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Purpose: Paclitaxel-induced cognitive impairment (PICI) is a frequent and severe adverse reaction of chemotherapy. Increased neuroinflammation related to neutrophil extracellular traps (NETs) may play a key role in PICI. Shaoyao Gancao Decoction (SGD) is a classic Chinese prescription with good neuroprotective activities. However, the action of SGD in PICI remains elusive. Herein, our work was set out to study the potential role and possible mechanism of SGD in PICI through network pharmacology, Mendelian analysis and animal experiments. Methods: First, network pharmacology analysis was performed to identify the potential active compounds and targets of SGD on PICI. Secondly, PICI mice model was established, and the neuroprotective effects of SGD on PICI mice were eveluated by using new object recognition, Morris water maze test and TUNEL staining. The impact of SGD on inflammatory factors, microglia activation and NETs formation were also studied by ELISA and immunofluorescence. The regulation of SGD on PTEN/PI3K/AKT pathway was detected by Western blot. Finally, Mendelian randomization was performed using genome-wide association analysis data of PTEN and cognitive disorders in OpenGWAS database. Results: Network pharmacological analysis revealed 105 active ingredients in SGD, and identified 124 targets associated with SGD and PICI. KEGG pathway analysis implied that PI3K-AKT signaling pathway maight be involved in the protective effect of SGD agianst PICI Animal experiments displayed that SGD significantly alleviated cognitive impairment induced by paclitaxel, and decreased neuronal apoptosis. Furthermore, SGD remarkably reduced IL-1β, TNF-α and microglia activation, while enhanced SOD activity in hippocampus. In addition, SGD could inhibit NETs formation, evidenced by decreasing the level of plasma MPO-DNA complex, as well as MPO and PAD4 expression. Western blotting assay suggested that SGD attenuated the elevated expression of PI3 K, AKT, p-AKT and PKC-α induced by paclitaxel, whereas decreased PTEN expression. The results of Mendelian randomization analysis further confirm that PTEN is an important therapeutic target for improving cognitive function. Conclusion: Collectively, our preliminary findings indicated that SGD can improve cognitive function of PICI mice. SGD may play a neuroprotective role by inhibiting NETs formation via PTEN/PI3K/AKT signaling pathway. SGD may be a potential alternative therapy for PICI.

Introduction and Aims: In the face of escalating oral cancer rates, the application of large language models like Generative Pretrained Transformer (GPT)-4 presents a novel pathway for enhancing public awareness about prevention and early detection. This research aims to explore the capabilities and possibilities of GPT-4 in addressing open-ended inquiries in the field of oral cancer., Methods: Using 60 questions accompanied by reference answers, covering concepts, causes, treatments, nutrition, and other aspects of oral cancer, evaluators from diverse backgrounds were selected to evaluate the capabilities of GPT-4 and a customized version. A P value under .05 was considered significant., Results: Analysis revealed that GPT-4 and its adaptations notably excelled in answering open-ended questions, with the majority of responses receiving high scores. Although the median score for standard GPT-4 was marginally better, statistical tests showed no significant difference in capabilities between the two models (P > .05). Despite statistical significance indicated diverse backgrounds of evaluators have statistically difference (P < .05), a post hoc test and comprehensive analysis demonstrated that both editions of GPT-4 demonstrated equivalent capabilities in answering questions concerning oral cancer., Conclusions: GPT-4 has demonstrated its capability to furnish responses to open-ended inquiries concerning oral cancer. Utilizing this advanced technology to boost public awareness about oral cancer is viable and has much potential. When it's unable to locate pertinent information, it will resort to their inherent knowledge base or recommend consulting professionals after offering some basic information. Therefore, it cannot supplant the expertise and clinical judgment of surgical oncologists and could be used as an adjunctive evaluation tool., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Osteoarthritis (OA) is the most common form of arthritis with well recognized multifactorial nature. While several environmental factors such as older age, obesity and previous joint injury are strongly associated with its development, a genetic influence on OA has been recognized for over 80 years. Identification of genes associated with OA has received considerable attention over the last two decades, aided by the rapidly evolving genotyping and sequencing technologies. More than 300 genomic loci have been identified to be associated with OA at different joints. These findings are likely to help our better understanding of the pathogenesis of OA and lead to important therapeutic and diagnostic advances in this most common disabling rheumatic disorder. This article will review the data that support the role of genetic factors in common idiopathic OA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Marine polysaccharide-based biomaterials possess a range of excellent functions and properties, such as antiviral, antioxidant, immune regulation, and promoting cell migration, and are widely used in modern medicine. In this study, a marine polysaccharide-based composite hydrogel was synthesized using carboxymethyl chitosan and oxidized fucoidan as matrix, and loads therapeutic drugs for the treatment of burn wounds infected with bacteria. The composite hydrogels can slowly release drugs at the wound site, providing a long-lasting therapeutic effect including antibacterial, antioxidant, and analgesic, in this way to facilitate the restoring of infected burn wounds by inhibiting bacterial infections, promoting cell migration, facilitating collagen regeneration, and restoring the abnormal alteration of factors such as IL-1β and CD86., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: In the treatment of malocclusion, continuous monitoring of the three-dimensional relationship between dental roots and the surrounding alveolar bone is essential for preventing complications from orthodontic procedures. Cone-beam computed tomography (CBCT) provides detailed root and bone data, but its high radiation dose limits its frequent use, consequently necessitating an alternative for ongoing monitoring., Objectives: We aimed to develop a deep learning-based cross-temporal multimodal image fusion system for acquiring root and jawbone information without additional radiation, enhancing the ability of orthodontists to monitor risk., Methods: Utilizing CBCT and intraoral scans (IOSs) as cross-temporal modalities, we integrated deep learning with multimodal fusion technologies to develop a system that includes a CBCT segmentation model for teeth and jawbones. This model incorporates a dynamic kernel prior model, resolution restoration, and an IOS segmentation network optimized for dense point clouds. Additionally, a coarse-to-fine registration module was developed. This system facilitates the integration of IOS and CBCT images across varying spatial and temporal dimensions, enabling the comprehensive reconstruction of root and jawbone information throughout the orthodontic treatment process., Results: The experimental results demonstrate that our system not only maintains the original high resolution but also delivers outstanding segmentation performance on external testing datasets for CBCT and IOSs. CBCT achieved Dice coefficients of 94.1 % and 94.4 % for teeth and jawbones, respectively, and it achieved a Dice coefficient of 91.7 % for the IOSs. Additionally, in the context of real-world registration processes, the system achieved an average distance error (ADE) of 0.43 mm for teeth and 0.52 mm for jawbones, significantly reducing the processing time., Conclusion: We developed the first deep learning-based cross-temporal multimodal fusion system, addressing the critical challenge of continuous risk monitoring in orthodontic