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IntroductionMedical image analysis is of tremendous importance in serving clinical diagnosis, treatment planning, as well as prognosis assessment. However, the image analysis process usually involves multiple modality-specific software and relies on rigorous manual operations, which is time-consuming and potentially low reproducible.MethodsWe present an integrated platform - uAI Research Portal (uRP), to achieve one-stop analyses of multimodal images such as CT, MRI, and PET for clinical research applications. The proposed uRP adopts a modularized architecture to be multifunctional, extensible, and customizable.Results and DiscussionThe uRP shows 3 advantages, as it 1) spans a wealth of algorithms for image processing including semi-automatic delineation, automatic segmentation, registration, classification, quantitative analysis, and image visualization, to realize a one-stop analytic pipeline, 2) integrates a variety of functional modules, which can be directly applied, combined, or customized for specific application domains, such as brain, pneumonia, and knee joint analyses, 3) enables full-stack analysis of one disease, including diagnosis, treatment planning, and prognosis assessment, as well as full-spectrum coverage for multiple disease applications. With the continuous development and inclusion of advanced algorithms, we expect this platform to largely simplify the clinical scientific research process and promote more and better discoveries.

Background: Nanocomposite Hydrogels (NHs) are 3D molecular networks formed by physically or covalently crosslinking polymer with nanoparticles or nanostructures, which are particularly suitable for serving as carriers for drug delivery systems. Many articles pertaining to the applications of Nanocomposite Hydrogels for drug delivery have been published, however, the use of bibliometric and visualized analysis in this area remains unstudied. The purpose of this bibliometric study intended to comprehensively analyze the knowledge domain, research hotspots and frontiers associated with the applications of Nanocomposite Hydrogels for drug delivery.Methods: We identified and retrieved the publications concerning the applications of NHs for drug delivery between 2003 and 2022 from Web of Science Core Collection Bibliometric and visualized analysis was utilized in this investigative study.Results: 631 articles meeting the inclusion criteria were identified and retrieved from WoSCC. Among those, 2,233 authors worldwide contributed in the studies, accompanied by an average annual article increase of 24.67%. The articles were co-authored by 764 institutions from 52 countries/regions, and China published the most, followed by Iran and the United States. Five institutions published more than 40 papers, namely Univ Tabriz (n = 79), Tabriz Univ Med Sci (n = 70), Islamic Azad Univ (n = 49), Payame Noor Univ (n = 42) and Texas A&M Univ (n = 41). The articles were published in 198 journals, among which the International Journal of Biological Macromolecules (n = 53) published the most articles, followed by Carbohydrate Polymers (n = 24) and ACS Applied Materials and Interfaces (n = 22). The top three journals most locally cited were Carbohydrate Polymers, Biomaterials and Advanced materials. The most productive author was Namazi H (29 articles), followed by Bardajee G (15 articles) and Zhang J (11 articles) and the researchers who worked closely with other ones usually published more papers. “Doxorubicin,” “antibacterial” and “responsive hydrogels” represent the current research hotspots in this field and “cancer therapy” was a rising research topic in recent years. “(cancer) therapeutics” and “bioadhesive” represent the current research frontiers.Conclusion: This bibliometric and visualized analysis offered an investigative study and comprehensive understanding of publications regarding the applications of Nanocomposite Hydrogels for drug delivery from 2003 to 2022. The outcome of this study would provide insights for researchers in the field of Nanocomposite Hydrogels applications for drug delivery.

The present study focused on the development of Cur-loaded SOHA nanogels (Cur-SHNGs) to enhance the topical administration of Cur. The physiochemical properties of Cur-SHNGs were characterized. Results showed that the morphology of the Cur-SHNGs was spherical, the average size was 171.37 nm with a zeta potential of −13.23 mV. Skin permeation experiments were carried out using the diffusion cell systems. It was found that the skin retention of Cur-SHNGs was significantly improved since it showed the best retention value (0.66 ± 0.17 μg/cm2). In addition, the hematoxylin and eosin staining showed that the Cur-SHNGs improved transdermal drug delivery by altering the skin microstructure. Fluorescence imaging indicated that Cur-SHNGs could effectively deliver the drug to the deeper layers of the skin. Additionally, Cur-SHNGs showed significant analgesic and anti-inflammatory activity with no skin irritation. Taken together, Cur-SHNGs could be effectively used for the topical delivery of therapeutic drugs.

