Search

Abstract The world is experiencing an increase in the frequency and intensity of extreme weather events, yet the influences of remote inland extreme weather events on the coastal ecosystem thousands of kilometers away remain poorly understood. Here we tracked the chain ecological effects of an extreme rainfall event in North China from terrestrial rivers to coastal aquaculture area of the eastern Shandong Peninsula. Our data suggest the autumn flood resulted from extreme rainfall event leads to abnormally low turbidity in the North Shandong Coastal Currents and coastal red tide blooms by introducing anomalous freshwater with an exceptionally high nitrogen-to-phosphorus ratio into the Bohai Sea. Lower salinity, stronger light conditions caused by limpid coastal currents, and phosphorus limitation resulting from red tide blooms account for huge kelp loss offshore of the eastern Shandong Peninsula. This study underscores the importance of considering multidisciplinary observation for risk management of unexpected extreme weather events.

Multifunctional wound dressings, enriched with biologically active agents for preventing or treating infections and promoting wound healing, along with cell delivery capability, are highly needed. To address this issue, composite scaffolds with potential in wound dressing applications were fabricated in this study. The poly-lactic acid/nanodiamonds (PLA/ND) scaffolds were first printed using melt electrowriting (MEW) and then coated with quaternized β-chitin (QβC). The NDs were well-dispersed in the printed filaments and worked as fillers and bioactive additions to PLA material. Additionally, they improved coating effectiveness due to the interaction between their negative charges (from NDs) and positive charges (from QβC). NDs not only increased the thermal stability of PLA but also benefitted cellular behavior and inhibited the growth of bacteria. Scaffolds coated with QβC increased the effect of bacteria growth inhibition and facilitated the proliferation of human dermal fibroblasts. Additionally, we have observed rapid extracellular matrix (ECM) remodeling on QβC-coated PLA/NDs scaffolds. The scaffolds provided support for cell adhesion and could serve as a valuable tool for delivering cells to chronic wound sites. The proposed PLA/ND scaffold coated with QβC holds great potential for achieving fast healing in various types of wounds.

Abstract Optical frequency combs provide a powerful tool for precise measurement of the optical frequency, holding significant importance in fields such as spectroscopy, optical communication and optical clock. The frequency stability of the comb line determines the precision of the frequency measurement, but the delicate interplay between high precision, low power consumption and integration still needs to be optimized. To this aim, here we demonstrate a frequency measurement scheme based on a fully stabilized electro-optic comb, in which the pump laser frequency and repetition rate are independently locked to the atomic transition and microwave signal. The measurement precision of the demonstrated wavemeter can reach sub-kHz-level, and the parallel measurement of multiple wavelengths can be performed. Therefore, by combining the technical scheme reported here with advanced integrated functional devices, our system is expected to provide a feasible solution for chip-scale frequency precision measurement and reference.

Online travel agency (OTA) platforms frequently engage in unfair behaviors that infringe on the legitimate rights and interests of consumers and airlines in the ticket sale market. Effective governance of the OTA platforms' misconduct has become an urgent topic. In order to address the governance dilemma of OTA platforms' misconduct, a tripartite evolutionary game model considering the collaborative supervision between airlines and consumers is constructed. This study analyzes the evolutionary path and stable strategy of the three participants, airlines, platforms and consumers by numerical simulation. The results show that some actions, such as airlines' strict control of ticket sales resources and high fines on the platform, reducing the cost of customers' rights protection, and effectively guiding online public opinion, can benefit airlines and consumers and enhance their willingness to cooperate in supervision. Legitimate consumer rights protection not only brings negative public opinion and image loss to airlines, but also to platforms, which can force airlines to impose stricter constraints on platforms and force platforms to strengthen self-restraint. Therefore, a market mechanism instead of government regulatory that can effectively suppress platforms misconduct should be established to promote platforms self-regulation through a collaborative effort between airlines and consumers. Some special measures that guide the interests of three participators are also provided.

The effects of plant protein sources (PPSs) on the health of the liver and intestine of the largemouth bass, Micropterus salmoides, were compared to verify the potential damaging effects of dietary fiber (DF). A diet containing 55% fish meal (FM) was used as the control. The test diets contained 25% soybean meal (SBM), rapeseed meal (RSM), cottonseed meal, or peanut meal, and the FM content was decreased to 30%. The protein and lipid contents of these five diets were balanced by casein and oil. Fish were raised for 8 weeks. The fish fed the diet containing PPS showed a trend of decreasing growth and apparent digestibility coefficients. The contents of total bile acid, lipid, and collagen in the liver were increased, and the mRNA expression levels of genes encoding inflammatory factors and enzymes involved in de novo fatty acid synthesis and bile acid synthesis were upregulated. Both the lipid and collagen contents in the liver were positively correlated with the DF content in the diet significantly. Morphology and histology showed reduced liver size, hepatic steatosis, and fibrosis in fish fed diets containing PPS. The lowest hepatosomatic index was observed in fish fed the SBM diet, and the most severe damage was observed in fish fed the RSM diet. No obvious histological abnormalities were observed in the hindgut. The bile acid profile in the liver could be used to distinguish the types of PPS very well by Fisher discriminant analysis. These results indicated that 25% of each of the four PPSs in the diet exceeded the tolerance range of largemouth bass and caused liver damage, which might be mediated by bile acid. DF in PPS might be an important agent contributing to liver damage.