treatments without additional radiation exposure. We hope that this study will catalyze transformative advancements in risk management strategies and treatment modalities, fundamentally reshaping the landscape of future orthodontic practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Human interferon α2 (IFNα2) is a cytokine with broad-spectrum antiviral activity, and its engineered forms are widely used to treat viral infections. However, IFNα2 may trigger proinflammatory responses and underlying side effects during treatment. Trefoil factor 2 (TFF2) is a secreted protein with anti-inflammatory properties. Here, we explored whether coupling IFNα2 to TFF2 in a two-in-one fusion form could combine the beneficial effects of both molecules on viral infections toward a more desirable treatment outcome. We engineered two forms of human IFNα2 and TFF2 fusion proteins, IFNα2-TFF2-Fc (ITF) and TFF2-IFNα2-Fc (TIF), and examined their properties in vitro in comparison to IFNα2 and TFF2 alone. RNA-Seq was further used to explore such comparison on dynamic gene regulation at transriptomic level. These in vitro assessments collectively indicated that TIF largely retained the antiviral activity of IFNα2 while being a weaker inflammation inducer, consistent with the presence of TFF2 activity. We further demonstrated the superiority of TIF over IFNα2 or TFF2 alone in treating influenza infection using a mouse infection model. Together, our study provided evidence supporting that, by possessing antiviral activity conferred by IFNα2 with complementation from TFF2 in suppressing the inflammatory side effects, the fusion proteins, particularly TIF, represent more effective agents against influenza and other respiratory viral infections than IFNα2 or TFF2 alone. It implies that merging two molecules with complementary functions holds potential for developing novel therapeutics against viral infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Skin wrinkles result from intrinsic aging processes and extrinsic influences, including prolonged exposure to ultraviolet radiation and tobacco smoking. Hence, the identification of wrinkles holds significant importance in skin aging and medical aesthetic investigation. Nevertheless, current methods lack the comprehensiveness to identify facial wrinkles, particularly those that may appear insignificant. Furthermore, the current assessment techniques neglect to consider the blurred boundary of wrinkles and cannot differentiate images with varying resolutions. This research introduces a novel wrinkle detection algorithm and a distance-based loss function to identify full-face wrinkles. Furthermore, we develop a wrinkle detection evaluation metric that assesses outcomes based on curve, location, and gradient similarity. We collected and annotated a dataset for wrinkle detection consisting of 1021 images of Chinese faces. The dataset will be made publicly available to further promote wrinkle detection research. The research demonstrates a substantial enhancement in detecting subtle wrinkles through implementing the proposed method. Furthermore, the suggested evaluation procedure effectively considers the indistinct boundaries of wrinkles and is applicable to images with various resolutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Glaucoma is one of the leading cause of blindness worldwide. Individuals affected by glaucoma, including patients and their family members, frequently encounter a deficit in dependable support beyond the confines of clinical environments. Seeking advice via the internet can be a difficult task due to the vast amount of disorganized and unstructured material available on these sites, nevertheless. This research explores how Large Language Models (LLMs) can be leveraged to better serve medical research and benefit glaucoma patients. We introduce Xiaoqing, a Natural Language Processing (NLP) model specifically tailored for the glaucoma field, detailing its development and deployment. To evaluate its effectiveness, we conducted two forms of experiments: comparative and experiential. In the comparative analysis, we presented 22 glaucoma-related questions in simplified Chinese to three medical NLP models (Xiaoqing LLMs, HuaTuo, Ivy GPT) and two general models (ChatGPT-3.5 and ChatGPT-4), covering a range of topics from basic glaucoma knowledge to treatment, surgery, research, management standards, and patient lifestyle. Responses were assessed for informativeness and readability. The experiential experiment involved glaucoma patients and non-patients interacting with Xiaoqing, collecting and analyzing their questions and feedback on the same criteria. The findings demonstrated that Xiaoqing notably outperformed the other models in terms of informativeness and readability, suggesting that Xiaoqing is a significant advancement in the management and treatment of glaucoma in China. We also provide a Web-based version of Xiaoqing, allowing readers to directly experience its functionality. The Web-based Xiaoqing is available at https://qa.glaucoma-assistant.com//qa., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Ocular Adnexal Lymphoma (OAL) is a non-Hodgkin's lymphoma that most often appears in the tissues near the eye, and radiotherapy is the currently preferred treatment. There has been a controversy regarding the prognostic factors for systemic failure of OAL radiotherapy, the thorough evaluation prior to receiving radiotherapy is highly recommended to better the patient's prognosis and minimize the likelihood of any adverse effects., Purpose: To investigate the risk factors that contribute to incomplete remission in OAL radiotherapy and to establish a hybrid model for predicting the radiotherapy outcomes in OAL patients., Methods: A retrospective chart review was performed for 87 consecutive patients with OAL who received radiotherapy between Feb 2011 and August 2022 in our center. Seven image features, derived from MRI sequences, were integrated with 122 clinical features to form comprehensive patient feature sets. Chemometric algorithms were then employed to distill highly informative features from these sets. Based on these refined features, SVM and XGBoost classifiers were performed to classify the effect of radiotherapy., Results: The clinical records of from 87 OAL patients (median age: 60 months, IQR: 52-68 months; 62.1% male) treated with radiotherapy were reviewed. Analysis of Lasso (AUC = 0.75, 95% CI: 0.72-0.77) and Random Forest (AUC = 0.67, 95% CI: 0.62-0.70) algorithms revealed four potential features, resulting in an intersection AUC of 0.80 (95% CI: 0.75-0.82). Logistic Regression (AUC = 0.75, 95% CI: 0.72-0.77) identified two features. Furthermore, the integration of chemometric methods such as CARS (AUC = 0.66, 95% CI: 0.62-0.72), UVE (AUC = 0.71, 95% CI: 0.66-0.75), and GA (AUC = 0.65, 95% CI: 0.60-0.69) highlighted six features in total, with an intersection AUC of 0.82 (95% CI: 0.78-0.83). These features included enophthalmos, diplopia, tenderness, elevated ALT count, HBsAg positivity, and CD43 positivity in immunohistochemical tests., Conclusion: The findings suggest the effectiveness of chemometric algorithms in pinpointing OAL risk factors, and the prediction model we proposed shows promise in helping clinicians identify OAL patients likely to achieve complete remission via radiotherapy. Notably, patients with a history of exophthalmos, diplopia, tenderness, elevated ALT levels, HBsAg positivity, and CD43 positivity are less likely to attain complete remission after radiotherapy. These insights offer more targeted management strategies for OAL patients. The developed model is accessible online at: https://lzz.testop.top/., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Deep learning-based super-resolution (SR) algorithms aim to reconstruct low-resolution (LR) images into high-fidelity high-resolution (HR) images by learning the low- and high-frequency information. Experts' diagnostic requirements are fulfilled in medical application scenarios through the high-quality reconstruction of LR digital medical images., Purpose: Medical image SR algorithms should satisfy the requirements of arbitrary resolution and high efficiency in applications. However, there is currently no relevant study