Search

The ultrasonic liquid phase exfoliation method has emerged as an essential research direction for graphene preparation due to its cost-effectiveness and ability to minimize defects. However, this method faces challenges related to processing throughput when scaled up for industrial production. In this study, industrial grade ultrasonic homogenizers with different frequencies and probe types were evaluated for the preparation of FLG. In each experiment, 1.5 kg of graphite slurry was treated using a cyclic ultrasonic system. The results demonstrated that the 25 kHz dumbbell probe produced the thinnest FLG with the lowest defect density. Moreover, applying a static pressure of 0.2 MPa in the cycle system enhanced the cavitation-induced exfoliation of graphite sheets, effectively reducing the layer count and distribution range of FLG. This method improves the conductivity while minimizing defect density.

Abstract The induction of regulated cell death (RCD) through photo/ultrasound sensitization therapeutic agents has gained significant attention as a vital approach to combat drug resistance in tumors. Aggregation‐induced emission (AIE) therapeutic agents generate reactive oxygen species through photo/ultrasound activation, which can synergize with RCD inducers or directly induce RCD, ultimately resulting in the death of tumor cells. The presented comprehensive review delves into recent advancements in AIE therapeutic agents designed to trigger RCD or synergize with RCD inducers, encompassing apoptosis, necroptosis, pyroptosis, immunogenic cell death, autophagy, ferroptosis, and cuproptosis. Additionally, the intricate regulatory mechanisms through which activatory‐AIE therapeutics influence distinct RCD pathways are examined. A forward‐looking perspective on future developments and pertinent challenges within this exciting realm is presented, anticipating the continued evolution of activatable AIE therapeutics as a transformative approach to enhance tumor therapy.

Ultrasonic Liquid Phase Exfoliation (LPE) has gathered attention from both scientific and industrial communities for its accessibility and cost-effectiveness in producing graphene. However, this technique has faced challenges such as low yield and long production time. In this study, we developed a cyclic ultrasonication system to exfoliate expanded graphite (EG) by applying static pressure to a flow chamber to address these challenges. Using deionized water (DIW) as solvent and polyvinylpyrrolidone (PVP) as dispersion, we obtained graphene slurries with an average lateral size of 7 μm and averaged number of layers of 3.5 layers, after 40 min of ultrasonication. After centrifugation, the yield of single and bilayer graphene was approximately 16 %. The findings showed that regulating hydrostatic pressure can effectively affect the lateral size and number of layers of few-layer graphene. The proposed method is of good potential for scaled-up production of few-layer graphene.

The bHLH transcription factors are important plant regulators against abiotic stress and involved in plant growth and development. In this study, SlALC, a gene coding for a prototypical DNA-binding protein in the bHLH family, was isolated, and SlALC-overexpression tomato (SlALC-OE) plants were generated by Agrobacterium-mediated genetic transformation. SlALC transgenic lines manifested higher osmotic stress tolerance than the wild-type plants, estimated by higher relative water content and lower water loss rate, higher chlorophyll, reducing sugar, starch, proline, soluble protein contents, antioxidant enzyme activities, and lower MDA and reactive oxygen species contents in the leaves. In SlALC-OE lines, there were more significant alterations in the expression of genes associated with stress. Furthermore, SlALC-OE fruits were more vulnerable to dehiscence, with higher water content, reduced lignin content, SOD/POD/PAL enzyme activity, and lower phenolic compound concentrations, all of which corresponded to decreased expression of lignin biosynthetic genes. Moreover, the dual luciferase reporter test revealed that SlTAGL1 inhibits SlALC expression. This study revealed that SlALC may play a role in controlling plant tolerance to drought and salt stress, as well as fruit lignification, which influences fruit dehiscence. The findings of this study have established a foundation for tomato tolerance breeding and fruit quality improvement.

The influence of small groups in evacuation cannot be ignored. However, the current simulations and experimental studies have oversimplified the settings of small groups and evacuation scenarios. A significant disparity exists between the findings of existing studies and real-world scenarios. This paper compiled data on the number and size of small groups and the location of small group members in built environments. Subsequently, a scenario with intricate functions and shapes was established, and finally, these data was employed in agent-based simulations. The data encompassed 50 small groups comprising a total of 111 members. These groups, ranging from 2 to 4 members each, exhibited spatial separations between members spanning from 1 m to 23 m. Simulation outcomes indicated a detrimental effect of small groups on overall evacuation. A significant and positive correlation was observed between the distance separating small group members and the escalation in evacuation time, total jam time, and evacuation distance. The data provides a foundation for configuring initial scenarios in small group evacuation experiments and simulations. The simulation results can provide a basis for hospital safety evacuation management.