BackgroundWe previously found that the respiratory epithelial cells could eliminate the invaded group A streptococcus (GAS) through autophagy induced by binding a fibronectin (Fn) binding protein (FnBp) expressed on the surface of GAS to plasma protein Fn and its receptor integrin α5β1 of epithelial cells. Is autophagy initiated by FnBp+ bacteria via FnBp-Fn-Integrin α5β1 axis a common event in respiratory epithelial cells?MethodsWe chose Staphylococcus aureus (S. aureus/S. a) and Listeria monocytogenes (L. monocytogenes/L. m) as representatives of extracellular and intracellular FnBp+ bacteria, respectively. The FnBp of them was purified and the protein function was confirmed by western blot, viable bacteria count, confocal and pull-down. The key molecule downstream of the action axis was detected by IP, mass spectrometry and bio-informatics analysis.ResultsWe found that different FnBp from both S. aureus and L. monocytogenes could initiate autophagy through FnBp-Fn-integrin α5β1 axis and this could be considered a universal event, by which host tries to remove invading bacteria from epithelial cells. Importantly, we firstly reported that S100A8, as a key molecule downstream of integrin β1 chain, is highly expressed upon activation of integrin α5β1, which in turn up-regulates autophagy.ConclusionsVarious FnBp from FnBp+ bacteria have the ability to initiate autophagy via FnBp-Fn-Integrin α5β1 axis to promote the removal of invading bacteria from epithelial cells in the presence of fewer invaders. S100A8 is a key molecule downstream of Integrin α5β1 in this autophagy pathway.

Heavy ion beam (HIB) is an effective physical mutagen that has been widely used in plant mutational breeding. Systemic knowledge of the effects caused by different HIB doses at developmental and genomic levels will facilitate efficient breeding for crops. Here we examined the effects of HIB systematically. Kitaake rice seeds were irradiated by ten doses of carbon ion beams (CIB, 25 – 300 Gy), which is the most widely used HIB. We initially examined the growth, development and photosynthetic parameters of the M1 population and found that doses exceeding 125 Gy caused significant physiological damages to rice. Subsequently, we analyzed the genomic variations in 179 M2 individuals from six treatments (25 – 150 Gy) via whole-genome sequencing (WGS). The mutation rate peaks at 100 Gy (2.66×10-7/bp). Importantly, we found that mutations shared among different panicles of the same M1 individual are at low ratios, validating the hypothesis that different panicles may be derived from different progenitor cells. Furthermore, we isolated 129 mutants with distinct phenotypic variations, including changes in agronomic traits, from 11,720 M2 plants, accounting for a 1.1% mutation rate. Among them, about 50% possess stable inheritance in M3. WGS data of 11 stable M4 mutants, including three lines with higher yields, reveal their genomic mutational profiles and candidate genes. Our results demonstrate that HIB is an effective tool that facilitates breeding, that the optimal dose range for rice is 67 – 90% median lethal dose (LD50), and that the mutants isolated here can be further used for functional genomic research, genetic analysis, and breeding.

AbstractBackground and Aim This study aims to validate the efficacy of the conventional non-invasive score in predicting significant fibrosis in metabolic-associated fatty liver disease (MAFLD) and to develop a non-invasive prediction model for MAFLD.Methods This cross-sectional study was conducted among 7701 participants with MAFLD from August 2018 to December 2023. All participants were divided into a training cohort and a validation cohort. The study compared different subgroups’ demographic, anthropometric, and laboratory examination indicators and conducted logistic regression analysis to assess the correlation between independent variables and liver fibrosis. Nomograms were created using the logistic regression model. The predictive values of noninvasive models and nomograms were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).Results Four nomograms were developed for the quantitative analysis of significant liver fibrosis risk based on the multivariate logistic regression analysis results. The nomogram’s area under ROC curves (AUC) was 0.710, 0.714, 0.748, and 0.715 in overall MAFLD, OW-MAFLD, Lean-MAFLD, and T2DM-MAFLD, respectively. The nomogram had a higher AUC in all MAFLD participants and OW-MAFLD than the other non-invasive scores. The DCA curve showed that the net benefit of each nomogram was higher than that of APRI and FIB-4. In the validation cohort, the AUCs of the nomograms were 0.722, 0.750, 0.719, and 0.705, respectively.Conclusion APRI, FIB-4, and NFS performed poorly predicting significant fibrosis in patients with MAFLD. The new model demonstrated improved diagnostic accuracy and clinical applicability in identifying significant fibrosis in MAFLD.

Abstract Acute coronary syndrome (ACS) is a serious cardiovascular disease. The ACS risk prediction model is of great significance during the hospitalisation of ACS patients. However, traditional machine learning methods are not effective in predicting risk events in the ACS treatment process because of sample imbalance and noise. In this letter, the multilayer perceptron (MLP) and ensemble method are combined and then ensemble‐MLPs are proposed, which has made two innovations: 1) increase the diversity of the base MLP classifier at the data level, structure level, and parameter level and 2) improve the ensemble performance by proposing a new ensemble method using f1‐score weighted average. Experiments have shown that the proposed method outperforms conventional ensemble MLP method and other traditional machine learning methods on the task of predicting risk events in the ACS treatment process.

Abstract Background Flower longevity is closely related to pollen dispersal and reproductive success in all plants, as well as the commercial value of ornamental plants. Mutants that display variation in flower longevity are useful tools for understanding the mechanisms underlying this trait. Heavy-ion beam irradiation has great potential to improve flower shapes and colors; however, few studies are available on the mutation of flower senescence in leguminous plants. Results A mutant (C416) exhibiting blossom duration eight times longer than that of the wild type (WT) was isolated in Lotus japonicus derived from carbon ion beam irradiation. Genetic assays supported that the delayed flower senescence of C416 was a dominant trait controlled by a single gene, which was located between 4,616,611 Mb and 5,331,876 Mb on chromosome III. By using a sorting strategy of multi-sample parallel genome sequencing, candidate genes were narrowed to the gene CUFF.40834, which exhibited high identity to ethylene receptor 1 in other model plants. A physiological assay demonstrated that C416 was insensitive to ethylene precursor. Furthermore, the dynamic changes of phytohormone regulatory network in petals at different developmental stages was compared by using RNA-seq. In brief, the ethylene, jasmonic acid (JA), and salicylic acid (SA) signaling pathways were negatively regulated in C416, whereas the brassinosteroid (BR) and cytokinin signaling pathways were positively regulated, and auxin exhibited dual effects on flower senescence in Lotus japonicus. The abscisic acid (ABA) signaling pathway is positively regulated in C416. Conclusion So far, C416 might be the first reported mutant carrying a mutation in an endogenous ethylene-related gene in Lotus japonicus, rather than through the introduction of exogenous genes by transgenic techniques. A schematic of the flower senescence of Lotus japonicus from the perspective of the phytohormone regulatory network was provided based on transcriptome profiling of petals at different developmental stages. This study is informative for elucidating the molecular mechanism of delayed flower senescence in C416, and lays a foundation for candidate flower senescence gene identification in Lotus japonicus. It also provides another perspective for the improvement of flower longevity in legume plants by heavy-ion beam.

