Mesoporous silica coated spicules for photodynamic therapy of metastatic melanoma.

We report on the fabrication of mesoporous silicon dioxide coated Haliclona sp. spicules (mSHS) to enhance the delivery of the insoluble photosensitizer protoporphyrin IX (PpIX) into deep skin layers and mediate photodynamic therapy for metastatic melanoma in mice. The mSHS are dispersed sharp edged and rod-like micro-particles with a length of approximate 143.6 ± 6.4 µm and a specific surface area of 14.9 ± 3.4 m2/g. The mSHS can be topically applied to the skin, adapting to any desired skin area and lesion site. The insoluble PpIX were incorporated into the mesoporous silica coating layers of mSHS (mSHS@PpIX) with the maximum PpIX loading capacity of 120.3 ± 3.8 µg/mg. The mSHS@PpIX significantly enhanced the deposition of PpIX in the viable epidermis (5.1 ± 0.4 µg/cm2) and in the dermis (0.5 ± 0.2 µg/cm2), which was 154 ± 11-fold and 22 ± tenfold higher than those achieved by SHS, respectively. Topical delivery of PpIX using mSHS (mSHS@PpIX) completely eradicated the primary melanoma in mice in 10 days without recurrence or metastasis over 60 days. These results demonstrate that mSHS can be a promising topical drug delivery platform for the treatment of diverse cutaneous diseases, such as metastatic melanoma.

Tough and Water-Resistant Bioelastomers with Active-Controllable Degradation Rates.

Biodegradable electronic devices have gained significant traction in modern medical applications. These devices are generally desired to have a long enough working lifetime for stable operation and allow for active control over their degradation rates after usage. However, current biodegradable materials used as encapsulations or substrates for these devices are challenging to meet the two requirements due to the constraints of inadequate water resistance, poor mechanical properties, and passive degradation characteristics. Herein, we develop a novel biodegradable elastomer named POC-SS-Res by introducing disulfide linkage and resveratrol (Res) into poly(1,8-octanediol-co-citrate) (POC). Compared to POC, POC-SS-Res exhibits good water resistance and excellent mechanical properties in PBS, providing effective protection for devices. At the same time, POC-SS-Res offers the unique advantage of an active-controllable degradation rate, and its degradation products express low biotoxicity. Good biocompatibility of POC-SS-Res is also demonstrated. Bioelectronic components encapsulated with POC-SS-Res have an obvious prolongation of working lifetime in PBS compared to that encapsulated with POC, and its degradation rate can be actively controlled by the addition of glutathione (GSH).

Citrate-Based Polyester Elastomer with Artificially Regulatable Degradation Rate on Demand.

Citrate-based polymers are commonly used to create biodegradable implants. In an era of personalized medicine, it is highly desired that the degradation rates of citrate-based implants can be artificially regulated as required during clinical applications. Unfortunately, current citrate-based polymers only undergo passive degradation, which follows a specific degradation profile. This presents a considerable challenge for the use of citrate-based implants. To address this, a novel citrate-based polyester elastomer (POCSS) with artificially regulatable degradation rate is developed by incorporating disulfide bonds (S-S) into the backbone chains of the crosslinking network of poly(octamethylene citrate) (POC). This POCSS exhibits excellent and tunable mechanical properties, notable antibacterial properties, good biocompatibility, and low biotoxicity of its degradation products. The degradation rate of the POCSS can be regulated by breaking the S-S in its crosslinking network using glutathione (GSH). After a period of subcutaneous implantation of POCSS scaffolds in mice, the degradation rate eventually increased by 2.46 times through the subcutaneous administration of GSH. Notably, we observed no significant adverse effects on its surrounding tissues, the balance of the physiological environment, major organs, and the health status of the mice during degradation.

An autonomous activation of interleukin-17 receptor signaling sustains inflammation and promotes disease progression.

