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Keloids are disfiguring pathological scars that could cause pain and pruritus. The conventional treatments, such as bolus injection of drugs or surgery, are invasive and require a personal visit to clinic. Microneedle (MN) technology has great potential to offer a self-administered and minimally invasive treatment of keloids. However, drugs delivered using MNs suffer from limited penetration in keloid tissue. This study demonstrates enhanced drug penetration in human keloid scar tissue by combining MN and sonophoresis.

Nanorobots hold great promise for integrated drug delivery systems that are responsive to molecular triggers. Herein, we successfully developed an automatic smart bionanorobot that has transport capability and recognizes and removes zinc ions from poisoned cells based on nanoscale polyhedral oligomeric silsesquioxane molecules. This intelligent bionanorobot can easily move inside and outside the cell and find zinc ions owing to its highly selective recognition to zinc ions and high cell permeability, especially the well-combined high penetration and strong binding energy. More importantly, it was also found that this intelligent bionanorobot can restore round HeLa cells to a normal fusiform cell morphology following high-concentration zinc treatment and does not interfere with cell proliferation and division. It was also shown by

Cell therapies for the treatment of skin disorders could benefit from simple, safe and efficient technology for the transdermal delivery of therapeutic cells. Conventional cell delivery by hypodermic-needle injection is associated with poor patient compliance, requires trained personnel, generates waste and has non-negligible risks of injury and infection. Here, we report the design and proof-of-concept application of cryogenic microneedle patches for the transdermal delivery of living cells. The microneedles are fabricated by stepwise cryogenic micromoulding of cryogenic medium with pre-suspended cells, and can be easily inserted into porcine skin and dissolve after deployment of the cells. In mice, cells delivered by the cryomicroneedles retained their viability and proliferative capability. In mice with subcutaneous melanoma tumours, the delivery of ovalbumin-pulsed dendritic cells via the cryomicroneedles elicited higher antigen-specific immune responses and led to slower tumour growth than intravenous and subcutaneous injections of the cells. Biocompatible cryomicroneedles may facilitate minimally invasive cell delivery for a range of cell therapies. Cryogenic microneedle patches can deliver mammalian cells before dissolving into the skin, as shown with the transdermal delivery of ovalbumin-pulsed dendritic cells in mice with subcutaneous tumours.

Many researchers are concerned that municipal solid waste (MSW) threatens public health, causing them to increasingly focus on odor pollution. In this study, the odor nuisance and health risk impacts of landfill surface gas on eight sensitive receptors were assessed. The emission rates of odor and 145 volatile organic compounds (VOCs) were acquired by considering various landfilling operations, including high-density polyethylene (HDPE) membrane removal (MR), landfill tipping area (TA), temporary HDPE membrane cover (MC), top of the HDPE membrane (LM) and dumping platform (DP). Furthermore, differences in landfill surface geometry, such as emission height and source area, and variations in residential living floors were considered in odor assessment with the air dispersion model. Based on these uncertain factors, normal-, medial-, and worst-case scenarios were defined to elucidate the odor nuisance effect and health risk impact. Four of the eight sensitive receptors, which were 2.6 km away from the landfill surface, basically experienced odor nuisance and health risk impacts. Dichloromethane exerted an indelible and crucial impact on body health based on a comprehensive investigation of aromatics, halocarbons, and other chemicals. The odor nuisance and health risk impacts were notable near the landfill, and the local environment was remarkably damaged.

Yeast productivity in lignocellulosic ethanol fermentation is clearly impeded by stress. Enhancing the robustness of xylose-fermenting yeast is important for improving lignocellulosic ethanol production. In this study, the glutathione biosynthesis pathway and acetic acid degradation pathway were strengthened to enhance yeast tolerance to stress due to elevated reactive oxygen species (ROS) and acetic acid. Dynamic feedback regulation of the anti-stress genetic circuits was achieved using stress-driven promoters discovered from the transcriptome to maintain low intracellular ROS, relieve the metabolic burden, and ultimately improve the robustness and ethanol production of yeast. The cell growth, xylose utilization and ethanol production of the engineered strain were enhanced under both stress and nonstress conditions. The engineered strain showed 49.5% and 17.5% higher ethanol productivity in laboratory media and industrial lignocellulosic media, respectively, at 36 °C compared with the parent strain. This study provides novel insights on the rational design and construction of feedback genetic circuits for dynamically improving yeast robustness.

