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Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply1. Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network2,3. Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN+ tip cells at the SI stage (APLN+ TipSI) advanced to TipSIII cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN+ TipSI cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1+ matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy.
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Células Endoteliales , Neoplasias , Neovascularización Patológica , Análisis de la Célula Individual , Humanos , Presentación de Antígeno , Comunicación Celular , Diferenciación Celular , Linaje de la Célula , Progresión de la Enfermedad , Estrés del Retículo Endoplásmico , Células Endoteliales/citología , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Linfangiogénesis , Neoplasias/irrigación sanguínea , Neoplasias/clasificación , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neovascularización Patológica/patología , Pericitos/patología , Pericitos/citología , Pericitos/metabolismo , Pronóstico , Receptores Notch/metabolismo , Transducción de Señal , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Animales , Pez CebraRESUMEN
Perovskite solar cells with the formula FA1-xCsxPbI3, where FA is formamidinium, provide an attractive option for integrating high efficiency, durable stability and compatibility with scaled-up fabrication. Despite the incorporation of Cs cations, which could potentially enable a perfect perovskite lattice1,2, the compositional inhomogeneity caused by A-site cation segregation is likely to be detrimental to the photovoltaic performance of the solar cells3,4. Here we visualized the out-of-plane compositional inhomogeneity along the vertical direction across perovskite films and identified the underlying reasons for the inhomogeneity and its potential impact for devices. We devised a strategy using 1-(phenylsulfonyl)pyrrole to homogenize the distribution of cation composition in perovskite films. The resultant p-i-n devices yielded a certified steady-state photon-to-electron conversion efficiency of 25.2% and durable stability.
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High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.
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Neoplasias Pulmonares , Factores de Transcripción , Humanos , Factores de Transcripción/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Histona Demetilasas/metabolismo , Histonas/metabolismo , Transformación Celular Neoplásica , Neoplasias Pulmonares/genética , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismoRESUMEN
Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits cancer cell growth in vitro and tumorigenesis in vivo. Targeting CARM1-mediated GATAD2A/2B methylation with CARM1 specific inhibitors potently inhibit breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires arginine methylation established by CARM1 on a key chromatin remodeler, and targeting such methylation might represent a promising therapeutic avenue in the clinic.
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Neoplasias de la Mama , Ensamble y Desensamble de Cromatina , Regulación Neoplásica de la Expresión Génica , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2 , Proteína-Arginina N-Metiltransferasas , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/metabolismo , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/genética , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Humanos , Femenino , Animales , Línea Celular Tumoral , Ciclo Celular/genética , Ratones , Metilación , Arginina/metabolismo , Carcinogénesis/genética , Activación TranscripcionalRESUMEN
The conjugation of terminal ammonium salt groups with perovskite surfaces is a frequently employed technique that aims to enhance the overall performance of perovskite materials, encompassing both bulk and surface properties. Particularly, it exhibits heightened efficacy when applied to surface modification, due to its ability to mitigate defect accumulation and facilitate facile binding with the receptive sites inherent to the perovskite structure. However, the interaction of the bulk ammonium group with PbI2 has the potential to form a low-dimensional phase of perovskite, which may obstruct carrier extraction at the interface. Therefore, the surface passivators (MeO-PFACl) are designed through intramolecular potential manipulation. The combinations of the electron-donating methoxy group and π-π conjugation of the phenyl ring reduce the local potential at the reactive site of formamidinium group, making it less likely to form a low-dimension phase with perovskite. This surface passivation strategy effectively suppresses the surface nonradiative recombination and promotes the interface carrier extraction. The devices treated with MeO-PFACl have demonstrated exceptional performance, achieving a peak power conversion efficiency (PCE) of 25.88%, with an average PCE of 25.37%. These works offer a novel principle for enhancing both the efficiency and stability of PSCs using ammonium-incorporated molecules without the induction of an additional phase layer.