available. Several SR research on natural images have accomplished the reconstruction of resolutions without limitations. However, these methodologies provide challenges in meeting medical applications due to the large scale of the model, which significantly limits efficiency. Hence, we suggest a highly effective method for reconstructing medical images at any desired resolution., Methods: Statistical features of medical images exhibit greater continuity in the region of neighboring pixels than natural images. Hence, the process of reconstructing medical images is comparatively less challenging. Utilizing this property, we develop a neighborhood evaluator to represent the continuity of the neighborhood while controlling the network's depth., Results: The suggested method has superior performance across seven scales of reconstruction, as evidenced by experiments conducted on panoramic radiographs and two external public datasets. Furthermore, the proposed network significantly decreases the parameter count by over 20× and the computational workload by over 10× compared to prior researches. On large-scale reconstruction, the inference speed can be enhanced by over 5×., Conclusion: The novel proposed SR strategy for medical images performs efficient reconstruction at arbitrary resolution, marking a significant breakthrough in the field. The given scheme facilitates the implementation of SR in mobile medical platforms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Dictamnine is a representative furan-containing hepatotoxic compound. Administration of dictamnine caused acute liver injury in mice and the metabolic activation of furan to reactive epoxy intermediate was responsible for the hepatotoxicity. This study aimed to characterize the protein adduction by endogenous hepatic aldehydes and investigate its role in dictamnine-induced hepatotoxicity. In the liver sample of dictamnine-treated mice, the protein adduction by five aldehydes was characterized as lysine residue-aldehyde adducts using high-resolution UPLC-Q/Orbitrap MS after exhaustive proteolytic digestion. The levels of protein adduct were increased at 2-3 h after the treatment with dictamnine. The formation of protein adduction increased with increasing doses of dictamnine. Inhibition of the bioactivation by CYP3A inhibitor ketoconazole prevented the protein adduction. Treatment with 2,3-dihydro-dictamnine, an analog of dictamnine that was unable to form the epoxy intermediate, did not lead to an increase in protein adduction. Application of aldehyde dehydrogenase-2 activator ALDA-1 or nucleophilic trapping reagent N-acetyl-L-lysine significantly reduced the protein adduction and attenuated dictamnine-induced liver injury without affecting the bioactivation. In conclusion, the metabolic activation of the furan ring of dictamnine resulted in the protein adduction by multiple hepatic aldehydes and the protein modification played a crucial role in dictamnine-induced liver injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The combined influences of species selection (Avicennia marina, Kandelia obovata) and site elevation (BSL site, below local mean sea level; ASL site, above local mean sea level) on the greenhouse gas fluxes (nitrous oxide (N 2 O), methane (CH 4 ) and carbon dioxide (CO 2 )) from restored mangrove soils are investigated in this study. Compared with the A. marina forest, soils in the K. obovata forest at ASL site have higher CO 2 fluxes, while higher N 2 O fluxes in the K. obovata forest are found at BSL site. The highest CH 4 fluxes are found at BSL site in the A. marina forest. At each elevation site, the A. marina forest has lower CO 2 -equivalent fluxes and carbon release in the form of carbon-containing gases. The results suggest that A. marina should be selected for mangrove restoration to minimize carbon release and reduce influence of greenhouse gas fluxes on the global greenhouse effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Flooding is one of the most widespread and catastrophic natural disasters. The exposure of cropland to floods is directly related to the quality of cropland and food security, so it is particularly important to map the spatiotemporal evolution of this exposure, with a specific focus on longer time series and higher resolution scales. This study is the first of its kind to analyse the worldwide spatiotemporal variability of Cropland Exposure to Flooding (CEF) with the 30 m resolution of Global Land Analysis & Discovery (GLAD) dataset during 2000-2019. The findings indicate that: (1) the global CEF area increased by a total of 83,429.50 km 2 or 7.75 %, from 2000 to 2019; (2) only North America's CEF showed a downward trend, and the region with the largest increase in CEF was South Asia; (3) the CEF in 23 river basins, including Ganges, Indus, Mississippi, Yangtze, and Danube, accounted for 79.88 % of the global total in 2019P; (4) in 2019P, China had the largest CEF globally, reaching 239,525.07 km 2 . The fastest growing CEF was India, contributing 16.36 % of the global CEF growth. The CEF of United States experienced a reduction trend; (5) two constructed indicators were used in evaluating the CEF of countries worldwide, and a total of 46 countries are considered to be at the highest level of risk, mainly in Europe and Asia. Based on these conclusions, we carried out a cold/hot spot analysis to reveal the spatial heterogeneity and possible driving factors in this phenomenon, and we offer management suggestions to limit the risks to cropland in the floodplains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Medical record images in EHR system are users' privacy and an asset, and there is an urgent need to protect this data. Image steganography can offer a potential solution. A steganographic model for medical record images is therefore developed based on StegaStamp. In contrast to natural images, medical record images are document images, which can be very vulnerable to image cropping attacks. Therefore, we use text region segmentation and watermark region localization to combat the image cropping attack. The distortion network has been designed to take into account the distortion that can occur during the transmission of medical record images, making the model robust against communication induced distortions. In addition, based on StegaStamp, we innovatively introduced FISM as part of the loss function to reduce the ripple texture in the steganographic image. The experimental results show that the designed distortion network and the FISM loss function term can be well suited for the steganographic task of medical record images from the perspective of decoding accuracy and image quality., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Finite-time stability analysis is a powerful tool for understanding the long-term behavior of epidemiological models and has been widely used to study the spread of infectious diseases such as COVID-19. In this paper, we present a finite-time stability analysis of a stochastic susceptible-infected-recovered (SIR) epidemic compartmental model with switching signals. The model includes a linear parameter variation (LPV) and switching system that represents the impact of external factors, such as changes in public health policies or seasonal variations, on the transmission rate of the disease. We use the Lyapunov stability theory to examine the long-term behavior of the model and determine conditions under which the disease is likely to die out or persist in the population. By taking advantage of the average dwell time method and Lyapunov functional (LF) method, and using novel inequality techniques the finite-time stability (FTS) criterion in linear matrix inequalities (LMIs) is developed. The finite-time stability of the resultant closed-loop system, with interval and linear parameter variation (LPV), is then guaranteed by state feedback controllers. By analyzing the modified SIR model with these interventions, we are able to examine the efficiency of different control measures and determine the most appropriate response to the COVID-19 pandemic and demonstrate the efficacy of the suggested strategy through simulation results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Elsevier Ltd. All rights reserved.)

