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Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection. Deep vein thrombosis after trauma (pt-DVT) patients undergo metabolic changes but a comprehensive characterization in humans is lacking. Here the authors integrate metabolome and proteome to reveal pt-DVT-related metabolic alterations and their function, and reveal potential biomarkers. [ABSTRACT FROM AUTHOR]

Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD. [ABSTRACT FROM AUTHOR]

DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.DNA hydroxymethylation (5hmC) is typically altered in age-related diseases. Here, the authors show that 5hmC accumulates in gene bodies, partially due to prolonged quiescence, and restricts the magnitude of transcriptional changes with age. [ABSTRACT FROM AUTHOR]

Acid protease is widely used in industries such as food processing and feed additives. In the study, low frequency magnetic field (LF-MF) as an aid enhances acid protease production by Aspergillus niger (A. niger). The study assessed mycelial biomass, the enzymic activity of the acidic protease and underlying mechanism. At low intensities, alternating magnetic field (AMF) is more effective than static magnetic fields (SMF). Under optimal magnetic field conditions, acid protease activity and biomass increased by 91.44% and 16.31%, as compared with the control, respectively. Maximum 19.87% increase in enzyme activity after magnetic field treatment of crude enzyme solution in control group. Transcriptomics analyses showed that low frequency alternating magnetic field (LF-AMF) treatment significantly upregulated genes related to hydrolases and cell growth. Our results showed that low-frequency magnetic fields can enhance the acid protease production ability of A. niger, and the effect of AMF is better at low intensities. The results revealed that the effect of magnetic field on the metabolic mechanism of A. niger and provided a reference for magnetic field-assisted fermentation of A. niger. [ABSTRACT FROM AUTHOR]

Hadal trenches are extreme environments situated over 6000 m below sea surface, where enormous hydrostatic pressure affects the biochemical cycling of elements. Recent studies have indicated that hadal trenches may represent a previously overlooked source of fixed nitrogen loss; however, the mechanisms and role of hydrostatic pressure in this process are still being debated. To this end, we investigate the effects of hydrostatic pressure (0.1 to 115 MPa) on the chemical profile, microbial community structure and functions of surface sediments from the Mariana Trench using a Deep Ocean Experimental Simulator supplied with nitrate and oxygen. We observe enhanced denitrification activity at high hydrostatic pressure under oxic conditions, while the anaerobic ammonium oxidation – a previously recognized dominant nitrogen loss pathway – is not detected. Additionally, we further confirm the simultaneous occurrence of nitrate reduction and aerobic respiration using a metatranscriptomic dataset from in situ RNA-fixed sediments in the Mariana Trench. Taken together, our findings demonstrate that hydrostatic pressure can influence microbial contributions to nitrogen cycling and that the hadal trenches are a potential nitrogen loss hotspot. Knowledge of the influence of hydrostatic pressure on anaerobic processes in oxygenated surface sediments can greatly broaden our understanding of element cycling in hadal trenches. Hadal trenches are the deepest oceanic ecosystems, with water depth over 6000 m, and are among the least explored habitats on Earth. This research demonstrates that high hydrostatic pressure enhances denitrification activity under oxic conditions, potentially making hadal trenches fixed nitrogen loss hotpots. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is associated with dairy mastitis, which causes serious economic losses to dairy farming industry. Antibacterial peptide NZX showed good antibacterial activity against S. aureus. This study aimed to evaluate pharmacokinetics and pharmacodynamics of NZX against S. aureus-induced mouse mastitis. NZX exhibited potent in vitro antibacterial activity against the test S. aureus strains (minimal inhibitory concentration (MIC): 0.23–0.46 μM), low mutant prevention concentration (MPC: 1.18–3.68 μM), and a long post antibiotic effect (PAE: 2.20–8.84 h), which was superior to those of lincomycin and ceftiofur. Antibacterial mechanisms showed that NZX could penetrate the cell membrane, resulting in obvious cell membrane perforation and morphological changes, and bind to intracellular DNA. Furthermore, NZX had a good stability in milk environment (retention rate: 85.36%, 24 h) than that in mammary homogenate (47.90%, 24 h). In mouse mastitis model, NZX (25–400 μg/gland) could significantly reduce the bacterial load of mammary tissue in a dose-dependent manner. In addition, NZX (100 μg/gland) could relieve the inflammatory symptoms of mammary tissue, and significantly decreased its pathological scores. The concentration–time curve of NZX (100 μg/gland) in the mammary tissue was plotted and the corresponding pharmacokinetic parameters were obtained by non-compartment model calculation. Those parameters of Tmax, T1/2, Cmax and AUC were 0.5 h, 35.11 h, 32.49 μg/g and 391 μg·h/g, respectively. Therefore, these results suggest that NZX could act as a promising candidate for treating dairy mastitis disease caused by S. aureus. Key points: • NZX could kill S. aureus by dual mechanism involved in membrane and DNA disruption • NZX could relieve S. aureus-induced mouse mastitis • Pharmacokinetic parameters of NZX in mouse mammary gland were obtained [ABSTRACT FROM AUTHOR]

This study identified the aroma profile of salmon by-product for high utilization of by-products, including hydrolysates of head, frame, and skin were treated with reducing sugars and thermal processing. Electronic nose (E-nose) and gas chromatography-mass spectrometry (GC–MS) coupled with gas chromatography–olfactometry (GC–O) were used to analyzed the aroma profile. A total of 140 and 90 volatile compounds were detected through E-nose and GC–MS respectively, and the main volatile compounds were aldehydes. A total of 23 odor active compounds were recognized using GC–O, and 3-methyl-butanal, heptanal, benzaldehyde, octanal, furfural, and methoxy-phenyl-oxime were identified as the aroma of salmon. Using multivariate analysis, the pattern between the pretreated samples and aroma profiles was confirmed, and there were clear separations among the samples. The results of this study provide the aroma profile of salmon by-products and are expected salmon by-products to be used as a potential food source. [ABSTRACT FROM AUTHOR]

Purpose: The vibration characteristics of gear transmission systems with a fault can be influenced by nonlinear factors. To obtain accurate fault vibration signals and analyze vibration characteristics, a nonlinear dynamic model of a fault gear transmission system considering these factors is required. Methods: A nonlinear dynamics model of a spur gear transmission system with a root crack is proposed, and the time-varying friction and dynamic backlash are considered in the model. First, the time-varying meshing stiffness (TVMS) is calculated by the potential energy method, and the effect of time-varying friction is fully considered. The dynamic backlash is obtained by the fractal theory. Then, the tooth surface roughness is seen as a link between friction and backlash, and they are calculated at the different tooth surface roughness. The vibration differential equations of the model can be deduced by the Lagrange equation. Finally, the equations are solved by the Runge–Kutta method to investigate the vibration characteristics. Results: The theoretical simulation results show that the change in tooth surface roughness can directly affect the friction coefficient and backlash of the tooth. Time-varying friction excites sidebands near the meshing frequency. The system adds new frequency components due to dynamic backlash, and these frequencies are only related to the microscopic changes in the tooth surface. Moreover, an early crack (1 mm) is not apparent in the time-domain waveforms, but amplitudes can surge in the high-frequency region in the time-frequency domain. The extent of fluctuation in the high-frequency region can be used to diagnose the damage degree of the crack. The same phenomenon is also obtained by experimental analysis. Conclusions: The influence of tooth surface roughness on the gear system is revealed by the model proposed in this paper. Precise fault characteristics of cracked gears are obtained. The experimental and simulation results can provide some references for the diagnosis of the crack defect extent. [ABSTRACT FROM AUTHOR]

