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1.
J Hazard Mater ; 472: 134440, 2024 Jul 05.
Article En | MEDLINE | ID: mdl-38723480

N6-methyladenosine (m6A) is the most common form of internal post-transcriptional methylation observed in eukaryotic mRNAs. The abnormally increased level of m6A within the cells can be catalyzed by specific demethylase fat mass and obesity-associated protein (FTO) and stay in a dynamic and reversible state. However, whether and how FTO regulates oxidative damage via m6A modification remain largely unclear. Herein, by using both in vitro and in vivo models of oxidative damage induced by arsenic, we demonstrated for the first time that exposure to arsenic caused a significant increase in SUMOylation of FTO protein, and FTO SUMOylation at lysine (K)- 216 site promoted the down-regulation of FTO expression in arsenic target organ lung, and therefore, remarkably elevating the oxidative damage via an m6A-dependent pathway by its specific m6A reader insulin-like growth factor-2 mRNA-binding protein-3 (IGF2BP3). Consequently, these findings not only reveal a novel mechanism underlying FTO-mediated oxidative damage from the perspective of m6A, but also imply that regulation of FTO SUMOylation may serve as potential approach for treatment of oxidative damage.


Adenosine , Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Oxidative Stress , RNA-Binding Proteins , Sumoylation , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Sumoylation/drug effects , Animals , Oxidative Stress/drug effects , Adenosine/analogs & derivatives , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Humans , Arsenic/toxicity , Mice , Male , Lung/drug effects , Lung/metabolism
2.
Small ; : e2401669, 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38573947

The anti-solvent-free fabrication of high-efficiency perovskite solar cells (PSCs) holds immense significance for the transition from laboratory-scale to large-scale commercial applications. However, the device performance is severely hindered by the increased occurrence of surface defects resulting from the lack of control over nucleation and crystallization of perovskite using anti-solvent methods. In this study, 2-(naphthalen-2-yl)ethylamine hydriodide (NEAI) is employed as the surface passivator for perovskite films without using any anti-solvent. Naphthalene demonstrates strong π-π conjugation, which aids in the efficient extraction of charge carriers. Additionally, the naphthalene-ring moieties form a tight attachment to the perovskite surface. After NEAI treatment, FA and I vacancies are selectively occupied by NEA+ and I- in NEAI respectively, thus effectively passivating the surface defects and isolating the surface from moisture. Ultimately, the optimized NEAI-treated device achieves a promising power conversion efficiency (PCE) of 24.19% (with a certified efficiency of 23.94%), featuring a high fill factor of 83.53%. It stands out as one of the reported high PCEs achieved for PSCs using the spin-coating technique without the need for any anti-solvent so far. Furthermore, the NEAI-treated device can maintain ≈87% of its initial PCE after 2000 h in ambient air with a relative humidity of 30% ± 5%.

3.
Neurochem Int ; 176: 105725, 2024 Jun.
Article En | MEDLINE | ID: mdl-38561151

Epilepsy constitutes a global health concern, affecting millions of individuals and approximately one-third of patients exhibit drug resistance. Recent investigations have revealed alterations in cerebral iron content in both epilepsy patients and animal models. However, the extant literature lacks a comprehensive exploration into the ramifications of modulating iron homeostasis as an intervention in epilepsy. This study investigated the impact of deferasirox, a iron ion chelator, on epilepsy. This study unequivocally substantiated the antiepileptic efficacy of deferasirox in a kainic acid-induced epilepsy model. Furthermore, deferasirox administration mitigated seizure susceptibility in a pentylenetetrazol-induced kindling model. Conversely, the augmentation of iron levels through supplementation has emerged as a potential exacerbating factor in the precipitating onset of epilepsy. Intriguingly, our investigation revealed a hitherto unreported discovery: ITPRIP was identified as a pivotal modulator of excitatory synaptic transmission, regulating seizures in response to deferasirox treatment. In summary, our findings indicate that deferasirox exerts its antiepileptic effects through the precise targeting of ITPRIP and amelioration of cerebral iron homeostasis, suggesting that deferasirox is a promising and novel therapeutic avenue for interventions in epilepsy.


