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The fisheries and aquaculture industry are known for generating substantial waste or by-products, often underutilized, or relegated to low-value purposes. However, this overlooked segment harbors a rich repository of valuable bioactive materials of which have a broad-spectrum of high-value applications. As the blue economy gains momentum and fisheries expand, sustainable exploitation of these aquatic resources is increasingly prioritized. In this review, we present a comprehensive overview of technology-enabled methods for extracting and transforming aquatic waste into valuable biomaterials and their recent advances in regenerative medicine applications, focusing on marine collagen, chitin/chitosan, calcium phosphate and bioactive-peptides. We discuss the inherent bioactive qualities of these "waste-to-resource" aquatic biomaterials and identify opportunities for their use in regenerative medicine to advance healthcare while achieving the Sustainable Development Goals., 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 B.V.)

Coordinated cell movement is a cardinal feature in tissue organization that highlights the importance of cells working together as a collective unit. Disruptions to this synchronization can have far-reaching pathological consequences, ranging from developmental disorders to tissue repair impairment. Herein, it is shown that metal oxide nanoparticles (NPs), even at low and non-toxic doses (1 and 10 µg mL -1 ), can perturb the coordinated epithelial cell rotation (CECR) in micropatterned human epithelial cell clusters via distinct nanoparticle-specific mechanisms. Zinc oxide (ZnO) NPs are found to induce significant levels of intracellular reactive oxygen species (ROS) to promote mitogenic activity. Generation of a new localized force field through changes in the cytoskeleton organization and an increase in cell density leads to the arrest of CECR. Conversely, epithelial cell clusters exposed to titanium dioxide (TiO 2 ) NPs maintain their CECR directionality but display suppressed rotational speed in an autophagy-dependent manner. Thus, these findings reveal that nanoparticles can actively hijack the nano-adaptive responses of epithelial cells to disrupt the fundamental mechanics of cooperation and communication in a collective setting., (© 2024 Wiley‐VCH GmbH.)

There is a paradigm shift in biomanufacturing toward continuous bioprocessing but cell-based manufacturing using adherent and suspension cultures, including microcarriers, hydrogel microparticles, and 3D cell aggregates, remains challenging due to the lack of efficient in-line bioprocess monitoring and cell harvesting tools. Herein, a novel label-free microfluidic platform for high throughput (≈50 particles/sec) impedance bioanalysis of biomass, cell viability, and stem cell differentiation at single particle resolution is reported. The device is integrated with a real-time piezo-actuated particle sorter based on user-defined multi-frequency impedance signatures. Biomass profiling of Cytodex-3 microcarriers seeded with adipose-derived mesenchymal stem cells (ADSCs) is first performed to sort well-seeded or confluent microcarriers for downstream culture or harvesting, respectively. Next, impedance-based isolation of microcarriers with osteogenic differentiated ADSCs is demonstrated, which is validated with a twofold increase of calcium content in sorted ADSCs. Impedance profiling of heterogenous ADSCs-encapsulated hydrogel (alginate) microparticles and 3D ADSC aggregate mixtures is also performed to sort particles with high biomass and cell viability to improve cell quality. Overall, the scalable microfluidic platform technology enables in-line sample processing from bioreactors directly and automated analysis of cell quality attributes to maximize cell yield and improve the control of cell quality in continuous cell-based manufacturing., (© 2024 Wiley‐VCH GmbH.)

Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastatic cancer progression, and current research, which relies heavily on 2D monolayer cultures, falls short in recapitulating the complexity of a 3D tumor microenvironment. To address this limitation, a transcriptomic meta-analysis is conducted on diverse cancer types undergoing EMT in 2D and 3D cultures. It is found that mechanotransduction is elevated in 3D cultures and is further intensified during EMT, but not during 2D EMT. This analysis reveals a distinct 3D EMT gene signature, characterized by extracellular matrix remodeling coordinated by angiopoietin-like 4 (Angptl4) along with other canonical EMT regulators. Utilizing hydrogel-based 3D matrices with adjustable mechanical forces, 3D cancer cultures are established at varying physiological stiffness levels. A YAP:EGR-1 mediated up-regulation of Angptl4 expression is observed, accompanied by an upregulation of mesenchymal markers, at higher stiffness during cancer EMT. Suppression of Angptl4 using antisense oligonucleotides or anti-cAngptl4 antibodies leads to a dose-dependent abolishment of EMT-mediated chemoresistance and tumor self-organization in 3D, ultimately resulting in diminished metastatic potential and stunted growth of tumor xenografts. This unique programmable 3D cancer cultures simulate stiffness levels in the tumor microenvironment and unveil Angptl4 as a promising therapeutic target to inhibit EMT and impede cancer progression., (© 2023 Wiley‐VCH GmbH.)

Trichostrongylus colubriformis is a parasitic helminth that primarily infects small ruminants, causing substantial economic losses in the livestock industry. Exploring the microbiome of this helminth might provide insights into the potential influence of its microbial community on the parasite's survival. We characterised the intestinal microbiome of T. colubriformis that had been collected from the duodenum of sheep, and compared the helminth microbiome with the duodenal microbiome of its host, aiming to identify contributions from the helminth's environment. At the same time, we explored the isolation of fastidious organisms from the harvested helminth. Primary alpha and beta diversity analyses of bacterial species revealed statistically significant differences between the parasite and the host, in terms of species richness and ecological composition. 16S rRNA differential abundance analysis showed that Mycoplasmoides and Stenotrophomonas were significantly present in T. colubriformis but not in the duodenal microbiome of the sheep. Furthermore, two bacteria, Aeromonas caviae and Aeromonas hydrophila, were isolated from T. colubriformis. Examinations of the genome highlight differences in genome size and profiles of antimicrobial resistance genes. Our results suggest that T. colubriformis carries a specific bacterial community that could be supporting the helminth's long-term survival in the host's digestive system., (© 2024. The Author(s).)

Insights into how biological systems respond to high- and low-dose acute environmental stressors are a fundamental aspect of exposome research. However, studying the impact of low-level environmental exposure in conventional in vitro settings is challenging. This study employed a three-dimensional (3D) biomimetic microfluidic lung-on-chip (μLOC) platform and RNA-sequencing to examine the effects of two model anthropogenic engineered nanoparticles (NPs): zinc oxide nanoparticles (Nano-ZnO) and copier center nanoparticles (Nano-CCP). The airway epithelium exposed to these NPs exhibited dose-dependent increases in cytotoxicity and barrier dysregulation (dominance of the external exposome). Interestingly, even nontoxic and low-level exposure (10 μg/mL) of the epithelium compartment to Nano-ZnO triggered chemotaxis of lung fibroblasts toward the epithelium. An increase in α smooth muscle actin (α-SMA) expression and contractile activity was also observed in these cells, indicating a bystander-like adaptive response (dominance of internal exposome). Further bioinformatics and network analysis showed that a low-dose Nano-ZnO significantly induced a robust transcriptomic response and upregulated several hub genes associated with the development of lung fibrosis. We propose that Nano-ZnO, even at a no observable effect level (NOEL) dose according to conventional standards, can function as a potent nanostressor to disrupt airway epithelium homeostasis. This leads to a cascade of profibrotic events in a cross-tissue compartment fashion. Our findings offer new insights into the early acute events of respiratory harm associated with environmental NPs exposure, paving the way for better exposomic understanding of this emerging class of anthropogenic nanopollutants.

