Ultralow Strain-Induced Emergent Polarization Structures in a Flexible Freestanding BaTiO3 Membrane.

The engineering of ferroic orders, which involves the evolution of atomic structure and local ferroic configuration in the development of next-generation electronic devices. Until now, diverse polarization structures and topological domains are obtained in ferroelectric thin films or heterostructures, and the polarization switching and subsequent domain nucleation are found to be more conducive to building energy-efficient and multifunctional polarization structures. In this work, a continuous and periodic strain in a flexible freestanding BaTiO3 membrane to achieve a zigzag morphology is introduced. The polar head/tail boundaries and vortex/anti-vortex domains are constructed by a compressive strain as low as ≈0.5%, which is extremely lower than that used in epitaxial rigid ferroelectrics. Overall, this study c efficient polarization structures, which is of both theoretical value and practical significance for the development of next-generation flexible multifunctional devices.

Photochemical Degradation of the New Nicotine Pesticide Acetamiprid in Water.

Acetamiprid is a novel nicotinic pesticide widely used in modern agriculture because of its low toxicity and specific biological target properties. The objective of this study was to understand the photolysis pattern of acetamiprid in the water column and elucidate its degradation products and mechanism. It was observed that acetamiprid exhibited different photolysis rates under different light source conditions in pure water, with ultraviolet > fluorescence > sunlight; furthermore, its photolysis half-life ranged from 17.3 to 28.6 h. In addition, alkaline conditions (pH 9.0) accelerated its photolysis rate, which increased with pH. Using gas chromatography-mass spectrometry, five direct photolysis products generated during the exposure of acetamiprid to pure water were successfully separated and identified. The molecular structure of acetamiprid was further analyzed using density functional theory, and the active photodegradation sites of acetamiprid were predicted. The mechanism of the photolytic transformation of acetamiprid in water was mainly related to hydroxyl substitution and oxidation. Based on these findings, a comprehensive transformation pathway for acetamiprid was proposed.

Intraoperative Resection Guidance and Rapid Pathological Diagnosis of Osteosarcoma using B7H3 Targeted Probe under NIR-II Fluorescence Imaging.

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen-section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3-IRDye800CW is synthesized by conjugating anti-B7H3 antibody and IRDye800CW. B7H3-IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2 mm) and lung metastatic lesions. The tumor-background ratio reaches 4.42 ± 1.77 at day 3. After incubating fresh human OS specimen with B7H3-IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin-eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3-IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS.

Construction and external validation of a scoring prediction model for mortality risk within 30 days of community-acquired pneumonia in children admitted to the pediatric intensive care unit: A multicenter retrospective case-control study.

In this study, we constructed and validated a scoring prediction model to identify children admitted to the pediatric intensive care unit (PICU) with community-acquired pneumonia (CAP) at risk for early death. Children with CAP who were admitted to the PICU were included in the training set and divided into death and survival groups according to whether they died within 30 days of admission. For univariate and multifactorial analyses, demographic characteristics, vital signs at admission, and laboratory test results were collected separately from the 2 groups, and independent risk factors were derived to construct a scoring prediction model. The ability of the scoring model to predict CAP-related death was validated by including children with CAP hospitalized at 3 other centers during the same period in the external validation set. Overall, the training and validation sets included 296 and 170 children, respectively. Univariate and multifactorial analyses revealed that procalcitonin (PCT), lactate dehydrogenase (LDH), activated partial thromboplastin time (APTT), and fibrinogen (Fib) were independent risk factors. The constructed scoring prediction model scored 2 points each for PCT ≥ 0.375 ng/mL, LDH ≥ 490 U/L, and APTT ≥ 31.8 s and 1 point for Fib ≤ 1.78 g/L, with a total model score of 0-7 points. When the score was ≥ 5 points, the sensitivity and specificity of mortality diagnosis in children with CAP were 72.7% and 87.5%, respectively. In the external validation set, the sensitivity, specificity, and accuracy of the scoring model for predicting the risk of CAP-related death were 64.0%, 92.4%, and 88.2%, respectively. Constructing a scoring prediction model is worth promoting and can aid pediatricians in simply and rapidly evaluating the risk of death in children with CAP, particularly those with complex conditions.