Considering the large volumes of treated water and incomplete elimination of pollutants, wastewater treatment plants (WWTPs) remain a considerable source of microplastics (MPs). Chlorine, the most frequently used disinfectant in WWTPs, has a strong oxidizing impact on MPs. However, little is documented, to date, about the impact of chlorination on the transformation of MPs and the subsequent environmental behaviors of the chlorinated MPs when released into the aquatic environment. This study explored the response of the physicochemical properties of specific thermoplastics, namely polyurethane (TPU) MPs and polystyrene (PS) MPs, to chlorination and their emerging pollutant [tetracycline (TC)] adsorption behavior in aqueous solution. The results indicated that the O/C ratio of the MP surface did not significantly change, and that there were increases in the O-containing functional groups of the TPU and PS MPs, after chlorination. The surface area of the chlorinated TPU MPs increased by 45 %, and that of the chlorinated PS increased by 21 %, compared with the pristine ones, which contributed to the TC adsorption. The adsorption isotherm fitting parameters suggested that the chlorinated TPU fitted the multilayer adsorption, and the chlorinated PS was inclined to the monolayer adsorption. The relative abundance of the O-containing functional groups, on the TPU surface, led to the release of CHCl3 molecules, and the clear surface irregularities and fissures occurred after chlorine treatment. No fissures were found on the surface of the chlorinated PS MPs. The hydrophobicity and electrostatic adsorption were proved to be the major impacts on the TC adsorption of the chlorinated MPs, and the subsequently formed hydrogen bonds led to the stronger adsorption capacity of the chlorinated TPU than the chlorinated PS MPs.

Intraguild predation (IGP), defined as killing and eating among potential competitors, is commonly observed in shallow lakes and is predicted to dampen trophic cascades and affect ecosystem properties (e.g. phytoplankton biomass or primary production). We tested this hypothesis by manipulating the density of two common lake predators, the small-sized fish Pelteobagrus fulvidraco (the intraguild predator) and the shrimp Exopalaemon modestus (the intraguild prey), in outdoor mesocosms containing natural phytoplankton and zooplankton communities. In single predator treatments, both predators induced a strong trophic cascade, as evidenced by extinction of the key herbivore, Daphnia pulex, and increasing phytoplankton biomass and chlorophyll a concentration. When the two predators were added together, however, the strength of collective predator effects on zooplankton and the cascading effects on phytoplankton growth were weaker than the sum of the individual predator effects. We attributed this antagonism among predators to intraguild predation as demonstrated by the lower shrimp catch per unit effort in the presence of fish. Our study suggests that common predators in subtropical shallow lakes may act antagonistically and thereby dampen trophic cascades in food webs. Thus, when implementing biomanipulation efforts to suppress algal growth via enhancing zooplankton herbivory, both the quantity and diversity of lake predator assemblies should be considered.

