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Ensuring military and police personnel protection is vital for urban security. However, the impact response mechanism of the UHMWPE laminate used in ballistic helmets and vests remains unclear, making it hard to effectively protect the head, chest, and abdomen. This study utilized 3D-DIC technology to analyze UHMWPE laminate's response to 9 mm lead-core pistol bullets traveling at 334.93 m/s. Damage mode and response characteristics were revealed, and an effective numerical calculation method was established that could reveal the energy conversion process. The bullet penetrated by 1.03 mm, causing noticeable fiber traction, resulting in cross-shaped failure due to fiber compression and aggregation. Bulge transitioned from circular to square, initially increasing rapidly, then slowing. Maximum in-plane shear strain occurred at ±45°, with values of 0.0904 and −0.0928. Model accuracy was confirmed by comparing strain distributions. The investigation focused on bullet-laminate interaction and energy conversion. Bullet's kinetic energy is converted into laminate's kinetic and internal energy, with the majority of erosion energy occurring in the first four equivalent sublaminates and the primary energy change in the system occurring at 75 μs in the fourth equivalent sublayer. The results show the damage mode and energy conversion of the laminate, providing theoretical support for understanding the impact response mechanism and improving the efficiency of protective energy absorption. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effect of IL‐10 on the phenotype polarization of macrophages and osteogenesis in diabetes mellitus type 2 (T2DM) rat jaw defects. Methods: Lipopolysaccharide (LPS) and interleukin‐10 (IL‐10) were chosen to induce the polarization of macrophages. In vitro assessment included wound‐healing assay, western blotting, and alizarin red staining after co‐culture of the bone marrow‐derived mesenchymal stem cells (BMSCs) and induced macrophages. For in vivo study, IL‐10 was loaded on GelMA‐Heparin and applied to bone defects of the alveolar ridge in diabetic rats, while Bio‐Oss Collagen, simple GelMA‐Heparin, and blank control groups were set for contrast experiment. The mandibles of rats were processed for micro‐computed tomography, histology, and immunohistochemistry 1 week and 4 weeks after the operation. Results: IL‐10 induced expression of arginase 1, TGF‐β1, EGR2, and Mannose Receptor (CD206), whereas LPS induced expression of iNOS, TNF‐α, IL‐6, CD80. The BMSCs co‐cultured with macrophages induced by IL‐10 showed increased migration, osteogenic differentiation, and mineralization in vitro. Notably, the IL‐10‐laden GelMA‐Heparin group showed quicker new bone formation and a higher M2/M1 ratio of macrophages in the jawbone defect area compared with the control groups. Conclusions: IL‐10 can stably induce macrophages to M2 type, thereby influencing BMSCs and improving the osteogenesis of jaw bone defects. [ABSTRACT FROM AUTHOR]

In greenhouse vegetable production, reductive soil disinfestation (RSD) effectively mitigates soil-borne diseases, yet its impact on the dynamics of soil organic carbon (SOC) has not been adequately examined. This study investigated the distribution of soil aggregates and the organic carbon retention mechanism following intensive RSD treatment. Greenhouse experiments, including control (CK), wheat straw (RSD), and wheat straw with chemical fertilizer (RSD + NP) treatments, indicated augmentation in the formation of macro-aggregates (>2 mm and 0.25–2 mm) under RSD, particularly in the RSD + NP treatment. Silty clay particles transform into macro- and micro-aggregates. Fourier infrared spectroscopy highlighted the augmentation of carbon-containing functional groups in SOC, with aliphatic carbon accumulating in macro-aggregates and aromatic carbon in silt clay. Laboratory culture experiments employing different C/N ratios (RSD1 with wheat straw, RSD2 with kiwifruit branches) underscored the beneficial impact of low C/N ratio organic matter on coarse and fine macro-aggregate content, mean weight diameter, geometric mean diameter, and reduced silt clay. Low C/N ratios enhance SOC retention in large aggregates, while high ratios stabilise micro-aggregate carbon. This research underscores the severe degradation in continuous greenhouse cropping systems and emphasises RSD's dual benefits—disease prevention and improved SOC retention. Implementing RSD requires careful consideration of organic material choices, specifically their C/N ratios, as a pivotal factor influencing SOC dynamics. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA) is an vital neurotransmitter, and the reaction to obtain GABA through biocatalysis requires coenzymes, which are therefore limited in the production of GABA. In this study, polyacrylamide hydrogels doped with chitosan and waste toner were synthesized for glutamate decarboxylase (GAD) and coenzyme co-immobilization to realize the production of GABA and the recovery of coenzymes. Enzymatic properties of immobilized GAD were discussed. The immobilized enzymes have significantly improved pH and temperature tolerance compared to free enzymes. In terms of reusability, after 10 repeated reuses of the immobilized GAD, the residual enzyme activity of immobilized GAD still retains 100% of the initial enzyme activity, and the immobilized coenzyme can also be kept at about 32%, with better stability and reusability. And under the control of no exogenous pH, immobilized GAD showed good performance in producing GABA. Therefore, in many ways, the new composite hydrogel provides another way for the utilization of waste toner and promises the possibility of industrial production of GABA. [ABSTRACT FROM AUTHOR]