Anticonvulsants , Brain , Deferasirox , Epilepsy , Homeostasis , Iron Chelating Agents , Iron , Deferasirox/pharmacology , Iron/metabolism , Animals , Homeostasis/drug effects , Homeostasis/physiology , Epilepsy/drug therapy , Epilepsy/metabolism , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Male , Brain/drug effects , Brain/metabolism , Iron Chelating Agents/pharmacology , Iron Chelating Agents/therapeutic use , Mice , Kindling, Neurologic/drug effects , Pentylenetetrazole/toxicity , Rats, Sprague-Dawley
4.
Nanomaterials (Basel) ; 13(7)2023 Mar 31.
Article En | MEDLINE | ID: mdl-37049332

All-inorganic perovskite solar cells are attractive photovoltaic devices because of their excellent optoelectronic performance and thermal stability. Unfortunately, the currently used efficient inorganic perovskite materials can spontaneously transform into undesirable phases without light-absorption properties. Studies have been carried out to stabilize all-inorganic perovskite by mixing low-dimensional perovskite. Compared with organic two-dimensional (2D) perovskite, inorganic 2D Cs2PbI2Cl2 shows superior thermal stability. Our group has successfully fabricated 2D/3D mixed-dimensional Cs2PbI2Cl2/CsPbI2.5Br0.5 films with increasing phase stability. The high boiling point of dimethyl sulfoxide (DMSO) makes it a preferred solvent in the preparation of Cs2PbI2Cl2/CsPbI2.5Br0.5 inorganic perovskite. When the perovskite films are prepared by the one-step solution method, it is difficult to evaporate the residual solvent molecules from the prefabricated films, resulting in films with rough surface morphology and high defect density. This study used the rapid precipitation method to control the formation of perovskite by treating it with methanol/isopropanol (MT/IPA) mixed solvent to produce densely packed, smooth, and high-crystallized perovskite films. The bulk defects and the carrier transport barrier of the interface were effectively reduced, which decreased the recombination of the carriers in the device. As a result, this effectively improved photoelectric performance. Through treatment with MT/IPA, the photoelectric conversion efficiency (PCE) of solar cells prepared in the N2 atmosphere increased from 13.44% to 14.10%, and the PCE of the device prepared in the air increased from 3.52% to 8.91%.

5.
Adv Mater ; 35(28): e2300302, 2023 Jul.
Article En | MEDLINE | ID: mdl-37074221

All-inorganic cesium lead halide flexible perovskite solar cells (f-PSCs) exhibit superior thermal stability compared to their organic-inorganic hybrid counterparts. However, their flexibility and efficiency are still below-par for practical viability. Herein, a design using a 0D Cs4 Pb(IBr)6 additive to transform tensile stress into compressive stress in the perovskite film, effectively preventing expansion of cracks for significantly improved mechanical durability, is reported. It is found that not only is improved flexibility obtained, but also the cell efficiency is increased for the all-inorganic flexible 3D CsPbI3- x Brx solar cells. The CsPbI2.81 Br0.19 f-PSC retains over 97% of its initial efficiency even after 60 000 flexing cycles at a curvature radius of 5 mm (R = 5 mm). Simultaneously, 0D Cs4 Pb(IBr)6 enhances the crystallinity of the CsPbI2.81 Br0.19 film and passivates the defects along the grain boundaries, effectively improving the photovoltaic performance of the all-inorganic f-PSCs. The highest power-conversion efficiency obtained is 14.25% with a short-circuit current density of 18.47 mA cm-2 , open-circuit voltage of 1.09 V, and fill factor of 70.67%. This strategy paves the way for further improvement of the mechanical durability of all-inorganic f-PSCs.


Calcium Compounds , Lead , Cesium , Oxides
6.
Materials (Basel) ; 15(8)2022 Apr 14.
Article En | MEDLINE | ID: mdl-35454575

All-inorganic Sb-perovskite has become a promising material for solar cell applications owing to its air stability and nontoxic lead-free constitution. However, the poor morphology and unexpected (001) orientation of Sb-based perovskite films strongly hinder the improvement of efficiency. In this work, two-dimensional Cs3Sb2ClxI9-x with (201) preferred orientation has been successfully fabricated by introducing thiourea (TU) to the precursor solution. The presence of the C=S functional group in TU regulates the crystallization dynamics of Cs3Sb2I9-xClx films and generates the (201) preferred orientation of Cs3Sb2ClxI9-x films, which could effectively improve the carrier transport and film morphology. As a result, the Cs3Sb2I9-xClx perovskite solar cells (PSCs) delivered a power conversion efficiency (PCE) of 2.22%. Moreover, after being stored in nitrogen at room temperature for 60 days, the devices retained above 87.69% of their original efficiency. This work demonstrates a potential pathway to achieve high-efficiency Sb-based PSCs.

