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Self-healing, stretchable, and moldable hydrogels have a great potential application in tissue engineering and soft robotics. Despite great success in reported hydrogels, it is still a great challenge to construct the moldable hydrogels with an ultrafast self-healing performance. Herein, the composite hydrogels (PBLH) with ultrafast self-healing, stretchable, and moldable properties were successfully constructed by poly (vinyl alcohol) (PVA), borate (B), ε-poly-l-lysine (EPL), and hyaluronic acid (HA) based on an efficient one-pot method. Fourier transform infrared spectroscopy, X-ray diffraction, and rheological measurements confirmed the formation of a dynamic network among PVA, B, EPL, and HA through the cross-linking of dynamic borate bonds, electrostatic interaction, and hydrogen bonding. Having fabricated the dynamic network structure, the damage gap of the composite hydrogels can heal within 1 min, presenting an excellent self-healing ability. Simultaneously, the composite hydrogels can be molded into various shapes, and the length of the composite hydrogels can be stretched to 15 times their original length. In addition, the composite hydrogels exhibited an excellent antibacterial property against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ). Our results illustrated that the composite hydrogels not only retain the advantages of traditional hydrogels but also possess ultrafast self-healing, outstanding stretchable and antibacterial properties, presenting a prospective candidate for constructing biomedical materials.

Alkaline water is toxic to cultured aquatic animals that frequently live in pH-neutral freshwater. Overfishing and habitat destruction have contributed to the decline in the wild sturgeon population; consequently, the domestic hybrid sturgeon has become an increasingly important commercial species in China. Hybrid sturgeons are widely cultured in alkaline water, but little is known about the effects of alkalinity stress on hybrid sturgeon liver tissues. We exposed hybrid sturgeons to four alkaline concentrations (3.14 ± 0.02 mmol/L, 7.57 ± 0.08 mmol/L, 11.78 ± 0.24 mmol/L and 15.46 ± 0.48 mmol/L). Histopathology, biochemical index assessment, gene expression level detection and metabolomics analysis were used to investigate the negative effects on liver functions following exposure to NaHCO 3 . Livers exposed to alkaline stress exhibited severe tissue injury and clear apoptotic characteristics. With increased exposure concentrations, the hepatic superoxide dismutase, catalase, glutathione peroxidase and alkaline phosphatase activities significantly decreased in a dose-dependent manner. NaHCO 3 exposure up-regulated the transcriptional levels of apoptosis/ferroptosis-related genes in livers. Similarly, the expression trends of interleukin-1β and heat shock protein genes also increased in high-alkalinity environments. However, the expression levels of complement protein 3 significantly decreased ( p < 0.05). Hepatic untargeted metabolomics revealed the alteration conditions of various metabolites associated with the antioxidant response, the ferroptosis process and amino acid metabolism (such as beta-alanine metabolism; alanine, aspartate and glutamate metabolism; and glycine, serine and threonine metabolism). These data provided evidence that NaHCO 3 impaired immune functions and the integrity of hybrid sturgeon liver tissues by mediating oxidative-stress-mediated apoptosis and ferroptosis. Our results shed light on the breeding welfare of domestic hybrid sturgeons and promote the economic development of fisheries in China.

This paper investigates the problem of exponential synchronization control for complex dynamical systems (CDNs) with input saturation. Considering the effects of transmission delay, a memory sampled-data controller is designed. A modified two-sided looped functional is constructed that takes into account the entire sampling period, which includes both current state information and delayed state information. This functional only needs to be positive definite at the sampling instants. Sufficient criteria and the controller design method are provided to ensure the exponential synchronization of CDNs with input saturation under the influence of transmission delay, as well as the estimation of the basin of attraction. Additionally, an optimization algorithm for enlarging the region of attraction is proposed. Finally, a numerical example is presented to verify the effectiveness of the conclusion.

Gene-editing technology, specifically the CRISPR-Cas13a system, has shown promise in breeding plants resistant to RNA viruses. This system targets RNA and, theoretically, can also combat RNA-based viroids. To test this, the CRISPR-Cas13a system was introduced into tomato plants via transient expression and into Nicotiana benthamiana through transgenic methods, using CRISPR RNAs (crRNAs) targeting the conserved regions of both sense and antisense genomes of potato spindle tuber viroid (PSTVd). In tomato plants, the expression of CRISPR-Cas13a and crRNAs substantially reduced PSTVd accumulation and alleviated disease symptoms. In transgenic N. benthamiana plants, the PSTVd levels were lower as compared to wild-type plants. Several effective crRNAs targeting the PSTVd genomic RNA were also identified. These results demonstrate that the CRISPR-Cas13a system can effectively target and combat viroid RNAs, despite their compact structures.

The mechanobiological response mechanism of the fenestrae of liver sinusoidal endothelial cells (LSECs) to the physical stiffness of the extracellular matrix (ECM) remains unclear. We investigated how the mechanical properties of their substrates affect the LSECs' fenestrae by the nitric oxide (NO)-dependent pathway and how they relate to the progression of hepatic sinus capillarization during liver fibrosis. We detected different stiffnesses of ECM in the progress of liver fibrosis (LF) and developed polyacrylamide hydrogel (PAM) substrates to simulate them. Softer stiffness substrates contributed to LSECs maintaining fenestrae phenotype in vitro. The stiffness of liver fibrosis tissue could be reversed in vivo via treatment with anti-ECM deposition drugs. Similarly, the capillarization of LSECs could be reversed by decreasing the ECM stiffness. Our results also indicate that the NO-dependent pathway plays a key regulatory role in the capillarization of ECM-LSECs. Our study reveals ECM-induced mechanotransduction of capillarized LSECs through a NO-dependent pathway via a previously unrevealed mechanotransduction mechanism. The elucidation of this mechanism may offer precise biomechanics-specific intervention strategies targeting liver fibrosis progression.

Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol-maleimide "click" chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine-BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants., Competing Interests: The authors declare no conflicts of interest.

For the tribological properties of nanoparticle-modified PTFE, a more comprehensive study has been conducted, but there is still some room for research on tribology behavior, tribofilm formation and structure evolution of polytetrafluoroethylene (PTFE) filled with α-Al 2 O 3 and SiO 2 nanoparticles during sliding against steel counterparts under different loads. At the same time, it establishes the linkage and mechanism between the maintenance of mechanical strength and the tribological application of polymers in service and provides corresponding scientific data and theoretical guidance for the long-lasting application of polymer lubrication materials. It is found that both composites exhibit good wear resistance across the pressure of 1 MPa to 10 MPa, with the α-Al 2 O 3 /PTFE composite demonstrating better performance stability compared to the SiO 2 /PTFE composite. The high wear resistance is attributed to the formation of tribofilms at the friction interface. For the α-Al 2 O 3 /PTFE, an island-like tribofilm is formed with a thickness ranging from 100 to 200 nm, while the tribofilm of the SiO 2 /PTFE composite is thinner, measuring approximately 50 to 100 nm, and manifests a striped pattern. The chemical composition, both at the surface and subsurface levels, as well as the morphology of the tribofilms, were studied using FTIR spectrometry, X-ray photoelectron spectroscopy (XPS), and FIB-TEM. It is found that the difference in thickness and microstructure of the tribofilms for the two composites is mainly due to the tribochemistry of the nanoparticles. The α-Al 2 O 3 nanoparticle plays a "cohesion" role during the formation of the tribofilm, which facilitates the formation of a thicker, more uniform, and stronger adhered tribofilm on the metallic counterpart, making it more robust against higher shear stress.

Concurrently achieving high growth rate and high quality in single-crystal diamonds (SCDs) is significantly challenging. The growth rate of SCDs synthesized by microwave plasma chemical vapor deposition (MPCVD) was enhanced by introducing N 2 into the typical CH 4 -H 2 gas mixtures. The impact of nitrogen vacancy (NV) center concentration on growth rate, surface morphology, and lattice binding structure was investigated. The SCDs were characterized through Raman spectroscopy, photoluminescence (PL) spectroscopy, and X-ray photoelectron spectroscopy. It was found that the saturation growth rate was increased up to 45 μm/h by incorporating 0.8-1.2% N 2 into the gas atmosphere, which is 4.5 times higher than the case without nitrogen addition. Nitrogen addition altered the growth mode from step-flow to bidimensional nucleation, leading to clustered steps and a rough surface morphology, followed by macroscopically pyramidal hillock formation. The elevation of nitrogen content results in a simultaneous escalation of internal stress and defects. XPS analysis confirmed chemical bonding between nitrogen and carbon, as well as non-diamond carbon phase formation at 0.8% of nitrogen doping. Furthermore, the emission intensity of NV-related defects from PL spectra changed synchronously with N 2 concentrations (0-1.5%) during diamond growth, indicating that the formation of NV centers activated the diamond lattice and facilitated nitrogen incorporation into it, thereby accelerating chemical reaction rates for achieving high-growth-rate SCDs.