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Intertumoral immune heterogeneity is a critical reason for distinct clinical benefits of immunotherapy in lung adenocarcinoma (LUAD). Tumor immunophenotype (immune 'Hot' or 'Cold') suggests immunological individual differences and potential clinical treatment guidelines. However, employing epigenome signatures to determine tumor immunophenotypes and responsive treatment is not well understood. To delineate the tumor immunophenotype and immune heterogeneity, we first distinguished the immune 'Hot' and 'Cold' tumors of LUAD based on five immune expression signatures. In terms of clinical presentation, the immune 'Hot' tumors usually had higher immunoactivity, lower disease stages and better survival outcomes than 'Cold' tumors. At the epigenome levels, we observed that distinct DNA methylation patterns between immunophenotypes were closely associated with LUAD development. Hence, we identified a set of five CpG sites as the immunophenotype-related methylation signature (iPMS) for tumor immunophenotyping and further confirmed its efficiency based on a machine learning framework. Furthermore, we found iPMS and immunophenotype-related immune checkpoints (IPCPs) could contribute to the risk of tumor progression, implying IPCP has the potential to be a novel immunotherapy blockade target. After further parsing of the role of iPMS-predicted immunophenotypes, we found immune 'Hot' was a protective factor leading to better survival outcomes when patients received the anti-PD-1/PD-L1 immunotherapy. And iPMS was also a well-performed signature (AUC = 0.752) for predicting the durable/nondurable clinical benefits. In summary, our study explored the role of epigenome signature in clinical tumor immunophenotyping. Utilizing iPMS to characterize tumor immunophenotypes will facilitate developing personalized epigenetic anticancer approaches.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/terapia , Biomarcadores de Tumor/genética , Epigenoma , Humanos , Inmunofenotipificación , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/terapiaRESUMEN
Long non-coding RNAs (lncRNAs) that emanate from enhancer regions (defined as enhancer-associated lncRNAs, or elncRNAs) are emerging as critical regulators in disease progression. However, their biological characteristics and clinical relevance have not been fully portrayed. Here, based on the traditional expression quantitative loci (eQTL) and our optimized residual eQTL method, we comprehensively described the genetic effect on elncRNA expression in more than 300 lymphoblastoid cell lines. Meanwhile, a chromatin atlas of elncRNAs relative to the genetic regulation state was depicted. By applying the maximum likelihood estimate method, we successfully identified causal elncRNAs for protein-coding gene expression reprogramming and showed their associated single nucleotide polymorphisms (SNPs) favor binding of transcription factors. Further epigenome analysis revealed two immune-associated elncRNAs AL662844.4 and LINC01215 possess high levels of H3K27ac and H3K4me1 in human cancer. Besides, pan-cancer analysis of 3D genome, transcriptome, and regulatome data showed they potentially regulate tumor-immune cell interaction through affecting MHC class I genes and CD47, respectively. Moreover, our study showed there exist associations between elncRNA and patient survival. Finally, we made a user-friendly web interface available for exploring the regulatory relationship of SNP-elncRNA-protein-coding gene triplets (http://bio-bigdata.hrbmu.edu.cn/elncVarReg). Our study provides critical mechanistic insights for elncRNA function and illustrates their implications in human cancer.
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Neoplasias , ARN Largo no Codificante , Cromatina/genética , Regulación de la Expresión Génica , Humanos , Funciones de Verosimilitud , Neoplasias/genética , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante/genéticaRESUMEN
KEY MESSAGE: Ten stable loci for freezing tolerance (FT) in wheat were detected by genome-wide association analysis. The putative candidate gene TaRPM1-7BL underlying the major locus QFT.ahau-7B.2 was identified and validated. Frost damage restricts wheat growth, development, and geographical distribution. However, the genetic mechanism of freezing tolerance (FT) remains unclear. Here, we evaluated FT phenotypes of 245 wheat varieties and lines, and genotyped them using a Wheat 90 K array. The association analysis showed that ten stable loci were significantly associated with FT (P < 1 × 10-4), and explained 6.45-26.33% of the phenotypic variation. In particular, the major locus QFT.ahau-7B.2 was consistently related to all nine sets of FT phenotypic data. Based on five cleaved amplified polymorphic sequence (CAPS) markers closely linked to QFT.ahau-7B.2, we narrowed down the target region to the 570.67-571.16 Mb interval (0.49 Mb) on chromosome 7B, in which four candidate genes were annotated. Of these, only TaRPM1-7BL exhibited consistent differential expression after low temperature treatment between freezing-tolerant and freezing-sensitive varieties. The results of cloning and whole-exome capture sequencing indicated that there were two main haplotypes for TaRPM1-7BL, including freezing-tolerant Hap1 and freezing-sensitive Hap2. Based on the representative SNP (+1956, A/G), leading to an amino acid change in the NBS domain, a CAPS marker (CAPS-TaRPM1-7BL) was developed and validated in 431 wheat varieties (including the above 245 materials) and 318 F2 lines derived from the cross of 'Annong 9267' (freezing-tolerant) × 'Yumai 9' (freezing-sensitive). Subsequently, the TaRPM1-7BL gene was silenced in 'Yumai 9' by virus-induced gene silencing (VIGS), and these silenced wheat seedlings exhibited enhanced FT phenotypes, suggesting that TaRPM1-7BL negatively regulates FT. These findings are valuable for understanding the complex genetic basis of FT in wheat.
