the VBNC induction process, and new effective strategies for eliminating VBNC-state cells need to be further studied. These findings provide a better understanding of VBNC-state occurrence, maintenance, detection, and absolute quantification, as well as metabolic studies of resuscitation resistance and ethanol production.IMPORTANCEBacteria may enter VBNC state under different harsh environments. Pathogenic VBNC bacteria cells in clinical and environmental samples pose a potential threat to public health because cells cannot be found by routine culture. The alcohol-producing Kpn VBNC state was not reported, and the influencing factors were unknown. The formation and recovery of VBNC state is a complete bacterial escape process. We evaluated the influence of multiple induction conditions on the formation of VBNC state and recovery from antibiotic and bacteriophage inhibition, and established a sensitive molecular method to enumerate the VBNC cells single-copy gene. The method can improve the sensitivity of pathogen detection in clinical, food, and environmental contamination monitoring, and outbreak warning. The study of the formation and recovery of VBNC-state cells under different stress environments will also promote the microbiological research on the development, adaptation, and resuscitation in VBNC-state ecology.
Asunto(s)
Klebsiella pneumoniae , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Antibacterianos/farmacología , Temperatura , Alcoholes/metabolismo , Alcoholes/farmacologíaRESUMEN
Background: The presence of peripheral inflammatory cells has been linked to the prognosis of cancer. This study aims to investigate the distinct roles of absolute neutrophil count (ANC) and absolute monocyte count (AMC) in differentiating renal cell carcinoma (RCC) from renal angiomyolipoma (RAML), as well as their prognostic significance in RCC. Methods: We conducted a comprehensive analysis of peripheral immune cell data, clinicopathological data, and tumor characteristics in patients diagnosed with RCC or RAML from January 2015 to December 2021. Receiver operating characteristic (ROC) curves, as well as univariate and multivariate analyses, were employed to assess the diagnostic utility of AMC and ANC in differentiating between RCC and RAML. Kaplan-Meier curve analysis was used to study the survival of RCC patients with different AMC and ANC. The prognostic value of AMC and ANC in RCC was investigated using COX univariate and multivariate analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used for bioinformatic correlation analysis. Results: A total of 1120 eligible patients were included in the study. The mean preoperative AMC and ANC in patients with RCC were found to be significantly higher compared to those in patients with RAML (P = 0.001 and P < 0.001, respectively). High preoperative AMC and ANC significantly correlated with smoking history, tumor length, gross hematuria, and high T Stage, N stage, and pathological grade. In multivariate analyses, an ANC> 3.205 *10^9/L was identified to be independently associated with the presence of RCC (HR = 1.618, P = 0.008). High AMC and ANC were significantly associated with reduced OS and PFS (P < 0.05), and ANC may be an independent prognostic factor. Public database analysis showed that signature genes of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) were highly expressed in ccRCC. Conclusions: Elevated preoperative ANC and AMC can distinguish RCC from RAML and predict poor prognosis in patients with RCC. Furthermore, the signature genes of TAMs and TANs exhibit high expression levels in clear cell RCC.
RESUMEN
Ammonia (NH3) in exhaled breath (EB) has been a biomarker for kidney function, and accurate measurement of NH3 is essential for early screening of kidney disease. In this work, we report an optical sensor that combines ultraviolet differential optical absorption spectroscopy (UV-DOAS) and spectral reconstruction fitting neural network (SRFNN) for detecting NH3 in EB. UV-DOAS is introduced to eliminate interference from slow change absorption in the EB spectrum while spectral reconstruction fitting is proposed for the first time to map the original spectra onto the sine function spectra by the principle of least absolute deviations. The sine function spectra are then fitted by the least-squares method to eliminate noise signals and the interference of exhaled nitric oxide. Finally, the neural network is built to enable the detection of NH3 in EB at parts per billion (ppb) level. The laboratory results show that the detection range is 9.50-12425.82 ppb, the mean absolute percentage error (MAPE) is 0.83%, and the detection accuracy is 0.42%. Experimental results prove that the sensor can detect breath NH3 and identify EB in simulated patients and healthy people. Our sensor will serve as a new and effective system for detecting breath NH3 with high accuracy and stability in the medical field.