Background: As the reduced eradication rate of Helicobacter pylori (H. pylori), we introduced string-test and quantitative PCR (qPCR) for susceptibility-guided therapy innovatively. The practicality of the string test was evaluated., Methods: It was an open-label, non-randomized, parallel, single-center study, in which subjects tested by 13 C- urea breath test (UBT) and string-qPCR were enrolled. Based on the results of string-qPCR, we calculated clarithromycin and levofloxacin resistance rates and gave 13 C-UBT positive patients 14 days susceptibility-guided bismuth quadruple therapy. In the empirical therapy group, we retrospectively analyzed the treatment results of 13 C-UBT positive patients also treated with bismuth quadruple at Shenzhen Luohu People's Hospital from January 2021 to May 2022. The eradication rate was compared between susceptibility-guided therapy and empirical therapy groups., Results: The diagnosis of H. pylori infection using the string-qPCR had an overall concordance rate of 95.9% with the 13 C-UBT results. Based on the results of string-qPCR, the clarithromycin and levofloxacin resistance rates were 26.1% and 31.8%, respectively. The patients who were given 14 days susceptibility-guided bismuth-based quadruple therapy achieved a high H. pylori eradication rate of 91.8%. Retrospective analysis of patient treatment data from January 2021 to May 2022 available in the hospital database revealed an overall success rate of 82.3% for those who received empirical bismuth-based quadruple therapies, which is marginally significantly lower than that of the string-qPCR susceptibility-guided group (p = 0.084)., Conclusion: The high treatment success rate of 91.8% indicates that the string-qPCR test is a valuable and feasible approach for clinical practice to help improve H. pylori treatment success rate., (© 2023 The Authors. Helicobacter published by John Wiley & Sons Ltd.)

Background: Intravenous immunoglobulin (IVIG) replacement therapy is increasingly in demand. This study focused on the characteristics of IVIG usage and associated factors toward the frequency status of IVIG among patients in Hospital Kuala Lumpur., Methods: A retrospective cross-sectional study was performed on patients who received IVIG in Hospital Kuala Lumpur. Data were extracted from the request forms for IVIG recorded in the Pharmacy Department from January 2018 until December 2019. Chi-squared test and t -test analysis were used for statistical analysis, and a P -value of < 0.05 was considered significant., Results: A total of 482 patients received IVIG in Hospital Kuala Lumpur. There were 243 (50.4%) females and 228 (47.3%) males with median age of the patients was 27 years old. The highest indications for IVIG among all patients were hypogammaglobulinemia and other deficiency states in 127 patients (26.3%). The most common indication for one-off treatment in adults was hypogammaglobulinemia and other deficiency states, 35%; whereas in paediatrics, it was Kawasaki disease, 20.3%. The highest indication for regular therapy among adult patients was chronic inflammatory demyelinating polyneuropathy (23.4%), while in paediatrics it was sepsis (31.1%). The clinical category was associated with the frequency status of IVIG usage in both adult and paediatric cohorts with P = 0.004 and P = 0.017, respectively., Conclusion: There were significant differences between the indication of one-off treatment and regular therapy among adult and paediatric patients. A national guideline on the prescription of IVIG for patients is instantly needed to help clinicians in prescribing IVIG appropriately., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2023.)

Background: Clinical pharmacy plays an integral role in optimizing inpatient care. Nevertheless, prioritising patient care remains a critical challenge for pharmacists in a hectic medical ward. In Malaysia, clinical pharmacy practice has a paucity of standardized tools to prioritise patient care., Aim: Our aim is to develop and validate a pharmaceutical assessment screening tool (PAST) to guide medical ward pharmacists in our local hospitals to effectively prioritise patient care., Method: This study involved 2 major phases; (1) development of PAST through literature review and group discussion, (2) validation of PAST using a three-round Delphi survey. Twenty-four experts were invited by email to participate in the Delphi survey. In each round, experts were required to rate the relevance and completeness of PAST criteria and were given chance for open feedback. The 75% consensus benchmark was set and criteria with achieved consensus were retained in PAST. Experts' suggestions were considered and added into PAST for rating. After each round, experts were provided with anonymised feedback and results from the previous round., Results: Three Delphi rounds resulted in the final tool (rearranged as mnemonic 'STORIMAP'). STORIMAP consists of 8 main criteria with 29 subcomponents. Marks are allocated for each criteria in STORIMAP which can be combined to a total of 15 marks. Patient acuity level is determined based on the final score and clerking priority is assigned accordingly., Conclusion: STORIMAP potentially serves as a useful tool to guide medical ward pharmacists to prioritise patients effectively, hence establishing acuity-based pharmaceutical care., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Gastrointestinal (GIT) helminthiasis is a global problem that affects livestock health, especially in small ruminants. One of the major helminth parasites of sheep and goats, Teladorsagia circumcincta, infects the abomasum and causes production losses, reductions in weight gain, diarrhoea and, in some cases, death in young animals. Control strategies have relied heavily on the use of anthelmintic medication but, unfortunately, T. circumcincta has developed resistance, as have many helminths. Vaccination offers a sustainable and practical solution, but there is no commercially available vaccine to prevent Teladorsagiosis. The discovery of new strategies for controlling T. circumcincta, such as novel vaccine targets and drug candidates, would be greatly accelerated by the availability of better quality, chromosome-length, genome assembly because it would allow the identification of key genetic determinants of the pathophysiology of infection and host-parasite interaction. The available draft genome assembly of T. circumcincta (GCA&#95;002352805.1) is highly fragmented and thus impedes large-scale investigations of population and functional genomics., Results: We have constructed a high-quality reference genome, with chromosome-length scaffolds, by purging alternative haplotypes from the existing draft genome assembly and scaffolding the result using chromosome conformation, capture-based, in situ Hi-C technique. The improved (Hi-C) assembly resulted in six chromosome-length scaffolds with length ranging from 66.6 Mbp to 49.6 Mbp, 35% fewer sequences and reduction in size. Substantial improvements were also achieved in both the values for N50 (57.1 Mbp) and L50 (5 Mbp). A higher and comparable level of genome and proteome completeness was achieved for Hi-C assembly on BUSCO parameters. The Hi-C assembly had a greater synteny and number of orthologs with a closely related nematode, Haemonchus contortus., Conclusion: This improved genomic resource is suitable as a foundation for the identification of potential targets for vaccine and drug development., (© 2023. The Author(s).)

Chronic wounds are non-healing wounds characterized by a prolonged inflammation phase. Excessive inflammation leads to elevated protease levels and consequently to a decrease in growth factors at wound sites. Stem cell secretome therapy has been identified as a treatment strategy to modulate the microenvironment of chronic wounds via supplementation with anti-inflammatory/growth factors. However, there is a need to develop better secretome delivery systems that are able to encapsulate the secretome without denaturation, in a sustained manner, and that are fully biocompatible. To address this gap, a recombinant squid suckerin-spider silk fusion protein is developed with cell-adhesion motifs capable of thermal gelation at physiological temperatures to form hydrogels for encapsulation and subsequent release of the stem cell secretome. Freeze-thaw treatment of the protein hydrogel results in a modified porous cryogel that maintains slow degradation and sustained secretome release. Chronic wounds of diabetic mice treated with the secretome-laden cryogel display increased wound closure, presence of endothelial cells, granulation wound tissue thickness, and reduced inflammation with no fibrotic scar formation. Overall, these in vivo indicators of wound healing demonstrate that the fusion protein hydrogel displays remarkable potential as a delivery system for secretome-assisted chronic wound healing., (© 2022 Wiley-VCH GmbH.)