Anti-interleukin-17 (IL-17) therapy has been used in various autoimmune diseases. However, the efficacy is unexpectedly limited in several IL-17-associated diseases, and the mechanism of limited efficacy remains unclear. Here, we show that a molecular complex containing the adaptor molecule Act1 and tyrosine phosphatase SHP2 mediated autonomous IL-17R signaling that accelerated and sustained inflammation. SHP2, aberrantly augmented in various autoimmune diseases, was induced by IL-17A itself in astrocytes and keratinocytes, sustaining chemokine production even upon anti-IL-17 therapies. Mechanistically, SHP2 directly interacted with and dephosphorylated Act1, which replaced Act1-TRAF5 complexes and induced IL-17-independent activation of IL-17R signaling. Genetic or pharmacologic inactivation of SHP2, or blocking Act1-SHP2 interaction, paralyzed both IL-17-induced and IL-17-independent signaling and attenuated primary or relapsing experimental autoimmune encephalomyelitis. Therefore, Act1-SHP2 complexes mediate an alternative pathway for autonomous activation of IL-17R signaling, targeting which could be a therapeutic option for IL-17-related diseases in addition to current antibody therapies.

Opportunistic bacteria with reduced genomes are effective competitors for organic nitrogen compounds in coastal dinoflagellate blooms.

BACKGROUND: Phytoplankton blooms are frequent events in coastal areas and increase the production of organic matter that initially shapes the growth of opportunistic heterotrophic bacteria. However, it is unclear how these opportunists are involved in the transformation of dissolved organic matter (DOM) when blooms occur and the subsequent impacts on biogeochemical cycles. RESULTS: We used a combination of genomic, proteomic, and metabolomic approaches to study bacterial diversity, genome traits, and metabolic responses to assess the source and lability of DOM in a spring coastal bloom of Akashiwo sanguinea. We identified molecules that significantly increased during bloom development, predominantly belonging to amino acids, dipeptides, lipids, nucleotides, and nucleosides. The opportunistic members of the bacterial genera Polaribacter, Lentibacter, and Litoricola represented a significant proportion of the free-living and particle-associated bacterial assemblages during the stationary phase of the bloom. Polaribacter marinivivus, Lentibacter algarum, and Litoricola marina were isolated and their genomes exhibited streamlining characterized by small genome size and low GC content and non-coding densities, as well as a smaller number of transporters and peptidases compared to closely related species. However, the core proteomes identified house-keeping functions, such as various substrate transporters, peptidases, motility, chemotaxis, and antioxidants, in response to bloom-derived DOM. We observed a unique metabolic signature for the three species in the utilization of multiple dissolved organic nitrogen compounds. The metabolomic data showed that amino acids and dipeptides (such as isoleucine and proline) were preferentially taken up by P. marinivivus and L. algarum, whereas nucleotides and nucleosides (such as adenosine and purine) were preferentially selected by L. marina. CONCLUSIONS: The results suggest that the enriched DOM in stationary phase of phytoplankton bloom is a result of ammonium depletion. This environment drives genomic streamlining of opportunistic bacteria to exploit their preferred nitrogen-containing compounds and maintain nutrient cycling. Video abstract.

Skin Delivery of siRNA Using Sponge Spicules in Combination with Cationic Flexible Liposomes.

We report the topical administration of sponge Haliclona sp. Spicules (SHS) combined with cationic flexible liposomes (CFL) to increase the delivery of small interfering RNA (siRNA) into viable skin cells in vitro and in vivo. SHS can be applied topically as novel microneedles to overcome skin barrier by creating plenty of new microchannels in stratum corneum. Subsequently, well-designed CFL can be also utilized topically as nanocarriers to overcome skin cells membrane by delivering siRNA to skin deep layers through these microchannels and thereby facilitating their cell internalization. The topical application of SHS in combination with CFL (0.05% of lipids, w/v), referred to as CFL(0.05%), enhanced siRNA skin penetration in vitro by 72.95 ± 2.97-fold compared to control group (p < 0.001). Further, the topical application of SHS in combination with CFL(0.05%) on female BALB/c mice skin resulted in 29.21% ± 1.41% of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) knockdown at all application area in vivo, which was not significantly different from the GAPDH protein knockdown rate in the subcutaneous injection center. However, the high knockdown rate only appears in the vicinity (<0.5 cm) of the injection center. In sum, this study provides a promising strategy of topical delivery of siRNA by the combined used of SHS and well-designed CFL.

