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Tumor immunotherapies have emerged as a promising frontier in the realm of cancer treatment. However, challenges persist in achieving localized, durable immunostimulation while counteracting the tumor's immunosuppressive environment. Here, we develop a natural mussel foot protein-based nanomedicine with spatiotemporal control for tumor immunotherapy. In this nanomedicine, an immunoadjuvant prodrug and a photosensitizer are integrated, which is driven by their dynamic bonding and non-covalent assembling with the protein carrier. Harnessing the protein carrier's bioadhesion, this nanomedicine achieves a drug co-delivery with spatiotemporal precision, by which it not only promotes tumor photothermal ablation but also broadens tumor antigen repertoire, facilitating in situ immunotherapy with durability and maintenance. This nanomedicine also modulates the tumor microenvironment to overcome immunosuppression, thereby amplifying antitumor responses against tumor progression. Our strategy underscores a mussel foot protein-derived design philosophy of drug delivery aimed at refining combinatorial immunotherapy, offering insights into leveraging natural proteins for cancer treatment.
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Ultrafast imaging can capture the dynamic scenes with a nanosecond and even femtosecond temporal resolution. Complementarily, phase imaging can provide the morphology, refractive index, or thickness information that intensity imaging cannot represent. Therefore, it is important to realize the simultaneous ultrafast intensity and phase imaging for achieving as much information as possible in the detection of ultrafast dynamic scenes. Here, we report a single-shot intensity- and phase-sensitive compressive sensing-based coherent modulation ultrafast imaging technique, shortened as CS-CMUI, which integrates coherent modulation imaging, compressive imaging, and streak imaging. We theoretically demonstrate through numerical simulations that CS-CMUI can obtain both the intensity and phase information of the dynamic scenes with ultrahigh fidelity. Furthermore, we experimentally build a CS-CMUI system and successfully measure the intensity and phase evolution of a multimode Q-switched laser pulse and the dynamical behavior of laser ablation on an indium tin oxide thin film. It is anticipated that CS-CMUI enables a profound comprehension of ultrafast phenomena and promotes the advancement of various practical applications, which will have substantial impact on fundamental and applied sciences.
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This study explores the influence of household technological advancements on children's nutritional intake, specifically within the context of the Chinese government's "Home Appliances Going to the Countryside" (HAGC) initiative. Utilizing data from the China Health and Nutrition Surveys of 2006, 2009, and 2011, we employed a Propensity Score Matching Difference-in-Differences (PSM-DID) framework to ascertain the repercussions of enhanced household technology on the dynamics of children's nutritional consumption patterns. Our analysis reveals that the HAGC-inspired integration of household appliances, including color televisions, washing machines, and refrigerators, has beneficially reshaped the nutritional consumption patterns of children, with a pronounced effect among female children. This finding remains consistent even when employing alternate methodological robustness tests. A deeper examination of the HAGC policy's mechanisms underscores the pivotal roles of parental time allocation, improved food storage capabilities, and augmented information accessibility as significant drivers bolstering children's nutritional intake. These insights bear considerable significance for strategizing interventions aimed at elevating the nutritional wellbeing of children in rural settings, offering valuable input for shaping public health policies tailored for such demographies.
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Optical-based imaging has improved from early single-location research to further sophisticated imaging in 2D topography and 3D tomography. These techniques have the benefit of high specificity and non-radiative safety for brain detection and therapy. However, their performance is limited by complex tissue structures. To overcome the difficulty in successful brain imaging applications, we conducted a simulation using 16 optical source types within a brain model that is based on the Monte Carlo method. In addition, we propose an evaluation method of the optical propagating depth and resolution, specifically one based on the optical distribution for brain applications. Based on the results, the best optical source types were determined in each layer. The maximum propagating depth and corresponding source were extracted. The optical source propagating field width was acquired in different depths. The maximum and minimum widths, as well as the corresponding source, were determined. This paper provides a reference for evaluating the optical propagating depth and resolution from an optical simulation aspect, and it has the potential to optimize the performance of optical-based techniques.