RESUMEN
The delay in wound healing caused by chronic wounds or pathological scars is a pressing issue in clinical practice, imposing significant economic and psychological burdens on patients. In particular, with the aging of the population and the increasing incidence of diseases such as diabetes, impaired wound healing is one of the growing health problems. MicroRNA (miRNA) plays a crucial role in wound healing and regulates various biological processes. Our results show that miR-618 was significantly upregulated during the inflammatory phase of wound healing.Subsequently, miR-618 promotes the secretion of pro-inflammatory cytokines and regulates the proliferation and migration of keratinocytes. Mechanistically, miR-618 binds to the target gene-Atp11b and inhibits the PI3K-Akt signaling pathway, inhibiting the epithelial-mesenchymal transition (EMT) of keratinocytes. In addition, the PI3K-Akt signaling pathway induces the enrichment of nuclear miR-618, and miR-618 binds to the promoter of Lin7a to regulate gene transcription. Intradermal injection of miR-618 antagomir around full-thickness wounds in peridermal mice effectively accelerates wound closure compared to control. In conclusion, miR-618 antagomir can be a potential therapeutic agent for wound healing.
Asunto(s)
Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Queratinocitos , MicroARNs , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Cicatrización de Heridas , MicroARNs/genética , MicroARNs/metabolismo , Animales , Queratinocitos/metabolismo , Cicatrización de Heridas/genética , Ratones , Movimiento Celular/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Transición Epitelial-Mesenquimal/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Humanos , Antagomirs/metabolismo , Antagomirs/farmacologíaRESUMEN
Molecular chaperone heat shock protein 90 (Hsp90) is a ubiquitous regulator that fine-tunes and remodels diverse client proteins, exerting profound effects on normal biology and diseases. Unraveling the mechanistic details of Hsp90's function requires atomic-level insights into its client interactions throughout the adenosine triphosphate-coupled functional cycle. However, the structural details of the initial encounter complex in the chaperone cycle, wherein Hsp90 adopts an open conformation while engaging with the client, remain elusive. Here, using nuclear magnetic resonance spectroscopy, we determined the solution structure of Hsp90 in its open state, bound to a disordered client. Our findings reveal that Hsp90 uses two distinct binding sites, collaborating synergistically to capture discrete hydrophobic segments within client proteins. This bipartite interaction generates a versatile complex that facilitates rapid conformational sampling. Moreover, our investigations spanning various clients and Hsp90 orthologs demonstrate a pervasive mechanism used by Hsp90 orthologs to accommodate the vast array of client proteins. Collectively, our work contributes to establish a unified conceptual and mechanistic framework, elucidating the intricate interplay between Hsp90 and its clients.
RESUMEN
Silkworm was the first domesticated insect and has important economic value. It has also become an ideal model organism with applications in genetic and expression studies. In recent years, the use of transgenic strategies has made the silkworm silk gland an attractive bioreactor for the production of recombinant proteins, in particular, piggyBac-mediated transgenes. However, owing to differences in regulatory elements such as promoters, the expression levels of exogenous proteins have not reached expectations. Here, we used targeted gene editing to achieve site-specific integration of exogenous genes on genomic DNA and established the fibroin light chain (FibL) in-fusion expression system by TALEN-mediated homology-directed recombination. First, the histidine-rich cuticular protein (CP) was successfully site-directed inserted into the native FibL, and the FibL-CP fusion gene was correctly transcribed and expressed in the posterior silk gland under the control of the endogenous FibL promoter, with a protein expression level comparable with that of the native FibL protein. Moreover, we showed based on molecular docking that the fusion of FibL with cuticular protein may have a negative effect on disulfide bond formation between the C-terminal domain of fibroin heavy chain (FibH) and FibL-CP, resulting in abnormal spinning and cocoon in homozygotes, indicating a significant role of FibL in silk protein formation and secretion. Our results demonstrate the feasibility of using the FibL fusion system to express exogenous proteins in silkworm. We expect that this bioreactor system will be used to produce more proteins of interest, expanding the application value of the silk gland bioreactor.
RESUMEN
Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.