Shut-in after fracturing is generally adopted for wells in shale oil reservoirs, and imbibition occurring in matrix nanopores has been proven as an effective way to improve recovery. In this research, a molecular dynamics (MD) simulation was used to investigate the effects of wettability and pressure on nanopore imbibition during shut-in for a typical shale reservoir, Jimsar. The results indicate that the microscopic advancement mechanism of the imbibition front is the competitive adsorption between "interfacial water molecules" at the imbibition front and "adsorbed oil molecules" on the pore wall. The essence of spontaneous imbibition involves the adsorption and aggregation of water molecules onto the hydroxyl groups on the pore wall. The flow characteristics of shale oil suggest that the overall push of the injected water to the oil phase is the main reason for the displacement of adsorbed oil molecules. Thus, shale oil, especially the heavy hydrocarbon component in the adsorbed layer, tends to slip on the walls. However, the weak slip ability of heavy components on the wall surface is an important reason that restricts the displacement efficiency of shale oil during spontaneous imbibition. The effectiveness of spontaneous imbibition is strongly dependent on the hydrophilicity of the matrix pore's wall. The better hydrophilicity of the matrix pore wall facilitates higher levels of adsorption and accumulation of water molecules on the pore wall and requires less time for "interfacial water molecules" to compete with adsorbed oil molecules. During the forced imbibition process, the pressure difference acts on both the bulk oil and the boundary adsorption oil, but mainly on the bulk oil, which leads to the occurrence of wetting hysteresis. Meanwhile, shale oil still existing in the pore always maintains a good, stratified adsorption structure. Because of the wetting hysteresis phenomenon, as the pressure difference increases, the imbibition effect gradually increases, but the actual capillary pressure gradually decreases and there is a loss in the imbibition velocity relative to the theoretical value. Simultaneously, the decline in hydrophilicity further weakens the synergistic effect on the imbibition of the pressure difference because of the more pronounced wetting hysteresis. Thus, selecting an appropriate well pressure enables cost savings and maximizes the utilization of the formation's natural power for enhanced oil recovery (EOR).

Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients' medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.

Retinal ischemia, after cerebral ischemia, is an easily overlooked pathophysiological problem in which inflammation is considered to play an important role. Pyroptosis is a kind of cell death pattern accompanied by inflammation. Homer scaffold protein 1 (Homer1) has anti-inflammation properties and protects against ischemic injury. However, little is known about pyroptosis following middle cerebral artery occlusion (MCAO)-induced retinal ischemia and the regulatory mechanisms involved by Homer1 for the development of pyroptosis. In the present study, retinal ischemic injury was induced in mice by permanent MCAO in vivo, and retinal ganglion cells (RGCs) were subjected to Oxygen and Glucose Deprivation (OGD) to establish an in vitro model. It was shown that TXNIP/NLRP3-mediated pyroptosis was located predominantly in RGCs, which gradually increased after retinal ischemia and peaked at 24 h after retinal ischemia. Interestingly, the RGCs pyroptosis occurred not only in the cell body but also in the axon. Notably, the occurrence of pyroptosis coincided with the change of Homer1 expression in the retina after retinal ischemia and Homer1 also co-localized with RGCs. It was demonstrated that overexpression of Homer1 not only alleviated RGCs pyroptosis and inhibited the release of pro-inflammatory factors but also led to the increase in phosphorylation of AMPK, inhibition of ER stress, and preservation of visual function after retinal ischemia. In conclusion, it was suggested that Homer1 may protect against MCAO-induced retinal ischemia and RGCs pyroptosis by inhibiting endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation after MCAO-induced retinal ischemia.

Gut microbiota dysbiosis has been reported as a risk factor in the development of type 2 diabetes mellitus (T2DM). Polysaccharides from Phellinus igniarius ( P. igniarius ) possess various properties that help manage metabolic diseases; however, their underlying mechanism of action remains unclear. Therefore, in this study, we aimed to evaluate the effect of P. igniarius polysaccharides (SH-P) on improving hyperglycemia in mice with T2DM and clarified its association with the modulation of gut microbiota and their metabolites using 16S rDNA sequencing and liquid chromatography-mass spectrometry. Fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. SH-P supplementation alleviated hyperglycemia symptoms in T2DM mice, ameliorated gut dysbiosis, and significantly increased the abundance of Lactobacillus in the gut. Pathway enrichment analysis indicated that SH-P treatment altered metabolic pathways associated with the occurrence and development of diabetes. Spearman's correlation analysis revealed that changes in the dominant bacterial genera were significantly correlated with metabolite levels closely associated with hyperglycemia. Additionally, FMT significantly improved insulin sensitivity and antioxidative capacity and reduced inflammation and tissue injuries, indicating improved glucose homeostasis. These results indicate that the ameliorative effects of SH-P on hyperglycemia are associated with the modulation of gut microbiota composition and its metabolites.

Tibetan sheep are already well adapted to cold season nutrient stress on the Tibetan Plateau. Rumen, an important nutrient for metabolism and as an absorption organ in ruminants, plays a vital role in the cold stress adaptations of Tibetan sheep. Ruminal microbiota also plays an indispensable role in rumen function. In this study, combined multiomics data were utilized to comprehensively analyze the interaction mechanism between rumen epithelial miRNAs and microbiota and their metabolites in Tibetan sheep under nutrient stress in the cold season. A total of 949 miRNAs were identified in the rumen epithelium of both cold and warm seasons. A total of 62 differentially expressed (DE) miRNAs were screened using FC > 1.5 and p value < 0.01, and a total of 20,206 targeted genes were predicted by DE miRNAs. KEGG enrichment analysis revealed that DE miRNA-targeted genes were mainly enriched in axon guidance(ko04360), tight junction(ko04530), inflammatory mediator regulation of TRP channels(ko04750) and metabolism-related pathways. Correlation analysis revealed that rumen microbiota, rumen VFAs and DE miRNAs were all correlated. Further study revealed that the targeted genes of cold and warm season rumen epithelial DE miRNAs were coenriched with differential metabolites of microbiota in glycerophospholipid metabolism (ko00564), apoptosis (ko04210), inflammatory mediator regulation of TRP channels (ko04750), small cell lung cancer (ko05222), and choline metabolism in cancer (ko05231) pathways. There are several interactions between Tibetan sheep rumen epithelial miRNAs, rumen microbiota, and microbial metabolites, mainly through maintaining rumen epithelial barrier function and host homeostasis of choline and cholesterol, improving host immunity, and promoting energy metabolism pathways, thus enabling Tibetan sheep to effectively respond to cold season nutrient stress. The results also suggest that rumen microbiota have coevolved with their hosts to improve the adaptive capacity of Tibetan sheep to cold season nutrient stress, providing a new perspective for the study of cold season nutritional stress adaptation in Tibetan sheep.

A composite film that features bismuth-antimony alloy nanoparticles uniformly embedded in a 3D hierarchical porous carbon skeleton is synthesized by the polyacrylonitrile-spreading method. The dissolved polystyrene is used as a soft template. The average diameter of the bismuth-antimony alloy nanoparticles is ~34.5 nm. The content of the Bi-Sb alloy has an impact on the electrochemical performance of the composite film. When the content of the bismuth-antimony alloy is 45.27%, the reversible capacity and cycling stability of the composite film are the best. Importantly, the composite film outperforms the bismuth-antimony alloy nanoparticles embedded in dense carbon film and the cube carbon nanobox in terms of specific capacity, cycling stability, and rate capability. The composite film can provide a discharge capacity of 322 mAh g -1 after 500 cycles at 0.5 A g -1 , 292 mAh g -1 after 500 cycles at 1 A g -1 , and 185 mAh g -1 after 2000 cycles at 10 A g -1 . The carbon film prepared by the spreading method presents a unique integrated composite structure that significantly improves the structural stability and electronic conductivity of Bi-Sb alloy nanoparticles. The 3D hierarchical porous carbon skeleton structure further enhances electrolyte accessibility, promotes Na + transport, increases reaction kinetics, and buffers internal stress.

