Dichlorodiphenyltrichloroethane for Malaria and Agricultural Uses and Its Impacts on Human Health.

Pesticides are widely used in agriculture and disease control, and dichlorodiphenyltrichloroethane (DDT) is one of the most used pesticides in human history. Besides its significant contributions in pest control in agriculture, DDT was credited as having saved millions of human lives for controlling malaria and other deadly insect-transmitted diseases. Even today, the use of DDT in some countries for malaria control cannot be replaced without endangering people who live there. The recent COVID-19 pandemic has changed our lives and reminded us of the challenges in dealing with infectious diseases, especially deadly ones including malaria. However, DDT and its metabolites are stable, persist long, are found in almost every corner of the world, and their persistent effects on humans, animals, and the environment must be seriously considered. This review will focus on the history of DDT use for agriculture and malaria control, the pathways for the spread of DDT, benefits and risks of DDT use, DDT exposure to animals, humans, and the environment, and the associated human health risks. These knowledge and findings of DDT will benefit the selection and management of pesticides worldwide.

Glucose sensing based on hydrogel grating incorporating phenylboronic acid groups.

We proposed a hydrogel grating sensor functionalized with phenylboronic acid (PBA) group for glucose concentration detection. A PBA functionalized polyacrylamide hydrogel film was first prepared via ultraviolet polymerization. Then, the diffraction grating was written on the hydrogel film via the femto-second (fs) laser point-by-point direct inscription. Binding between the PBA groups in the hydrogel and glucose molecules would lead to the swelling of hydrogel and the thus grating structure, thus modifying the diffraction properties of the grating. We experimentally characterized the swelling and transmission of the grating with different glucose concentrations. Sensitivity of the sensor was defined as variations in relative diffraction efficiency in response to glucose concentration changes, and was experimentally found to 0.61%/mM. The proposed sensor showed fast response towards the presence of glucose, and its reusability and biocompatibility were also confirmed. The use of fs-laser inscription technique does not require a pre-fabricated template, and would allow to directly modify the fabrication parameters such as scanning speed, pulse energy and frequency. Therefore, one is able to conveniently optimize the grating structure and improve the inscription efficiency. The proposed hydrogel grating could be potentially fabricated into wearable sensors, namely, contact lenses, for continuous monitoring of tear glucose level with rapid response.

Pinecone-Inspired Nanoarchitectured Smart Microcages Enable Nano/Microparticle Drug Delivery.

Drug delivery plays a vital role in medicine and health, but the on-demand delivery of large-sized drugs using stimuli-triggered carriers is extremely challenging. Most present capsules consist of polymeric dense shells with nanosized pores (<10 nm), thus typically lack permeability for nano/microparticle drugs. Here, a pinecone-inspired smart microcage with open network shells, assembled from cellulose nanofibrils (CNFs), is reported for nano/microparticle drug delivery. The approach allows the nanoarchitectured, functionalized CNFs to assemble into mechanically robust, haystack-like network shells with tunable large-through pores and polypeptide-anchored points on a large scale. Such open network shells can intelligently open/close triggered by lesion stimuli, making the therapy "always on-demand." The resulting pinecone-inspired microcages exhibit integrated properties of superior structural stability, superhydrophilicity, and pH-triggered, smart across-shell transport of emerging antimicrobial silver nanoparticles and bioactive silicate nanoplatelets (sizes of >100 nm), which enable both extraordinary anti-infection and bone regeneration. This work provides new insights into the design and development of multifunctional encapsulation and delivery carriers for medical and environmental applications.

Iron overload threatens the growth of osteoblast cells via inhibiting the PI3K/AKT/FOXO3a/DUSP14 signaling pathway.