Asunto(s)
Candida auris , Técnicas de Amplificación de Ácido Nucleico , Recombinasas , Técnicas de Amplificación de Ácido Nucleico/métodos , Humanos , Recombinasas/metabolismo , Candida auris/genética , Candidiasis/diagnóstico , Candidiasis/microbiología , Límite de Detección , ADN de Hongos/genética , ADN de Hongos/análisisRESUMEN
Sulfur compounds (SO2, CS2, H2S and OCS) are common toxic pollutants in the atmospheric environment, and the absorption spectroscopy technique can indeed help to realize online monitoring of their concentrations. However, nonlinear effects that occur during absorption spectroscopy measurements have a serious impact on the measurement of the absorption cross-sections (ACSs) of sulfur compounds, leading to serious deviations in both the substance absorption properties and concentrations obtained based on ACS analysis. In this paper, the maximum effective ACSs of sulfur compounds in the linear region are obtained by considering the influence of nonlinear effects and eliminating interference factors such as oxygen and photolysis. In addition, the nonlinear effects are found to be greatly attenuated in spectra with broad band absorption characteristics by comparing the oscillatory absorption spectra before and after the differential treatment and by comparing the change in the oscillatory ACS with the broad band ACS. The experimental results show that the effective ACSs of SO2, CS2, H2S, and OCS with a resolution of 0.23 nm are 14.15 × 10-18 cm2 per molecule, 5.61 × 10-16 cm2 per molecule, 7.09 × 10-18 cm2 per molecule, and 3.20 × 10-19 cm2 per molecule, respectively. So far, it is the largest ACS obtained at room temperature and atmospheric pressure, which is of great significance for online measurement of sulfur compounds.
RESUMEN
PURPOSE: To evaluate the diagnostic efficacy of a developed artificial intelligence (AI) platform incorporating deep learning algorithms for the automated detection of intracranial aneurysms in time-of-flight (TOF) magnetic resonance angiography (MRA). METHOD: This retrospective study encompassed 3D TOF MRA images acquired between January 2023 and June 2023, aiming to validate the presence of intracranial aneurysms via our developed AI platform. The manual segmentation results by experienced neuroradiologists served as the "gold standard". Following annotation of MRA images by neuroradiologists using InferScholar software, the AI platform conducted automatic segmentation of intracranial aneurysms. Various metrics including accuracy (ACC), balanced ACC, area under the curve (AUC), sensitivity (SE), specificity (SP), F1 score, Brier Score, and Net Benefit were utilized to evaluate the generalization of AI platform. Comparison of intracranial aneurysm identification performance was conducted between the AI platform and six radiologists with experience ranging from 3 to 12 years in interpreting MR images. Additionally, a comparative analysis was carried out between radiologists' detection performance based on independent visual diagnosis and AI-assisted diagnosis. Subgroup analyses were also performed based on the size and location of the aneurysms to explore factors impacting aneurysm detectability. RESULTS: 510 patients were enrolled including 215 patients (42.16 %) with intracranial aneurysms and 295 patients (57.84 %) without aneurysms. Compared with six radiologists, the AI platform showed competitive discrimination power (AUC, 0.96), acceptable calibration (Brier Score loss, 0.08), and clinical utility (Net Benefit, 86.96 %). The AI platform demonstrated superior performance in detecting aneurysms with an overall SE, SP, ACC, balanced ACC, and F1 score of 91.63 %, 92.20 %, 91.96 %, 91.92 %, and 90.57 % respectively, outperforming the detectability of the two resident radiologists. For subgroup analysis based on aneurysm size and location, we observed that the SE of the AI platform for identifying tiny (diameterï¼3mm), small (3 mm ≤ diameterï¼5mm), medium (5 mm ≤ diameterï¼7mm) and large aneurysms (diameter ≥ 7 mm) was 87.80 %, 93.14 %, 95.45 %, and 100 %, respectively. Furthermore, the SE for detecting aneurysms in the anterior circulation was higher than that in the posterior circulation. Utilizing the AI assistance, six radiologists (i.e., two residents, two attendings and two professors) achieved statistically significant improvements in mean SE (residents: 71.40 % vs. 88.37 %; attendings: 82.79 % vs. 93.26 %; professors: 90.07 % vs. 97.44 %; P < 0.05) and ACC (residents: 85.29 % vs. 94.12 %; attendings: 91.76 % vs. 97.06 %; professors: 95.29 % vs. 98.82 %; P < 0.05) while no statistically significant change was observed in SP. Overall, radiologists' mean SE increased by 11.40 %, mean SP increased by 1.86 %, and mean ACC increased by 5.88 %, mean balanced ACC promoted by 6.63 %, mean F1 score grew by 7.89 %, and Net Benefit rose by 12.52 %, with a concurrent decrease in mean Brier score declined by 0.06. CONCLUSIONS: The deep learning algorithms implemented in the AI platform effectively detected intracranial aneurysms on TOF-MRA and notably enhanced the diagnostic capabilities of radiologists. This indicates that the AI-based auxiliary diagnosis model can provide dependable and precise prediction to improve the diagnostic capacity of radiologists.