Converting lignin into high value-added products is essential to reduce our dependence on petroleum resources and protect our environment. In this work, TiO 2 and g-C 3 N 4 are loaded in the lignin-derived carbon nanofibers (LCNFs) and an efficient LCNFs-based photocatalytic material (TiO 2 /g-C 3 N 4 @LCNFs) is developed. The spinnability of lignin solution, the chemical structure and morphology of the LCNFs, and the catalytic degradation property of the TiO 2 /g-C 3 N 4 @LCNFs for Rhodamine B (RhB) are systematically investigated. The TiO 2 /g-C 3 N 4 @LCNFs achieve a 92.76 % degradation rate of RhB under UV-vis irradiation, which is close to or higher than most reported carbon fiber-based photocatalysts. The excellent degradation property of the photocatalysts can be ascribed to the synergy of TiO 2 and g-C 3 N 4 , which improves the excitation efficiency of electron and hole, and prolongs the lifetime of electron-hole pairs. We envision that our work will provide some guidance for the development of efficient photocatalysts based on biomass-derived fiber materials., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abdominal adhesions are a class of serious complications following abdominal surgery, resulting in a complicated and severe syndrome and sometimes leading to a Gordian knot. Traditional therapies employ hydrogels synthesized using complicated chemical formulations-often with click chemistry or thermal responsive hydrogel. The complicated synthesis process and severe conditions limit the extent of the hydrogels' applications. In this work, poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) polymer was synthesized to self-assemble into physical hydrogels due to the inter- and intramolecular ion interactions. The strong static interaction bonding density has a substantial impact on the gelation and physicochemical properties, which is beneficial to clinical applications and offers a novel way to obtain the desired hydrogel for a specific biomedical application. Intriguingly, this PSBMA polymer can be customized into a transient network with outstanding antifouling capability depending on the ion concentration. As ion concentration increases, the PSBMA hydrogel dissociated completely, endowing it as a candidate for adhesion prevention. In the cecum-sidewall model, the PSBMA hydrogel demonstrated superior anti-adhesion properties than commercial HA hydrogel. Furthermore, we have demonstrated that this PSBMA hydrogel could inhibit the inflammatory response and encourage anti-fibrosis resulting in adhesion prevention. Most surprisingly, the recovered skins of cecum and sidewall are as smooth as the control skin without any scar and damage. In conclusion, a practical hydrogel was synthesized using a facile method based on purely zwitterionic materials, and this ion-sensitive, antifouling adjustable supramolecular hydrogel with great clinic transform potential is a promising barrier for preventing postoperative tissue adhesion. STATEMENT OF SIGNIFICANCE: The development of hydrogels with satisfactory coverage, long retention time, facile synthetic method, and good biocompatibility is vital for preventing peritoneal adhesions. Herein, we developed a salt sensitive purely zwitterionic physical hydrogel poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) hydrogel to effectively prevent postoperative and recurrent abdominal adhesions. The hydrogel was simple to synthesize and easy to use. In the cecum-sidewall model, PSBMA hydrogel could instantaneously adhere and fix on irregular surfaces and stay in the wound for more than 10 days. The PSBMA hydrogel could inhibit the inflammatory response, encourage anti-fibrosis, and restore smoothness to damaged surfaces resulting in adhesion prevention. Overall, the PSBMA hydrogel is a promising candidate for the next generation of anti-adhesion materials to meet clinical needs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The utilization of auxiliary electrode can improve substantially the electrokinetic remediation efficiency of heavy metal contaminated soil. The increase in the auxiliary electrode performance is the key to further promote the electrokinetic remediation efficiency. In this study, two kinds of auxiliary electrodes, pure FeOCl and doped FeOCl with W and S, were prepared and used in the electrokinetic remediation of Cr(VI) contaminated soil. The system equipped with the auxiliary electrode doped FeOCl brought more stable system current (202 mA) and more uniform electric field than blank group (130 mA). The reduction rate of Cr(VI) was increased by 50% due to the presence of Fe 2+ and S 2- . The accelerating migration of ions by auxiliary electrode was responsible for the improvement in electrokinetic remediation efficiency. Density functional theory (DFT) calculation showed that Cl vacancy formation energies of pure FeOCl, S-doped FeOCl (S/FeOCl) and W-doped FeOCl (W/FeOCl) were 1.29, 1.15 and 1.49 eV respectively, and the ion diffusion barriers were 0.093, 0.099 and 0.148 eV respectively. Calculation results indicated that the doping of S was conducive to the diffusion of Cl ions, and the bonding of W-Cl was stronger than Fe-Cl. The charging and discharging process of auxiliary electrode became easier due to the formation of lower vacancy in S-doped FeOCl, which could bring a higher current for the electrokinetic remediation system. The electrochemical performance of FeOCl doped with W and S was improved obviously. This study provided a further explanation for the positive role of auxiliary electrode in electrokinetic remediation system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) is a minimally invasive and locally effective treatment method, which has been used in the clinical treatment of a variety of superficial tumors. In recent years, PDT has received extensive attention due to its induction of immunogenic cell death (ICD). However, the repair mechanism of tumor cells and low immune response limit the further development of PDT. To this end, a multifunctional biomimetic nanoplatform 4T1Mem@PGA-Ce6/Ola (MPCO) is developed to co-deliver the photosensitizer Chlorin e6 (Ce6) and Olaparib (Ola) with the function of preventing DNA repair. The nanoplatform shows efficient tumor targeting and cellular internalization properties due to cell membrane camouflage, and Ce6 and Ola produce a significant synergistic anti-tumor effect under laser irradiation. Meanwhile, the nanoplatform can also activate the cyclic guanosine monophosphate-adenosine monophosphate