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Recently, coral-associated microorganisms have attracted widespread attention, and most of these studies have focused on stony and soft corals. However, our knowledge of the diversity and bioactivity of microorganisms in gorgonian corals is still limited. In this study, the biodiversity of microbes in two gorgonian corals (Leptogorgia rigida and Menella kanisa) from the South China Sea was investigated by combining traditional culture method with molecular biology technique (bacterial 16S or fungal internal transcribed spacer (ITS) rRNA gene sequences). A total of 216 bacterial and 98 fungal isolates were obtained using 4 different isolation media. These isolates were identified and belonged to 31 bacterial and 12 fungal species, suggesting an unexpectedly diverse microbial community harbored in the South China Sea gorgonian corals L. rigida and M. kanisa. Furthermore, 56% of the tested microbial isolates displayed various antifouling activities against four biofouling organisms (including two microfouling bacteria Micrococcus luteus and Shewanella onedensis, and two macrofouling organisms Bugula neritina and Balanus amphitrite). Among the microbial isolates with antifouling activity, Bacillus firmus SCAU-038 and Streptomyces parvulus SCAU-062 displayed moderate or strong antifouling activity against all tested biofouling organisms. This is the first study on the biodiversity and antifouling activity of microorganisms associated with gorgonians L. rigida and M. kanisa from the South China Sea. These results contribute to the further understanding of microorganisms associated with gorgonian corals and provide potential resources for new natural antifouling agents., 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.)

Purpose: To assess whether diffusion-weighted imaging (DWI) with Compressed SENSE (CS) and deep learning (DL-CS-DWI) can improve image quality and lesion detection in patients at risk for hepatocellular carcinoma (HCC)., Methods: This single-center prospective study enrolled consecutive at-risk participants who underwent 3.0 T gadoxetate disodium-enhanced MRI. Conventional DWI was acquired using parallel imaging (PI) with SENSE (PI-DWI). In CS-DWI and DL-CS-DWI, CS but not PI with SENSE was used to accelerate the scan with 2.5 as the acceleration factor. Qualitative and quantitative image quality were independently assessed by two masked reviewers, and were compared using the Wilcoxon signed-rank test. The detection rates of clinically-relevant (LR-4/5/M based on the Liver Imaging Reporting and Data System v2018) liver lesions for each DWI sequence were independently evaluated by another two masked reviewers against their consensus assessments based on all available non-DWI sequences, and were compared by the McNemar test., Results: 67 participants (median age, 58.0 years; 56 males) with 197 clinically-relevant liver lesions were enrolled. Among the three DWI sequences, DL-CS-DWI showed the best qualitative and quantitative image qualities (p range, <0.001-0.039). For clinically-relevant liver lesions, the detection rates (91.4%-93.4%) of DL-CS-DWI showed no difference with CS-DWI (87.3%-89.8%, p = 0.230-0.231) but were superior to PI-DWI (82.7%-85.8%, p = 0.015-0.025). For lesions located in the hepatic dome, DL-CS-DWI demonstrated the highest detection rates (94.8%-97.4% vs 76.9%-79.5% vs 64.1%-69.2%, p = 0.002-0.045) among the three DWI sequences., Conclusion: In patients at high-risk for HCC, DL-CS-DWI improved image quality and detection for clinically-relevant liver lesions, especially for the hepatic dome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Intravascular lithotripsy is effective and safe for managing coronary calcification; however, available devices are limited, and complex lesions have been excluded in previous studies. This study aimed to investigate the effectiveness and safety of a novel intravascular lithotripsy system for severe calcification in a population with complex lesions., Methods: CALCI-CRACK (treatment of severe calcified coronary lesions with a novel intracoronary shock wave lithotripsy system) (ChiCTR2100052058) was a prospective, single-arm, multicentre study. The primary end point was the procedural success rate. Major safety end points included major adverse cardiovascular events (MACE) and target lesion failure (TLF) at 30 days and 6 months, and severe angiographic complications. Calcification morphology was assessed in the optical coherence tomography (OCT) subgroup., Results: In total, 242 patients from 15 high-volume Chinese centres were enrolled, including 26.45% of patients with true bifurcation lesions, 3.31% with severely tortuous vessels, and 2.48% with chronic total occlusion, respectively. The procedural success rate was 95.04% (95% confidence interval 91.50%-97.41%), exceeding the prespecified performance goal of 83.4% (P < 0.001). The 30-day and 6-month MACE rates were 4.13% and 4.55%, respectively. TLF rates at those time points were 1.24% and 1.65%, respectively. Severe angiographic complications occurred in 0.42% of patients. In the OCT subgroup (n = 93), 93.55% of calcified lesions were fractured, and minimal lumen area increased from 1.55 ± 0.55 mm 2 to 4.91 ± 1.22 mm 2 after stent implantation, with acute gain rate of 245 ± 102%., Conclusions: The novel intravascular lithotripsy system is effective and safe for managing severely calcified coronary lesions in a cohort that included true bifurcation lesions, severely tortuous vessels, and chronic total occlusion., Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100052058., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Sepsis is a potentially fatal condition arising from an abnormal immune response to an infection, which can result in organ failure and even death. To explore the mechanism underlying the dysregulated immune response during sepsis and identify potential therapeutic targets, single-cell RNA sequencing (scRNA-seq) and immune repertoire analysis were conducted to depict the cellular landscape of peripheral blood cells in septic mice. We observed significant alterations in the number and proportion of peripheral blood cell populations driven by sepsis. By combining single-cell gene expression profiles and B cell receptor (BCR) repertoire analysis, we discerned that infection inflicted serious damage on the antigen presentation ability of B cells and the diversity of BCR in a short time. In addition, we found that the cecal ligation and puncture procedure in mice inhibited the communication signals of CD4 + and CD8 + T cells and decreased the interactions between B cells and other cells. Our study provides detailed insights into the dynamic changes in the biological characteristics of peripheral blood cells driven by sepsis and provides important advances in our understanding of immune disorders during sepsis., 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. Acknowledgments We gratefully acknowledge the participation of Shanghai OE Biotech Co., Ltd for the support of construction of single cell sequencing Library, and thanks Mr. Zhengshan Chen (Laboratory of Advanced Biotechnology) for the support of data analysis and visualization. This study was supported by grants from the National Natural Science Foundation of China (82170229)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Prokaryotes play crucial roles in hydrothermal vent ecosystems, yet their interactions with heavy metals are not well understood. This study explored the diversity of prokaryotic communities and their correlations with heavy metals and nutrient elements in hydrothermal sediments from Okinawa Trough. A total of 117 bacterial genera in 26 bacterial phyla and 10 archaeal classes in 3 archaeal phyla were identified, including dominant prokaryotic phyla Planctomycetes, Acidobacteria, Verrucomicrobia, and Euryarchaeota. Furthermore, Fe (39.61 mg/g), Mn (2.84 mg/g) and Ba (0.36 mg/g) were found to be the most abundant heavy metals in the Okinawa hydrothermal sediments. Notably, the concentrations of Zn, Ba, Mn, total organic carbon, and total nitrogen significantly increased, whereas the total sulfur concentration distinctively decreased at sampling sites farther from hydrothermal vents. These changes corresponded with reductions in prokaryotic abundance and diversity. Most heavy metals, including Mn, Fe, Co, Cu and As, presented significant positive correlations with a number of prokaryotic genera in the nearby sediment samples. In contrast, both positive and negative correlations with prokaryotes were observed in remote sediment. The keystone taxa include Magnetospirillum, GOUTA19, Lysobacter, Kaistobacter, Treponema, and Clostridium were detected through prokaryote interspecies interactions. The functional predictions revealed significant genes involved in carbon fixation, nitrogen/sulfur cycling, heat shock protein, and metal resistance pathways. Structural equation modeling confirmed that metal and nutrient elements directly influence the composition of prokaryotic communities, which in turn affects the relative abundance of functional genes., 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.)