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Plantones , Triticum , Congelación , Plantones/genética , Triticum/genética , Estudio de Asociación del Genoma Completo , Fenotipo , Sitios de Carácter CuantitativoRESUMEN
Computational neuroscience studies have shown that the structure of neural variability to an unchanged stimulus affects the amount of information encoded. Some artificial deep neural networks, such as those with Monte Carlo dropout layers, also have variable responses when the input is fixed. However, the structure of the trial-by-trial neural covariance in neural networks with dropout has not been studied, and its role in decoding accuracy is unknown. We studied the above questions in a convolutional neural network model with dropout in both the training and testing phases. We found that trial-by-trial correlation between neurons (i.e., noise correlation) is positive and low dimensional. Neurons that are close in a feature map have larger noise correlation. These properties are surprisingly similar to the findings in the visual cortex. We further analyzed the alignment of the main axes of the covariance matrix. We found that different images share a common trial-by-trial noise covariance subspace, and they are aligned with the global signal covariance. This evidence that the noise covariance is aligned with signal covariance suggests that noise covariance in dropout neural networks reduces network accuracy, which we further verified directly with a trial-shuffling procedure commonly used in neuroscience. These findings highlight a previously overlooked aspect of dropout layers that can affect network performance. Such dropout networks could also potentially be a computational model of neural variability.
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Redes Neurales de la Computación , Corteza Visual , NeuronasRESUMEN
Sensory perception is dramatically influenced by the context. Models of contextual neural surround effects in vision have mostly accounted for Primary Visual Cortex (V1) data, via nonlinear computations such as divisive normalization. However, surround effects are not well understood within a hierarchy, for neurons with more complex stimulus selectivity beyond V1. We utilized feedforward deep convolutional neural networks and developed a gradient-based technique to visualize the most suppressive and excitatory surround. We found that deep neural networks exhibited a key signature of surround effects in V1, highlighting center stimuli that visually stand out from the surround and suppressing responses when the surround stimulus is similar to the center. We found that in some neurons, especially in late layers, when the center stimulus was altered, the most suppressive surround surprisingly can follow the change. Through the visualization approach, we generalized previous understanding of surround effects to more complex stimuli, in ways that have not been revealed in visual cortices. In contrast, the suppression based on center surround similarity was not observed in an untrained network. We identified further successes and mismatches of the feedforward CNNs to the biology. Our results provide a testable hypothesis of surround effects in higher visual cortices, and the visualization approach could be adopted in future biological experimental designs.
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Corteza Visual , Campos Visuales , Estimulación Luminosa/métodos , Redes Neurales de la Computación , Corteza Visual/fisiología , Neuronas/fisiología , Percepción Visual/fisiologíaRESUMEN
PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.