Active bubble-generating microneedles (MNs) upon skin interstitial fluid (ISF) contact facilitate deeper and more efficient delivery of intradermal therapeutics. However, bubble-generating MN platforms are sensitive to moisture, which limits their variety to load various functional drugs. This article presents a frozen immersion method that facilitates both hydrophobic and hydrophilic drug loading onto bubble-generating MNs without compromising both drug and MN properties. The formed bubbles upon ISF contact induce distinct vortex flow that produces a propulsion force to enhance drug transportation. The efficiency of transdermal drug delivery is further enhanced by sonophoresis. The drug delivery efficiency of this platform is first evaluated ex vivo using fresh mouse skins and human keloid tissues. Later, in the tumor-bearing mouse model, the platform enhances the skin penetration of photosensitizers (i.e., methylene blue) and correspondingly improves the efficacy of photodynamic therapy. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Ministry of Health (MOH) National Medical Research Council (NMRC) Submitted/Accepted version This project is supported by the Singapore Agency for Science, Technology and Research (A*STAR) Science and Engineering Research Council Additive Manufacturing for Biological Materials (AMBM) program (A18A8b0059). C.X. acknowledges the funding support from the City University of Hong Kong (#9610472), General Research Fund (GRF) from the University Grants Committee of Hong Kong (UGC) Research Grant Council (RGC) (#9042951 and 9043133), and NSFC/ RGC Joint Research Scheme (#N_CityU118/20). L.L. acknowledges the funding support from the Singapore Ministry of Health’s National Medical Research Council under its Open Fund Individual Research Grant (MOH-OFIRG19may-0009), and the Ministry of Education Singapore under its Academic Research Funding Tier 2 (MOE-T2EP30120-0001).

Increased recruitment of small-sized fish following biomanipulation by reducing the biomass of plankti-benthivorous fish, not least in (sub)tropical lakes, may deteriorate water quality and thereby potentially hamper the recovery of submerged macrophytes. Filter-feeding bivalves remove suspended particles from the water and may, thereby, somewhat or fully counteract this negative effect of the increasing abundance of small-sized fish. So far, only few studies have investigated the interactive effects of fish and bivalves on water clarity and macrophyte growth. We conducted a 2 &times, 2 factorial designed outdoor mesocosm experiment with two densities of small crucian carp Carassius carassius (low 10 g m&minus, 2 and high 40 g m&minus, 2) and two densities of bivalves Corbicula fluminea (low 204 g m&minus, 2 and high 816 g m&minus, 2). We found significant interactive effect of fish and bivalves on the growth of the macrophyte Vallisneria natans. In the low density bivalve regime, the relative growth rates, root mass, root:shoot ratio and number of tubers were 30.3%, 30.8%, 21.6% and 27.8% lower in the high than in the low density fish treatments, while the decrease was less pronounced in the high density bivalve regime: 1.2%, 8.7%, 2.1% and 13.3%, respectively. Thus, bivalves reduced the negative effects of fish, not least when bivalve density was high. The weaker effects of small fish on plants in the high- than in the low-density C. fluminea regime can be attributed to lower total suspended solids (TSS) and Chl a in the first week of the experiment. Better light conditions further stimulated the growth of benthic algae, potentially increasing the removal of nutrients from the water and reducing fish-driven resuspension of the sediment. In addition, high densities of C. fluminea also enriched the sediment total nitrogen (TN) and total phosphorus (TP) content, favouring plant growth as indicated by an increase in leaf tissue TN and TP contents. Our results demonstrate that filter-feeding bivalves can alleviate harmful effects of small fish by prolonging a clear-water state that facilitates submerged macrophyte growth. Addition of the bivalve C. fluminea can be a promising tool for the restoration of submerged macrophytes in shallow eutrophic lakes, in particular lakes containing small, rapidly reproducing fish that due to their small sizes are not capable of controlling the bivalves.

Pigs are the most promising models for the study of wound healing and hypertrophic scarring because they are anatomically and physiologically similar to human beings. The Red Duroc pig and Mini Bama pig are two swine models that have attracted a lot of attention. The aim of the present study was to examine and compare the scarring process in a red Duroc pig and a Mini Bama pig, providing knowledge for researchers and clinicians to enable them to choose the most suitable pig model for studies., Lay Summary Pigs, with an anatomical and physiological skin architecture similar to that of the human, have been studied extensively as models for wound healing and scarring. However, the red Duroc pig, as a frequently used animal model for human wound/scar-related research, has the shortcoming of rapid growth in size and weight, which gives rise to difficulty in its handling and brings about enormous cost. The Mini Bama pig grows much slower and can be a potential replacement. This study compares wound healing and subsequent scarring between the Duroc and Mini Bama pigs with a time span of 35 weeks. Other than clinical appearance at week 35, when the Duroc scars showed an obvious hyperpigmentation while the Mini Bama scars showed slight hypopigmentation, the trends of change in shape, histological appearance (epidermis thickness) and collagen deposition in the tissues are similar in both types of pigs.