Polysaccharides from diverse origins exhibit notable bioactivities, particularly their capacity to exert antitumor and immune-enhancing effects. Concurrently, ferroptosis emerges as a distinctive form of regulated cell death characterized by iron-dependent lipid peroxidation, potentially influencing the demise of specific tumor cells and organismal homeostasis. Recent scholarly attention has increasingly focused on utilizing polysaccharides to modulate tumor cell ferroptosis and manipulate cellular immune responses. This article provides an in-depth analysis of contemporary research concerning using polysaccharides to augment antitumor immunity and combat malignancies. Central to our discourse is examining the pivotal role of polysaccharides in mediating ferroptosis, bolstering immune surveillance, and elucidating the interplay between polysaccharides and antitumor immunity. Furthermore, a comprehensive synthesis of the multifaceted roles of polysaccharides in antitumor and immunomodulatory contexts is provided. Recent advances in understanding how polysaccharides enhance immune function by inducing ferroptosis cell death are explained. Lastly, unresolved inquiries are outlined, and potential avenues for future research are proposed, focusing on the translational applications of polysaccharides in antitumor immunotherapy., 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.)

Ulvan, a sulfated polysaccharide extracted from Ulva spp., has garnered significant attention in the food and pharmaceutical industries due to its potential health benefits. These include immunomodulation, antiviral, anti-inflammatory, anti-hyperlipidemic, and anti-cancer effects. Nonetheless, practical applications in these fields remain limited due to an incomplete understanding of its gelation mechanisms. Additionally, the underlying mechanisms of its gelation have not been completely understood and thoroughly reviewed. The primary objective is to provide current insights into ulvan's gelling mechanisms and potential health impacts. This review also delves into the existing applications of ulvan polysaccharides. By unraveling these aspects, the information provided in this work is expected to deepen our understanding of ulvan's gelation mechanisms and its prospective role in enhancing health, holding promise for advancements in the fields of food science and disease prevention. This work's theoretical insights contribute significantly to a deeper understanding of these aspects, which holds paramount importance in unleashing the full potential of ulvan and elevating its scientific significance., 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.)

Purpose: To investigate longitudinal thoracic aorta injury using 3-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) parameters and to evaluate their value for predicting the subsequent main adverse cardiovascular events (MACEs) in breast cancer patients receiving anthracyclines., Methods: Between July 2020 and July 2021, eighty-eight female participants with breast cancer scheduled to receive anthracyclines with or without trastuzumab prospectively enrolled. Each subjects underwent 4D flow MRI at baseline, 3 and 6 months in relation to baseline. The diameter, peak velocity (Vpeak), wall shear stress (WSS), pulse wave velocity (PWV), energy loss (EL) and pressure gradient (PG) of thoracic aorta were measured. The association between these parameters and subsequent MACEs was performed by Cox proportional hazard models., Results: Ten participants had subsequently MACEs. The V peak and PG gradually decreased and the WSS, PWV and EL progressively increased at 3 and 6 months compared with baseline. Adjusted multivariable analysis showed that the WSS of the proximal, mid- and distal ascending aorta [HR, 1.314 (95% confidence interval (CI): 1.003, 1.898)], [HR, 1.320 (95% CI: 1.002, 1.801)] and [HR, 1.322 (95% CI: 1.001, 1.805)] and PWV of ascending aorta [HR, 2.223 (95% CI: 1.010, 4.653)] at 3 months were associated with subsequent MACEs. Combined WSS and PWV of ascending aorta at 3 months yielded the highest AUC (0.912) for predicting subsequent MACEs., Conclusion: Combined WSS and PWV of ascending aorta at 3 months is helpful for predicting the subsequent MACEs in breast cancer patients treated by anthracyclines., Competing Interests: Declaration of competing interest One of our authors (Xiaoyong Zhang) is an employee of Philips Healthcare. This author only provided technical support and did not participant in the analysis and/or control of the study data., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lysimachia capillipes Hemsl., a traditional Chinese medicine (TCM), is commonly prescribed for its anti-inflammatory and anti-tumor properties. Pharmacological studies have demonstrated that Lysimachia capillipes Hemsl. saponins (LCS) are the primary bioactive component. However, its mechanism for treating colorectal cancer (CRC) is still unknown. Increasing evidence suggests a close relationship between CRC, intestinal flora, and host metabolism. Thus, this study aims to investigate the mechanism of LCS amelioration of CRC from the perspective of the gut microbiome and metabolome. As a result, seven gut microbiotas and fourteen plasma metabolites were significantly altered between the control and model groups. Among them, one gut microbiota genera (Monoglobus) and six metabolites (Ureidopropionic acid, Cytosine, L-Proline, 3-hydroxyanthranilic acid, Cyclic AMP and Suberic acid) showed the most pronounced callback trend after LCS administration. Subsequently, the correlation analysis revealed significant associations between 68 pairs of associated metabolites and gut microbes, with 13 pairs of strongly associated metabolites regulated by the LCS. Taken together, these findings indicate that the amelioration of CRC by LCS is connected to the regulation of intestinal flora and the recasting of metabolic abnormalities. These insights highlight the potential of LCS as a candidate drug for the treatment of CRC., Competing Interests: Declaration of competing interest The authors have declared that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this article, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To investigate the feasibility of T1rho-weighted imaging in differentiating malignant from benign breast lesions and to explore the additional value of T1rho to conventional MRI., Materials and Methods: We prospectively enrolled consecutive women with breast lesions who underwent preoperative T1rho-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) between November 2021 and July 2023. The T1rho, apparent diffusion coefficient (ADC), and semi-quantitative parameters from DCE-MRI were obtained and compared between benign and malignant groups. The diagnostic performance was analyzed and compared using receiver operating characteristic (ROC) curves and the Delong Test., Results: This study included 113 patients (74 malignant and 39 benign lesions). The mean T1rho value in the benign group (92.61 ± 22.10 ms) was significantly higher than that in the malignant group (72.18 ± 16.37 ms) (P < 0.001). The ADC value and time to peak (TTP) value in the malignant group (1.13 ± 0.45 and 269.06 ± 106.01, respectively) were lower than those in the benign group (1.57 ± 0.45 and 388.30 ± 81.13, respectively) (all P < 0.001). T1rho combined with ADC and TTP showed good diagnostic performance with an area under the curve (AUC) of 0.896, a sensitivity of 81.0%, and a specificity of 87.1%. The specificity and sensitivity of the combination of T1rho, ADC, and TTP were significantly higher than those of the combination of ADC and TTP (87.1% vs. 84.6%, P < 0.005; 81.0% vs. 77.0%, P < 0.001)., Conclusion: T1rho-weighted imaging was a feasible MRI sequence for differentiating malignant from benign breast lesions. The combination of T1rho, ADC and TTP could achieve a favorable diagnostic performance with improved specificity and sensitivity, T1rho could serve as a supplementary approach to conventional MRI., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Marine fungal exopolysaccharides play a crucial role in immunoregulation. In this investigation, a novel polysaccharide was extracted from the culture medium of the marine fungus Aspergillus medius SCAU-236. Compositional analysis revealed a structure composed of glucose units with (1,4)-α-D-Glcp, (1,3,4)-β-D-Glcp, and (1,4,6)-α-D-Glcp, along with side chains of 1-α-D-Glcp linked to carbon 6 of (1,4,6)-α-D-Glcp and carbon 3 of (1,3,4)-β-D-Glcp. Functional evaluations on RAW264.7 macrophage cells demonstrated Aspergillus medius polysaccharide (ASMP)'s effects on cell proliferation, nitric oxide levels, and the secretion of TNF-α, IL-6, and IL-1β cytokines. Additionally, metabolomics indicated ASMP's potential to modulate macrophage immune function by impacting key regulatory molecules, including COX-2, iNOS, Nrf2, SLC7A11, GPX4, and ACSL4. The Nrf2/SLC7A11/GPX4 axis and ACSL4 were suggested to be involved in ASMP-induced ferroptosis, leading to increased reactive oxygen species (ROS) levels and lipid peroxidation. These findings propose a unique mechanism by which ASMP exerts immunomodulatory effects through ferroptosis induction, contributing to the understanding of marine-derived compounds in immunomodulation research., 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.)