Laser-induced graphene (LIG) is a three-dimensional graphene structure fabricated through the irradiation of a polymer substrate with laser energy (or fluence, equivalently). This methodology offers a cost-effective and facile means of producing 3D nanostructures, yielding graphene materials characterized by extremely high surface area and superior electrical properties, rendering them advantageous for various electrochemical applications. Nonetheless, it is imperative to acknowledge that the structures and material properties of LIG are subject to substantial variations contingent upon processing parameters, thereby underscoring the necessity for systematic inquiry and systematic comprehension of processing conditions, such as fluence and multi-passing, and resultant outcomes. Herein, we explored the impact of different laser fluence levels on the structural and material properties of LIG. We, especially, focused on how laser fluence affected substrate temperature and found that it caused polyimide (PI) substrate pyrolysis, resulting in changes in 3D structures and material density to LIG properties. We also investigated the effects of a multi-passing process on 3D LIG structures and material qualities, varying fluences, and temperature fluctuations. Lastly, we assessed electrochemical properties using LIGs produced under different conditions as working electrodes, leading to distinct impedance profiles and cyclic voltammetry (CV) curves. These variations were linked to the unique structural and material characteristics of the LIG samples. [ABSTRACT FROM AUTHOR]

This study proposes a new medical image encryption scheme based on Josephus traversing and hyperchaotic Lorenz system. First, a chaotic sequence is generated through hyperchaotic system. This hyperchaotic sequence is used in the scrambling and diffusion stages of the algorithm. Second, in the scrambling process, the image is initially confused by Josephus scrambling, and then the image is further confused by Arnold map. Finally, generated hyperchaos sequence and exclusive OR operation is used for the image to carry on the positive and reverse diffusion to change the pixel value of the image and further hide the effective information of the image. In addition, the information of the plaintext image is used to generate keys used in the algorithm, which increases the ability of resisting plaintext attack. Experimental results and security analysis show that the scheme can effectively hide plaintext image information according to the characteristics of medical images, and is resistant to common types of attacks. In addition, this scheme performs well in the experiments of robustness, which shows that the scheme can solve the problem of image damage in telemedicine. It has a positive significance for the future research. [ABSTRACT FROM AUTHOR]

Targeted protein degradation (TPD) technology has gradually become widespread in the past 20 years, which greatly boosts the development of disease treatment. Contrary to small inhibitors that act on protein kinases, transcription factors, ion channels, and other targets they can bind to, targeted protein degraders could target "undruggable targets" and overcome drug resistance through ubiquitin–proteasome pathway (UPP) and lysosome pathway. Nowadays, some bivalent degraders such as proteolysis-targeting chimeras (PROTACs) have aroused great interest in drug discovery, and some of them have successfully advanced into clinical trials. In this review, to better understand the mechanism of degraders, we elucidate the targeted protein degraders according to their action process, relying on the ubiquitin–proteasome system or lysosome pathway. Then, we briefly summarize the study of PROTACs employing different E3 ligases. Subsequently, the effect of protein of interest (POI) ligands, linker, and E3 ligands on PROTAC degradation activity is also discussed in detail. Other novel technologies based on UPP and lysosome pathway have been discussed in this paper such as in-cell click-formed proteolysis-targeting chimeras (CLIPTACs), molecular glues, Antibody-PROTACs (Ab-PROTACs), autophagy-targeting chimeras, and lysosome-targeting chimeras. Based on the introduction of these degradation technologies, we can clearly understand the action process and degradation mechanism of these approaches. From this perspective, it will be convenient to obtain the development status of these drugs, choose appropriate degradation methods to achieve better disease treatment and provide basis for future research and simultaneously distinguish the direction of future research efforts. Protein is degraded by proteasome pathway and lysosome pathway. [ABSTRACT FROM AUTHOR]

In the big data environment, Socially Aware Networking (SAN) can obtain a large amount of status data and social contacts of network nodes. If the information is fully analyzed and utilized, it will effectively improve the energy efficiency and performance of SAN. To address this issue, Energy and Cache Aware Routing Algorithm (ECARA) is proposed that comprehensively utilizes node energy and cache information. First, a probability model of encounters is established by using the historical encounter information between nodes in the network. Then, the residual energy ratio of the node is introduced. They are used to predict the delivery probability of the current node. At the same time, a node cache utilization ratio model is also established. In the end, the algorithm comprehensively considers the prediction value of delivery probability and node cache utilization ratio. The optimal relay node is selected to forward the message. Through the forwarding of many relay nodes, the message is finally delivered to the destination node. Simulation results demonstrate that the ECARA exhibits a superior message delivery ratio compared to other classical algorithms. It also can effectively prevent network congestion and improve network throughput. [ABSTRACT FROM AUTHOR]

The low activity and yield of antimicrobial peptides (AMPs) are pressing problems. The improvement of activity and yield through modification and heterologous expression, a potential way to solve the problem, is a research hot-pot. In this work, a new plectasin-derived variant L-type AP138 (AP138L-arg26) was constructed for the study of recombination expression and druggablity. As a result, the total protein concentration of AP138L-arg26 was 3.1 mg/mL in Pichia pastoris X-33 supernatant after 5 days of induction expression in a 5-L fermenter. The recombinant peptide AP138L-arg26 has potential antibacterial activity against selected standard and clinical Gram-positive bacteria (G+, minimum inhibitory concentration (MIC) 2–16 µg/mL) and high stability under different conditions (temperature, pH, ion concentration) and 2 × MIC of AP138L-arg26 could rapidly kill Staphylococcus aureus (S. aureus) (> 99.99%) within 1.5 h. It showed a high safety in vivo and in vivo and a long post-antibiotic effect (PAE, 1.91 h) compared with vancomycin (1.2 h). Furthermore, the bactericidal mechanism was revealed from two dimensions related to its disruption of the cell membrane resulting in intracellular potassium leakage (2.5-fold higher than control), and an increase in intracellular adenosine triphosphate (ATP), and reactive oxygen species (ROS), the decrease of lactate dehydrogenase (LDH) and further intervening metabolism in S. aureus. These results indicate that AP138L-arg26 as a new peptide candidate could be used for more in-depth development in the future. Key points: • The AP138L-arg26 was expressed in the P. pastoris expression system with high yield • The AP138 L-arg26 showed high stability and safety in vitro and in vivo • The AP138L-arg26 killed S. aureus by affecting cell membranes and metabolism [ABSTRACT FROM AUTHOR]

A gear-bearing dynamic model is presented to investigate the vibration features of the system with a misaligned shaft angle. The time-varying mesh stiffness (TVMS), time-varying pressure angle and eccentricity are considered in the model. In addition, a new expression of the load distribution function of the tooth is proposed to obtain accurate effects of the misaligned shaft angle on the TVMS. Based on the proposed model, the vibration of the system and the TVMS are solved jointly. This model is solved by the fourth-order Runge–Kutta, and the TVMS is calculated by the energy potential method where one mesh stiffness value is determined by each time-varying misaligned shaft angle. Effects of the misaligned shaft angle on the vibration features are analyzed by the mode, time-domain, frequency-domain and statistical indicator features. Meanwhile, experimental research is provided to verify theoretical results. The results show that the misaligned shaft angle can affect the mode of the system and decline the meshing stiffness. The change in the natural frequency is related to the decrease in stiffness. The gear torsional vibration signal is more sensitive to the misaligned shaft angle than the bearing translation signal. The purpose of this research is to provide some useful references in the numerical modeling gear system and monitor the contact state of the teeth. [ABSTRACT FROM AUTHOR]