As a new environmentally friendly and sustainable green solvent, deep eutectic solvent (DES) was considered to be the most suitable alternative solvent for ionic liquids, with wide application. In this study, we reported a novel method of the synthesis of Fe3O4 nanoparticles (Nano-Fe3O4) in the natural deep eutectic solvent (NADES) of betaine/urea. Compared with traditional synthetic methods, this method of synthesising magnetic nanoparticles with the NADES as solvent possesses the superiority of mild reaction conditions, no need for nitrogen protection and short time-consuming. The yield of Nano-Fe3O4 synthesised in the NADES was as high as 94.9%. The synthesised Nano-Fe3O4 were coated with silicon and used to immobilise β-glucosidase extracted from Agrocybe aegerit. The results showed that the immobilisation efficiency of the β-glucosidase was 87.5% and the immobilisation yield was 86.2%. The optimum reaction conditions of the immobilised β-glucosidase were 55 °C and pH 6.0. In addition, the thermostability, pH stability and storage stability of the β-glucosidase were greatly improved after its immobilisation on the Nano-Fe3O4. After reused for 10 cycles, the residual activity of the immobilised β-glucosidase was still more than 72.4%. From multiple perspectives, the synthesised Nano-Fe3O4 in the NADES seems to be an excellent carrier for enzyme immobilisation. [ABSTRACT FROM AUTHOR]

Featured Application: In this study, an improved ZS thinning algorithm combined with a de-noising algorithm is proposed for track line detection; this algorithm can realize the detection function under complex road conditions, different weather and other scene conditions, and has higher feasibility and effectiveness. In the field of intelligent driving of freight trains, determining the track line ahead of the train is an important function in the autopilot technology of such trains. Combining the characteristics of freight railway tracks, we conduct an in-depth analysis of the shortcomings of object detection technology in extracting track lines and propose an improved Zhang–Suen (ZS) thinning theory for a railway track line recognition algorithm. Through image preprocessing and single pixel thinning steps, a continuous track line is obtained and then processed by a denoising algorithm to obtain a complete track line. Experimental results show that the track extracted by our method has good continuity and less noise. It can simultaneously perform track detection on straight roads, curves and turnouts, and is suitable for changing weather conditions such as sunny daytime, mild rainy daytime, cloudy daytime, night with lamp lighting and night without lamp lighting conditions. [ABSTRACT FROM AUTHOR]

Enzyme immobilization provides ideal operating conditions for enzymes stabilization and sustainable recycling. In this work, as a kind of clay material, montmorillonite (MTL) was chosen for immobilizing the β-glucosidase extracted from Agrocybe aegirit. The immobilized β-glucosidase via partly cross-linking enzyme aggregates (pCLEAs) formed by self-catalysis provided biocatalysts with satisfactory thermal and pH stability. Compared to the glutaraldehyde cross-linked, the immobilized β-glucosidase (β-G-pCLEAs@MTL) exhibited significantly higher immobilization efficiency (IE) and immobilization yield (IY), which were 80.6% and 76.9%, respectively. The β-G-pCLEAs@MTL also showed better stability and preferable reusability. And the activity of the β-G-pCLEAs@MTL remained 85.0% after 5 cycles and 74.7% after 10 cycles. Therefore, the method based on the pre- crosslinking to form pCLEAs and after-immobilization can effectively improve IY and IE. In addition, MTL seems to be a good alternative carrier to immobilize other enzymes for industrial application. [ABSTRACT FROM AUTHOR]

