Premature Degradation Research Articles

Risk-averse maintenance scheduling of generation units in combined heat and power systems with demand response

The periodic outage planning of generation units for maintenance services is critical for their economic operation. Ignoring it can lead to premature degradation, high repair costs, and system reliability deterioration due to unexpected outages. Accordingly, generation maintenance scheduling (GMS) can optimally handle this challenge. In a power system with combined heat and power (CHP), although CHP units can efficiently supply power and heat demand, continuous operation of such units can cause an increase in unexpected failure rate and repair costs. Accordingly, this research accomplishes GMS coordination in CHP-integrated energy systems to optimally determine the maintenance plan of units. Firstly, the yearly GMS is planned and then the short-term generation scheduling is optimized. The proposed GMS problem is modeled as a mixed-integer nonlinear programming problem while considering the technical constraints, CHP feasible operation region, and power and heat balance. Moreover, the uncertainty in the market price is considered and the CVaR measure is employed to deal with the risks in the GMS. Furthermore, demand response is also assumed in the short-term generation scheduling while evaluating the impact of the yearly GMS. Numerical simulations with scenario-based optimization are used to evaluate the proposed CHP GMS problem with uncertainty in market price.

Premature degeneration of tapetum cells causes monogenically controlled environmentally stable male sterility in psyllium

AbstractPsyllium (Plantago ovata Forsk.) is an important medicinal species cultivated throughout the semi‐arid areas in India. The seed coat, commercially known as psyllium husk, is used as a laxative for treating irritation of gastro‐intestinal tract and relieving constipation. There is an urgent need to enhance its productivity to make the crop more profitable. Artificial crossing is difficult in the species because of its small‐sized sessile florets that are compactly arranged on a soft inflorescence axis. Male sterility has been reported in the species; however, no conclusive studies have been conducted to reveal the inheritance, mode of action, and cytogenetic basis of male sterility. Hence, the purpose of this study was to determine (a) the histological and cytogenetic bases of anther development and microsporogenesis in male‐sterile and fertile plant types and (b) the genetic basis of male sterility. The study revealed that male sterility in psyllium was not attributable to meiotic abnormality or to tetrad abnormalities, but it was attributable to premature degradation of the tapetum layer, which subsequently causes the microspore degeneration, resulting in nonproduction of pollen grains. Male sterility was controlled by a single recessive gene, which was found to be stable across years and hence can easily be bred into any psyllium genotypes of breeders’ choice. Newly developed male‐sterility‐maintainer line can be used to generate new sets of male‐sterile lines for hybrid seed production or harnessing hybrid vigor in the field.

Mechanism of the growth and development of the posterior silk gland and silk secretion revealed by mutation of the fibroin light chain in silkworm

Silkworm, as a model organism, has very high economic value due to its silk secretion ability. Although a large number of studies have attempted to elucidate the mechanism of silk secretion, it remains unclear. In this study, the fibroin light chain (Fib-L) gene of silkworm was subjected to CRISPR/Cas9 editing, which yielded premature termination of translation at 135 aa. Compared with those of the wild type, the posterior silk glands (PSGs) of the homozygous mutants on the third day of the fifth instar showed obvious premature degeneration. Comparative transcriptome and proteomic analyses of the PSGs of wild-type individuals, heterozygous mutants and homozygous mutants were performed on the fourth day of the fifth instar. A GO enrichment analysis showed that the differentially expressed genes (DEGs) between homozygous mutants and wild-type individuals were enriched in cytoskeleton-related terms, and a KEGG enrichment analysis showed that the upregulated DEGs between homozygous mutants and wild-type individuals were enriched in the phagosome and apoptosis pathways. These results indicated that apoptosis was activated prematurely in the PSGs of homozygous mutants. Furthermore, autophagy and heat shock response were activated in the PSGs of homozygous mutants, as demonstrated by an analysis of the DEGs related to autophagy and heat shock. A comparative proteomic analysis further confirmed that autophagy, apoptosis and the heat shock response were activated in the PSGs of homozygous mutants, which led to premature degradation of the PSGs. These results provide insights for obtaining a more in-depth understanding of the mechanism of silk secretion in silkworms.

Enzymatic Assays to Explore Viral mRNA Capping Machinery.