Objective: Two-photon polymerization (TPP) utilizes an optical nonlinear absorption process to initiate the polymerization of photopolymerizable materials. To date, it is the only technique capable of fabricating complex 3D microstructures with finely adjusted geometry on the cell and sub-cell scales. TPP shows a very promising potential in biomedical applications related to high-resolution features, including drug delivery, tissue engineering, microfluidic devices, and so forth. Therefore, it is of high significance to grasp the global scientific achievements in this field. An analysis of publications concerning the applications of TPP in the biomedical field was performed, and the knowledge domain, research hotspots, frontiers, and research directions in this topic were identified according to the research results.Methods: The publications concerning TPP applications in biomedical field were retrieved from WoSCC between 2003 and 2022, Bibliometrics and visual analysis employing CiteSpace software and R-language package Bibliometrix were performed in this study.Results: A total of 415 publications regarding the TPP applications in the biomedical field were retrieved from WoSCC, including 377 articles, and 38 review articles. The studies pertaining to the biomedical applications of TPP began back in 2003 and showed an upward trend constantly. Especially in the recent 5 years, studies of TPP in biomedical field have increased rapidly, with the number of publications from 2017 to 2021 accounting for 52.29% of the total. In terms of output, China was the leading country and Chinese Acad Sci, Tech Inst Phys and Chem was the leading institution. The United States showed the closest cooperation with other countries. ACS applied materials and interfaces was the most prolific journal (n = 13), followed by Biofabrication (n = 11) and Optics express (n = 10). The journals having the top cited papers were Biomaterials, Advanced materials, and Applied physic letters. The most productive author was Aleksandr Ovsianikov (27 articles). Meanwhile, researchers who had close cooperation with other researchers were also prolific authors. “cell behavior”, " (tissue engineering) scaffolds”, “biomaterials,” and “hydrogel” were the main co-occurrence keywords and “additional manufacturing”, “3D printing,” and “microstructures” were the recent burst keywords. The Keyword clusters, “stem cells,” and “mucosal delivery”, appeared recently. A paper reporting unprecedented high-resolution bull models fabricated by TPP was the most locally cited reference (cited 60 times). “Magnetic actuation” and “additive manufacturing” were recently co-cited reference clusters and an article concerning ultracompact compound lens systems manufactured by TPP was the latest burst reference.Conclusion: The applications of TPP in biomedical field is an interdisciplinary research topic and the development of this field requires the active collaboration of researchers and experts from all relevant disciplines. Bringing up a better utilization of TPP as an additive manufacturing technology to better serve the biomedical development has always been the research focus in this field. Research on stem cells behaviors and mucosal delivery based on microstructures fabricated using TPP were becoming new hotspots. And it can be predicted that using TPP as a sourcing technique to fabricate biomedical-related structures and devices is a new research direction. In addition, the research of functional polymers, such as magnetic-driven polymers, was the frontier topic of TPP biomedical applications.

The needs for high-resolution, well-defined and complex 3D microstructures in diverse fields call for the rapid development of novel 3D microfabrication techniques. Among those, two-photon polymerization (TPP) attracted extensive attention owing to its unique and useful characteristics. As an approach to implementing additive manufacturing, TPP has truly 3D writing ability to fabricate artificially designed constructs with arbitrary geometry. The spatial resolution of the manufactured structures via TPP can exceed the diffraction limit. The 3D structures fabricated by TPP could properly mimic the microenvironment of natural extracellular matrix, providing powerful tools for the study of cell behavior. TPP can meet the requirements of manufacturing technique for 3D scaffolds (engineering cell culture matrices) used in cytobiology, tissue engineering and regenerative medicine. In this review, we demonstrated the development in 3D microfabrication techniques and we presented an overview of the applications of TPP as an advanced manufacturing technique in complex 3D biomedical scaffolds fabrication. Given this multidisciplinary field, we discussed the perspectives of physics, materials science, chemistry, biomedicine and mechanical engineering. Additionally, we dived into the principles of tow-photon absorption (TPA) and TPP, requirements of 3D biomedical scaffolders, developed-to-date materials and chemical approaches used by TPP and manufacturing strategies based on mechanical engineering. In the end, we draw out the limitations of TPP on 3D manufacturing for now along with some prospects of its future outlook towards the fabrication of 3D biomedical scaffolds.