Mesoporous silica nanoparticles have highly versatile structural properties that are suitable for a plethora of applications including catalysis, separation, and nanotherapeutics. We report a one-pot synthesis strategy that generates bimodal mesoporous silica nanoparticles via coassembly of a structure-directing Gemini surfactant (C 16-3-16 ) with a tetraethoxysilane/(3-aminopropyl)triethoxysilane-derived sol additive. Synthesis temperature enables control of the nanoparticle shape, structure, and mesopore architecture. Variations of the aminosilane/alkylsilane molar ratio further enable programmable adjustments of hollow to core-shell and dense nanoparticle morphologies, bimodal pore sizes, and surface chemistries. The resulting Gemini-directed aminated mesoporous silica nanoparticles have excellent carbon dioxide adsorption capacities and antimicrobial properties against Escherichia coli . Our results provide an enhanced understanding of the structure formation of multiscale mesoporous inorganic materials that are desirable for numerous applications such as carbon sequestration, water remediation, and biomedical-related applications.

The widespread use of engineered nanomaterials (ENMs) in food products necessitates the understanding of their impact on the gastrointestinal tract (GIT). Herein, we screened several representative food-borne comparator ENMs ( i.e. ZnO, SiO 2 and TiO 2 nanoparticles (NPs)) and report that human colon cancer cells can insidiously exploit ZnO NP-induced adaptive response to acquire resistance against several chemotherapeutic drugs. By employing a conditioning and challenge treatment regime, we demonstrate that repeated exposure to a non-toxic dose of ZnO NPs (20 μM) could dampen the efficacy of cisplatin, paclitaxel and doxorubicin by 10-50% in monolayer culture and 3D spheroids of human colon adenocarcinoma cells. Structure-activity relationship studies revealed a complex interplay between nanoparticle surface chemistry and cell type in determining the chemoresistance-inducing effect, with silica coated ZnO NPs having a negligible influence on the anticancer treatment. Mechanistically, we showed that the pro-survival paracrine signaling was potentiated and propagated by a subset of ZnO NP "stressed" (Zn 2+ +/ROS+) cells to the surrounding "bystander" (Zn 2+ +/ROS-) cells. Transcriptome profiling, bioinformatics analysis and siRNA gene knockdown experiments revealed the nuclear factor erythroid 2-related factor 2 (Nrf2) as the key modulator of the ZnO NP-induced drug resistance. Our findings suggest that a ROS-inducing ENM can emerge as a nano-stressor, capable of regulating the chemosensitivity of colon cancer cells.

Gastrointestinal helminths are a global health issue, for humans as well as domestic animals. Most studies focus on the tissues that are infected with the parasite, but here we studied the ileum, a tissue that is rarely infected by helminths. We tested whether inflammation in the ileum contributes to the development and severity of diarrhoea, by comparing sheep that are susceptible (n = 4) or resistant (n = 4) to the disease. We analyzed the ileum transcriptome using RNASeq sequencing approach and various bioinformatics tools including FastQC, STAR, featureCounts, DESeq2, DAVID, clusterProfiler, Cytoscape (ClusterONE) and EnrichR. We identified 243 differentially expressed genes (DEGs), of which 118 were up-regulated and 125 were down-regulated DEGs in the diarrhoea-susceptible animals compared to the diarrhoea-resistant animals. The resulting DEGs were functionally enriched for biological processes, pathways and gene set enrichment analysis. The up-regulated DEGs suggested that an inflammatory immune response was coupled with genes involved in 'Th2 immune response' and 'anti-inflammatory response'. The down-regulated DEGs were related to ion transport, muscle contraction and pathways preventing inflammation. We conclude that i) susceptibility to helminth-induced diarrhoea involves an inflammatory response at a non-infectious site; ii) down-regulation of pathways preventing inflammation can contribute to the severity of diarrhoea; and iii) genes involved in anti-inflammatory responses can reduce the inflammation and diarrhoea., (© 2022. The Author(s).)

Pertussis also known as whooping cough is a respiratory infection in humans particularly with severe symptoms in infants and usually caused by Bordetella pertussis. However, Bordetella parapertussis can also cause a similar clinical syndrome. During 2012 to 2015, from nasal swabs sent from different provinces to the pertussis reference laboratory of Pasture Institute of Iran for pertussis confirmation, seven B. parapertussis isolates were identified by bacterial culture, biochemical tests, and the presence of IS1001 insertion in the genome. The expression of pertactin (Prn) as one the major virulence factor for bacterial adhesion was investigated using western blot. Moreover, the genomic characteristic of one recently collected isolate, IRBP134, from a seven-month infant was investigated using Illumina NextSeq sequencing protocol. The results revealed the genome with G+C content 65% and genome size 4.7 Mbp. A total of 81 single nucleotide polymorphisms and 13 short insertions and deletions were found in the genome compared to the B. parapertussis 12822 as a reference genome showing ongoing evolutionary changes. A phylogeny relationship of IRBP134 was also investigated using global B. parapertussis available genomes., (© 2022. The Author(s).)

Waste electronic and electrical equipment are complex mixtures of valuable and/or toxic materials, which pose serious challenges in their recycling or disposal, for example, electrical transmission wires insulated in polyvinyl chloride materials. These materials are frequently found contaminated with toxic chemical elements, such as Pb, Hg, Cr, or Cd, and are discarded without decontamination. To resolve this problem, we developed a microwave-assisted extraction process to remove toxic metals from plastic e-waste. We processed diluted (30 wt%) citric acid at 210 °C for 1 h inside a pressurized vessel heated by microwave, and found it was suitable not only for the extraction of the toxic metals (∼100%) but also for a significant plastic recovery (>50 wt%). To predict an optimized process window, the support vector regression machine learning algorithm was applied, which reduced the amount of experimentation required while still giving accurate results. Conditions optimized for the reference sample also led to maximum extraction of toxic metals from real-life extension cord waste. We also report that the recovered plastic's properties remained intact after the extraction., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Organic electrochemical transistors (OECTs) have recently attracted attention due to their high transconductance and low operating voltage, which makes them ideal for a wide range of biosensing applications. Poly-3,4-ethylenedioxythiophene:poly-4-styrenesulfonate (PEDOT:PSS) is a typical material used as the active channel layer in OECTs. Pristine PEDOT:PSS has poor electrical conductivity, and additives are typically introduced to improve its conductivity and OECT performance. However, these additives are mostly either toxic or not proven to be biocompatible. Herein, a biocompatible ionic liquid [MTEOA][MeOSO 3 ] is demonstrated to be an effective additive to enhance the performance of PEDOT:PSS-based OECTs. The influence of [MTEOA][MeOSO 3 ] on the conductivity, morphology, and redox process of PEDOT:PSS is investigated. The PEDOT:PSS/[MTEOA][MeOSO 3 ]-based OECT exhibits high transconductance (22.3 ± 4.5 mS μm -1 ), high μC* (the product of mobility μ and volumetric capacitance C*) (283.80 ± 29.66 F cm -1 V -1 s -1 ), fast response time (∼40.57 μs), and excellent switching cyclical stability. Next, the integration of sodium (Na + ) and potassium (K + ) ion-selective membranes with the OECTs is demonstrated, enabling selective ion detection in the physiological range. In addition, flexible OECTs are designed for electrocardiography (ECG) signal acquisition. These OECTs have shown robust performance against physical deformation and successfully recorded high-quality ECG signals.