In eukaryotes, mRNA is modified by the addition of the 7‐methylguanosine (m7G) 5′ cap to protect mRNA from premature degradation, thereby enhancing translation and enabling differentiation between self (endogenous) and non‐self RNAs (e. g., viral ones). Viruses often develop their own mRNA capping pathways to augment the expression of their proteins and escape host innate immune response. Insights into this capping system may provide new ideas for therapeutic interventions and facilitate drug discovery, e. g., against viruses that cause pandemic outbreaks, such as beta‐coronaviruses SARS‐CoV (2002), MARS‐CoV (2012), and the most recent SARS‐CoV‐2. Thus, proper methods for the screening of large compound libraries are required to identify lead structures that could serve as a basis for rational antiviral drug design. This review summarizes the methods that allow the monitoring of the activity and inhibition of enzymes involved in mRNA capping.

Study of damage to rockbolts used in the foundations of protection structures against gravitational hazards

Fully grouted rockbolts are used to anchor protection structures against natural gravitational hazards. In recent years, contractors have observed a premature degradation of the steel bars of these rockbolts. In the dimensioning of a rockbolt, the choice of the steel bar is currently made only on its pure tensile strength. The objective of this study is to identify whether the degradations observed in situ are related to the metallurgical nature of the bar steel and/or the load conditions. 16 damaged rockbolts were taken from four different sites in the Alpine area. They were subjected to a metallurgical analysis and a supplementary analysis of their environment. In conclusion, it was underlined that the damages were due to a lack of knowledge of the effective loads transmitted by the snow-filled structures, but also to a lack of consideration of the deformation behaviour of the foundation. The loads applied to these rockbolt bars generated a bending depending on the nature of the surrounding ground. It has been shown that these loads can occur in successive jolts and with modification of their orientation in relation to the number of links between the rockbolt and the protection structure.

Predicted N-terminal N-linked glycosylation sites may underlie membrane protein expression patterns in Saccharomyces cerevisiae.

N-linked glycosylation is one type of posttranslational modification that proteins undergo during expression. The following describes the effects of N-linked glycosylation on high-level membrane protein expression in yeast with an emphasis on Saccharomyces cerevisiae. N-linked glycosylation is highlighted here as an important consideration when preparing membrane protein gene constructs for expression in S. cerevisiae, which continues to be used as a workhorse in both research and industrial applications. Non-native N-linked glycosylation commonly occurs during the heterologous expression of mammalian proteins in many yeast species which can have important immunological consequences when used in the production of biotherapeutic proteins or peptides. Further, non-native N-linked glycosylation can lead to improper protein folding and premature degradation, which can impede high-level expression yields and hinder downstream analysis. Multiple strategies are presented in this article, which suggest different methods that can be implemented to circumvent the unwanted consequences of N-linked glycosylation during the expression process. These considerations may have long-term benefits for high-level protein production in S. cerevisiae across a broad spectrum of expression targets with special emphasis placed on G-protein coupled receptors, one of the largest families of membrane proteins.

Composite Filament Made from Post-used Styrofoam and Corn Husk Fiber for Fuse Deposition Modeling

ABSTRACT This research aimed at developing composite filament for fuse deposition modeling (FDM) application was carried out by recycling post-used expanded polystyrene foam (EPS) as a binding matrix for natural fibers derived from corn husk (CH) waste. The recycled polystyrene (rPS) resin, CH fibers, and predefined amount of processing aid were primarily compounded using a Brabender® internal mixer to produce composite masterbatch feedstock. The composite masterbatch was further blended with measured amount of rPS resin, and the mixtures were extruded into composite filament containing different weight percentage (wt%) of CH fiber loading, ranging from 2.5 to 10 wt%. The 3D printability of the composite filament was assessed through observation on melt flow behavior and viscosity of the molten composite material subjected to typical FDM process conditions, where tensile dumbbell specimen was produced. Through repeated attempts carried out to FDM 3D-print the rPS/CH fiber filled composite filament, the result suggested that higher FDM extrusion percentage was required to produce quality part from composite filament with increase fiber content from 2.5 to 7.5 wt%. Composite filament with 10 wt% fiber loading failed to be printed due to premature thermal degradation and the slightly higher melt viscosity that tend to clog the printer nozzle.

RNA-binding protein Maca is crucial for gigantic male fertility factor gene expression, spermatogenesis, and male fertility, in Drosophila.