A clear understanding of cropland expansion dynamics and their effects is vital for cropland protection and food security. However, the trajectories of cropland expansion have been less discussed. This study referred to the modes of landscape expansion and assessed the cropland expansion trajectory in three urban agglomerations in the Yangtze River Economic Belt and its impact on cropland fragmentation. Specifically, we identified three cropland expansion trajectories using the landscape expansion index, namely, infilling, edge-expansion, and outlying. Moreover, the surface relief amplitude model was employed to characterize the relief amplitude effect on cropland expansion trajectories. By coupling landscape metrics (e.g., patch density, landscape shape index, the largest patch index, and aggregation index) and Spearman correlation analysis, the relationship between cropland expansion trajectories and cropland fragmentation was assessed. Results show that (1) three urban agglomerations experience cropland expansion, in which the edge-expansion trajectory is primary, followed by infilling and outlying trajectories; (2) the cumulative frequency curve indicates that infilling and edge-expansion trajectories are likely to be distributed in low topographic relief amplitude regions, while the outlying trajectory is located in relatively higher topographic relief amplitude regions; and (3) infilling and edge-expansion trajectories contribute to a significantly positive relationship with the decrease of cropland fragmentation, while the outlying trajectory has a negative relationship with cropland fragmentation. This research highlights that cropland protection policies should considerably focus on the trajectory of cropland expansion, not only request the total area of cropland in a dynamic balance.

Soil erosion is a land degradation process that may threaten the sustainability of ecosystem as well as cause severe social and economic problems. The studies on the effect of ecological restoration policies on soil erosion have been well documented, while the spatial relationships and spillover effects of the policies on soil erosion have been rarely scrutinized, though it is of great policy implications in soil erosion control. Based on the analysis of the spatio-temporal evolution of soil erosion in 107 counties of Shaanxi Province with Revised Universal Soil Loss Equation, this study employs a panel spatial Durbin model (SDM) with multi-source data for 107 counties from 2000 to 2015 to investigate the spatial effects of the Sloping Land Conversion Program (SLCP) on soil erosion control with investment data of SLCP. The results show that during 2000–2015, the average amount of soil erosion exhibited a significant downtrend contributed by the continuous investment of SLCP. The spatial economic results demonstrate that the own effect, as well as the spillover effect of investment on soil erosion control, is significant and positive. A 0.1 billion CNY increase in investment in a county will result in a reduction of the total soil erosion by 288.69 thousand t/a, of which 63% is contributed to the own direct effect on local soil erosion control and the 37% of it is contributed to the spillover effect on the neighbors. Moreover, rainfall has a significant and positive moderating effect on the mitigation effect of SLCP on soil erosion at county scale; the marginal contribution of investment of SLCP on soil erosion control in the county with less rainfall is greater than that with more rainfall. These findings contribute to further our understanding of the long-term effects of ecological restoration policies and transboundary ecological governance.

Nowadays, both urbanization and cropland expansion are hot issues. However, research related to the spatiotemporal interaction between urbanization and cropland expansion and their socioeconomic determinants remains scarce. Accordingly, this research takes the urban agglomeration in the middle reaches of the Yangtze River (MRUA) as the research area by combining spatial analysis, sensitivity analysis, and the spatial gravity model. To achieve this goal, we identified the area of the construction land expansion and cropland expansion, the sensitivity of cropland expansion to construction land expansion, and the shifting trajectory of gravity centers of construction land expansion and cropland expansion and their interaction during 2000–2020, respectively. Additionally, the geographically weighted regression model was utilized to explore the spatiotemporal heterogeneity of four socioeconomic determinants of the interaction between construction land expansion and cropland expansion. The results are as follows: 1) the area of the expanded construction land and the expanded cropland and the sensitivity of cropland expansion to construction land expansion show an overall increasing pattern; 2) the gravity center of the expanded construction land shifted toward the northeast, whereas that of the expanded cropland moved to the southeast but with similar moving distances (17.83 and 15.37 km, respectively); 3) the GDP has an increasing positive effect on the interaction of the construction land expansion and cropland expansion, whereas the investment in fixed assets shows an increasing negative effect during 2000–2020. The GDP in the agricultural sector and population displays a stable influence. This article offers a solution for decision makers to promote the interaction between construction land and cropland.

