Effects of pickle brine and glycine addition on biogenic amine production in pickle fermentation.

This study investigated the effects of different pickle brines and glycine additions on biogenic amine formation in pickle fermentation. The results showed that the brines with higher biogenic amine content led to the production of more biogenic amines in the simulated pickle fermentation system. This was related to the abundance of biogenic amine-producing microorganisms in the microbial communities of the brines. Metagenome analysis of the brines and metatranscriptome analysis of the fermentation systems showed that putrescine was primarily from Lactobacillus, Oenococcus, and Pichia, while histamine and tyramine were primarily from Lactobacillus and Tetragenococcus. Addition of glycine significantly reduced the accumulation of biogenic amines in the simulated pickle fermentation system by as much as 70 %. The addition of glycine had no inhibitory effect on the amine-producing microorganisms, but it down-regulated the transcription levels of the genes for enzymes related to putrescine synthesis in Pichia, Lactobacillus, and Oenococcus, as well as the histidine decarboxylase genes in Lactobacillus and Tetragenococcus. Catalytic reaction assay using crude solutions of amino acid decarboxylase extracted from Lactobacillus brevis showed that the addition of glycine inhibited 45 %-55 % of ornithine decarboxylase and tyrosine decarboxylase activities. This study may provide a reference for the study and control of the mechanism of biogenic amine formation in pickle fermentation.

Efficacy of daprodustat for patients on dialysis with anemia: systematic review and network meta-analysis.

Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl hydroxylase of hypoxia-inducible factor, recombinant human erythropoietin (rhEPO), and iron supplements. We conducted this study to test our postulation; daprodustat is superior to rhEPO and other conventional treatments respecting efficacy and safety parameters. We made systematic search through PubMed, Web of Science, Scopus, and Cochrane. Seven unique trials were eventually included for systematic review; six of them with a sample size of 759 patients entered our network meta-analysis (NMA). Daprodustat 25-30 mg was associated with the greatest change in serum hemoglobin (MD=1.86, 95%CI= [1.20; 2.52]), ferritin (MD= -180.84, 95%CI= [-264.47; -97.20]), and total iron binding capacity (TIBC) (MD=11.03, 95%CI= [3.15; 18.92]) from baseline values. Dialysis-dependent patients with anemia had a significant increment in serum Hemoglobin and TIBC and a reduction in serum ferritin, in a dose-dependent manner, when administered daprodustat.

Exploring glycine root uptake dynamics in phosphorus and iron deficient tomato plants during the initial stages of plant development.

BACKGROUND: Phosphorus (P) and iron (Fe) deficiencies are relevant plants nutritional disorders, prompting responses such as increased root exudation to aid nutrient uptake, albeit at an energy cost. Reacquiring and reusing exudates could represent an efficient energy and nitrogen saving strategy. Hence, we investigated the impact of plant development, Fe and P deficiencies on this process. Tomato seedlings were grown hydroponically for 3 weeks in Control, -Fe, and -P conditions and sampled twice a week. We used Isotope Ratio Mass-Spectrometry to measure δ13C in roots and shoots after a 2-h exposure to 13C-labeled glycine (0, 50, or 500 µmol L-1). Plant physiology was assessed with an InfraRed Gas Analyzer and ionome with an Inductively Coupled Plasma Mass-Spectrometry. RESULTS: Glycine uptake varied with concentration, suggesting an involvement of root transporters with different substrate affinities. The uptake decreased over time, with -Fe and -P showing significantly higher values as compared to the Control. This highlights its importance during germination and in nutrient-deficient plants. Translocation to shoots declined over time in -P and Control but increased in -Fe plants, suggesting a role of Gly in the Fe xylem transport. CONCLUSIONS: Root exudates, i.e. glycine, acquisition and their subsequent shoot translocation depend on Fe and P deficiency. The present findings highlight the importance of this adaptation to nutrient deficiencies, that can potentially enhance plants fitness. A thorough comprehension of this trait holds potential significance for selecting cultivars that can better withstand abiotic stresses.

Reversing the directionality of reactions between non-oxidative pentose phosphate pathway and glycolytic pathway boosts mycosporine-like amino acid production in Saccharomyces cerevisiae.