During spermatogenesis, the process in which sperm for fertilization are produced from germline cells, gene expression is spatiotemporally highly regulated. In Drosophila, successful expression of extremely large male fertility factor genes on Y-chromosome spanning some megabases due to their gigantic intron sizes is crucial for spermatogenesis. Expression of such extremely large genes must be challenging, but the molecular mechanism that allows it remains unknown. Here we report that a novel RNA-binding protein Maca, which contains two RNA-recognition motifs, is crucial for this process. maca null mutant male flies exhibited a failure in the spermatid individualization process during spermatogenesis, lacked mature sperm, and were completely sterile, while maca mutant female flies were fully fertile. Proteomics and transcriptome analyses revealed that both protein and mRNA abundance of the gigantic male fertility factor genes kl-2, kl-3, and kl-5 (kl genes) are significantly decreased, where the decreases of kl-2 are particularly dramatic, in maca mutant testes. Splicing of the kl-3 transcripts was also dysregulated in maca mutant testes. All these physiological and molecular phenotypes were rescued by a maca transgene in the maca mutant background. Furthermore, we found that in the control genetic background, Maca is exclusively expressed in spermatocytes in testes and enriched at Y-loop A/C in the nucleus, where the kl-5 primary transcripts are localized. Our data suggest that Maca increases transcription processivity, promotes successful splicing of gigantic introns, and/or protects transcripts from premature degradation, of the kl genes. Our study identified a novel RNA-binding protein Maca that is crucial for successful expression of the gigantic male fertility factor genes, spermatogenesis, and male fertility.

Real-time computational imaging of reverse osmosis membrane scaling under intermittent operation

Small-scale photovoltaic-powered reverse osmosis (PVRO) could be a game-changer for off-the-grid water-stressed communities. However, cost and maintainability issues, due to membrane fouling, remain potentially major limitations of intermittently run PVRO. In particular, there is a common perception that this intermittent operation causes premature membrane degradation but has not been fully evaluated to date. This study seeks to understand the impacts of intermittent operation on mineral scaling propagation in PVRO through real-time imaging and post-operation morphological analysis of the scales. Lab-mixed synthetic groundwater, supersaturated with CaSO4, was used as the feedwater to scale BW30 RO membranes. Then, scaling growth on a statistically significant portion of a spacer-filled RO crossflow channel was imaged in real-time. Comparison between continuous (24 h) and intermittent (8 h/d × 3 d) experiments did not indicate any negative effect of periodic shutdowns on flux decline, which is contrary to the perception that intermittent operation decrease membrane permeability. In-situ imaging further supported this observation and highlighted a slower growth of intensive scaling spots under intermittent operation. After intermittent shut-off periods, the scaling distribution on the membrane appeared thinner and more uniform, hinting a momentary osmotic backflow at the end of each intermittent cycle. Scanning electron microscopy also confirmed the reduced CaSO4 scale growth and a different morphological structure of the scales under intermittent RO operation. This macro-scale imaging and postprocessing approach can aid in the development of optimized backwash and rinsing cycles, reducing fouling-related irreversible damage to the membrane and increasing the accessibility of PVRO for remote communities.

Systematic Assessment of GATA2 Genetic Variation Reveals the Presence of Novel Disease-Causing Synonymous Exonic Mutations