Asunto(s)
Aprendizaje Profundo , Aneurisma Intracraneal , Angiografía por Resonancia Magnética , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/diagnóstico , Angiografía por Resonancia Magnética/métodos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Imagenología Tridimensional/métodos , Anciano , Sensibilidad y Especificidad , Encéfalo/diagnóstico por imagenRESUMEN
OBJECTIVE: To investigate the clinical effect of human acellular dermal matrix (HADM) combined with split-thickness skin graft in repairing lacunar soft tissue defects of the lateral heel after calcaneal fracture. METHODS: From June 2018 to October 2020, providers repaired 11 cases of lacunar soft tissue defects at the lateral part of the heel using HADM combined with split-thickness skin graft. After thorough debridement, the HADM was trimmed and filled into the lacunar defect area. Once the wound was covered, a split-thickness skin graft and negative-pressure wound therapy were applied. Providers evaluated the appearance, scar, ductility of the skin graft site, appearance of the donor site, healing time, and any reoperation at follow-up. RESULTS: Of the 11 cases, 8 patients achieved successful wound healing by primary intention. Three patients showed partial necrosis in the edge of the skin graft, but the wound healed after standard wound care. Evaluation at 6 and 12 months after surgery showed that all patients had wound healing and mild local scarring; there was no obvious pigmentation or scar formation in the donor skin area. The average healing time was 37.5 days (range, 24-43 days). CONCLUSIONS: The HADM combined with split-thickness skin graft is a simple and effective reconstruction method for lacunar soft tissue defect of the lateral heel after calcaneal fracture. In this small sample, the combination demonstrated few infections, minor scar formation, few donor site complications, and relatively short hospital stays.
Asunto(s)
Dermis Acelular , Calcáneo , Talón , Trasplante de Piel , Traumatismos de los Tejidos Blandos , Cicatrización de Heridas , Humanos , Masculino , Femenino , Calcáneo/lesiones , Calcáneo/cirugía , Adulto , Talón/lesiones , Talón/cirugía , Trasplante de Piel/métodos , Persona de Mediana Edad , Cicatrización de Heridas/fisiología , Traumatismos de los Tejidos Blandos/cirugía , Fracturas Óseas/cirugíaRESUMEN
Rechargeable aqueous zinc-ion batteries (RAZIBs) have received extensive attention because of their advantages of low cost, high safety, and nontoxicity. However, problems such as dissolution of the active cathode material, dendrites/passivation of the zinc anode, and slow reaction kinetics hindered their further applications. In this work, a crystalline/amorphous composite-type material composed of crystalline MnCO3 and amorphous MnOx was prepared and used as the cathode material for RAZIBs. The MnCO3@amorphous MnOx (MnCO3@A-MnOx) composite possesses the merits of both the pure crystalline phase of MnCO3 and the amorphous phase of MnOx, which can deliver better electrochemical performance than the corresponding single component in repeated cycles. In addition, crystalline MnCO3 undergoes a complex phase transition to the active MnO2 during the first charge process, providing the composite with a stable structure and additional electrochemical capacity. The electrochemical measurement results indicate that the MnCO3@A-MnOx electrode can display high reversible discharge capacity at 0.1 A g-1, excellent rate performance at 5.0 A g-1, and long cycling stability over 2000 cycles, showing great potential as a cathode material for high-performance RAZIBs.