BACKGROUND: Mycosporine-like amino acids (MAAs) are a class of strongly UV-absorbing compounds produced by cyanobacteria, algae and corals and are promising candidates for natural sunscreen components. Low MAA yields from natural sources, coupled with difficulties in culturing its native producers, have catalyzed synthetic biology-guided approaches to produce MAAs in tractable microbial hosts like Escherichia coli, Saccharomyces cerevisiae and Corynebacterium glutamicum. However, the MAA titres obtained in these hosts are still low, necessitating a thorough understanding of cellular factors regulating MAA production. RESULTS: To delineate factors that regulate MAA production, we constructed a shinorine (mycosporine-glycine-serine) producing yeast strain by expressing the four MAA biosynthetic enzymes from Nostoc punctiforme in Saccharomyces cerevisiae. We show that shinorine is produced from the pentose phosphate pathway intermediate sedoheptulose 7-phosphate (S7P), and not from the shikimate pathway intermediate 3-dehydroquinate (3DHQ) as previously suggested. Deletions of transaldolase (TAL1) and phosphofructokinase (PFK1/PFK2) genes boosted S7P/shinorine production via independent mechanisms. Unexpectedly, the enhanced S7P/shinorine production in the PFK mutants was not entirely due to increased flux towards the pentose phosphate pathway. We provide multiple lines of evidence in support of a reversed pathway between glycolysis and the non-oxidative pentose phosphate pathway (NOPPP) that boosts S7P/shinorine production in the phosphofructokinase mutant cells. CONCLUSION: Reversing the direction of flux between glycolysis and the NOPPP offers a novel metabolic engineering strategy in Saccharomyces cerevisiae.

[Efficacy and safety analysis of hypoxia-inducible factor prolyl hydroxylase inhibitors for anemia in low-risk myelodysplastic syndromes patients].

Myelodysplastic syndromes is a heterogeneous group of myeloid neoplastic disorders originating from hematopoietic stem cells and manifesting as pathological bone marrow hematopoiesis and a high risk of transformation to acute myeloid leukemia. In low-risk patients, the therapeutic goal is to improve hematopoiesis and quality of life. Roxadustat is the world's first oral small-molecule hypoxia-inducible factor prolyl hydroxylase inhibitor, which, unlike conventional erythropoietin, corrects anemia through various mechanisms. In this study, we retrospectively analyzed the changes in anemia, iron metabolism, lipids and inflammatory indexes in patients with low-risk myelodysplastic syndromes to evaluate its therapeutic efficacy and safety, and to provide theoretical and practical data for the application of roxadustat in myelodysplastic syndromes.

[Efficacy and safety of roxadustat in the treatment of refractory non-severe aplastic anemia].

Objective: To evaluate the efficacy and safety of roxadustat in patients with refractory non-severe aplastic anemia (NSAA) . Methods: The clinical data of patients with refractory NSAA who had been treated with roxadustat continuously for at least 3 months and followed up for more than 6 months at Peking Union Medical College Hospital from October 2020 to August 2022 were retrospectively collected. The demographic information, clinical data, treatment efficacy, adverse reactions, and outcomes were evaluated, and the factors influencing efficacy were analyzed. Results: A total of 41 patients were included. The male-to-female ratio was 16∶25, and the median age was 52 (18-84) years. The median duration of roxadustat treatment was 5 (3-20) months, and the median follow-up was 15 (6-26) months. Hematologic improvement-erythroid (HI-E) was 12.2%, 29.3%, 46.3%, 43.9%, and 30.3% at 1, 2, 3, 6, and 12 months, respectively. The rate of transfusion independence was 28.5%, 38.1%, and 33.3% at 3, 6, and 12 months, respectively. Hemoglobin returned to normal in some patients after treatment with roxadustat. The incidence of adverse events was 22%, all of which were grade Ⅰ-Ⅱ and recoverable. No factors that could affect HI-E were identified. By the end of follow-up, 45% of the patients relapsed, with a median time to relapse of 7 (3-12) months. No clonal evolution was observed, and one patient died. Conclusion: Roxadustat effectively improved anemia with good tolerance in patients with refractory NSAA.

Three-dimensional polymer phenylethnylcopper/nitrogen doped graphene aerogel electrode coupled with Fe3O4 NPs nanozyme: Toward sensitive and robust photoelectrochemical detection of glyphosate in agricultural matrix.