Among its different clinical presentations, GATA2 deficiency had been recognized as the most frequent hereditary predisposition to pediatric myelodysplastic syndromes (MDS), accounting for 15% of MDS with excess of blasts (MDS-EB), with a particularly high prevalence among children with monosomy 7 (37%). A pattern of three major classes of germline mutations can be recognized in the roughly 350 reported cases with GATA2 deficiency: I) protein truncating (stop-gain, frameshift, splice-site), II) missense within or adjacent to zinc finger 2 (ZnF2), and, III) noncoding substitutions in the conserved EBOX-GATA-ETS regulatory region in intron 4, (NM_032638.4). The rare aberrations (class IV) include in frame indels and whole gene deletions. For the purpose of this study we introduced the above classification to systematically categorize various types of GATA2 variations and to assess the prevalence and pathogenic significance of silent (synonymous) substitutions, referred to as class V.Our study cohort consisted of 723 children and adolescents with primary MDS enrolled in prospective registry of the European Working Group of childhood MDS (EWOG-MDS). Typical GATA2 germline mutations were found in 69/723 cases. Additional 28 GATA2-deficient individuals with heterogeneous phenotypes diagnosed at our institutions were added to the analysis. We excluded patients with secondary MDS, in which GATA2 is not etiologically involved as previously reported by our group. Results were compared to those of 138632 individuals in the Genome Aggregation Database (GnomAD). Various in-silico prediction tools to evaluate deleteriousness were employed, and selected mutations were investigated in a GATA reporter system.First, we categorized the “typical” germline GATA2 mutations identified in 96 patients. Class I = truncating mutations were present in 51.5% (49/96), class II = missense in ZnF2 in 37.5% (36/96), class III = deep intron 4 in 8.3% (8/96) and class IV = other in 3.15% (3/96) of patients. Genotype-phenotype analysis failed to establish a significant correlation. We next systematically assessed the prevalence of other potentially pathogenic coding variants. Missense alterations p.Ala164Thr, p.Pro161Ala, and p.Pro250Ala (present in 34.8%, 1.6% and 0.9% GnomAD individuals) were neither significantly enriched, nor they displayed “synergistic” co-occurrence in pediatric MDS. This essentially depicts an unlikely role in MDS predisposition. We further performed transactivation activity in a GATA reporter system for p.Pro161Ala and observed no significant alteration.Finally, we focused on the evaluation of synonymous exonic substitutions resulting in nucleotide exchange without alteration of protein sequence. Recent cancer studies proposed that synonymous mutations might alter protein folding and stability, also such variants can introduce novel splice sites leading to premature RNA degradation. The synonymous substitutions that are common according to GnomAD: p.Pro5Pro (88.3% GnomAD), p.Thr188Thr (8.0%) and p.Ala411Ala (4.3%) showed similar frequencies in our patient cohort. Ultimately, we identified 6 patients with 5 novel or very rare synonymous exonic substitutions, referred to as “class V” variants (Fig. 1): p.Thr117Thr found in 2 unrelated pedigrees, p.Gly327Gly, p.Leu217Leu, p.Ala341Ala, and p.Pro472Pro (detected in 0, 0, 2, 6, and 70 out of >130 Tsd. GnomAD individuals, respectively). Median age at MDS diagnosis was 12 (4-15) years and 4/6 patients have acquired monosomy 7.In silico prediction assigned a high chance of splice defects to p.Thr117Thr, p.Leu217Leu, and p.Ala341Ala variants. Sequencing from blood of 2 unrelated patients with p.Thr117Thr confirmed complete loss of mutated allele in mRNA as compared to 50:50% distribution in DNA; while the degradation of p.Leu217Leu mutant mRNA was less prominent. Expectedly, GATA reporter assays performed for synonymous variants did not reveal altered transactivation. Further ongoing studies aim at detailed examination of altered splicing and characterization of protein stability.In sum, we establish that noncoding substitutions in GATA2, believed thus far to be silent, constitute a novel disease-causing mutational class. In contrast, rare SNPs (p.Pro161Ala and p.Pro250Ala) have a likely neutral effect towards MDS predisposition. DisclosuresLübbert:Ratiopharm: Other: Study drug valproic acid; Janssen-Cilag: Other: Travel Funding, Research Funding; Celgene: Other: Travel Funding.

Cohesive and adhesive degradation in PET-based photovoltaic backsheets subjected to ultraviolet accelerated weathering

Delamination between layers in photovoltaic (PV) backsheets is often reported in the literature, causing voids that can collect moisture, diminish module backside heat dissipation, and reduce the backsheet’s effectiveness as a physical barrier. While backsheets with weathering-resistant fluoropolymer outer layers have traditionally been used in modules, more recent backsheets using non-fluoropolymer outer layers, such as polyethylene terephthalate (PET), have been developed. These backsheets have shown signs of premature degradation, and their adhesion degradation, in particular, has not been widely studied. In the present work, the single cantilever beam (SCB) adhesion test was used to quantify the adhesion energy in two commercially available PET-based backsheets. To study the effect of minor changes in formulation, the backsheets were obtained from same manufacturer and product line but during different years. To study the effect of environmental variables on adhesion degradation, the backsheets were subjected to artificial weathering at controlled temperature, humidity, and ultraviolet (UV) radiation in an indoor weathering chamber, and the adhesion energy was quantified at several intervals of exposure time. Layering structure, composition, and adhesion failure mode were compared between the backsheets, using Raman and infrared spectroscopy and thermogravimetric analysis. The results show a large difference in initial (unexposed) adhesion energy between the backsheets, despite very similar structures and compositions. Following exposure, adhesion energy dropped significantly, primarily due to thermo-hydrolytic degradation of the polyurethane (PU)-based adhesive layers. Significant UV-induced adhesion degradation of the PET outer layer surface was also observed. The study represents an important step in understanding adhesion degradation in PET-based backsheets, suggesting ways in which adhesion integrity – and, correspondingly, module service life – can be improved.