Aortic injuries are the second leading cause of death after head injuries due to traffic accidents, and strain-induced injuries are becoming increasingly prominent. The quantitative study of aortic strain injury allows for a rapid assessment of the degree of aortic injury after an accident and timely diagnosis of the pathology of aortic injury. It is more reliable than diagnosis based on clinical symptoms alone and it is faster than diagnosis based on imaging. Based on the porcine aortic tensile and injury tests, this study obtained the maximum stress threshold of the aorta that can withstand tensile stress and the safe stress threshold under tensile action, which provides a more detailed data reference about aortic injury in the field of internal medicine. Injuries to the aorta under various degrees of traction were analyzed in detail. A comprehensive and quantitative evaluation criterion for aortic strain injury was proposed, which provides a more in-depth reference for the mechanism of aortic strain injury. In addition, combining it with current imaging promises a combination of numbers and shapes for rapid and accurate diagnosis of aortic strain injury. [ABSTRACT FROM AUTHOR]

Cysteine (Cys) is a significant biological mercaptan that achieves key roles in several important physiological processes, such as reversible redox homeostasis in living organisms. Abnormal levels of Cys in the human body are directly related to many diseases. In this work, we constructed a sensitive sensor (Cys-NR) by connecting a Cys recognition group to a Nile red derivative. Due to photo-induced electron transfer (PET), the Cys-NR probe showed little fluorescence at 650 nm. With the addition of Cys to the assay solution, the chlorine unit of the probe was substituted by the thiol group of Cys. Further, the amino and sulfhydryl groups in cysteine underwent an intramolecular rearrangement, which led to the Cys-NR probe water solution turning from colorless to pink with an enhancement in fluorescence. The red fluorescence at 650 nm increased about 20 times. Based on the turn-on signal, a selective Cys detection method is developed. The probe signal is not affected by various potential interferences or other competing biothiols and the limit of detection (LOD) is determined to be 0.44 μM. In addition, the probe is further employed for imaging of Cys in live cells, revealing good biological imaging ability that could provide a new way of intracellular Cys detection. [ABSTRACT FROM AUTHOR]

Introduction: The Chinese Diabetes Society recommends basal insulin and glucagon-like peptide-1 receptor agonists as an add-on therapy to first-line oral antihyperglycemic drugs for people with type 2 diabetes (T2D). Fixed-ratio combination of insulin glargine 100 U/ml (iGlar) and lixisenatide (iGlarLixi) is known to improve glycemic control in adults with T2D. However, the pharmacokinetics of iGlarLixi has not been evaluated in Chinese participants. The present study evaluated pharmacokinetics and safety of two iGlarLixi (10 U/10 μg and 30 U/15 μg) doses following single subcutaneous administration in healthy Chinese participants. Methods: This was a Phase 1, single-center, open-label, parallel-group, randomized study in healthy Chinese adults who were randomized to receive a single dose of iGlarLixi with either 1:1 (10 U/10 μg) or 2:1 (30 U/15 μg) ratio of iGlar and lixisenatide. Primary objectives include assessment of pharmacokinetics of iGlar in iGlarLixi 30 U/15 μg group and the pharmacokinetics of lixisenatide in both the groups (iGlarLixi 10 U/10 μg and iGlarLixi 30 U/15 μg). Safety and tolerability were also assessed. Results: In iGlarLixi 30 U/15 μg group, iGlar concentrations were low and quantifiable in three of ten participants, while its main metabolite (M1) was quantifiable in all participants, reflecting rapid conversion of iGlar to M1. Median INS-tmax was 14.00 h for iGlar and 13.00 h post-dose for M1. Absorption of lixisenatide was similar in both dose groups with median tmax of 3.25 and 2.00 h post-dose in both groups. The exposure increase was dose proportionate with a 1.5-fold increase in the lixisenatide dose. Adverse events observed were consistent with those previously reported with iGlar or lixisenatide. Conclusion: iGlarLixi administration resulted in early absorption of both iGlar and lixisenatide with a good tolerability profile in healthy Chinese participants. These results are consistent with the previously published data from other geographic regions. Trial registration: U1111-1194-9411. [ABSTRACT FROM AUTHOR]

Static magnetic fields (SMFs) exhibit numerous biological effects and regulate the proliferation and differentiation of several adult stem cells. However, the role of SMFs in the self-renewal maintenance and developmental potential of pluripotent embryonic stem cells (ESCs) remains largely uninvestigated. Here, we show that SMFs promote the expression of the core pluripotent markers Sox2 and SSEA-1. Furthermore, SMFs facilitate the differentiation of ESCs into cardiomyocytes and skeletal muscle cells. Consistently, transcriptome analysis reveals that muscle lineage differentiation and skeletal system specification of ESCs are remarkably strengthened by SMF stimuli. Additionally, when treated with SMFs, C2C12 myoblasts exhibit an increased proliferation rate, improved expression of skeletal muscle markers and elevated myogenic differentiation capacity compared with control cells. Together, our data show that SMFs effectively promote muscle cell generation from pluripotent stem cells and myoblasts. The noninvasive and convenient physical stimuli can be used to increase the production of muscle cells in regenerative medicine and the manufacture of cultured meat in cellular agriculture. [ABSTRACT FROM AUTHOR]

Bovine Lf (bLf) possesses high amino acid sequence homology (69%) and it displays in many cases a similar bioactivity when compared to human Lf (hLf). Lactoferrin (Lf) is a multifunctional iron-binding glycoprotein that is specifically produced by exocrine glands and it is also expressed at high levels in neutrophils in mammals. Natural Lf and the well-characterized N-terminal synthetic peptide of Lf, known as lactoferricin (for a review see Gifford et al. [18]), both inhibited the proteolytic priming of the viral spike protein by transmembrane protease serine 2, thereby blocking the virus from entering the cell (Ohradanova-Repic et al. [39]). Although holo- and apo-Lf often display similar bioactivities, the different localization of holo- and apo-Lf in the cell may suggest a different mode of action for Lf with different levels of iron saturation (Jenssen et al. [25]). [Extracted from the article]