Supplemental material, Supplemental_material for Comparison of hypertrophic scarring on a red Duroc pig and a Guangxi Mini Bama pig by Xiaoyu Ning, Kai Yang, Wei Shi and Chenjie Xu in Scars, Burns & Healing

Harvesting energy from raindrops has attracted extensive efforts due to the wide distribution of precipitation and vast potential applications. Among the various approaches developed for this purpose, droplets-based electricity generators (DEGs) based on electrostatic induction have been becoming an outstanding option in the aspect of output voltage and instantaneous power density. Performance dependence of DEGs on the device configuration and the dominating factors have to be revealed for the further optimization. Here, we comprehensively investigated the performance of DEGs with three different configurations, i.e., bottom-electrode, top-electrode and double-electrode, and found that water-to-ground capacitance played an important role in determining the device output. Besides, the conductivity of water shows notable influence on the device performance, tap water with a conductivity around 300 μS/cm shows the highest efficiency in our measurements. Adapting an optimized power management circuit, the pulsed-like output of DEGs is converted to a constant voltage output of variable amplitudes, which is successfully used to charge a smart phone. Our results shed light on possible ways to further optimize the DEG configuration and their potential applications.

Abnormal scarring is a hyper-proliferative wound healing disorder, which causes itch, pain, psychological distress, and even limiting limb mobility. Unfortunately, no satisfactory treatment exists to date. Drug screening identifies suitable drugs or drug combinations that inhibit abnormal scarring from a large selection of candidates. However, current techniques are often laborious and technically complex. Herein, we adopt a near-infrared fluorescence probe (FNP1) for fibroblast activation protein (FAP)α, a biomarker overexpressed in skin fibroblasts derived from abnormal scars, to rapidly assess (30 min) drug candidates for the treatment. FNP1 has high sensitivity, even detecting FAPα up-regulation with as little as 0.016 ng/mL TGFβ1, 125-fold lower than typical culture concentrations. The identified drug candidates (RepSox and Thiazovivin) show similar potent anti-scarring activity as the existing anti-scarring compounds and further suppress the expression of other scar biomarkers including connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), and collagen type 1 (COL1A1).

Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near-infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloid cells, skin cells from abnormal scar fibrous lesions. As keloid cells have high expression levels of fibroblast activation protein-alpha (FAPα), the probe (FNP1) is designed to have a caged NIR dye and a FAPα-cleavable peptide substrate linked by a self-immolative segment. FNP1 can quickly and specifically turn on its fluorescence at 710 nm by 45-fold in the presence of FAPα, allowing it to effectively recognize keloid cells from normal skin cells. Integration of FNP1 with a simple microneedle-assisted topical application enables sensitive detection of keloid cells in metabolically-active human skin tissue with a theoretical limit of detection down to 20 000 cells. MOE (Min. of Education, S’pore) Accepted version

The effects of Lactobacillus bulgaricus, Rhodopseudomonas palustris, Issatchenkia orientalis and anaerobic sludge on anaerobic digestion of microalgae to organic fertilizer were studied. High-throughput sequencing was used to analyze characteristics of microbial community structure during anaerobic digestion of microalgae using different inocula. Lactobacillales and Saccharomycetales were more likely to become dominant bacteria and eukaryotes. The relative abundance of Lactobacillales was 98.15%, 88.61% and 81.73% of total bacteria at the beginning, middle and end of the experiment, respectively. Meanwhile, the relative abundance of Saccharomycetales was 90.91%, 98.41% and 98.8% of eukaryotes at the beginning, middle and end of the experiment, respectively. At the end of digestion, the microcystin content in the reactor inoculated with Issatchenkia orientalis decreased to 0.71 μg/kg, which met drinking water standards. Rhodopseudomonas palustris did not become a dominant microorganism and had the most negative impact on the atmosphere. Volatile organic compounds were 11.92 mg/kg while the odor concentration reached 97,724 ou/m3. The organic matter content in reactors inoculated with specific groups of microbial agents, which was higher than the standard required for bio-organic fertilizer, occupying over 96% dry weight. In addition, the effective microorganism counts of Issatchenkia orientalis and Lactobacillus bulgaricus in fermentation products reached 1.8E+09 colony-forming units (cfu)/g and 1.6E+09 cfu/g, respectively, which are suitable values for microbial fertilizer.

