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We present deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) for co-mapping of mRNAs and proteins in a formaldehyde-fixed tissue slide via next-generation sequencing (NGS). Parallel microfluidic channels were used to deliver DNA barcodes to the surface of a tissue slide, and crossflow of two sets of barcodes, A1-50 and B1-50, followed by ligation in situ, yielded a 2D mosaic of tissue pixels, each containing a unique full barcode AB. Application to mouse embryos revealed major tissue types in early organogenesis as well as fine features like microvasculature in a brain and pigmented epithelium in an eye field. Gene expression profiles in 10-µm pixels conformed into the clusters of single-cell transcriptomes, allowing for rapid identification of cell types and spatial distributions. DBiT-seq can be adopted by researchers with no experience in microfluidics and may find applications in a range of fields including developmental biology, cancer biology, neuroscience, and clinical pathology.
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Código de Barras de DNA Taxonômico , Genômica , Especificidade de Órgãos/genética , Animais , Automação , Encéfalo/embriologia , Análise por Conglomerados , DNA Complementar/genética , Embrião de Mamíferos/metabolismo , Olho/embriologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Microfluídica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Análise de Célula Única , Transcriptoma/genéticaRESUMO
Achieving both high efficiency and long-term stability is the key to the commercialization of perovskite solar cells (PSCs)1,2. However, the diversity of perovskite (ABX3) compositions and phases makes it challenging to fabricate high-quality films3-5. Perovskite formation relies on the reaction between AX and BX2, whereas most conventional methods for film-growth regulation are based solely on the interaction with the BX2 component. Herein, we demonstrate an alternative approach to modulate reaction kinetics by anion-π interaction between AX and hexafluorobenzene (HFB). Notably, these two approaches are independent but work together to establish 'dual-site regulation', which achieves a delicate control over the reaction between AX and BX2 without unwanted intermediates. The resultant formamidinium lead halides (FAPbI3) films exhibit fewer defects, redshifted absorption and high phase purity without detectable nanoscale δ phase. Consequently, we achieved PSCs with power conversion efficiency (PCE) up to 26.07% for a 0.08-cm2 device (25.8% certified) and 24.63% for a 1-cm2 device. The device also kept 94% of its initial PCE after maximum power point (MPP) tracking for 1,258 h under full-spectrum AM 1.5 G sunlight at 50 ± 5 °C. This method expands the range of chemical interactions that occur in perovskite precursors by exploring anion-π interactions and highlights the importance of the AX component as a new and effective working site to improved photovoltaic devices with high quality and phase purity.
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Accumulating evidence has demonstrated that F-box protein 22 (FBXO22) participates in tumour development and progression in various types of human malignancies. However, the functions and detailed molecular mechanisms of FBXO22 in osteosarcoma tumorigenesis and progression remain elusive. In this study, we aimed to determine the effects of FBXO22 on the cell proliferation, migration and invasion of osteosarcoma cells using cell counting kit-8 and Matrigel Transwell approaches. Moreover, we explored the molecular mechanisms by which FBXO22 mediated oncogenesis and progression in osteosarcoma via Western blotting, immunoprecipitation and ubiquitination. We found that FBXO22 depletion inhibited the proliferation, migration and invasion of osteosarcoma cells, whereas FBXO22 overexpression increased the proliferation and motility of osteosarcoma cells. Mechanistically, FBXO22 promoted the ubiquitination and degradation of FoxO1 in osteosarcoma cells. FBXO22 depletion reduced cell proliferation and motility via regulation of FoxO1. Taken together, our findings provide new insight into FBXO22-induced osteosarcoma tumorigenesis. The inhibition of FBXO22 could be a promising strategy for the treatment of osteosarcoma.
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Movimento Celular , Proliferação de Células , Proteínas F-Box , Proteína Forkhead Box O1 , Regulação Neoplásica da Expressão Gênica , Osteossarcoma , Ubiquitinação , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Osteossarcoma/genética , Humanos , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Movimento Celular/genética , Linhagem Celular Tumoral , Proteólise , Progressão da Doença , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/genética , Invasividade Neoplásica , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Receptores Citoplasmáticos e NuclearesRESUMO
Quantum random numbers play a crucial role in diverse applications, including cryptography, simulation, and artificial intelligence. In contrast to predictable algorithm-based pseudo-random numbers, quantum physics provides new avenues for generating theoretically true random numbers by exploiting the inherent uncertainty contained in quantum phenomena. Here, we propose and demonstrate a quantum random number generator (QRNG) using a prepared broadband squeezed state of light, where the randomness of the generated numbers entirely originates from the quantum noise introduced by squeezing operation rather than vacuum noise. The relationship between entropy rate and squeezing level is analyzed. Furthermore, we employ a source-independent quantum random number protocol to enhance the security of the random number generator.