RESUMEN
Kluyveromyces marxianus, a thermotolerant, fast-growing, Crabtree-negative yeast, is a promising chassis for the manufacture of various bioproducts. Although several genome editing tools are available for this yeast, these tools still require refinement to enable more convenient and efficient genetic modification. In this study, we engineered the K. marxianus NBRC 104275 strain by impairing the nonhomologous end joining and enhancing the homologous recombination machinery, which resulted in improved homology-directed repair effective on homology arms of up to 40 bp in length. Additionally, we simplified the CRISPR-Cas9 editing system by constructing a strain for integrative expression of Cas9 nuclease and plasmids bearing different selection markers for gRNA expression, thereby facilitating iterative genome editing without the need for plasmid curing. We demonstrated that tRNA was more effective than the hammerhead ribozyme for processing gRNA primary transcripts, and readily assembled tRNA-gRNA arrays were used for multiplexed editing of at least four targets. This editing tool was further employed for simultaneous scarless in vivo assembly of a 12-kb cassette from three fragments and marker-free integration for expressing a fusion variant of fatty acid synthase, as well as the integration of genes for starch hydrolysis. Together, the genome editing tool developed in this study makes K. marxianus more amenable to genetic modification and will facilitate more extensive engineering of this nonconventional yeast for chemical production.
RESUMEN
Magnetic resonance imaging (MRI) is instrumental in the noninvasive evaluation of tumor tissues in patients subjected to chemotherapy, thereby yielding essential diagnostic data crucial for the prognosis of tumors and the formulation of therapeutic strategies. Currently, commercially available MRI contrast agents (CAs) predominantly consist of mononuclear gadolinium(III) complexes. Because there is only one Gd(III) atom per molecule, these CAs often require administration in high doses to achieve the desired contrast quality, which inevitably leads to some adverse events. Herein, we develop a six-nuclei, apoptosis-targeting T1 CA, Gd6-ZnDPA nanoprobe, which consists of a hexanuclear gadolinium nanocluster (Gd6) with an apoptosis-targeting group (ZnDPA). The amplification of Gd(III) by the hexanuclear structure generates its high longitudinal relaxivity (44.67 mM-1 s-1, 1T) and low r1/r2 ratio (0.68, 1T). Based on the Solomon-Bloembergen-Morgan (SBM) theory, this notable improvement is primarily ascribed to a long correlation tumbling time (τR). More importantly, the Gd6-ZnDPA nanoprobe shows excellent tumor apoptosis properties with an enhanced MR signal ratio (â¼74%) and a long MRI imaging acquisition time window (â¼48 h) in 4T1 tumor-bearing mice. This study introduces an experimental gadolinium-based CA for the potential imaging of tumor apoptosis in the context of MRI.
RESUMEN
OBJECTIVE: This study aims to 1) explore the association between autistic traits and eating behaviors in Chinese preschoolers; 2) explore the mediating role of sensory processing patterns on the relation of autistic traits and eating-related behaviors; and 3) examine home nurturing environment as a moderator between autistic traits and eating-related behaviors. We hypothesize that there is a significant association between autistic traits and eating behaviors, which is mediated by sensory processing patterns and moderated by the home nurturing environment. METHOD: 509 children aged 3-4 years participated in this cross-sectional research. They were assessed using the Social Responsiveness Scale-Second Edition (SRS-2) for autistic traits, the Chinese Preschoolers' Eating Behavior Questionnaire (CPEBQ) for eating-related behaviors, the Short Sensory Profile-Second Edition (SSP-2) for sensory processing patterns, and the Children Home Nurture Environment Questionnaire (CHNEQ) for home nurturing environment. Mediation regression analyses were used to examine the role of sensory processing patterns, while moderation analyses to examine the role of home nurturing environment. RESULTS: We observed a positive association between autistic traits and eating behavior problems among typically developed children. Sensory processing patterns significantly mediated the impact of autistic traits on children's eating-related behaviors and home nurturing environment also moderated this relationship. DISCUSSION: Our research suggests that Chinese preschoolers with higher autistic traits may face more eating challenges when they possess more heightened sensory processing patterns, while living in supportive home environments helps to improve their eating behaviors. These findings contribute to the understanding of how and to what extent eating problems are influenced by autistic traits, and they offer insight into the alleviation of eating problems from the perspectives of sensory patterns and family nurturing environments.