In this study, the ultralow specific surface area clay vermiculite (VMT) was selected to be a catalyst support for the NH3-SCR process, and the active components MnCeFeOx loaded on vermiculite was just like curling on ice from the TEM results. The de-NOx performance of Mn–Ce–Fe/VMT exhibited almost complete NO conversion with a gas hourly space velocity (GHSV) of 15,300 h−1 at 150 °C, which was 25% and 10% higher than that of Mn/VMT and Mn–Ce/VMT, respectively. Ce and Fe co-doping improved the BET surface area, the quantities of active Mn4+, the acid sites and NH3 adsorption energy of Mn/VMT, all of which contributed to the increase in low-temperature SCR activity. In situ DRIFT measurements suggested that NOx removal over Mn–Ce–Fe/VMT followed both Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) mechanisms at 150 °C, but the E-R mechanism played a dominant role. Corresponding Mn–Ce–Fe/VMT monolithic catalysts reached 90% NO conversion with a GHSV of 4000 h-1.

BackgroundInfants with respiratory syncytial virus (RSV)-associated bronchiolitis are at increased risk of childhood asthma. Recent studies demonstrated that certain infections induce innate immune memory (also termed trained immunity), especially in macrophages, to respond more strongly to future stimuli with broad specificity, involving in human inflammatory diseases. Metabolic reprogramming increases the capacity of the innate immune cells to respond to a secondary stimulation, is a crucial step for the induction of trained immunity. We hypothesize that specific metabolic reprogramming of lung trained macrophages induced by neonatal respiratory infection is crucial for childhood allergic asthma.ObjectiveTo address the role of metabolic reprogramming in lung trained macrophages induced by respiratory virus infection in allergic asthma.MethodsNeonatal mice were infected and sensitized by the natural rodent pathogen Pneumonia virus of mice (PVM), a mouse equivalent strain of human RSV, combined with ovalbumin (OVA). Lung CD11b+ macrophages in the memory phase were re-stimulated to investigate trained immunity and metabonomics. Adoptive transfer, metabolic inhibitor and restore experiments were used to explore the role of specific metabolic reprogramming in childhood allergic asthma.ResultsPVM infection combined with OVA sensitization in neonatal mice resulted in non-Th2 (Th1/Th17) type allergic asthma following OVA challenge in childhood of mice. Lung CD11b+ macrophages in the memory phage increased, and showed enhanced inflammatory responses following re-stimulation, suggesting trained macrophages. Adoptive transfer of the trained macrophages mediated the allergic asthma in childhood. The trained macrophages showed metabolic reprogramming after re-stimulation. Notably, proline biosynthesis remarkably increased. Inhibition of proline biosynthesis suppressed the development of the trained macrophages as well as the Th1/Th17 type allergic asthma, while supplement of proline recovered the trained macrophages as well as the allergic asthma.ConclusionProline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood. Proline metabolism could be a well target for prevention of allergic asthma in childhood.

MADS-box is a class of transcriptional regulators that are ubiquitous in plants and plays important roles in the process of plant growth and development. Identification and analysis of blueberry MADS-box genes can lay a foundation for their function investigations. In the present study, 249 putative MADS-box genes were identified in the blueberry genome. Those MADS-box genes were distributed on 47 out of 48 chromosomes. The phylogenetic and evolutionary analyses showed that blueberry MADS-box genes were divided into 131 type I members and 118 type II members. The type I genes contained an average of 1.89 exons and the type II genes contained an average of 7.83 exons. Motif analysis identified 15 conserved motifs, of which 4 were related to the MADS domain and 3 were related to the K-box domain. A variety of cis-acting elements were found in the promoter region of the blueberry MADS-box gene, indicating that the MADS-box gene responded to various hormones and environmental alterations. A total of 243 collinear gene pairs were identified, most of which had a Ka/Ks value of less than 1. Nine genes belonging to SEP, AP3/PI, and AGL6 subfamilies were screened based on transcriptomic data. The expression patterns of those nine genes were also verified using quantitative PCR, suggesting that VcMADS6, VcMADS35, VcMADS44, VcMADS58, VcMADS125, VcMADS188, and VcMADS212 had potential functions in blueberry fruit ripening. The results of this study provide references for an in-depth understanding of the biological function of the blueberry MADS-box genes and the mechanism of blueberry fruit ripening.

In this work, we report the green production of few-layer bio-Graphene (bG) through liquid exfoliation of graphite in the presence of bovine serum albumin. Microscopic characterization evaluated the quality of the produced nanomaterial, showing the presence of 3–4-layer graphene. Moreover, spectroscopic techniques also confirmed the quality of the resulted bG, as well as the presence of bovine serum albumin on the graphene sheets. Next, for the first time, bG was used as support for the simultaneous covalent co-immobilization of three enzymes, namely β-glucosidase, glucose oxidase, and horseradish peroxidase. The three enzymes were efficiently co-immobilized on bG, demonstrating high immobilization yields and activity recoveries (up to 98.5 and 90%, respectively). Co-immobilization on bG led to an increase of apparent KM values and a decrease of apparent Vmax values, while the stability of the nanobiocatalysts prevailed compared to the free forms of the enzymes. Co-immobilized enzymes exhibited high reusability, preserving a significant part of their activity (up to 72%) after four successive catalytic cycles at 30 °C. Finally, the tri-enzymatic nanobiocatalytic system was applied in three-step cascade reactions, involving, as the first step, the hydrolysis of p-Nitrophenyl-β-D-Glucopyranoside and cellobiose.