7.
PeerJ ; 10: e12891, 2022.
Article En | MEDLINE | ID: mdl-35186482

Based on two years of field experiments, under different soil tillage methods and straw management practices, which included conventional tillage (CT), subsoiling (SS), rotary tillage (RT), and no-tillage (NT), combined with either straw return (S) or straw removal (0), we characterized the dynamic changes in Δ13C among three height layers [upper (U, 240 cm above the ground), middle (M, 120 cm above the ground), and lower (L, 30 cm above the ground)] of the summer maize canopy. The Δ13C, the factors affecting it, and the relationships between Δ13C and soil water content (SWC), the leaf area index (LAI), canopy microclimate, and the CO2 concentration were elucidated. The results indicated that the Δ13C of summer maize at the pre-filling stage was greater than that at the post-filling stage. Δ13C also varied at different heights, with the order of the Δ13C values being L > U > M. Among the different tillage methods, the Δ13C values were ordered SSS > CTS > RTS > NTS. SSS and NTS significantly increased the LAI; air temperature and relative humidity tended to gradually decrease with the increase in height of summer maize. Correlation analyses of the various influencing factors and Δ13C showed that SWC, LAI, air temperature, and CO2 concentration were all positively correlated with Δ13C, in which LAI and air temperature were significantly or extremely significantly positively correlated with Δ13C. In addition, we show that Δ13C can be used as a prediction index for summer maize yield, providing a theoretical basis for future yield research that may save precious time in summer maize breeding efforts.


Agriculture , Zea mays , Agriculture/methods , Carbon Isotopes/analysis , Carbon Dioxide/analysis , Plant Breeding , Soil , Water/analysis
8.
Article En | MEDLINE | ID: mdl-34697548

OBJECTIVE: To explore the effect of applying binocular visual training after slanted lateral rectus recession on orthophoric rate and binocular visual function recovery on patients with convergence insufficiency-type intermittent exotropia (CI-IXT). METHODS: A total of 76 CI-IXT child patients treated at the Strabismus and Pediatric Ophthalmology Department of our hospital from June 2019 to June 2020 were selected as the research objects, and those who met the inclusion criteria were equally divided into group A (63 eyes) and group B (61 eyes) according to the sealed envelope randomization. All child patients accepted the slanted lateral rectus recession, and after that, those in group A accepted the binocular visual training and those in group B accepted the conventional visual function rehabilitation training, so as to compare their position of eye, the best corrected visual acuity, etc., after training for statistical analysis. RESULTS: Compared with group B after one month of surgery, group A had significantly less patients with grade I binocular vision function (P < 0.001) and more patients with grade II and III vision function (P < 0.05); between group A and group B, after 3 months and 6 months of treatment, the number of eyes with normal stereoscopic vision was significantly higher in group A (P < 0.05); at 15 days, 1 month, 3 months, and 6 months of treatment, the visual strain scores of group A were significantly lower (P < 0.001); after treatment, the number of orthophoria eyes was significantly higher in group A (P < 0.001), while the numbers of overcorrected eyes and undercorrected eyes were significantly higher in group B (P < 0.001); and the total incidence rate of adverse reactions was significantly lower in group A (P < 0.05). CONCLUSION: Applying binocular visual training to child patients with CI-IXT after slanted lateral rectus recession can promote the recovery of binocular vision and ensure higher safety, and further study will help to establish a better solution for the affected children.

