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The poor operational stability of perovskite light-emitting diodes (PeLEDs) remains a major obstacle to their commercial application. Achieving high brightness and quantum efficiency at low driving voltages, thus effectively reducing heat accumulation, is key to enhancing the operational lifetime of PeLEDs. Here, we present a breakthrough, attaining a record-low driving voltage while maintaining high brightness and efficiency. By thoroughly suppressing interface recombination and ensuring excellent charge transport, our PeLEDs, with an emission peak at 515 nanometers, achieve a maximum brightness of 90,295 candelas per square meter and a peak external quantum efficiency of 27.8% with an ultralow turn-on voltage of 1.7 volts (~70% bandgap voltage). Notably, Joule heat is nearly negligible at these low driving voltages, substantially extending the operational lifetime to 7691.1 hours. Our optimized strategies effectively tackle stability issue through thermal management, paving the way for highly stable PeLEDs.

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In recent years, minimally invasive biopsy techniques have been widely used to generate small tissue samples that require processing in clinical pathology. However, small paraffin-embedded tissues are prone to loss due to their small size. To prevent the loss of small tissues, researchers have employed nonbiological embedding materials for preembedding, but this approach can lead to cumbersome experimental procedures and increase the chances of tissue loss. This study aimed to develop a convenient decellularized embedding material derived from biological membrane tissues to effectively protect small tissues from loss during paraffin embedding. This study decellularized three types of fresh animal-derived membrane tissues and selected the small intestine as the most suitable decellularized raw material through attempts at softening, comparing physical properties, and using tissue as the starting material. Subsequently, small tissues from various tissue sources were embedded, followed by H&E staining, Masson staining, immunofluorescence staining, and immunohistochemical staining. The decellularized material derived from biomembrane tissues (DMBT) developed in this study can reduce the loss of small tissues without the need for preembedding, thereby shortening the embedding process. This provides a new pathological embedding tool for future laboratory and clinical research and work.•The fat layer of the pig's small intestine is scraped off, and chemical reagents are used to defat and decellularize it.•Chemical reagents are used to soften and make the pig's small intestine transparent, and the decellularized pig's small intestine is dried.•DMBT is used for embedding and staining the biological tissue.

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Enhanced spontaneous bladder contractions (SBCs) have been thought one of the important underlying mechanisms for detrusor overactivity (DO). Piezo1 channel has been demonstrated involved in bladder function and dysfunction in rodents. We aimed to investigate the modulating role of Piezo1 in SBCs activity of human bladder. Human bladder tissues were obtained from 24 organ donors. SBCs of isolated bladder strips were recorded in organ bath. Piezo1 expression was examined with reverse transcription-quantitative polymerase chain reaction and immunofluorescence staining. ATP and acetylcholine release in cultured human urothelial cells was measured. Piezo1 is abundantly expressed in the bladder mucosa. Activation of Piezo1 with its specific agonist Yoda1 (100 nM-100 µM) enhanced the SBCs activity in isolated human bladder strips in a concentration-dependent manner. The effect of Yoda1 mimicked the effect of a low concentration (30 nM) of carbachol, which can be attenuated by removing the mucosa, blocking muscarinic receptors with atropine (1 µM), and blocking purinergic receptors with pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS, 30 µM), but not by tetrodotoxin (1 µM). Activation of urothelial Piezo1 with Yoda1 (30 µM) or hypotonic solution induced the release of ATP and acetylcholine in cultured human urothelial cells. In patients with benign prostatic hyperplasia, greater Piezo1 expression was observed in bladder mucosa from patients with DO than patients without DO. We conclude that upregulation and activation of Piezo1 may contribute to DO generation in patients with bladder outlet obstruction by promoting the urothelial release of ATP and acetylcholine. Inhibition of Piezo1 may be a novel therapeutic approach in the treatment of overactive bladder.