Previous studies have reported the correlations between bacterial communities and coral bleaching, but the knowledge of fungal roles in coral bleaching is still limited. In this study, the taxonomic and functional diversities of fungi in unbleached, partly bleached and bleached stony coral Acropora intermedia were investigated through the ITS-rRNA gene next-generation sequencing. An unexpected diversity of successfully classified fungi (a total of 167 fungal genera) was revealed in this study, and the partly bleached coral samples gained the highest fungal diversity, followed by bleached and unbleached coral samples. Among these fungi, 122 genera (nearly 73.2%) were rarely found in corals in previous studies, such as Calostoma and Morchella, which gave us a more comprehensive understanding of coral-associated fungi. Positively correlated fungal genera (Calostoma, Corticium, Derxomyces, Fusicolla, Penicillium and Vishniacozyma) and negative correlated fungal genera (Blastobotrys, Exophiala and Dacryopinax) with the coral bleaching were both detected. It was found that a series of fungal genera, dominant by Apiotrichum, a source of opportunistic infections, was significantly enriched; while another fungal group majoring in Fusicolla, a probiotic fungus, was distinctly depressed in the bleached coral. It was also noteworthy that the abundance of pathogenic fungi, including Fusarium, Didymella and Trichosporon showed a rising trend; while the saprotrophic fungi, including Tricladium, Botryotrichum and Scleropezicula demostrated a declining trend as the bleaching deteriorating. The rising of pathogenic fungi and the declining of saprotrophic fungi revealed the basic rules of fungal community transitions in the coral bleaching, but the mechanism of coral-associated fungal interactions still lacks further investigation. Overall, this is an investigation focused on the differences of fungal communities at taxonomic and functional levels in stony coral A. intermedia under different bleaching statuses, which provides a better comprehension of the correlations between fungal communities and the coral bleaching., 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.)

With the increasing influx of microplastics (MPs) into the environment, their potential toxicity represents an increasing threat to human health. However, there is a lack of relevant research surrounding the biological toxicity associated with pre-exposure to MPs under pathological conditions. To fill this gap, we established a mouse model of fulminant hepatic failure after 14 days of pre-exposure to polystyrene (PS) MPs and investigated its biological response process under combined stimulation with lipopolysaccharide (LPS)/d-galactosamine (d-GalN) and PS-MPs. The results indicated that the stress response from exposure to PS-MPs exacerbated the death induced by LPS/d-GalN and reinforced the potential of liver damage in mice. The dominant roles of inflammation promotion, reactive oxygen species (ROS), and neutrophil extracellular traps in this process were confirmed by cellular reactive oxygen species assays and experiments on oxidative stress and inflammatory responses in the liver. Transcriptomic analysis revealed that PS-MPs exacerbated the expression levels of neutrophil extracellular traps in mice treated with LPS/d-GalN, and weakened the expression of genes involved in pathways related to peroxisome, taurine, and hypotaurine metabolism, which was further validated by reverse-transcription quantitative polymerase chain reaction. This study addresses the knowledge gap regarding the adverse effects caused by a pathological state upon exposure to MPs and provides a theoretical reference for further assessment of the underlying health risks of MPs., 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.)

Background Aims: Sufficient doses of viable CD34+ (vCD34) hematopoietic progenitor cells (HPCs) are crucial for engraftment. Additional-day apheresis collections can compensate for potential loss during cryopreservation but incur high cost and additional risk. To aid predicting such losses for clinical decision support, we developed a machine-learning model using variables obtainable on the day of collection., Methods: In total, 370 consecutive autologous HPCs, apheresis-collected since 2014 at the Children's Hospital of Philadelphia, were retrospectively reviewed. Flow cytometry was used to assess vCD34% on fresh products and thawed quality control vials. The ratio of vCD34% thawed to fresh, which we call "post-thaw index," was used as an outcome measure, with a "poor" post-thaw index defined as <70%. HPC CD45 normalized mean fluorescence intensity (MFI) was calculated by dividing CD45 MFI of HPCs to the CD45 MFI of lymphocytes in the same sample. We trained XGBoost, k-nearest neighbor and random forest models for the prediction and calibrated the best model to minimize falsely-reassuring predictions., Results: In total, 63 of 370 (17%) products had a poor post-thaw index. The best model was XGBoost, with an area under the receiver operator curve of 0.83 evaluated on an independent test data set. The most important predictor for a poor post-thaw index was the HPC CD45 normalized MFI. Transplants after 2015, based on the lower of the two vCD34% values, showed faster engraftment than older transplants, which were based on fresh vCD34% only (average 10.6 vs 11.7 days, P = 0.0006)., Conclusions: Transplants taking into account post-thaw vCD34% improved engraftment time in our patients; however, it came at the cost of unnecessary multi-day collections. The results from applying our predictive algorithm retrospectively to our data suggest that more than one-third of additional-day collections could have been avoided. Our investigation also identified CD45 nMFI as a novel marker for assessing HPC health post-thaw., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Until now, relatively little is known about marine-derived fungal polysaccharides and their activities. Exopolysaccharide AVP141-A was isolated from the broth of marine-derived fungus Aspergillus versicolor SCAU141 and purified by Diethylaminoethyl-Sepharose Fast Flow and Sephadex G-100. The structural characteristics of AVP141-A was studied by chemical analysis together with high-performance gel permeation chromatography, ion chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The results showed that AVP141-A with the molecular weight of 5.10 kDa was mainly composed of →4)-α-D-Glcp-(1→, branched by α-D-Glcp-(1→ and →6)-α-D-Glcp-(1→ at C-6 positions of the glucan backbone. In particular, sulfate ester (approximately 3.62 %) was found in AVP141-A, which was frequently considered to occur in marine-derived microbial polysaccharides rather than other microbial polysaccharides. Furthermore, AVP141-A significantly enhanced the activity of the inflammatory factors NO, COX-2 and TNF-α in RAW264.7 macrophages by activating the MAPK/p38 and NF-κB/p65 pathways. In addition, metabolomic analysis revealed that most of the pathways with significant changes in RAW264.7 macrophages treated with AVP141-A were amino acid-related pathways, and arginine was the characteristic metabolite. In conclusion, this study identified AVP141-A as a marine fungus-derived sulfated exopolysaccharide with potential for development as an immune activator., 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. Published by Elsevier B.V.)

Osteoporosis is an age-related metabolic disease of bone, resulting in bone pain and even bone fragility and brittle fracture. Inhibiting overactive osteoclasts while promoting osteoblast activity is an ideal way to treat osteoporosis. Previous studies have demonstrated that natural compounds, such as curcumin (Cur) have dual roles both in promoting bone formation and inhibiting bone resorption, making them promising candidates for osteoporosis treatment. However, their poor water solubility, high dosage of curative effect and significant toxicity to other organs have largely limited their clinical translations. In this study, a novel method was reported to conjugate Cur and poly(amidoamine) dendrimers (PAD) using hexachlorocyclotriphosphazene (HCCP) as the linkage through a one-pot reaction, forming stable and uniform Cur loaded nanospheres (HCCP-Cur-PAD, HCP NPs). Owing to the hydrophilicity of PAD and hydrophobicity of Cur, HCP NPs can self-assemble into nanoparticles with particle size of 138.8 ± 78.7 nm and display excellent water dispersity. The loading capacity of Cur can reach 27.2% and it can be released from HCP NPs with pH-responsiveness. In vitro experimental results demonstrated that the HCP NPs entered lysosomes by endocytosis and proved dual anti-osteoporosis effects of inhibiting osteoclasts and promoting osteoblasts., 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.)

Human activities have given rise to metal contamination in the constituents of mangrove ecosystems, posing a critical threat to sediment microorganisms; hence, it is of great importance to comprehend the effects of metals on the microbial communities in mangrove sediments. This study was the first to explore the response of the bacterial diversity and community structure to nine metals (As, Co, Cr, Cu, Mn, Ni, Pb, V and Zn) and organic matter fractions (including total organic carbon (TOC), total nitrogen (TN), and total sulfur (TS)) in mangrove wetlands from Zhanjiang, China, using 16S rRNA high-throughput sequencing technology and Spearman correlation analysis. The results showed that these nine metals were scattered differently in different mangrove sediments, and the metals and organic matter fractions jointly affected the bacterial communities in the sediments. Several metals displayed significant positive correlations with the abundances of the phylum Bacteroidetes and the genera Actibacter and Sphingobacterium but significant negative correlations with the abundances of two genera Holophaga and Caldithrix. Furthermore, the abundances of the phylum Actinobacteria and many bacterial genera showed significant positive or negative responses to the levels of the three organic matter fractions. Interestingly, the levels of a number of bacterial genera that exhibited increased abundance with high levels of metals and TS might be reduced with high TOC and TN, and vice versa: the levels of genera that exhibited decreased abundance with high levels of metals and TS might be increased with high TOC and TN. Overall, many bacterial groups showed different response patterns to each metal or organic matter fraction, and these metals together with organic matter fractions influenced the bacterial diversity and community structure in mangrove sediments., 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.)