To overcome various factors that limit crop production and to meet the growing demand for food by the increasing world population. Seed priming technology has been proposed, and it is considered to be a promising strategy for agricultural sciences and food technology. This technology helps to curtail the germination time, increase the seed vigor, improve the seedling establishment, and enhance the stress tolerance, all of which are conducive to improving the crop yield. Meanwhile, it can be used to reduce seed infection for better physiological or phytosanitary quality. Compared to conventional methods, such as the use of water or chemical-based agents, X-rays, gamma rays, electron beams, proton beams, and heavy ion beams have emerged as promising physics strategies for seed priming as they are time-saving, more effective, environmentally friendly, and there is a greater certainty for yield improvement. Ionizing radiation (IR) has certain biological advantages over other seed priming methods since it generates charged ions while penetrating through the target organisms, and it has enough energy to cause biological effects. However, before the wide utilization of ionizing priming methods in agriculture, extensive research is needed to explore their effects on seed priming and to focus on the underlying mechanism of them. Overall, this review aims to highlight the current understanding of ionizing priming methods and their applicability for promoting agroecological resilience and meeting the challenges of food crises nowadays.

Lycium barbarum polysaccharide (LBP) as one of the main bioactive constituents of the fruit of Lycium barbarum L. (LBL.) has many pharmacological activities, but its antihyperglycemic activity is not fully understood yet. This study investigated the hypoglycemic and renal protective effects of LBP on high-fat diet/streptozotocin- (HFD/STZ-) induced diabetic nephropathy (DN) in mice. Blood glucose was assessed before and after 8-week administration of LBP, and the homeostasis model assessment-insulin resistance (HOMA-IR) index was calculated for evaluating the antidiabetic effect of LBP. Additionally, serum creatinine (sCr), blood urea nitrogen (BUN), and urine microalbumin were tested to evaluate the renal function. HE and PAS stainings were performed to evaluate the morphology and injury of the kidney. The results showed that LBP significantly reduces the glucose level and ameliorates the insulin resistance of diabetic mice. Importantly, LBP improves renal function by lowering the levels of sCr, BUN, and microalbumin in diabetic mice and relieves the injury in the renal glomeruli and tubules of the DN mice. Furthermore, LBP attenuates renal inflammation as evidenced by downregulating the mRNA levels of TNFα, IL1 β, IL6, and SAA3 in the renal cortex, as well as reducing the elevated circulating level and protein depositions of SAA3 in the kidney. In addition, our western blot results showed that NF-κB p65 nuclear translocation and the degradation of inhibitory κB-α (IκBα) occurred during the progress of inflammation, and such activated signaling was restrained by LBP. In conclusion, our findings suggest that LBP is a potential antidiabetic agent, which ameliorates the inflammation in DN through inhibiting NF-κB activation.

Respiratory syncytial virus (RSV) is a major respiratory pathogen in infants. The early formalin-inactivated RSV not only failed to protect infants against infection, but also was associated with enhanced pulmonary inflammatory disease upon natural infection. A safe and effective vaccine should prevent the inflammatory disease and provide protection. Immune memory is the cornerstone of vaccines. In this study, we evaluated three types of immune memory T cells, antibodies, and lung inflammation of a vaccine candidate G1F/M2, which includes a neutralizing epitope fragment of RSV G protein and a cytotoxic T lymphocyte epitope of M2 protein, with toll-like receptor 9 agonist CpG2006 as an adjuvant by intranasal (i.n.) and intraperitoneal (i.p.) immunization protocols. The results indicated that immunization of mice with G1F/M2 + CpG i.p. induced significantly higher level of CD4+ or CD8+ central memory (TCM), Th1-type effector memory (TEM), and balanced ratio of IgG1/IgG2a, but lower level of lung tissue-resident memory (TRM), compared with immunization with G1F/M2 + CpG i.n., G1F/M2 i.n., or G1F/M2 i.p. Following RSV challenge, the mice immunized with G1F/M2 + CpG i.p. showed higher level of Th1-type responses, remarkably suppressed inflammatory cytokines and histopathology in lungs, compared with mice immunized with G1F/M2 + CpG i.n., G1F/M2 i.n., or G1F/M2 i.p. These results suggested that high level of TCM and Th1 type of TEM in spleens may contribute to inhibition of lung inflammation, while high level of TRM in lungs and lack of or weak Th1-type immune memory in spleens may promote lung inflammation following RSV challenge.

Abstract Background The efficient utilization of lignocellulosic biomass for biofuel production has received increasing attention. Previous studies have investigated the pretreatment process of biomass, but the detailed enzymatic hydrolysis process of pretreated biomass remains largely unclear. Thus, this study investigated the pretreatment efficiency of dilute alkali, acid, hydrogen peroxide and its ultimate effects on enzymatic hydrolysis. Furthermore, to better understand the enzymatic digestion process of alkali-pretreated sweet sorghum straw (SSS), multimodal microscopy techniques were used to visualize the enzymatic hydrolysis process. Result After pretreatment with alkali, an enzymatic hydrolysis efficiency of 86.44% was obtained, which increased by 99.54% compared to the untreated straw (43.23%). The FTIR, XRD and SEM characterization revealed a sequence of microstructural changes occurring in plant cell walls after pretreatment, including the destruction of lignin–polysaccharide interactions, the increase of porosity and crystallinity, and reduction of recalcitrance. During the course of hydrolysis, the cellulase dissolved the cell walls in the same manner and the digestion firstly occurred from the middle of cell walls and then toward the cell wall corners. The CLSM coupled with fluorescent labeling demonstrated that the sclerenchyma cells and vascular bundles in natural SSS were highly lignified, which caused the nonproductive bindings of cellulase on lignin. However, the efficient delignification significantly increased the accessibility and digestibility of cellulase to biomass, thereby improving the saccharification efficiency. Conclusion This work will be helpful in investigating the biomass pretreatment and its structural characterization. In addition, the visualization results of the enzymatic hydrolysis process of pretreated lignocellulose could be used for guidance to explore the lignocellulosic biomass processing and large-scale biofuel production.