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We have developed a portfolio of antibody-based modules that can be prefabricated as standalone units and snapped together in plug-and-play fashion to create uniquely powerful multifunctional assemblies. The basic building blocks are derived from multiple pairs of native and modified Fab scaffolds and protein G (PG) variants engineered by phage display to introduce high pair-wise specificity. The variety of possible Fab-PG pairings provides a highly orthogonal system that can be exploited to perform challenging cell biology operations in a straightforward manner. The simplest manifestation allows multiplexed antigen detection using PG variants fused to fluorescently labeled SNAP-tags. Moreover, Fabs can be readily attached to a PG-Fc dimer module which acts as the core unit to produce plug-and-play IgG-like assemblies, and the utility can be further expanded to produce bispecific analogs using the "knobs into holes" strategy. These core PG-Fc dimer modules can be made and stored in bulk to produce off-the-shelf customized IgG entities in minutes, not days or weeks by just adding a Fab with the desired antigen specificity. In another application, the bispecific modalities form the building block for fabricating potent Bispecific T-cell Engagers (BiTEs), demonstrating their efficacy in cancer cell-killing assays. Additionally, the system can be adapted to include commercial antibodies as building blocks, greatly increasing the target space. Crystal structure analysis reveals that a few strategically positioned interactions engender the specificity between the Fab-PG variant pairs, requiring minimal changes to match the scaffolds for different possible combinations. This plug-and-play platform offers a user-friendly and versatile approach to enhance the functionality of antibody-based reagents in cell biology research.

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Rice leaf diseases have an important impact on modern farming, threatening crop health and yield. Accurate semantic segmentation techniques are crucial for segmenting diseased leaf parts and assisting farmers in disease identification. However, the diversity of rice growing environments and the complexity of leaf diseases pose challenges. To address these issues, this study introduces an innovative semantic segmentation algorithm for rice leaf pests and diseases based on the Transformer architecture AISOA-SSformer. First, it features the sparse global-update perceptron for real-time parameter updating, enhancing model stability and accuracy in learning irregular leaf features. Second, the salient feature attention mechanism is introduced to separate and reorganize features using the spatial reconstruction module (SRM) and channel reconstruction module (CRM), focusing on salient feature extraction and reducing background interference. Additionally, the annealing-integrated sparrow optimization algorithm fine-tunes the sparrow algorithm, gradually reducing the stochastic search amplitude to minimize loss. This enhances the model's adaptability and robustness, particularly against fuzzy edge features. The experimental results show that AISOA-SSformer achieves an 83.1% MIoU, an 80.3% Dice coefficient, and a 76.5% recall on a homemade dataset, with a model size of only 14.71 million parameters. Compared with other popular algorithms, it demonstrates greater accuracy in rice leaf disease segmentation. This method effectively improves segmentation, providing valuable insights for modern plantation management. The data and code used in this study will be open sourced at https://github.com/ZhouGuoXiong/Rice-Leaf-Disease-Segmentation-Dataset-Code.

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Precise disease detection is crucial in modern precision agriculture, especially in ensuring the health of tomato crops and enhancing agricultural productivity and product quality. Although most existing disease detection methods have helped growers identify tomato leaf diseases to some extent, these methods typically target fixed categories. When faced with new diseases, extensive and costly manual annotation is required to retrain the dataset. To overcome these limitations, this study proposes a multimodal model PDC-VLD based on the open-vocabulary object detection (OVD) technology within the VLDet framework, which can accurately identify new tomato leaf diseases without manual annotation by using only image-text pairs. First, we developed a progressive visual transformer-convolutional pyramid module (PVT-C) that effectively extracts tomato leaf disease features and optimizes anchor box positioning using the self-supervised learning algorithm DINO, suppressing interference from irrelevant backgrounds. Then, a context feature guided module (CFG) was adopted to address the low adaptability and recognition accuracy of the model in data-scarce environments. To validate the model's effectiveness, we constructed a tomato leaf disease image dataset containing 4 base classes and 2 new categories. Experimental results show that the PDC-VLD model achieved 61.2% on the main evaluation metric mAP novel 50 , and 56.4% on mAP novel 75 , 87.7% on mAP base 50 , 81.0% on mAP all 50 , and 45.5% on average recall, outperforming existing OVD models. Our research provides an innovative solution for efficiently and accurately detecting new diseases, substantially reducing the need for manual annotation, and offering critical technical support and practical reference for agricultural workers.