A SnSb alloy nanoparticle/porous carbon fiber (PCF) composite was prepared using a novel centrifugal spinning technology with subsequent thermal treatment. In SnSb/PCF composite, the SnSb nanoparticles are uniformly distributed in N-doped carbon fiber matrix due to the created porous structure. The centrifugal spinning can significantly increase the production rate of the fiber composites and the as-prepared SnSb/PCF composite demonstrated small particle size with uniform distribution, mesoporous structure which can facilitate the diffusion of electrolyte and N-doped carbon matrix that is beneficial to the acceleration of the electron transfer. Consequently, SnSb@CFs-20 exhibits a promising electrochemical performance in lithium storage.

To enhance the cycle stability of sulfur cathode for a high energy Li-S battery system, a novel sulfur@carbon nanocube (S@CNC) composite was prepared by encapsulating sulfur into micropores of CNCs by thermal treatment of a mixture of sublimed sulfur and CNCs. Electrochemical results demonstrated that encapsulating sulfur into individual insulated CNCs could effectively inhibit the aggregation of sulfur, eliminate excessive contact of sulfur species with the electrolyte and help confine the soluble lithium polysulfides. Additionally, the large surface area and thin shells of CNC hosts could facilitate rapid transport of Li+ ions and electrons to achieve superior rate capability and stable cycling performance.

Reestablishment of submerged macrophytes is considered important when restoring shallow eutrophic lakes. To improve water clarity and consequently the growth conditions of macrophytes, removal of plankti-benthivorous fish has been used. In sub-tropical shallow lakes, however, rapid recruitment of small fish, especially benthivores during restoration, may hamper early reestablishment of submerged macrophytes. Crucian carp (Carassius carassius) and Vallisneria natans are common species dominated in sub-tropical shallow lakes. To investigate the effect of small benthivorous fish on the growth of Vallisneria natans, a 28-day outdoor controlled experiment was undertaken in 12 mesocosms with three densities of Carassius carassius − low (10 g m−2), high (40 g m−2) and no fish (all in four replicates). The results showed that the fish significantly increased chlorophyll-a concentrations and periphyton biomass in both fish treatments, most significantly at high density for Chl a. This concurs with an increase in nutrient concentrations, likely mediated by fish sediment disturbance and excretion, and a reduction of zooplankton biomass (less algal grazing). Increased concentrations of inorganic suspended solids with increasing fish density further enhanced turbidity, causing shading of the macrophytes. Accordingly, the relative growth rate, ramet number and root/leaf ratio of V. natans decreased significantly at low and high fish density compared with the controls, but the effects did not depend on fish density. However, mean leaf length rose with increasing fish density, likely to allow the plants to obtain more light. Overall, our results show that not only large-bodied carp, as demonstrated frequently, but also small-sized crucian carp posed a constraint on submerged macrophyte reestablishment, and we conclude that crucian carp may hamper restoration efforts in sub-tropical shallow lakes. Restoration by biomanipulation should therefore target also small-sized crucian carp.