9.
PeerJ ; 9: e11099, 2021.
Article En | MEDLINE | ID: mdl-33828919

BACKGROUND: Soil degradation is one of the main problems in agricultural production and leads to decreases in soil quality and productivity. Improper farming practices speed this process and are therefore not conducive to food security. The North China Plain (NCP) is a key agricultural area that greatly influences food security in China. To explore the effects of different tillage measures on aggregate-associated organic carbon (AOC), the accumulation and transport of dry matter, and maize yield, and to identify the most suitable tillage method for use on the NCP, a field experiment was conducted at Shandong Agricultural University from 2016-2017 using plots that have been farmed using conservation tillage since 2002. METHODS: In this study, Zhengdan 958 summer maize was used as the test material and undisturbed soil and plant samples were obtained under four tillage methods-no-tillage (NT, tillage depth: 0 cm); rotary tillage (RT, tillage depth: 10 cm); conventional tillage (CT, tillage depth: 20 cm); subsoiling (SS, tillage depth: 40 cm)-which were used to determine the AOC and dry matter contents, as well as the yields of two summer maize growing seasons. Each sample was replicated three times and the AOC content was determined via potassium dichromate oxidation colorimetry. Potassium dichromate oxidized organic carbon in organic matter was employed to reduce hexadecent chromium into green trivalent chromium. Colorimetry was then used to determine the amount of reduced trivalent chromium and calculate the organic matter content. RESULTS: The resulting data were statistically analyzed and the results showed that, compared with CT, the AOC contents with NT and SS increased by 5.65% and 9.73%, respectively, while that with RT decreased by 0.12%. Conventional tillage resulted in the highest mean dry matter weight when the maize reached maturity, which was 19.19%, 9.83%, and 3.38% higher than those achieved using NT, RT, and SS, respectively. No significant difference was found between CT and SS treatments, both of which tended to increase the accumulation of dry matter as well as its contribution of assimilates to grain yield post-anthesis. Compared with CT, the mean yield increased at a rate of 0.18% with SS, while yields declined at rates of 17.17% and 11.15 with NT and RT, respectively. The yield with NT was the lowest, though the harvest indices with NT and SS were higher than those with RT and CT. Overall, SS increased the accumulation of dry matter and its contribution of assimilates to grain yields post-anthesis, as well as the AOC content and yields, making it the ideal tillage method for the NCP.

10.
J Ophthalmol ; 2020: 1702695, 2020.
Article En | MEDLINE | ID: mdl-33520294

PURPOSE: To report on an improved botulinum toxin injection with conjunctival microincision for beginners, and to determine the effectiveness of botulinum toxin A (BTXA) in the treatment of patients with acute acquired comitant esotropia (AACE). METHODS: Medical records of 29 AACE patients were retrospectively analyzed. BTXA was injected into the unilateral or bilateral medial rectus muscle with conjunctival microincision without electromyographic guidance. Success was defined as total horizontal deviation ≤10 prism diopters (PD) and evidence of binocular vision. RESULTS: Twenty-nine patients were included, of whom 22 were male and 7 were female. The mean age at onset was 14.2 ± 7.4 (range, 4-34) years. The mean time from onset of AACE to injection was 18.4 ± 20.3 (range, 1-96) weeks. All patients completed at least 6 months of follow-up, and the mean follow-up after BTXA injection was 12.3 ± 4.8 months (range, 7-24 months). Neurological evaluation and brain magnetic resonance imaging (MRI) were unremarkable in all patients. The mean spherical equivalent refraction was -1.22 ± 2.85D and -0.97 ± 2.80D in the right and left eyes, respectively. Mean preinjective esotropia was 38.4 ± 18.9 PD (range, +10-+80 PD) at near and 40.2 ± 17.7 PD (range, +20-+80 PD) at far distance. The mean angle of deviation at 6 months after injection was 0.6 ± 4.1 PD (range, -3-+15 PD) at near and 3.0 ± 5.9 PD (range, 0-+20 PD) at far distance. There was significant difference in the angle of deviation at near and far fixation between pre-BTXA and post-BTXA 6 months (p < 0.001, p < 0.001, resp.). There was no significant difference in the angle of deviation at near and far fixation between post-BTXA 6 months and post-BTXA at final follow-up (p = 0.259 and 0.326, resp.). Mean stereoacuity improved from 338 to 88 arc seconds. During the follow-up period, 5 of 29 patients had recurrent esotropia. Two patients refused all further treatment, and the other 3 patients required incisional strabismus surgery. The success rates were 86.2% (25/29) at 6 months and 82.8% (24/29) at final follow-up. CONCLUSION: Conjunctival microincision injection of botulinum toxin is a practical and safe method for beginners to locate an extraocular muscle, which is as effective as the traditional methods. Botulinum toxin injection can be preferred as the first-line treatment for AACE patients with potential binocular vision.