Oxidative-stress-induced apoptosis of granulosa cells is considered to be a main driver of follicular atresia. Increasing evidence suggests a protective effect of melatonin against oxidative damage but the mechanism remains unclear. The aim of this study is to investigate the effects of melatonin on mitophagy and apoptosis of bovine ovarian granulosa cells under oxidative stress, and to clarify the mechanism. Our results indicate that melatonin inhibited H 2 O 2 -induced apoptosis and mitochondrial injury of bovine ovarian granulosa cells, as revealed by decreased apoptosis rate, reactive oxygen species (ROS) levels, Ca 2+ concentration, and cytochrome C release and increased mitochondrial membrane potential (ΔΨm). Simultaneously, melatonin promoted mitophagy of bovine ovarian granulosa cells through increasing the expression of PTEN-induced putative kinase 1 (PINK1), PARKIN, BECLIN1, and LC3II/LC3I; decreasing the expression of sequestosome 1 (SQSMT1); and promoting mitophagosome and lysosome fusion. After treatment with a mitophagy inhibitor CsA, we found that melatonin alleviated apoptosis and mitochondrial injury through promoting mitophagy in bovine ovarian granulosa cells. Furthermore, melatonin promoted the expression of silent information regulator 1 (SIRT1) and decreased the expression level of forkhead transcription factors class O (type1) (FoxO1). By treatment with an SIRT1 inhibitor EX527 or FoxO1 overexpression, the promotion of melatonin on mitophagy as well as the inhibition on mitochondrial injury and apoptosis were reversed in bovine ovarian granulosa cells. In conclusion, our results suggest that melatonin could promote mitophagy to attenuate oxidative-stress-induced apoptosis and mitochondrial injury of bovine ovarian granulosa cells via the SIRT1/FoxO1 signaling pathway.

Mutations in HOXA1 can lead to diseases such as Bosley-Salih-Alorainy syndrome, involving severe cardiovascular malformations. However, the role of HOXA1 in cardiac morphogenesis remains unclear. hoxa1a is a homologous gene to human HOXA1 in zebrafish. We used CRISPR to make hoxa1a -null zebrafish that exhibited multiple heart malformations. In situ hybridization and sections revealed the morphological changes in mutants: enlarged ventricle with thickened myocardium and increased trabeculae, intensified OFT and inadequate heart looping, with electrocardiography supporting these pathological changes. High-speed photography captured cardiac pumping and revealed a significant decrease in cardiac output. Furthermore, lacking hoxa1a led to posterior body abnormality that affected movement ability, corresponding with the motor development delay in patients. Upregulation of hox paralogues in hoxa1a -null fish implied a compensatory mechanism between hox genes. Accordingly, we successfully constructed a hoxa1a -null model with a cardiac disease pattern which occurred in human HOXA1 -associated heart malformation. The study of hoxa1a in zebrafish can further promote the understanding of hox genes and related diseases.

Protein kinases of the MAPK cascade family (MAPKKK-MAPKK-MAPK) play an essential role in plant stress response and hormone signal transduction. However, their role in the cold hardiness of Prunus mume (Mei), a class of ornamental woody plant, remains unclear. In this study, we use bioinformatic approaches to assess and analyze two related protein kinase families, namely, MAP kinases (MPKs) and MAPK kinases (MKKs), in wild P. mume and its variety P. mume var. tortuosa . We identify 11 PmMPK and 7 PmMKK genes in the former species and 12 PmvMPK and 7 PmvMKK genes in the latter species, and we investigate whether and how these gene families contribute to cold stress responses. Members of the MPK and MKK gene families located on seven and four chromosomes of both species are free of tandem duplication. Four, three, and one segment duplication events are exhibited in PmMPK , PmvMPK, and PmMKK , respectively, suggesting that segment duplications play an essential role in the expansion and evolution of P. mume and its gene variety. Moreover, synteny analysis suggests that most MPK and MKK genes have similar origins and involved similar evolutionary processes in P. mume and its variety. A cis-acting regulatory element analysis shows that MPK and MKK genes may function in P. mume and its variety's development, modulating processes such as light response, anaerobic induction, and abscisic acid response as well as responses to a variety of stresses, such as low temperature and drought. Most PmMPKs and PmMKKs exhibited tissue-specifific expression patterns, as well as time-specific expression patterns that protect them through cold. In a low-temperature treatment experiment with the cold-tolerant cultivar P. mume 'Songchun' and the cold-sensitive cultivar 'Lve', we find that almost all PmMPK and PmMKK genes, especially PmMPK3/5/6/20 and PmMKK2/3/6 , dramatically respond to cold stress as treatment duration increases. This study introduces the possibility that these family members contribute to P. mume 's cold stress response. Further investigation is warranted to understand the mechanistic functions of MAPK and MAPKK proteins in P. mume development and response to cold stress.

The molecular weight of lignin extracted from lignocellulosic biomass is an important factor in determining its valorization in industrial processes. Herein, this work aims to explore the extraction of high molecular weight and bioactive lignin from water chestnut shells under mild conditions. Five kinds of deep eutectic solvents were prepared and applied to isolate lignin from water chestnut shells. The extracted lignin was further characterized with element analysis, gel permeation chromatography, and Ultraviolet-visible and Fourier-transform infrared spectroscopy. The distribution of pyrolysis products was identified and quantified with thermogravimetric analysis-Fourier-transform infrared spectroscopy and pyrolysis-gas chromatograph-mass spectrometry. The results showed that choline chloride/ethylene glycol/ p -toluenesulfonic acid (1:1.8:0.2 molar ratio) exhibited the highest fractionation efficiency for lignin (84.17% yield) at 100 °C for 2 h. Simultaneously, the lignin showed high purity (90.4%), high relative molecular weight (37,077 g/mol), and excellent uniformity. Furthermore, the aromatic ring structure of lignin remained intact, consisting mainly of p -hydroxyphenyl, syringl, and guaiacyl subunits. The lignin generated a large number of volatile organic compounds during the depolymerization process, mainly composed of ketones, phenols, syringols, guaiacols, esters, and aromatic compounds. Finally, the antioxidant activity of the lignin sample was evaluated with the 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay; the lignin from water chestnut shells showed excellent antioxidant activity. These findings confirm that lignin from water chestnut shells has a broad application prospect in valuable chemicals, biofuels and bio-functional materials.

Gadopentetic acid and gadodiamide are paramagnetic gadolinium-based contrast agents (GBCAs) that are routinely used for dynamic contrast-enhanced magnetic resonance imaging (MRI) to monitor disease progression in cancer patients. However, growing evidence indicates that repeated administration of GBCAs may lead to gadolinium (III) cation accumulation in the cortical bone tissue, skin, basal ganglia, and cerebellum, potentially leading to a subsequent slow long-term discharge of Gd 3+ . Gd 3+ is a known activator of the TRPC5 channel that is implicated in breast cancer's resistance to chemotherapy. Herein, we found that gadopentetic acid (Gd-DTPA, 1 mM) potentiated the inward and outward currents through TRPC5 channels, which were exogenously expressed in HEK293 cells. Gd-DTPA (1 mM) also activated the Gd 3+ -sensitive R593A mutant of TRPC5, which exhibits a reduced sensitivity to GPCR-G q/11 -PLC dependent gating. Conversely, Gd-DTPA had no effect on TRPC5-E543Q, a Gd 3+ insensitive TRPC5 mutant. Long-term treatment (28 days) of human breast cancer cells (MCF-7 and SK-BR-3) and adriamycin-resistant MCF-7 cells (MCF-7/ADM) with Gd-DTPA (1 mM) or gadodiamide (GDD, 1 mM) did not affect the IC 50 values of ADM. However, treatment with Gd-DTPA or GDD significantly increased TRPC5 expression and decreased the accumulation of ADM in the nuclei of MCF-7 and SK-BR-3 cells, promoting the survival of these two breast cancer cells in the presence of ADM. The antagonist of TRPC5, AC1903 (1 μM), increased ADM nuclear accumulation induced by Gd-DTPA-treatment. These data indicate that prolonged GBCA treatment may lead to increased breast cancer cell survival owing to the upregulation of TRPC5 expression and the increased ADM resistance. We propose that while focusing on providing medical care of the best personalized quality in the clinic, excessive administration of GBCAs should be avoided in patients with metastatic breast cancer to reduce the risk of promoting breast cancer cell drug resistance.