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Efficient diode-pumped continuous-wave (CW) and wavelength tunable Tm:YAP lasers based on the vibronic and electronic transitions are investigated. A total maximum output power of 4.1 W is achieved with multi-wavelength output around 2162 nm and 2274 nm, corresponding to a slope efficiency of 29.8% for a 3 at. % Tm:YAP crystal. A maximum output power of 2.48 W with a slope efficiency of 25.4% is obtained at 2146 nm for a 4 at. % Tm:YAP crystal. Using a birefringent filter (BF), the emission wavelengths of the Tm:YAP laser are tuned over spectral ranges of 59 nm from 2115 nm to 2174 nm and 127 nm from 2267 nm to 2394 nm, respectively, which is the first demonstration of wavelength tunable Tm:YAP laser based on the electronic transition 3H4â3H5 and vibronic transition 3F4â3H6, to the best of our knowledge. The results show great potentials of the Tm:YAP crystal for realizing efficient lasers in the spectral range of 2.1-2.4 µm.
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Quantum dense coding (QDC) means to transmit two classical bits by only transferring one quantum bit, which has enabled high-capacity information transmission and strengthened system security. Continuous-variable QDC offers a promising solution to increase communication rates while achieving seamless integration with classical communication systems. Here, we propose and experimentally demonstrate a high-speed quantum radio-frequency-over-light (RFOL) communication scheme based on QDC with an entangled state, and achieve a practical rate of 20 Mbps through digital modulation and RFOL communication. This scheme bridges the gap between quantum technology and real-world communication systems, which bring QDC closer to practical applications and offer prospects for further enhancement of metropolitan communication networks.
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Magnetic polymer composites have been widely utilized in potential applications in material science, such as reduction of dyes, immunodiagnostics, biomedicals, and magnetically controllable photonic crystals owing to large surface areas, fast separation, and recyclable performance. In this work, anisotropic magnetic particles were prepared by seeded emulsion polymerization, with morphologies of "Fe3O4-shell", "hemisphere-like", "raspberry-like", "multiple lobes-like", and "sandwich-like". Poly(styrene/divinylbenzene/mono-2-(methacryloxy)ethyl succinate)@ Fe3O4 (P(St/DVB/MMES)@Fe3O4) were the seed microspheres, and P(St/DVB/MMES)@Fe3O4@polymer particles are achieved by seeded emulsion polymerizations. The morphology of the particles depends on polymerization conditions (monomer ratios and surfactant), particle properties, and so on. Then, the minimum surface free energy change principles were used to predict the equilibrium morphologies of the magnetic polymer composites. Through theory, the model gives the correct tendency and good agreement with the equilibrium morphology which was in tandem with TEM results. Lastly, after in situ surface deposition of Ag nanoparticles, magnetic composite particles with sandwich-like morphology were applied for the catalytic degradation of 4-nitrophenol (4-NP) reacting with NaBH4. The apparent rate coefficient is 0.0069 s-1, and it can keep mainly about 80% efficiency in catalysis after five cycles.