11.
Methods Mol Biol ; 1777: 233-248, 2018.
Article En | MEDLINE | ID: mdl-29744839

The design, formulation, and immunological evaluation of self-assembling peptide materials is relatively straightforward. Indeed, one of the advantages of synthetic self-assembling peptides is that one can progress from initial concept to in vivo testing in a matter of days. However, because these materials are supramolecular, working with them is not without some practical challenges, and subtle changes in design, synthesis, handling, and formulation can affect the materials' immunogenicity. This chapter is intended to communicate some of these practical aspects of working with these materials that are not always enumerated in conventional research papers. Epitope considerations, peptide synthesis, purification, storage, nanofiber formation, quality control, immunological evaluation, and the overall phenotypic characteristics of the immune responses to be expected from these materials are discussed.


Drug Design , Peptides/chemistry , Peptides/immunology , Animals , Epitopes/chemistry , Epitopes/immunology , Immunity , Immunization , Immunoassay , Mice , Peptides/chemical synthesis , Peptides/pharmacology , Quality Control
12.
Sci Total Environ ; 635: 1102-1109, 2018 Sep 01.
Article En | MEDLINE | ID: mdl-29710565

No-tillage management practices reduce net CO2 losses from farmland and keep soil from degrading, but also decrease winter wheat grain yield and water use efficiency (WUE) in the North China Plain (NCP). Suitable management practices, namely, the choice of genotypes, could enhance crop yield and WUE; however, how the WUE and CO2 exchange responds to no-tillage practices and winter wheat genotypes remains unclear. In the 2015-2016 and 2016-2017 winter wheat growing seasons in the NCP, a field experiment was carried out, and tested two tillage methods (no-tillage with mulching and conventional tillage) and two winter wheat genotypes ('Tainong 18' and 'Jimai 22'). The goal of the study was to identify the relationship between winter wheat grain yield, water consumption, and carbon emissions in no-tillage practices. The results showed that, compared to conventional tillage, no-tillage significantly reduced the net CO2-C cumulative emissions and water consumption; however, the grain yield was significantly reduced by 6.8% and 12.0% in the first and second growing seasons, respectively. Compared with Jimai 22, Tainong 18 had a compensatory effect on the yield reduction caused by no-tillage. As a result, the yield carbon utilization efficiency (R) and WUE were the highest in no-tillage with Tainong 18 (NT18), and the carbon emission per unit water consumption was the lowest in NT18. The results support the idea that a combination of no-tillage with genotype can improve the regulation of soil carbon emissions and water consumption of winter wheat, thus, providing theoretical support for sustainable crop production and soil development in the NCP.


Agriculture/methods , Conservation of Natural Resources/methods , Triticum/growth & development , Water Supply/statistics & numerical data , Carbon , China , Crop Production/methods , Seasons , Soil , Triticum/genetics , Water
13.
Medchemcomm ; 9(1): 138-148, 2018.
Article En | MEDLINE | ID: mdl-29629068

Self-assembled peptide nanofibers raise significant antibody and T cell responses without adjuvants, but the mechanism by which they achieve this has not been fully elucidated. Myeloid differentiation primary response gene 88 (MyD88) previously has been shown to be critical for the antibody response to antigens presented by peptide nanofibers. The present study sought to determine the cell subset in which MyD88 is essential for T cell responses. Mice deficient in MyD88 or CD11c+ cells had severely attenuated T cell responses. However, mice lacking MyD88 in only CD11c+ cells remained capable of internalizing, processing, and presenting nanofiber-derived epitopes to stimulate T cell responses. The necessity of inflammasome pathway was ruled out. Using adoptive transfer models where MyD88 was eliminated in CD4+ T cells or in the host, we observed that deficiency only in T cells or only in the host had no impact on the T cell response to nanofiber vaccines. Therefore, knocking out MyD88 in either antigen presenting cells (APCs) or CD4 T cells could not compromise the CD4 T cell responses, suggesting that self-assembled peptide nanofibers trigger redundant MyD88-dependent and MyD88-independent signaling pathways in APCs and T cells. Similar redundancy has been observed for other adjuvants, and this is discussed.