Weaning is a crucial period in the pig's life cycle, which is frequently followed by gastrointestinal (GI) infections, diarrhea and even death. This study focused on the impact of bovine lactoferrin (bLF) supplementation on the intestinal health of weaning piglets. Weaning piglets (Duroc × Landrace × Yorkshire, 23 days) were randomly allocated into four groups, which included negative control group (CON): basic diet; positive control group (ANT): basic diet + 20 mg/kg flavomycin + 100 mg/kg aureomycin; treatment group bLF-A: basic diet + 1 g/kg bLF; treatment group bLF-B: basic diet + 3 g/kg bLF. The result showed that dietary supplementation of bLF can improve growth performance and reduce diarrhea, which exhibits dose-dependency (P < 0.05). Compared with CON group, supplementation with bLF significantly improved immunity, and increased villus height and ratio of villus height/crypt depth at the small intestinal mucosa (P < 0.05). The mRNA expression of claudin-1, occludin and ZO-1 was greatly increased in the ileum of bLF group on days 7 and 14 (P < 0.05). Furthermore, the supplementation of bLF increased the abundance of Lactobacillus and Bifidobacterium and decreased the abundance of Escherichia coli in the cecum on day 7 (P < 0.05). The dietary supplementation of bLF enhanced the growth performance, reduced diarrhea rate in weaning piglets by improving intestinal immunity, morphology and barrier function, balancing intestinal microbiota. And bLF can be a promising feed additive in relieving stress situation of weaning piglets. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluated the bioequivalence of ezetimibe/rosuvastatin fixed dose combination compared to the concomitant administration of individual formulations (ezetimibe and rosuvastatin) in Chinese healthy subjects under fasting conditions. Methods: This was a phase I, randomized, open-label, two-treatment, two-period, two-sequence, crossover study conducted in healthy Chinese participants under fasting conditions. Cmax, AUC0–t, and AUC0–∞ from test and individual reference formulations were evaluated to assess bioequivalence. The safety assessments included adverse events (AEs)/treatment-emergent adverse events (TEAEs), potential clinically significant abnormalities (PCSAs) in vital signs, 12-lead electrocardiogram (12-ECG), and clinical laboratory parameters. Results: Of the 68 subjects enrolled, 67 were treated. Systemic exposure to rosuvastatin based on Cmax, AUC0–t, and AUC0–∞ was similar in both treatments, with respective arithmetic values 12.4 ng/ml, 117 ng·h/mL, and 120 ng·h/mL for test formulation and 12.7 ng/ml, 120 ng·h/mL, and 123 ng·h/mL for reference formulations. Similarly, systemic exposure to unconjugated ezetimibe was 4.14 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for the test formulation and 3.80 ng/ml, 89.7 ng·h/mL, and 102 ng·h/mL for reference formulations. Systemic exposure to total ezetimibe was 70.5 ng/ml, 664 ng·h/mL, and 718 ng·h/mL for test formulation and 60.2 ng/ml, 648 ng·h/mL, and 702 ng·h/mL for reference formulations. The point estimates for rosuvastatin unconjugated ezetimibe and total ezetimibe were in the acceptable range of 0.80–1.25. No deaths or serious adverse events were reported. Conclusions: Fixed dose combination of ezetimibe/rosuvastatin (10 mg/10 mg) achieved bioequivalence with reference to commercial tablets. Trial Registration Number: CTR20202108. [ABSTRACT FROM AUTHOR]

We investigated the relationship between dyslipidemia and drug-induced liver injury (DILI), especially the level of triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) in severe DILI. In this single-centered retrospective study, of 326 patients with DILI, 221 patients were analyzed. Control groups include medication using group and acute hepatitis B group. The relationship between dyslipidemia and DILI was estimated. Demographic and clinical features were analyzed. Dyslipidemia and TG/HDL-C ratios were compared between DILI and control groups, DILI mild group and severe group. The area under the receiver-operating characteristic curve (AUC) was used to evaluate the credibility of the relationship and to find cut-off points. Dyslipidemia is related to DILI when compared with medication using control group (AOR 4.60; 95% CI 2.81–7.54; P < 0.01) and compared with acute hepatitis B group (AOR 2.12; 95% CI 1.37–3.29; P < 0.01). Dyslipidemia is associated with the severity of DILI (AOR 25.78; 95% CI 7.63–87.1; P < 0.01). TG/HDL-C ratio is higher in DILI group than that of medication using control group, also higher in severe DILI group than that of mild DILI group. AUCs for TG/HDL-C ratio to indicate the severity of DILI was 0.89 (P < 0.05), the cut-off point was 2.35. Dyslipidemia and TG/HDL-C ratio were related to DILI occurrence. Severe liver injury in DILI was associated with dyslipidemia and elevated TG/HDL-C ratio. [ABSTRACT FROM AUTHOR]

Using the observations of the 630-nm all-sky imagers (ASIs) located in the geomagnetic conjugate points in the American sector from 2014 to 2017, this study statistically analyzed the features of conjugate equatorial plasma bubbles (EPBs), including their occurrence rate, zonal width, location and zonal drift velocity. The results show that the occurrence rate of the EPBs that occur simultaneously at geomagnetic conjugate points is ∼84%. The zonal widths of the EPBs are mainly ∼100 km, and the width differences of EPBs between the northern and southern hemispheres are mainly within ±30 km. The zonal displacements of the center locations of the northern and southern EPBs are within ±50 km. The zonal drift velocities of the northern and southern EPBs are nearly equal. However, it should be noted that the velocity of the EPBs in the northern hemisphere is 10% faster than that in the southern hemisphere. The results suggest that conjugate EPBs are common. Moreover, the non-conjugate EPBs in the northern and southern hemisphere can occur occasionally, which is probably associated with the different ionospheric backgrounds between the two hemispheres. The features of the conjugate EPBs as shown in this study provides support for the nowcasting of EPBs in the conjugate hemispheres. [ABSTRACT FROM AUTHOR]

Fault signals measured from a damaged rolling bearing usually exhibit amplitude modulation (AM)-frequency modulation (FM) properties. For this kind of signal, the demodulation technique is an effective and common method. In the demodulation techniques, a variety of energy operator (EO) tools have been available due to high computational efficiency and self-adaptability to transient signals. Hence, an alternative energy measure is proposed in this work. The new demodulation technique is achieved by combining a multiresolution higher-order symmetric difference sequence with the envelope-derivative operator (EDO). The multiresolution higher-order symmetric envelope-derivative operator (MHOS-EDO) can extract the weak bearing fault characteristics in a harsh environment without any pre-filtering. Especially in the presence of vibration interferences, its unique energy transformation can eliminate the influence of vibration interferences, so that the vibration interferences will no longer appear in the energy spectrum. Through simulation and practical experiments, the superiority of MHOS-EDO in dealing with noise and interfering components is demonstrated. Meanwhile, the comparison results reveal that the MHOS-EDO outperforms some previous EO and some other bearing fault identification methods. [ABSTRACT FROM AUTHOR]

According to the characteristic that mineralized-anomaly samples have larger reconstruction errors, traditional autoencoder networks have been applied widely in mineralized-anomaly identification. However, they easily ignore spatial coupling information of multi-source ore-indicating factors have lower generalization abilities caused by excessive feature redundancies, and rely on known non-mineralization samples when they are utilized in mineralized-anomaly identification. This paper utilizes a convolutional sparse autoencoder network for realizing mineralized-anomaly identification. The proposed method retains the extraction of spatial coupling correlations of geological and geochemical variables through the addition of convolutional operations, learning the relationship between mineralized-features and the locations of mineralization, and being conducive to analyzing results with geological structures. The establishment of sparse terms of using ReLU activation functions and adding sparsity constraints into the objective loss function improves the generalization ability of the whole network through suppression of several feature units to reduce redundant features. Moreover, the isolated forest is employed as an autonomous extractor of background multichannel image samples, overcoming the limitation of traditional autoencoder networks that rely on labeled non-mineralization samples. The integration of convolutional sparse autoencoder network and isolated forest can accurately predict more known mineral deposits (68.96%) in smaller prospective areas (16.77%) in the Fengxian District, Shaanxi Province, China. The obtained mineralized-anomaly map reveals that most of the known mineralization is distributed in the delineated areas of larger reconstruction errors, demonstrating that this approach can effectively identify mineralized-anomalies without relying on prior knowledge. [ABSTRACT FROM AUTHOR]

DNMT1 is a DNA methyltransferase that catalyzes and maintains methylation in CpG dinucleotides. It blocks the entrance of DNA into the catalytic pocket via the replication foci targeting sequence (RFTS) domain. Recent studies have shown that an H3-tail-conjugated two-mono-ubiquitin mark (H3Ub2) activates DNMT1 by binding to the RFTS domain. However, the activation mechanism of DNMT1 remains unclear. In this work, we combine various sampling methods of extensive simulations, including conventional molecular dynamics, Gaussian-accelerated molecular dynamics, and coarse-grained molecular dynamics, to elucidate the activation mechanism of DNMT1. Geometric and energy analyses show that binding of H3Ub2 to the RFTS domain of DNMT1 results in the bending of the α4-helix in the RFTS domain at approximately 30°–35°, and the RFTS domain rotates ∼20° anti-clockwise and moves ∼3 Å away from the target recognition domain (TRD). The hydrogen-bonding network at the RFTS-TRD interface is significantly disrupted, implying that the RFTS domain is dissociated from the catalytic core, which contributes to activating the auto-inhibited conformation of DNMT1. These results provide structural and dynamic evidence for the role of H3Ub2 in regulating the catalytic activity of DNMT1. [ABSTRACT FROM AUTHOR]