Clostridium acetobutylicum (C. acetobutylicum) has considerable potential for use in bioenergy development. Owing to the repeated use of traditional mutagenesis methods, the strains have developed a certain tolerance. The rheology of the bioprocess and the downstream processing of the product heavily depend on the ability of C. acetobutylicum mutants to produce butanol. Carbon ion beam irradiation has advantages over traditional mutation methods for fermentative production because of its dose conformity and superb biological effectiveness. However, its effects on the specific productivity of the strains have not been clearly understood. In this study, we screened five mutants through carbon ion beam irradiation; mutant Y217 achieved a butanol-production level of 13.67 g/L, exceeding that of wild-type strain ATCC 824 (i.e., 9.77 g/L). In addition, we found that the mutant maintained normal cell membrane integrity under the stimulation of 15 g/L butanol, whereas the intracellular macromolecules of wild-type strain ATCC 824 leaked significantly. Subsequently, we used the response surface methodology (RSM) to determine if the mutant cell membrane integrity improved the butanol tolerance. We verified that with the addition of butanol, the mutant could be fermented to produce 8.35 g/L butanol, and the final butanol concentration in the fermentation broth could reach 16.15 g/L. In this study, we proved that under butanol stress, mutant Y217 features excellent butanol production and tolerance and cell membrane integrity and permeability; no prior studies have attempted to do so. This will serve as an interesting and important illustration of the complexity of genetic control of the irradiation mutation of C. acetobutylicum strains. It may also prove to be useful in the bioengineering of strains of the mutant for use in the predevelopment stage.

Genetic variations are an important source of germplasm diversity, as it provides an allele resource that contributes to the development of new traits for plant breeding. Gamma rays have been widely used as a physical agent for mutation creation in plants, and their mutagenic effect has attracted extensive attention. However, few studies are available on the comprehensive mutation profile at both the large-scale phenotype mutation screening and whole-genome mutation scanning. In this study, biological effects on M1 generation, large-scale phenotype screening in M2 generation, as well as whole-genome re-sequencing of seven M3 phenotype-visible lines were carried out to comprehensively evaluate the mutagenic effects of gamma rays on Arabidopsis thaliana. A total of 417 plants with visible mutated phenotypes were isolated from 20,502 M2 plants, and the phenotypic mutation frequency of gamma rays was 2.03% in Arabidopsis thaliana. On average, there were 21.57 single-base substitutions (SBSs) and 11.57 small insertions and deletions (InDels) in each line. Single-base InDels accounts for 66.7% of the small InDels. The genomic mutation frequency was 2.78 × 10−10/bp/Gy. The ratio of transition/transversion was 1.60, and 64.28% of the C > T events exhibited the pyrimidine dinucleotide sequence; 69.14% of the small InDels were located in the sequence with 1 to 4 bp terminal microhomology that was used for DNA end rejoining, while SBSs were less dependent on terminal microhomology. Nine genes, on average, were predicted to suffer from functional alteration in each re-sequenced line. This indicated that a suitable mutation gene density was an advantage of gamma rays when trying to improve elite materials for one certain or a few traits. These results will aid the full understanding of the mutagenic effects and mechanisms of gamma rays and provide a basis for suitable mutagen selection and parameter design, which can further facilitate the development of more controlled mutagenesis methods for plant mutation breeding.

Stretchable electronics are of great significance for the development of the next-generation smart interactive systems. Here, we propose an intrinsically stretchable organic tribotronic transistor (SOTT) without a top gate electrode, which is composed of a stretchable substrate, silver nanowire electrodes, semiconductor blends, and a nonpolar elastomer dielectric. The drain-source current of the SOTT can be modulated by external contact electrification with the dielectric layer. Under 0-50% stretching both parallel and perpendicular to the channel directions, the SOTT retains great output performance. After being stretched to 50% for thousands of cycles, the SOTT can survive with excellent stability. Moreover, the SOTT can be conformably attached to the human hand, which can be used for tactile signal perception in human-machine interaction and for controlling smart home devices and robots. This work has realized a stretchable tribotronic transistor as the tactile sensor for smart interaction, which has extended the application of tribotronics in the human-machine interface, wearable electronics, and robotics.

Induced pluripotent stem cells (iPSCs) can be used to generate different types of somatic cells in vitro, including neuronal cells. Here, a human iPSC line was generated from the peripheral blood mononuclear cells of a healthy 39-year-old individual. The resulting iPSCs were integration-free, maintained the normal karyotype, expressed pluripotency stem cell markers, and were demonstrated to be capable of differentiating into cells representative of the three embryonic germ layers. Furthermore, we showed that this iPSC line could be differentiated into neural stem cells. Taken together, this generated iPSC line could be useful to test multiple differentiation protocols, and also serve as a control for investigating drug development and disease mechanisms.