Substitution of lead (Pb) with environmentally friendly germanium (Ge) is a very important and promising method to reduce the toxicity and improve the efficiency and stability of perovskite films for practical applications in light-emitting diodes (LEDs) and solar cells. However, a previous study shows that the efficiency of LEDs based on the germanium–lead (Ge–Pb) perovskites will decrease as the Ge content exceeds 30%, due to trap-assisted recombination. Here we demonstrate highly luminescent sky-blue Ge0.3Pb0.7-based perovskite films with photoluminescence quantum efficiencies (PLQEs) of up to 48%, showing a relative improvement of 17% over similarly prepared Ge-free, Pb-based ones. The PL stability of the Ge0.3Pb0.7-based perovskite films is also relatively improved compared to that of the Pb-based ones. The reasons of the PL efficiency and stability improvement are discussed in this study. The symmetry-adapted shear strain variations related to the suppression of the Jahn–Teller distortion after Ge substituting could play an important role in increasing the stability of the Ge-inclusion perovskites. [ABSTRACT FROM AUTHOR]

• Back bulge bottom shape changes from circle to diamond, and then to square shape. • The front face shows square-shaped bullet holes and a cross-shaped failure. • Strain distribution shows an L-shape and the max value is around 0.18. • 80.64% of bullet's kinetic energy converts to laminate's kinetic & internal energy. Soldier protection is crucial in contemporary localized conflicts, However, the impact response mechanism of UHMWPE laminate as the insert plate of ballistic helmet and bulletproof vest is still unclear. This study utilized 3D-DIC technology to analyze the impact response of UHMWPE laminates subjected to a 9 mm lead-core pistol bullet at a velocity of 334.93 m/s. The damage mode and response characteristics of the back surface were revealed; an effective numerical calculation method was established and could reveal the energy conversion process. The bullet penetrated the front face with 1.01 mm, resulting in a cross-shaped failure feature due to fiber bundle compression and aggregation. The numerical model confirmed its accuracy by comparing the height, width, and inplane strain distribution within the inplane of the bulge with experimental results. It further investigated the interaction between the bullet and the laminate, and energy transformation. The bullet's kinetic energy decreased by 80.64 %, in which the laminate absorbs 30.84 % of the bullet's energy as internal energy and 35.06 % as kinetic energy, meanwhile the bullet's internal energy increases by 11.77 %. The results show the damage mode and energy transformation of laminate, which provides theoretical support for revealing the impact response mechanism and improving the protective energy absorption efficiency. [ABSTRACT FROM AUTHOR]

Harmful algal blooms (HABs) have occurred frequently in coastal waters of China, imposing negative effects on the marine ecological environment. A dataset of HABs and terrestrial runoff was collected and analyzed in this study, and factors responsible for HABs were further explored. Frequency and expansion of HABs peaked between 2001 and 2007, and although they have declined slightly since then, they have remained quite high. Frequency and accumulative area of HABs peaked in 2004–2005, and most occurred from April to August during these years. HABs occurred frequently in the Changjiang (Yangtze River) estuary, and Prorocentrum donghaiense, Noctiluca scientillans, Karenia mikimotoi, and Skeletonema costatum were the main algal species. The increases of eutrophication, the abnormal sea surface temperature caused by climate and ocean currents, and the species invasion caused by the discharge of ballast water may be important factors for the long-term outbreak of HABs in the Chinese coastal waters. These findings provide a better understanding of HABs in China, which will be helpful to further prevention and control. [ABSTRACT FROM AUTHOR]