BACKGROUND: Presently, glyphosate (Gly) is the most extensively used herbicide globally, Nevertheless, its excessive usage has increased its accumulation in off-target locations, and aroused concerns for food and environmental safety. Commonly used detection methods, such as high-performance liquid chromatography and gas chromatography, have limitations due to expensive instruments, complex pre-processing steps, and inadequate sensitivity. Therefore, a facile, sensitive, and reliable Gly detection method should be developed. RESULTS: A photoelectrochemical (PEC) sensor consisting of a three-dimensional polymer phenylethnylcopper/nitrogen-doped graphene aerogel (PPhECu/3DNGA) electrode coupled with Fe3O4 NPs nanozyme was constructed for sensitive detection of Gly. The microscopic 3D network of electrodes offered fast transfer routes for photo-generated electrons and a large surface area for nanozyme loading, allowing high signal output and analytical sensitivity. Furthermore, the use of peroxidase-mimicking Fe3O4 NPs instead of natural enzyme improved the stability of the sensor against ambient temperature changes. Based on the inhibitory effect of Gly on the catalytic activity Fe3O4 NPs, the protocol achieved Gly detection in the range of 5 × 10-10 to 1 × 10-4 mol L-1. Additionally, feasibility of the detection was confirmed in real agricultural matrix including tea, maize seedlings, maize seeds and soil. SIGNIFICANCE: This work achieved facile, sensitive and reliable analysis towards Gly, and it was expected to inspire the design and utilization of 3D architectures in monitoring agricultural chemicals in food and environmental matrix.

Genotoxicological and physiological effects of glyphosate and its metabolite, aminomethylphosphonic acid, on the freshwater invertebrate Lymnaea stagnalis.

Aminomethylphosphonic acid (AMPA) is the main metabolite in the degradation of glyphosate, a broad-spectrum herbicide, and it is more toxic and persistent in the environment than the glyphosate itself. Owing to their extensive use, both chemicals pose a serious risk to aquatic ecosystems. Here, we explored the genotoxicological and physiological effects of glyphosate, AMPA, and the mixed solution in the proportion 1:1 in Lymnaea stagnalis, a freshwater gastropod snail. To do this, adult individuals were exposed to increasing nominal concentrations (0.0125, 0.025, 0.050, 0.100, 0.250, 0.500 µg/mL) in all three treatments once a week for four weeks. The genotoxicological effects were estimated as genomic damage, as defined by the number of micronuclei and nuclear buds observed in hemocytes, while the physiological effects were estimated as the effects on somatic growth and egg production. Exposure to glyphosate, AMPA, and the mixed solution caused genomic damage, as measured in increased frequency of micronuclei and nuclear buds and in adverse effects on somatic growth and egg production. Our findings suggest the need for more research into the harmful and synergistic effects of glyphosate and AMPA and of pesticides and their metabolites in general.

ASS1 inhibits triple-negative breast cancer by regulating PHGDH stability and de novo serine synthesis.

Argininosuccinate synthase (ASS1), a critical enzyme in the urea cycle, acts as a tumor suppressor in many cancers. To date, the anticancer mechanism of ASS1 has not been fully elucidated. Here, we found that phosphoglycerate dehydrogenase (PHGDH), a key rate-limiting enzyme in serine synthesis, is a pivotal protein that interacts with ASS1. Our results showed that ASS1 directly binds to PHGDH and promotes its ubiquitination-mediated degradation to inhibit serine synthesis, consequently suppressing tumorigenesis. Importantly, the tumor suppressive effects of ASS1 were strongly abrogated by PHGDH knockout. In addition, ASS1 knockout and knockdown partially rescued cell proliferation when serine and glycine were depleted, while the inhibitory effect of ASS1 overexpression on cell proliferation was restored by the addition of serine and glycine. These findings unveil a novel role of ASS1 and suggest that the ASS1/PHGDH serine synthesis pathway is a promising target for cancer therapy.

Glyphosate presence in human sperm: First report and positive correlation with oxidative stress in an infertile French population.