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Dysregulation of the transforming growth factor-ß (TGF-ß) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug-resistant CSCs. Through a genome-wide CRISPR activation screen utilizing stem-like drug-resistant properties as a readout, the TGF-ß receptor-associated binding protein 1 (TGFBRAP1) is identified as a TGF-ß-inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF-ß receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF-ß signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly-ubiquitination and proteasomal degradation. Moreover, hyperactive TGF-ß signaling in turn up-regulates TGFBRAP1 expression in drug-resistant CSC-like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF-ß signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF-ß signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1-mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF-ß signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.

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Patients with radiation-induced meningioma (RIM), most of whom had received head radiation therapy or had been exposed to ionizing radiation during childhood or adolescence, are at risk of developing cranial meningiomas throughout their lifetimes because of the long latency period. Although intermediate-to-high-dose ionizing radiation exposure is an established risk factor for RIM, risk factors for low-dose RIM remain incompletely defined. This study presents the case of a 56-year-old woman diagnosed with radiation-induced giant meningioma 2.5 years after undergoing an interventional embolization procedure for a brain aneurysm. This is the first report of RIM attributable to a brain intervention with an extremely short latency period. The total radiation dose received by the patient during the operation was 1367.3 mGy, representing a low dose. Our case report strengthens the evidence that even low radiation doses can increase the risk of RIM. These findings provide a realistic basis for the theoretical study of RIM and suggest some new ideas for RIM treatment. The need for caution in the use of radioactive treatments and optimization of interventional procedures is highlighted.

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The increasing need for energy storage devices with high energy density has led to significant interest in Li-metal batteries (LMBs). However, the use of commercial electrolytes in LMBs is problematic due to their flammability, inadequate performance at low temperatures, and tendency to promote the growth of lithium dendrites and other flaws. This study introduces a localized high-concentration electrolyte (LHCE) that addresses these issues by employing non-flammable electrolyte components and incorporating carefully designed additives to enhance flame retardancy and low-temperature performance. By incorporating additives to optimize the electrolyte, it is possible to attain inorganic-dominated solid electrolyte interphases on both the cathode and anode. This achievement results in a uniform deposition of lithium, as well as the suppression of electrolyte decomposition and cathode deterioration. Consequently, this LHCE achieve over 300 stable cycles for both LiNi0.9Mn0.05Co0.05O2||Li cells and LiCoO2||Li cells, as well as 50 cycles for LiNi0.8Mn0.1Co0.1O2 (NCM811||Li) pouch cells. Furthermore, NCM811||Li cells maintain 84% discharge capacity at -20 °C, in comparison to the capacity at room temperature. The utilization of this electrolyte presents novel perspectives for the safe implementation of LMBs.

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Tomato leaf disease control in the field of smart agriculture urgently requires attention and reinforcement. This paper proposes a method called LAFANet for image-text retrieval, which integrates image and text information for joint analysis of multimodal data, helping agricultural practitioners to provide more comprehensive and in-depth diagnostic evidence to ensure the quality and yield of tomatoes. First, we focus on six common tomato leaf disease images and text descriptions, creating a Tomato Leaf Disease Image-Text Retrieval Dataset (TLDITRD), introducing image-text retrieval into the field of tomato leaf disease retrieval. Then, utilizing ViT and BERT models, we extract detailed image features and sequences of textual features, incorporating contextual information from image-text pairs. To address errors in image-text retrieval caused by complex backgrounds, we propose Learnable Fusion Attention (LFA) to amplify the fusion of textual and image features, thereby extracting substantial semantic insights from both modalities. To delve further into the semantic connections across various modalities, we propose a False Negative Elimination-Adversarial Negative Selection (FNE-ANS) approach. This method aims to identify adversarial negative instances that specifically target false negatives within the triplet function, thereby imposing constraints on the model. To bolster the model's capacity for generalization and precision, we propose Adversarial Regularization (AR). This approach involves incorporating adversarial perturbations during model training, thereby fortifying its resilience and adaptability to slight variations in input data. Experimental results show that, compared with existing ultramodern models, LAFANet outperformed existing models on TLDITRD dataset, with top1, top5, and top10 reaching 83.3% and 90.0%, and top1, top5, and top10 reaching 80.3%, 93.7%, and 96.3%. LAFANet offers fresh technical backing and algorithmic insights for the retrieval of tomato leaf disease through image-text correlation.