Physical mutagens, such as carbon-ion beams (CIBs) and gamma rays (GRs), induce mutations with high frequency at a relatively low dose and are more user-friendly and environment-friendly in mutation breeding. Previous studies showed that CIBs induced large sized deletions and insertions, and chromosomal rearrangements, whereas GRs induce shorter deletions and insertions, and more frequent base substitutions. However, the difference on the genomic level between CIB- and GR-induced mutations remains to be clarified. In the present study, we re-sequence six mutagenized lines derived from CIB irradiation and four mutagenized lines derived from GRs. A total of 283 and 381 variations are induced in these mutants by CIBs and GRs, respectively, including single base substitutions (SBSs), small insertion and deletions (InDels), multiple nucleotide variants (MNVs). SBSs are the most abundant type of mutation and single base transition is the main form for SBSs. CIB-induced InDels accounted for 25.44% of the total variations, while GR-induced InDels accounted for 17.85%. On the contrary, the frequency of MNVs induced by GRs was approximately 2.19 times that induced by CIBs, which indicates CIBs induced increased InDels, whereas GRs induced increased MNVs. Notably, multiple base deletions (≥5 bp) were induced at a much higher frequency by CIBs than by GRs. We also find mutations induced by CIBs and GRs are unevenly distributed on chromosomes. Unusual high-frequency (HF) and low-frequency (LF) mutation regions are discovered by analyzing mutations per 1Mb along the genome. The mutation frequency within the HF regions were significantly higher than the LF regions (P < 0.05). A large majority of SBSs, InDels, and MNVs induced by CIBs and GRs occurred in upstream and downstream regions. Our study compares difference of mutation profiles induced by the CIB irradiation and GR on rice genomes, and give some clues for understanding the mutagenesis mechanism of physical radiation and improving the mutagenesis efficiency.

Previous research on the binding of SA (SA) and calcium ions mainly concentrated on the high concentration solutions and formation of gels. While it was hard to provide details of the behaviors of SA polymer during the binding process. In order to study individual polymer, all the experiments were carried out on diluted solutions in this research. The morphological change of SA self-assembly under the effects of calcium ions was observed using atomic force microscopy, and the change of molecular dimension with the addition of calcium ions was characterized through viscosity data. The SA showed a tendency to form network on the initial addition of calcium ions and the chains broke into rods or particles along with continuous addition of calcium ions. Roughness of images, diameter of the network holes, and the width of chains or rods were measured to support the shape features that combined with the data of viscosity, we proposed a modified three-step hypothesis to interpret the SA binding behaviors in “egg-box” model.

Heavy-ion irradiation is a powerful mutagen and is widely used for mutation breeding. In this study, using whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) techniques, we comprehensively characterized these dynamic changes caused by mutations at three time points (48, 96, and 144 h after irradiation) and the expression profiles of rice seeds irradiated with C ions at two doses. Subsequent WGS analysis revealed that more mutations were detected in response to 40 Gy carbon ion beam (CIB) irradiation than 80 Gy of CIB irradiation at the initial stage (48 h post-irradiation). In the mutants generated from both irradiation doses, single-base substitutions (SBSs) were the most frequent type of mutation induced by CIB irradiation. Among the mutations, the predominant ones were C:T and A:G transitions. CIB irradiation also induced many short InDel mutations. RNA-seq analysis at the three time points showed that the number of differentially expressed genes (DEGs) was highest at 48 h post-irradiation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DEGs showed that the “replication and repair” pathway was enriched specifically 48 h post-irradiation. These results indicate that the DNA damage response (DDR) and the mechanism of DNA repair tend to quickly start within the initial stage (48 h) after irradiation.

Objectives: The aim of this study was to explore the pathogenic mechanism of group A Streptococcus (GAS) and to investigate how GAS evades phagocytosis by immune cells. Methods: The classical inflammatory signaling pathway of macrophages infected with GAS was investigated by protein microarray, real-time PCR, Western blot, immunoprecipitation, and flow cytometry. Results: GAS induced a lower level of inflammatory mediators in macrophages than either the Gram-positive Staphylococcus aureus or the Gram-negative Escherichia coli. Therefore, the conventional inflammatory signal pathway was investigated. It was found that GAS and S. aureus induced both toll-like receptor (TLR)2 and TLR4 expression, while Gram-negative E. coli only activated TLR4 in RAW264.7 cells. Although MyD88, the main adaptor protein, was activated by the three pathogens, there was no difference in MyD88 expression in macrophages. Nuclear factor kappa B (NF-κB) is the classical transcription factor of inflammatory signals, and the results of the present study showed that GAS, similar to E. coli, induced a weaker p65 nuclear translocation compared to S. aureus. Interestingly, GAS activated NF-κB by inducing p65–p52 heterodimer, but not the classical heterodimer of NF-κB (p65–p50), while E. coli activated NF-κB by inducing both p65–p50 and p65–p52 heterodimers. Conclusions: Compared to S. aureus and E. coli infection, GAS induced a weaker nuclear translocation and distinct combination of NF-κB subunits in macrophages, which probably leads to a weak inflammatory response.

Ionizing radiation (IR) can result in serious genomic instability and genotoxicity by causing DNA damage. Carbon ion (CI) beams and X-rays are typical IRs and possess high-linear energy transfer (LET) and low-LET, respectively. In this article, a comet assay that was optimized by decreasing the electrophoresis time (8 minutes) and voltage (0.5 V/cm) was performed to elucidate and quantify the DNA damage induced by CI or X-rays radiation. Two quantitative methods for the comet assay, namely, comet score and olive tail moment, were compared, and the appropriate means and parameter values were selected for the present assay. The dose–effect relationship for CI or X-rays radiation and the DNA repair process were studied in yeast cells. These results showed that the quadratic function fitted the dose–effect relationship after CI or X-rays exposure, and the trend for the models fitted the dose–effect curves for various repair times was precisely described by the cubic function. A kinetics model was also creatively used to describe the process of DNA repair, and equations were calculated within repairable ranges that could be used to roughly evaluate the process and time necessary for DNA repair.