Ultrahigh molecular weight polyethylene (UHMWPE) fiber orthogonally laid laminate is widely used in ballistic protection due to its excellent properties. Research on its response under bullet impact is meaningful for understanding the antiballistic mechanism and designing personal protection. In this article, three‐dimensional digital image correlation measurement and analysis method is applied to study the response of UHMWPE orthogonally laid laminates under the impact of pistol bullets. A corresponding smoothed particle hydrodynamics (SPH)–finite element method coupled numerical model is established to study the impact phenomenon. The bullet model is developed using the SPH method. The laminate is developed with multiple equivalent sublaminate finite element models. The experimental results show the damage mode and back‐face features of the laminate. First, the damage mode has two stages: the first stage includes a small number of layers that are penetrated on the impact surface and the second stage includes the expansion of the back‐face deformation. Second, the average maximum bulge height in three repeated experiments is 14.59 mm. Third, the average maximum velocity of the bulge apex position in experiments on the z‐axis is 92.32 m/s. Fourth, the maximum and minimum back‐face in‐plane shear values are 0.0893 and −0.0928, respectively. Finally, the numerical results have good agreement with the experimental results and show that the compression waves mainly propagate along the x and y directions. The experimental results can provide quantifiable features for studying the impact responses of UHMWPE laminates. The numerical model could be applied to study features that cannot be measured by experiments. [ABSTRACT FROM AUTHOR]

Background. Male reproductive damage, as a common complication of diabetes mellitus (DM), is getting more attention lately. We aimed to explore the protective effects and mechanism of cornuside (Cor) modulating gut microbiota to alleviate diabetes mellitus- (DM-) induced testicular damage. Methods. KK-Ay mice with reproductive damage were randomly divided into the model and Cor treatment groups, and the C57BL/6J mice were used as the normal group. These mice were orally administered Cor for 8 weeks. Results. Cor administration ameliorated the diabetes-related symptoms of polydipsia and polyphagia and lowered the fasting blood glucose (FBG) level. The results of pathological injury showed that Cor improved testicular lesions (the rupture of seminiferous tubules, degeneration of germ cells, and structural shrinkage and separation from each other) in DM model mice. Cor significantly increased the testis/body weight ratio, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in KK-Ay mice. Cor also protected from reproductive damage by inhibiting apoptosis in the testes of KK-Ay mice. Moreover, Cor significantly increased the sperm count and sperm motility. Additionally, 16S rDNA sequencing analysis showed that Cor could notably reverse the changes in the distribution of gut microbiota and decrease the abundance of Weissella confusa (Weissella), Clostridium sp. ND2 (Clostridium sensu stricto 1), uncultured bacterium (Roseburia), Anaerotruncus colihominis DSM 17241 (Anaerotruncus), [Clostridium] leptum (Anaerotruncus), unidentified (Ruminococcus 1), and uncultured bacterium (Bilophila), which may be a potential biomarker for diagnosing the testicular injury caused by DM. Meanwhile, the heat map of phylum level suggested that the testicular injury caused by DM is closely related to gut microbiota. Conclusions. Cor could alleviate DM-induced testicular damage, probably by modulating the gut microbiota. [ABSTRACT FROM AUTHOR]

The electron transfer between Pd and Au as well as oxygen vacancies in MnO x species can synergistically promote and speed up the formation and adsorption of HCOO*, leading to the outstanding formic acid oxidation performance. [Display omitted] • MnO x is beneficial to speed up FAO conversion during reaction. • PdAu-MnO x /C possesses FAO performance with high specific and mass activity. • Best adsorption of HCOO* happened on Pd-Au bridge by introducing Au. • By the DFT, oxygen vacancies make HCOO* formation from HCOOH easier. Developing high efficient Palladium-metal-based electrocatalysts is of great significance for formic acid oxidation (FAO) reaction. Here, we experimentally synthesize PdAu alloy composited with MnOx electrocatalyst (PdAu-MnOx/C) and illustrate its remarkable FAO performance. By virtue of theory studies, we find that Pd-Au bridges have superior adsorption ability towards HCOO* and oxygen vacancies in MnOx make HCOO* formation from HCOOH easier, synergistically lead to the outstanding FAO performance with specific activity and mass activity of 19.0 mA cm−2 and 4539 mA mg−1 Pd+Au respectively, which are 2.6 times and 3.5 times higher than commercial Pd/C. This work shed some light toward development of high-performance Pd-based electrocatalysts for FAO. [ABSTRACT FROM AUTHOR]