Iron overload is a common stress in the development of cells. Growing evidence has indicated that iron overload is associated with osteoporosis. Therefore, enhancing the understanding of iron overload would benefit the development of novel approaches to the treatment of osteoporosis. The purpose of the present study was to analyze the effect of iron overload on osteoblast cells, via the MC3T3-E1 cell line, and to explore its possible underlying molecular mechanisms. Ferric ammonium citrate (FAC) was utilized to simulate iron overload conditions in vitro. FAC-induced iron overload strongly suppressed proliferation of osteoblast cells and induced apoptosis. Moreover, iron overload strongly suppressed the expression of dual-specificity phosphatase 14 (DUSP14). Additionally, overexpression of DUSP14 protected osteoblast cells from the deleterious effects of iron overload, and this protective effect was mediated by FOXO3a. Additionally, matrine rescued the function of DUSP14 in osteoblast cells. Most importantly, our analysis demonstrated the essential role of the PI3K/AKT/FOXO3a/DUSP14 signaling pathway in the defense against iron overload in osteoblast cells. Overall, our results not only elucidate deleterious effects of iron overload, but also unveil its possible signaling pathway in osteoblast cells.

Silver nanoparticles present high intracellular and extracellular killing against Staphylococcus aureus.

OBJECTIVES: Bone and joint infections caused by Staphylococcus aureus are becoming increasingly difficult to treat due to rising antibiotic resistance, resilient biofilms and intracellular survival of S. aureus. It has been challenging to identify and develop antimicrobial agents that can be used to kill extracellular and intracellular bacteria while having limited toxicity towards host cells. In addressing this challenge, this study investigates the antimicrobial efficacy and toxicity of silver nanoparticles (AgNPs). METHODS: Intracellular bacteria were generated using a co-culture model of human osteoblast cells and S. aureus. Extracellular and intracellular S. aureus were treated with AgNPs, antibiotics and their combinations, and numbers of colonies were quantified. Toxicity of AgNPs against human osteoblast cells was determined by quantifying the number of viable cells after treatment. RESULTS: AgNPs demonstrated excellent antimicrobial activity against extracellular S. aureus with a 100% killing efficacy at concentrations as low as 56 µM, along with a high intracellular killing efficacy of 76% at 371 µM. AgNPs were non-toxic or slightly toxic towards human osteoblasts at the concentrations studied (up to 927 µM). Moreover, smaller-sized (40 nm) AgNPs were more efficacious in killing bacteria compared with their larger-sized (100 nm) counterparts and synergistic antimicrobial effects against extracellular bacteria were observed when AgNPs were combined with gentamicin. CONCLUSIONS: AgNPs and their combination with antibiotics have demonstrated high extracellular and intracellular bacterial killing and presented unique aspects for potential clinical applications, especially for chronic and recurrent infections where intracellular bacteria may be the cause.

Two-Dimensional Graphene Family Material: Assembly, Biocompatibility and Sensors Applications.

Graphene and its chemically exfoliated derivatives-GO and rGO-are the key members of graphene family materials (GFM). The atomically thick crystal structure and the large continuous π conjugate of graphene imparts it with unique electrical, mechanical, optical, thermal, and chemical properties. Although those properties of GO and rGO are compromised, they have better scalability and chemical tunability. All GFMs can be subject to noncovalent modification due to the large basal plane. Besides, they have satisfying biocompatibility. Thus, GFMs are promising materials for biological, chemical and mechanical sensors. The present review summarizes how to incorporate GFMs into different sensing system including fluorescence aptamer-based sensors, field-effect transistors (FET), and electrochemical sensors, as well as, how to covalently and/or non-covalently modify GFMs to achieve various detection purpose. Sensing mechanisms and fabrication strategies that will influence the sensitivity of different sensing system are also reviewed.

Optimized adipose tissue engineering strategy based on a neo-mechanical processing method.