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The feasibility of self-cultivating anammox granules for enhancing wastewater nitrogen removal was investigated in a nitrification-denitrification flocculent sludge system. Desirable nitrogen removal efficiency of 84 ± 4 % was obtained for the influent carbon to nitrogen ratio of 1-1.3 (NH4+-N: 150-200 mg N/L) via alternate anaerobic/oxic/anoxic mode. Meanwhile, some red granular sludge was formed in the system. The abundance and activity of anaerobic ammonia oxidation bacteria (AnAOB) increased from 'not detected' in seed sludge to 0.57 % and 29.4 ± 0.7 mg N/(g mixed liquor volatile suspended solids·h) in granules, respectively, suggesting successful cultivation of anammox granules. Furthermore, some denitrifying bacteria with capability of partial denitrification were enriched, such as Candidatus Competibacter (2.45 %) and Thauera (5.75 %), which could cooperate with AnAOB, facilitating AnAOB enrichment. Anammox was dominant in nitrogen removal with the contribution to nitrogen removed above 68.8 ± 0.3 %. The strategy of self-cultivating anammox granules could promote the application of anammox.
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Aguas del Alcantarillado , Aguas Residuales , Aguas del Alcantarillado/microbiología , Nitrificación , Desnitrificación , Oxidación Anaeróbica del Amoníaco , Nitrógeno , Reactores Biológicos/microbiología , Oxidación-Reducción , Anaerobiosis , BacteriasRESUMEN
Piezoelectric poly(vinylidene fluoride) (PVDF) and its copolymers have been widely investigated for applications in wearable electric devices and sensing systems, owing to their intrinsic piezoelectricity and superior flexibility. However, their weak piezoelectricity poses major challenges for practical applications. To overcome these challenges, we propose a two-step synthesis approach to fabricate sandwich-structured piezoelectric films (BaTiO3@PDA/PVDF/BaTiO3@PDA) with significantly enhanced ferroelectric and piezoelectric properties. As compared to pristine PVDF films or conventional 0-3 composite films, a maximum polarization (Pmax) of 11.24 µC/cm2, a remanent polarization (Pr) of 5.83 µC/cm2, and an enhanced piezoelectric coefficient (d33 â¼ 14.6 pC/N) were achieved. Simulation and experimental results have demonstrated that the sandwich structure enhances the ability of composite films to withstand higher poling electric fields in comparison with 0-3 composites. The sandwich-structured piezoelectric films are further integrated into a wireless sensor system with a high force sensitivity of 288 mV/N, demonstrating great potential for movement monitoring applications. This facile approach shows great promise for the large-scale production of composite films with remarkable flexibility, ferroelectricity, and piezoelectricity for wearable sensing devices.
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Significance: Over 100 monoclonal antibodies have been approved by the U.S. Food and Drug Administration (FDA) for clinical use; however, a paucity of knowledge exists regarding the injection site behavior of these formulated therapeutics, particularly the effect of antibody, formulation, and tissue at the injection site. A deeper understanding of antibody behavior at the injection site, especially on blood oxygenation through imaging, will help design improved versions of the therapeutics for a wide range of diseases. Aim: The aim of this research is to understand the dynamics of monoclonal antibodies at the injection site as well as how the antibody itself affects the functional characteristics of the injection site [e.g., blood oxygen saturation (sO2)]. Approach: We employed triple-wavelength equipped functional photoacoustic imaging to study the dynamics of dye-labeled and unlabeled monoclonal antibodies at the site of injection in a mouse ear. We injected a near-infrared dye-labeled (and unlabeled) human IgG4 isotype control antibody into the subcutaneous space in mouse ears to analyze the injection site dynamics and quantify molecular movement, as well as its effect on local hemodynamics. Results: We performed pharmacokinetic studies of the antibody in different regions of the mouse body to show that dye labeling does not alter the pharmacokinetic characteristics of the antibody and that mouse ear is a viable model for these initial studies. We explored the movement of the antibody in the interstitial space to show that the bolus area grows by â¼300% over 24 h. We discovered that injection of the antibody transiently reduces the local sO2 levels in mice after prolonged anesthesia without affecting the total hemoglobin content and oxygen extraction fraction. Conclusions: This finding on local oxygen saturation opens a new avenue of study on the functional effects of monoclonal antibody injections. We also show the suitability of the mouse ear model to study antibody dynamics through high-resolution imaging techniques. We quantified the movement of antibodies at the injection site caused by the interstitial fluid, which could be helpful for designing antibodies with tailored absorption speeds in the future.