Diaveridine (DVD) is widely used for the prevention and treatment of coccidiosis and leucocytozoonosis infections in food-producing animals. To gain a better understanding of DVD metabolism and pharmacokinetics in healthy Landrace/Doric Cross castrated male pigs and both female and male Cobb 500 broiler chickens, a method involving radioactive tracing coupled with LC/MS-IT-TOF was developed for the identification and quantitation of DVD and its metabolites in pig and chicken plasma, and then was applied to investigate DVD pharmacokinetics. A simple MCX solid phase extraction procedure was adopted for sample preparation. After a single oral administration of 3H-DVD (10 mg/kg BW), three radioactive compounds (D0: DVD; D1: 3′-desmethyl-DVD; and D2: monoglucuronide of 3′-desmethyl-DVD) were identified in pig plasma, while only two radioactive compounds (D0 and D2) were identified in chicken plasma. In both species, the Cmax values for all detected compounds were reached at 2 h after dosing. The Cmax order was D2 (1.38 μg/ml) > D0 (0.49 μg/ml) > D1 (0.24 μg/ml) in pigs and D0 (1.55 μg/ml) > D2 (0.27 μg/ml) in chickens. The longer t1/2 (elimination half-life) of D0 contributed to the slow elimination of DVD-related compounds. The t1/2β of D0 in pigs (66.41 h) was significantly longer than that in chickens (48.30 h), but the t1/2 of total DVD-related metabolites in pigs (42.86 h) was lower than that in chickens (56.11 h). These findings suggested that the metabolism and pharmacokinetics of DVD in pigs and chickens were significantly different, and that this would affect its effectiveness, toxicology, and food safety in these animals.

Lysozymes are naturally occurring enzymes present in a variety of biological organisms, such as bacteria, fungi, and animal bodily secretions and tissues. It is also the main ingredient of many ethnomedicines. It is well known that lysozymes and lysozyme-like enzymes can be used as anti-bacterial agents by degrading bacterial cell wall peptidoglycan that leads to cell death, and can also inhibit fungi, yeasts, and viruses. In addition to its direct antimicrobial activity, lysozyme is also an important component of the innate immune system in most mammals. Increasing evidence has shown the immune-modulatory effects of lysozymes against infection and inflammation. More recently, studies have revealed the anti-cancer activities of lysozyme in multiple types of tumors, potentially through its immune-modulatory activities. In this review, we summarized the major functions and underlying mechanisms of lysozymes derived from animal and plant sources. We highlighted the therapeutic applications and recent advances of lysozymes in cancers, hypertension, and viral diseases, aiming toseeking alternative therapies for standard medical treatment bypassing side effects. We also evaluated the role of lysozyme as a promising cancer marker for prognosis to indicate the outcomes recurrence for patients.

IntroductionHR+/HER2− breast cancer (BC) has a much lower pathological complete response (pCR) rate to neoadjuvant chemotherapy (NAC). Therefore, to better stratify the relapse risk for HR+/HER2− non-pCR populations, it is essential to accurate identification new prognostic markers.Materials and MethodsThe study retrospectively analyzed 105 stage II–III patients who were diagnosed with HR+/HER2− BC and received NAC followed by breast and axilla surgery between 2013 and 2019 in Sun Yat-Sen University Cancer Center. The Miller–Payne (MP) grading system was used to evaluate pathological responses to NAC. The 70-gene signature was used to classify the prognosis signatures.ResultsAmong the 105 patients, the study demonstrated that larger tumor size and lower progesterone receptor level at baseline and larger tumor size postoperative were statistically significantly associated with worse disease-free survival (DFS) (p = 0.004, p = 0.021, and p = 0.001, respectively). Among 54 patients who underwent the 70-gene assays, 26 (48.1%) had a low-risk signature; 28 (51.9%) patients had a high-risk signature. Patients with poor response (MP grades 1–2) were more likely to with a high-risk 70-gene signature than those with good response (MP grades 4–5). The final analysis showed that DFS was longer in the low-risk group than in the high-risk group [52.4 vs. 36.1 months of the median DFS, hazard ratio (HR) for recurrence, 0.29; 95% confidence interval (CI), 0.10–0.80; p = 0.018]. DFS was longer in the good response (MP grades 3–4) group than in the poor response (MP grades 1–2) group (94.7% vs. 60% of the patients free from recurrence; HR, 0.16; 95% CI, 0.05–0.47; p = 0.037). When stratified by MP grades combined with the 70-gene signature, subgroup analyses showed the good-response low-risk group with the best DFS, whereas the poor-response high-risk group showed the worst DFS (p = 0.048). Due to the short median follow-up time of 34.5 months (5.9–75.1 months), MP grades and the 70-gene signature did not show significant prognostic value for overall survival.ConclusionThe study showed that analysis of MP grades combined with the 70-gene signature with residual NAC-resistant breast samples has a significant correlation with DFS.