The performance of an active-quenching single-photon avalanche diode (SPAD) array that is based on the tri-state gates of a field programmable gate array (FPGA) is presented. The array is implemented by stacking a bare 4 × 4 N-on-P SPAD array on a bare FPGA die, and the electrodes of the SPAD pixels and the I/O ports of the FPGA are connected through wire bonding within the same package. The active quenching action on each SPAD pixel is performed by using the properties of the tri-state gates of the FPGA. Digital signal processing, such as pulse counters, data encoders, and command interactions, is also performed by using the same FPGA. The breakdown voltage of the SPAD pixels, with an active area of 60 μm × 60 μm, is 47.2-48.0 V. When the device is reverse biased at a voltage of ~50.4 V, a response delay of ~50 ns, a dead time of 157 ns, a dark count rate of 2.44 kHz, and an afterpulsing probability of 6.9% are obtained. Its peak photon detection probability (PDP) reaches 17.0% at a peak wavelength of 760 nm and remains above 10% at 900 nm. This hybrid integrated SPAD array is reconfigurable and cost effective.

Farnesoid X receptor (FXR) is a nuclear receptor known to play protective roles in anti-hepatocarcinogenesis and regulation of the basal metabolism of glucose, lipids, and bile acids. FXR expression is low or absent in HBV-associated hepatocarcinogenesis. Full-length HBx and HBx C-terminal truncation are frequently found in clinical HCC samples and play distinct roles in hepatocarcinogenesis by interacting with FXR or FXR signaling. However, the impact of C-terminal truncated HBx on the progression of hepatocarcinogenesis in the absence of FXR is unclear. In this study, we found that one known FXR binding protein, a C-terminal truncated X protein (HBx C40) enhanced obviously and promoted tumor cell proliferation and migration by altering cell cycle distribution and inducing apoptosis in the absence of FXR. HBx C40 enhanced the growth of FXR-deficient tumors in vivo. In addition, RNA-sequencing analysis showed that HBx C40 overexpression could affect energy metabolism. Overexpressed HSPB8 aggravated the metabolic reprogramming induced by down-regulating glucose metabolism-associated hexokinase 2 genes in HBx C40-induced hepatocarcinogenesis. Overall, our study suggests that C-terminal truncated HBx C40 synergizes with FXR deficiency by altering cell cycle distribution as well as disturbing glucose metabolism to promote HCC development.

In the process of China's economic transformation, enterprises urgently need to use green innovation networks to realize corporate sustainability. Based on resource-based theory, this study explores the internal mechanism and boundary conditions of green innovation network embeddedness that affect corporate environmental responsibility. This paper conducts an empirical study based on panel data of listed companies engaged in green innovation in China from 2010 to 2020. Drawing on network embeddedness theory and resource-based theory, we found that relational and structural embeddedness influenced green reputation, which affected corporate environmental responsibility. We also identified the importance of ethical leadership and examined its role in moderating the effect of green innovation network embeddedness. A further investigation revealed that the impact of network embeddedness on corporate environmental responsibility was particularly pronounced in the samples of enterprises with high-level political ties, loose financing restrictions, and nonstate ownership. Our findings highlight the advantages of embedded green innovation networks and offer theoretical references and recommendations for enterprises considering network participation. Enterprises should attach great importance to the network embedding strategy of green innovation for corporate environmental responsibility and actively integrate the concept of green development into network relationship embedding and network structure embedding. Moreover, the relevant government department should provide necessary environment incentive policies according to the enterprise's development needs, especially for the enterprises with low-level political ties, high financing restrictions, and state ownership.

Using waste clay brick powder (RBP) to partially replace cement in the preparation of concrete, is one way to recycle construction waste. In order to investigate the physical and mechanical properties and volume stability of recycled micropowder ultra-high-performance concrete (UHPC), the basic mechanical and shrinkage properties of recycled micropowder UHPC were studied at replacement rates of 10%, 20%, 30%, 40% and 50%. The results show that: (1) When the activated recycled brick powder is used to replace the cement, the compressive strength, flexural strength and splitting tensile strength of the UHPC initially increase and then decrease with the increase in the substitution rate. When the substitution rate is 10%, the 28 d compressive strength, flexural strength and splitting tensile strength of the UHPC are the highest; (2) Replacing cement with recycled brick powder can reduce the autogenous shrinkage of the UHPC, and the autogenous shrinkage rate of the UHPC decreases with the increase in the brick powder replacement rate. The drying shrinkage of the UHPC can be reduced by replacing cement with recycled brick powder. The drying shrinkage of the UHPC initially decreases, and then increases, with the increase in the replacement rate of brick powder. When the replacement rate of the brick powder was 30%, the drying shrinkage of the UHPC was the least, and this was 49.7% lower than that in the benchmark group. The prediction models of autogenous shrinkage and drying shrinkage are in good agreement with the experimental results, which can be used to predict the shrinkage development of recycled brick powder UHPC.

Purpose: This study aims to investigate the impact of aggregation methods used for the generation of texture features on their robustness of nasopharyngeal carcinoma (NPC) based on 18 F-FDG PET/CT images., Methods: 128 NPC patients were enrolled and 95 texture features were extracted for each patient including six feature families under different aggregation methods. For GLCM and GLRLM features, six aggregation methods were considered. For GLSZM, GLDZM, NGTDM and NGLDM features, three aggregation methods were considered. The robustness of the features affected by aggregation methods was assessed by the pair-wise intra-class correlation coefficient (ICC). Furthermore, the effects of discretization and partial volume correction (PVC) on the percent of ICC categories of all texture features were evaluated by overall ICC instead of the pair-wise ICC., Results: There were 12 features with excellent pair-wise ICCs varying aggregation methods, namely joint average, sum average, autocorrelation, long run emphasis, high grey level run emphasis, short run high grey level emphasis, long run high grey level emphasis, run length variance, SZM high grey level emphasis, DZM high grey level emphasis, high grey level count emphasis and dependence count percentage. For GLCM and GLRLM features, 19/25 and 14/16 features showed excellent pair-wise ICCs varying aggregation methods (averaged and merged) on the same dimensional features (2D, 2.5D or 3D). Different discretization levels and partial volume corrections lead to consistent robustness of textural features affected by aggregation methods., Conclusion: Different dimensional features with the same aggregation methods showed worse robustness compared with the same dimensional features with different aggregation methods. Different discretization levels and PVC algorithms had a negligible effect on the percent of ICC categories of all texture features.

The flame-retardant polyamide 66 composites (FR-PA66) were prepared by in situ loading of amino-functionalized polyphosphazene microspheres (HCNP), which were synthesized in the laboratory and confirmed by a Fourier transform infrared spectrometer (FTIR), scanning electron microscope (SEM), and transmission electron microscope (TEM). The thermal stabilities and flame retardancy of FR-PA66 were measured using thermogravimetric analysis (TGA), a thermogravimetric infrared instrument (TG-IR), the limiting oxygen index (LOI), the horizontal and vertical combustion method (UL-94), and a cone calorimeter. The results illustrate that the volatile matter of FR-PA66 mainly contains carbon dioxide, methane 4 , and water vapor under heating, accompanied by the char residue raising to 14.1 wt% at 600 °C and the value of the LOI and UL-94 rating reaching 30% and V-0, respectively. Moreover, the addition of HCNP decreases the peak of the heat release rate (pHRR), total heat release (THR), mass loss (ML), and total smoke release (TSR) of FR-PA66 to 373.7 kW/m 2 , 106.7 MJ/m 2 , 92.5 wt%, and 944.8 m 2 /m 2 , respectively, verifying a significant improvement in the flame retardancy of PA66.