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

AbstractNanocarriers (NCs) have emerged as powerful tools to improve drug solubility, to promote drug transport across membranes, to protect their payload from premature degradation, and to deliver drugs in a controlled and targeted manner. Their performance strongly depends on the surface chemistry, which governs their interaction with the biological environment. Bioinert and stealth surface features are advantageous to avoid unintended interactions with endogenous surfaces at off‐target sites and with the immune system, whereas at the target site these carriers should be highly interactive guaranteeing intracellular delivery of their payload. These key surface properties—bioinert and stealth versus interactive at the target site—are in contradiction to each other so that the best compromise between them has to be found. Alternatively, surface structures interacting preferentially with the membrane of target cells can be utilized. Stimuli‐responsive surfaces able to convert from bioinert and stealth to interactive at the target site have been recently introduced. A deepened understanding of how these different approaches influence the performance of NCs in the body is of particular importance in order to improve their efficacy. This review focuses on the surface chemistry of NCs providing the best compromise between bioinert and stealth versus interactive features.

Simulation of corrosion field measurement on reinforced concrete using BEM

Reinforced concrete (RC) corrosion is a leading of structural deterioration and premature degradation for the infrasturctures, with significant affected for safety, durability and reability. Therefore, early assessment of RC corrosion is important to prevent deterioration of the structure. The objective of this paper is to apply Boundary Element Method (BEM) for improving reinforced concrete (RC) corrosion assessment using field measurement data. In this study, the potential on whole domain of concrete structures was modeled by Laplace equation. The Laplace equation was solved by BEM, hence the potential on the concrete structure can be determined. The field data were measured by using half-cell potential technique and collected from an existing house in Aceh region that struck by the 2004 Sumatra tsunami. The simulation results show the use of BEM can improve the RC corrosion assessment. According to ASTM C876, the distribution of potential values on the concrete surface above the corroded area were in range -200 mV to -350 mV that indicated active corrosion was occurred. It can be inferred, the method can improve the field measurement data since it has capability to predict the corrosion profiles of reinforcing steel in more precise.

Process-Property Relationships for Melt-Spun Poly(lactic acid) Yarn.

Poly(lactic acid) (PLA) is an attractive biomaterial due to its biocompatibility, biodegradability, and fiber-forming ability. However, the polymer is highly susceptible to both hydrolytic and thermal degradation during processing. Melt processing conditions typically involve high temperature and shear, whereas to prevent premature degradation, PLA needs to be processed under the mildest conditions that still yield the desired yarn properties. Thus, there is a need to determine the optimum processing conditions to achieve the desired properties of extruded PLA yarn. This study focuses on the effect of melt-spinning process parameters on the mechanical and physicochemical properties of the resulting PLA yarn and to derive their process–property relationships. The study compares the effect of process parameters like melt temperature, throughput through the spinneret, take-up speed at the wind-up roller, draw ratio, and drawing temperature on the yarn properties such as the yarn size (linear mass density), tenacity, elongation at break, crystallinity, and molecular weight. Depending on the combination of process parameters, the resulting PLA yarn had a yarn size ranging from 6.2 to 101.6 tex, tenacity ranging from 2.5 to 34.1 gf/tex, elongation at break ranging from 4 to 480%, and degree of crystallinity ranging from 14.6 to 62.2%. Certain combinations of processing parameters resulted in higher process-induced degradation, as evident from the reduction in molecular weight, ranging from 7.6% reduction to 20.5% reduction. Findings from this study increase our understanding on how different process parameters can be utilized to achieve the desired properties of the as-spun and drawn PLA yarn while controlling process-induced premature degradation.