For the lifetime assessment of the running safety of a train in aggressive environments and earthquake-prone areas, the effects of corrosion on seismic performance must be considered. Research on the running safety of trains, including corrosion damage, is limited, despite the fact that seismic safety assessment of trains on high-speed railway bridges has been extensively examined. In this work, the running safety of a train was evaluated using a time-varying corroded bridge finite-element model established in OpenSees. Two pier types were considered, and three ground-motion types were selected for performing seismic performance evaluations. Subsequently, the seismic response of the corroded bridge-track structure under an earthquake was analyzed. The spectrum intensity was used as the structural response index for the running safety assessment of trains under earthquakes, and the long-term safety of trains on bridges with different pier heights and earthquake types, considering different corroding deterioration, was evaluated. The results indicate that under low-level earthquakes, piers are primarily in a linear elastic state and least influenced by corrosion; whereas under high-level earthquakes, the running safety of trains on a bridge significantly deteriorates after corrosion, particularly for high-pier bridges, mainly because the corroded piers are more likely to yield lower post-yield stiffness. The results of this study suggest that in the seismic safety assessment of trains on corroded bridges, time-varying seismic performance characteristics should be considered. [ABSTRACT FROM AUTHOR]

Background and Objective: The combination of rosuvastatin and ezetimibe has promising clinical benefits with a significant safety and tolerability profile. However, there is a lack of clinical data supporting the drug–drug interaction (DDI) in Chinese population. Thus, the aim of this study is to assess the potential pharmacokinetic DDI between rosuvastatin and ezetimibe in a Chinese population. Methods: In this randomized, open-label, phase 1 study, 12 healthy volunteers were randomized to three treatment groups: 10 mg rosuvastatin plus 10 mg ezetimibe, 10 mg rosuvastatin alone, and 10 mg ezetimibe alone under fasting conditions. The plasma concentrations of rosuvastatin and ezetimibe were determined, and the pharmacokinetic parameters were calculated. Primary endpoints were peak plasma concentration (Cmax), area under the curve from zero to last measurement (AUC0–t), and area under the curve from zero to infinity (AUC0–∞) that were log-transformed, and co-administration was compared with monotherapy to evaluate the DDI. Results: The geometric mean ratios (GMRs) of rosuvastatin with 90% confidence intervals (CIs) were 0.94 (0.80–1.12) for Cmax, 0.96 (0.85–1.08) for AUC0–t, and 0.96 (0.86–1.07) for AUC0–∞ when administered in combination with ezetimibe versus administered alone. The GMRs of unconjugated ezetimibe and total ezetimibe with 90% CIs were 1.15 (1.00–1.32) and 0.93 (0.80–1.07) for Cmax, 0.96 (0.84–1.10) and 0.95 (0.83–1.08) for AUC0–t, and 1.06 (0.96–1.18) and 0.94 (0.80–1.11) for AUC0–∞, respectively, when administered in combination with rosuvastatin versus administered alone. Conclusion: Co-administration of rosuvastatin and ezetimibe showed no clinically significant pharmacokinetic interactions in a healthy Chinese population. [ABSTRACT FROM AUTHOR]

The purpose of this study is to explore the differences in the steroid metabolic network between hyperandrogenic and non-hyperandrogenic women with polycystic ovary syndrome (PCOS). A sensitive liquid chromatography-tandem mass spectrometry (LC–MS/MS) was employed for the quantification of 36 kinds of serum steroids in 80 PCOS women during their follicular phase. Compared with those in non-hyperandrogenemia PCOS women (NA-PCOS), the levels of 17-hydroprogesterone (P = 0.009), androstenedione (P < 0.001), total testosterone (P < 0.001), dihydrotestosterone (P = 0.025), estrone (P = 0.007), and estradiol (P < 0.001) were increased in hyperandrogenemia PCOS (HA-PCOS) women. It was suggested that HA-PCOS may have increased activity of P450c17 (17-hydropregnenolone/pregnenolone, P = 0.008), 3βHSD2 (androstenedione/dehydroepiandrosterone, P = 0.004), and 17βHSD3 (testosterone/dehydroepiandrosterone, P = 0.01) and decreased activity of 5α reductase (dihydrotestosterone/testosterone, P = 0.008). Moreover, the ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH) was found to be related to these increased steroids and enzyme activities. In conclusion, the HA-PCOS and the NA-PCOS women showed different steroid profiles, and the different enzyme activities in steroidogenic pathway may be the main reason for the difference. [ABSTRACT FROM AUTHOR]

La0.8Sr0.2MnO3 (LSM) catalyst has been successfully prepared by solid phase method (G-LSM-T), sol–gel method (C-LSM-T) and molten salt method (S-LSM-T), using as-prepared MnCO3 microspheres as templates, respectively. It was shown that the S-LSM-550 catalyst presented well-formed perovskite structures, large specific surface area (49.65m2/g) and promising catalytic activity in CO oxidation, which T50 and T90 for CO conversion over fresh S-LSM-550 were 145.14 °C and 170.73 °C. The S-LSM-550 calcined at 550 °C for 2 h exhibited excellent thermal stability and catalytic activity compared with the samples prepared by solid phase method and sol–gel method. Its superior catalytic performance could be greatly attributed to its stable microstructure, high surface Mn4+/Mn3+ molar ratio and more available surface adsorbed oxygen species. [ABSTRACT FROM AUTHOR]

Wound healing is a complicated process that can be susceptible toward infection caused by bacteria. The surging drug resistance has become one of the biggest challenges to the treatment of these infections in public health. Herein, a new asymmetrical aza-boron-dipyrromethene (ABDP) probe is prepared and encapsulated with cholesterol-modified polyethylene glycol polymer (Chol-PEG 2000-NH 2) to construct a PTT/PDT dual-modality antibacterial agent (the ABDP NPs) and provide a new material for the treatment of MRSA-based infections. The ABDP NPs show remarkable wide UV–Vis absorption at 300–850 nm and superior bactericidal effects against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Methicillin-resistant S. aureus (MRSA), which can be controlled by a phototheranostic antibacterial switch (808 nm laser). Histological analysis indicates that wounds treated by the ABDP NPs plus NIR laser irradiation exhibit more complete re-epithelialization, abundant collagen fibers, and higher hair follicle numbers than the vancomycin-treated group. This study provides a promising perspective using aza-BODIPY dye for the treatment of multidrug-resistant bacteria-based infections and clinical applications in the future. [ABSTRACT FROM AUTHOR]