Objective: As a newly developed technique, focused microwave breast hyperthermia (FMBH) can provide accurate and cost-effective treatment of breast tumors with low side effect. A clinically feasible FMBH system requires a guidance technique to monitor the microwave power distribution in the breast. Compressive thermoacoustic tomography (CTT) is a suitable guidance approach for FMBH, which is more cost-effective than MRI. However, no experimental validation based on a realized FMBH-CTT system has been reported, which greatly hinders the further advancement of this novel approach. Methods: We developed a preclinical system prototype for the FMBH-CTT technique, containing a microwave phased antenna array, a microwave source, an ultrasound transducer array and associated data acquisition module. Results: Experimental results employing homogeneous and inhomogeneous breast-mimicking phantoms demonstrate that the CTT technique can offer reliable guidance for the entire process of the FMBH. In addition, small phase noises do not deteriorate the overall performance of the system prototype. Conclusion: The realized preclinical FMBH-CTT system prototype is capable for noninvasive, accurate and low-side-effect breast tumor treatment with effective guidance. Significance: The experimentally validated FMBH-CTT system prototype provides a feasible paradigm for CTT guided FMBH, establishes a practical platform for future improvement of this technique, and paves the way for potential clinical translation. [ABSTRACT FROM AUTHOR]

Radix Rehmanniae and Cornus Officinalis (RR-CO) have been widely used as "nourishing Yin and tonifying kidney" herb pairs for the treatment of diabetes mellitus (DM) and its complications in traditional Chinese medicine (TCM). Based on the theory of "kidney governing reproduction" in TCM, the aim of this study was to investigate the therapeutic effects of RR-CO on DM-induced reproduction damage through regulating testicular glycolysis. Moreover, the regulation of AGEs/RAGE/HIF-1α axis on the testicular glycolysis process has also been studied. Spontaneous DM model KK-Ay mice were used to investigate the protective effect of RR, CO, RR-CO on DM-induced reproductive disturbances. RR, CO, RR-CO improved DM-induced renal and testicular morphology damages. Moreover, the impaired spermatogenesis, germ cell apoptosis and motility in testis induced upon DM were also attenuated by RR, CO or RR-CO, accompanied by an increased level of glycolysis metabolomics such as l-lactate, d-Fructose 1,6-bisphosphate, etc. Meanwhile, glucose membrane transporters (GLUT1, GLUT3), monocarboxylate transporter 4 (MCT4) expression, lactate dehydrogenase (LDH) activity, HIF-1α were upregulated by RR, CO and RR-CO treatment compared with the model group, whereas AGE level and RAGE expression were decreased with the drug administration. The RR-CO group was associated with superior protective effects in comparison to RR, CO use only. Aminoguanidine (Ami) and FPS-ZM1, the AGEs and RAGE inhibitors, were used as a tool drug to study the mechanism, showing different degrees of protection against DM-induced reproductive damage. This work preliminarily sheds light on the herb pair RR-CO exhibited favorable effects against DM-induced reproductive disturbances through enhancing testicular glycolysis, which might be mediated by AGEs/RAGE/HIF-1α axis. [ABSTRACT FROM AUTHOR]