Most previous studies on antifouling (AF) agents have focused on the influence of biofilm formation constituted by single or multiple cultured microbial species, and very few studies have analyzed the relationship between environmentally friendly AF compounds and marine fouling microbial communities (MFMCs). This is the first investigation of the impact of three environmentally friendly alkaloids (5-chlorosclerotiamide, circumdatin F and notoamide C) produced by the deep-sea-derived fungus Aspergillus westerdijkiae on MFMCs using high-throughput Illumina sequencing in a field test. The results of this study showed that the three alkaloids could significantly decrease the coverage of marine microflora (p < 0.05) and affect the composition and diversity of MFMCs on polyvinyl chloride (PVC) plates. Furthermore, 5-chlorosclerotiamide and notoamide C could completely inhibit many macrofouler-inductive-bacteria, such as Pseudoalteromonas and Pseudomonas, and promote the anti-macrofouler-bacteria, such as Winogradskyella, from 0.21% to more than 10% of the MFMCs on PVC plates. These results suggested that 5-chlorosclerotiamide and notoamide C could influence the compositions of MFMCs and make it unfavorable for the settlement of macrofoulers, by reducing the abundance of macrofouler-inductive-bacteria and promoting the percentage of anti-macrofouler-bacteria on PVC plates. The present study provides a new way to evaluate the effect of environmentally friendly AF compounds and obtain a better understanding of the antifouling process., 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 © 2021. Published by Elsevier B.V.)

Aims: Liver fibrosis is a growing public health concern without effective medical treatment. Recent reports have indicated that inhibitors of apoptosis proteins (IAPs) were potential targets for idiopathic pulmonary fibrosis therapy. However, their roles have not been well identified in liver fibrosis., Methods: The expression of IAPs were examined in human liver tissue and experimental mouse models. Liver fibrosis in CCl 4 -induced mouse models were investigated by Sirius red staining, RT-PCR, Western blotting after hepatocytes-specific cIAP2 knockout or IAPs inhibitor APG-1387 treatment. The underlying molecular mechanism of APG-1387 action was explored by apoptosis analysis, matrix metalloprotein 9 (MMP9) inhibition, neutrophils depletion, and CC Motif Chemokine Ligand 5 (CCL5) gene knockout in vitro and in vivo., Findings: Our study showed that increased expression of cIAP2 was associated with liver fibrosis severity in liver tissues. Deletion of cIAP2 from hepatocytes or degrading cIAPs by APG-1387 ameliorated liver fibrosis induced by CCl 4 . APG-1387 treatment exhibited increased expression of MMP9 and resulted in higher ratio of MMP9 to tissue inhibitor of metalloproteinase-1. MMP9 was mainly derived from CCL5 chemotactic neutrophils. Further, MMP9 inhibition by CTT peptide, neutrophil depletion by Ly6G antibody or CCL5 deficiency blocked the anti-fibrotic effects of APG-1387 in vivo., Significance: These results suggested that cIAPs, especially cIAP2, might play a novel role in the pathogenesis of liver fibrosis, and targeting cIAPs represented a promising therapeutic strategy for liver fibrosis by increasing MMP9 expression induced by CCL5 chemotactic neutrophils., (Copyright © 2021. Published by Elsevier Inc.)