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The widespread use of biogas slurry could potentially raise the environmental risk of antibiotics. Dissolved organic matter (DOM), as the most active part of biogas slurry, was able to interact with antibiotics and play a crucial role in the structure and function of soil and aquatic ecosystems. The recent shifts in global climate patterns have garnered significant attention due to their substantial impact on temperature, thereby exerting a direct influence on the characteristics of DOM and subsequently on the environmental behavior of antibiotics. However, there is limited research concerning the impact of temperature on the binding of DOM and antibiotics. Thus, this study aimed to explore the temperature-dependent structural transformation and driving factors of biogas slurry-derived DOM (BSDOM). Additionally, the binding characteristics between BSDOM and the commonly used antibiotic norfloxacin (NOR) at different temperatures were studied by using multi spectroscopic methods and two-dimensional correlation spectroscopy (2D-COS) analysis. The results suggested that the temperature-dependent structural transformation of BSDOM was reversible, with a slight lag in the transition temperature under cooling (13 °C for heating and 17 °C for cooling). Heating promoted the conversion of protein-like to humic-like substances while cooling favored the decomposition of humic-like substances. BSDOM and NOR were static quenching, with oxygen-containing functional groups such as C-O and -OH playing an important role. Temperature influenced the order of binding, the activity of the protein fraction, and its associated functional groups. At temperatures of 25 °C and 40 °C, the fluorescent components were observed to exhibit consistent binding preferences, whereby the humic-like component demonstrated a greater affinity for NOR compared to the protein-like component. However, the functional group binding order exhibited an opposite trend. At 10 °C, a new protein-like component appeared and bound preferentially to NOR, when no C-O stretch corresponding to the amide was observed. The finding will contribute to a comprehensive understanding of the interaction mechanisms between DOM and antibiotics under climate change, as well as providing a theoretical basis to reduce the environmental risks of biogas slurry and antibiotics.
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Matéria Orgânica Dissolvida , Norfloxacino , Temperatura , Biocombustíveis , Ecossistema , Espectrometria de Fluorescência/métodos , Substâncias Húmicas/análise , Antibacterianos , ProteínasRESUMO
Pancreatobililary cancers are fatal solid tumors that pose a significant threat to human life. It is imperative to investigate novel small molecule active compounds for controlling these cancers. Heterocyclic compounds (e. g. gemcitabine) and multi-substituted alkenes (e. g. resveratrol) are commonly applied in tumor treatment. Researchers have proposed that the synthesis of new trisubstituted alkenes containing heteroaromatic rings by combining these two scaffolds may be a fresh strategy to develop new active molecules. In this study, we utilized alkenyl bromide and heteroaryl boronic acid as substrates, employing Suzuki coupling to generate a series of triarylethylenes featuring nitrogen, oxygen, and sulfur atoms. Through inâ vitro experiments, the results indicated that some compounds exhibited remarkable anti-tumor efficacy (e. g. IC50[3be, GBC-SD]=0.13â µM and IC50[3be, PANC-1]=0.27â µM). The results further demonstrated that the antitumor efficacy of these compounds was dependent on the heteroatom, π-system, skeleton-bonding site, and substituent type.
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BACKGROUND AND AIM: Colorectal cancer is a prevalent malignancy worldwide, and right hemicolectomy is a common surgical procedure for its treatment. However, postoperative incisional infections remain a significant complication, leading to prolonged hospital stays, increased healthcare costs, and patient discomfort. Therefore, this study aims to utilize machine learning models, including random forest, support vector machine, deep learning models, and traditional logistic regression, to predict factors associated with incisional infection following right hemicolectomy for colon cancer. METHODS: Clinical data were collected from 322 patients undergoing right hemicolectomy for colon cancer, including demographic information, preoperative chemotherapy status, body mass index (BMI), operative time, and other relevant variables. These data are divided into training and testing sets in a ratio of 7:3. Machine learning models, including random forest, support vector machine, and deep learning, were trained using the training set and evaluated using the testing set. RESULTS: The deep learning model exhibited the highest performance in predicting incisional infection, followed by random forest and logistic regression models. Specifically, the deep learning model demonstrated higher area under the receiver operating characteristic curve (ROC-AUC) and F1 score compared to other models. These findings suggest the efficacy of machine learning models in predicting risk factors for incisional infection following right hemicolectomy for colon cancer. CONCLUSIONS: Machine learning models, particularly deep learning models, offer a promising approach for predicting the risk of incisional infection following right hemicolectomy for colon cancer. These models can provide valuable decision support for clinicians, facilitating personalized treatment strategies and improving patient outcomes.
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Colectomia , Neoplasias do Colo , Aprendizado de Máquina , Infecção da Ferida Cirúrgica , Humanos , Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/diagnóstico , Idoso , Fatores de Risco , Estudos Retrospectivos , Modelos Logísticos , Máquina de Vetores de SuporteRESUMO
Cross conjugation, though prevalent in many organic compounds, is typically considered less effective for electron delocalization compared to linear conjugation. Consequently, it is rarely used as the backbone structure for semiconducting conjugated polymers. In this study, we designed and synthesized a novel building block, TIDP, which features a central cyclic dipeptide with cross conjugation characteristics. Strong intramolecular hydrogen bonding interactions confer TIDP with a highly rigid and coplanar conformation. Importantly, theoretical calculations reveal that π electrons are well delocalized across the entire structure, despite its low aromaticity. Conjugated polymers incorporating TIDP exhibit high charge carrier mobilities, demonstrating the effective π electrons delocalization of this innovative building block. Our findings show that with rational design, cross conjugation can achieve effective π electrons delocalization, providing a valuable approach for developing high-performance conjugated polymers for organic electronic materials.