Enhancing soil health and nutrient cycling through soil amendments: Improving the synergy of bacteria and fungi.

The synergy between bacteria and fungi is a key determinant of soil health and have a positive effect on plant development under drought conditions, with the potentially enhancing the sustainability of amending soil with natural materials. However, identifying how soil amendments influence plant growth is often difficult due to the complexity of microorganisms and their links with different soil amendment types and environmental factors. To address this, we conducted a field experiment to examine the impact of soil amendments (biochar, Bacillus mucilaginosus, Bacillus subtilis and super absorbent polymer) on plant growth. We also assessed variations in microbial community, links between fungi and bacteria, and soil available nutrients, while exploring how the synergistic effects between fungus and bacteria influenced the response of soil amendments to plant growth. This study revealed that soil amendments reduced soil bacterial diversity but increased the proportion of the family Enterobacteriaceae, Nitrosomonadaceae, and also increased soil fungal diversity and the proportion of the sum of the family Lasiosphaeriaceae, Chaetomiaceae, Pleosporaceae. Changes in soil microbial communities lead to increase the complexity of microbial co-occurrence networks. Furthermore, this heightened network complexity enhanced the synergy of soil bacteria and fungi, supporting bacterial functions related to soil nutrient cycling, such as metabolic functions and genetic, environmental, and cellular processes. Hence, the BC and BS had 3.0-fold and 0.5-fold greater root length densities than CK and apple tree shoot growth were increased by 62.14 %,50.53 % relative to CK, respectively. In sum, our results suggest that the synergistic effect of bacteria and fungi impacted apple tree growth indirectly by modulating soil nutrient cycling. These findings offer a new strategy for enhancing the quality of arable land in arid and semi-arid regions.

A new ratiometric fluorescent probe for rapid and highly selective detection of Cysteine in bovine serum.

As one of the most fundamental thiol compounds in the human body, cysteine (Cys) is involved in maintaining redox balance. Abnormal Cys levels can lead to various diseases. In this work, we successfully synthesized a fluorescent probe (CTBA) that can specifically detect Cys using acrylate as the reaction site, and CTBA has met the selectivity and anti-interference for Cys detection under optimized conditions. The linear range for Cys detection is between 0.05 and 100 µM and the detection limit is 0.0381 µM. Finally, this probe is used to detect the Cys content in three bovine serum samples and the test results are satisfactory.

Responses and correlation among ER stress, Ca2+ homeostasis, and fatty acid metabolism in Penaeus vannamei under ammonia stress.