In this work, a simple but effective method based on Gamma-ray initiated polymerization was reported for the first time through direct irradiation of CNCs and ionic liquid monomer to obtain poly (ionic liquids) functionalized CNCs (IL@CNCs). The adsorptive removal of Congo red (CR) from aqueous solution by IL@CNCs was also examined and the influence of contact time, pH values, initial concentrations and temperature on adsorption behavior was investigated in detail. Under the same adsorption conditions, the adsorption capacity was increased from 59.72 mg/g (CNCs) to 195.83 mg/g (IL@CNCs). The results of the adsorption isotherm and adsorption kinetics showed that the experimental data were more suitable to be described by the Freundlich isotherm adsorption model and the pseudo-second-order model. The adsorption process of CR on the surface of the adsorbent was endothermic and spontaneous. When the aqueous solution was acidic, it was more conducive to the adsorption of CR. At 100% breakthrough, the value of adsorption capacity is 199.95 mg/g and the value of partition coefficient is 9.64. Moreover, the adsorption capacity is expected to be further improved through adjustment of polymerization parameters and this method can also be used for preparation other poly (ionic liquids) modified composites., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Arsenic trioxide (ATO) has confirmed as a global pollutant, the toxic effect of which was not fully understood and lack effective therapies to against its associated toxicities. Curcumin (Cur) is a beneficial natural pigment for its antioxidant and anti-inflammatory properties. The purpose of this paper was to illustrate the antagonism of Cur against ATO-induced neurotoxicity. A total of 40 ducks were divided randomly into 4 groups and conducted via bite and sup for 28 days: control group (Control); 2 mg/kg ATO group (Low ATO); 4 mg/kg ATO group (Middle ATO); 8 mg/kg ATO group (High ATO); 400 mg/kg Cur group + 8 mg/kg ATO (Cur+ATO). The results showed that ATO exposure can hinder the duck growth and arsenic element accumulation rate increased in a dose-dependent manner. We observed neuronal shrinkage and vacuolize of HE staining in the ATO-treated group. In addition, SOD activity and T-AOC level reduced while MDA content increased in the ATO-exposed group. ATO exposure can decrease the expression of anti-oxidation related mRNA and proteins (Nrf2, SOD-1, GPX-1, CAT, Trx and HO-1) and anti-inflammatory makers (IL-4, IL-10), increased the expression of Keap1, NF-κB and pro-inflammatory makers (TNF-α, IL-1β, IL-18, IL-2, IL-6, INOS and COX-2). ATO treated might cause blood-brain barrier (BBB) damage through degradation of the tight junction proteins (TJs) occludin and ZO-1. Importantly, the experimental results also showed that Cur can alleviate oxidative stress, inflammatory response and BBB injury caused by ATO exposure through Nrf2 and NF-κB signaling pathway. The results suggested Cur exerted as a food additive and provided novel potential benefits of ATO toxicology in inflammation of the brain., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The adsorption applications of MXene-based adsorbents have intensively investigated recently. However, the performance of MXene-based adsorbents has been largely limited owing to their lack of functional groups and adsorptive sites. Therefore, surface functionalization of MXene is an important route to achieve better performance for environmental adsorption. Herein, polyionic liquid functionalized MXene (named as MXene-PIL) was prepared through a multi-component reaction and adsorptive removal of iodine by MXene-PIL was also evaluated. The successful generation of PIL on MXene was confirmed by a series of characterization measurements. Furthermore, the effects of contact time, iodine concentration, environmental temperature and other factors on the adsorption performance of MXene-PIL were investigated. Adsorption kinetic analysis including pseudo-first-order dynamic model, pseudo-second-order dynamic model and Weber-Morris model, adsorption thermodynamic analysis such as Langmuir and Freundlich models and Van't Hoff equation were used for further analysis the adsorption behavior of iodine by MXene-PIL. We demonstrated that the adsorption capacity could be as high as about 170 mg/g, which is obviously larger than the unmodified MXene and most of other reported adsorbents. Taken together, a simple strategy has been developed for in-situ generation of PIL on MXene and the resultant composites show potential application for adsorptive removal of iodine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this work, a novel imidazoles-MXene hybrid composite, namely polyimidazoles chain overlaying on the surface of MXene (Ti 3 C 2 @IMIZ), was prepared by a simple method. Through this strategy, imidazoles can be in situ growth on the surface of MXenes via a facile multicomponent reaction using chitosan as a renewable reactant. Based on the characterization results, we demonstrated that a thin layer imidazoles with an ordered chain structure was embedded on the surface of Ti 3 C 2 , which resulted in the formation of a novel imidazoles-MXene hybrid composite. The adsorption performance of Ti 3 C 2 @IMIZ for removal environmental pollutants was evaluated using heavy metal ions of Cr(Ⅵ) as adsorbate. Detailed adsorption characteristics of Ti 3 C 2 @IMIZ including operational factors, adsorption kinetics and isotherms models were investigated. XPS analysis showed that Cr(VI) was converted to Cr(III) with low toxicity during the adsorption process. The adsorption of Cr(VI) and reduction of Cr(VI) to Cr(III) contribute to elimination of Cr(VI) species. The adsorption behavior and process analysis show that the adsorption mechanism is mainly physical adsorption through electrostatic interaction. The excellent reproducibility suggests that Ti 3 C 2 @IMIZ may be a potential candidate for remove of Cr(Ⅵ) in actual sewage treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Heavy metal pollution has become a serious environmental problem in mangrove ecosystems and has attracted more attention. Most of previous studies have mainly focused on the effects of heavy metals on bacterial communities in mangrove sediments. This study was the first to investigate the effects of heavy metals (e.g., As, Co, Cr, Cu, Mn, Ni, Pb, V and Zn) and organic matter fractions (including total organic carbon (TOC), total nitrogen (TN), and total sulfur (TS)) on the fungal communities in mangrove sediments from Techeng Isle, South China. The results of this study indicated that the average contents of Mn, Pb and V of 8.30-161.80 μg/g presented relatively higher pollution levels, while the concentrations of Zn, Cr, Cu and Ni of 0.80-21.93 μg/g were lower than those recorded in other mangrove ecosystems. Furthermore, the sediment fungal community structures responded differently to the nine heavy metals and three organic matter fractions. Heavy metals Cr, Pb and V displayed significant positive correlations with Eutypella (P < 0.05), whereas significant negative correlations with Cystobasidium, Lulworthia, Cladosporium, Lulwoana and Cephalotheca (P < 0.05). In addition, the effects of heavy metals and TS on many fungal genera were opposite to those of TOC and TN. Fungal genera that decreased with high TOC and TN contents may be increased with high heavy metal contents and TS, and vice versa, and the genera that increased with high TOC and TN contents may be decreased with high heavy metals and TS. Our results suggested that many heavy metals, such as Cr, Pb and V, were sensitive to several fungal genera in mangrove sediments, and heavy metals together with organic matter fractions may participate and shape the fungal communities in mangrove sediments., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Arsenic (As) and antimony (Sb) are commonly accumulated environmental pollutants that often coexist in nature and cause serious widespread biological toxicity. To investigate the nephrotoxicity induced by As and Sb in detail, we explored the mechanism by which As and Sb cotreatment induced autophagy and pyroptosis in vivo and in vitro. In this study, mice were treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony trichloride (SbCl 3 ) by intragastric intubation for 60 days. TCMK-1 cells were treated with ATO (12.5 μM), SbCl 3 (25 μM) or a combination of As and Sb for 24 h. The results of the in vivo experiment demonstrated that As or/and Sb exposure could induce histopathological changes in the kidneys, and increase the levels of biochemical indicators of nephrotoxicity. In addition, As and Sb can co-induce oxidative stress, which further activate autophagy and pyroptosis. In an in vitro experiment, As and/or Sb coexposure increased ROS generation and decreased MMP. Moreover, the results of related molecular experiments further confirmed that As and Sb coactivated autophagy and pyroptosis. In conclusion, our results indicated that As and Sb co-exposure could cause autophagy and pyroptosis via the ROS pathway, and these two metals might have a synergistic effect on nephrotoxicity., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Arsenic (As) and antimony (Sb) are known as an environmental contaminant with cardiotoxicity properties. The endoplasmic reticulum (ER) is the largest calcium reservoir in the cell, and its calcium homeostasis disorder plays a vital role in endoplasmic reticulum stress (ERS) and apoptosis. The objective of this study was to investigate whether As and Sb induced apoptosis via endoplasmic reticulum stress (ERS) linked to calcium homeostasis disturbance. In this study, thirty-two adult mice were gavage-fed daily with As 2 O 3 (4 mg/kg), SbCl 3 (15 mg/kg) and co-treat with SbCl 3 (15 mg/kg) and As 2 O 3 (4 mg/kg) daily for 60 days. It was observed that As or/and Sb caused histopathological lesions and ER expansion of the heart. Meanwhile, the gene expression of ER Ca 2+ release channels (RyR2 and IP3R) and calmodulin-dependent protein kinase II (CaMKII) increased while the levels of mRNA and protein of ER Ca 2+ uptake channel (SERCA2) downregulated significantly compared to the controls. Then, As or/and Sb induced ERS and triggered the ER apoptotic pathway by activating unfolded protein response (UPR)-associated genes ((PERK, ATF6, IRE1, XBP1, JNK, GRP78), and apoptosis-related genes (Caspase12, Caspase3, p53, CHOP). Above indicators in As + Sb group became more severe than that of As group and Sb group. Overall, our results proved that the cardiotoxicity caused by As or/and Sb might be concerning disturbing calcium homeostasis, which induced apoptosis through the ERS pathway., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Cellulose nanocrystals (CNCs) are a class of sustainable nanomaterials that are obtained from plants and microorganisms. These naturally derived nanomaterials are of abundant hydroxyl groups, well biocompatibility, low cost and biodegradable potential, making them suitable and promising candidates for various applications, especially in biomedical fields. In this review, the recent advances and development on the preparation, surface functionalization and biomedical applications of CNCs-based materials have been summarized and outlined. The main context of this paper could be divided into the following three parts. In the first part, the preparation strategies based on physical, chemical, enzymatic and combination techniques for preparation of CNCs have been summarized. The surface functionalization methods for synthesis CNCs-based materials with designed properties and functions were outlined in the following section. Finally, the current state about applications of CNCs-based materials for tissue engineering, medical hydrogels, biosensors, fluorescent imaging and intracellular delivery of biological agents have been highlighted. Moreover, current issues and future directions about the above aspects have also pointed out and discussed. We believe this review will attract great research attention of scientists from materials, chemistry, biomedicine and other disciplines. It will also provide some important insights on the future development of CNCs-based materials especially in biomedical fields., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Arsenic trioxide (ATO) has been known as common environmental pollution, and is deemed to a threat to global public health. Curcumin (Cur) is a phytoconstituent, which has been demonstrated to have antioxidant effects. In the current experiment, we investigated the efficacy of Cur against ATO-induced kidney injury and explored the potential molecular mechanisms that have not yet been fully elucidated in ducks. The results showed that treatment with Cur attenuated ATO-induced body weight loss, reduced the content of ATO in the kidney, and improved ATO-induced kidney pathological damage. Cur also remarkably alleviated the ascent of ATO-induced MDA level and activated the Nrf2 pathway. Using the TEM, we found Cur relieved mitochondrial swelling, autolysosomes generating and nuclear damage. Simultaneously, Cur was found that it not only significantly reduced autophagy-related mRNA and protein levels (mTOR, LC3-Ⅰ, LC3-Ⅱ, Atg-5, Beclin1, Pink1 and Parkin) and but also decreased apoptosis-related mRNA and protein expression levels (cleaved caspase-3, Cytc, p53 and Bax). Furthermore, through nontargeted metabolomics analysis, we observed that lipid metabolism balance was disordered by ATO exposure, while Cur administration alleviated the disturbance of lipid metabolism. These results showed ATO could induce autophagy and apoptosis by overproducing ROS in the kidney of ducks, and Cur might relieve excessive autophagy, apoptosis and disturbance of lipid metabolism by regulating oxidative stress. Collectively, our findings explicate the potential therapeutic value of Cur as a new strategy to a variety of disorders caused by ATO exposure., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper studies the problem of cooperative searching for dynamical moving targets by multiple unmanned aerial vehicles (UAVs). The environmental information possessed by UAVs is inconsistent due to packet losses of shared environmental information in communication channels and the discrepancies of detected information among different UAVs. To unify the environmental information among UAVs, the lost information is compensated for by an improved Least Square Method (LSM) which incorporates the target location model into the fitting function to enhance data fitting precision. The Weighted Averaging Method (WAM) is used to merge multiple source information where the weight coefficients are set based on the uncertain values of environmental information. To search for dynamic targets and then automatically re-enter into search areas for UAVs, a Modified Genetic Algorithm (MGA) and rolling optimization techniques are utilized to generate real-time paths for UAVs. Simulation results and comparison studies with existing methods validate the effectiveness of the above cooperative searching strategy., 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 © 2021 ISA. Published by Elsevier Ltd. All rights reserved.)