Draft Genome Sequence of Pelagicola sp. Strain LXJ1103, Isolated from Coastal Surface Seawater.

Pelagicola sp. strain LXJ1103, a representative of a new species in the family Rhodobacteraceae, was isolated from the coastal surface waters in Xiamen, China. Here, we announce the draft genome sequence and initial findings from a preliminary analysis of strain LXJ1103.

Broadband light trapping based on periodically textured ZnO thin films.

Transparent conductive front electrodes (TCFEs) deployed in photovoltaic devices have been extensively studied for their significance in transporting carriers, coupling and trapping the incident photons in high-performing solar cells. The trade-off between the light-transmission, electrical, and scattering properties for TCFEs to achieve a broadband improvement in light absorption in solar cells while maintaining a high electrical performance has become the key issue to be tackled. In this paper, we employ self-assembled polystyrene (PS) spheres based on a sauna-like method as a template, followed by a double-layer deposition and then successfully fabricate highly-transparent, well-conductive, and large-scale periodically-textured ZnO TCFEs with broadband light trapping properties. A sheet resistance below 15 Ω sq(-1) was achieved for the periodically-textured ZnO TCFEs, with a concomitant average transmission of 81% (including the glass substrate) in the 400-1100 nm spectral range, a haze improvement in a broadband spectral range, and a wider scattering angular domain. The proposed approach affords a promising alternative method to prepare periodically-textured TCFEs, which are essential for many optoelectronic device semiconductors, such as photovoltaic and display applications.

Cytosolic BolA Plays a Repressive Role in the Tolerance against Excess Iron and MV-Induced Oxidative Stress in Plants.

The BolA-like protein is present in all eukaryotes, and it is able to form complex with monothiol glutaredoxin of the same subcellular compartments, suggesting that the BolA-like protein has essential function in eukaryotes, and that the function is associated with its partner glutaredoxin. Some studies have indicated a role for BolA proteins in Fe-S cluster synthesis or in redox homeostasis. However, the physiological function of BolA proteins remains to be elucidated. Here, we report the characterization of an insertion mutant of BolA3 in Arabidopsis. Among the four AtBolA proteins found in Arabidopsis, the AtBolA3 was the only BolA located in the cytosol of plant cells. It was highly expressed in roots. AtBolA3 was able to interact with the cytosolic monothiol glutaredoxin, AtGRXS17. The bola3 mutant did not show any notable phenotype under normal growth condition, but rather grew better than wild type under some stresses. The bola3 mutant was more tolerant to excess iron and the MV-induced oxidative stress than wild type. It displayed no necrosis in leaves, developed longer roots, accumulated more iron and higher Fe-S protein activities in roots. In addition, the mutant possessed a more potent antioxidant defense to scavenge ROS species. Taken together, our data indicated that the cytosolic AtBolA3 has a suppressive role in the tolerance to excess iron and the MV-induced oxidative stress in plants. AtBolA3 seems to be a repressor under some stress conditions.

Trade-offs of the opto-electrical properties of a-Si:H solar cells based on MOCVD BZO films.