The role of endoplasmic reticulum (ER) stress, Ca2+ homeostasis, and fatty acid metabolism in the environmental adaptation of aquatic animals is significant, but further confirmation of the relationship between these factors is needed. This study aimed to investigate the responses and correlations among ER stress, Ca2+ homeostasis, and fatty acid metabolism in Penaeus vannamei under ammonia stress. A total of 640 P. vannamei weighing 3.0 ± 0.4 g were selected and exposed to different total ammonia concentrations (0 mg/L for the control group and 3.80, 7.60, and 11.40 mg/L for the stress groups). The experiment involved a 96 h ammonia stress period to assess indicators related to ER stress, Ca2+ homeostasis, and fatty acid metabolism. The experimental results revealed that after 12 h, exposure to ammonia induced the ER stress response in the hepatopancreas of the shrimp. The groups exposed to concentrations of 3.8 mg/L and 7.6 mg/L exhibited an increase in ER Ca2+ efflux, a decrease in influx, an elevation in mitochondrial Ca2+ influx, an enhanced energy demand within the organism, and substantial consumption of triglycerides. The 11.3 mg/L group exhibited a significant enhancement in fatty acid metabolism. At 24 h, the ER stress response induced by ammonia in the shrimp exhibited a gradual recovery. In the 7.6 mg/L and 11.3 mg/L groups, the ER Ca2+ influx and efflux exhibited significant enhancements, while the mitochondrial Ca2+ influx decreased and the organism's energy demand increased. Moreover, there was a substantial enhancement in fatty acid metabolism. At 48 h, the ER stress response disappeared in each stress group, ER Ca2+ efflux was reduced, triglycerides were consumed, and the body's energy homeostasis was basically restored. At 96 h, a stress response reoccurred in the ER in each stress group, resulting in increased influx of Ca2+ into the ER, augmented energy demand within the organism, and notable enhancement in fatty acid metabolism. Pearson correlation analysis revealed a significant positive correlation between the NH3-N content in the hepatopancreas and the expression of ER stress-related genes, as well as between ER Ca2+ influx/efflux and energy homeostasis/fatty acid metabolism. The findings indicate that the stress induced by ammonia triggers an ER stress response in P. vannamei, resulting in ER Ca2+ efflux and mitochondrial Ca2+ influx, which, in turn, enhances fatty acid metabolism to generate additional energy for adaptation in stressful environments. This study contributes to a deeper understanding of the environmental adaptability of P. vannamei in the context of Ca2+ homeostasis.

Quantitative visualization of myocardial ischemia-reperfusion-induced cardiac lesions via ferroptosis magnetic particle imaging.

Myocardial ischemia-reperfusion (MI/R) injury is a complication in vascular reperfusion therapy for MI, occurring in approximately 60% of patients. Ferroptosis is an important process in the development of MI/R cardiac lesions. Transferrin receptor 1 (TfR1), a marker of ferroptosis, corresponds to the changes in MI/R cardiac lesions and is expected to be a biomarker for detecting MI/R-induced ferroptosis. However, the noninvasive in vivo visualization of ferroptosis in MI/R is a big challenge. Thus, this study aimed to develop a novel multimodal imaging platform to identify markers of MI/R cardiac lesions in vivo through targeting TfR1. Methods: Magnetic particle imaging (MPI) modality for ferroptosis based on superparamagnetic cubic-iron oxide nanoparticles (SCIO NPs), named feMPI, has been developed. FeMPI used TfR1 as a typical biomarker. The feMPI probe (SCIO-ICG-CRT-CPPs NPs, CCI NPs) consists of SCIO NPs, TfR1-targeting peptides (CRT), cell-penetrating peptides (CPPs), and indocyanine green (ICG). The specificity and sensitivity of CCI NPs in the MI/R mouse model were evaluated by MPI, magnetic resonance imaging (MRI), and near-infrared (NIR) fluorescent imaging. Results: The intensity of the MPI signal correlates linearly with the percentage of infarct area in MI/R stained by TTC, enabling a quantitative assessment of the extent of cardiac lesions. Notably, these findings are consistent with the standard clinical biochemical indicators in MI/R within the first 24 h. FeMPI detects cardiac injury approximately 48 h prior to the current clinical imaging detection methods of MI/R. Conclusion: The feMPI strategy can be a powerful tool for studying the process of MI/R-induced ferroptosis in vivo, providing clues for molecular imaging and drug development of ferroptosis-related treatments.

Comparative Study of Indocyanine Green Fluorescence Imaging in Lung Cancer with Near-Infrared-I/II Windows.