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Carbapenémicos , Trasplante de Pulmón , Humanos , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Receptores de Trasplantes , Pulmón , Tamizaje Masivo , Trasplante de Pulmón/efectos adversosRESUMEN
Mixed lead-tin (PbSn) perovskite solar cells (PSCs) possess low toxicity and adjustable bandgap for both single-junction and all-perovskite tandem solar cells. However, the performance of mixed PbSn PSCs still lags behind the theoretical efficiency. The uncontrollable crystallization and the resulting structural defect are important reasons. Here, the bidirectional anions gathering strategy (BAG) is reported by using Methylammonium acetate (MAAc) and Methylammonium thiocyanate (MASCN) as perovskite bulk additives, which Ac- escapes from the perovskite film top surface while SCN- gathers at the perovskite film bottom in the crystallization process. After the optoelectronic techniques, the bidirectional anions movement caused by the top-down gradient crystallization is demonstrated. The layer-by-layer crystallization can collect anions in the next layer and gather at the broader, enabling a controllable crystallization process, thus getting a high-quality perovskite film with better phase crystallinity and lower defect concentration. As a result, PSCs treated by the BAG strategy exhibit outstanding photovoltaic and electroluminescent performance with a champion efficiency of 22.14%. Additionally, it demonstrates excellent long-term stability, which retains ≈92.8% of its initial efficiency after 4000 h aging test in the N2 glove box.
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OBJECTIVE: Lidocaine, a common local anesthetic in medical practice, exhibits anticancer properties across various tumor types. In this study, we aimed to investigate the effects and mechanisms of lidocaine on oral squamous cell carcinoma. METHODS: Cell viability and proliferation were assessed through CCK-8 and EdU assays. Transwell assays were used to analyze cell migration and invasion. Immunofluorescence assays were conducted to determine MMP9 levels. In vivo tumor growth was evaluated using a tumor xenograft model, and Ki67 and MMP9 levels were determined using immunohistochemistry. N6 -methyladenosine levels were assessed using dot plots and ELISA. mRNA and protein levels were examined through reverse transcription-quantitative PCR or western blot analysis. The association between IGF2BP2 and caveolin-1 was validated through RIP and luciferase reporter assays. RESULTS: Lidocaine exhibited suppressive effects on the viability, migration, invasion, and tumor formation of oral squamous cell carcinoma. IGF2BP2 expression correlated with poor survival and was downregulated by lidocaine. Lidocaine reduced caveolin-1 stability by decreasing IGF2BP2 levels. Caveolin-1 overexpression partially reversed the suppressive effects of lidocaine on the progression of oral squamous cell carcinoma cells. CONCLUSION: Lidocaine exerts an anticancer role in oral squamous cell carcinoma via IGF2BP2-mediated regulation of caveolin-1 stability.
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OBJECTIVE: This study aimed to explore and analyze the factors affecting the incidence of pneumonia after coronary artery bypass grafting (CABG) to provide reference for the prevention of such situation. METHODS: A total of 500 patients who underwent CABG in a hospital were selected. From March 2019 to March 2022, 410 patients without pneumonia and 90 patients with pneumonia were divided into groups A and B. The influencing factors and pathogen composition of postoperative pneumonia were discussed and analyzed. RESULTS: Univariable analysis results showed that age, cardiac function grade, occurrence of smoking, operation time, tracheal intubation time, suspended red-blood-cell transfusion and hospital stay in group B were higher than those in group A. Multivariable logistic analysis results showed that operation time, smoking history, and tracheal intubation time were risk factors for pneumonia after CABG. Among the 90 patients with postoperative pneumonia, 90 had pathogens, 81 had Gram-negative bacteria, 4 had Gram-positive bacteria, and 5 had fungi. CONCLUSIONS: Patients after CABG were more likely to develop pneumonia. Operation time, smoking history, and tracheal intubation time were the risk factors of pneumonia after CABG. Most of these patients had Gram-negative bacteria. Patient intervention based on the influencing factors can effectively prevent the occurrence of postoperative pneumonia.