Arsenic and antimony are coexisting cumulative environmental pollutants that cause severe and extensive biological toxicity. However, their interactions and toxic mechanisms in the liver remain to be fully elucidated. In this study, a total of sixty 4-week-old mice were divided into four groups and treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony (Sb) for 60 days. The results demonstrated that biochemical indicators of hepatotoxicity (ALT, AST, ALP) were upregulated in all treated groups. Additionally, the oxidative burden of the liver was increased in the cotreated groups compared with the individual toxicant-treated groups. Meanwhile, mitochondrial injury, autophagosomes, hepatic-congestion and karyopyknosis were obviously observed in cotreated groups. Additionally, coupled with serum biochemical index (TG, TC), histopathology examination and metabolomics results, we found that cotreatment with ATO and Sb resulted in lipid metabolism disorder and steatosis of liver tissues. Our further investigation found that the levels of pro-apoptotic (Caspase-3, Caspase-9, Bax, P53, Cytc) and mitophagy (LC3-B, P62, PINK1, Parkin) indexes in the cotreated groups were markedly increased, whereas the levels of anti-apoptosis index (Bcl-2) were decreased. Collectively, these results show that co-exposure to ATO and Sb can cause abnormal liver energy metabolism and oxidative stress. Moreover, mitophagy and apoptosis play important roles in the mechanisms of arsenic/antimony cytotoxicity to mouse livers., 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 © 2021 Elsevier B.V. All rights reserved.)

Herein, a novel strategy for surface functionalization and drug loading of cellulose nanocrystals (CNCs) through formation of hydrazone bonds between functionalized CNCs and aldehyde group containing polyethylene glycol (CHO-PEG)/anticancer drug doxorubicin (DOX) was reported for the first time. DOX could be loaded on PEGylated CNCs with high capacity and released from drug complexes (P-CNCs-D) with pH dependent behavior. The biological evaluation results demonstrated that drug carriers (CNCs-EBO-NH) showed negative cytotoxicity while DOX could be transported into cells and exhibits desirable anticancer effects. As compared with other method, the method developed in this work is rather simple and effective and can be achieved for simultaneous for surface functionalization and drug loading in a one-pot route. This work will open a new avenue for fabrication of various multifunctional composites based on other carbohydrate polymers or materials and to explore their applications in biomedical fields., (Copyright © 2021. Published by Elsevier B.V.)

Algal polysaccharide activates macrophages to alter physiologic biomarkers to drive the immunomodulatory phenotype, but it lacks specific biomarkers involved in the biochemical underpinning process. Here, we undertook an extensive analysis of the RAW 264.7 macrophages induced by an immunostimulating sulfated polysaccharide from Caulerpa racemosa var. peltata (CRVP-1) employing combined transcriptomic, proteomic, and metabolomic analyses to reveal the molecular details occurring in the CRVP-1-induced immunomodulatory process. The omics profiling of CRVP-1-activated macrophage demonstrated a total of 8844 genes (4354 downregulated and 4490 upregulated), 1243 proteins (620 downregulated and 623 upregulated), and 68 metabolites (52 downregulated and16 upregulated). Further, the co-mapped correlation network of omics combined with Western blot and immunofluorescence staining indicated that the cluster of differentiation 14 (CD14) might assist Toll-like receptor 4 (TLR4) involved in nuclear factor kappa-B (NF-κB) signaling pathway to drive the immunomodulatory phenotype. Together, our results discover novel physiologic biomarkers in the immunomodulatory activities of algal polysaccharides., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The microplastics pollution in wild aquatic organisms has been described by many studies. However, few studies focused on the farmed ones and MPs impacts on their gut microbiota under natural conditions. Here, we present the first detection of MPs in shrimp ponds and Litopenaeus vannamei. We also globally, firstly and preliminarily investigate the association between colonization of microorganism on MPs and intestinal microbiota under natural conditions. Microplastics (5129 ± 1176 items/kg d.w.) in sediments were mainly pellets, mostly white and blue, and in size less than 1 mm. Microplastics (14.08 ± 5.70 items/g w.w.) in shrimps were higher than that in mostly wild aquatic organisms and positively correlated with that in sediments. Blue fibers in small size (<0.5 mm) were dominant in shrimps. The bacterial communities and their microbial function on MPs were similar with that in shrimp gut, with higher diversity and richness in bacteria communities colonized on MPs. Network analysis demonstrated that the colonization of microorganism on MPs were associated with shrimp intestinal microbiota. Results suggest that except for toxicity reported previously, the effects on intestinal microbiota induced by MPs were possibly because of the biofilm on their surfaces as well, causing notable impacts on aquatic animals., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Seven new compounds including five aromatic butenolide analogues (1-5), one quinazolinone alkaloid (6) and one benzoic acid derivative (7), along with eleven known co-metabolites (8-18), were isolated from Aspergillus terreus SCAU011, a fungus from the rhizosphere sediment of a mangrove plant Rhizophora stylosa. The structures of these isolates were established by a combination of MS, NMR and ECD data analyses, as well as chemical method. Compound 3 is a rare ring-open aromatic butenolide, while 6 represents the first natural ring-open benzomalvin-type quinazolinone alkaloid. Also, the previously reported structures for asperlides A-C were proposed to be revised in the present work. The COX-2 inhibitory, α-glucosidase inhibitory, antioxidant and antibacterial activities of all the compounds were assessed. While compounds 4, 6, 11 and 18 exhibited better COX-2 inhibitory activity than the positive control celecoxib, compounds 9 and 10 showed significant α-glucosidase inhibitory activity with IC 50 values of 56.1 and 12.9 μM, respectively. Meanwhile, half of the tested samples (1, 8-11 and 15-17) exerted similar or better antioxidant activity compared with the reference drug curcumin, and compounds 3, 9, 17 and 18 displayed moderate antibacterial effect against Staphylococcus aureus., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The ecological stress caused by microplastic (MP) pollution in marine environments has attracted global attention. However, few studies have investigated the relationship between MP pollution and the microbial community in natural sediments. This study was the first to systematically characterize MP pollution (i.e., its abundance, shape, size and color) and investigate its relationship with the bacterial community in coastal sediments from Guangdong, South China, by microscopic observation and Illumina sequencing. The results of this study indicated that the abundance of microplastics (MPs), which was 344 ± 24 items/kg in 33 coastal sediments from 11 sites from South China, represented a relatively high level of MP pollution. MPs with sizes of <0.5 m, 0.5-1.0 mm and 1-2 mm accounted for the highest proportion (75%) in the sediments. Fiber/film (82%) and white/blue (91%) were the dominant shapes and colors, respectively, in all MP samples. Furthermore, the abundances, three shapes (fiber, film and fragment), three sizes (<0.5 mm, 0.5-1.0 mm and 1-2 mm), and two colors (blue and white) of MPs displayed positive correlations with some potential pathogens, including Vibrio, Pseudomonas, Bacillus and Streptococcus, but exhibited negative correlations with an environmentally friendly bacterial genus, Sphingomonas (which degrades various hazardous organic compounds), indicating that MPs might increase the potential ecological risks of coastal sediments. Our results may help to elucidate the relationship between MP pollution and the microbial community in coastal sediments., 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 © 2020 Elsevier B.V. All rights reserved.)