Asunto(s)
Conducta Alimentaria , Ambiente en el Hogar , Humanos , Preescolar , Masculino , Femenino , Conducta Alimentaria/psicología , Estudios Transversales , Encuestas y Cuestionarios , China , Trastorno Autístico/psicología , Conducta Infantil/psicología , Sensación , Pueblo Asiatico/psicología , Pueblos del Este de AsiaRESUMEN
A recently proposed "Hyperfocusing hypothesis" suggests that schizotypy is associated with a more narrow but more intense way of allocating attention. The current study aims to test a vital prediction of this hypothesis in a social context, that schizotypy may be related to greater difficulty overcoming the distracting effects of gaze. This could cause a longer time to respond to targets that are invalidly cued by gaze. The current study tested this prediction in a modified Posner cueing paradigm by using P3 as an indicator for attentional resources. Seventy-four young healthy individuals with different levels of schizotypy were included, they were asked to detect the location of a target that was cued validly or invalidly by the gaze and head orientation. The results revealed that (a) schizotypy is associated with hyperfocusing on gaze direction, leading to greater difficulty overcoming the distracting effect of gaze. The higher the trait-schizotypy score, the more time needed to respond to targets that were invalidly cued by gaze (b) schizotypy is associated with reduced P3 which is directed by social communicative stimuli. The higher the trait-schizotypy score, the smaller the amplitude of P3 (c) the relationship between schizotypal traits and response times of the gaze-invalid condition is fully intermediated by P3. The findings of the current study suggest the P3 component may be a crucial neural mechanism underlying joint attention deficits in schizophrenia.
Asunto(s)
Atención , Señales (Psicología) , Fijación Ocular , Trastorno de la Personalidad Esquizotípica , Humanos , Masculino , Femenino , Adulto Joven , Trastorno de la Personalidad Esquizotípica/fisiopatología , Atención/fisiología , Fijación Ocular/fisiología , Electroencefalografía , Adulto , Potenciales Relacionados con Evento P300/fisiología , Adolescente , Tiempo de Reacción/fisiología , Estimulación LuminosaRESUMEN
Wide-bandgap (WBG) perovskites play a crucial role in perovskite-based tandem cells. Despite recent advances using self-assembled monolayers (SAMs) to facilitate efficiency breakthroughs, achieving precise control over the deposition of such ultrathin layers remains a significant challenge for large-scale fabrication of WBG perovskite and, consequently, for the tandem modules. To address these challenges, we propose a facile method that integrates MeO-2PACz and Me-4PACz in optimal proportions (Mixed SAMs) into the perovskite precursor solution, enabling the simultaneous codeposition of WBG perovskite and SAMs. This technique promotes the spontaneous formation of charge-selective contacts while reducing defect densities by coordinating phosphonic acid groups with the unbonded Pb2+ ions at the bottom interface. The resulting WBG perovskite solar cells (PSCs) demonstrated a power conversion efficiency of 19.31% for small-area devices (0.0585 cm2) and 17.63% for large-area modules (19.34 cm2), highlighting the potential of this codeposition strategy for fabricating high-performance, large-area WBG PSCs with enhanced reproducibility. These findings offer valuable insights for advancing WBG PSCs and the scalable fabrication of modules.
RESUMEN
Si3N4 bioceramics were fabricated using GPS and SPS method with MgO-RE2O3 (RE = La, Nd, Gd, Ho and Lu) sintering additives. The effect of sintering methods and sintering additives on the grain growth, mechanical, antimicrobial properties and color of Si3N4 bioceramics were studied. Samples sintered with GPS are composed of ß-Si3N4 and samples sintered with SPS are composed of α-Si3N4 and ß-Si3N4. The growth of ß-Si3N4 grains in samples sintered with GPS are more adequate. Samples sintered with GPS exhibit a S. aureus inactivation rate up to 98% and a bright color appearance with a hardness of about 13 GPa and a fracture toughness up to 7.5 MPa m1/2, suitable for dental implants. And samples sintered with SPS exhibit a hardness of about 17 GPa and a fracture toughness about 6 MPa m1/2.