Environmental exposure to endocrine disruptors, such as pesticides, could contribute to a decline of human fertility. Glyphosate (GLY) is the main component of Glyphosate Based Herbicides (GBHs), which are the most commonly herbicides used in the world. Various animal model studies demonstrated its reprotoxicity. In Europe, GLY authorization in agriculture has been extended until 2034. Meanwhile the toxicity of GLY in humans is still in debate. The aims of our study were firstly to analyse the concentration of GLY and its main metabolite, amino-methyl-phosphonic acid (AMPA) by LC/MS-MS in the seminal and blood plasma in an infertile French men population (n=128). We secondly determined Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) using commercial colorimetric kits and some oxidative stress biomarkers including malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) by ELISA assays. We next analysed potential correlations between GLY and oxidative stress biomarkers concentration and sperm parameters (sperm concentration, progressive speed, anormal forms). Here, we detected for the first time GLY in the human seminal plasma in significant proportions and we showed that its concentration was four times higher than those observed in blood plasma. At the opposite, AMPA was undetectable. We also observed a strong positive correlation between plasma blood GLY concentrations and plasma seminal GLY and 8-OHdG concentrations, the latter reflecting DNA impact. In addition, TOS, Oxidative Stress Index (OSI) (TOS/TAS), MDA blood and seminal plasma concentrations were significantly higher in men with glyphosate in blood and seminal plasma, respectively. Taken together, our results suggest a negative impact of GLY on the human reproductive health and possibly on his progeny. A precaution principle should be applied at the time of the actual discussion of GLY and GBHs formulants uses in Europe by the authorities.

Intracellular Delivery of Plasmid DNA Using Amphipathic Helical Cell-Penetrating Peptides Containing Dipropylglycine.

Cell-penetrating peptides (CPPs) serve as potent vehicles for delivering membrane-impermeable compounds, including nucleic acids, into cells. In a previous study, we reported the successful intracellular delivery of small interfering RNAs (siRNAs) with negligible cytotoxicity using a peptide containing an unnatural amino acid (dipropylglycine). In the present study, we employed the same seven peptides as the previous study to evaluate their efficacy in delivering plasmid DNA (pDNA) intracellularly. Although pDNA and siRNA are nucleic acids, they differ in size and biological function, which may influence the optimal peptide sequences for their delivery. Herein, three peptides demonstrated effective pDNA transfection abilities. Notably, only one of the three peptides previously exhibited efficient gene-silencing effect with siRNA. These findings validate our hypothesis and offer insights for the personalized design of CPPs for the delivery of pDNA and siRNA.

In-vitro biofilm removal from TiUnite® implant surface with an air polishing and two different plasma devices.

BACKGROUND: We investigated the efficacy of two different cold atmospheric pressure jet plasma devices (CAP09 and CAPmed) and an air polishing device with glycine powder (AP) either applied as monotherapies or combined therapies (AP + CAP09; AP + CAPmed), in microbial biofilm removal from discs with anodised titanium surface. METHODS: Discs covered with 7-day-old microbial biofilm were treated either with CAP09, CAPmed, AP, AP + CAP09 or AP + CAPmed and compared with negative and positive controls. Biofilm removal was assessed with flourescence and electron microscopy immediately after treatment and after 5 days of reincubation of the treated discs. RESULTS: Treatment with CAP09 or CAPmed did not lead to an effective biofilm removal, whereas treatment with AP detached the complete biofilm, which however regrew to baseline magnitude after 5 days of reincubation. Both combination therapies (AP + CAP09 and AP + CAPmed) achieved a complete biofilm removal immediately after cleaning. However, biofilm regrew after 5 days on 50% of the discs treated with the combination therapy. CONCLUSION: AP treatment alone can remove gross biofilm immediately from anodised titanium surfaces. However, it did not impede regrowth after 5 days, because microorganisms were probably hidden in holes and troughs, from which they could regrow, and which were inaccessible to AP. The combination of AP and plasma treatment probably removed or inactivated microorganisms also from these hard to access spots. These results were independent of the choice of plasma device.

Multifunctional 2D hemin-bridged MOF for the efficient removal and dual-mode detection of organophosphorus pesticides.

The high-residual and bioaccumulation property of organophosphorus pesticides (OPs) creates enormous risks towards the ecological environment and human health, promoting the research for smart adsorbents and detection methods. Herein, 2D hemin-bridged MOF nanozyme (2D-ZHM) was fabricated and applied to the efficient removal and ultrasensitive dual-mode aptasensing of OPs. On the one hand, the prepared 2D-ZHM contained Zr-OH groups with high affinity for phosphate groups, endowing it with selective recognition and high adsorption capacity for OPs (285.7 mg g-1 for glyphosate). On the other hand, the enhanced peroxidase-mimicking biocatalytic property of 2D-ZHM allowed rapid H2O2-directed transformation of 3,3',5,5'-tetramethylbenzidine to oxidic product, producing detectable colorimetric or photothermal signals. Using aptamers of specific recognition capacity, the rapid quantification of two typical OPs, glyphosate and omethoate, was realized with remarkable sensitivity and selectivity. The limit of detections (LODs) of glyphosate were 0.004 nM and 0.02 nM for colorimetric and photothermal methods, respectively, and the LODs of omethoate were 0.005 nM and 0.04 nM for colorimetric and photothermal methods, respectively. The constructed dual-mode aptasensing platform exhibited outstanding performance for monitoring OPs in water and fruit samples. This work provides a novel pathway to develop MOF-based artificial peroxidase and integrated platform for pollutant removal and multi-mode aptasensing.