BACKGROUND: We compare the application of intravenous indocyanine green (ICG) fluorescence imaging in lung cancer with near-infrared-I (NIR-I) and near-infrared-II (NIR-II) windows. METHODS: From March to December 2022, we enrolled patients who received an intravenous injection of ICG (5 mg/kg) 1 day before the planned lung cancer surgery. The lung cancer nodules were imaged by NIR-I/II fluorescence imaging systems, and the tumor-to-normal-tissue ratio (TNR) was calculated. In addition, the fluorescence intensity and signal-to-background ratio (SBR) of capillary glass tubes containing ICG covered with different thicknesses of lung tissue were measured by NIR-I/II fluorescence imaging systems. RESULTS: In this study, 102 patients were enrolled, and the mean age was 59.9 ± 9.2 years. A total of 96 (94.1%) and 98 (96.1%) lung nodules were successfully imaged with NIR-I and NIR-II fluorescence, and the TNR of NIR-II was significantly higher than that of NIR-I (3.9 ± 1.3 versus 2.4 ± 0.6, P < 0.001). In multiple linear regression, solid nodules (P < 0.001) and squamous cell carcinoma (P < 0.001) were independent predictors of a higher TNR of NIR-I/II. When capillary glass tubes were covered with lung tissue whose thickness was more than 2 mm, the fluorescence intensity and the SBR of NIR-II were significantly higher than those of NIR-I. CONCLUSIONS: We verified the feasibility of NIR-II fluorescence imaging in intravenous ICG lung cancer imaging for the first time. NIR-II fluorescence can improve the TNR and penetration depth of lung cancer with promising clinical prospects.

iPUNet: Iterative Cross Field Guided Point Cloud Upsampling.

Point clouds acquired by 3D scanning devices are often sparse, noisy, and non-uniform, causing a loss of geometric features. To facilitate the usability of point clouds in downstream applications, given such input, we present a learning-based point upsampling method, i.e., which generates dense and uniform points at arbitrary ratios and better captures sharp features. To generate feature-aware points, we introduce cross fields that are aligned to sharp geometric features by self-supervision to guide point generation. Given cross field defined frames, we enable arbitrary ratio upsampling by learning at each input point a local parameterized surface. The learned surface consumes the neighboring points and 2D tangent plane coordinates as input, and maps onto a continuous surface in 3D where arbitrary ratios of output points can be sampled. To solve the non-uniformity of input points, on top of the cross field guided upsampling, we further introduce an iterative strategy that refines the point distribution by moving sparse points onto the desired continuous 3D surface in each iteration. Within only a few iterations, the sparse points are evenly distributed and their corresponding dense samples are more uniform and better capture geometric features. Through extensive evaluations on diverse scans of objects and scenes, we demonstrate that iPUNet is robust to handle noisy and non-uniformly distributed inputs, and outperforms state-of-the-art point cloud upsampling methods.

Mechanically Gated Transistor.

Silicon-based field effect transistors have underpinned the information revolution in the last 60 years, and there is a strong desire for new materials, devices, and architectures that can help sustain the computing power in the age of big data and artificial intelligence. Inspired by the Piezo channels, a mechanically gated transistor abandoning electric gating altogether, achieving an ON/OFF ratio over three orders of magnitude under a mechanical force of hundreds of nN is developed. The two-terminal device utilizes flexoelectric polarization induced by strain gradient, which modulates the carrier concentration in a Van der Waals structure significantly, and it mimics Piezo channels for artificial tactile perception. This simple device concept can be easily adapted to a wide range of semiconducting materials, helping promote the fusion between mechanics and electronics in a similar way as mechanobiology.

Autonomous dental robotic surgery for zygomatic implants: A two-stage technique.

Zygomatic implants (ZIs) can be a treatment option for patients with severe atrophy in the maxilla, but deviation during ZI placement could lead to serious complications. Surgical guides and dynamic navigation have been used to improve the accuracy of ZI placement, but both techniques are subject to human error. A 2-stage technique is described that enabled an autonomous dental robot to overcome mouth-opening restrictions for ZI placement. The technique enables the complete digitalization of ZI placement, further improving the accuracy of the drilling process.

Autonomous robotic surgery for zygomatic implant placement and immediately loaded implant-supported full-arch prosthesis: a preliminary research.