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Nowadays, the rapidly development of advanced antidetection technology raises stringent requirements for microwave absorption materials (MAMs) to focus more attention on wider bandwidth, thinner thickness, and lower density. Adding magnetic medium to realize broadband absorption may usually result in the decline of service performance and accelerating corrosion of MAMs. Chiral MAMs can produce extra magnetic loss without adding magnetic medium due to the unique electromagnetic cross polarization effect. However, more efforts should be taken to furtherly promote efficient bandwidth of chiral MAMs and reveal attenuation mode and modulation method of chiral structure. Herein, a novel superhelical nano-microstructure based on chiral polyaniline and helical polypyrrole is successfully achieved via in situ polymerization strategy. The enhanced multiscale-chiral synergistic effect contributes to broaden effective absorption bandwidth, covering 8.6 GHz at the thickness of 3.6 mm, and the minimum reflection loss can reach -51.3 dB simultaneously. Besides, to further explain response modes and loss mechanism of superhelical nano-microstructures, the electromagnetic simulation and test analysis are applied together to reveal their synergistic enhancement attenuation mechanism. Taken together, this strategy gives a new thought of how to design, prepare, and optimize the hierarchical structure materials to achieving broadband and high-performance microwave absorption.
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A high-efficiency, high-energy, narrow bandwidth, hundred-nanosecond pulse width 355â nm ultraviolet (UV) laser was realized. A high-energy single-frequency 1064â nm fundamental laser was demonstrated firstly with multistage end-pumped preamplifiers and side-pumped main amplifiers. The corresponding pulse energy, repetition rate, pulse duration, bandwidth, and beam quality factor M2 were determined to be 221â mJ, 100â Hz, 156â ns, 2.25â MHz, and 1.23, respectively. By using type-I phase-matching LBO crystal for second harmonic generation (SHG) and type-II phase-matching LBO crystal for the sum frequency generation of the third harmonic, 67â mJ, a narrow bandwidth 355â nm UV laser was obtained with a pulse width of 137â ns and an energy stability of RMS < 1.2%@2â h. The fundamental to UV optical conversion efficiency was 30.3%. Our results provided a new way for generating high-energy, narrow bandwidth hundred-nanosecond 355â nm UV lasers used for direct-detection Doppler wind lidar (DWL) system.
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As the critical device of microwave photonics and optical communication, the low-loss and high-efficiency optical phase shifter has attracted intense attention in photonic integrated circuits. However, most of their applications are restricted to a particular band. Little is known about the characteristics of broadband. In this paper, an SiN-MoS2 integrated broadband racetrack phase shifter is demonstrated. The coupling region and the structure of the racetrack resonator are elaborately designed to improve the coupling efficiency at each resonance wavelength. The ionic liquid is introduced to form a capacitor structure. Then, the effective index of the hybrid waveguide can be efficiently tuned by adjusting the bias voltage. We achieve a phase shifter with a tunable range covering all the WDM bands and even up to 1900â nm. The highest phase tuning efficiency is measured to be 72.75â pm/V at 1860â nm, and the corresponding half-wave-voltage-length product is calculated as 0.0608â V·cm.
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Cancer stands as a serious malady, posing substantial risks to human well-being and survival. This underscores the paramount necessity to explore and investigate novel antitumor medications. Nitrogen-containing compounds, especially those derived from natural sources, form a highly significant category of antitumor agents. Among these, antitumor agents with six-membered aromatic nitrogen heterocycles have consistently attracted the attention of chemists and pharmacologists. Accordingly, we present a comprehensive summary of synthetic strategies and clinical implications of these compounds in this review. This entails an in-depth analysis of synthesis pathways for pyridine, quinoline, pyrimidine, and quinazoline. Additionally, we explore the historical progression, targets, mechanisms of action, and clinical effectiveness of small molecule inhibitors possessing these structural features.