ABSTRACT Screening promising L. thermophiles with high productivity, high efficiency and strong adaptability are very important in lactic acid industry. For this purpose, 80MeV/u carbon ions were applied to irradiate L. thermophiles. After high-throughput screening, a mutant, named SRZ50, was obtained. Different carbon sources or nitrogen sources were provided to investigate carbon or nitrogen source utilization between mutant SRZ50 and wild type, and different fermentation periods were also chose to study fermentation characteristic between mutant SRZ50 and wild type. The results showed that mutant SRZ50 exhibited the enhanced L-(+)-lactic acid production from wild type. When glucose or fructose was the sole carbon source, the L(+)-lactic acid production by mutant SRZ50 was both the highest, respectively, 23.16 ± 0.72 g/L or 23.24 ± 0.66 g/L, which had a significant increase from that of wild type (P

Group A streptococcus (GAS), a common pathogen, is able to escape host immune attack and thus survive for longer periods of time. One of the mechanisms used by GAS is the upregulated expression of immunosuppressive molecules, which leads to a reduction in the production of inflammatory cytokines in immune cells. In the present study, we found that macrophages produced lower levels of proinflammatory cytokines (IL-1β, TNF-α, IL-6) when challenged with GAS than they did when challenged with Escherichia coli (E. coli). Simultaneously, in a mouse model of lung infection, GAS appeared to induce a weaker inflammatory response compared to E. coli. Our data also indicated that the expression of the A20 transcriptional regulator was higher in GAS-infected macrophages than that in macrophages infected with E. coli, and that high expression of A20 correlated with a reduction in the production of TRAF6. SiRNA targeting of A20 led to the increased production of TRAF6, IL-1β, TNF-α, and IL-6, suggesting that A20 inhibits synthesis of these key proinflammatory cytokines. We also investigated the pathway underlying A20 production and found that the synthesis of A20 depends on My88, and to a lower extent on TNFR1. Finally, we showed a significant reduction in the expression of A20 in macrophages stimulated by M protein-mutant GAS, however, a speB-GAS mutant, which is unable to degrade M protein, induced a greater level of A20 production than wild type GAS. Collectively, our data suggested that M protein of GAS was responsible for inducing A20 expression in macrophages, which in turn down-regulates the inflammatory cytokine response in order to facilitate GAS in evading immune surveillance and thus prolong survival in the host.

Whether telomere structure integrity is related to radiosensitivity is not well investigated thus far. In this study, we investigated the relation between telomere instability and radiation-induced accelerated senescence. Partial knockdown of DNA-dependent catalytic subunit of protein kinase (DNA-PKcs) in human breast cancer cell line MCF-7 was established by small interfering RNA. Radiosensitivity of control and DNA-PKcs knockdown MCF-7 cells was analyzed by clonogenetic assay. Cell growth was measured by real-time cell electronic sensing. Senescence and apoptosis were evaluated by β-galactosidase histochemical staining and fluorescence-activated cell sorting, respectively. DNA damage was determined by long polymerase chain reaction (PCR). Telomere length and integrity were analyzed by real-time PCR and cytogenetic assay, respectively. DNA-PKcs knockdown MCF-7 cells were more sensitive to X-irradiation than control cells. Further investigation revealed that accelerated senescence is more pronounced than apoptosis in cells after radiation, particularly in DNA-PKcs knockdown cells. The cytogenetic assay and kinetics of DNA damage repair revealed that the role of telomere end-capping in DNA-PKcs, rather than DNA damage repair, was more relevant to radiosensitivity. To our knowledge, this is the first study to show that DNA-PKcs plays an important role in radiation-induced accelerated senescence via maintenance of telomere integrity in MCF-7 cells. These results could be useful for future understanding of the radiation-induced genome instability and its consequences.

Heavy-ion beam irradiation is one of the principal methods used to create mutants in plants. Research on mutagenic effects and molecular mechanisms of radiation is an important subject that is multi-disciplinary. Here, we re-sequenced 11 mutagenesis progeny (M3) Arabidopsis thaliana lines derived from carbon-ion beam (CIB) irradiation, and subsequently focused on substitutions and small insertion-deletion (INDELs). We found that CIB induced more substitutions (320) than INDELs (124). Meanwhile, the single base INDELs were more prevalent than those in large size (≥2 bp). In details, the detected substitutions showed an obvious bias of C > T transitions, by activating the formation of covalent linkages between neighboring pyrimidine residues in the DNA sequence. An A and T bias was observed among the single base INDELs, in which most of these were induced by replication slippage at either the homopolymer or polynucleotide repeat regions. The mutation rate of 200-Gy CIB irradiation was estimated as 3.37 × 10−7 per site. Different from previous researches which mainly focused on the phenotype, chromosome aberration, genetic polymorphism, or sequencing analysis of specific genes only, our study revealed genome-wide molecular profile and rate of mutations induced by CIB irradiation. We hope our data could provide valuable clues for explaining the potential mechanism of plant mutation breeding by CIB irradiation.

The lentil (Lens culinaris Medik.) belongs to the most important leguminous plants in Asia. It is a very popular and highly nutritious food. However, small pod size and low yield limit its agricultural use. Through irradiation mutagenesis of dry lentil seeds by 12C6+ ion beam, we found some lines with excellent agricultural traits in M2 progeny at doses of 90 Gy (grey), such as height increase and improvement of the number of branches and three-seed pods as well as seeds with increased grain yield. Six generations of irradiated lentils were screened for these traits. In the M8 generation, the grain yield of three high-yielding lentil lines (lines hyl-1, hyl-2, and hyl-3) reached 212.4%, 195.3% and 190.8%, respectively, of the non-irradiated controls. The results indicated that crop improvement was stable inherited across the generations. Statistical analysis revealed that the increase in grain yield was due to increased total pod number and seeds per pod. Fortunately, adverse effects of irradiation (e.g. reduced germination rates and poor pollen vitality) disappeared over the eight generations. In conclusion, we present a practical method for the improvement of lentils through radiation breeding, leading to high yielding cultivars, which could support the use of this crop in agriculture.