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Chemodynamic therapy (CDT) is a novel antitumor strategy that employs Fenton or Fenton-like reactions to generate highly toxic hydroxyl radical (OH•) from hydrogen peroxide (H2O2) for inducing tumor cell death. However, the antitumor efficacy of the CDT strategy is harshly limited by the redox homeostasis of tumor cells; especially the OH • is easily scavenged by glutathione (GSH) and the intracellular H2O2 level is insufficient in the tumor cells. Herein, we propose the Mn2+-menadione (also known as vitamin K3, MK3) cascade biocatalysis strategy to disrupt the redox homeostasis of tumor cells and induce a OH• storm, resulting in enhanced CDT effect. A nanoliposome encapsulating Mn-MK3 (Mn-MK3@LP) was prepared for the treatment of hepatic tumors in this study. After Mn-MK3@LPs were taken up by tumor cells, menadione could facilitate the production of intracellular H2O2 via redox cycling, and further the cytotoxic OH • burst was induced by Mn2+-mediated Fenton-like reaction. Moreover, high-valent manganese ions were reduced by GSH and the depletion of GSH further disrupted the redox homeostasis of tumor cells, thus achieving synergistically enhanced CDT. Overall, both cellular and animal experiments confirmed that the Mn-MK3@LP cascade biocatalysis nanoliposome exhibited excellent biosafety and tumor suppression efficacy. This study may provide deep insights for developing novel CDT-based strategies for tumor therapy.

Asunto(s)

Glutatión , Peróxido de Hidrógeno , Radical Hidroxilo , Vitamina K 3 , Animales , Radical Hidroxilo/química , Radical Hidroxilo/metabolismo , Humanos , Ratones , Glutatión/metabolismo , Glutatión/química , Vitamina K 3/química , Vitamina K 3/farmacología , Biocatálisis , Línea Celular Tumoral , Manganeso/química , Oxidación-Reducción/efectos de los fármacos , Ratones Endogámicos BALB C , Liposomas/química , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Ratones Desnudos , Células Hep G2 , Antineoplásicos/farmacología , Antineoplásicos/química , Nanopartículas/química , Hierro

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BACKGROUND: Regulatory B cells (Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs (miRNAs), miR-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and miR-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs (mBregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. METHODS: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce miR-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. RESULTS: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of mBregs in the circulating blood were significantly impaired. miR-29a-3p was found to be a regulator of mBregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5 (NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of mBregs. The inhibition of miR-29a-3p in CD19+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into mBregs. In addition, the observed enhancement of differentiation and immunosuppressive function of mBregs upon miR-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. CONCLUSIONS: miR-29a-3p was found to be a crucial regulator for mBregs differentiation and immunosuppressive function. Silencing miR-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

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Antígenos CD19 , Linfocitos B Reguladores , Antígeno CD24 , Diferenciación Celular , Trasplante de Hígado , MicroARNs , Humanos , MicroARNs/metabolismo , MicroARNs/genética , Linfocitos B Reguladores/inmunología , Linfocitos B Reguladores/metabolismo , Antígenos CD19/metabolismo , Antígenos CD19/genética , Masculino , Antígeno CD24/metabolismo , Antígeno CD24/genética , Transducción de Señal , Rechazo de Injerto/inmunología , Rechazo de Injerto/genética , Femenino , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Persona de Mediana Edad , Tolerancia Inmunológica , Células Cultivadas , Adulto , Fenotipo , Memoria Inmunológica

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In the world's first pig-to-human cardiac cytomegalovirus (PCMV), xenotransplant and elevated levels of porcine key factors contributing to patient mortality were considered. This has renewed attention on PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effectively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infection capabilities. This opens up possibilities for the future production of pig populations with antiviral functionalities.