Background: The recurrence of retinal detachment following rhegmatogenous retinal detachment (RRD) is a relatively common complication that can lead to reduced visual acuity and requires further surgery. The purpose of this study was to investigate the risk factors and visual outcomes of recurrent RRD following pars plana vitrectomy (PPV) with silicone oil tamponade for primary RRD. Methods: This was a retrospective follow-up study of 343 eyes that underwent initial PPV surgery with silicone oil tamponade for primary RRD. Patients were divided into a recurrence group and a reattachment group. The main outcome measures included causative factors, visual outcomes related to the recurrence of RRD, and the perioperative factors most affecting the recurrence of RRD. Results: After retinal reattachment, we observed RRD recurrence after PPV for primary RRD in 42 out of 343 eyes (12.2%) during the follow-up period. Most causes of recurrence (69%) occurred within 6 months of surgery. Multivariate logistic regression analysis showed that a PVR ≥ Grade C (odds ratio [OR]: 4.015; 95% confidence interval [CI] 1.721–9.367; P = 0.001) was a significant predictor for the development of recurrent RRD. Compared with the reattachment group, the recurrence group exhibited a significant decline in best-corrected visual acuity (BCVA) at the last follow-up visit (P = 0.000). Eyes with PVR prior to primary surgery, or at the diagnosis of re-detachment, showed a worse final BCVA. Conclusions: Our analysis shows that the predominant risk factor for the recurrence of RRD is a PVR ≥ Grade C. PVR prior to primary surgery, or at the diagnosis of re-detachment, was also shown to limit the recovery of final visual acuity. [ABSTRACT FROM AUTHOR]

The peroxidase-like activity of MXene@Fe3O4 nanocomposites and the relevant colorimetric application have been investigated for the first time. According to a kinetic study, MXene@Fe3O4 nanocomposites displayed higher peroxidase activity than their individual components, and the catalytic process followed a ping-pong mechanism. The improved peroxidase-like activity of the MXene@Fe3O4 nanocomposites was obtained due to the synergetic impact of the Fe3O4 and MXene phases, the huge ion-accessible interface, and quick electron transfer channels in the nanocomposites. In the presence of hydrogen peroxide (H2O2), the MXene@Fe3O4 nanocomposites can catalyze the reaction of the colorless substrate 3, 3, 5, 5-tetramethylbenzidine (TMB) into oxidized TMB which revealed a blue color at 652 nm. After the introduction of glutathione (GSH), the blue color was gradually fading owing to the hydroxyl radical scavenging effect of glutathione. A colorimetric detection platform based on the peroxidase-like activity of the MXene@Fe3O4 nanocomposites was developed for H2O2 and GSH with a detection limit of 0.4 μM and 0.5 μM, respectively. The calibration plot for glutathione detection is calculated by absorbance difference at 652 nm, which ranged from 0.5 to 10 μM with a detection limit of 0.2 μM. The recoveries of GSH with different concentrations ranged from 93.76 to 108.50% and the relative standard deviation from 0.30 to 5.96%. This work significantly extends the application of MXene@Fe3O4 nanocomposites in the construction of colorimetric sensors and reveals a satisfactory result in real sample analysis. [ABSTRACT FROM AUTHOR]

Electrical stimulation therapy has attracted widespread attention for its advantages of promoting cell proliferation and tissue regeneration, accelerating skin barrier restoration, and reducing scars. Its effect on accelerating wound healing has been clinically proven. However, traditional electrical stimulation therapy requires large power supply devices, which are inconvenient to carry and use. Therefore, self-powered flexible nano-piezoelectric membranes were developed in this work, which can generate electric field under mechanical stimulation to effectively eliminate bacteria and accelerate wound healing. In this work, poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) piezoelectric membranes were fabricated by electrospinning, and better piezoelectric properties were obtained by adding tetrabutylammonium chloride (TBAC), and their antibacterial and pro-healing effects were investigated with or without mechanical stimulation. Results showed that the output voltage of P(VDF-TrFE)/TBAC piezoelectric membrane was about 5.3 times higher than that of P(VDF-TrFE). Furthermore, the P(VDF-TrFE)/TBAC piezoelectric membrane had excellent antibacterial effect against both Escherichia coli and Staphylococcus aureus after mechanical stimulation, and the inhibition rates of Staphylococcus aureus and Escherichia coli were 71.43% and 97.25%, respectively. Meanwhile, the results of in vivo and in vitro healing promotion experiments showed that P(VDF-TrFE)/TBAC piezoelectric membrane was effective in promoting cell growth and wound healing after mechanical stimulation, the wound was almost completely healed on the 7th day, and the healing rate was increased by about 37% compared with the blank. The P(VDF-TrFE)/TBAC flexible piezoelectric membrane is effective in electrical stimulation for wound healing, and it has potential applications in wound treatment. [ABSTRACT FROM AUTHOR]

Wireless sensor networks (WSNs) are being employed in a growing variety of fields for efficient monitoring and data collection about events that would be impossible with conventional computing platforms. WSNs are self-organizing networks that collects and processes important information via their resource-constrained sensor nodes and provide valuable information about happening events. The unattended nature of sensor nodes in these networks makes them vulnerable to a wide range of threats, and the resource limitations imposed on their nodes complicate things even more while monitoring the target regions. This study relies on an identity-based encryption (IBE) approach to protect these nodes' resources while ensuring that they collect valuable data from the target regions. IBE simplifies the key generation process in these networks and at the same time improves the network security up to a sufficient level. For this purpose, an identity-based encryption online/offline (IBOOE) algorithm is proposed as a more acceptable solution to the security concerns of these nodes. IBOOE improves on the previous algorithm, i.e., IBE, by splitting the encryption into two phases: offline and online. The offline phase is mainly responsible for complicated and resource-intensive operations, e.g. exponential operation and pairing operation. The online phase, on the other hand, is mainly responsible for relatively easy calculations such as integer multiplication or hash operation. The comparison of the proposed IBOOE against the state of the art work, i.e., IBE, clearly demonstrates the efficiency and effectiveness of the proposed work. [ABSTRACT FROM AUTHOR]

Post-tanning process is crucial to improve the physical properties of leather in leather manufacture. However, enormous amounts of organic wastewater are produced, due to the poor binding of dyes and fatliquoring agents, especially in chrome-free leather production. In this study, a strategy to facilitate adsorption of the anionic leather chemicals by collagen fibers in the chrome-free leather processing by regulating the metal molar ratio of MgAl layered double oxide (MgAl-LDO) has been reported. MgAl layered double hydroxide (MgAl-LDH) with different metal molar ratios are prepared by co-precipitation and used as the precursors to prepare MgAl-LDO with different metal molar ratios by calcining method. The results indicate that the charge density of MgAl-LDH laminate increases with decrease in the metal molar ratio. The MgAl-LDO shows a more uniform distribution within crust leather compared to MgAl-LDH. Ts and the thickening rate of the leather tanned by MgAl-LDO are higher than that of MgAl-LDH. Furthermore, dye concentration, COD, and SS of dyeing and fatliquoring wastewater all decrease with decreasing metal molar ratio due to the increase in charge density of MgAl-LDO and favors adsorption of anionic leather chemicals including dyes and fatliquoring agents on leather. The results offer a significant reference for the application of LDH-based nanomaterials in eco-leather manufacture to facilitate the adsorption of anionic leather chemicals. [ABSTRACT FROM AUTHOR]