Decellularized adipose tissue (DAT) represents a promising scaffold for adipose tissue engineering. However, the unique and prolonged lipid removal process required for adipose tissue can damage extracellular matrix (ECM) constituents. Moreover, inadequate vascularization limits the recellularization of DAT in vivo. We proposed a neo-mechanical protocol for rapidly breaking adipocytes and removing lipid content from adipose tissue. The lipid-depleted adipose tissue was then subjected to a fast and mild decellularization to fabricate high-quality DAT (M-DAT). Adipose liquid extract (ALE) derived from this mechanical process was collected and incorporated into M-DAT to further optimize in vivo recellularization. Ordinary DAT was fabricated and served as a control. This developed strategy was evaluated based on decellularization efficiency, ECM quality, and recellularization efficiency. Angiogenic factor components and angiogenic potential of ALE were evaluated in vivo and in vitro. M-DAT achieved the same decellularization efficiency, but exhibited better retention of ECM components and recellularization, compared with those with ordinary DAT. Protein quantification revealed considerable levels of angiogenic factors (basic fibroblast growth factor, epidermal growth factor, transforming growth factor-ß1, and vascular endothelial growth factor) in ALE. ALE promoted tube formation in vitro and induced intense angiogenesis in M-DAT in vivo; furthermore, higher expression of the adipogenic factor PPARγ and greater numbers of adipocytes were evident following ALE treatment, compared with those in the M-DAT group. Mechanical processing of adipose tissue led to the production of high-quality M-DAT and angiogenic factor-enriched ALE. The combination of ALE and M-DAT could be a promising strategy for engineered adipose tissue construction.

Biomimetic Layer-by-Layer Self-Assembly of Nanofilms, Nanocoatings, and 3D Scaffolds for Tissue Engineering.

Achieving surface design and control of biomaterial scaffolds with nanometer- or micrometer-scaled functional films is critical to mimic the unique features of native extracellular matrices, which has significant technological implications for tissue engineering including cell-seeded scaffolds, microbioreactors, cell assembly, tissue regeneration, etc. Compared with other techniques available for surface design, layer-by-layer (LbL) self-assembly technology has attracted extensive attention because of its integrated features of simplicity, versatility, and nanoscale control. Here we present a brief overview of current state-of-the-art research related to the LbL self-assembly technique and its assembled biomaterials as scaffolds for tissue engineering. An overview of the LbL self-assembly technique, with a focus on issues associated with distinct routes and driving forces of self-assembly, is described briefly. Then, we highlight the controllable fabrication, properties, and applications of LbL self-assembly biomaterials in the forms of multilayer nanofilms, scaffold nanocoatings, and three-dimensional scaffolds to systematically demonstrate advances in LbL self-assembly in the field of tissue engineering. LbL self-assembly not only provides advances for molecular deposition but also opens avenues for the design and development of innovative biomaterials for tissue engineering.

Theranostic, pH-Responsive, Doxorubicin-Loaded Nanoparticles Inducing Active Targeting and Apoptosis for Advanced Gastric Cancer.

This study developed a kind of magnetic-polymer nanocarrier with folate receptor-targeting and pH-sensitive multifunctionalities to carry doxorubicin (DOX) for treatment of advanced gastric cancer (AGC). Folate-conjugated, pH-sensitive, amphiphilic poly(ß-aminoester) self-assembled with hydrophobic oleic acid-modified iron oxide nanoparticles, and the resulting hydrophobic interaction area is a reservoir for lipophilic DOX (F-P-DOX). Confocal microscopy illustrated that F-P-DOX treatment could keep higher DOX accumulation in cells than P-DOX (without folate conjugation), and therefore get a higher efficiency of DOX internalization at pH 6.5 than at pH 7.4. Electron microscope characterization and real-time polymerase chain reaction revealed cell apoptosis promoted by F-P-DOX. The better efficacy of F-P-DOX on GC than free DOX and P-DOX was determined by MTT assay and xenograft model. Moreover, the accumulation of F-P-DOX in the tumor site was detected by magnetic resonance imaging (MRI). All those observations suggest F-P-DOX could be a promising theranostic candidate for AGC treatment.

Nanomedicine as an innovative therapeutic strategy for pediatric cancer.