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PURPOSE: To report the indications, surgical techniques, and outcomes of repeat keratoplasty and evaluate the risk factors for graft failure in the Chinese population. METHODS: The medical records of 216 patients (243 cases) who underwent at least two keratoplasties at a leading eye hospital in southern China between 2011 and 2020 were retrospectively reviewed. Indications and surgical procedures for repeat corneal transplantation were analyzed. Kaplan-Meier survival analysis was used to determine the graft survival rate after repeat keratoplasty. A multivariable survival model was used to assess the risk factors. RESULTS: Repeated keratoplasties increased continuously from 2011 to 2020 (P = 0.002). The most common primary indication was infectious keratitis (38.7%), and the most common reason for repeat keratoplasty was graft rejection (30.04%). Regraft techniques included penetrating keratoplasty (PK) in 165 cases (67.9%), deep lamellar keratoplasty (DALK) in 52 cases (21.40%), and endothelial keratoplasty (EK) in 26 cases (10.7%). Median survival was 5.3, 6.8, and 6.4 years for PK, DALK, and EK, respectively. The 5-year survival rate was 53.5%, 66.6%, and 69.8% for PK, DALK, and EK, respectively. The median LogMAR visual acuity was 1.4 for PK, 0.75 for DALK, and 1.2 for EK at the end of the follow-up. Multivariate analysis revealed that graft rejection is a risk factor for repeat keratoplasty failure (P = 0.002). CONCLUSIONS: DALK and EK may provide better outcomes than PK in treating graft failure. Preventing and treating postoperative graft rejection may be key to improving regraft survival. These findings will aid in the management of failed corneal grafts.

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Enfermedades de la Córnea , Rechazo de Injerto , Supervivencia de Injerto , Reoperación , Agudeza Visual , Humanos , Masculino , Estudios Retrospectivos , Femenino , Factores de Riesgo , Reoperación/estadística & datos numéricos , Persona de Mediana Edad , China/epidemiología , Enfermedades de la Córnea/cirugía , Adulto , Rechazo de Injerto/epidemiología , Anciano , Estudios de Seguimiento , Trasplante de Córnea/métodos , Adulto Joven , Adolescente , Insuficiencia del Tratamiento , Incidencia , Anciano de 80 o más Años , Complicaciones Posoperatorias/epidemiología , Queratoplastia Penetrante/métodos , Niño

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Redox is a unique, programmable modality capable of bridging communication between biology and electronics. Previous studies have shown that the E. coli redox-responsive OxyRS regulon can be re-wired to accept electrochemically generated hydrogen peroxide (H2O2) as an inducer of gene expression. Here we report that the redox-active phenolic plant signaling molecule acetosyringone (AS) can also induce gene expression from the OxyRS regulon. AS must be oxidized, however, as the reduced state present under normal conditions cannot induce gene expression. Thus, AS serves as a "pro-signaling molecule" that can be activated by its oxidation-in our case by application of oxidizing potential to an electrode. We show that the OxyRS regulon is not induced electrochemically if the imposed electrode potential is in the mid-physiological range. Electronically sliding the applied potential to either oxidative or reductive extremes induces this regulon but through different mechanisms: reduction of O2 to form H2O2 or oxidation of AS. Fundamentally, this work reinforces the emerging concept that redox signaling depends more on molecular activities than molecular structure. From an applications perspective, the creation of an electronically programmed "pro-signal" dramatically expands the toolbox for electronic control of biological responses in microbes, including in complex environments, cell-based materials, and biomanufacturing.