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Puente de Arteria Coronaria , Neumonía , Humanos , Incidencia , Puente de Arteria Coronaria/efectos adversos , Neumonía/epidemiología , Neumonía/etiología , Neumonía/prevención & control , Factores de Riesgo , Intubación Intratraqueal/efectos adversos , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
To assess the impact of topical vancomycin (TV) application in decreasing sternal wound infections (SWIs) post cardiac surgery (CS), we lead a meta-analysis. Twenty-three thousand seven hundred and forty five participants had CS at the outset of the investigations, according to a thorough evaluation of the literature done up to November 2022; 8730 of them used TV, while 15 015 were controls. To assess the effectiveness of TV application in lowering SWIs following CS, odds ratios (OR) with 95% confidence intervals (CIs) were computed with dichotomous technique with a fixed- or random-effect model. The TV had significantly lower SWIs post CS (OR, 0.34; 95% CI, 0.20-0.57; P < .001), and deep SWIs post CS (OR, 0.26; 95% CI, 0.11-0.65; P = .004) compared with control as shown in Figures 2 and 3. Yet, there was no significant difference found amongst TV and control in superficial SWIs post CS (OR, 0.30; 95% CI, 0.07-1.30; P = .011). The TV had significantly lower SWIs, and deep SWIs post CS, and no significant difference was found in superficial SWIs post CS compared with control. The low number of included studies in this meta-analysis for superficial SWIs calls for precaution when analysing the outcomes.
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Procedimientos Quirúrgicos Cardíacos , Vancomicina , Humanos , Vancomicina/uso terapéutico , Antibacterianos/uso terapéutico , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/prevención & control , Resultado del Tratamiento , Esternón/cirugía , Procedimientos Quirúrgicos Cardíacos/efectos adversosRESUMEN
Ion migration is a notorious phenomenon observed in ionic perovskite materials. It causes several severe issues in perovskite optoelectronic devices such as instability, current hysteresis, and phase segregation. Here, we report that, in contrast to lead halide perovskites (LHPs), no ion migration or phase segregation was observed in tin halide perovskites (THPs) under illumination or an electric field. The origin is attributed to a much stronger Sn-halide bond and higher ion migration activation energy (Ea ) in THPs, which remain nearly constant under illumination. We further figured out the threshold Ea for the absence of ion migration to be around 0.65â eV using the CsSny Pb1-y (I0.6 Br0.4 )3 system whose Ea varies with Sn ratios. Our work shows that ion migration does not necessarily exist in all perovskites and suggests metallic doping to be a promising way of stopping ion migration and improving the intrinsic stability of perovskites.
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Photovoltaic technology with low weight, high specific power in cold environments, and compatibility with flexible fabrication is highly desired for near-space vehicles and polar region applications. Herein, we demonstrate efficient low-temperature flexible perovskite solar cells by improving the interfacial contact between electron-transport layer (ETL) and perovskite layer. We find that the adsorbed oxygen active sites and oxygen vacancies of flexible tin oxide (SnO2 ) ETL layer can be effectively decreased by incorporating a trace amount of titanium tetrachloride (TiCl4 ). The effective defects elimination at the interfacial increases the electron mobility of flexible SnO2 layer, regulates band alignment at the perovskite/SnO2 interface, induces larger perovskite crystal growth, and improves charge collection efficiency in a complete solar cell. Correspondingly, the improved interfacial contact transforms into high-performance solar cells under one-sun illumination (AM 1.5G) with efficiencies up to 23.7 % at 218â K, which might open up a new era of application of this emerging flexible photovoltaic technology to low-temperature environments such as near-space and polar regions.
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OBJECTIVE: Recent studies have provided insights into the gut microbiota in autism spectrum disorder (ASD); however, these studies were restricted owing to limited sampling at the unitary stage of childhood. Herein, we aimed to reveal developmental characteristics of gut microbiota in a large cohort of subjects with ASD combined with interindividual factors impacting gut microbiota. DESIGN: A large cohort of 773 subjects with ASD (aged 16 months to 19 years), 429 neurotypical (NT) development subjects (aged 11 months to 15 years) were emolyed to determine the dynamics change of gut microbiota across different ages using 16S rRNA sequencing. RESULT: In subjects with ASD, we observed a distinct but progressive deviation in the development of gut microbiota characterised by persistently decreased alpha diversity, early unsustainable immature microbiota, altered aboudance of 20 operational taxonomic units (OTUs), decreased taxon detection rate and 325 deregulated microbial metabolic functions with age-dependent patterns. We further revealed microbial relationships that have changed extensively in ASD before 3 years of age, which were associated with the severity of behaviour, sleep and GI symptoms in the ASD group. This analysis demonstrated that a signature of the combination of 2 OTUs, Veillonella and Enterobacteriaceae, and 17 microbial metabolic functions efficiently discriminated ASD from NT subjects in both the discovery (area under the curve (AUC)=0.86), and validation 1 (AUC=0.78), 2 (AUC=0.82) and 3 (AUC=0.67) sets. CONCLUSION: Our large cohort combined with clinical symptom analysis highlights the key regulator of gut microbiota in the pathogenesis of ASD and emphasises the importance of monitoring and targeting the gut microbiome in future clinical applications of ASD.