The current fertilizer recommendations for melon plantation have many limitations and exhibit deficiencies regarding future development. Therefore, in this study, the optimal quantities of fertilizer, in terms of the effects of single factors and interaction effects, are studied. There were significant interaction effects between N and P, N and K, P and K; the contents of soluble protein, vitamin C (Vc), and soluble sugar in melon could be improved using the optimal fertilization ratios. The optimal ratio of N:P:K was 2.33:1:3.85, with the amounts of N, P 2 O 5 , and K 2 O, respectively, being 157.5, 67.58, and 260.38 kg/hm 2 , yielding 8.73 g/kg of soluble protein in melon. The optimal ratio of N:P:K was 2.03:1:3.36, with amounts of N, P 2 O 5 , and K 2 O being 157.50, 77.40, and 260.38 kg/hm 2 , respectively, yielding 25.32 g/kg Vc content in melon. Finally, the optimal ratio of N:P:K was 1.53:1:3.36, with the amounts of N, P 2 O 5 , and K 2 O being 118.07, 77.40, respectively, and 260.38 kg/hm 2 , yielding 13.34% soluble sugar content in melon.

The GRAS gene family is one of the most important families of transcriptional factors that have diverse functions in plant growth and developmental processes including axillary meristem patterning, signal-transduction, cell maintenance, phytohormone and light signaling. Despite their importance, the function of GRAS genes in pitaya fruit ( Selenicereus undatus L.) remains unknown. Here, 45 members of the HuGRAS gene family were identified in the pitaya genome, which was distributed on 11 chromosomes. All 45 members of HuGRAS were grouped into nine subfamilies using phylogenetic analysis with six other species: maize, rice, soybeans, tomatoes, Medicago truncatula and Arabidopsis. Among the 45 genes, 12 genes were selected from RNA-Seq data due to their higher expression in different plant tissues of pitaya. In order to verify the RNA-Seq data, these 12 HuGRAS genes were subjected for qRT-PCR validation. Nine HuGRAS genes exhibited higher relative expression in different tissues of the plant. These nine genes which were categorized into six subfamilies inlcuding DELLA ( HuGRAS-1 ), SCL-3 ( HuGRAS-7 ), PAT1 ( HuGRAS-34 , HuGRAS-35 , HuGRAS-41 ), HAM ( HuGRAS-37 ), SCR ( HuGRAS-12 ) and LISCL ( HuGRAS-18 , HuGRAS-25 ) might regulate growth and development in the pitaya plant. The results of the present study provide valuable information to improve tropical pitaya through a molecular and conventional breeding program.

Reduced imine cage (RCC3) was covalently bonded to the surface of silica spheres, and then the secondary amine group of the molecular cage was embedded in non-polar C10 for modification to prepare a novel RCC3-C10@silica HPLC stationary phase with multiple separation functions. Through infrared spectroscopy, thermogravimetric analysis and nitrogen adsorption-desorption characterization, it was confirmed that RCC3-C10 was successfully bonded to the surface of silica spheres. The resolution of RCC3-C10@silica in reversed-phase separation mode is as high as 2.95, 3.73, 3.27 and 4.09 for p-phenethyl alcohol, 1-phenyl-2-propanol, p-methylphenethyl alcohol and 1-phenyl-1-propanol, indicating that the stationary phase has excellent chiral resolution performance. In reversed-phase and hydrophilic separation modes, RCC3-C10@silica realized the separation and analysis of a total of 70 compounds in 8 classes of Tanaka mixtures, alkylbenzene rings, polyphenyl rings, phenols, anilines, sulfonamides, nucleosides and flavonoids, and the analysis of a variety of chiral and achiral complex mixtures have been completed at the same time. Compared with the traditional C18 commercial column, RCC3-C10@silica exhibits better chromatographic separation selectivity, aromatic selectivity and polar selectivity. The multifunctional separation mechanism exhibited by the stationary phase originates from various synergistic effects such as hydrophobic interaction, π-π interaction, hydrogen bonding and steric interaction provided by RCC3 and C10 groups. This work provides flexible selectivity and application prospects for novel multi-separation functional chromatographic columns.

The extent to which drivers' collision avoidance maneuvers affect the safety margins of sideslip and rollover is not captured by road geometric design theory. To quantify the effects of drivers' collision avoidance maneuvers on the safety margins of sport utility vehicles (SUVs) on horizontal curve and grade combinations, a modified 8-degree-of-freedom multibody model based on SUVs was developed. The model was then used to calculate the design safety margins of sideslip and rollover for steady states and the actual safety margins for collision avoidance maneuvers. Subsequently, the design safety margin reduction rate (the difference between the design and actual safety margins divided by the design safety margin) was calculated and used to assess the safety margins. The results showed that the safety margins of SUVs were significantly reduced by braking, lane changing, and lane changing with braking. The marginal effects indicated that the greater the deceleration and the shorter the lane change duration, the greater the effect on the safety margins, particularly the sideslip safety margin. Furthermore, when the SUV was driven at 80 km·h -1 on grades with a horizontal curve radius of 270 m and 400 m, the sideslip safety margin with emergency braking (deceleration over -4.5 m·s -2 ) was reduced by 71% and 21%, and the rollover safety margin was reduced by 11% and 5%, respectively. Under these conditions, an emergency lane change (lane change duration less than 2 s) caused the SUV to sideslip and reduced the rollover safety margin by 47% (curve radius 270 m) and 45% (curve radius 400 m). Therefore, drivers' collision avoidance maneuvers are a factor that cannot be neglected in alignment design.

Glymphatic dysfunction has been linked to cognitive decline in several neurodegenerative diseases. In cerebral small vessel disease (CSVD), the mechanism of white matter hyperintensities (WMH)-related cognitive impairment (CI) is still under investigation. The diffusion tensor image (DTI) analysis along the perivascular space (ALPS) method has been considered to be a reliable parameter to evaluate glymphatic function. Therefore, we applied the ALPS-index to determine the influence of glymphatic function on CI in CSVD. In total, 137 CSVD patients (normal cognitive group, mild CI group, and dementia group) and 52 normal controls were included in this study. The ALPS-index was calculated based on the DTI. Correlation analyses and mediation analysis were conducted to examine the relationship between glymphatic function and cognition. Remarkable differences in the ALPS-index were observed between subjects with and without CI. The ALPS-index was negatively correlated with age, WMH volume, and general cognitive function in all CSVD patients. In the mild CI group, the ALPS-index was independently positively related to episodic memory, and mediated the relationship between WMH volume and episodic memory. In conclusion, the ALPS-index is a potential marker for early recognition of CI in CSVD. Glymphatic dysfunction mediates the relationship between WMH and CI in CSVD.

As an important equipment for high-speed railway (HSR) to obtain electric power from outside, the state of the pantograph will directly affect the operation safety of HSR. In order to solve the problems that the current pantograph detection method is easily affected by the environment, cannot effectively deal with the interference of external scenes, has a low accuracy rate and can hardly meet the actual operation requirements of HSR, this study proposes a pantograph detection algorithm. The algorithm mainly includes three parts: the first is to use you only look once (YOLO) V4 to detect and locate the pantograph region in real-time; the second is the blur and dirt detection algorithm for the external interference directly affecting the high-speed camera (HSC), which leads to the pantograph not being detected; the last is the complex background detection algorithm for the external complex scene "overlapping" with the pantograph when imaging, which leads to the pantograph not being recognized effectively. The dirt and blur detection algorithm combined with blob detection and improved Brenner method can accurately evaluate the dirt or blur of HSC, and the complex background detection algorithm based on grayscale and vertical projection can greatly reduce the external scene interference during HSR operation. The algorithm proposed in this study was analyzed and studied on a large number of video samples of HSR operation, and the precision on three different test samples reached 99.92%, 99.90% and 99.98%, respectively. Experimental results show that the algorithm proposed in this study has strong environmental adaptability and can effectively overcome the effects of complex background and external interference on pantograph detection, and has high practical application value.

CH 4 can be separated from low-concentration coal bed methane (LCCBM) by using the hydrate-based gas separation (HBGS) method. To study the contribution of different cyclic organic compounds to the separation of CH 4 in LCCBM, an LCCBM hydrate model was constructed. Based on the Monte Carlo and molecular dynamics theory, we simulated the effect of three cyclic organic compounds-cyclopentane (CP), cyclopentanone (CP-one), and cyclopentanol (CP-ol)-on the stability of the LCCBM hydrate at P = 2 MPa, various temperatures, and discussed the structural stability of the hydrate in depth in terms of final snapshots, radial distribution function, mean square displacement, diffusion coefficient, and potential energy change. The results showed that for the CH 4 -N 2 LCCMM gas mixture, CP showed the best facilitation effect compared to the other two cyclic compounds by maintaining the stability of the LCCBM hydrate well at T = 293 K. The promotion effect of CP-one is between CP and CP-ol, and when the temperature increases to T = 293 K, the oxygen atoms in the water molecule can maintain the essential stability of the hydrate structure, although the orderliness decreases significantly. Moreover, the structure of the hydrate model containing CP-ol is destroyed at T = 293 K, and the eventual escape of CH 4 and N 2 molecules in solution occurs as bubbles. The research results are important for further exploration of the mechanism of action of cyclic promoter molecules with LCCBM hydrate molecules and promoter preferences.