Multicomponent reactions (MCRs) have attracted broad interest for preparation of functional nanomaterials especially for the synthesis of functional polymers. Herein, we utilized an "old" MCR, the four-component Ugi reaction, to synthesize disulfide bond containing poly(PEG-TPE-DTDPA) amphiphilic copolymers with aggregation-induced emission (AIE) feature. This four-component Ugi reaction was carried out under rather mild reaction conditions, such as room temperature, no gas protection and absent of catalysts. The amphiphilic poly(PEG-TPE-DTDPA) copolymers with high number-average molecular weight (up to 86,440 Da) can self-assemble into claviform fluorescent polymeric nanoparticles (FPNs) in aqueous solution, and these water-dispersed nanoparticles exhibited strong emission, large Stokes shift (142 nm), low toxicity and remarkable ability in cellular imaging. Moreover, owing to the introduction of 3,3'-dithiodipropionic acid with disulfide bond, the resultant AIE-active poly(PEG-TPE-DTDPA) could display reduction-responsiveness and be utilized for synthesis of photothermal agents in-situ. Therefore, the AIE-active poly(PEG-TPE-DTDPA) could be promising for controlled intracellular delivery of biological activity molecules and fabrication of multifunctional AIE-active materials. Therefore, these novel AIE-active polymeric nanoparticles could be of great potential for various biomedical applications, such as biological imaging, stimuli-responsive drug delivery and theranostic applications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Halloysite nanotubes (HNTs) are a kind of aluminosilicate clay with a unique hollow tubular structure that has been intensively explored for various applications especially in biomedical fields owing to their excellent biocompatibility, biodegrading potential and low cost. Surface modification of HNTs with functional polymers will greatly improve their properties and endow new functions for biomedical applications. In this work, a light-induced reversible addition-fragmentation chain transfer (RAFT) polymerization was introduced to successfully prepare HNTs based fluorescent HNTs/poly(PEGMA-Fl) composites in the presence of oxygen using diacrylate-fluorescein and poly (ethylene glycol) methyl ether methacrylate (PEGMA) as the monomers. Without other catalysts, heating, and deoxygenation procedure, the polymerization process can take place under mild conditions. Besides, owing to the introduction of fluorescein and PEGMA on the surface of HNTs, the resultant HNTs/poly(PEGMA-Fl) composites display high water dispersibility and stable fluorescence. The results from cell viability examination and confocal laser scanning microscopy also demonstrated that HNTs/poly(PEGMA-Fl) composites could be internalized by L929 cells with bright fluorescence and low cytotoxicity. Taken together, we developed a novel photo-initiated RAFT polymerization method for the fabrication of HNTs based fluorescent polymeric composites with great potential for biomedical applications. More importantly, many other multifunctional HNTs based polymer composites could also be fabricated through a similar strategy owing to good designability of RAFT polymerization., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bovine hoof wall with an alpha keratin structure, as the interface between the ground and the body, can protect the bony skeleton from the impact and the destruction. Microstructure and mechanical properties of the bovine hoof wall are investigated by scanning electron microscope (SEM), transmission electron microscope (TEM) and quasi-static mechanical tests. Mechanical results show that the mean J-integral values of the LD specimens parallel to the tubular axis are higher than those of the TD specimens normal to the tubular axis, and the fracture toughness reaches the peak values (21 kJ/m 2 , 33 kJ/m 2 for the TD and the LD specimens, respectively) at 16.5% moisture content. The morphology results show that the laminated keratin structure can form the extensive strain-transition interfaces and the tubules played an important role in twisting crack propagation. Angles of the laminated structures within the inter-tubular materials are not a uniform distribution varying from 0° to 90° against to the tubular axis. The interlocking interface in the tubular structure can provide increased the contact area and contribute to the bonding strength between the layers. We also propose models to illustrate the morphological structure and the crack propagation mechanism of the bovine hoof wall. This structure with the strong fracture resistance ability will provide a new inspiration for design of structural materials and architectures., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Carbon nanotubes (CNTs) are a novel type of one-dimensional carbon nanomaterials that have been widely utilized for biomedical applications such as drug delivery, cancer photothermal treatment owing to their high surface area and unique interaction with cell membranes. However, their biomedical applications are still impeded by some drawbacks, including poor water dispersibility, lack of functional groups and toxicity. Therefore, surface modification of CNTs to overcome these issues should be importance and of great interest. In this work, we reported for the first time that CNTs could be surface modification through the combination of Diels-Alder (D-A) reaction and redox polymerization, this strategy shows the advantages of mild reaction conditions, water tolerance, low temperature and hydroxyl-surfaced initiator. In this modification procedure, the hydroxyl groups were introduced on the surface of CNTs through the D-A reaction that was adopted for grafting the copolymers, which were initiated by the Ce(IV)/HNO 3 redox system using the hydrophilic and biocompatible poly(ethylene glycol) methyl ether methacrylate (PEGMA) and carboxyl-rich acrylic acid (AA) as monomers. The final CNTs-OH-PAA@PEGMA composites were characterized by a series of characterization techniques. The drug loading and release results suggested that anticancer agent cis‑platinum (CDDP) could be loaded on CNTs-OH-PAA@PEGMA composites through coordination with carboxyl groups and drug release behavior could be controlled by pH. More importantly, the cell viability results clearly demonstrated that CNTs-OH-PAA@PEGMA composites displayed low toxicity and the drug could be transported in cells and still maintain their therapeutic effects., Competing Interests: Declaration of competing interest The authors declared that there is no conflict of interest., (Copyright © 2019. Published by Elsevier B.V.)

Background & Aims: Although CD8 + T cell exhaustion hampers viral control during chronic HBV infection, the pool of CD8 + T cells is phenotypically and functionally heterogeneous. Therefore, a specific subpopulation of CD8 + T cells should be further investigated. This study aims to dissect a subset of CD8 + T cells expressing C-X-C motif chemokine receptor 5 (CXCR5) in chronic HBV infection., Methods: The frequency of CXCR5 + CD8 + T cells and the levels of C-X-C motif chemokine ligand 13 (CXCL13), a chemokine of CXCR5, were measured in patients with chronic HBV infection. C57BL/6, interleukin (IL)-21 receptor- or B cell-deficient mice were hydrodynamically injected with pAAV-HBV1.2 plasmids. Phenotype and functions of peripheral and intrahepatic CXCR5 + and CXCR5 - CD8 + T cells were assessed., Results: CXCR5 + CD8 + T cells were partially exhausted but possessed a stronger antiviral ability than the CXCR5 - subset in patients with chronic HBV infection; moreover, CXCR5 + CD8 + T cells were associated with a favorable treatment response in patients with chronic hepatitis B (CHB). High levels of CXCL13 from patients with CHB facilitated the recruitment of intrahepatic CXCR5 + CD8 + T cells, and this subpopulation produced high levels of HBV-specific interferon (IFN)-γ and IL-21. Notably, PD1 (programmed death 1) blockade and exogenous IL-21 enhanced the production of IFN-γ. More strikingly, mice injected with CXCR5 + CD8 + T cells showed remarkably decreased expression of HBsAg. Additionally, an impaired production of HBV-specific IFN-γ from intrahepatic CXCR5 + CD8 + T cells was observed in IL-21 receptor- or B cell-deficient mice., Conclusion: CXCL13 promotes the recruitment of CXCR5 + CD8 + T cells to the liver, and this subpopulation improves viral control in chronic HBV infection. The identification of this unique subpopulation may contribute to a better understanding of CD8 + T cell functions and provide a potential immunotherapeutic target in chronic HBV infection., Lay Summary: Exhaustion of CD8 + T cells is an important factor in the development of chronic hepatitis B virus (HBV) infection. CD8 + T cells expressing the receptor CXCR5 are partially exhausted, but have potent antiviral activity, as they produce high levels of HBV-specific cytokines in chronic HBV infection. Increased expression of CXCL13 within the liver facilitates the recruitment of CXCR5 + CD8 + T cells and establishes effective immune control of HBV infection., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Nanodiamond (ND) has been widely studied as a new type of carbon nanomaterials that is expected to be used as a promising candidate in various fields especially in the field of biomedicine. However, its poor water dispersibility and insufficient controlled release limit its practical applications. In this paper, ND-based composites with pH-responsive hydrazone bonds were successfully prepared by a simple chemical reaction between ester groups and hydrazine hydrate, in which ester groups were conjugated on the surface of ND via thiol-ene click reaction. On the other hand, CHO-PEG and doxorubicin hydrochloride (DOX) were linked on the carriers through formation of hydrazone bonds, resulting in improving water dispersibility and high drug loading capacity. The structure, thermal stability, surface morphology and particle size of ND carriers were characterized by different equipment. Results demonstrated that we have successfully prepared these functionalized ND. The release rate of DOX in acidic environment was significantly greater than that in normal physiological environment. More importantly, cell viability and optical imaging results showed that ND-based composites possess good biocompatibility, therapeutic effect, and could successfully transport DOX to HepG2 cells. Considering the above results, we believe that our new ND carriers will become promising candidates for intracellular controlled drug delivery and cancer treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