The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non‐typical development (Non‐TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one‐carbon metabolites, on gene pathways and neurodevelopment. Genome‐wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies‐Learning Early Signs. Sixteen different one‐carbon metabolites, including folic acid, betaine, 5′‐methyltretrahydrofolate (5‐MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non‐TD and ASD, and to one‐carbon metabolites. Using differential gene expression analysis, six transcripts (TGR‐AS1, SQSTM1, HLA‐C, and RFESD) were associated with child outcomes (ASD, Non‐TD, and TD) with genome‐wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co‐expressed gene modules significantly correlated with 5‐MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5‐MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co‐expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one‐carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. Lay Summary Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non‐typical neurodevelopment and were associated with maternal nutrients. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) damages male reproduction at multiple levels, such as endocrine secretion, spermatogenesis and penile erection. We herein investigated the protective effects and mechanism of loganin targeting the advanced glycation end products (AGEs)/receptor for AGEs (RAGE)/p38 mitogen‐activated protein kinase (p38MAPK)/NF‐κB signalling pathway. Loganin relieved the general DM symptoms and decreased the blood glucose level of KK‐Ay DM mice. Haematoxylin‐eosin staining demonstrated that loganin ameliorated testicular histology and function and enhanced the activities of testis‐specific markers lactate dehydrogenase (LDH), acid phosphatase (ACP) and gamma‐glutamyl transferase (γ‐GT). Loganin also showed evident anti‐oxidative stress, anti‐apoptotic and anti‐inflammatory effects on DM‐induced reproductive damage by restoring glutathione (GSH) level and superoxide dismutase (SOD) activity, as well as reducing reactive oxygen species (ROS) level and Bax/Bcl‐2 ratio in vivo and in vitro. Western blotting exhibited that loganin significantly inhibited the AGEs/RAGE/p38MAPK/NF‐κB signalling pathway. Acridine orange and ethidium bromide staining (AOEB) and Western blotting showed that loganin in combination with inhibitors of RAGE, p38MAPK and NF‐κB exerted stronger anti‐apoptotic effects on AGE‐induced GC‐2 cell damage compared with loganin alone. In conclusion, loganin can protect against DM‐induced reproductive damage, probably by suppressing the AGEs/RAGE/p38MAPK/NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Ultra-high-molecular-weight polyethylene (UHMWPE) fiber laminate is currently widely used in ballistic protection for its exceptional physical and mechanical properties. However, the dynamic compressive mechanism of UHMWPE laminate remains poorly understood. Therefore, the stress–strain relationship, the influence of different thickness, area, and shape, and the maximum stress and fracture stress are studied in both out-of-plane and in-plane directions under quasi-static and dynamic loading using a universal test machine, Split Hopkinson pressure bar (SHPB), and high-speed camera. Furthermore, numerical models with cohesive elements are developed. The results indicate a dependency on strain rate and loading direction. Firstly, the stress–strain curve of dynamic testing can be divided into different zones according to different loading directions and strain rates. Secondly, with the increase of the strain rate in the dynamic testing, the maximum stress and fracture stress increase as well; relatively speaking, the fracture stress in the out-of-plane direction is greater than the fracture stress in the in-plane direction. Thirdly, both experiment and simulation indicate that the thickness does not influence the modulus clearly the in out-of-plane direction but influences the modulus in the in-plane direction. Fourthly, the fracture stress of dynamic testing is higher than the fracture stress of quasi-static testing in both directions. Finally, the numerical results show good agreement with the experiment in terms of the maximum stress and failure form. [ABSTRACT FROM AUTHOR]

Pyruvate formation in Escherichia coli strain ALS929 containing mutations in the aceEF, pfl, poxB, pps, and ldhA genes that encode the pyruvate dehydrogenase complex, pyruvate formate lyase, pyruvate oxidase, phosphoenolpyruvate synthase, and lactate dehydrogenase, respectively is reported. Out of the four nutrient limitation conditions, growth under acetate limitation resulted in the highest glycolytic flux, pyruvate formation rate, and pyruvate yield.

The saw-tooth chip formation is one of the main machining characteristics in cutting of titanium alloys. The numerical simulation of saw-tooth chip formation, however, is still not accurate, since most of these numerical simulation models are based on traditional finite element method, which have difficulties in handling extremely large deformation that always occurs in the cutting process. Furthermore, these models adopt the Johnson–Cook damage constitutive law that is implemented in commercial codes such as ABAQUS® and LS-DYNA® to describe the dynamic mechanical properties of material, but Johnson–Cook damage constitutive law cannot account for the material of behavior due to strain softening and the dynamic recrystallization mechanism that occurs in the cutting process of Ti–6Al–4. Therefore, this work introduces a material constitutive model named hyperbolic tangent (TANH) and an improved smooth particle hydrodynamics method, and then develops an improved cutting model for Ti–6Al–4V titanium alloy through our in-house code to predict saw-tooth chip morphology and cutting forces. When compared to the experiments and Johnson–Cook damage model, the improved cutting model better explains and predicts the shear localized saw-tooth chip deformation as well as cutting forces. [ABSTRACT FROM AUTHOR]