Aroma is an important factor in fruit quality. Passiflora edulis (passion fruit) is popular among consumers because of its rich flavor and nutritional value. Esters are the main components of the volatile aroma of passion fruit. Lipoxygenase (LOX), as the first key enzyme upstream of esters, may play an important role in the formation of passion fruit aroma. In this study, a total of 12 passion fruit LOX ( PeLOX ) members were screened out based on the Passiflora edulis genome database, which were distributed unevenly on 6 chromosomes, all containing the highly conserved lipoxygenase domain and some containing the PLAT domain. The gene structure, evolutionary analysis and cis-acting elements of the family members were predicted in this study. Transcriptome analysis showed that 12 PeLOX genes had different degrees of response to different abiotic stresses (drought stress, salt stress, cold stress, and high temperature). PeLOX1 , PeLOX2 , PeLOX7 , PeLOX11 , and PeLOX12 responded significantly to various abiotic stresses, while PeLOX8 and PeLOX9 had little change in expression in all stresses. Quantitative real-time PCR (qRT-PCR) in six tissues revealed that the 12 PeLOX genes exhibited tissue expression specificity, and the relative expression of most genes were particularly high in the roots, stems, and fruits. Focusing on passion fruit ripening and ester synthesis, the transcriptomic analysis showed that with the increase in fruit development and fruit maturity, the expression levels of PeLOX1 , PeLOX9 , PeLOX11 , and PeLOX12 showed downregulated expression, while PeLOX2 and PeLOX4 showed upregulated expression. In particular, the upregulation trend of PeLOX4 was the most obvious, and the qRT-PCR results were consistent with the transcriptome result. Pearson correlation analysis showed that with the development and ripening of fruit, the expression level of PeLOX4 , LOX enzyme activity and total ester content all showed an increasing trend, in particular during the period when the peel was red and shrank (from T2 to T3 stage), the esters' contents increased by 37.4 times; the highest expression levels were all in the T3 period. The results indicated that PeLOX4 may be a candidate gene involved in fruit ripeness and the formation of volatile aroma compounds, with the increase in fruit ripening, the expression level of PeLOX4 increased and the LOX enzyme activity increased accordingly, thereby promoting the synthesis of volatile esters in fruit pulp. Our discovery lays the foundation for the functional study of LOX in passion fruit.

Ganoderma tsugae is well known as a medicinal mushroom in China and many Asian countries, while its fermentation technique and corresponding pharmacological activity are rarely reported. In this study, a wild G. tsugae strain (G42) with high triterpenoid content was screened from nine strains by rice solid-state fermentation, and 53.86 mg/g triterpenoids could be produced under optimized conditions; that is, inoculation amount 20%, fermentation temperature 27 °C, and culture time 45 days. The hepatoprotective activity of G42 ethanol extract was evaluated by CCl 4 -induced liver injury in mice, in which changes in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), oxidation-related factors, and inflammatory cytokines in serum or liver samples demonstrated the therapeutic effect. In addition, the ethanol extract of G42 reduced the incidence of necrosis and inflammatory infiltration, and decreased protein expression levels of phosphor-nuclear factor-κB (NF-κB), interleukin-Iβ (IL-1β), and nuclear factor erythroid-2-related factor 2 (NRF2). The chemical composition of the ethanol extract was analyzed by high-resolution mass spectrometry and molecular networking. Three main triterpenoids, namely platycodigenin, cucurbitacin IIb, and ganolecidic acid B were identified. This work provided an optimized fermentation method for G. tsugae , and demonstrated that its fermentation extract might be developed as a functional food with a hepatoprotective effect.

Excessive input of nitrogen fertilizer not only causes a great waste of resources but brings about a series of ecological and environmental problems. Although Small Auxin Up-regulated RNAs (SAURs) participate in diverse biological processes, the function of SAURs in the nitrogen starvation response has not been well-studied. Here, we identified 308 TaSAURs in wheat and divided them into 10 subfamilies. The promoter regions of most TaSAURs contain hormone responsive elements, and their expression levels change under the treatment of different hormones, such as IAA, MeJA, and ABA. Interestingly, overexpression of one of the TaSAUR family members, a nitrogen starvation responsive gene, TaSAUR66-5B, can promote the growth of Arabidopsis and wheat roots. In addition, overexpression of TaSAUR66-5B in Arabidopsis up-regulates the expression levels of auxin biosynthesis related genes, suggesting that overexpression TaSAUR66-5B may promote root growth by increasing the biosynthesis of auxin. Furthermore, overexpression of TaSAUR66-5B in wheat can increase the biomass and grain yields of transgenic plants, as well as the nitrogen concentration and accumulation of both shoots and grains, especially under low nitrogen conditions. This study provides important genomic information of the TaSAUR gene family and lays a foundation for elucidating the functions of TaSAURs in improving nitrogen utilization efficiency in wheat.

Bacillus subtilis A-5 has the capabilities of high-molecular-weight γ-PGA production, antagonism to plant pathogenic fungi, and salt/alkaline tolerance. This multifunctional bacterium has great potential for enhancing soil fertility and plant security in agricultural ecosystem. The genome size of B. subtilis A-5 was 4,190,775 bp, containing 1 Chr and 2 plasmids (pA and pB) with 43.37% guanine-cytosine content and 4605 coding sequences. The γ-PGA synthase gene cluster was predicted to consist of pgsBCA and factor ( pgsE ). The γ-PGA-degrading enzymes were mainly pgdS, GGT, and cwlO. Nine gene clusters producing secondary metabolite substances, namely, four unknown function gene clusters and five antibiotic synthesis gene clusters (surfactin, fengycin, bacillibactin, subtilosin&#95;A, and bacilysin), were predicted in the genome of B. subtilis A-5 using antiSMASH. In addition, B. subtilis A-5 contained genes related to carbohydrate and protein decomposition, proline synthesis, pyruvate kinase, and stress-resistant proteins. This affords significant insights into the survival and application of B. subtilis A-5 in adverse agricultural environmental conditions.

This paper reports a MEMS capacitive pressure sensor (CPS) based on the operating principle of touch mode. The CPS was designed and fabricated using wafer-level self-packaged MEMS processes. The variable capacitance sensing structure was vacuum-sealed in a cavity using the Si-glass anodic bonding technique, and the embedded Al feedthrough lines at the Si-glass interface were used to realize the electrical connections between the parallel plate electrodes and the electrode pads through Al vias. The optimal design of the CPS structure was performed to trade-off the performance and reliability using finite element simulation. The CPS based on a circular-shaped diaphragm with a radius of 2000 µm and a thickness of 40 µm exhibits good comprehensive performance with a sensitivity of 52.3 pF/MPa and a nonlinearity of 2.7%FS in the pressure range of 100-500 kPa when the ambient temperature is less than 50 °C.

Purpose: This multi-center study aims to investigate the prognostic value of context-aware saliency-guided radiomics in 18 F-FDG PET/CT images of head and neck cancer (HNC)., Methods: 806 HNC patients (training vs. validation vs. external testing: 500 vs. 97 vs. 209) from 9 centers were collected from The Cancer Imaging Archive (TCIA). There were 100/384 and 60/123 oropharyngeal carcinoma (OPC) patients with human papillomavirus (HPV) status in training and testing cohorts, respectively. Six types of images were used for radiomics feature extraction and further model construction, namely (i) the original image (Origin), (ii) a context-aware saliency map (SalMap), (iii, iv) high- or low-saliency regions in the original image (highSal or lowSal), (v) a saliency-weighted image (SalxImg), and finally, (vi) a fused PET-CT image (FusedImg). Four outcomes were evaluated, i.e., recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), and disease-free survival (DFS), respectively. Multivariate Cox analysis and logistic regression were adopted to construct radiomics scores for the prediction of outcome (Rad&#95;Ocm) and HPV-status (Rad&#95;HPV), respectively. Besides, the prognostic value of their integration (Rad&#95;Ocm&#95;HPV) was also investigated., Results: In the external testing cohort, compared with the Origin model, SalMap and SalxImg achieved the highest C-indices for RFS (0.621 vs. 0.559) and MFS (0.785 vs. 0.739) predictions, respectively, while FusedImg performed the best for both OS (0.685 vs. 0.659) and DFS (0.641 vs. 0.582) predictions. In the OPC HPV testing cohort, FusedImg showed higher AUC for HPV-status prediction compared with the Origin model (0.653 vs. 0.484). In the OPC testing cohort, compared with Rad&#95;Ocm or Rad&#95;HPV alone, Rad&#95;Ocm&#95;HPV performed the best for OS and DFS predictions with C-indices of 0.702 ( p = 0.002) and 0.684 ( p = 0.006), respectively., Conclusion: Saliency-guided radiomics showed enhanced performance for both outcome and HPV-status predictions relative to conventional radiomics. The radiomics-predicted HPV status also showed complementary prognostic value.