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

Glyphosate-environmental variables interaction: How does it affect the parasite Chordodes nobilii?

The worldwide used herbicide Glyphosate can interact with environmental variables, but there is limited information on the influence of environmental stressors on its toxicity. Environmental changes could modify glyphosate effects on non-target organisms, including parasites such as gordiids. The freshwater microscopic larvae of the gordiid Chordodes nobilii are sensitive to several pollutants and environmental variables, but their combined effect has not been evaluated yet. The aim of this study was to evaluate the impact of temperature, pH and exposure time on the toxicity of Glyphosate to C. nobilii larvae. A protocol was followed to evaluate the infectivity of larvae treated with factorial combinations of concentration (0 and 0.067 mg/L), exposure time (24 and 48 h), temperature (18, 23 and 28 °C), and pH (7, 8 and 9). The reference values were 23 °C, pH 8 and 48 h. The interaction effect on the infectivity of gordiid larvae was assessed post-exposure using Aedes aegyptii larvae as host. Results were evaluated using GLMM, which does not require data transformation. The modeling results revealed three highly significant triple interactions. Glyphosate toxicity varied depending on the combination of variables, with a decrease being observed after 24 h-exposure at pH 7 and 23 °C. Glyphosate and 28 °C combination led to slightly reduced infectivity compared to temperature alone. This study is the first to report the combined effects of glyphosate, temperature, pH and time on a freshwater animal. It demonstrates that a specific combination of factors determines the effect of glyphosate on a non-target organism. The potential use of C. nobilli as a bioindicator is discussed. In the context of global warming and considering that the behavioral manipulation of terrestrial hosts by gordiids can shape community structure and the energy flow through food webs, our results raise concerns about possible negative effects of climate change on host-parasite dynamics.

Mitigating glyphosate levels in surface waters: Long-term assessment in an agricultural catchment in Belgium.

The increasing concern over pesticide pollution in water bodies underscores the need for effective mitigation strategies to support the transition towards sustainable agriculture. This study assesses the effectiveness of landscape mitigation strategies, specifically vegetative buffer strips, in reducing glyphosate loads at the catchment scale under realistic conditions. Conducted over six years (2014-2019) in a small agricultural region in Belgium, our research involved the analysis of 732 water samples from two monitoring stations, differentiated by baseflow and event-driven sampling, and before (baseline) and after the implementation of mitigation measures. The results indicated a decline in both the number and intensity of point source losses over the years. Additionally, there was a general decrease in load intensity; however, the confluence of varying weather conditions (notably dry years during the mitigation period) and management practices (the introduction of buffer strips) posed challenges for a statistically robust evaluation of each contributing factor. A reduction of loads was measured when comparing mitigation with baseline, although this reduction is not statistically significant. Glyphosate loads during rainfall events correlated with a rainfall index and runoff ratio. Overall, focusing the mitigation strategy on runoff and erosion was a valid approach. Nevertheless, challenges remain, as evidenced by the continuous presence of glyphosate in baseflow conditions, highlighting the complex dynamics of pesticide transport. The study concludes that while progress has been made towards reducing pesticide pollution, the complexity of interacting factors necessitates further research. Future directions should focus on enhancing farmer engagement in mitigation programs and developing experiments with more intense data collection that help to assess underlying dynamics of pesticide pollution and the impact of mitigation strategies in more detail, contributing towards the goal of reducing pesticide pollution in water bodies.

A Method for Rigorously Selective Capture and Simultaneous Fluorescent Labeling of N-Terminal Glycine Peptides.

Although chemical methods for the selective derivatization of amino acid (AA) side chains in peptides and proteins are available, selective N-terminal labeling is challenging, especially for glycine, which has no side chain at the α-carbon position. We report here a double activation at glycine's α-methylene group that allows this AA to be differentiated from the other 19 AAs. A condensation reaction of dibenzoylmethane with glycine results in the formation of an imine, and subsequent tautomerization is followed by intramolecular cyclization, leading to the formation of a fluorescent pyrrole ring. Additionally, the approach exhibits compatibility with AAs possessing reactive side chains. Further, the method allows for selective pull-down assays of N-terminal glycine peptides from mixtures without prior knowledge of the N-terminal peptide distribution.