Background: Helminth parasitism is a world-wide problem in livestock industries, with major impacts on health, welfare and productivity. The role of the gut microbiota in host-helminth interactions in ruminants has been extensively examined and the present study added to this body of knowledge by assessing the effects of resistance and susceptibility to helminth infection in the gastro-intestinal tract (GIT). Australian Sheep Breeding Values (ASBVs) for faecal egg count (FEC) were used to select the 10 highly helminth-susceptible (High-FEC) and 10 highly helminth-resistant (Low-FEC) sheep. FEC status was confirmed during the experiment. Using samples from the faeces and the lumen of the rumen, abomasum, duodenum, jejunum, ileum, caecum, and colon, DNA was extracted and used for 16 rRNA gene amplicon sequencing., Results: The most frequent genera identified along the GIT were Eubacterium, Oscillibacter, and Ruminococcus. Intersectoral-specialization zones were identified along the GIT, with the duodenum displaying major differences between the High-FEC and Low-FEC animals in values for alpha and beta diversity. After taking all samples into account and adjusting for GIT segment, the High-FEC and Low-FEC sheep differed significantly for four genera Butyrivibrio, Mycoplasma, Lachnoclostridium and Succiniclasticum. In the duodenum, the abundances of Aminipila, Lachnoclostridium and Mogibacterium differed significantly between the High-FEC and Low-FEC sheep. In the ileum, on the other hand, the genus Mycoplasma was significantly depleted in the Low-FEC group., Conclusions: The gastro-intestinal microbial profile varies widely between helminth-resistant and helminth-susceptible sheep. Each GIT section appears to support a particular bacterial composition leading to inter-sectoral differences among the various microbial communities. The microbial populations were most rich and diverse in the duodenum of helminth-resistant sheep, comprising bacterial genera that generally ferment carbohydrates. This observation suggests that helminth-resistant sheep can reorganize the duodenal microbiome taxa which may restrict the development of parasites., (© 2022. The Author(s).)

Reuse of electronic wastes is a critical aspect for a more sustainable circular economy as it provides the simplest and most direct route to extend the lifespan of non-renewable resources. Herein, the distinctive surface and micro topographical features of computer electronic-plastic (E-plastic) scraps were unconventionally repurposed as a substrate material to guide the growth and differentiation of human adipose-derived mesenchymal stem cells (ADSCs). Specifically, the E-plastics were scavenged from discarded computer components such as light diffuser plate (polyacrylates), prismatic sheet (polyethylene terephthalate), and keyboards (acrylonitrile butadiene styrene) were cleaned, sterilized, and systematically characterized to determine the identity of the plastics, chemical constituents, surface features, and leaching characteristics. Multiparametric analysis revealed that all the E-plastics could preserve stem-cell phenotype and maintain cell growth over 2 weeks, rivalling the performance of commercial tissue-culture treated plates as cell culture plastics. Interestingly, compared to commercial tissue-culture treated plastics and in a competitive adipogenic and osteogenic differentiation environment, ADSCs cultured on the keyboard and light diffuser plastics favoured bone cells formation while the grating-like microstructures of the prismatic sheet promoted fat cells differentiation via the process of contact guidance. Our findings point to the real possibility of utilizing discarded computer plastics as a "waste-to-resource" material to programme stem cell fate without further processing nor biochemical modification, thus providing an innovative second-life option for E-plastics from personal computers., 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.)

Gastrointestinal helminths infect livestock causing health problems including severe diarrhoea. To explore the underlying biological mechanisms relating to development and control of diarrhoea, we compared 4 sheep that were susceptible to development of diarrhoea with 4 sheep that were diarrhoea-resistant. Transcriptomes in the tissues where the parasites were located were analyzed using RNASeq. By considering low-diarrhoea sheep as control, we identified 114 genes that were down-regulated and 552 genes that were up-regulated genes in the high-diarrhoea phenotype. Functional analysis of DEGs and PPI sub-network analysis showed that down-regulated genes in the high-diarrhoea phenotype were linked to biological processes and pathways that include suppression of 'antigen processing and presentation', 'immune response', and a list of biological functional terms related to 'suppression in immune tolerance'. On the other hand, up-regulated genes in the high-diarrhoea phenotype probably contribute to repair processes associated with tissue damage, including 'extracellular matrix organization', 'collagen fibril organization', 'tissue morphogenesis', 'circulatory system development', 'morphogenesis of an epithelium', and 'focal adhesion'. The genes with important roles in the responses to helminth infection could be targeted in breeding programs to prevent diarrhoea., (© 2022. The Author(s).)

Improving the efficiencies of organic compound degradations by catalytic materials is a challenging materials research field. In our research, we successfully synthesized cobalt-based polyoxometalates (CoV-POMs) via a simple crystallization-driven self-assembly method. The incorporation of the newly synthesized CoV-POMs into peroxymonosulphate (PMS), forming a mixture, greatly enhancing the catalytic activation for a complete degradation of dye solution. The positive synergic effect between CoV-POMs and PMS was substantiated by a relatively meager degradation of less than 10% in the system without CoV-POMs, in which CoV-POMs played a vital role to activate PMS towards free radicals generation for dye degradation. Methylene blue (MB) and rhodamine B (RB) dyes were completely decolorized under 60 min with the presence of 40 mg/L CoV-POMs and 150 mg/L PMS. The CoV-POMs/PMS system was pH dependance with a lower dye degradation efficiency at elevated pH. The effect of pH was more prominent in RB dye, in which the degradation efficiency dropped drastically from 93.3% to 41.12% with the increase in the solution pH from 7 to 11. The quenching tests suggested that sulfate radicals were the dominant active species involving in the dye degradation reaction. Besides MB and RB dyes, CoV-POMs/PMS system also showed significant activity towards the degradation of phenol red (PR) and methyl orange (MO) dyes. In the biological test, CoV-POMs exhibited non-toxic behavior towards normal cells that reduced safety concern for the large-scale wastewater treatment application. In addition, the testing divulged the anticancer property of CoV-POMs with more than 35 % of A549 lung adenocarcinoma and MDA-MB-231 breast adenocarcinoma were killed with 250 mg/L CoV-POMs. The selective lethality of CoV-POMs towards cancer cells was found to be caused by different extents of cellular apoptosis. In overall, the synthesized bifunctional CoV-POMs manifested superior activities in the examined applications, specifically dye degradation and anticancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The increasing amount of e-waste plastics needs to be disposed of properly, and removing the brominated flame retardants contained in them can effectively reduce their negative impact on the environment. In the present work, TBBPA-bis-(2,3-dibromopropyl ether) (TBBPA-DBP), a novel brominated flame retardant, was extracted by ultrasonic-assisted solvothermal extraction process. Response Surface Methodology (RSM) achieved by machine learning (support vector regression, SVR) was employed to estimate the optimum extraction conditions (extraction time, extraction temperature, liquid to solid ratio) in methanol or ethanol solvent. The predicted optimum conditions of TBBPA-DBP were 96 min, 131 mL g -1 , 65 °C, in MeOH, and 120 min, 152 mL g -1 , 67 °C in EtOH. And the validity of predicted conditions was verified., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Nano-enabled, toner-based printing equipment emit nanoparticles during operation. The bioactivity of these nanoparticles as documented in a plethora of published toxicological studies raises concerns about their potential health effects. These include pro-inflammatory effects that can lead to adverse epigenetic alterations and cardiovascular disorders in rats. At the same time, their potential to alter DNA repair pathways at realistic doses remains unclear. In this study, size-fractionated, airborne particles from a printer center in Singapore were sampled and characterized. The PM 0.1 size fraction (particles with an aerodynamic diameter less than 100 nm) of printer center particles (PCP) were then administered to human lung adenocarcinoma (Calu-3) or lymphoblastoid (TK6) cells. We evaluated plasma membrane integrity, mitochondrial activity, and intracellular reactive oxygen species (ROS) generation. Moreover, we quantified DNA damage and alterations in the cells' capacity to repair 6 distinct types of DNA lesions. Results show that PCP altered the ability of Calu-3 cells to repair 8oxoG:C lesions and perform nucleotide excision repair, in the absence of acute cytotoxicity or DNA damage. Alterations in DNA repair capacity have been correlated with the risk of various diseases, including cancer, therefore further genotoxicity studies are needed to assess the potential risks of PCP exposure, at both occupational settings and at the end-consumer level., (Copyright © 2022. Published by Elsevier B.V.)