OBJECTIVES: A patient with extensive atrophy of the alveolar ridge in the posterior portion of the maxilla was selected to complete an experimental and clinical case of the robotic zygomatic implant to investigate the viability of an implant robotic system in clinical use. METHODS: The preoperative digital information was collected, and the implantation position and personalized optimization marks needed for robot surgery were designed in advance in a repair-oriented way. The resin models and marks of the patient's maxilla and mandible are all printed in 3D. Custom-made special precision drills and handpiece holders for robotic zygomatic implants were used to perform model experiments and compare the accuracy of the robotic zygomatic implant group (implant length = 52.5 mm, n = 10) with the alveolar implant group (implant length = 18 mm, n = 20). Based on the results of extraoral experiments, a clinical case of robotic surgery for zygomatic implant placement and immediate loading of implant-supported full arch prosthesis was carried out. RESULTS: In the model experiment, the zygomatic implant group reported an entry point error of 0.78 ± 0.34 mm, an exit point error of 0.80 ± 0.25 mm, and an angle error of 1.33 ± 0.41degrees. In comparison, the alveolar implant group (control group) reported an entry point error of 0.81 ± 0.24 mm, an exit point error of 0.86 ± 0.32 mm, and an angle error of 1.71 ± 0.71 degrees. There was no significant difference between the two groups (p > 0.05). In clinical cases, the average entry point error of two zygomatic implants is 0.83 mm, the average exit point error is 1.10 mm and the angle error is 1.46 degrees. CONCLUSIONS: The preoperative planning and surgical procedures developed in this study provide enough accuracy for robotic zygomatic implant surgery, and the overall deviation is small, which is not affected by the lateral wall deviation of maxillary sinus.

High-Throughput Scanning Second-Harmonic-Generation Microscopy for Polar Materials.

The Materials Genome Initiative aims to discover, develop, manufacture, and deploy advanced materials at twice the speed of conventional approaches. To achieve this, high-throughput characterization is essential for the rapid screening of candidate materials. In this study, a high-throughput scanning second-harmonic-generation microscope with automatic partitioning, accurate positioning, and fast scanning is developed that can rapidly probe and screen polar materials. Using this technique, typical ferroelectrics, including periodically poled lithium niobate crystals and PbZr0.2 Ti0.8 O3 (PZT) thin films are first investigated, whereby the microscopic domain structures are clearly revealed. This technique is then applied to a compositional-gradient (100-x)%BaTiO3 -x%SrTiO3 film and a thickness-gradient PZT film to demonstrate its high-throughput capabilities. Since the second-harmonic-generation signal is correlated with the macroscopic remnant polarization over the probed region determined by the laser spot, it is free of artifacts arising from leakage current and electrostatic interference, while materials' symmetries and domain structures must be carefully considered in the data analysis. It is believed that this work can help promote the high-throughput development of polar materials and contribute to the Materials Genome Initiative.

The role of phosphatidylcholine 34:1 in the occurrence, development and treatment of ulcerative colitis.

Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.

How to Regulate the Infringements of Geographical Indications of Agricultural Products-An Empirical Study on Judicial Documents in China.

Under the background of China's strategy of becoming a powerful agricultural country, geographical indications (GIs) of agricultural products, as an important intellectual property right to enable Chinese agriculture to develop with high quality, have a strong effect of strengthening and promoting agriculture. However, there are a large number of infringements of GIs among agricultural products in judicial practice, which not only greatly damage the economic and social values of GIs of agricultural products, but also bring huge food safety hazards to consumers and hinder the overall protection of intellectual property rights in China. On this basis, this paper, with the help of a quasi-case research method, integrates the facts of relevant cases, the focus of disputes, the application of law, and other case elements to realize the case similarity judgment based on the legal argumentation model. With the help of the retrieval tool of "Peking University Magic Weapon", this paper provides statistics on the civil cases of infringement of GIs of agricultural products in China from 1 January 2014 to 31 July 2022 and sets different retrieval conditions for two searches. After two screenings, 245 valid samples were obtained, and the judicial patterns of infringement disputes over GIs of agricultural products in China were systematically sorted out from the distribution of plaintiff and defendant, the distribution of infringement types, the basis of adjudication, and the standard of compensation. It was found that the plaintiff types showed double simplification, the infringement types took edge infringement as the basic form, and the general trademark provisions occupied the main position in legal applications. Then, the main litigation points, such as the dispute over the identification of GIs of agricultural products, the dispute over the use of geographical names, and the dispute over tort liability, are summarized, so as to dig out the characteristics of the implicitness of infringement, the expectation of implementation, and the concreteness of aspects. On this basis, the regulatory path of the infringement of GIs of agricultural products is put forward, such as introducing procuratorial public interest litigation, multi-agents cooperating to implement all-round supervision, and reasonably determining the amount of damages.