Neurexins control the strength and precise timing of glycinergic inhibition in the auditory brainstem.

Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are involved in shaping functional properties of the glycinergic synapses, which mediate prominent inhibition in the brainstem and spinal cord. To address these issues, we examined the role of neurexins in a model glycinergic synapse between the principal neuron in the medial nucleus of the trapezoid body (MNTB) and the principal neuron in the lateral superior olive (LSO) in the auditory brainstem. Combining RNAscope with stereotactic injection of AAV-Cre in the MNTB of neurexin1/2/3 conditional triple knockout mice, we showed that MNTB neurons highly express all isoforms of neurexins although their expression levels vary remarkably. Selective ablation of all neurexins in MNTB neurons not only reduced the amplitude but also altered the kinetics of the glycinergic synaptic transmission at LSO neurons. The synaptic dysfunctions primarily resulted from an impaired Ca2+ sensitivity of release and a loosened coupling between voltage-gated Ca2+ channels and synaptic vesicles. Together, our current findings demonstrate that neurexins are essential in controlling the strength and temporal precision of the glycinergic synapse, which therefore corroborates the role of neurexins as key presynaptic organizers in all major types of fast chemical synapses.

Flexible, biodegradable ultrasonic wireless electrotherapy device based on highly self-aligned piezoelectric biofilms.

Biodegradable piezoelectric devices hold great promise in on-demand transient bioelectronics. Existing piezoelectric biomaterials, however, remain obstacles to the development of such devices due to difficulties in large-scale crystal orientation alignment and weak piezoelectricity. Here, we present a strategy for the synthesis of optimally orientated, self-aligned piezoelectric γ-glycine/polyvinyl alcohol (γ-glycine/PVA) films via an ultrasound-assisted process, guided by density functional theory. The first-principles calculations reveal that the negative piezoelectric effect of γ-glycine originates from the stretching and compression of glycine molecules induced by hydrogen bonding interactions. The synthetic γ-glycine/PVA films exhibit a piezoelectricity of 10.4 picocoulombs per newton and an ultrahigh piezoelectric voltage coefficient of 324 × 10-3 volt meters per newton. The biofilms are further developed into flexible, bioresorbable, wireless piezo-ultrasound electrotherapy devices, which are demonstrated to shorten wound healing by ~40% and self-degrade in preclinical wound models. These encouraging results offer reliable approaches for engineering piezoelectric biofilms and developing transient bioelectronics.

Preparation of natural high-mannose-type oligosaccharides (Glc1Man9GlcNAc2) with the asparagine-glycine-threonine as consensus sequence from chicken egg yolk.

High-mannose-type glycan structure of N-glycoproteins plays important roles in the proper folding of proteins in sorting glycoprotein secretion and degradation of misfolded proteins in the endoplasmic reticulum (ER). The Glc1Man9GlcNAc2 (G1M9)-type N-glycan is one of the most important signaling molecules in the ER. However, current chemical synthesis strategies are laborious, warranting more practical approaches for G1M9-glycopeptide development. Wang et al. reported the procedure to give G1M9-Asn-Fmoc through chemical modifications and purifications from 40 chicken eggs, but only 3.3 mg of G1M9-glycopeptide was obtained. Therefore, better methods are needed to obtain more than 10 mg of G1M9-glycopeptide. In this study, we report the preparation of G1M9-glycopeptide (13.2 mg) linking Asn-Gly-Thr triad as consensus sequence from 40 chicken eggs. In this procedure, λ-carrageenan treatment followed by papain treatment was used to separate the Fc region of IgY antibody that harbors high-mannose glycans. Moreover, cotton hydrophilic interaction liquid chromatography was adapted for easy purification. The resulting G1M9-Asn(Fmoc)-Gly-Thr was identified by nuclear magnetic resonance and mass spectroscopy. G1M9-Asn(Fmoc)-Gly, G1M9-Asn(Fmoc), and G1M9-OH were also detected by mass spectroscopy. Here, our developed G1M9-tripeptide might be useful for the elucidation of glycoprotein functions as well as the specific roles of the consensus sequence.