synthase-interferon gene stimulator signaling (cGAS-STING) pathway to produce cytokines. The damage-associated molecular patterns induced by ICD can work with these cytokines to recruit and stimulate the maturation of dendritic cells and induce the systemic anti-tumor immune response. Overall, this multifunctional biomimetic nanoplatform integrating PDT, chemotherapy, and immunotherapy is highlighted here to boost anti-tumor therapy. STATEMENT OF SIGNIFICANCE: Self-repair of DNA damage is the most important reason for the failure of primary tumor eradication and the formation of secondary and metastatic tumors. To address this issue, a multifunctional biomimetic nanoplatform 4T1Mem@PGA-Ce6/Ola (MPCO) was developed to integrate a photosensitizer Chlorine a6 and a poly (ADP-ribose) polymerase inhibitor Olaparib. With tumor targeting ability and controlled release of drugs, the MPCO was expected to enhance tumor immunogenicity and facilitate antitumor immunity through the induction of immunogenic cell death as well as the activation of the cGAS-STING pathway. This study develops a promising combination strategy against tumors and has substantial implications for the prognosis of patients with breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Targeting the interaction between the spike protein receptor binding domain (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2) is a potential therapeutic strategy for treating coronavirus disease 2019 (COVID-19). However, we still lack small-molecule drug candidates for this target due to the missing knowledge in the hot spots for the protein-protein interaction. Here, we used NanoBiT technology to identify three Ginkgolic acids from an in-house traditional Chinese medicine (TCM) library, and they interfere with the S-RBD/ACE2 interplay. Our pseudovirus assay showed that one of the compounds, Ginkgolic acid C17:1 (GA171), significantly inhibits the entry of original SARS-CoV-2 and its variants into the ACE2-overexpressed HEK293T cells. We investigated and proposed the binding sites of GA171 on S-RBD by combining molecular docking and molecular dynamics simulations. Site-directed mutagenesis and surface plasmon resonance revealed that GA171 specifically binds to the pocket near R403 and Y505, critical residues of S-RBD for S-RBD interacting with ACE2. Thus, we provide structural insights into developing new small-molecule inhibitors and vaccines against the proposed S-RBD binding site., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The abandonment phenomenon is familiar in China. It threatens food security and seriously affects the sustainable development of society, the economy, and the natural environment. However, monitoring and mapping abandoned cropland on a large scale remains a challenge because of its complex land-use change process. According to the World Food and Agriculture Organization, cropland not used for agricultural production for more than 5 years is defined as abandoned cropland. This study uses the Landsat high-precision long-time series product to detect cropland nationwide from 1990 to 2019 by using the sliding window method on Google Earth Engine to profile the spatial distribution, intensity, trend, frequency, and recultivation of abandoned cropland. Between 1992 and 2015, the results illustrate that the total area of abandoned cropland in China was 559,170.26 km 2 , 18.59 % of the cropland area. Excluding the recultivated cropland area, China's abandoned cropland area amounted to 392,156.24 km 2 , 13.03 % of the total cropland. Cropland abandonment is mainly distributed in the second terrain gradient in midwestern and southwestern regions such as Inner Mongolia and Gansu. It rarely happens in western and eastern coastal areas. A high abandonment rate area usually has high elevation and slope. The light index is negatively correlated with the abandonment rate in suburban areas. This study is the first to map the spatiotemporal distribution of abandoned cropland in China with high precision at 30 m resolution. It provides an important basis for policies regarding the recultivation of abandoned cropland., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Although the effective drugs or vaccines have been developed to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), their efficacy may be limited for the viral evolution and immune escape. Thus, it is urgently needed to develop the novel broad-spectrum antiviral agents to control the coronavirus disease 2019 (COVID-19) global pandemic. The 3C-like protease (3CL pro ) is a highly conserved cysteine proteinase that plays a pivotal role in processing the viral polyprotein to create non-structural proteins (nsps) for replication and transcription of SARS-CoV-2, making it an attractive antiviral target for developing broad-spectrum antiviral agents against SARS-CoV-2. In this study, we identified Thonzonium bromide as an inhibitor of SARS-CoV-2 3CL pro with an IC 50 value of 2.04 ± 0.25 μM by fluorescence resonance energy transfer (FRET)-based enzymatic inhibition assay from the FDA-approved drug library. Next, we determined the inhibitory activity of Thonzonium bromide analogues against SARS-CoV-2 3CL pro and analyzed their structure-activity relationship (SAR). Interestingly, Thonzonium bromide showed better inhibitory activity than other analogues. Further fluorescence quenching assay, enzyme kinetics analysis, circular dichroism (CD) analysis and molecular docking studies showed that Thonzonium bromide inhibited SARS-CoV-2 3CL pro activity by firmly occupying the catalytic site and inducing conformational changes of the protease. In addition, Thonzonium bromide didn't exhibit inhibitory activity on human chymotrypsin C (CTRC) and Dipeptidyl peptidase IV (DPP-IV), indicating that it had a certain selectivity. Finally, we measured the inhibitory activities of Thonzonium bromide against 3CL pro of SARS-CoV, MERS-CoV and HCoV-229E and found that it had the broad-spectrum inhibitory activity against the proteases of human coronaviruses. These results provide the possible mechanism of action of Thonzonium bromide, highlighting its potential efficacy against multiple human coronaviruses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China., Methods: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed., Results: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes., Conclusion: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes., (Copyright © 2021 Canadian Ophthalmological Society. All rights reserved.)