NIR-II fluorescence imaging-guided colorectal cancer surgery targeting CEACAM5 by a nanobody.

BACKGROUND: Surgery is the cornerstone of colorectal cancer (CRC) treatment, yet complete removal of the tumour remains a challenge. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescent molecular imaging is a novel technique, which has broad application prospects in tumour surgical navigation. We aimed to evaluate the ability of CEACAM5-targeted probe for CRC recognition and the value of NIR-II imaging-guided CRC resection. METHODS: We constructed the probe 2D5-IRDye800CW by conjugated anti-CEACAM5 nanobody (2D5) with near-infrared fluorescent dye IRDye800CW. The performance and benefits of 2D5-IRDye800CW at NIR-II were confirmed by imaging experiments in mouse vascular and capillary phantom. Then mouse colorectal cancer subcutaneous tumour model (n = 15), orthotopic model (n = 15), and peritoneal metastasis model (n = 10) were constructed to investigate biodistribution of probe and imaging differences between NIR-I and NIR-II in vivo, and then tumour resection was guided by NIR-II fluorescence. Fresh human colorectal cancer specimens were incubated with 2D5-IRDye800CW to verify its specific targeting ability. FINDINGS: 2D5-IRDye800CW had an NIR-II fluorescence signal extending to 1600 nm and bound specifically to CEACAM5 with an affinity of 2.29 nM. In vivo imaging, 2D5-IRDye800CW accumulated rapidly in tumour (15 min) and could specifically identify orthotopic colorectal cancer and peritoneal metastases. All tumours were resected under NIR-II fluorescence guidance, even smaller than 2 mm tumours were detected, and NIR-II had a higher tumour-to-background ratio than NIR-I (2.55 ± 0.38, 1.94 ± 0.20, respectively). 2D5-IRDye800CW could precisely identify CEACAM5-positive human colorectal cancer tissue. INTERPRETATION: 2D5-IRDye800CW combined with NIR-II fluorescence has translational potential as an aid to improve R0 surgery of colorectal cancer. FUNDINGS: This study was supported by Beijing Natural Science Foundation (JQ19027), the National Key Research and Development Program of China (2017YFA0205200), National Natural Science Foundation of China (NSFC) (61971442, 62027901, 81930053, 92059207, 81227901, 82102236), Beijing Natural Science Foundation (L222054), CAS Youth Interdisciplinary Team (JCTD-2021-08), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16021200), the Zhuhai High-level Health Personnel Team Project (Zhuhai HLHPTP201703), the Fundamental Research Funds for the Central Universities (JKF-YG-22-B005) and Capital Clinical Characteristic Application Research (Z181100001718178). The authors would like to acknowledge the instrumental and technical support of the multi-modal biomedical imaging experimental platform, Institute of Automation, Chinese Academy of Sciences.

Atomic Origins of Enhanced Ferroelectricity in Nanocolumnar PbTiO3 /PbO Composite Thin Films.