Lantibiotics represent a large untapped pipeline of attractive scaffolds for the development of novel antibiotics. Saturation mutagenesis was employed to substitute every amino acid of a lantibiotic called mutacin 1140 (MU1140), creating an unbiased expression library of 418 variants that was used to study the permissiveness to mutagenesis and the "drugability" of several compounds. Contrasting previous reports, the results from this study supported that not all residues involved in lanthionine bridge formation were critical for maintaining optimal activity. While substitutions in lanthionine bridges in Ring A, C, and D invariably lead to inactive variants, permissive substitutions in Abu8 and Ala11 (Ring B) were observed, albeit infrequently. Further, the data generated suggested that the unsaturated bond from Dha5 (Ser5) may not be critically involved in Lipid‐II binding but still important for conferring optimal activity. This study identified additional permissive mutations of Ser5, including Ser5His, Ser5Met, Ser5Gln, and Ser5Leu. In contrast, no permissive substitutions were identified for Dhb14, which suggested that this residue may be critical for optimal activity. Novel blueprints are proposed for directing further development of MU1140 variants and other lantibiotics, which may enable the rational design, development, manufacture, and formulation of an entirely new class of anti‐infectives. Lantibiotics represent a large untapped pipeline of attractive scaffolds for the development of novel antibiotics. Saturation mutagenesis was employed to substitute every amino acid of the core peptide of a lantibiotic called mutacin 1140, creating an unbiased expression library of 418 variants that was used to study the structure–activity relationship of key residues. Blueprints are proposed for directing further development of therapeutic lantibiotics, which enable the rational design, development, manufacture, and formulation of an entirely new class of anti‐infectives. [ABSTRACT FROM AUTHOR]

This study aimed to describe the expression profiles of microRNAs (miRNAs) from mammary gland tissues collected from dairy cows with Streptococcus agalactiae-induced mastitis and to identify differentially expressed miRNAs related to mastitis. The mammary glands of Chinese Holstein cows were challenged with Streptococcus agalactiae to induce mastitis. Small RNAs were isolated from the mammary tissues of the test and control groups and then sequenced using the Solexa sequencing technology to construct two small RNA libraries. Potential target genes of these differentially expressed miRNAs were predicted using the RNAhybrid software, and KEGG pathways associated with these genes were analysed. A total of 18 555 913 and 20 847 000 effective reads were obtained from the test and control groups, respectively. In total, 373 known and 399 novel miRNAs were detected in the test group, and 358 known and 232 novel miRNAs were uncovered in the control group. A total of 35 differentially expressed miRNAs were identified in the test group compared to the control group, including 10 up-regulated miRNAs and 25 down-regulated miRNAs. Of these miRNAs, miR-223 exhibited the highest degree of up-regulation with an approximately 3-fold increase in expression, whereas miR-26a exhibited the most decreased expression level (more than 2-fold). The RNAhybrid software predicted 18 801 genes as potential targets of these 35 miRNAs. Furthermore, several immune response and signal transduction pathways, including the RIG-I-like receptor signalling pathway, cytosolic DNA sensing pathway and Notch signal pathway, were enriched in these predicted targets. In summary, this study provided experimental evidence for the mechanism underlying the regulation of bovine mastitis by miRNAs and showed that miRNAs might be involved in signal pathways during S. agalactiae-induced mastitis. [ABSTRACT FROM PUBLISHER]

Intracranial hemorrhage remains the most feared complication in tissue plasminogen activator (tPA) thrombolysis for ischemic stroke. However, the underlying molecular mechanisms are still poorly elucidated. In this study, we reported an important role of caveolin-1 (Cav-1) s-nitrosylation in matrix metalloproteinase (MMP)-2 and 9 secretion from tPA-treated ischemic endothelial cells. Brain vascular endothelial cells (bEND3) were exposed to oxygen-glucose deprivation (OGD) for 2 h before adding recombinant human tPA for 6 h. This treatment induced a significant increase of MMP2 and 9 in the media of bEND3 cells and a simultaneous degradation of fibronectin and laminin β-1, the two main components of extracellular matrix (ECM). Inhibition of MMP2 and 9 with SB-3CT completely blocked the degradation of fibronectin and laminin β-1. ODG+tPA treatment led to Cav-1 shedding from bEND3 cells into the media. Notably, OGD triggered nitric oxide (NO) production and S-nitrosylationof Cav-1 (SNCav-1). Meanwhile tPA induced activation of ERK signal pathway and stimulates the secretion of SNCav-1. Pretreatment of bEND3 cells with C-PTIO (a NO scavenger) or U0126 (a specific ERK inhibitor) significantly reduced OGD-induced S-nitrosylation of Cav-1 in cells and blocked the secretion of Cav-1 and MMP2 and 9 into the media as well as the degradation of fibronectin and laminin β-1 in OGD and tPA-treated cells. These data indicate that OGD-triggered Cav-1 S-nitrosylation interacts with tPA-induced ERK activation to augment MMP2 and 9 secretion and subsequent ECM degradation, which may account for the exacerbation of ischemic blood brain barrier damage following tPA thrombolysis for ischemic stroke. [ABSTRACT FROM AUTHOR]