14.
Sci Rep ; 7(1): 16888, 2017 12 04.
Article En | MEDLINE | ID: mdl-29203857

This study was conducted to quantify the potential for CO2 fixation in the above-ground biomass of summer maize (Zea mays L.) under different tillage and residue retention treatments. The treatments were paired and included conventional tillage with straw removed (CT0), conventional tillage with straw retained (CTS), no-till with straw removed (NT0), no-till with straw retention (NTS), subsoiling with straw removed (SS0), and subsoiling with straw retained (SSS). The results indicated that NTS and SSS can enhance translocation of photosynthates to grains during the post-anthesis stage. SSS showed the highest total production (average of 7.8 Mg ha-1), carbon absorption by crop (Cd) (average of 9.2 Mg C ha-1), and total C absorption (Ct) (average of 40.4 Mg C ha-1); and NTS showed the highest contribution of post-anthesis dry matter translocation to grain yield (average of 74%). Higher CO2 emission intensity and CO2 fixation efficiency (CFE) were observed for straw retention treatments. In comparison with CTS, the mean CFE (%) over four years increased by 26.3, 19.0, 16.5, and 9.4 for NT0, SS0, NTS, and SSS, respectively. Thus, SSS and NTS systems offer the best options for removing CO2 from the atmosphere while enhancing crop productivity of summer maize in the North China Plain.


Agriculture/methods , Biomass , Carbon Dioxide/metabolism , Zea mays/metabolism , Carbon Cycle , Carbon Dioxide/chemistry , Soil/chemistry , Zea mays/growth & development
15.
Biomaterials ; 149: 1-11, 2017 Dec.
Article En | MEDLINE | ID: mdl-28982051

Active immunotherapies raising antibody responses against autologous targets are receiving increasing interest as alternatives to the administration of manufactured antibodies. The challenge in such an approach is generating protective and adjustable levels of therapeutic antibodies while at the same time avoiding strong T cell responses that could lead to autoimmune reactions. Here we demonstrate the design of an active immunotherapy against TNF-mediated inflammation using short synthetic peptides that assemble into supramolecular peptide nanofibers. Immunization with these materials, without additional adjuvants, was able to break B cell tolerance and raise protective antibody responses against autologous TNF in mice. The strength of the anti-TNF antibody response could be tuned by adjusting the epitope content in the nanofibers, and the T-cell response was focused on exogenous and non-autoreactive T-cell epitopes. Immunization with unadjuvanted peptide nanofibers was therapeutic in a lethal model of acute inflammation induced by intraperitoneally delivered lipopolysaccharide, whereas formulations adjuvanted with CpG showed comparatively poorer protection that correlated with a more Th1-polarized response. Additionally, immunization with peptide nanofibers did not diminish the ability of mice to clear infections of Listeria monocytogenes. Collectively this work suggests that synthetic self-assembled peptides can be attractive platforms for active immunotherapies against autologous targets.


Nanofibers/chemistry , Peptides/immunology , Tumor Necrosis Factor-alpha/immunology , Animals , Antibodies, Monoclonal/immunology , Antibody Formation , B-Lymphocytes/immunology , Bacterial Vaccines , Drug Discovery , Epitopes , Female , Immunotherapy, Active , Inflammation/immunology , Inflammation/therapy , Lipopolysaccharides/pharmacology , Listeriosis/immunology , Listeriosis/prevention & control , Mice, Inbred C57BL , Particle Size , Peptides/chemistry , Peptides/pharmacology , T-Lymphocytes/immunology , Vaccines, Subunit
16.
ACS Nano ; 10(10): 9274-9286, 2016 Oct 25.
Article En | MEDLINE | ID: mdl-27680575

Biomaterials created from supramolecular peptides, proteins, and their derivatives have been receiving increasing interest for both immunological applications, such as vaccines and immunotherapies, as well as ostensibly nonimmunological applications, such as therapeutic delivery or tissue engineering. However, simple rules for either maximizing immunogenicity or abolishing it have yet to be elucidated, even though immunogenicity is a prime consideration for the design of any supramolecular biomaterial intended for use in vivo. Here, we investigated a range of physicochemical properties of fibrillized peptide biomaterials, identifying negative surface charge as a means for completely abolishing antibody and T cell responses against them in mice, even when they display a competent epitope. The work was facilitated by the modularity of the materials, which enabled the generation of a set of co-assembled fibrillar peptide materials with broad ranges of surface properties. It was found that negative surface charge, provided via negatively charged amino acid residues, prevented T cell and antibody responses to antigen-carrying assemblies because it prevented uptake of the materials by antigen-presenting cells (APCs), which in turn prevented presentation of the epitope peptide in the APCs' major histocompatibility class II molecules. Conversely, positive surface charge augmented the uptake of fibrillized peptides by APCs. These findings suggest that some surface characteristics, such as extensive negative charge, should be avoided in vaccine design using supramolecular peptide assemblies. More importantly, it provides a strategy to switch off potentially problematic immunogenicity for using these materials in nonimmunological applications.