Nanocomposite films hold great promise for multifunctional devices by integrating different functionalities within a single film. The microstructure of the precipitate/secondary phase is an essential element in designing composites' properties. The interphase strain between the matrix and secondary phase is responsible for strain-mediated functionalities, such as magnetoelectric coupling and ferroelectricity. However, a quantitative microstructure-dependent interphase strain characterization has been scarcely studied. Here, it is demonstrated that the PbTiO3 (PTO)/PbO composite system can be prepared in nano-spherical and nanocolumnar configurations by tuning the misfit strain, confirmed by a three-dimensional reconstructive microscopy technique. With the atomic resolution quantitative microscopy with a depth resolution of a few nanometers, it is discovered that the strained region in PTO is much larger and more uniform in nanocolumnar compared to nano-spherical composites, resulting in much enhanced ferroelectric properties. The interphase strain between PbO and PTO in the nanocolumnar structure leads to a giant c/a ratio of 1.20 (bulk value of 1.06), accompanied by a Ti polarization displacement of 0.48 Å and an effective ferroelectric polarization of 241.7 µC cm-2 , three times compared to the bulk value. The quantitative atomic-scale strain and polarization analysis on the interphase strain provides an important guideline for designing ferroelectric nanocomposites.

Enhanced glypican-3-targeted identification of hepatocellular carcinoma with liver fibrosis by pre-degrading excess fibrotic collagen.

Most hepatocellular carcinomas (HCCs) occur in cirrhotic livers, but unequivocal diagnosis of early HCC from the fibrotic microenvironment remains a formidable challenge with conventional imaging strategies, mainly because of the massive fibrotic collagen deposition leading to hepatic nodules formation and dysfunction of contrast agent metabolism. Here, we developed a "sweep-and-illuminate" imaging strategy, pre-degrade hepatic fibrotic collagen with collagenase I conjugated human serum albumin (HSA-C) and then targeting visualize HCC lesion with GPC3 targeting nanoparticles (TSI NPs, TJ2 peptide-superparamagnetic iron oxide-indocyanine green) via fluorescence imaging (FLI) and magnetic particle imaging (MPI). TSI NPs delineated a clear boundary of HCC and normal liver, and the tumor-to-background ratios (TBRs) detected by FLI and MPI were 5.43- and 1.34-fold higher than the non-targeted group, respectively. HSA-C could degrade 24.7% fibrotic collagen, followed by 27.2% reduction of nonspecific NPs retention in mice with liver fibrosis. In a pathological state in which HCC occurs in the fibrotic microenvironment, HSA-C-mediated pre-degradation of fibrotic collagen reduced background signal interference in fibrotic tissues and enhanced the intratumoral uptake of TSI NPs, resulting in the clear demarcation between HCC and liver fibrosis, and the TBR was increased 2.61-fold compared to the group without HSA-C pretreatment. We demonstrated the feasibility of combined pre-degradation of fibrotic collagen and application of a GPC3-targeted FLI/MPI contrast agent for early HCC identification, as well as its clinical value in the management of patients with advanced liver fibrosis. STATEMENT OF SIGNIFICANCE: Given that liver fibrosis hinders early detection and treatment options of hepatocellular carcinomas (HCCs), we report a "sweep-and-illuminate" imaging strategy to enhance the efficiency of HCC identification by modulating the irreversible liver fibrosis. We first "sweep" nonspecific interference of contrast agent by pre-degrading fibrotic collagen with human serum albumin-carried collagenase I (HSA-C); and then specifically "illuminate" HCC lesions with GPC3-targeted-SPIO-ICG nanoparticles (TSI NPs). HSA-C can degrade 24.7% fibrotic collagen, followed by 27.2% reduction of nonspecific NPs retention in mice with liver fibrosis. Furthermore, in HCC models coexisting with liver fibrosis, the combined application of HSA-C and TSI NPs can clarify the demarcation between HCC and liver fibrosis with a 2.61-fold increase in the tumor-to-background ratio. This study may expand the potential of combinatorial biomaterials for early HCC diagnosis.