Currently, multidrug resistance (MDR) is one of the major reasons for failure in clinical cancer chemotherapy. Overexpression of the ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which significantly increases the efflux of anticancer drugs from tumor cells, enhances MDR. In the past few decades, four generations of P-gp inhibitors have appeared. However, they are limited in clinical application due to their severe toxic side effects. As a P-gp inhibitor and carrier for loading chemotherapy agents, TPGS has received increasing attention due to its advantages and unique properties of reversing MDR. TPGS is an amphipathic agent that increases the solubility of most chemotherapy drugs and decreases severe side effects. In addition, TPGS is an excellent carrier with P-gp-inhibiting ability. In this review, we summarize the latest articles on TPGS-based nanodelivery systems to prevent MDR., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Multidrug resistance (MDR) in tumor has long been considered a major factor in the failure of tumor chemotherapy. P-glycoprotein (P-gp)-mediated drug efflux plays a significant role in the MDR of tumor. Herein, paclitaxel (PTX) and P-gp inhibitor quercetin (QC) co-loaded and chondroitin sulfate (ChS)-coated mesoporous silica nanoparticles (MSNs) (MSNs-ChS@PQ) were developed to reverse MDR in breast cancer and improve chemotherapy efficacy. The dual drug-loaded nanoparticles (NPs) showed a nanoscale size of ∼ 227.2 nm and redox-responsive drug release property. In vitro cell experiments showed that NPs exhibited CD44 receptor-mediated active targeting in MCF-7/ADR cells. The dual drug-loaded NPs had lower IC 50 value, higher apoptosis rate, obvious G2M phase arrest as well as stronger microtubule destruction in MCF-7/ADR cells compared to PTX-loaded NPs, suggesting that QC addition, significantly, improved the sensitivity of MCF-7/ADR cells to PTX. Further study found that QC-loaded NPs down-regulated the expression of P-gp. Notably, the dual drug-loaded NPs exhibited tumor-targeting ability, prolonged tumor retention time and effective anti-tumor effect without obvious toxicity to normal tissues in vivo. Taken together, our research provides a viable approach to overcome MDR in breast cancer., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Kidney cancer usually shows no symptoms until the tumor is relatively large, and current drugs fail to stop the tumor recurrence. The transcriptional factor Runt-related transcription factor 3 (RUNX3) has been reported to function as a tumor suppressor in many types of cancers., Methods: Kidney cancer and adjacent normal tissues were collected from 12 patients to test the expression of RUNX3 by real-time quantitative PCR, immunoblotting, and immunohistochemistry. Promoter methylation status of RUNX3 was determined using methylation analysis from 103 patient samples. Kidney cancer cell lines and xenograft mouse model were used to investigate the promoter methylation and cancer progression through inhibitor treatment and loss/gain-of-function experiments., Results: RUNX3 was significantly downregulated in kidney cancer tissues and cells, which could be elevated by higher methylation status at its promoter region. RUNX3 promoter methylation was positively correlated with poor prognosis of kidney cancer. RUNX3 loss-of-function promoted the cell proliferation, migration, and invasion of kidney cancer cells, in contrast, RUNX3 overexpression inhibited the cancer cell progression. This study provides the first instance of the effect of RUNX3 expression and its promoter methylation status on kidney cancer., Conclusion: Targeting RUNX3 pathway and its promoter methylation are potential therapeutic strategies to treat kidney cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This report aims to explore how LINC00691 regulates the proliferation and invasion of gastric cancer (GC). Clinical tissue and serum samples, as well as specimens in the Cancer Genome Atlas (TCGA) database, were used to analyse the expression of LINC00691 in GC. Our data indicated that the expression of LINC00691 in GC was significantly higher than that in healthy controls and was associated with clinicopathological features and survival time. In the GC cell lines MKN-45 and HGC-27, the knockdown of LINC00691 suppressed proliferation, colony formation, migration, and invasion. Bioinformatics analysis and luciferase reporter gene experiments showed that LINC00691 activated Lin28 transcription. Western blot analysis indicated that the knockdown of LINC00691 contributed to the decreased expression of p-JAK2 and p-STAT3 in GC cells. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway inhibitor ruxolitinib effectively suppressed the effects of LINC00691. In addition, both LINC00691 and Lin28 promoted the expression of epidermal growth factor (EGF). Therefore, our study clarified that LINC00691 is highly expressed in GC and is a potential biomarker for GC diagnosis and prognosis. LINC00691 promotes the proliferation and invasion of GC cells by activating Lin28 transcription and facilitating EGF expression through the JAK/STAT signalling pathway, which provides new ideas for targeted therapy of GC., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Three-dimensionally ordered macroporous (3DOM) Co 3 O 4 -CeO 2 catalysts with controllable Co/Ce molar ratios synthesized by colloidal crystal template method were developed to catalyze the NO x -assisted soot oxidation for the first time, and the obtained 3DOM Co 3 O 4 -CeO 2 catalysts exhibited highly enhanced soot oxidation activity. Detailed characterizations of 3DOM Co 3 O 4 -CeO 2 catalysts revealed that the highly enhanced soot oxidation activity was originated from the synergistic promoting effect by combining the macroporous effect resulted from the unique 3DOM framework, the chemical nature associated with more Co 3+ reactive sites, the surface enrichment of Ce species and the improved redox properties. Meanwhile, the high NO x storage and oxidation capacity resulted from the integrated respective merits of Co 3 O 4 and CeO 2 also accounted for the enhanced soot oxidation activity via NO x -assisted mechanism. Furthermore, the 3DOM Co 3 O 4 -CeO 2 catalysts demonstrated strong stability because of the surface enrichment of Ce species improving the thermal stability and the robust 3DOM framework inhibiting the structural collapse, showing their potential applications under practical conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The present study assessed the effect of short-term exposure to PM 2.5 of daily outpatient visits for respiratory diseases. Electronic records of daily outpatient visits were collected from two large general hospitals in Lanzhou, China from 01 January 2007 to 31 December 2016. Daily air pollution data from the Lanzhou Environmental Monitoring Station and daily meteorological data from the Lanzhou Meteorological Bureau were collected in the same period. A distributed lag non-linear model, based on a gender and age groups, was applied to analyse the exposure-response relationship between the air pollutants, and the daily outpatient visits for respiratory diseases. From 2007 to 2016, the PM 2.5 concentrations were associated with an increase in the daily outpatient visits for respiratory diseases in Lanzhou. In addition, a lag effect was observed and this effect was the strongest on day 1. For every 10 μg/m 3 increase in the PM 2.5 concentration, the daily outpatient visits for respiratory diseases increased by 0.53% (95% CI: 0.22%-0.84%). People aged 18 years or younger were most sensitive to PM 2.5 , and the influence of PM 2.5 was more significant for females than for males. The cumulative effect of the PM 2.5 concentration for the number of outpatient visits was greater than its daily effect, and the cumulative effect peaked on day 12. From day 0 to day 14, every 10-μg/m 3 increase in the PM 2.5 concentration had a statistically significant cumulative effect on the outpatient visits for respiratory diseases among individuals aged 18 years or younger (p < 0.05), reaching a maximum value on day 14 (PM 2.5 : RR = 1.0213, 95% CI: 1.0128-1.0299)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Electrospinning, as a nanotechnology, is able to produce polymeric fibers materials with nanoscale structure which are also named electrospun fibers material (EFM). These EFMs can be used in many biomedical applications such as wound dressing, tissue engineering, and medical textile materials. Over the last decades, electrospun nanofibers also have been applied to drug delivery such as orodispersible film, solid dispersion and various controlled release dosage forms due to many properties such as high surface to volume ratio, high porous, ease of fabrication and adaptability and so on. This review focuses on the recent advances in biomedical application of EFM, controlled drug release from EFM and devices for producing sophisticated EFM. The processing parameters which influence the physicochemical properties of the resulting EFM are also summarized as well as scaling up techniques for mass production of EFM., (Copyright © 2018. Published by Elsevier B.V.)