17.
J Biomed Mater Res A ; 104(8): 1853-62, 2016 08.
Article En | MEDLINE | ID: mdl-27129604

Biomaterials used in the context of tissue engineering or wound repair are commonly designed to be "nonimmunogenic." However, previously it has been observed that self-assembled peptide nanofiber materials are noninflammatory despite their immunogenicity, suggesting that they may be appropriate for use in wound-healing contexts. To test this hypothesis, mice were immunized with epitope-containing peptide self-assemblies until they maintained high antibody titers against the material, then gels of the same peptide assemblies were applied within full-thickness dermal wounds. In three different murine dermal-wounding models with different baseline healing rates, even significantly immunogenic peptide assemblies did not delay healing. Conversely, adjuvanted peptide assemblies, while raising similar antibody titers to unadjuvanted assemblies, did delay wound healing. Analysis of the healing wounds indicated that compared to adjuvanted peptide assemblies, the unadjuvanted assemblies exhibited a progression of the dominant T-cell subset from CD4(+) to CD8(+) cells in the wound, and CD4(+) cell populations displayed a more Th2-slanted response. These findings illustrate an example of a significant antibiomaterial adaptive immune response that does not adversely affect wound healing despite ongoing antibody production. This material would thus be considered "immunologically compatible" in this specific context rather than "nonimmunogenic," a designation that is expected to apply to a range of other protein- and peptide-based biomaterials in wound-healing and tissue-engineering applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1853-1862, 2016.


Adaptive Immunity/drug effects , Awards and Prizes , Biocompatible Materials/pharmacology , Internship and Residency , Peptides/pharmacology , Wound Healing/drug effects , Adjuvants, Immunologic/pharmacology , Amino Acid Sequence , Animals , Antibody Formation/drug effects , Cytokines/metabolism , Freund's Adjuvant/pharmacology , Mice, Inbred C57BL , Nanofibers/chemistry , Ovalbumin/immunology , Peptides/chemistry , Phenotype , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Tissue Scaffolds/chemistry
18.
Acta Biomater ; 30: 62-71, 2016 Jan.
Article En | MEDLINE | ID: mdl-26584836

The majority of current vaccines depend on a continuous "cold chain" of storage and handling between 2 and 8°C. Vaccines experiencing temperature excursions outside this range can suffer from reduced potency. This thermal sensitivity results in significant losses of vaccine material each year and risks the administration of vaccines with diminished protective ability, issues that are heightened in the developing world. Here, using peptide self-assemblies based on the fibril-forming peptide Q11 and containing the epitopes OVA323-339 from ovalbumin or ESAT651-70 from Mycobacterium tuberculosis, the chemical, conformational, and immunological stability of supramolecular peptide materials were investigated. It was expected that these materials would exhibit advantageous thermal stability owing to their adjuvant-free and fully synthetic construction. Neither chemical nor conformational changes were observed for either peptide when stored at 45°C for 7days. ESAT651-70-Q11 was strongly immunogenic whether it was stored as a dry powder or as aqueous nanofibers, showing undiminished immunogenicity even when stored as long as six months at 45°C. This result was in contrast to ESAT651-70 conjugated to a protein carrier and adjuvanted with alum, which demonstrated marked thermal sensitivity in these conditions. Antibody titers and affinities were undiminished in mice for OVA323-339-Q11 if it was stored as assembled nanofibers, yet some diminishment was observed for material stored as a dry powder. The OVA study was done in a different mouse strain and with a different prime/boost regimen, and so it should not be compared directly with the study for the ESAT epitope. This work indicates that peptide self-assemblies can possess attractive thermal stability properties in the context of vaccine development. STATEMENT OF SIGNIFICANCE: Almost all current vaccines must be maintained within a tight and refrigerated temperature range, usually between 2 and 8°C. This presents significant challenges for their distribution, especially in the developing world. Here we report on the surprisingly robust thermal stability of a self-assembled peptide vaccine. In particular a self-assembled peptide vaccine containing a tuberculosis epitope maintained all of its potency in mice when exposed to an extreme thermal treatment of six months at 45°C. In a different mouse model, we investigated another model epitope and found some storage conditions where potency was diminished. Overall this study illustrates that some self-assembled peptide vaccines can have remarkable thermal stability.