Childhood cancer is the leading cause of mortality in children between 1 and 14 years of age. Malignancy accounts for 18 % of overall childhood mortality. Therapeutic advances in the field of pediatric oncology have helped to increase survival. Nanotechnology is the modification of materials at a nanoscale and can be used to deliver therapeutic agents. Examples of nanotechnology applications are organic self-assembled amphiphilic polymers, non-organic nanocarriers such as nanotubes and quantum dots. Each of these has their own utility in different settings. Application of nanotechnology in medicine has been extensively studied. Examples of pediatric tumors that received special attention are: neuroblastoma, retinoblastoma, central nervous system tumors and musculoskeletal tumors. This review will summarize the application of nanomedicine as an innovative management strategy in pediatric oncology.

Low density methacrylated pea, corn, and tapioca starch covalent cryogels with excellent elasticity and water/oil absorption capacity.

Porous starch materials are promising in several applications as renewable natural biomaterials. This study reports an approach combining methacrylation of starch and chemical crosslinked cryogelation to fabricate highly elastic macroporous starch (ST-MA) cryogels with impressed water/oil absorption capacity and wet thermal stability among starch based porous materials. Five different types of starch, including pea, normal corn, high amylose corn, tapioca, and waxy maize starch with different amylose content, have been studied. The methacrylation degree is not related with amylose content. All cryogels exhibited excellent compressive elasticity enduring 90 % deformation without failure and good robustness in cyclic tests. The ST-MA cryogels from pea starch exhibited the highest Young's modulus and compressive strength among five types of starch. These covalent cryogels exhibit high wet-thermal stability and enzymatic hydrolysis stability, while still are biodegradable. The dry ST-MA sponges (2 wt%) showed outstanding liquid absorption capacity, absorbing ~40 folds (g/g) of water or ~ 36 folds (g/g) of oil respectively. All types of starch have similar liquid absorption performance. This study provides a universal approach to fabricate highly elastic covalent starch macroporous materials with impressed liquid absorption capacity and outstanding stability, especially wet-thermal stability, and may expand their applications.

Antimicrobial Peptide Identified via Machine Learning Presents Both Potent Antibacterial Properties and Low Toxicity toward Human Cells.

Preventing infection is a critical clinical challenge; however, the extensive use of antibiotics has resulted in remarkably increased antibiotic resistance. A variety of antibiotic alternatives including antimicrobial peptides (AMPs) have been studied. Unfortunately, like most conventional antibiotics, most current AMPs have shown significantly high toxicity toward the host, and therefore induce compromised host responses that may lead to negative clinical outcomes such as delayed wound healing. In this study, one of the AMPs with a short length of nine amino acids was first identified via machine learning to present potentially low cytotoxicity, and then synthesized and validated in vitro against both bacteria and mammalian cells. It was found that this short AMP presented strong and fast-acting antimicrobial properties against bacteria like Staphylococcus aureus, one of the most common bacteria clinically, and it targeted and depolarized bacterial membranes. This AMP also demonstrated significantly lower (e.g., 30%) toxicity toward mammalian cells like osteoblasts, which are important cells for new bone formation, compared to conventional antibiotics like gentamicin, vancomycin, rifampin, cefazolin, and fusidic acid at short treatment times (e.g., 2 h). In addition, this short AMP demonstrated relatively low toxicity, similar to osteoblasts, toward an epithelial cell line like BEAS-2B cells.

Duo-role Platelet-rich Plasma: temperature-induced fibrin gel and growth factors' reservoir for microneedles to promote hair regrowth.

INTRODUCTION: Alopecia concerns more than half our adult population. Platelet-rich plasma (PRP) has been applied in skin rejuvenation and hair loss treatment. However, the pain and bleeding during injection and the troublesome for fresh preparation of each action limit PRP's in-depth applying dedication to clinics. OBJECTIVES: We report a temperature-sensitive PRP induced fibrin gel included in a detachable transdermal microneedle (MN) for hair growth. RESULTS: PRP gel interpenetrated with the photocrosslinkable gelatin methacryloyl (GelMA) to realize sustained release of growth factors (GFs) and led to 14% growth in mechanical strength of a single microneedle whose strength reached 1.21 N which is sufficient to penetrate the stratum corneum. PRP-MNs' release of VEGF, PDGF, and TGF-ß were characterized and quantitatively around the hair follicles (HFs) for 4-6 days consecutively. PRP-MNs promoted hair regrowth in mice models. From transcriptome sequencing, PRP-MNs induced hair regrowth through angiogenesis and proliferation. The mechanical and TGF-ß sensitive gene Ankrd1 was significantly upregulated by PRP-MNs treatment. CONCLUSION: PRP-MNs show convenient, minimally invasive, painless, inexpensive manufacture, storable and sustained effects in boosting hair regeneration.