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Escherichia coli , Oxidación-Reducción , Transducción de Señal , Escherichia coli/genética , Escherichia coli/metabolismo , Peróxido de Hidrógeno , Regulón/genética , Regulación Bacteriana de la Expresión Génica , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Fenoles/química , Fenoles/metabolismo

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The long-term high-fat diet (HFD) can cause myocardial lipotoxicity, which is characterized pathologically by myocardial hypertrophy, fibrosis, and remodeling and clinically by cardiac dysfunction and heart failure in patients with obesity and diabetes. Circular RNAs (circRNAs), a novel class of noncoding RNA characterized by a ring formation through covalent bonds, play a critical role in various cardiovascular diseases. However, few studies have been conducted to investigate the role and mechanism of circRNA in myocardial lipotoxicity. Here, we found that circ_005077, formed by exon 2-4 of Crmp1, was significantly upregulated in the myocardium of an HFD-fed rat. Furthermore, we identified circ_005077 as a novel ferroptosis-related regulator that plays a role in palmitic acid (PA) and HFD-induced myocardial lipotoxicity in vitro and in vivo. Mechanically, circ_005077 interacted with Cyclophilin A (CyPA) and inhibited its degradation via the ubiquitination proteasome system (UBS), thus promoting the interaction between CyPA and p47phox to enhance the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase responsible for ROS generation, subsequently inducing ferroptosis. Therefore, our results provide new insights into the mechanisms of myocardial lipotoxicity, potentially leading to the identification of a novel therapeutic target for the treatment of myocardial lipotoxicity in the future.

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Ciclofilina A , Dieta Alta en Grasa , Ferroptosis , Animales , Ratas , Ciclofilina A/metabolismo , Miocardio/metabolismo , Obesidad/metabolismo

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BACKGROUND: In boron neutron capture therapy (BNCT)-a form of binary radiotherapy-the primary challenge in treatment planning systems for dose calculations arises from the time-consuming nature of the Monte Carlo (MC) method. Recent progress, including the use of neural networks (NN), has been made to accelerate BNCT dose calculations. However, this approach may result in significant dose errors in both the tumor and the skin, with the latter being a critical organ in BNCT. Furthermore, owing to the lack of physical processes in purely NN-based approaches, their reliability for clinical dose calculations in BNCT is questionable. PURPOSE: In this study, a physically constrained MC-NN (PCMC-NN) coupling algorithm is proposed to achieve fast and accurate computation of the BNCT three-dimensional (3D) therapeutic dose distribution. This approach synergizes the high precision of the MC method with the speed of the NN and utilizes physical conservation laws to constrain the coupling process. It addresses the time-consuming issue of the traditional MC method while reducing dose errors. METHODS: Clinical data were collected from 113 glioblastoma patients. For each patient, the 3D dose distributions for both the coarse and detailed dose grids were calculated using the MC code PHITS. Among these patients, the data from 14 patients were allocated to the test set, 9 to the validation set, and the remaining to the training set. A neural network, 3D-Unet, was built based on the coarse grid dose and patient CT information to enable fast and accurate computation of the 3D detailed grid dose distribution of BNCT. RESULTS: Statistical evaluations, including relative deviation, dose deviation, mean absolute error (MAE), and mean absolute percentage error (MAPE) were conducted. Our findings suggested that the PCMC-NN algorithm substantially outperformed the traditional NN and interpolation methods. Furthermore, the proposed algorithm significantly reduced errors, particularly in the skin and GTV, and improved computational accuracy (hereinafter referred to simply as 'accuracy') with a MAPE range of 1.6%-4.0% and a maximum MAE of 0.3 Gy (IsoE) for different organs. The dose-volume histograms generated by the PCMC-NN aligned well with those obtained from the MC method, further validating its accuracy. CONCLUSIONS: The PCMC-NN algorithm enhanced the speed and accuracy of BNCT dose calculations by combining the MC method with the NN algorithm. This indicates the significant potential of the proposed algorithm for clinical applications in optimizing treatment planning.