A short bioinspired octapeptide, GV8, can self-assemble under mild conditions into biodegradable supramolecular physical hydrogels with high storage modulus and good biocompatibility. GV8 hydrogels can encapsulate both single or multiple macromolecular protein-based therapeutics in a simple one-pot formulation manner, making it a promising candidate to address challenges faced by existing synthetic polymer or peptide hydrogels with complex gelation and drug-encapsulation processes. Alongside its versatility, the hydrogel exhibits concentration-dependent storage modulus and controlled drug-release action. We demonstrate that GV8 hydrogels loaded with adipose-derived mesenchymal stem cells (ADMSC) secretome remain mechanically robust, and exhibit promising potential for wound healing applications by preserving secretome activity while maintaining a constant supply of ADMSC secretome to promote epithelial cell migration. Overall, our work highlights the potential of GV8 peptide hydrogel as a versatile and safe carrier for encapsulation and delivery of macromolecular therapeutics. STATEMENT OF SIGNIFICANCE: Supramolecular peptide hydrogels are a popular choice for protein-based macromolecular therapeutics delivery; however, despite the development of abundant hydrogel systems, several challenges limit their adaptability and practical applications. GV8 short peptide hydrogel circumvents these drawbacks and demonstrates the ability to function as a versatile growth factor (GF) encapsulant. It can encapsulate precise concentrations of complex adipose-derived mesenchymal stem cells secretome mixtures with a one-pot formulation approach and perform controlled release of GFs with preserved activity without compromising the self-assembly and mechanical properties of the hydrogel's supramolecular network. The significance of GV8 hydrogel lies in its gelation simplicity and versatility to encapsulate and deliver macromolecular therapeutics, thus representing a promising biomaterial for regenerative medicine applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Primary amyloidosis is a rare systemic disorder often associated with multiple organ dysfunction. The most common form, light chain amyloidosis, has an estimated age-adjusted incidence of 5.1-12.8 cases per million person-years. Spine involvement is extremely uncommon. We present the case of a young Asian man with newly diagnosed amyloidosis involving the lumbar spine among multiple organs with a pathological vertebral fracture that required urgent spine surgery. We believe this is the first reported case to discuss the perianaesthetic challenges in the management of lumbar spine amyloidosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Focal adhesions (FAs) are specialized structures that enable cells to sense their extracellular matrix rigidity and transmit these signals to the interior of the cells, bringing about actin cytoskeleton reorganization, FA maturation, and cell migration. It is known that cells migrate towards regions of higher substrate rigidity, a phenomenon known as durotaxis. However, the underlying molecular mechanism of durotaxis and how different proteins in the FA are involved remain unclear. Zyxin is a component of the FA that has been implicated in connecting the actin cytoskeleton to the FA. We have found that knocking down zyxin impaired NIH3T3 fibroblast's ability to sense and respond to changes in extracellular matrix in terms of their FA sizes, cell traction stress magnitudes and F-actin organization. Cell migration speed of zyxin knockdown fibroblasts was also independent of the underlying substrate rigidity, unlike wild type fibroblasts which migrated fastest at an intermediate substrate rigidity of 14 kPa. Wild type fibroblasts exhibited durotaxis by migrating toward regions of increasing substrate rigidity on polyacrylamide gels with substrate rigidity gradient, while zyxin knockdown fibroblasts did not exhibit durotaxis. Therefore, we propose zyxin as an essential protein that is required for rigidity sensing and durotaxis through modulating FA sizes, cell traction stress and F-actin organization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yip, Zhang, Chong, Cheruba, Woon, Chua, Goh, Yang, Tay, Koh and Chiam.)

Two-dimensional (2D) nanomaterials (NM) have emerged as promising platforms for antibacterial applications. However, the inherent "flatness" of 2D NM often limits the loading of antimicrobial components needed for synergistic bactericidal actions. Here, inspired by the highly ornamented siliceous frustules of diatoms, we prepared 2D ultrathin (<20 nm) and rigid "nanofrustule" plates via the out-of-plane growth of cetyltrimethylammonium bromide (CTAB) directed silica mesostructures on the surfaces of 2D graphene oxide nanosheets. The nanofrustules were characterized by the presence of mesoporous channels with a pore size of 3 nm and a high specific surface area of 674 m 2 g -1 . S -nitrosothiol-modification on the silica surfaces enables the development of a novel anti-infective nitric oxide (NO) releasing NO-nanofrustule system. The cage-like mesoporous silica architecture enabled a controlled and sustainable release of NO from the NO-nanofrustules under physiological conditions. The NO-nanofrustules displayed broad antibacterial effects against Staphylococcus aureus and Escherichia coli with a minimum inhibitory concentration of 250 μg ml -1 . Mechanistic studies revealed that the antibacterial property of NO-nanofrustules was attained via a unique "capture-and-release" mode-of-action. The first step entailed the capture of the bacteria by the NO-nanofrustules to form micro-aggregates. This was followed by the release of high levels of NO to the captured bacteria to elicit a potent anti-infective effect. In combination with the lack of cytotoxicity in human dermal cells, the 2D hybrid NO-nanofrustules may be utilized to combat wound infections in clinical settings.

Three-dimensional (3D) biomaterials with physiologically relevant and experimentally tractable biomechanical features are important platforms to advance our understanding of the influence of tissue mechanics in disease progression. Herein, an interpenetrating network (IPN) of collagen and alginate 3D culture system with tunable extracellular microstructure and mechanics is exploited as a tumor stroma proxy to study phenotypic plasticity of colorectal cancer-associated fibroblasts (CAF). In combination with Next Generation Sequencing (NGS) data analysis, we demonstrated that tuning the storage modulus of the IPN hydrogel between 49 and 419 Pa can trigger a reversible switch between an inflammatory (i-state, α-SMA low IL-6 high ) and myofibroblastic (m-state, α-SMA high IL-6 low ) state in CAF that is dependent on the polymer network confinement effect and ROS-HIF1-α mechanotransduction signaling axis. Secretome from m-state CAF upregulated several epithelial-mesenchymal-transition (EMT) transcripts and induced robust scattering in DLD-1, HCT116, and SW480 human colorectal adenocarcinoma, while the EMT-inducing capacity is muted in i-state CAF, suggestive of an anti-tumorigenic role. Our findings were further validated through Gene Expression Profiling Interactive Analysis (GEPIA), which showed that cytokines secreted at higher levels by i-state CAF are correlated (p < 0.05) with good overall colorectal cancer patient survival. Therefore, 3D network density and spatial cellular confinement are critical biophysical determinants that can profoundly influence CAF states, paracrine signaling, and EMT-inducing potential. STATEMENT OF SIGNIFICANCE: The communication between cancer cells and cancer-associated fibroblasts (CAF) contributes to tumor metastasis. CAF represent a diverse population of cellular subsets that can either promote or restrain tumor progression. However, the origin and cause of CAF heterogeneity remain elusive, limiting CAF-directed therapies for clinical use. We studied the dynamic phenotypes of CAF using a 3D physio-mimetic culture platform consisting of an interpenetrating collagen-alginate network. Combined with transcriptomic stratification and correlative analysis using cancer patient dataset, we showed phenotypic interconversion between inflammatory and myofibroblastic states, with anti- and pro-tumorigenic functions, in human colorectal CAF. This multidisciplinary study reveals the functional diversity of colorectal CAF caused by biophysical cues. The finding will influence the development of new CAF biomarkers and cancer therapies., 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 Ltd.)