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Antineoplásicos , Compostos Heterocíclicos , Humanos , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/química , Nitrogênio/química , Antineoplásicos/farmacologia , Antineoplásicos/químicaRESUMO
Traditional microwave absorbing materials (MAMs) have exposed more and more problems in multi-spectrum detection and a harsh service environment, which hinder their further application. Bionic materials and structures have attracted more and more attention from researchers in the field of stealth materials due to their excellent properties, such as high strength and high conductivity, along with easy access to scale adjustability and structural design. By introducing the concept of bionics into their structural design and material design, we can obtain highly efficient stealth materials with multiple properties. In addition, the concept of multispectral stealth is furthered by comparing the difference in the principle and methods of achievement between radar stealth and infrared stealth. This paper fundamentally summarizes the research status of bionic structure design ideas in stealth materials, analyzing the structure-activity relationship between the structural size effect and electromagnetic characteristics from low order to high order. Then, the design ideas and universal strategies of typical bionic structures are summarised and an idea for the integrated design of radar absorption compatible with infrared stealth is put forward. This will provide profound insights for the application of biomimetic stealth materials and the future development of intelligent-response and dynamically adjustable materials.
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Aim: To explore whether immune checkpoint inhibitors (ICIs) increase the incidence of radiation-induced brain injury in lung cancer patients with brain metastases. Methods: According to whether they received ICIs within 6 months before and after cranial radiotherapy (CRT), all patients were divided into two groups: ICIs + CRT group and CRT + non-ICIs group. Results: The incidence of radiation necrosis (RN) in the CRT + ICIs group was 14.3%, while that in the CRT + non-ICIs group was 5.8% (p = 0.090). If ICIs were used within 3 months of CRT, there was statistical significance. A maximum diameter of brain metastasis >3.3 cm and cumulative radiation dose of metastatic lesions >75.7 Gy were risk factors for RN. Conclusion: ICIs could increase the risk of RN, especially when used within 3 months of CRT.
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Lesões Encefálicas , Neoplasias Encefálicas , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Neoplasias Encefálicas/secundário , Imunoterapia/efeitos adversosRESUMO
Glioblastoma (GBM) is regarded as an incurable disease due to its poor prognosis and limited treatment options. Virotherapies were once utilized on cancers for their oncolytic effects. And they are being revived on GBM treatment, as accumulating evidence presents the immunogenic effects of virotherapies in remodeling immunosuppressive GBM microenvironment. In this review, we focus on the immune responses induced by oncolytic virotherapies and viral vectors in GBM. The current developments of GBM virotherapies are briefly summarized, followed by a detailed depiction of their immune response. Limitations and lessons inferred from earlier experiments and trials are discussed. Moreover, we highlight the importance of engaging the immune responses induced by virotherapies into the multidisciplinary management of GBM.
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Neoplasias Encefálicas , Glioblastoma , Terapia Viral Oncolítica , Vírus Oncolíticos , Neoplasias Encefálicas/terapia , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Vírus Oncolíticos/genética , Microambiente TumoralRESUMO
A modified Frantz-Nodvik (F-N) equation and a simple one-dimensional unfolded slicing model for numerically simulating high-power Innoslab picosecond amplifier are developed for the first time. The anisotropic stimulated emission cross-section of laser crystal, the influence of the tilted optical path, the spatial overlap of the seed and pump laser, as well as the pump absorption saturation effect are considered. Based on the as-developed model, 4-, 6- and 8-pass schemes high-power Nd:YVO4 Innoslab picosecond amplifiers are designed with output powers of 76.2 W, 81.4 W, and 85.5 W, respectively. The experimental results agree well with that of numerical simulation, indicating that our model is a powerful tool and paves a new way for designing and optimizing high-power Innoslab picosecond laser amplifier.
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Gradient-based optimization combined with the adjoint method has been demonstrated to be an efficient way to design a nano-structure with a vast number of degrees of freedom. However, most inverse-designed photonic devices are applied as linear photonic devices. Here, we demonstrate the nonlinear optical response in inverse-designed integrated splitters fabricated on a SiN platform. The splitting ratio is tunable under different incident powers. The thermo-optical effect can be used as an effective approach for adjusting the nonlinear optical response threshold and modulation depth of the device. These promising results indicate the great potential of inverse-designed photonic devices in nonlinear optics and optical communications.