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Anestesia , Técnicas Fotoacústicas , Ratones , Humanos , Animales , Anticuerpos Monoclonales , Tejido Subcutáneo , Inmunoglobulina GRESUMEN
Conventional indirect X-ray detectors employ scintillating phosphors to convert X-ray photons into photodiode-detectable visible photons, leading to low conversion efficiencies, low spatial resolutions, and optical crosstalk. Consequently, X-ray detectors that directly convert photons into electric signals have long been desired for high-performance medical imaging and industrial inspection. Although emerging hybrid inorganic-organic halide perovskites, such as CH3 NH3 PbI3 and CH3 NH3 PbBr3 , exhibit high sensitivity, they have salient drawbacks including structural instability, ion motion, and the use of toxic Pb. Here, this work reports an ultrastable, low-dose X-ray detector comprising KTaO3 perovskite films epitaxially grown on a Nb-doped strontium titanate substrate using a low-cost solution method. The detector exhibits a stable photocurrent under high-dose irradiation, high-temperature (200 °C), and aqueous conditions. Moreover, the prototype KTaO3 -film-based detector exhibits a 150-fold higher sensitivity (3150 µC Gyair -1 cm-2 ) and 150-fold lower detection limit (<40 nGyair s-1 ) than those of commercial α-Se-based direct detectors. Systematic investigations reveal that the high stability of the detector originates from the strong covalent bonds within the KTaO3 film, whereas the low detection limit is due to a lattice-gradient-driven built-in electric field and the high insulating property of KTaO3 film. This study unveils a new path toward the fabrication of green, stable, and low-dose X-ray detectors using oxide perovskite films, which have significant application potential in medical imaging and security operations.
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BACKGROUND AND OBJECTIVE: Photoacoustic computed tomography (PACT) is a non-invasive biomedical imaging technology that has developed rapidly in recent decades, especially has shown potential for small animal studies and early diagnosis of human diseases. To obtain high-quality images, the photoacoustic imaging system needs a high-element-density detector array. However, in practical applications, due to the cost limitation, manufacturing technology, and the system requirement in miniaturization and robustness, it is challenging to achieve sufficient elements and high-quality reconstructed images, which may even suffer from artifacts. Different from the latest machine learning methods based on removing distortions and artifacts to recover high-quality images, this paper proposes an adaptive machine learning method to firstly predict and complement the photoacoustic sensor channel data from sparse array sampling and then reconstruct images through conventional reconstruction algorithms. METHODS: We develop an adaptive machine learning method to predict and complement the photoacoustic sensor channel data. The model consists of XGBoost and a neural network named SS-net. To handle data sets of different sizes and improve the generalization, a tunable parameter is used to control the weights of XGBoost and SS-net outputs. RESULTS: The proposed method achieved superior performance as demonstrated by simulation, phantom experiments, and in vivo experiment results. Compared with linear interpolation, XGBoost, CAE, and U-net, the simulation results show that the SSIM value is increased by 12.83%, 6.78%, 21.46%, and 12.33%. Moreover, the median R2 is increased by 34.4%, 8.1%, 28.6%, and 84.1% with the in vivo data. CONCLUSIONS: This model provides a framework to predict the missed photoacoustic sensor data on a sparse ring-shaped array for PACT imaging and has achieved considerable improvements in reconstructing the objects. Compared with linear interpolation and other deep learning methods qualitatively and quantitatively, our proposed methods can effectively suppress artifacts and improve image quality. The advantage of our methods is that there is no need for preparing a large number of images as the training dataset, and the data for training is directly from the sensors. It has the potential to be applied to a wide range of photoacoustic imaging detector arrays for low-cost and user-friendly clinical applications.