Here we investigated nationwide clinical Bordetella pertussis isolated during 2005-2017 from different provinces of Iran, a country with more than 50 years whole cell vaccine immunisation history. Our results revealed the ongoing increase in the population of ptxP3/fim3-2 B. pertussis isolates in different provinces which were differentiated into nine clades. The largest clade (clade 8) which was previously found to be prevalent in Tehran was also prevalent across the country and clade 5 with ptxP3/prn9 genotype has also increased in frequency (14% of all ptxP3 isolates) in recent years. Furthermore, we detected the first ptxP3 B. pertussis isolates that does not express filamentous hemagglutinin (FhaB) as one of the major antigens of the pathogen and a key component of the acellular pertussis vaccine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Feeding freshwater crayfish species with different diets not only affects the water quality but also induces the abundance of various microbial communities in their digestive tracts. In this context, very limited research has been undertaken to understand the impacts of various protein incorporated aqua-diets on the characteristics of water and its microbial communities. In this study, we have critically analysed the water quality parameters including pH, dissolved oxygen, nitrate, nitrite, ammonia and phosphorus, as well as bacterial communities under marron (Cherax cainii) aquaculture, fed fishmeal (FM) and poultry by-product meal (PBM)-based diets for 60 days. The results unveiled that over the time, feeding has significant impacts on organic waste accumulation, especially ammonia, nitrate, nitrite and phosphate, while no effects were observed on pH and dissolved oxygen. Analysis of 16S rRNA sequence data of water sample indicated significant (P < 0.05) shift of microbial abundance in post-fed FM and PBM water with the evidence of microbial transmission from the gut of marron. Post-fed marron resulted in a significant correlation of Hafnia, Enterobacter, Candidatus Bacilloplasma and Aquitella with the quality and microbial population of water. The results of this study generated valuable knowledge database of microbes-water relationship for better health management practices and production of marron aquaculture fed with FM and PBM diets in under restricted feeding regime with the feeding ratios provided., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Hyperspectral imaging (HSI) provides additional information compared to regular color imaging, making it valuable in areas such as biomedicine, materials inspection and food safety. However, HSI is challenging because of the large amount of data and long measurement times involved. Compressed sensing (CS) approaches to HSI address this, albeit subject to tradeoffs between image reconstruction accuracy, time and generalizability to different types of scenes. Here, we develop improved CS approaches for HSI, based on parallelized multitrack acquisition of multiple spectra per shot. The multitrack architecture can be paired up with either of the two compatible CS algorithms developed here: (1) a sparse recovery algorithm based on block compressed sensing and (2) an adaptive CS algorithm based on sampling in the wavelet domain. As a result, the measurement speed can be drastically increased while maintaining reconstruction speed and accuracy. The methods were validated computationally both in noiseless as well as noisy simulated measurements. Multitrack adaptive CS has a ∼10 times shorter measurement plus reconstruction time as compared to full sampling HSI without compromising reconstruction accuracy across the sample images tested. Multitrack non-adaptive CS (sparse recovery) is most robust against Poisson noise at the expense of longer reconstruction times.

Despite being a rich source of bioactive compounds, the current exploitation of aquatic biomass is insufficient. Majority of the aquaculture industry side-streams are currently used for low-value purposes such as animal feed or composting material, with low economical returns. To maximize resource reuse and minimize waste generation, valorization efforts should be augmented with the aim to produce high-value products. Herein, we present a novel aquaculture wastes-derived multi-scale osteoconductive hybrid biocomposite that is composed of chemically crosslinked American bullfrog (Rana catesbeiana) skin-derived type I tropocollagen nanofibrils (~22.3 nm) network and functionalized with micronized (~1.6 μm) single-phase hydroxyapatite (HA) from discarded snakehead (Channa micropeltes) fish scales. The bioengineered construct is biocompatible, highly porous (>90%), and exhibits excellent osteoconductive properties, as indicated by robust adhesion and proliferation of human fetal osteoblastic 1.19 cell line (hFOB 1.19). Furthermore, increased expression level of osteo-related ALPL and BGLAP mRNA transcripts, as well as enhanced osteocalcin immunoreactivity and increasing Alizarin red S staining coverage on the hybrid biocomposite was observed over 21 days of culture. Collectively, the devised "waste-to-resource" platform represents a sustainable waste valorization strategy that is amendable for advanced bone repair and regeneration applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are key mediators of communication among cells, and clinical utilities of EVs-based biomarkers remain limited due to difficulties in isolating EVs from whole blood reliably. We report a novel inertial-based microfluidic platform for direct isolation of nanoscale EVs (exosomes, 50 to 200 nm) and medium-sized EVs (microvesicles, 200 nm to 1 μm) from blood with high efficiency (three-fold increase in EV yield compared to ultracentrifugation). In a pilot clinical study of healthy (n = 5) and type 2 diabetes mellitus (T2DM, n = 9) subjects, we detected higher EV levels in T2DM patients (P < 0.05), and identified a subset of "high-risk" T2DM subjects with abnormally high (∼10-fold to 50-fold) amounts of platelet (CD41a+) or leukocyte-derived (CD45+) EVs. Our in vitro endothelial cell assay further revealed that EVs from "high-risk" T2DM subjects induced significantly higher vascular inflammation (ICAM-1 expression) (P < 0.05) as compared to healthy and non-"high-risk" T2DM subjects, reflecting a pro-inflammatory phenotype. Overall, the EV isolation tool is scalable, and requires less manual labour, cost and processing time. This enables further development of EV-based diagnostics, whereby a combined immunological and functional phenotyping strategy can potentially be used for rapid vascular risk stratification in T2DM.

Mechanistic understanding of atherosclerosis is largely hampered by the lack of a suitable in vitro human arterial model that recapitulates the arterial wall structure, and the interplay between different cell types and the surrounding extracellular matrix (ECM). This work introduces a novel microfluidic endothelial cell (EC)-smooth muscle cell (SMC) 3D co-culture platform that replicates the structural and biological aspects of the human arterial wall for modeling early atherosclerosis. Using a modified surface tension-based ECM patterning method, we established a well-defined intima-media-like structure, and identified an ECM composition (collagen I and Matrigel mixture) that retains the SMCs in a quiescent and aligned state, characteristic of a healthy artery. Endothelial stimulation with cytokines (IL-1β and TNFα) and oxidized low-density lipoprotein (oxLDL) was performed on-chip to study various early atherogenic events including endothelial inflammation (ICAM-1 expression), EC/SMC oxLDL uptake, SMC migration, and monocyte-EC adhesion. As a proof-of-concept for drug screening applications, we demonstrated the atheroprotective effects of vitamin D (1,25(OH)2D3) and metformin in mitigating cytokine-induced monocyte-EC adhesion and SMC migration. Overall, the developed arterial wall model facilitates quantitative and multi-factorial studies of EC and SMC phenotype in an atherogenic environment, and can be readily used as a platform technology to reconstitute multi-layered ECM tissue biointerfaces.