Electroencephalograph (EEG) plays a significant role in the diagnostics process of epilepsy, but the detection rate is unsatisfactory when the length of interictal EEG signals is relatively short. Although the deliberate attacking theories for undirected brain network based on node removal method can extract potential network features, the node removal method fails to sufficiently consider the directionality of brain electrical activities. To solve the problems above, this study proposes a feature tensor-based epileptic detection method of directed brain networks. First, a directed functional brain network is constructed by calculating the transfer entropy of EEG signals between different electrodes. Second, the edge removal method is used to imitate the disruptions of brain connectivity, which may be related to the disorder of brain diseases, to obtain a sequence of residual networks. After that, topological features of these residual networks are extracted based on graph theory for constructing a five-way feature tensor. To exploit the inherent interactions among multiple modes of the feature tensor, this study uses the Tucker decomposition method to get a core tensor which is finally reshaped into a vector and input into the support vectors machine (SVM) classifier. Experiment results suggest that the proposed method has better epileptic screening performance for short-term interictal EEG data.

Xinnao shutong (XNST) capsules have been clinically used in China to treat cerebrovascular diseases. Previous studies have demonstrated that XNST has significant neuroprotective effects against acute cerebral ischemic stroke. The present study investigated the effects and mechanisms of XNST treatment following chronic cerebral hypoperfusion. Thirty-six adult male Sprague-Dawley rats were treated with XNST or vehicle following permanent bilateral common carotid artery (BCCA) ligation. Body weight was recorded on days 0, 3, 7, 14, 28, and 42 post-surgery. The Morris water maze (MWM) test was used to assess cognitive function in rats. Immunofluorescent staining and western blot were used to assess the severity of neuronal plasticity, white matter injury, and the numbers and/or phenotypic changes incurred to microglia. Protein levels of p-AKT (Thr308) and p-ERK (Thr202/Tyr204) were detected 42 days after BCCA ligation was performed. The results indicate that XNST treatment significantly reduced escape latency, decreased the frequency of platform crossing compared to the vehicle group. Synaptophysin, protein levels improved and white matter injury ameliorated following XNST treatment. Meanwhile, XNST reduced the number of M1 microglia and increased the number of M2 microglia. Furthermore, p-AKT (Thr308) and p-ERK (Thr202/Tyr204) levels were increased 42 days following BCCA ligation. In summary, our results suggest that XNST mitigates memory impairments by restoration of neuronal plasticity and by modulation of microglial polarization following chronic cerebral hypoperfusion in rats.

Xinnao shutong (XNST) capsules have been clinically used in China to treat cerebrovascular diseases. Previous studies have demonstrated that XNST has significant neuroprotective effects against acute cerebral ischemic stroke. The present study investigated the effects and mechanisms of XNST treatment following chronic cerebral hypoperfusion. Thirty-six adult male Sprague-Dawley rats were treated with XNST or vehicle following permanent bilateral common carotid artery (BCCA) ligation. Body weight was recorded on days 0, 3, 7, 14, 28, and 42 post-surgery. The Morris water maze (MWM) test was used to assess cognitive function in rats. Immunofluorescent staining and western blot were used to assess the severity of neuronal plasticity, white matter injury, and the numbers and/or phenotypic changes incurred to microglia. Protein levels of p-AKT (Thr308) and p-ERK (Thr202/Tyr204) were detected 42 days after BCCA ligation was performed. The results indicate that XNST treatment significantly reduced escape latency, decreased the frequency of platform crossing compared to the vehicle group. Synaptophysin, protein levels improved and white matter injury ameliorated following XNST treatment. Meanwhile, XNST reduced the number of M1 microglia and increased the number of M2 microglia. Furthermore, p-AKT (Thr308) and p-ERK (Thr202/Tyr204) levels were increased 42 days following BCCA ligation. In summary, our results suggest that XNST mitigates memory impairments by restoration of neuronal plasticity and by modulation of microglial polarization following chronic cerebral hypoperfusion in rats. [ABSTRACT FROM AUTHOR]