The filamentous ascomycete Aspergillus niger is well known for its ability to accumulate citric acid for the hydrolysis of starchy materials. To improve citric acid productivity, heavy ion beam mutagenesis was utilized to produce mutant A.niger strains with enhanced production of citric acid in this work. It was demonstrated that a mutant HW2 with high concentration of citric acid was isolated after carbon ion irradiation with the energy of 80Mev/μ, which was obvious increase higher than the original strain from liquefied corn starch as a feedstock. More importantly, with the evidence from the expression profiles of key genes and enzyme activity involved in the starch hydrolysis process between original strain and various phenotype mutants, our results confirmed that different transcript levels of key genes involving in starch hydrolysis process between original strain and mutants could be a significant contributor to different citric acid concentration in A.niger, such as, amyR and glaA, which therefore opened a new avenue for constructing genetically engineered A.niger mutants for high-yield citric acid accumulation in the future. As such, this work demonstrated that heavy ion beam mutagenesis presented an efficient alternative strategy to be developed to generate various phenotype microbe species mutants for functional genes research.

A large proportion of mutants with altered pigment features have been obtained via exposure to heavy-ion beams, a technique that is efficient for trait improvement in the breeding of plants and algae. However, little is known about the underlying mechanisms by which the photosynthetic pigments are altered by heavy-ion irradiation. In our study, the photosynthetic characteristics of progenies from carbon-ion irradiated Selenastrum capricornutum were investigated. Five progenies deficient in chlorophyll a were isolated after carbon-ion exposure. Photosynthetic characteristics, photoprotection capacity and gene expression of the light-harvesting complex in these progenies were further characterized by the measurement of chlorophyll fluorescence parameters (Fv/Fm, ФPSII, NPQ, ETR), the de-epoxidation state of the xanthophyll cycle, the amount of lutein and quantitative real-time PCR. High maximum quantum yield of photosystem II at day 10 and high thermal dissipation ability were observed in progenies #23 and #37 under normal culture condition. Progenies #18, #19 and #20 showed stronger resistance against high levels of light steps than the control group (612-1077 μmol photons m -2 s -1, p< 0.05). The progenies #20 and #23 exhibited strong photoprotection by thermal dissipation and quenching of 3Chl* after 24 h of high light treatment. The mRNA levels of Lhcb5, Lhcbm5 and Lhcbm1 of the light-harvesting complex revealed markedly differential expression in the five progenies irradiated by carbon-ion beams. This work indicates that photosynthetic efficiency, photoprotection ability and the expression of light-harvesting antennae in unicellular green algae can be markedly influenced by irradiation. To our knowledge, this is the first report on changes in the photosynthetic pigments of green algae after treatment with carbon-ion beams.

The unicellular green microalga Desmodesmus sp. S1 can produce more than 50% total lipid of cell dry weight under high light and nitrogen-limitation conditions. After irradiation by heavy (12)C(6+) ion beam of 10, 30, 60, 90 or 120 Gy, followed by screening of resulting mutants on 24-well microplates, more than 500 mutants were obtained. One of those, named D90G-19, exhibited lipid productivity of 0.298 g L(-1)⋅d(-1), 20.6% higher than wild type, likely owing to an improved maximum quantum efficiency (Fv/Fm) of photosynthesis under stress. This work demonstrated that heavy-ion irradiation combined with high-throughput screening is an effective means for trait improvement. The resulting mutant D90G-19 may be used for enhanced lipid production.

Background: We previously found that the respiratory epithelial cells could eliminate the invaded group A streptococcus (GAS) through autophagy induced by binding a fibronectin (Fn) binding protein (FnBp) expressed on the surface of GAS to plasma protein Fn and its receptor integrin α5β1 of epithelial cells. Is autophagy initiated by FnBp+ bacteria via FnBp-Fn-Integrin α5β1 axis a common event in respiratory epithelial cells? Methods: We chose Staphylococcus aureus (S. aureus/S. a) and Listeria monocytogenes (L. monocytogenes/L. m) as representatives of extracellular and intracellular FnBp+ bacteria, respectively. The FnBp of them was purified and the protein function was confirmed by western blot, viable bacteria count, confocal and pull-down. The key molecule downstream of the action axis was detected by IP, mass spectrometry and bio-informatics analysis. Results: We found that different FnBp from both S. aureus and L. monocytogenes could initiate autophagy through FnBp-Fn-integrin α5β1 axis and this could be considered a universal event, by which host tries to remove invading bacteria from epithelial cells. Importantly, we firstly reported that S100A8, as a key molecule downstream of integrin β1 chain, is highly expressed upon activation of integrin α5β1, which in turn up-regulates autophagy. Conclusions: Various FnBp from FnBp+ bacteria have the ability to initiate autophagy via FnBp-Fn-Integrin α5β1 axis to promote the removal of invading bacteria from epithelial cells in the presence of fewer invaders. S100A8 is a key molecule downstream of Integrin α5β1 in this autophagy pathway. [ABSTRACT FROM AUTHOR]

Aqueous-phase chemistry of glyoxal (GL) with reduced nitrogen compounds (RNCs) plays a significant source of secondary brown carbon (SBrC), which is one of the largest uncertainties in climate predictions. However, few studies have revealed that SBrC formation is affected by multifunctional RNCs, which has a non-negligible atmospheric abundance. Hence, we performed theoretical and experimental approaches to investigate the reaction mechanisms and kinetics of the mixtures for ammonium sulfate (AS), multifunctional amine (monoethanolamine, MEA) and GL. Our experiments indicate that the light-absorption and the growth rate are enhanced in MEA-GL mixture relative to AS-GL and MEA-AS-GL mixtures, and MEA reactions of the chromophores by more efficiently than the analogous AS reactions. Quantum chemical calculations show that the formation and propagation of oligomers proceed via four-step nucleophilic addition reactions in three reaction systems. The presence of MEA provides the extra two branched chains to affect the natural charges and steric hindrance of intermediates, facilitated the formation of chromophores. Molecule dynamics simulations reveal that the interfacial and interior attraction on the aqueous aerosols with MEA is more pronounced for small α-dicarbonyls, to facilitate the further engagement in the aqueous-phase reactions. Our results show a possible missing source for SBrC formation on urban, regional and global scales. [ABSTRACT FROM AUTHOR]