Boron-doped zinc oxide (BZO) films, deposited by metal-organic chemical vapor deposition (MOCVD), have been widely used as front electrodes in thin-film solar cells due to their native pyramidal surface structure, which results in efficient light trapping. This light trapping effect can enhance the short-circuit current density (Jsc) of solar cells. However, nanocracks or voids in the silicon active layer may form when the surface morphology of the BZO is too sharp; this usually leads to degraded electrical properties of the cells, such as open-circuit voltage (Voc) and the fill factor (FF), which in turn decreases efficiency (Eff) [Bailat et al., Photovoltaic Energy Conversion, Conference Record of the 2006 IEEE 4th World Conference on. IEEE, 2006, vol. 2, pp. 1533-1536]. In this paper, an etching and coating method was proposed to modify the sharp "pyramids" on the surface of the BZO films. As a result, an evident enhancement was achieved for these modified, BZO-based cells' Voc, FF, and Eff, although the Jsc exhibited a small decrease. In order to increase the Jsc and maintain the improved electrical properties (Voc, FF) of the cell, a thin BZO coating, deposited by MOCVD, was introduced to coat the sputtering-treated BZO film. Finally, we optimized the trade-off among the Voc, FF, and Jsc, that is, we identified a regime with an increase of the Jsc as well as a further improvement of the other electrical properties.

Soybean Fe-S cluster biosynthesis regulated by external iron or phosphate fluctuation.

KEY MESSAGE: Iron and phosphorus are essential for soybean nodulation. Our results suggested that the deficiency of Fe or P impairs nodulation by affecting the assembly of functional iron-sulfur cluster via different mechanisms. Iron (Fe) and phosphorus (P) are important mineral nutrients for soybean and are indispensable for nodulation. However, it remains elusive how the pathways of Fe metabolism respond to the fluctuation of external Fe or P. Iron is required for the iron-sulfur (Fe-S) cluster assembly in higher plant. Here, we investigated the expression pattern of Fe-S cluster biosynthesis genes in the nodulated soybean. Soybean genome encodes 42 putative Fe-S cluster biosynthesis genes, which were expressed differently in shoots and roots, suggesting of physiological relevance. Nodules initiated from roots of soybean after rhizobia inoculation. In comparison with that in shoots, iron concentration was three times higher in nodules. The Fe-S cluster biosynthesis genes were activated and several Fe-S protein activities were increased in nodules, indicating that a more effective Fe-S cluster biosynthesis is accompanied by nodulation. Fe-S cluster biosynthesis genes were massively repressed and some Fe-S protein activities were decreased in nodules by Fe deficiency, leading to tiny nodules. Notably, P deficiency induced a similar Fe-deficiency response in nodules, i.e, certain Fe-S enzyme activity loss and tiny nodules. However, distinct from Fe-deficient nodules, higher iron concentration was accumulated and the Fe-S cluster biosynthesis genes were not suppressed in the P-deficiency-treated nodules. Taken together, our results showed that both Fe deficiency and P deficiency impair nodulation, but they affect the assembly of Fe-S cluster maybe via different mechanisms. The data also suggested that Fe-S cluster biosynthesis likely links Fe metabolism and P metabolism in root and nodule cells of soybean.

Genes for iron-sulphur cluster assembly are targets of abiotic stress in rice, Oryza sativa.

Iron-sulphur (Fe-S) cluster assembly occurs in chloroplasts, mitochondria and cytosol, involving dozens of genes in higher plants. In this study, we have identified 41 putative Fe-S cluster assembly genes in rice (Oryza sativa) genome, and the expression of all genes was verified. To investigate the role of Fe-S cluster assembly as a metabolic pathway, we applied abiotic stresses to rice seedlings and analysed Fe-S cluster assembly gene expression by qRT-PCR. Our data showed that genes for Fe-S cluster assembly in chloroplasts of leaves are particularly sensitive to heavy metal treatments, and that Fe-S cluster assembly genes in roots were up-regulated in response to iron toxicity, oxidative stress and some heavy metal assault. The effect of each stress treatment on the Fe-S cluster assembly machinery demonstrated an unexpected tissue or organelle specificity, suggesting that the physiological relevance of the Fe-S cluster assembly is more complex than thought. Furthermore, our results may reveal potential candidate genes for molecular breeding of rice.