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Redes Neurales de la Computación , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Fantasmas de Imagen , Aprendizaje Automático , Algoritmos , Artefactos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Objective: Acute myocardial infarction (AMI) is characterized by heart damage resulting from blocked blood flow. Prompt diagnosis is vital for timely treatment and saving lives. This study aimed to evaluate the diagnostic value of cTnl, NT-pro BNP, and a combined test in AMI patients. Methods: In this study, a retrospective observational design was employed, and we selected 221 patients with AMI admitted to our hospital within a 3-year period as the research subjects and included them in the AMI group. Additionally, 200 patients from the control group, who visited our hospital for physical examinations, were selected to compare the expressions of cardiac Troponin I (cTnl) and N-Terminal pro-B-type Natriuretic Peptide (NT-pro BNP) between the two groups. Receiver Operating Characteristic (ROC) curves were constructed to analyze the diagnostic value of cTnl combined with NT-pro BNP for AMI. Furthermore, AMI patients were categorized into four groups based on the New York Heart Association (NYHA) classification (grades I, II, III, and IV). The differences in cTnl, NT-pro BNP, and Left Ventricular Ejection Fraction (LVEF) were compared among the AMI patients with different cardiac function grades to analyze their correlation and diagnostic value in assessing the severity of AMI-related cardiac insufficiency. Results: The levels of cTnl and NT-pro BNP in AMI patients were significantly higher than those in the control group, and their combined detection effectively facilitated the diagnosis of AMI occurrence. Moreover, cTnl and NT-pro BNP concentrations increased with the severity of cardiac dysfunction (NYHA grades) and showed a notable negative correlation with LVEF. Furthermore, the combined testing of cTnl and NT-pro BNP demonstrated significant value in evaluating the severity of AMI in patients. Conclusions: The combined detection of cTnl and NT-pro BNP holds considerable application value in diagnosing AMI occurrence and assessing its severity.
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Infarto del Miocardio , Péptido Natriurético Encefálico , Humanos , Volumen Sistólico/fisiología , Estudios Retrospectivos , Función Ventricular Izquierda , Infarto del Miocardio/diagnóstico por imagen , BiomarcadoresRESUMEN
Imaging into thick scattering medium is a long-standing challenge. Beyond the quasi-ballistic regime, multiple scattering scrambles the spatiotemporal information of incident/emitted light, making canonical imaging based on light focusing nearly impossible. Diffusion optical tomography (DOT) is one of the most popular approach to look inside scattering medium, but quantitatively inverting the diffusion equation is ill-posed, and prior information of the medium is typically necessary, which is nontrivial to obtain. Here, we show theoretically and experimentally that, by synergizing the one-way light scattering characteristic of single pixel imaging with ultrasensitive single photon detection and a metric-guided image reconstruction, single photon single pixel imaging can serve as a simple and powerful alternative to DOT for imaging into thick scattering medium without prior knowledge or inverting the diffusion equation. We demonstrated an image resolution of 12 mm inside a 60 mm thick (â¼ 78 mean free paths) scattering medium.