Background: The urea breath test (UBT) is widely used for diagnosing Helicobacter pylori infection. In the Shenzhen Kuichong People's Hospital, some UBT findings were contradictory to the histology outcomes, therefore this study aimed to assess and compare the diagnostic performance of both 13 C- and 14 C-UBT assays., Methods: We recruited 484 H. pylori-treatment naïve patients, among which 217 and 267 were tested by the 13 C-UBT or 14 C-UBT, respectively. The cutoff value for H. pylori positivity based on manufacturer's instruction was 4% delta over baseline (DOB) for the 13 C-UBT, and 100 disintegrations per minute (DPM) for the 14 C-UBT. Gastric biopsies of the antrum and corpus were obtained during endoscopy for histopathology., Results: In patients who were tested using the 13 C-UBT kit, histopathology was positive in 136 out of 164 UBT-positive patients (82.9% concordance), and negative in 46 out of 53 UBT-negative cases (86.8% concordance). For the 14 C-UBT-tested patients, histopathology was positive for H. pylori in 186 out of 220 UBT-positive patients (84.5% concordance), and negative in 41 out of 47 UBT-negative cases (87.2% concordance). While the 13 C-UBT and 14 C-UBT each had a high sensitivity level of 95.1% and 96.9%, respectively, their specificity was low, at 62.2% and 54.7%, respectively. By using new optimal cutoff values and including an indeterminate range (3-10.3% DOB for 13 C-UBT and 87-237 DPM for 14 C-UBT), the specificity values can be improved to 76.7% and 76.9% for the 13 C- and 14 C-UBT, respectively., Conclusions: The establishment of an indeterminate range is recommended to allow for repeated testing to confirm H. pylori infection, and thereby avoiding unnecessary antibiotic treatment., Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000041570. Registered 29 December 2020- Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=66416&htm=4.

3D cellular spheroids/microcarriers (100 µm-1 mm) are widely used in biomanufacturing, and non-invasive biosensors are useful to monitor cell quality in bioprocesses. In this work, a novel microfluidic approach for label-free and continuous-flow monitoring of single spheroid/microcarrier (hydrogel and Cytodex) based on electrical impedance spectroscopy using co-planar Field's metal electrodes is reported. Through numerical simulation and experimental validation, two unique impedance signatures (|Z LF | (60 kHz), |Z HF | (1 MHz)) which are optimal for spheroid growth and viability monitoring are identified. Using a closed-loop recirculation system, it is demonstrated that |Z LF | increases with breast cancer (MCF-7) spheroid biomass, while higher opacity (impedance ratio |Z HF |/|Z LF |) indicates cell death due to compromised cell membrane. Anti-cancer drug (paclitaxel)-treated spheroids also exhibit lower |Z LF | with increased cell dissociation. Interestingly, impedance characterization of adipose-derived mesenchymal stem cell differentiation on Cytodex microcarriers reveals that adipogenic cells (higher intracellular lipid content) exhibit higher impedance than osteogenic cells (more conductive due to calcium ions) for both microcarriers and single cell level. Taken together, the developed platform offers great versatility for multi-parametric analysis of spheroids/microcarriers at high throughput (≈1 particle/s), and can be readily integrated into bioreactors for long-term and remote monitoring of biomass and cell quality., (© 2021 Wiley-VCH GmbH.)

Plastics in waste electronics (E-plastics) account for approximately 20% of the entire global electronic waste (E-waste) stream. Most of the E-plastics are not recycled as the presence of toxic additives (e.g. heavy metals, brominated flame retardants (BFRs), antimony, etc.) have associated environmental and health concerns. However, the majority of the studies are focused on quantitative assessment of the toxic constituents in E-plastics, while empirical information regarding the potential toxic effects in humans is largely lacking. To gain a deeper appreciation into the toxicological profile of E-plastics, in situ time-dependent exposures of 6 different human cell lines to a panel of 8 representative E-plastics recovered from liquid crystal displays (LCD), keyboards, screen frames, and wire insulators were conducted. Although several hazardous elements (e.g. Pb, As, Sb, Zn, Cu, etc) were detected at concentrations that far exceed the limit values permitted by the Restriction of Hazardous Substances Directive and EU Directives in the panel E-plastics, in-depth analysis of the 144 unique cell viability data points and live-dead staining experiments suggest that the acute and sub-chronic toxic effects of E-plastics in direct contact with human cells are negligible. These observations agreed with the inductively coupled plasma-optical emission spectrometry data, which revealed that leaching of these toxic additives into the biological milieu is not sufficiently high to trigger a cytotoxic response up to a continuous culture period of 2 weeks. The novel insights gained from this study are posited to further clarify the uncertainty associated with the safety and circular economy implementation of E-plastics., 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 Ltd. All rights reserved.)

The rise of electronic waste (e-waste) generation around the globe has become a major concern in recent times and its recycling is mostly focused on the recovery of valuable metals, such as gold, silver, and copper, etc. However, e-waste consists of a significant weight fraction of plastics (25-30%) which are either discarded or incinerated. There is a growing need for recycling of these e-waste plastics. The majority of them are made from high-quality polymers (composites), such as acrylonitrile butadiene styrene (ABS), high impact polystyrene (HIPS), polycarbonate (PC), polyamide (PA), polypropylene (PP) and epoxies. These plastics are often contaminated with hazardous materials, such as brominated flame retardants (BFRs) and heavy metals (such as Pb and Hg). Under any thermal stress (thermal degradation), the Br present in the e-waste plastics produces environmentally hazardous pollutants, such as hydrogen bromide or polybrominated diphenyl ethers/furans (PBDE/Fs). The discarded plastics can lead to the leaching of toxins into the environment. It is important to remove the toxins from the e-waste plastics before recycling. This review article gives a detailed account of e-waste plastics recycling and recovery using thermochemical processes, such as extraction (at elevated temperature), incineration (combustion), hydrolysis, and pyrolysis (catalytic/non catalytic). A basic framework of the existing processes has been established by reviewing the most interesting findings in recent times and the prospects that they open in the field recycling of e-waste plastics., 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 Ltd. All rights reserved.)

The potential genotoxic effects of engineered nanomaterials (ENMs) may occur through the induction of DNA damage or the disruption of DNA repair processes. Inefficient DNA repair may lead to the accumulation of DNA lesions and has been linked to various diseases, including cancer. Most studies so far have focused on understanding the nanogenotoxicity of ENM-induced damages to DNA, whereas the effects on DNA repair have been widely overlooked. The recently developed fluorescence multiplex-host-cell reactivation (FM-HCR) assay allows for the direct quantification of multiple DNA repair pathways in living cells and offers a great opportunity to address this methodological gap. Herein an FM-HCR-based method is developed to screen the impact of ENMs on six major DNA repair pathways using suspended or adherent cells. The sensitivity and efficiency of this DNA repair screening method were demonstrated in case studies using primary human small airway epithelial cells and TK6 cells exposed to various model ENMs (CuO, ZnO, and Ga 2 O 3 ) at subcytotoxic doses. It was shown that ENMs may inhibit nucleotide-excision repair, base-excision repair, and the repair of oxidative damage by DNA glycosylases in TK6 cells, even in the absence of significant genomic DNA damage. It is of note that the DNA repair capacity was increased by some ENMs, whereas it was suppressed by others. Overall, this method can be part of a multitier, in vitro hazard assessment of ENMs as a functional, high-throughput platform that provides insights into the interplay of the properties of ENMs, the DNA repair efficiency, and the genomic stability.