Platelet Vesicles Synergetic with Biosynthetic Cellulose Aerogels for Ultra-Fast Hemostasis and Wound Healing.

Achieving hemostasis in penetrating and irregular wounds is challenging because the hemostasis factor cannot arrive at the bleeding site, and substantial bleeding will wash away the blood clot. Since the inherently gradual nature of blood clot formation takes time, a physical barrier is needed before blood clot formation. Herein, an ultra-light and shape memory hemostatic aerogel consisting of oxidized bacterial cellulose (OBC) and platelet extracellular vesicles (pVEs) is reported. The OBC-pVEs aerogel provides a physical barrier for the bleeding site by self-expansion, absorbing the liquid from blood to concentrate platelets and clotting factors and accelerating the clot formation by activating platelets and transforming fibrinogen into fibrin. In the rat liver and tail injury models, the blood loss decreases by 73% and 59%, and the bleeding times are reduced by 55% and 62%, respectively. OBC-pVEs aerogel has also been shown to accelerate wound healing. In conclusion, this work introduces an effective tool for treating deep, non-compressible, and irregular wounds and offers valuable strategies for trauma bleeding and wound treatment.

Ultra-Hydrophobic Gauze Driving Super-Haemostasis.

Controlling bleeding by applying pressing cotton gauze is the most facile treatment in prehospital emergencies. However, the wettable nature of cotton fibers leads to unnecessary blood loss due to excessive blood absorption, inseparable adhesion-induced pain, and pliable to infection. Here, a kind of ultra-hydrophobic haemostatic anti-adhesive gauze whose surface is loaded with polydimethylsiloxane (PDMS) and hydrophobic-modified cellulose nanocrystals (CNCs), achieving a water contact angle of ≈160° is developed. It is demonstrated that the mechanism by which hydrophobic CNCs promote blood clotting is associated with their ability to activate coagulation factors, contributing to fibrin formation, and promoting platelet activation. The blood-restricting effect results from the low surface energy layer formed by PDMS and then the alkyl chains of hydrophobic CNCs are combined. The produced ultra-hydrophobic gauze resists blood flow and diffusion, decreases blood loss, is effortlessly peelable, and minimizes pathogen adhesion. Compared to the commercial cotton gauze, this gauze achieved effective haemostasis and antiadhesion by reducing blood loss by more than 90%, shortening haemostasis time by more than 75%, lowering peeling force by more than 90% and minifying bacterium attachment by more than 95%. This work presents promising applications in terms of prehospital first aid.

Correction: Janus N,N-dimethylformamide as a solvent for a gradient porous wound dressing of poly(vinylidene fluoride) and as a reducer for in situ nano-silver production: anti-permeation, antibacterial and antifouling activities against multi-drug-resistant bacteria both in vitro and in vivo.

[This corrects the article DOI: 10.1039/C8RA03234C.].

Early infiltrating NKT lymphocytes attenuate bone regeneration through secretion of CXCL2.

Trauma rapidly mobilizes the immune response of surrounding tissues and activates regeneration program. Manipulating immune response to promote tissue regeneration shows a broad application prospect. However, the understanding of bone healing dynamics at cellular level remains limited. Here, we characterize the landscape of immune cells after alveolar bone injury and reveal a pivotal role of infiltrating natural killer T (NKT) cells. We observe a rapid increase in NKT cells after injury, which inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and impair alveolar bone healing. Cxcl2 is up-regulated in NKT cells after injury. Systemic administration of CXCL2-neutralizing antibody or genetic deletion of Cxcl2 improves the bone healing process. In addition, we fabricate a gelatin-based porous hydrogel to deliver NK1.1 depletion antibody, which successfully promotes alveolar bone healing. In summary, our study highlights the importance of NKT cells in the early stage of bone healing and provides a potential therapeutic strategy for accelerating bone regeneration.