Nano-Enabled Pesticides in Agriculture: Budding Opportunities and Challenges

Nano enabled plant protectant is an advancement approach to deal with the difficulties of dosedependent toxicity, solubility, degradation, leaching and health issues of conventional pesticides. The main idea behind incorporation of nanoformulation is their controlled delivery and release to prevent premature degradation of active ingredient under the influence of changing environment conditions. Nanocarriers (nanocapsules, nanospheres, micelles, nanogels, nanoemulsions, nanodispersion and inorganic material) alters the properties of active ingredients and provide controlled release kinetics with, better dissolvability, low dose, enhanced stability and long lasting pest-control efficiency. This review critically assesses the incredible potential of various nanocarriers, their methods of preparation and biological effectiveness. It additionally features the potential and issues with nanoformulations of botanical insecticides and essential oils. The study also accounts performances of nano-enabled products, their challenges with respect to field application and assessment of new environmental risks.

A V-Mn Redox Flow Battery for Concomitant Energy Storage and Hydrogen Production

Redox flow battery (RFB) has drawn considerable attention past years for large-scale energy storage applications. However, RFB’s suffer from low energy density and premature degradation failures were reported due to uncontrolled electrolyte imbalance, limiting their commercialization. To address those concerns, we proposed in 2014 an innovative concept called ''dual-circuit redox flow battery’’[1]. This system is distinct from the conventional RFB in that the former includes a secondary energy platform, in which electrical energy can be converted into hydrogen via mediated water electrolysis. In fact, the positive and the negative charged redox species can be circulated in external catalytic bed reactors (out of the electrochemical cell), where they will respectively act as electron mediators (donor and acceptor) to carry out water oxidation and proton reduction over the catalysts. The dual-flow circuit RFB has the advantage to store energy beyond the capacity of the conventional RFB due to the higher volumetric capacity of the hydrogen energy carrier. Furthermore, mediated water electrolysis gives the opportunity to decouple oxygen evolution and hydrogen evolution reactions in time and in space, unlike conventional technologies (e.g alkaline and polymer electrolyte membrane electrolysers). This feature enables to avoid O2 and H2 recombination, addressing materials degradation and safety concerns. Additionally, the temporal/spatial separation of water splitting reactions allows us to design bed reactors using less active and cheaper electrocatalysts and facilitates the electrolytes rebalancing.In this work, a complete proof-of-concept of a novel dual-flow circuit based on a vanadium-manganese RFB has been demonstrated (Figure 1). First, we studied the influence of Ti(IV) or V(V) additives on Mn(III) stability in high acidic medium. V(V) was observed to enhance the stability of Mn(III) as compared to Ti(IV), which is of high interest for improving the performances and the cyclability of the system [2]. Then, the chemical discharges of Mn and V electrolytes over Mo2C and RuO2 electrocatalysts were demonstrated. Additionally, we elaborated a kinetic model as a predictive tool for the vanadium-mediated hydrogen evolution on Mo2C electrocatalyst [3]. Finally, the V-Mn redox flow battery was designed at lab-scale and was operated up to 50 cycles between 20 and 80% SOC at 50 mA/cm– 2. The catalytic bed reactors were designed using an innovative approach for fast and cheap catalyst preparation. Hydrogen production was carried out at 10 bars and the system achieved an overall efficiency of 70%.[1] V. Amstutz et al., « Renewable hydrogen generation from a dual-circuit redox flow battery », Energy Environ. Sci., vol. 7, no 7, p. 2350-2358, juin 2014, doi: 10.1039/C4EE00098F.[2] D. Reynard, S. Maye, P. Peljo, V. Chanda, H. H. Girault, et S. Gentil, « Vanadium–Manganese Redox Flow Battery: Study of MnIII Disproportionation in the Presence of Other Metallic Ions », Chemistry – A European Journal, vol. 26, no 32, p. 7250-7257, juin 2020, doi: 10.1002/chem.202000340.[3] D. Reynard, G. Bolik-Coulon, S. Maye, et H. H. Girault, « Hydrogen production on demand by redox-mediated electrocatalysis: A kinetic study », Chemical Engineering Journal, p. 126721, août 2020, doi: 10.1016/j.cej.2020.126721. Figure 1 Schematic of the dual-circuit V-Mn redox flow battery for concomitant energy storage and hydrogen production Figure 1