Recently, increasing regulatory and public attention has been paid to the exposure risks of antibiotics due to their occurrence and antibiotic resistance worldwide. However, limited information on antibiotic levels in general populations is available. Forty antibiotics, including 9 sulfonamides, 5 fluoroquinolones, 4 macrolides, 4 tetracyclines, 3 chloramphenicols, 12 β-lactams and 3 others, were analyzed in 107 serum samples of normal adults collected from a hospital in Dalian, North China, between 2015 and 2016 using solid-phase extraction (SPE) coupled with HPLC-MS/MS. The results clearly showed that antibiotics were present in the serum of these adults. Specifically, 28 antibiotics were detected in the samples, with detection frequencies ranging from 0.9% to 17.8%. The total antibiotic concentrations in 26.2% of the serum samples were between the LOD and 20.0ng/mL. Importantly, the maximum concentrations of 5 antibiotics (trimethoprim, ciprofloxacin, cefaclor, lincomycin and erythromycin) were above 1000ng/mL in 3.7% of the samples. Furthermore, the detection frequencies of 5 veterinary antibiotics, 7 human antibiotics and 16 human/veterinary antibiotics in the serum samples were 23.4%, 17.8% and 29.0%, respectively. Significant differences of the veterinary antibiotics between female and male adults and of the sulfonamides between different BMI (body mass index) groups were observed (p<0.05). The concentrations of sulfonamides in elderly individuals were significantly higher (p<0.05) than those in young people. Finally, our results showed that almost all of the adults had no health risks related to exposure to antibiotics at such levels despite the high effect ratio (ER=1.74) for azithromycin in one sample. This study is the first to report the current status of antibiotics in human blood, which can help in better understanding the long-term effects of antibiotics on general populations and in identifying susceptible populations that are at high risk to antibiotic exposure., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this study, novel paclitaxel (PTX) loaded hybrid liposomes for oral PTX delivery were prepared through incorporating PTX loaded polyion complex micelles comprised of positively charged Pluronic F127-Polyethylenimine (PF127-PEI) copolymer and negatively charged sodium cholate (CA) into liposomes consisted of phospholipid molecules. According to the results, this kind of PTX-loaded hybrid liposomes showed improved PTX encapsulation efficiency, sustained PTX release, and enhanced PTX absorption in intestine. The mechanism for enhancing absorption was demonstrated in connection with inhibition of the efflux mediated by multidrug resistance protein, intestinal P-gp. In pharmacokinetic study, the absolute oral bioavailability of PTX loaded in hybrid liposomes had reached to 37.91%. All of these results demonstrated that the application of this novel PTX loaded hybrid liposomes is a strategy with great potential for highly effective oral PTX delivery., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A novel nanocarrier of heparin (Hep) modified graphene oxide (GO) was fabricated via a linker (adipic dihydrazide) and used as a pH-sensitive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for anti-tumor therapy. The finally obtained nanocarrier was GO-ADH-Hep with better stability, blood compatibility and biocompatibility confirmed by the hemolytic test and in vitro cytotoxicity study. Its safety issue was greatly improved via Hep modification. The amount of DOX loaded onto GO-ADH-Hep was significantly high and dependent on pH value. The release rate of DOX from GO-ADH-Hep/DOX was pH-sensitive and much-slower than that of free DOX solution suggesting the sustained drug-release capacity of this prepared nanocomplexes. In addition, the results of cytotoxicity study illustrated that this fabricated nanocomplexes displayed effective cytotoxicity to MCF-7 and HepG2 cells. What's more, the results of the in vivo pharmacokinetic study was also indicated that the GO-ADH-Hep/DOX nanocomplexes could significantly prolong the retention time of DOX in vivo and this was consistent with the in vitro drug release performance. And finally, according to the biodistribution study, DOX delivered by GO-ADH-Hep could reduce cardiotoxicity deriving from DOX solution and also decrease the pulmonary toxicity deriving from unmodified GO. Based on the in vitro and in vivo investigations, the fabricated GO-ADH-Hep could be a promising candidate as an ideal nano-carrier for drug delivery and anti-cancer therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The design of internal stimuli-responsive nanocarriers has been extensively used for delivery of various active compounds including drugs, peptides and genes. These nanosystems are not only designed for improved solubility, enhanced bioavailability, and prolonged blood circulation time, furthermore, they can be tailored chemically to achieve selective drug release at the desired sites of action, which can enable them to bypass physiological or pathological obstacles and achieve enhanced therapeutic efficacy. This review presents current functional moieties responsive to a variety of internal stimuli, including pH, redox, enzyme, temperature. Their design strategies and biomedical applications are also highlighted in detail. It is expected that this review can provide inspiration and impetus for exploiting more promising internal stimuli-responsive nano-systems for drug delivery., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Currently, targeted nanoparticles (NPs) are rapidly being developed to overcome various bottlenecks of antitumor agents, such as poor solubility in aqueous solution, poor pharmacokinetics, a lack of selectivity and undesirable side effects in healthy tissues. In recent years, chitosan, a cationic polysaccharide, has been widely explored for the targeted delivery of antitumor agents due to its unique physicochemical and biological properties, such as biocompatibility, biodegradability, mucoadhesive feature, absorption enhancement and active functional groups for chemical modifications. This article reviews the recent developments in various target-specific nanoparticles based on chitosan and its derivatives, including passive, active and stimuli-sensitive targeting strategies. In addition, the target mechanisms and the key efficacy factors are illuminated., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Hydrophobically-modified polymers based on chondroitin sulfate with different degree of substitution (DS) of deoxycholic acid (DOCA) were developed for docetaxel delivery. Chondroitin sulfate-deoxycholic acid (CSAD) bioconjugates were synthesized via the linker of adipic dihydrazide by amide bond. They were characterized with spherical shape, mean diameter of around 165.2nm and negative zeta potential (-14.87 to -20.53mV). An increase of DOCA DS reduced size of nanoparticles, while increasing drug loading efficiency. Drug release in vitro showed a triphasic sustained pattern and higher accumulative drug release percentage was observed with increased DS of DOCA on polymer. Self-assemblies with higher DS also had enhanced internalization of nanoparticles and stronger cytotoxicity at the cellular level. The self-assemble nanoparticles demonstrate to be excellent targeting drug delivery systems and the desired therapeutics can be achieved via the alteration of DS., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A novel amphiphilic and pH-responsive copolymer, pluronie P123-poly(β-amino ester) (P123-PAE), was firstly designed and synthesized using a Michael-type step polymerization. Nano-sized polymeric micelles based on P123-PAE block copolymer were prepared by self-assembly. Curcumin (Cur), a potential cancer therapy drug, was efficiently encapsulated into the P123-PAE micelles to enhance anticancer efficacy. The obtained Cur loaded P123-PAE micelles (Cur-P123-PAE) presented a spherical shape and high drug loading (18.4%). Interestingly, when the media pH decreased from 7.4 to 5.5, the particle size of the micelles shrank from 152.5nm to 122.1nm due to the protonation