As potential alternatives to conventional semiconductor quantum dots, fluorescent carbon quantum dots (CQDs) have received increasing research attention in biomedical fields owing to their splendid advantages of low cytotoxicity, strong fluorescence and excellent water dispersion. However, the preparation procedures of CQDs with designable chemical properties and functions are complicated and low efficient. In this work, we developed a facile, economical and straightforward strategy to prepare CQDs by a one-step thiol-ene click reaction between multiwalled carbon nanotubes (CNTs) and thiomalic acid (TA). The successful synthesis of CQDs was confirmed by a series of characterization data. The results manifested that CQDs were well combined with TA through surface thiol-ene click chemistry. In addition, the optical property is also desirable, the maximum emission wavelength was located in 500 nm and CQDs still could emit strong blue fluorescent light after irradiation with UV irradiation for 3 h. Besides, the pH value makes no significant changes for fluorescence emission wavelength of CQDs and CQDs can emit strongest fluorescence in weak acid solution. Furthermore, CQDs could be internalized by cells and show great cell dyeing performance and low cytotoxicity. All these features imply that TA functionalized CQDs possess great potential for biological imaging. The one-step thiol-ene click strategy provided a novel tool to prepare functionalized CQDs with great potential for biomedical applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Fluorescent hydroxyapatite (HAp) nanoparticles have received significant attention in biomedical fields due to their outstanding advantages, such as low immunogenicity, excellent biocompatibility and biodegradability. However, fluorescent HAp nanoparticles with well controlled size and morphology are coated with hydrophobic molecules and their biomedical applications are largely restricted by their poor dispersibility in physiological solutions. Therefore, surface modification of these hydrophobic fluorescent HAp nanoparticles to render them water dispersibility is of utmost importance for biomedical applications. In this work, we reported for the first time for preparation of water-dispersible hydrophilic fluorescent Eu 3+ -doped HAp nanoparticles (named as HAp-PEOTx) through the cationic ring-opening polymerization using hydrophilic and biocompatible 2-ethyl-2-oxazoline (EOTx) as the monomer. The characterization techniques, such as nuclear magnetic resonance (NMR) spectroscopy, transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) have been used to characterize these samples. Results confirmed that we could successfully obtain the hydrophilic fluorescent HAp-PEOTx composites through the strategy described above. These fluorescent HAp-PEOTx composites display great water dispersibility, unique fluorescent properties and excellent biocompatibility, making them promising for in vitro bioimaging applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Surface modification of carbon nanotubes (CNTs) through controlled living polymerization has demonstrated to be a useful route for preparation of CNTs based polymer composites. However, surface oxidation of CNTs is often required to generate functional groups, which can be further utilized for immobilization of polymerization initiator and grafting polymers. The surface oxidation procedure is rather complex, high energy cost, low efficient and will destroy the structure of CNTs. Therefore, the development of simple and efficient strategies for preparation of CNTs based composites should be of great research interest and raised much attention recently. In this work, a novel mussel inspired strategy that combination of ATRP and ring-opening reaction has been developed for simultaneous preparation of glycosylated and PEGylated CNTs for the first time. CNTs were first coated with polydopamine (PDA) through self-polymerization of dopamine under alkaline aqueous solution. Then polymerization initiator was immobilized on CNT-PDA through simple esterification and amidation reaction to obtain CNT-PDA-Br. The PEGylated CNTs were synthesized through ATRP using CNT-PDA-Br as initiator and polyethylene glycol monoester acrylate and itaconic anhydride (IA) as the monomers. Finally, glucosamine was conjugated with IA via ring-opening reaction. The successful preparation of glycosylated and PEGylated CNTs (CNT-PDA-Poly(PEGMA-co-IA)-Glu) was confirmed by a number of characterization techniques in details. The obtained CNTs based composites showed improved aqueous dispersibility and desirable cytocompatibility, implying their biomedical application potential. As compared with the conventional covalent strategies, the mussel inspired method described in this work will not destroy the structure for introduction functional groups on the surface of CNTs, that can occur under rather mild experimental conditions, including room temperature, short reaction time and aqueous solution. On the other hand, the mussel inspired chemistry can also be used for surface modification of almost any materials regardless of their size, morphology and compositions. Therefore, we believe that the mussel inspired strategy should be a general method for fabrication of various polymer composites for different applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Fluorescent nanodiamond (ND) has been regarded as one of the most promising fluorescent nanoprobes owing to their chemical inert, biocompatibility, optical properties, and rich surface chemistry. The fluorescent ND has been mainly fabricated through high-energy ion beam irradiation of type Ib diamonds and subsequent thermal annealing. The generation of nitrogen-vacancy centers is the reason for the fluorescence. However, the physical method is relatively complicated and it need to expensive equipment as well as high cost. On the other hand, the resultant fluorescent ND particles are lack of functional groups and difficult to be dispersed in aqueous solution. Therefore, the development of facile methods to direct preparation of fluorescent ND and surface modification with functional polymers is of great research interest for expanding the biomedical applications of fluorescent ND. In this report, a facile strategy was reported for the first time to prepare hydrophilic polymers functionalized fluorescent ND (named as ND-PhE-PETOx) composites through the ring-opening polymerization and simultaneous simple nucleophilic substitution reaction using the non-fluorescent detonation ND as the raw material. The obtained fluorescent ND composites were characterized by various characterization techniques in details. The as-obtained ND-PhE-PETOx composites exhibit high water dispersibility, low toxicity and strong fluorescence intensity. Cell uptake results indicating that the fluorescent ND based composites can be effectively internalized by cells. Taken together, we have developed a novel and simple method for the preparation of fluorescent ND based composites, which show excellent physicochemical properties and great potential for biomedical applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The preparation of fluorescent inorganic-organic polymer composites for biomedical applications has become one of the most interest research focuses recently. In this work, we reported a novel method for the preparation of Tb 3+ -doped luminescent layered double hydroxides (LDHs) based composites by taken advantage of a one-pot supramolecular chemistry. The adamantane can be immobilized on the surface of Tb 3+ -doped LDHs to obtain LDH-Ad, which could be further utilized for modified by the β-cyclodextrin (β-CD) containing hyperbranched polyglycerols (β-CD-HPG) through the host-guest interaction. Based on the characterization results, we demonstrated that the hyperbranched polyglycerol could be facilely introduced on these fluorescent Tb 3+ -doped LDHs through the method described in this work. The obtained Tb 3+ -doped LDHs based polymer composites (LDHs-β-CD-HPG) display improved water dispersibility and still maintain their fluorescence. The results based on various biological assays suggest that LDHs-β-CD-HPG polymer composites are of low cytotoxicity and their cell uptake behavior can be effectively traced using confocal laser imaging. All of the above results demonstrated that the fluorescent Tb 3+ -doped LDHs based polymer composites could be effectively surface modified with hydrophilic hyperbranched polymers through a one-pot facile host-guest interaction and the resultant fluorescent composites are of excellent physicochemical properties and display great potential for biomedical applications. This novel surface modification method should also be important for fabrication of other multifunctional composites and therefore great advanced the development of biomedical applications of fluorescent LDHs based polymer composites and related materials., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background & Aims: CD100 is constitutively expressed on T cells and can be cleaved from the cell surface by matrix metalloproteases (MMPs) to become soluble CD100 (sCD100). Both membrane-bound CD100 (mCD100) and sCD100 have important immune regulatory functions that promote immune cell activation and responses. This study investigated the expression and role of mCD100 and sCD100 in regulating antiviral immune responses during HBV infection., Methods: mCD100 expression on T cells, sCD100 levels in the serum, and MMP expression in the liver and serum were analysed in patients with chronic HBV (CHB) and in HBV-replicating mice. The ability of sCD100 to mediate antigen-presenting cell maturation, HBV-specific T cell activation, and HBV clearance were analysed in HBV-replicating mice and patients with CHB., Results: Patients with CHB had higher mCD100 expression on T cells and lower serum sCD100 levels compared with healthy controls. Therapeutic sCD100 treatment resulted in the activation of DCs and liver sinusoidal endothelial cells, enhanced HBV-specific CD8 T cell responses, and accelerated HBV clearance, whereas blockade of its receptor CD72 attenuated the intrahepatic anti-HBV CD8 T cell response. Together with MMP9, MMP2 mediated mCD100 shedding from the T cell surface. Patients with CHB had significantly lower serum MMP2 levels, which positively correlated with serum sCD100 levels, compared with healthy controls. Inhibition of MMP2/9 activity resulted in an attenuated anti-HBV T cell response and delayed HBV clearance in mice., Conclusions: MMP2/9-mediated sCD100 release has an important role in regulating intrahepatic anti-HBV CD8 T cell responses, thus mediating subsequent viral clearance during HBV infection., Lay Summary: Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. The clearance of HBV relies largely on an effective T cell immune response, which usually becomes dysregulated in chronic HBV infection. Our study provides a new mechanism to elucidate HBV persistence and a new target for developing immunotherapy strategies in patients chronically infected with HBV., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)