Content Delivery Network (CDN) technology is one of the core technologies for performance optimization of mobile WEB applications, but it often encounters bottlenecks in video storage. In this paper, based on studying the basic technical model of distributed real-time transcoding CDN, we propose an overall technical architecture of a distributed real-time transcoding CDN system, present the business process of distributed real-time transcoding CDN resource negotiation in the model, design a resource storage policy model and algorithm, including the hot storage ratio resource storage value evaluation method and storage resource allocation algorithm. Through simulation experiments, we verify the technical efficiency of the distributed real-time transcoding CDN system by simulation experiments.

Male germ cells directly affect the reproduction of males; however, their accurate isolation and culture in vitro is extremely challenging, hindering the study of germ cell development and function. CRISPR/dcas9, as an efficient gene reprogramming system, has been verified to promote the transdifferentiation of pluripotent stem cells into male germ cells by editing target genes. In our research, we explored the expression pattern of the germ cell related genes bmp4 , dazl, nanos3 and sycp2 in Hu sheep testicular development and constructed the overexpression model using the CRISPR/dcas9 system. The results indicated that four genes showed more expression in testis tissue than in other tissues, and that bmp4 , dazl and sycp2 present higher expression levels in nine-month-old sheep testes than in three-month-olds, while nanos3 expressed the opposite trend ( p < 0.05). In addition, the expression of four potential genes in spermatogenic cells was slightly different, but they were all expressed in sheep Leydig cells. To verify the potential roles of the four genes in the process of inducing differentiation of male germ cells, we performed cell transfection in vitro. We found that the expression of the germ cell related genes Prdm1, Prdm14, Mvh and Sox17 were significantly increased after the overexpression of the four genes in Leydig cells, and the co-transfection effect was the most significant ( p < 0.05). Our results illustrate the crucial functions of bmp4 , dazl , nanos3 and sycp2 in Hu sheep testis development and verified the effectiveness of the overexpression model that was constructed using the CRISPR/dcas9 system, which provided a basis for further male germ cell differentiation in vitro.

Mild traumatic brain injury (mTBI) without skull fracturing is the most common occurrence of all TBIs and is considered as a serious public health concern. Animal models of mTBI are essential to investigation of TBI and its effects. In the current study, we developed and characterized a reproducible mouse model of mild TBI, meanwhile, the effects of this mTBI model, as well as repetitive mTBIs (rmTBIs), on the endothelial function of mouse aortas were also studied. In variety of closed-head models of mTBI, impact velocity, weight, and dwell time are the main parameters that affect the severities of injury. Here, we used a device, converting parameters of velocity, tip weight, and dwell time into impact force, to develop a mouse model of close-head mTBI. Mice were subjected to a mild TBI induced by the impact forces of 500, 600, 700 and 800 kdyn, respectively. Later, brain injuries were assessed histologically and molecularly. Systemic and brain inflammation were measured by plasma cytokine assay and glial fibrillary acidic protein (GFAP) staining. The composite neurobehavioral test revealed significant acute functional deficits in mice after mTBI, corresponding to the degree of injury. Mice brain undergoing mTBI had significant elevated GFAP staining. Plasma cytokines interleukin-1β (IL-1β) and superoxide dismutase (SOD) were significantly increased within 2 h after mTBI. Taken together, these data suggest that the mTBI mouse model introduce within our study exhibits good repeatability and comparable pathological characters. Moreover, we used this mTBI mouse model to determine the effect of single or rmTBIs on systemic vasoconstriction and relaxation. The isometric-tension results indicate that rmTBIs induce a pronounced and long-lasting endothelial dysfunction in mouse aorta.

This paper presents the design and optimization of a novel MEMS tuning fork gyroscope microstructure. In order to improve the mechanical sensitivity of the gyroscope, much research has been carried out in areas such as mode matching, improving the quality factor, etc. This paper focuses on the analysis of mode shape, and effectively optimizes the decoupling structure and size of the gyroscope. In terms of structural design, the vibration performance of the proposed structure was compared with other typical structures. It was found that slotting in the middle of the base improved the transmission efficiency of Coriolis vibration, and opening arc slots between the tines reduced the working modal order and frequency. In terms of size optimization, the Taguchi method was used to optimize the relevant feature sizes of the gyroscope. Compared with the initial structure, the transmission efficiency of Coriolis vibration of the optimized gyroscope was improved by about 18%, and the working modal frequency was reduced by about 2.7 kHz. Improvement of these two indicators will further improve the mechanical sensitivity of the gyroscope.

A two-stage isothermal amplification method, which consists of a first-stage basic recombinase polymerase amplification (RPA) and a second-stage fluorescence loop-mediated isothermal amplification (LAMP), as well as a microfluidic-chip-based portable system, were developed in this study; these enabled parallel detection of multiplex targets in real time in around one hour, with high sensitivity and specificity, without cross-contamination. The consumption of the sample and the reagent was 2.1 μL and 10.6 μL per reaction for RPA and LAMP, respectively. The lowest detection limit (LOD) was about 10 copies. The clinical amplification of about 40 nasopharyngeal swab samples, containing 17 SARS-CoV-2 (severe acute respiratory syndrome coronavirus) and 23 measles viruses (MV), were parallel tested by using the microfluidic chip. Both clinical specificity and sensitivity were 100% for MV, and the clinical specificity and sensitivity were 94.12% and 95.83% for SARS-CoV-2, respectively. This two-stage isothermal amplification method based on the microfluidic chip format offers a convenient, clinically parallel molecular diagnostic method, which can identify different nucleic acid samples simultaneously and in a timely manner, and with a low cost of the reaction reagent. It is especially suitable for resource-limited areas and point-of-care testing (POCT).

High lead-tin bronze is widely used in the selection of wear-resistant parts such as bearings, bearing bushes, aerospace pump rotors, turbines, and guide plates because of its excellent wear resistance, thermal conductivity, fatigue resistance, and strong load-bearing capacity. At present, high lead-tin bronze is used as a material for bimetal cylinders, which cannot meet the requirements of high-strength, anti-wear in actual working conditions under high temperature, high speed, and heavy load conditions, and is prone to de-cylinder, cylinder holding, copper sticking, etc. The reason for the failure of cylinder body parts is that the strength of copper alloy materials is insufficient, the proportion of lead in the structure is serious, and the wear resistance of the material is reduced. Therefore, it has important theoretical significance and application value to carry out research on the comprehensive properties of high-performance lead-tin bronze materials and reveal the strengthening and toughening mechanism. In this paper, The ZCuPb20Sn5 alloy is taken as the main research object, and the particle size, microstructure, mechanical properties, and friction of lead particles in ZCuPb20Sn5 alloy are systematically studied after single addition of B in ZCuPb20Sn5 alloy liquid. This paper takes ZCuPb20Sn5 alloy as the research object to study the effect of adding B on the morphology, microstructure, mechanical properties, and friction and wear properties of ZCuPb20Sn5 alloy lead particles, and discusses the strengthening and toughening mechanism of ZCuPb20Sn5 alloy under the action of B, and prepares a double high-performance lead-tin bronze alloy for metal cylinders. The main research results are as follows: The addition of B elements has an obvious refining effect on the α (Cu) equiaxed grains and lead particles in ZCuPb20Sn5 alloy. The average size of lead particles decreases from 30.0 µm to 24.8 µm as the B content increases from 0 wt.% to 0.1 wt.%. The reason for grain refinement is that B is easily concentrated at the grain boundary during the ZCuPb20Sn5 alloy solidification process, which affects the diffusion of solute atoms at the solidification interface, inhibits the grain growth, refines the grain, and hinders the sinking and homogenizes distribution between dendrites of lead; the tensile strength of the ZCuPb20Sn5 alloy improves. Relatively without B, when the addition of P is 0.1 wt.%, the tensile strength is the largest at 244.04 MPa, which enhances 13%; the maximum hardness gets 75.0 HB, which enhances 13.6%, as well as elongation get the maximum value at 17.2%. The main mechanism is that the addition of B forms a high melting point submicron Ni 4 B 3 phase in the lead-tin bronze alloy. The Ni 4 B 3 phase is dispersed in the matrix and strengthens the matrix. With the increase in B content (more than 0.1 wt.%), the Ni 4 B 3 phase changes from sub-micron degree granular to micron degree block-like, and some defects such as shrinkage and porosity appear in the structure, resulting in a decrease in mechanical properties.