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Algoritmos , Terapia por Captura de Neutrón de Boro , Método de Montecarlo , Redes Neurales de la Computación , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Terapia por Captura de Neutrón de Boro/métodos , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Dosis de Radiación

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Increasing the charging cutoff voltage of LiCoO2 to 4.6 V is significant for enhancing battery density. However, the practical application of Li‖LiCoO2 batteries with a 4.6 V cutoff voltage faces significant impediments due to the detrimental changes under high voltage. This study presents a novel bifunctional electrolyte additive, 2-(trifluoromethyl)benzamide (2-TFMBA), which is employed to establish a stable and dense cathode-electrolyte interface (CEI). Characterization results reveal that an optimized CEI is achieved through the synergistic effects of the amide groups and trifluoromethyl groups within 2-TFMBA. The resulting CEI not only enhances the structural stability of LiCoO2 but also serves as a high-speed lithium-ion conduction channel, which expedites the insertion and extraction of lithium ions. The Li‖LiCoO2 batteries with 0.5 wt% 2-TFMBA achieves an 84.7% capacity retention rate after enduring 300 cycles at a current rate of 1 C, under a cut-off voltage of 4.6 V. This study provides valuable strategic insights into the stabilization of cathode materials in high-voltage batteries.

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Acquired resistance to immunotherapy remains a critical yet incompletely understood biological mechanism. Here, using a mouse model of pancreatic ductal adenocarcinoma (PDAC) to study tumor relapse following immunotherapy-induced responses, we find that resistance is reproducibly associated with an epithelial-to-mesenchymal transition (EMT), with EMT-transcription factors ZEB1 and SNAIL functioning as master genetic and epigenetic regulators of this effect. Acquired resistance in this model is not due to immunosuppression in the tumor immune microenvironment, disruptions in the antigen presentation machinery, or altered expression of immune checkpoints. Rather, resistance is due to a tumor cell-intrinsic defect in T-cell killing. Molecularly, EMT leads to the epigenetic and transcriptional silencing of interferon regulatory factor 6 (Irf6), rendering tumor cells less sensitive to the pro-apoptotic effects of TNF-α. These findings indicate that acquired resistance to immunotherapy may be mediated by programs distinct from those governing primary resistance, including plasticity programs that render tumor cells impervious to T-cell killing.

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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Línea Celular Tumoral , Recurrencia Local de Neoplasia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/metabolismo , Inmunoterapia , Transición Epitelial-Mesenquimal/genética , Microambiente Tumoral

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Wolbachia bacteria (phylum Proteobacteria) are ubiquitous intracellular parasites of diverse invertebrates. In insects, coevolution has forged mutualistic associations with Wolbachia species, influencing reproduction, immunity, development, pathogen resistance, and overall fitness. However, the impact of Wolbachia on other microbial associates within the insect microbiome, which are crucial for host fitness, remains less explored. The diamondback moth (Plutella xylostella), a major pest of cruciferous vegetables worldwide, harbors the dominant Wolbachia strain plutWB1, known to distort its sex ratio. This study investigated the bacterial community diversity and dynamics across different developmental life stages and Wolbachia infection states in P. xylostella using high-throughput 16S rDNA amplicon sequencing. Proteobacteria and Firmicutes dominated the P. xylostella microbiome regardless of life stage or Wolbachia infection. However, the relative abundance of dominant genera, including an unclassified genus of Enterobacteriaceae, Wolbachia, Carnobacterium, and Delftia tsuruhatensis, displayed significant stage-specific variations. While significant differences in bacterial diversity and composition were observed across life stages, Wolbachia infection had no substantial impact on overall diversity. Nonetheless, relative abundances of specific genera differed between infection states. Notably, Wolbachia exhibited a stable, high relative abundance across all stages and negatively correlated with an unclassified genus of Enterobacteriaceae, Delftia tsuruhatensis, and Carnobacterium. Our findings provide a foundational understanding of the complex interplay between the host, Wolbachia, and the associated microbiome in P. xylostella, paving the way for a deeper understanding of their complex interactions and potential implications for pest control strategies.