Transplantation of microencapsulated islet cells holds great potential for the treatment of type 1 diabetes mellitus. However, its clinical translation is hampered by the peri-transplantation loss of islet viability and functionality in the microcapsules. In this work, a novel islet cells biomimetic microencapsulant material that is based on the interpenetrating networks of alginate and extracellular matrix (ECM) hydrogel composite (AEC) is presented. The ECM component is derived from human lipoaspirate. In situ encapsulation of pancreatic β islet cells (MIN6 β-cells) can be achieved via ionotropic gelation of the alginate matrix and thermal-induced gelation of the pepsin-solubilized ECM pre-gel. Due to the enhanced cell-matrix interaction, islets encapsulated within the AEC microcapsules (≈640 µm) display sevenfold increase in cell growth over 1 week of culture and characteristic glucose-stimulated insulin response in vitro. The results show that the AEC microcapsule is a potent platform to bioaugment the performance of islet cells., (© 2020 Wiley-VCH GmbH.)

Objectives: Drug resistance of Helicobacter pylori is a major clinical problem worldwide. The objective of the present study was to investigate the prevalence of antibiotic-resistant H. pylori in the city of Shenzhen in China, as well as to identify the genetic mutations specifically associated with drug resistance rather than unrelated phylogenetic signals., Methods: Antibiotic susceptibility testing was performed on 238 clinical strains successfully isolated from H. pylori-positive dyspeptic patients who underwent gastroscopy at the Department of Gastroenterology in Shenzhen People's Second Hospital. Following WGS of all strains using Illumina technology, mutation and phylogenetic analyses were performed., Results: The resistance rates were 84.9%, 35.3%, 25.2% and 2.1% for metronidazole, clarithromycin, ciprofloxacin and rifampicin, respectively. An A2143G conversion in the 23S rRNA gene was the primary mutation observed in clarithromycin-resistant strains, whilst N87K/I and D91G/N/Y in GyrA were detected in ciprofloxacin-resistant strains. In RdxA, our results demonstrated that only R16H/C and M21A are significant contributors to metronidazole resistance; there were 15 other sites, but these are phylogenetically related and thus unrelated to metronidazole resistance., Conclusions: There is a high prevalence of metronidazole, clarithromycin and ciprofloxacin resistance and a low prevalence of rifampicin resistance in H. pylori from Shenzhen, China. Omission of phylogenetically related sites will help to improve identification of sites genuinely related to antibiotic resistance in H. pylori and, we believe, other species., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that hypoxic tumours synthesize hypoxia-sensitive proteins for packing into EVs to modulate their microenvironment for cancer progression. In the current report, we employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia sensitive proteins in tumour-derived EVs protein. The results revealed that hypoxia stimulated cells to synthesize EVs proteins involved in enhancing tumour cell proliferation (NRSN2, WISP2, SPRX1, LCK), metastasis (GOLM1, STC1, MGAT5B), stemness (STC1, TMEM59), angiogenesis (ANGPTL4), and suppressing host immunity (CD70). In addition, functional clustering analyses revealed that tumour hypoxia was strongly associated with rapid synthesis and EV loading of lysosome-related hydrolases and membrane-trafficking proteins to enhance EVs secretion. Moreover, lung cancer-derived EVs were also enriched in signalling molecules capable of inducing epithelial-mesenchymal transition in recipient cancer cells to promote their migration and invasion. Together, these data indicate that lung-cancer-derived EVs can act as paracrine/autocrine mediators of tumorigenesis and metastasis in hypoxic microenvironments. Tumour EVs may, therefore, offer novel opportunities for useful biomarkers discovery and therapeutic targeting of different cancer types and at different stages according to microenvironmental conditions.

The development of environmentally benign hydrometallurgical processes to treat spent lithium-ion batteries (LIBs) is a critical aspect of the electronic-waste circular economy. Herein, as an alternative to the highly explosive H 2 O 2 , discarded orange peel powder (OP) is valorized as a green reductant for the leaching of industrially produced LIBs scraps in citric acid (H 3 Cit) lixiviant. The reductive potential of the cellulose- and antioxidant-rich OP was validated using the 3,5-dinitrosalicylic acid and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid assays. Leaching parameters such as OP concentration (200 mg), processing temperature (100 °C), H 3 Cit concentration (1.5 M), reaction duration (4 h), and slurry density (25 g/mL) were systematically optimized to achieve 80-99% leaching efficiencies of Ni, Mn, Co, and Li from the LIB "black mass". Importantly, solid side-streams generated by the OP-enabled leaching displayed negligible cytotoxicity in three different human cell lines, suggesting that the process is environmentally safe. As a proof of concept, Co(OH) 2 was selectively recovered from the green lixiviant and subsequently utilized to fabricate new batches of LiCoO 2 (LCO) coin cell batteries. Galvanostatic charge-discharge test revealed that the regenerated batteries exhibited initial charge and discharge values of 120 and 103 mAh/g, respectively, which is comparable to the performance of commercial LCO batteries. The use of fruit peel waste to recover valuable metals from spent LIBs is an effective, ecofriendly, and sustainable strategy to minimize the environmental footprint of both waste types.

Exogenous sources of amino acids are essential nutrients to fuel cancer growth. Here, the increased demand for amino acid displayed by cancer cells is unconventionally exploited as a design principle to replete cancer cells with apoptosis inducing nanoscopic porous amino acid mimics (Nano-PAAM). A small library consisting of nine essential amino acids nanoconjugates (30 nm) are synthesized, and the in vitro anticancer activity is evaluated. Among the Nano-PAAMs, l-phenylalanine functionalized Nano-PAAM (Nano-pPAAM) has emerged as a novel nanotherapeutics with excellent intrinsic anticancer and cancer-selective properties. The therapeutic efficacy of Nano-pPAAM against a panel of human breast, gastric, and skin cancer cells could be ascribed to the specific targeting of the overexpressed human large neutral amino acid transporter SLC7A5 (LAT-1) in cancer cells, and its intracellular reactive oxygen species (ROS) inducing properties of the nanoporous core. At the mechanistic level, it is revealed that Nano-pPAAM could activate both the extrinsic and intrinsic apoptosis pathways to exert a potent "double-whammy" anticancer effect. The potential clinical utility of Nano-pPAAM is further investigated using an MDA-MB-231 xenograft in NOD scid gamma mice, where an overall suppression of tumor growth by 60% is achieved without the aid of any drugs or application of external stimuli., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Exposure to inhaled anthropogenic nanomaterials (NM) with dimension <100 nm has been implicated in numerous adverse respiratory outcomes. Although studies have identified key NM physiochemical determinants of pneumonic nanotoxicity, the complex interactive and cumulative effects of NM exposure, especially in individuals with preexisting inflammatory respiratory diseases, remain unclear. Herein, the susceptibility of primary human small airway epithelial cells (SAEC) exposed to a panel of reference NM, namely, CuO, ZnO, mild steel welding fume (MSWF), and nanofractions of copier center particles (Nano-CCP), is examined in normal and tumor necrosis factor alpha (TNF-α)-induced inflamed SAEC. Compared to normal SAEC, inflamed cells display an increased susceptibility to NM-induced cytotoxicity by 15-70% due to a higher basal level of intracellular reactive oxygen species (ROS). Among the NM screened, ZnO, CuO, and Nano-CCP are observed to trigger an overcompensatory response in normal SAEC, resulting in an increased tolerance against subsequent oxidative insults. However, the inflamed SAEC fails to adapt to the NM exposure due to an impaired nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated cytoprotective response. The findings reveal that susceptibility to pulmonary nanotoxicity is highly dependent on the interplay between NM properties and inflammation of the alveolar milieu., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)