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Trastorno del Espectro Autista , Microbioma Gastrointestinal , Microbiota , Trastorno del Espectro Autista/metabolismo , Niño , Estudios de Cohortes , Microbioma Gastrointestinal/genética , Humanos , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: Seed dormancy and germination determine wheat resistance to pre-harvest sprouting and thereby affect grain yield and quality. Arabidopsis VQ genes have been shown to influence seed germination; however, the functions of wheat VQ genes have not been characterized. RESULTS: We identified 65 TaVQ genes in common wheat and named them TaVQ1-65. We identified 48 paralogous pairs, 37 of which had Ka/Ks values greater than 1, suggesting that most TaVQ genes have experienced positive selection. Chromosome locations, gene structures, promoter element analysis, and gene ontology annotations of the TaVQs showed that their structures determined their functions and that structural changes reflected functional diversity. Transcriptome-based expression analysis of 62 TaVQ genes and microarray analysis of 11 TaVQ genes indicated that they played important roles in diverse biological processes. We compared TaVQ gene expression and seed germination index values among wheat varieties with contrasting seed dormancy and germination phenotypes and identified 21 TaVQ genes that may be involved in seed dormancy and germination. CONCLUSIONS: Sixty-five TaVQ proteins were identified for the first time in common wheat, and bioinformatics analyses were used to investigate their phylogenetic relationships and evolutionary divergence. qRT-PCR data showed that 21 TaVQ candidate genes were potentially involved in seed dormancy and germination. These findings provide useful information for further cloning and functional analysis of TaVQ genes and introduce useful candidate genes for the improvement of PHS resistance in wheat.
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Germinación , Latencia en las Plantas , Grano Comestible , Germinación/genética , Filogenia , Latencia en las Plantas/genética , Triticum/genéticaRESUMEN
Light-trapping design is a good strategy to obtain ultra-thin solar cells without sacrificing conversion efficiency. If applied to III-V compound multi-junction solar cells (MJSCs), it not only can greatly reduce the cell cost and weight, but also improve its radiation tolerance when operating in space. This paper formulates all subcell absorptance in an arbitrary N-junction solar cell with an ideal front textured surface and perfect rear mirror, including the effects of complex absorption and luminescence coupling in the stack. Taking the well-known InGaP/GaAs/InGaAs triple-junction solar cell (3J) for instance, the ultra-thin design and the conversion efficiency both in radiative limit and that with subcell internal radiative efficiency below-unity are predicted. Our results show that such front-textured 3J with top-subcell thickness varying from 200 to 500â nm can enhance light absorption so significantly that more than 28% of top-subcell, 56% of middle-subcell, and 90% of bottom-subcell thickness will be cut down when compared with the smooth-surfaced 3J. Typically, (350â nm, 315â nm, 28â nm) is recommended as the optimal design for the front-textured 3J with an experimental efficiency of over 38%. For the same benchmarks on photocurrent of 15.1 mA/cm2 or detailed balance limit of 44%, the minimum total thickness (all subcells only) in the front-textured 3J is only 1453â nm, that is even 71% of that in the rear-textured 3J, quantitatively revealing front texturization has a greater potential for material cut-down than rear texturization. Finally, the impacts of non-ideal scattering texturization on cell performance and ultra-thin design are also discussed. This work provides theoretical guidance for experimental studies on ultra-thin and high-efficient MJSCs with various light-trapping strategies.