of PAE blocks, and the zeta potential of the P123-PAE micelles changed from weakly positive (1.5mV) to highly positive (9.0mV) over a pH range from 7.4 to 5.5. In vitro drug release studies demonstrated that the release rate of Cur was markedly influenced by pH. In vitro cytotoxicity tests showed that all the blank micelles were non-toxic. Cur-P123-PAE exhibited similar antitumor effect against MCF-7 and HepG2 cells compared to solubilized Cur solution. Using Coumarin-6 as a fluorescence probe, it was observed that Cur-P123-PAE micelles experienced longer circulation followed by accumulation at tumor tissues with stronger fluorescence intensity. The results of pharmacokinetics studies showed that the P123-PAE micelles could significantly prolong the retention time of Cur in vivo., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR-MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0 nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP-TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP-TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR-MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75 mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR-MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG-PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Graphene, a rapidly rising star, has gained extensive research interests lately due to its excellent properties--such as the exceptional optical, electrical, thermal and mechanical features--which are superior to other materials, so it is called "two-dimensional magical materials". This article presents diverse types and various properties of graphene-based materials, and the current methods for the surface modifications of the graphene-based materials are briefly described. In addition, the in vivo and in vitro cytotoxicity of graphene-based materials are comprehensively discussed. What's more, a summary of its biomedical applications such as drug/gene delivery, photothermal therapy, photodynamic therapy and multimodality therapy is also offered. Finally, an outlook of the graphene-based materials and the challenges in this field are briefly discussed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The neural differentiation of embryonic stem cells (ESCs) is of great significance for understanding of the mechanism of diseases. Histone post-translational modifications (HPTMs) play a key role in the regulation of ESCs differentiation. Here, we combined the stable isotope chemical derivatization with nano-HPLC-mass spectrometry (MS) for comprehensive analysis and quantification of histone post-translational modifications (HPTMs) in mouse embryonic stem cells (mESCs) and neural progenitor cells (mNPCs) that was derived from ESCs. We identified 85 core HPTM sites in ESCs and 78HPTM sites in NPCs including some novel lysine modifications. Our quantitative analysis results further revealed the changes of HPTMs from ESCs to NPCs and suggested effect of combinational HPTMs in the differentiation. This study demonstrates that HPLC-MS-based quantitative proteomics has a considerable advantage on quantification of combinational PTMs and expands our understanding of HPTMs in the differentiation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Based on the advantages of adhesion preparations and the application status of microspheres (MSs) in mucous delivery, this paper primarily reviews the bioadhesive MSs via transmucosal administration routes, including the mucosa in alimentary tract and other lumens. Particularly, the detailed researches about of celladhesive MSs and some new-style bioadhesive MSs are mentioned. Furthermore, this review attempts to reveal the advances of bioadhesive MSs as cell-selective bioadhesion systems and the stimuli-responsive MSs as location-specific drug delivery systems. Although these MSs show powerful strength, some far-sighted ideas should be brought on agendas. In the future, mechanisms should be put under tight scrutiny and more attention should be focused on the excellent bioadhesive materials and the 'second generation mucoadhesives'. Meaningful clinical applications of these novel MSs are also of current concerns and need more detailed researches., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Nanogel has attracted considerable attention as one of the most versatile drug delivery systems especially for site-specific and/or time-controlled delivery of bioactive agents owing to their combining features of hydrogel and nanoparticle. Physically synthesized nanogels can offer a platform to encapsulate various types of bioactive compounds, particularly hydrophobic drugs and biomacromolecules, but they have poor mechanical stability, whereas nanogels prepared by chemical cross-link have a wider application and larger flexibility. As an ideal drug-delivery carrier, nanogel has excellent drug loading capacity, high stability, biologic consistence and response to a wide variety of environmental stimuli. Nowadays, targeting and response especially multi-response of the nanogel system for drug delivery have become an issue in research. And the application study of nanogels mainly focuses on antitumor agents and proteins. This review focuses on the formation of nanogels (physical and chemical cross-linking) and their release behavior. Recent application of nanogels is also discussed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

To contribute toward effective exploitation and utilization of spent mushroom compost (SMC) of Ganoderma lucidum (SMC-G), a water-soluble polysaccharide of GPS was extracted, and then two fractions (GPS-1 and GPS-2) were purified from SMC-G. The optimum conditions for GPS extraction were optimized by the central composite design (CCD) and the GPS yield reached 3.84% at a ratio of water to material of 34.5, a precipitation time of 19.82h, and pH of 7.88. Characteristic analysis showed that GPS-1 and GPS-2 were heteropolysaccharides, and had glycosidic structures (OH, CH, CO and COC). Both GPS and its fractions showed potential antioxidant activities by scavenging hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and increasing the reducing power in vitro; and by improving the CAT activities, and lowing the LPO and MDA contents in vivo, respectively. The results provided a reference for the exploitation of SMC-G which would be significant to sustainable development of industry and agriculture, environmental protection and full utilization of resources., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Curcumin, a natural polyphenol compound, has been widely reported for diverse pharmacological effects and already been investigated for eye diseases. However, the water-insolubility of curcumin and the inherent penetration barriers in cornea make it difficult for curcumin to enter eye. This work aimed to develop ion-sensitive curcumin-loaded Pluronic P123 (P123)/D-a-tocopheryl polyethylene glycolsuccinate (TPGS) mixed micelle in situ gels (CUR-MM-ISGs) to prolong ocular retention time and improve cornea permeability. Central composite design-response surface methodology was applied for the optimization of curcumin-loaded P123/TPGS mixed micelles (CUR-MMs). Characterization tests showed that CUR-MMs were in spherical shape with small size and low critical micelle concentration. After dispersing the micelles in gellan gum solution (0.2%, w/w) at the ratio of 3:1 and 1:1 (v/v), respectively, CUR-MM-ISGs were formed and presented transparent appearance. Sustained release profile was obtained in vitro for both CUR-MM-ISGs (3:1 or 1:1, v/v). The irritation test proved that CUR-MM-ISGs as ophthalmic formulations were gentle and biocompatible towards ocular tissues. In addition, the ex vivo corneal penetration study indicated that the cumulative drug permeation amount of CUR-MM-ISGs (3:1, v/v) was respectively 1.16-fold and 1.32-fold higher than CUR-MM-ISGs (1:1, v/v) and curcumin solution. It can be concluded from these results that the developed ion-sensitive mixed micelle in situ gel system is a potential ophthalmic delivery carrier for curcumin as a poorly soluble drug., (Copyright © 2015 Elsevier B.V. All rights reserved.)