Antigens, Bacterial , Bacterial Proteins , Mycobacterium tuberculosis/immunology , Nanofibers/chemistry , Peptides , Tuberculosis Vaccines , Animals , Antigens, Bacterial/chemistry , Antigens, Bacterial/immunology , Antigens, Bacterial/pharmacology , Bacterial Proteins/chemistry , Bacterial Proteins/immunology , Bacterial Proteins/pharmacology , Female , Mice , Nanofibers/ultrastructure , Peptides/chemistry , Peptides/immunology , Peptides/pharmacology , Tuberculosis Vaccines/chemistry , Tuberculosis Vaccines/immunology , Tuberculosis Vaccines/pharmacology
19.
Ying Yong Sheng Tai Xue Bao ; 26(6): 1765-71, 2015 Jun.
Article Zh | MEDLINE | ID: mdl-26572030

To explore the effects of different tillage methods and straw recycling on soil respiration and microbial activity in summer maize field during the winter wheat and summer maize double cropping system, substrate induced respiration method and CO2 release method were used to determine soil microbial biomass carbon, microbial activity, soil respiration, and microbial respiratory quotient. The experiment included 3 tillage methods during the winter wheat growing season, i.e., no-tillage, subsoiling and conventional tillage. Each tillage method was companied with 2 straw management patterns, i.e., straw recycling and no straw. The results indicated that the conservation tillage methods and straw recycling mainly affected 0-10 cm soil layer. Straw recycling could significantly improve the microbial biomass carbon and microbial activity, while decrease microbial respiratory quotient. Straw recycling could improve the soil respiration at both seedling stage and anthesis, however, it could reduce the soil respiration at filling stage, wax ripeness, and harvest stage. Under the same straw application, compared with conventional tillage, the soil respiration and microbial respiratory quotient in both subsoiling and no-tillage were reduced, while the microbial biomass carbon and microbial activity were increased. During the summer maize growing season, soil microbial biomass carbon and microbial activity were increased in straw returning with conservation tillage, while the respiratory quotient was reduced. In 0-10 cm soil layer, compared with conventional tillage, straw recycling with subsoiling and no-tillage significantly increased soil microbial biomass carbon by 95.8% and 74.3%, and increased soil microbial activity by 97.1% and 74.2%, respectively.


Agriculture/methods , Soil Microbiology , Soil/chemistry , Triticum , Zea mays , Biomass , Carbon/analysis , Carbon Dioxide/analysis , Recycling
20.
ScientificWorldJournal ; 2014: 180219, 2014.
Article En | MEDLINE | ID: mdl-25147835

Demand for food security and the current global warming situation make high and strict demands on the North China Plain for both food production and the inhibition of agricultural carbon emissions. To explore the most effective way to decrease soil CO2 emissions and maintain high grain yield, studies were conducted during the 2012 and 2013 summer maize growing seasons to assess the effects of wheat straw mulching on the soil CO2 emissions and grain yield of summer maize by adding 0 and 0.6 kg m(-2) to fields with plant densities of 100,000, 75,000, and 55,000 plants ha(-1). The study indicated that straw mulching had some positive effects on summer maize grain yield by improving the 1000-kernel weight. Meanwhile, straw mulching effectively controlled the soil respiration rate and cumulative CO2 emission flux, particularly in fields planted at a density of 75,000 plants ha(-1), which achieved maximum grain yield and minimum carbon emission per unit yield. In addition, soil microbial biomass and microbial activity were significantly higher in mulching treatments than in nonmulching treatments. Consequently, summer maize with straw mulching at 75,000 plants ha(-1) is an environmentally friendly option in the North China Plain.


Agriculture , Carbon Dioxide/chemistry , Seasons , Soil/chemistry , Zea mays/growth & development , China
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