Alginate, the most abundant polysaccharides of brown algae, consists of various proportions of uronic acid epimers α -L-guluronic acid (G) and β -D-mannuronic acid (M). Alginate oligosaccharides (AOs), the degradation products of alginates, exhibit excellent bioactivities and a great potential for broad applications in pharmaceutical fields. Alginate lyases can degrade alginate to functional AOs with unsaturated bonds or monosaccharides, which can facilitate the biorefinery of brown algae. On account of the increasing applications of AOs and biorefinery of brown algae, there is a scientific need to explore the important aspects of alginate lyase, such as catalytic mechanism, structure, and property. This review covers fundamental aspects and recent developments in basic information, structural characteristics, the structure-substrate specificity or catalytic efficiency relationship, property, molecular modification, and applications. To meet the needs of biorefinery systems of a broad array of biochemical products, alginate lyases with special properties, such as salt-activated, wide pH adaptation range, and cold adaptation are outlined. Withal, various challenges in alginate lyase research are traced out, and future directions, specifically on the molecular biology part of alginate lyases, are delineated to further widen the horizon of these exceptional alginate lyases.

Studies have shown that bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into dermal fibroblasts to participate in skin-repairing. However, at present, little is known about how microgravity affects dermal fibroblastic differentiation of BMSCs in space. The aim of this study was to investigate the effect of simulated microgravity (SMG) on the differentiation of BMSCs into dermal fibroblasts and the related molecular mechanism. Here, using a 2D-clinostat device to simulate microgravity, we found that SMG inhibited the differentiation and suppressed the Wnt/β-catenin signaling and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2). After upregulating the Wnt/β-catenin signaling with lithium chloride (LiCl) treatment, we found that the effect of the differentiation was restored. Moreover, the Wnt/β-catenin signaling was upregulated when phosphorylation of ERK1/2 was activated with tert-Butylhydroquinone (tBHQ) treatment. Taken together, our findings suggest that SMG inhibits dermal fibroblastic differentiation of BMSCs by suppressing ERK/β-catenin signaling pathway, inferring that ERK/β-catenin signaling pathway may act as a potential intervention target for repairing skin injury under microgravity conditions.

Prunus mume blossom is an edible flower that has been used in traditional Chinese medicine for thousands of years. Flavonoids are one of the most active substances in Prunus mume blossoms. The optimal ultrasonic-assisted enzymatic extraction of flavonoids from Prunus mume blossom (FPMB), the components of FPMB, and its protective effect on injured cardiomyocytes were investigated in this study. According to our results, the optimal extraction process for FPMB is as follows: cellulase at 2.0%, ultrasonic power at 300 W, ultrasonic enzymolysis for 30 min, and an enzymolysis temperature of 40 °C. FPMB significantly promoted the survival rate of cardiomyocytes and reduced the concentration of reactive oxygen species (ROS). FPMB also improved the activities of proteases caspase-3, caspase-8, and caspase-9 in cardiomyocytes. The cardiomyocyte apoptosis rate in mice was significantly reduced by exposure to FPMB. These results suggest that the extraction rate of FPMB may be improved by an ultrasonic-assisted enzymatic method. FPMB has a protective effect on the injured cardiomyocytes.

Modern agriculture contributes significantly to greenhouse gas emissions, and agriculture has become the second biggest source of carbon emissions in China. In this context, it is necessary for China to study the nexus of agricultural economic growth and carbon emissions. Taking Jilin province as an example, this paper applied the environmental Kuznets curve (EKC) hypothesis and a decoupling analysis to examine the relationship between crop production and agricultural carbon emissions during 2000-2018, and it further provided a decomposition analysis of the changes in agricultural carbon emissions using the log mean Divisia index (LMDI) method. The results were as follows: (1) Based on the results of CO 2 EKC estimation, an N-shaped EKC was found; in particular, the upward trend in agricultural carbon emissions has not changed recently. (2) According to the results of the decoupling analysis, expansive coupling occurred for 9 years, which was followed by weak decoupling for 5 years, and strong decoupling and strong coupling occurred for 2 years each. There was no stable evolutionary path from coupling to decoupling, and this has remained true recently. (3) We used the LMDI method to decompose the driving factors of agricultural carbon emissions into four factors: the agricultural carbon emission intensity effect, structure effect, economic effect, and labor force effect. From a policymaking perspective, we integrated the results of both the EKC and the decoupling analysis and conducted a detailed decomposition analysis, focusing on several key time points. Agricultural economic growth was found to have played a significant role on many occasions in the increase in agricultural carbon emissions, while agricultural carbon emission intensity was important to the decline in agricultural carbon emissions. Specifically, the four factors' driving direction in the context of agricultural carbon emissions was not stable. We also found that the change in agricultural carbon emissions was affected more by economic policy than by environmental policy. Finally, we put forward policy suggestions for low-carbon agricultural development in Jilin province.

Quantitative measurement of single cells can provide in-depth information about cell morphology and metabolism. However, current live-cell imaging techniques have a lack of quantitative detection ability. Herein, we proposed a label-free and quantitative multichannel wide-field interferometric imaging (MWII) technique with femtogram dry mass sensitivity to monitor single-cell metabolism long-term in situ culture. We demonstrated that MWII could reveal the intrinsic status of cells despite fluctuating culture conditions with 3.48 nm optical path difference sensitivity, 0.97 fg dry mass sensitivity and 2.4% average maximum relative change (maximum change/average) in dry mass. Utilizing the MWII system, different intrinsic cell growth characteristics of dry mass between HeLa cells and Human Cervical Epithelial Cells (HCerEpiC) were studied. The dry mass of HeLa cells consistently increased before the M phase, whereas that of HCerEpiC increased and then decreased. The maximum growth rate of HeLa cells was 11.7% higher than that of HCerEpiC. Furthermore, HeLa cells were treated with Gemcitabine to reveal the relationship between single-cell heterogeneity and chemotherapeutic efficacy. The results show that cells with higher nuclear dry mass and nuclear density standard deviations were more likely to survive the chemotherapy. In conclusion, MWII was presented as a technique for single-cell dry mass quantitative measurement, which had significant potential applications for cell growth dynamics research, cell subtype analysis, cell health characterization, medication guidance and adjuvant drug development.

A non-contact heartbeat/respiratory rate monitoring system was designed using narrow beam millimeter wave radar. Equipped with a special low sidelobe and small-sized antenna lens at the front end of the receiving and transmitting antennas in the 120 GHz band of frequency-modulated continuous-wave (FMCW) system, this sensor system realizes the narrow beam control of radar, reduces the interference caused by the reflection of other objects in the measurement background, improves the signal-to-clutter ratio (SCR) of the intermediate frequency signal (IF), and reduces the complexity of the subsequent signal processing. In order to solve the problem that the accuracy of heart rate is easy to be interfered with by respiratory harmonics, an adaptive notch filter was applied to filter respiratory harmonics. Meanwhile, the heart rate obtained by fast Fourier transform (FFT) was modified by using the ratio of adjacent elements, which helped to improve the accuracy of heart rate detection. The experimental results show that when the monitoring system is 1 m away from the human body, the probability of respiratory rate detection error within ±2 times for eight volunteers can reach 90.48%, and the detection accuracy of the heart rate can reach 90.54%. Finally, short-term heart rate measurement was realized by means of improved empirical mode decomposition and fast independent component analysis algorithm.