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Photoacoustic imaging combines high optical absorption contrast and deep acoustic penetration, and can reveal structural, molecular, and functional information about biological tissue non-invasively. Due to practical restrictions, photoacoustic imaging systems often face various challenges, such as complex system configuration, long imaging time, and/or less-than-ideal image quality, which collectively hinder their clinical application. Machine learning has been applied to improve photoacoustic imaging and mitigate the otherwise strict requirements in system setup and data acquisition. In contrast to the previous reviews of learned methods in photoacoustic computed tomography (PACT), this review focuses on the application of machine learning approaches to address the limited spatial sampling problems in photoacoustic imaging, specifically the limited view and undersampling issues. We summarize the relevant PACT works based on their training data, workflow, and model architecture. Notably, we also introduce the recent limited sampling works on the other major implementation of photoacoustic imaging, i.e., photoacoustic microscopy (PAM). With machine learning-based processing, photoacoustic imaging can achieve improved image quality with modest spatial sampling, presenting great potential for low-cost and user-friendly clinical applications.
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Advanced applications of biomacromolecular assemblies require a stringent degree of control over molecular arrangement, which is a challenge to current synthetic methods. Here we used a neighbor-controlled patterning strategy to build multicomponent peptide fibrils with an unprecedented capacity to manipulate local composition and peptide positions. Eight peptides were designed to have regulable nearest neighbors upon co-assembly, which, by simulation, afforded 412 different patterns within fibrils, with varied compositions and/or peptide positions. The fibrils with six prescribed patterns were experimentally constructed with high accuracy. The controlled patterning also applies to functionalities appended to the peptides, as exemplified by arranging carbohydrate ligands at nanoscale precision for protein recognition. This study offers a route to molecular editing of inner structures of peptide assemblies, prefiguring the uniqueness and richness of patterning-based material design.
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Péptidos , Proteínas , Péptidos/química , Conformación MolecularRESUMEN
Mapping diverse cellular components with high spatial resolution is important to interrogate biological systems and study disease pathogenesis. Conventional optical imaging techniques for mapping biomolecular profiles with differential staining and labeling methods are cumbersome. Different types of cellular components exhibit distinctive characteristic absorption spectra across a wide wavelength range. By virtue of this property, a lab-made wide-band optical-resolution photoacoustic microscopy (wbOR-PAM) system, which covers wavelengths from the ultraviolet and visible to the shortwave infrared regions, was designed and developed to capture multiple cellular components in 300-µm-thick brain slices at nine different wavelengths without repetitive staining and complicated processing. This wbOR-PAM system provides abundant spectral information. A reflective objective lens with an infinite conjugate design was applied to focus laser beams with different wavelengths, avoiding chromatic aberration. The molecular components of complex brain slices were probed without labeling. The findings of the present study demonstrated a distinctive absorption of phospholipids, a major component of the cell membrane, brain, and nervous system, at 1690 nm and revealed their precise distribution with microscopic resolution in a mouse brain, for the first time. This novel imaging modality provides a new opportunity to investigate important biomolecular components without either labeling or lengthy specimen processing, thus, laying the groundwork for revealing cellular mechanisms involved in disease pathogenesis.
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The Grüneisen parameter is a primary parameter of the initial sound pressure signal in the photoacoustic effect, which can provide unique biological information and is related to the temperature change information of an object. The accurate measurement of this parameter is of great significance in biomedical research. Combining X-ray-induced acoustic tomography and conventional X-ray computed tomography, we proposed a method to obtain the absolute Grüneisen parameter. The theory development, numerical simulation, and biomedical application scenarios are discussed. The results reveal that our method not only can determine the Grüneisen parameter but can also obtain the body internal temperature distribution, presenting its potential in the diagnosis of a broad range of diseases.