Coated recombinant Escherichia coli for delayed release of β-mannanase in the water-based fracturing fluid

A low-temperature active glycosyl hydrolase family 26(GH26) β-mannanase (Man37) was identified in Bacillus velezensis BS-37 by gene mining. The β-mannanase Man37 contained a signal peptide at the N-terminus. The Man37 and Man37△1−25 (without the signal peptide sequence) coding sequences were successfully expressed in Escherichia coli BL21(DE3) using the pET-28a(+) vector. The specific activity of the purified Man37 and Man37△1−25 with guar gum as substrate was 98.12 and 150.34 U/mg, respectively. Man37△1−25 was superior to Man37 due to its higher specific activity and soluble expression. The temperature and pH range of Man37△1−25 was 20−55 °C and pH5.0–10.0, respectively. The enzyme could effectively reduce the viscosity of fracturing fluid from 6200 to 1000 mPa·s after 10 min at 25 °C, which demonstrates its application potential as a gel-breaker in low-temperature hydrocarbon reservoirs. Uncoated recombinant Man37△1−25 cells could completely reduce the viscosity of water-based fracturing fluid within only 3 h, while was greatly prolonged to 18 h with coating polyethylenimine-glutaraldehyde (PEI-GA). Thus, this study provides an effective solution for premature degradation caused by the addition of water-based fracturing fluid together with a short-acting gel-breaker.

Self‐Amplification Immunomodulatory Strategy for Tissue Regeneration in Diabetes Based on Cytokine‐ZIFs System

AbstractDysfunctional macrophages and excessive inflammatory responses lead to severe tissue regeneration disorders in diabetes. Herein, a function‐oriented self‐amplification immunomodulatory (SAI) strategy based on an interleukin‐33 (IL‐33) loaded zeolitic imidazolate frameworks (IL@ZIF) nano‐platform is proposed to treat tissue regeneration disorders by restoring macrophage function and reconstructing immune microenvironment in diabetes. It is found that ZIFs effectively protect IL‐33 from premature degradation. In the wound area, the released Zn2+ not only improves the antioxidant capacity of macrophages to avoid reactive oxygen species‐induced dysfunction, but also upregulates IL‐33 receptor (ST2L) expression and triggers M2 macrophages polarization. Subsequently, the released IL‐33 significantly amplifies M2 macrophage polarization through IL‐33/ST2L signaling, resulting in a reversal of the pro‐inflammatory microenvironment of diabetic wounds. This synergistic effect endows the nano‐platform with an excellent ability to accelerate tissue regeneration in vitro and in vivo. Overall, this IL@ZIF mediated function‐oriented SAI strategy provides new alternatives for the treatment of tissue regeneration disorders in diabetes.

Degradation of Drug Delivery Nanocarriers and Payload Release: A Review of Physical Methods for Tracing Nanocarrier Biological Fate.

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.

Partial Rescue of F508del-CFTR Stability and Trafficking Defects by Double Corrector Treatment.

Deletion of phenylalanine at position 508 (F508del) in the CFTR chloride channel is the most frequent mutation in cystic fibrosis (CF) patients. F508del impairs the stability and folding of the CFTR protein, thus resulting in mistrafficking and premature degradation. F508del-CFTR defects can be overcome with small molecules termed correctors. We investigated the efficacy and properties of VX-445, a newly developed corrector, which is one of the three active principles present in a drug (Trikafta®/Kaftrio®) recently approved for the treatment of CF patients with F508del mutation. We found that VX-445, particularly in combination with type I (VX-809, VX-661) and type II (corr-4a) correctors, elicits a large rescue of F508del-CFTR function. In particular, in primary bronchial epithelial cells of CF patients, the maximal rescue obtained with corrector combinations including VX-445 was close to 60–70% of CFTR function in non-CF cells. Despite this high efficacy, analysis of ubiquitylation, resistance to thermoaggregation, protein half-life, and subcellular localization revealed that corrector combinations did not fully normalize F508del-CFTR behavior. Our study indicates that it is still possible to further improve mutant CFTR rescue with the development of corrector combinations having maximal effects on mutant CFTR structural and functional properties.