Hydrogels, swellable hydrophilic polymer networks fabricated through chemical cross-linking or physical entanglement are increasingly utilized in various biomedical applications over the past few decades. Hydrogel-based microparticles, dressings and microneedle patches have been explored to achieve safe, sustained and on-demand therapeutic purposes toward numerous skin pathologies, through incorporation of stimuli-responsive moieties and therapeutic agents. More recently, these platforms are expanded to fulfill the diagnostic and monitoring role. Herein, the development of hydrogel technology to achieve diagnosis and monitoring of pathological skin conditions are highlighted, with proteins, nucleic acids, metabolites, and reactive species employed as target biomarkers, among others. The scope of this review includes the characteristics of hydrogel materials, its fabrication procedures, examples of diagnostic studies, as well as discussion pertaining clinical translation of hydrogel systems.

This work reports a frozen spray-coating method for the fabrication of double-layered microneedles (MNs). Taking swellable methacrylated hyaluronic acid (MeHA)-derived MNs as the model, both hydrophobic molecules (Nile red, Cy5) and hydrophilic ones (FITC, FITC-Dextran, Insulin) can be homogeneously coated without impacting the mechanical properties of the original MeHA MNs. The prepared double-layered MNs can execute multiple roles. It is demonstrated that insulin-coated MeHA double-layered MNs allow the effective delivery of the insulin into circulation of mice for controlling the blood glucose level while they also permit the extraction of skin interstitial fluid for the timely analysis of the biomarker (glucose).

Cell therapies for the treatment of skin disorders could benefit from simple, safe and efficient technology for the transdermal delivery of therapeutic cells. Conventional cell delivery by hypodermic-needle injection is associated with poor patient compliance, requires trained personnel, generates waste and has non-negligible risks of injury and infection. Here, we report the design and proof-of-concept application of cryogenic microneedle patches for the transdermal delivery of living cells. The microneedles are fabricated by stepwise cryogenic micromoulding of cryogenic medium with pre-suspended cells, and can be easily inserted into porcine skin and dissolve after deployment of the cells. In mice, cells delivered by the cryomicroneedles retained their viability and proliferative capability. In mice with subcutaneous melanoma tumours, the delivery of ovalbumin-pulsed dendritic cells via the cryomicroneedles elicited higher antigen-specific immune responses and led to slower tumour growth than intravenous and subcutaneous injections of the cells. Biocompatible cryomicroneedles may facilitate minimally invasive cell delivery for a range of cell therapies.

Novel intelligent cellulose/4-vinyl-phenylboronic acid (VPBA) composite bio-hydrogels with glucose and pH-responsiveness were successfully prepared via electron beam irradiation technology at room temperature. The composites were characterized by Fourier transform infrared spectrum (FT-IR) and X-ray photoelectron spectroscopy (XPS). The electron beam irradiation results in the appearance of carbonyl in the polymerization of 4-ethenyl-phenylboronic acid, grafting and cross linking reaction in composites, and a novel composite hydrogel was formed between the poly-4-ethenyl-phenylboronic acid and cellulose matrix. By means of the incorporation of phenylboronic acid groups, the composite hydrogels with pH and glucose responsive properties was produced, and glucose responsive properties were investigated by the self-regulation of insulin release of composite hydrogel through a serial glucose solution with different concentrations, which is having great potential applications in many fields.

Nano-TiO 2 was synthesized with titanium sulfate by a simple economical microwave-assisted-hydrolysis method, and it was successfully coated on semi-organic-matter sulfonated coal (SC). SC as a semi-organic matter was first chosen as the substrate of nano-TiO 2 . Their surface morphology and structure were investigated by scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The hybrid nano-composite photocatalyst exhibited a good photocatalytic activity in degrading methylene blue (MB). Results revealed that under the assistance of microwave-process, the anatase TiO 2 can be synthesized at low temperature (around 100 °C), presents a strong crystalline and has a good photocatalytic performance.

China had a long tradition of astronomy. But, like in other cultures, astronomy in ancient China was essentially positional. The study of the physical nature of celestial bodies has only been a recent development. Knowledge about astrophysics began to be transmitted to China in the middle of the nineteenth century by Western Christian missionaries. With the downfall of the Imperial Qing Dynasty and the founding of the Republic of China in 1912 astronomy began to be seen not as paraphernalia of Imperial rule but as a science with its focus on astrophysics.