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Ultrasonic (US) transducers have been widely used in the field of ultrasonic and photoacoustic imaging system in recent years, to convert acoustic and electrical signals into each other. As the core part of imaging systems, US transducers have been extensively studied and achieved remarkable progress recently. Imaging systems employing conventional rigid US transducers impose certain constraints, such as not being able to conform to complex surfaces and comfortably come into contact with skin and the sample, and meet the applications of continuous monitoring and diagnosis. To overcome these drawbacks, significant effort has been made in transforming the rigid US transducers to become flexible and wearable. Flexible US transducers ensure self-alignment to complex surfaces and maximize the transferred US energy, resulting in high quality detection performance. The advancement in flexible US transducers has further extended the application range of imaging systems. This review is intended to summarize the most recent advances in flexible US transducers, including advanced functional materials optimization, representative US transducers designs and practical applications in imaging systems. Additionally, the potential challenges and future directions of the development of flexible US transducers are also discussed.
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In this work, we propose and demonstrate the ring-arrayed Pearcey Gaussian chirp beams (RAPGCBs) synthesized by multiple two-dimensional Pearcey beams. The general analytical formula for the propagation of RAPGCBs is presented. We find that, depending on synthesized number n, the profiles of the beams present different polygonal shapes, and the autofocusing properties can be controlled by chirp factor ß. Furthermore, we study the properties of the RAPGCBs carrying optical vortices (OVs). It shows that a single OV or two positive OVs form an autofocusing hollow field, and opposite OVs will annihilate, which results in greatly increased autofocusing ability. Our experimental results agree with the simulations. Such beams have potential applications in particle trapping and biology medical fields.
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Photoacoustic spectroscopy (PAS) combines the advantages of high sensitivity, high specificity and zero background, which is very suitable for trace gas detection. Cantilever-enhanced photoacoustic spectroscopy (CEPAS) utilizes highly sensitive mechanical cantilevers to further enhance the photoacoustic signal and shows a gas concentration detection limit of parts per trillion. This review is intended to summarize the recent advancements in CEPAS based on different displacement detection methods, such as Michelson interference, Fabry-Perot interference, light intensity detection, capacitive, piezoelectric and piezoresistive detection. Fundamental mechanisms and technical requirements of CEPAS are also provided in the literature. Finally, potential challenges and further opportunities are also discussed.
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This paper examined the effects of household technology on child health using evidence from the Chinese government's "Home Appliances Going to the Countryside" policy. A difference-in-differences approach was employed to examine 2000 to 2015 data from the China Health and Nutrition Survey data from before the policy in 2007 to after the policy was implemented. It was found that the policy-induced household technology adoption significantly increased child health, especially girls' health. Various sensitivity tests proved this finding to be robust. The potential paths through which household technology improved child health were also examined from which it was found that parental care for children and increased nutrition were effective paths between household technology and health status. These results could guide policymakers when constructing and developing a supportive child health system in China.
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Política de Planificación Familiar , Niño , Salud Infantil , China , Femenino , Humanos , Política Pública , TecnologíaRESUMEN
Long-duration in vivo simultaneous imaging of multiple anatomical structures is useful for understanding physiological aspects of diseases, informative for molecular optimization in preclinical models, and has potential applications in surgical settings to improve clinical outcomes. Previous studies involving simultaneous imaging of multiple anatomical structures, for example, blood and lymphatic vessels as well as peripheral nerves and sebaceous glands, have used genetically engineered mice, which require expensive and time-consuming methods. Here, an IgG4 isotype control antibody is labeled with a near-infrared dye and injected into a mouse ear to enable simultaneous visualization of blood and lymphatic vessels, peripheral nerves, and sebaceous glands for up to 3 h using photoacoustic microscopy. For multiple anatomical structure imaging, peripheral nerves and sebaceous glands are imaged inside the injected dye-labeled antibody mass while the lymphatic vessels are visualized outside the mass. The efficacy of the contrast agent to label and localize deep medial lymphatic vessels and lymph nodes using photoacoustic computed tomography is demonstrated. The capability of a single injectable contrast agent to image multiple structures for several hours will potentially improve preclinical therapeutic optimization, shorten discovery timelines, and enable clinical treatments.