This study aims to evaluate levels of D-dimer and serum lipid in different types of pancreatitis, and the relationship between D-dimer and dyslipidemia, especially triglyceride to HDL-C ratio (TG/HDL-C) in different types of pancreatitis. We analyzed the D-dimer and dyslipidemia levels in acute pancreatitis (AP), recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). A single-centered retrospective study was conducted on 1013 patients diagnosed with AP, RAP or CP. Only patients hospitalized within 24 h of onset were included, and 204 patients were enrolled in pancreatitis groups. 68 normal persons without pancreatitis, malignant diseases, pregnancy, or organ failure, who had health check-ups, were enrolled in the control group. Blood samples were taken within 24 h of admission. The relevant information on epidemiology and etiology was collected. D-dimer and serum lipid levels in different types of pancreatitis were analyzed. Furthermore, the area under the receiver-operating characteristic curve (AUC) was used to estimate the validity of the predictor and to define optimal cut-off points for prediction. We found that D-dimer and TG/HDL-C ratio could distinguish mild AP (MAP) and non-MAP in AP and RAP patients. The D-dimer level was related to TG/HDL-C ratio and severity of pancreatitis, with the coefficient correlation of 0.379 and 0.427(p < 0.05), respectively. TG/HDL-C was related to D-dimer in different types of pancreatitis. Logistic regression analysis was conducted in the parameters at admission like alcohol abuse, dyslipidemia and coagulation disturbance in distinguishing AP and RAP groups from the control group, and the parameter like diabetes in RAP and CP groups significantly increased compared with that of the control group. The value of D-dimer level and TG/HDL-C ratio in predicting the severity of AP and RAP was confirmed but there was no significant difference between CP group and the control group. The D-dimer level was related to dyslipidemia and TG/HDL-C ratio. [ABSTRACT FROM AUTHOR]

An immunosuppressive tumour microenvironment is a major obstacle in the control of pancreatic and other solid cancers1–3. Agonists of the stimulator of interferon genes (STING) protein trigger inflammatory innate immune responses to potentially overcome tumour immunosuppression4. Although these agonists hold promise as potential cancer therapies5, tumour resistance to STING monotherapy has emerged in clinical trials and the mechanism(s) is unclear5–7. Here we show that the administration of five distinct STING agonists, including cGAMP, results in an expansion of human and mouse interleukin (IL)-35+ regulatory B cells in pancreatic cancer. Mechanistically, cGAMP drives expression of IL-35 by B cells in an IRF3-dependent but type I interferon-independent manner. In several preclinical cancer models, the loss of STING signalling in B cells increases tumour control. Furthermore, anti-IL-35 blockade or genetic ablation of IL-35 in B cells also reduces tumour growth. Unexpectedly, the STING–IL-35 axis in B cells reduces proliferation of natural killer (NK) cells and attenuates the NK-driven anti-tumour response. These findings reveal an intrinsic barrier to systemic STING agonist monotherapy and provide a combinatorial strategy to overcome immunosuppression in tumours.Systemic treatment of pancreatic cancer with STING agonist stimulates regulatory B cells to express immunosuppressive cytokine IL-35, which weakens the anti-tumour function of natural killer cells. [ABSTRACT FROM AUTHOR]

Research on unethical pro-organizational behavior (UPB) has predominantly focused on its antecedents, while overlooking how engaging in such behavior might affect employees' psychological experience and their downstream work behaviors. Integrating cognitive dissonance theory with the moral identity literature, we argue that engaging in UPB restricts moral identity internalization as a result of attempts to alleviate the cognitive dissonance about moral self-regard, which in turn translates into decreased organizational citizenship behavior and increased counterproductive workplace behavior. Moreover, employees' construal level weakens these indirect effects by alleviating the negative effect of engaging in UPB on moral identity internalization. The results from one experimental study and one multi-wave, multisource field study provide support for these predictions. Our research extends knowledge on the negative consequences of UPB for actors and organizations. [ABSTRACT FROM AUTHOR]

Two novel coordination polymers {[Cu4(H2dam-dap)4(ClO4)2]·2ClO4}n (1) and [Cu3(H2dam-dap)2(N3)2(NO3)2]n (2) have been obtained through the copper salts and 3-(3-Amino-propylimino)-butan-2-one oxime (H3dam-dap) ligand, which was synthesized by one-pot reaction in the preparation process of complexes. Single-crystal X-Ray analysis shows that complex 1 displays a cage-like 12-MC-4 metallacrown structural unit with the sides exhibiting Cu–N–O repeat units, and the cage-like structures have been linked into one 1D chain by the bridges of ClO4− anions; 2 possesses trinuclear [Cu3(H2dam-dap)2]4+ unit with three Cu ion locating in a linear arrangement, and the adjacent trinuclear units are linked into a 2D coordination polymer by bridging nitrate anions. Magnetic studies reveal that 1 displays ferromagnetic coupling between metal centres, and 2 exhibits antiferromagnetic interaction and field-induced frequency-dependent behavior. [ABSTRACT FROM AUTHOR]

This paper examines the impact of home country institutions on corporate social responsibility (CSR) of multinational enterprises from emerging markets (EM-MNEs). Taking the Belt and Road Initiative (BRI) as an example and using a sample with 2052 firm-year observations from China over the period 2008–2018, we find that the BRI exerts a positive and significant effect on overall CSR of Chinese MNEs involved in the BRI and the positive effect is stronger for Chinese state-owned MNEs. In addition, only two dimensions of CSR (Employee Relations and Products) are improved significantly under the pressure of BRI. Finally, we examine the interactive effect of home- and host- country institutions on Chinese MNEs' CSR and find the positive impact of the BRI on MNEs' CSR performance is stronger in host countries with a higher level of CSR related institutional pressure. These results provide practical suggestions for the Chinese government and MNEs to further improve CSR under the BRI, and enrich our understanding of the interactive effect between home- and host-country institutions on enhancing Chinese MNEs' reputation and promoting regional cooperation with countries along the BRI. [ABSTRACT FROM AUTHOR]

As consumers increasingly prefer "all-natural" and healthy foods, there has been increasing demand for non-toxic, residual-free, and environmentally friendly food processing techniques. Researchers and developers have shown increasing interest in innovative electrical processing techniques for the treatment of foods. Among electrotechnologies, induced electric fields (IEF) demonstrates the potential advantages to food processing. It combined with thermal effect and non-thermal effect has been explored for sterilization, modification, and extraction of agro-food materials. It is a sister electrotechnology of ohmic heating, which does not require the use of electrodes. Despite valuable contributions to the literature, there still lack of knowledge regarding the application of IEF treatment to food products. It has proven effective in inactivating microorganisms and enzymes in foods, changing biomacromolecule contents, extracting active constituents, and enhancing chemical reactions. This paper provides an overview of current application of IEFs in the treatment of foods. Issues relevant to electric field processing (e.g., basic principles, formulas) are also examined as they affect IEF techniques. Future perspectives and challenges related to technological application of IEFs are outlined in an effort to fill research gaps. IEF processing is projected to become a key technology in the food industry. [ABSTRACT FROM AUTHOR]

This paper presents an efficient cooperative multi-populations swarm intelligence algorithm based on the Harris Hawks optimization (HHO) algorithm, named CMPMO-HHO, to solve multi-/many-objective optimization problems. Specifically, this paper firstly proposes a novel cooperative multi-populations framework with dual elite selection named CMPMO/des. With four excellent strategies, namely the one-to-one correspondence framework between the optimization objectives and the subpopulations, the global archive for information exchange and cooperation among subpopulations, the logistic chaotic single-dimensional perturbation strategy, and the dual elite selection mechanism based on the fast non-dominated sorting and the reference point-based approach, CMPMO/des achieves considerably high performance on solutions convergence and diversity. Thereafter, in each subpopulation, HHO is used as the single objective optimizer for its impressive high performance. Notably, however, the proposed CMPMO/des framework can work with any other single objective optimizer without modification. We comprehensively evaluated the performance of CMPMO-HHO on 34 multi-objective and 19 many-objective benchmark problems and extensively compared it with 13 state-of-the-art multi/many-objective optimization algorithms, three variants of CMPMO-HHO, and a CMPMO/des based many-objective genetic algorithm named CMPMO-GA. The results show that by taking the advantages of the CMPMO/des framework, CMPMO-HHO achieves promising performance in solving multi/many-objective optimization problems. [ABSTRACT FROM AUTHOR]