Microgels sense wounds' temperature, pH and glucose.

Wound healing concerns almost all bed-side related diseases. With our increasing comprehension of healing nature, the physical and chemical natures behind the wound microenvironment have been decoupled. Wound care demands timely screening and prompt diagnosis of wound complications such as infection and inflammation. Biosensor by the way of exhaustive collection, delivery, and analysis of data, becomes indispensable to arrive at an ideal healing upshot and controlling complications by capturing in-situ wound status. Electrochemical based sensors carry some potential unstable performance subjected to the electrical circuitry and power access and contamination. The colorimetric sensors are free from those concerns. We report that microsensors designed from O/W/O of capillary fluids can continuously monitor wound temperature, pH and glucose concentration. We combined three different types of microgels to encapsulate liquid crystals of cholesterol, nontoxic fuel litmus and two glucose-sensitizing enzymes. A smartphone applet was then developed to convert wound healing images to RGB of digitalizing data. The microgel dressing effectively demonstrates the local temperature change, pH and glucose levels of the wound in high resolution where a microgel is a 'pixel'. They are highly responsive, reversible and accurate. Monitoring multiple physicochemical and physiological indicators provides tremendous potential with insight into healing processing.

Analyzing Mushroom Structural Patterns of a Highly Compressible and Expandable Hemostatic Foam for Gastric Perforation Repair.

Nature presents the most beautiful patterns through evolving. Here, a layered porous pattern in golden ratio (0.618) is reported from a type of mushroom -Dictyophora Rubrovalvata stipe (DRS). The hierarchical structure shows a mathematical correlation with the golden ratio. This unique structure leads to superior mechanical properties. The gradient porous structure from outside to innermost endows it with asymmetrical hydrophilicity. A mathematical model is then developed to predict and apply to 3D printed structures. The mushroom is then explored to repair gastric perforation because the stomach is a continuous peristaltic organ, and the perforated site is subject to repeated mechanical movements and pressure changes. At present, endoscopic clipping is ineffective in treating ulcerative perforation with fragile surrounding tissues. Although endoscopic implant occlusion provides a new direction for the treatment of gastric ulcers, but the metal or plastic occluder needs to be removed, requiring a second intervention. Decellularized DRS (DDRS) is found with asymmetric water absorption rate, super-compressive elasticity, shape memory, and biocompatibility, making it a suitable occluder for the gastric perforation. The efficacy in blocking gastric perforation and promoting healing is confirmed by endoscopic observation and tissue analysis during a 2-month study.

Highly efficient semiconductor modules making controllable parallel microchannels for non-compressible hemorrhages.

Nature makes the most beautiful solution to involuted problems. Among them, the parallel tubular structures are capable of transporting fluid quickly in plant trunks and leaf stems, which demonstrate an ingenious evolutionary design. This study develops a mini-thermoelectric semiconductor P-N module to create gradient and parallel channeled hydrogels. The modules decrease quickly the temperature of polymer solution from 20 °C to -20 °C within 5 min. In addition to the exceptional liquid absorption rate, the foams exhibited shape memory mechanics. Our mini device universally makes the inspired structure in such as chitosan, gelatin, alginate and polyvinyl alcohol. Non-compressible hemorrhages are the primary cause of death in emergency. The rapid liquid absorption leads to fast activation of coagulation, which provides an efficient strategy for hemostasis management. We demonstrated this by using our semiconductor modules on collagen-kaolin parallel channel foams with their high porosity (96.43%) and rapid expansion rate (2934%). They absorb liquid with 37.25 times of the own weight, show 46.5-fold liquid absorption speed and 24-fold of blood compared with random porous foams. These superior properties lead to strong hemostatic performance in vitro and in vivo.