• A co-immobilization system of dual-enzyme and coenzyme was successfully constructed. • The immobilized enzymes presented improved stability and fine reusability. • The system realized chiral (R)−1-phenylethanol highly selective production and coenzyme effective recycling. Coenzymes are required in the reaction catalyzed by oxidoreductases. The research on coenzyme regeneration has always been a hot topic in the field of biological catalysis. In this work, we tried to construct a co-immobilization system of glucose dehydrogenase (GDH), (R)-1-phenylethanol dehydrogenase ((R)-PEDH) and coenzyme with functional magnetic nanoparticles as carriers, so as to realize chiral (R)-1-phenylethanol highly selective production and coenzyme effective recycling. The enzymatic properties of immobilized enzymes were explored. The results showed that the immobilized enzymes had improved stability and fine reusability. In addition, during the catalytic coupling reaction at a final concentration of 2.63 μM NAD+, the total turnover number (TTN) was as high as 924, and the volumetric productivity of (R)-1-phenylethanol was 37.06 mg·L−1·h−1. After reused for 10 cycles, the catalytic efficiency of immobilized coenzyme can still be maintained at more than 30%. From multiple perspectives, the immobilized dual-enzymes and coenzyme system seems to be a multifunctional system for (R)-1-phenylethanol production and coenzyme regeneration. [ABSTRACT FROM AUTHOR]

Background: Wilson disease (WD) is an autosomal recessive disease caused by mutations in ATP7B encoding a copper transporter. Consequent copper accumulation results in a variable WD clinical phenotype involving hepatic, neurologic, and psychiatric symptoms, without clear genotype–phenotype correlations. The goal of this study was to analyze alterations in DNA methylation at the whole-genome level in liver and blood from patients with WD to investigate epigenomic alterations associated with WD diagnosis and phenotype. We used whole-genome bisulfite sequencing (WGBS) to examine distinct cohorts of WD subjects to determine whether DNA methylation could differentiate patients from healthy subjects and subjects with other liver diseases and distinguish between different WD phenotypes. Results: WGBS analyses in liver identified 969 hypermethylated and 871 hypomethylated differentially methylated regions (DMRs) specifically identifying patients with WD, including 18 regions with genome-wide significance. WD-specific liver DMRs were associated with genes enriched for functions in folate and lipid metabolism and acute inflammatory response and could differentiate early from advanced fibrosis in WD patients. Functional annotation revealed that WD-hypermethylated liver DMRs were enriched in liver-specific enhancers, flanking active liver promoters, and binding sites of liver developmental transcription factors, including Hepatocyte Nuclear Factor 4 alpha (HNF4A), Retinoid X Receptor alpha (RXRA), Forkhead Box A1 (FOXA1), and FOXA2. DMRs associated with WD progression were also identified, including 15 with genome-wide significance. However, WD DMRs in liver were not related to large-scale changes in proportions of liver cell types. DMRs detected in blood differentiated WD patients from healthy and disease control subjects, and distinguished between patients with hepatic and neurologic WD manifestations. WD phenotype DMRs corresponded to genes enriched for functions in mental deterioration, abnormal B cell physiology, and as members of the polycomb repressive complex 1 (PRC1). 44 DMRs associated with WD phenotype tested in a small validation cohort had a predictive value of 0.9. Conclusions: We identified a disease-mechanism relevant epigenomic signature of WD that reveals new insights into potential biomarkers and treatments for this complex monogenic disease. [ABSTRACT FROM AUTHOR]

The cover image, a rotating multimedia painting by master artist Pierre H. Matisse, is based on the Research Article Blueprints for the Rational Design of Therapeutic Mutacin 1140 Variants by Johan A. Kers et al., https://doi.org/10.1111/cbdd.13365. Molecular model design credit: Rudramani Pokhrel and Prem Chapagain (Florida International University). [ABSTRACT FROM AUTHOR]