The convolutional neural networks used widely in mineral prospectivity prediction usually perform mixed feature extraction for multichannel inputs. This results in redundant features and impacts further improvement of predictive performance. To solve this limitation, this paper utilized convolutional autoencoder networks to mine latent high-level features for each predictor variable in parallel to prevent the mixing of features and to enhance the feature mapping outcomes of each channel. Convolutional autoencoder networks, as unsupervised learning methods, can handle input images with high-dimensional features. They can train samples without differences such that the reconstructed outputs can restore inputs as accurately as possible to reduce the extraction of irrelevant feature information. Moreover, convolutional autoencoder networks focus on finding the fewest features for representing all inputs, and the extracted features express internal spatial relations at a high level. It is helpful to improve the performance of metallogenic prediction. Hence, this paper arranged these obtained features into one-dimensional vectors to establish the inputs of classifiers. Through modeling with four classifiers (logistic regression, support vector machine, artificial neural network, and random forest), we achieved different models for mineral prospectivity prediction. According to the comprehensive evaluations, the random forest model outperformed the other models. Taking the prediction of gold deposits in the Fengxian region of Southern Qinling in China as an example, the predictive capability of the proposed integrated method was shown to be effective and reliable. The predicted high-potential areas can provide significant guidance for gold deposit exploration in the study area. [ABSTRACT FROM AUTHOR]

Key message: A superior allele of wheat gene TaGL3.3-5B was identified and could be used in marker-assisted breeding in wheat. Identifying the main genes which mainly regulate the yield-associated traits can significantly increase the wheat production. In this study, gene TaGL3.3 was cloned from common wheat according to the sequence of OsPPKL3. A SNP in the 8th exon of TaGL3.3-5B, T/C in coding sequence (CDS), which resulted in an amino acid change (Val/Ala), was identified between the low 1000-kernel weight (TKW) wheat Chinese Spring and the high TKW wheat Xinong 817 (817). Subsequently, association analysis in the mini-core collection (MCC) and the recombinant inbred lines (RIL) revealed that the allele TaGL3.3-5B-C (from 817) was significantly correlated with higher TKW. The high frequency of TaGL3.3-5B-C in the Chinese modern wheat cultivars indicated that it was selected positively in wheat breeding programs. The overexpression of TaGL3.3-5B-C in Arabidopsis resulted in shorter pods and longer grains than those of wild-type counterparts. Additionally, TaGL3.3 expressed a tissue-specific pattern in wheat as revealed by qRT-PCR. We also found that 817 showed higher expression of TaGL3.3 than that in Chinese Spring (CS) during the seed development. These results demonstrate that TaGL3.3 plays an important role in the formation of seed size and weight. Allele TaGL3.3-5B-C is associated with larger and heavier grains that are beneficial to wheat yield improvement. [ABSTRACT FROM AUTHOR]

Wound infection caused by Staphylococcus aureus (S. aureus) is a great challenge which has caused significant burden and economic loss to the medical system. NZ2114, a plectasin-derived peptide, is an antibacterial agent for preventing and treating S. aureus infection, especially for methicillin-resistant S. aureus (MRSA) infection. Here, three-dimensional reticulated antimicrobial peptide (AMP) NZ2114 hydrogels were developed based on hydroxypropyl cellulose (HPC) and sodium alginate (SA); they displayed sustained and stable release properties (97.88 ± 1.79% and 91.1 ± 10.52% release rate in 72 h, respectively) and good short-term cytocompatibility and hemocompatibility. But the HPC-NZ2114 hydrogel had a smaller pore size (diameter 0.832 ± 0.420 μm vs. 3.912 ± 2.881 μm) and better mechanical properties than that of the SA-NZ2114 hydrogel. HPC/SA-NZ2114 hydrogels possess efficient antimicrobial activity in vitro and in vivo. In a full-thickness skin defect model, the wound closure of the 1.024 mg/g HPC-NZ2114 hydrogel group was superior to those of the SA-NZ2114 hydrogel and antibiotic groups on day 7. The HPC-NZ2114 hydrogel accelerated wound healing by reducing inflammation and promoting the production of vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and angiogenesis (CD31) through histological and immunohistochemistry evaluation. These data indicated that the HPC-NZ2114 hydrogel is an excellent candidate for S. aureus infection wound dressing. Key points: •NZ2114 hydrogels showed potential in vitro bactericidal activity against S. aureus •NZ2114 hydrogels could release continuously for 72 h and had good biocompatibility •NZ2114 hydrogels could effectively promote S. aureus-infected wound healing [ABSTRACT FROM AUTHOR]

Bark is an essential component of tree branches, yet its role in controlling branch-leached dissolved organic matter (DOM) characteristics remains unknown in forests. Here, we collected branches (about 1.5 cm in diameter) of two evergreen coniferous trees, two deciduous broadleaf trees, and three evergreen broadleaf trees from a subtropical forest in southern China, and subsequently used a bark removal experiment to determine the effects of bark on branch-derived DOM quantity and bioavailability. Regardless of tree type, the presence of bark reduced tree branch-leached dissolved organic carbon (DOC), dissolved total nitrogen (DTN), and dissolved total phosphorus (DTP) productions. Moreover, DOC, DTN, and DTP productions leached from the branches containing bark were always much lower than the expected values summed from barks and the branches without bark. The presence of bark increased DOM aromaticity in the broadleaf tree branch leachates but reduced DOM aromaticity in the coniferous tree branch leachates. During 42 days of incubation, the presence of bark decreased broadleaf tree branch-leached DOM bioavailability and the relative increments of aromaticity, whereas the opposite trends were observed for the coniferous tree branch-leached DOM. Tree branch-derived DOM bioavailability correlated negatively with SUVA254 values, but exhibited no relationship with either DOC:DTN ratio or DOC:DTP ratio. These observations highlight that tree bark can prevent DOM leaching from branches and regulate branch-leached DOM bioavailability via its effect on DOM aromaticity in subtropical forests. [ABSTRACT FROM AUTHOR]

High-throughput sequencing of the 16S ribosomal RNA (16S rRNA) gene has been successfully applied to explore the microbial structure and dynamics in various environments. The distinctive microbial communities in oceanic trench sediments are expected because of the extremely high pressure and V-shape topology that caused the isolation from the other marine sediments. However, they have only been primarily targeted using 'universal' primers that provide variable performances for different environments. It is necessary to design specific primers to improve the detection resolution of unique microbial groups in oceanic trenches. Here, we designed one pair of bacterial and two pairs of archaeal specific primers based on 16S rRNA gene full-length sequences that truly come from trench sediment and tested their performances in 30 oceanic trench sediment samples. An in silico analysis showed that the V3–V4 hypervariable region was the most informative and representative for oceanic trench microbial groups. Compared with the 'universal' primers, 46 bacterial families were only detected by newly designed primer B344F/B749R, and eight archaeal families were only detected by the newly designed primer A306F/A713R which covered the one or two orders of magnitude more ASVs (amplicon sequence variants) (1,470,216) in the tested total 30 samples. Moreover, A306F/A713R had the largest number of observed ASVs suggesting its better performance in discovering more archaeal species which were easily ignored in universal primer-based experiments for oceanic trench sediments. The novel primers designed in this research could be a better option to access the unique microbial communities in extreme oceanic trench sediments. Key points • Defining V3–V4 as the most adequate hypervariable region for archaea and bacteria from oceanic trench sediments. • Three sets of bacterial and archaeal primers appear validity and advantage in revealing the real trench microbial communities. • The novel primers provide a better option to specifically detect the unique microbial communities in extreme oceanic trench sediments. [ABSTRACT FROM AUTHOR]