Silica (SiO2), accounting for the main component of fly ash, plays a vital role in the heterogeneous formation of polychlorinated thianthrenes/dibenzothiophenes (PCTA/DTs) in high-temperature industrial processes. Silica clusters, as the basic units of silica, provide reasonable models to understand the general trends of complex surface reactions. Chlorothiophenols (CTPs) are the most crucial precursors for PCTA/DT formation. By employing density functional theory, this study examined the formation of 2-chlorothiophenolate from 2-CTP adsorbed on the dehydrated silica cluster ((SiO2)3) and the hydroxylated silica cluster ((SiO2)3O2H4). Additionally, this study investigated the formation of pre-PCTA/DTs, the crucial intermediates involved in PCTA/DT formation, from the coupling of two adsorbed 2-chlorothiophenolates via the Langmuir–Hinshelwood (L–H) mechanism and the coupling of adsorbed 2-chlorothiophenolate with gas-phase 2-CTP via the Eley–Rideal (E–R) mechanism on silica clusters. Moreover, the rate constants for the main elementary steps were calculated over the temperature range of 600–1200 K. Our study demonstrates that the 2-CTP is more likely to adsorb on the termination of the dehydrated silica cluster, which exhibits more effective catalysis in the formation of 2-chlorothiophenolate compared with the hydroxylated silica cluster. Moreover, the E–R mechanism mainly contributes to the formation of pre-PCTAs, whereas the L–H mechanism is prone to the formation of pre-PCDTs on dehydrated and hydroxylated silica clusters. Silica can act as a relatively mild catalyst in facilitating the heterogeneous formation of pre-PCTA/DTs from 2-CTP. This research provides new insights into the surface-mediated generation of PCTA/DTs, further providing theoretical foundations to reduce dioxin emission and establish dioxin control strategies.

Moldy corn produces aflatoxin and gibberellin, which can have adverse effects on human health if consumed. Mold is a significant factor that affects the safe storage of corn. If not detected and controlled in a timely manner, it will result in substantial food losses. Understanding the infection patterns of mold on corn kernels and the changing characteristics of the internal structure of corn kernels after infection is crucial for guiding innovation and optimizing detection methods for moldy corn. This knowledge also helps maintain corn storage and ensure food safety. This study was based on X-ray tomography technology to non-destructively detect changes in the structural characteristics of moldy corn kernels. It used image processing technology and model reconstruction algorithms to obtain the 3D model of the embryo, pores and cracks, endosperm and seed coat, and kernels of moldy corn kernels; qualitative analysis of the characteristic changes of two-dimensional slice grayscale images and 3D models of moldy corn kernels; and quantitative analysis of changes in the volume parameters of corn kernels, embryos, endosperm, and seed coats as a whole. It explored the detection method of moldy corn kernels based on a combination of X-ray tomography technology and deep learning algorithms. The analysis concluded that mold infection in maize begins in the embryo and gradually spreads and that mold damage to the tissue structure of maize kernels is irregular in nature. The overall volume parameter changes of corn kernels, embryos, endosperm, and seed coats in the four stages of 0 d, 5 d, 10 d, and 15 d showed a trend of first increasing and then decreasing. The ResNet50 model was enhanced for detecting mold on maize kernels, achieving an accuracy of over 93% in identifying mold features in sliced images of maize kernels. This advancement enabled the non-destructive detection and classification of the degree of mold in maize kernel samples. This article studies the characterization of the characteristic changes of moldy corn kernels and the detection of mildew, which will provide certain help for optimizing the monitoring of corn kernel mildew and the development of rapid detection equipment.

In the domain of remote sensing research, the extraction of roads from high-resolution imagery remains a formidable challenge. In this paper, we introduce an advanced architecture called PCCAU-Net, which integrates Pyramid Pathway Input, CoordConv convolution, and Dual-Inut Cross Attention (DCA) modules for optimized performance. Initially, the Pyramid Pathway Input equips the model to identify features at multiple scales, markedly enhancing its ability to discriminate between roads and other background elements. Secondly, by adopting CoordConv convolutional layers, the model achieves heightened accuracy in road recognition and extraction against complex backdrops. Moreover, the DCA module serves dual purposes: it is employed at the encoder stage to efficiently consolidate feature maps across scales, thereby fortifying the model’s road detection capabilities while mitigating false positives. In the skip connection stages, the DCA module further refines the continuity and accuracy of the features. Extensive empirical evaluation substantiates that PCCAU-Net significantly outperforms existing state-of-the-art techniques on multiple benchmarks, including precision, recall, and Intersection-over-Union(IoU). Consequently, PCCAU-Net not only represents a considerable advancement in road extraction research, but also demonstrates vast potential for broader applications, such as urban planning and traffic analytics.

NAC transcription factors are commonly involved in the plant response to drought stress. A transcriptome analysis of root samples of the soybean variety ‘Jiyu47’ under drought stress revealed the evidently up-regulated expression of GmNAC19, consistent with the expression pattern revealed by quantitative real-time PCR analysis. The overexpression of GmNAC19 enhanced drought tolerance in Saccharomyces cerevisiae INVSc1. The seed germination percentage and root growth of transgenic Arabidopsis thaliana were improved in comparison with those of the wild type, while the transgenic soybean composite line showed improved chlorophyll content. The altered contents of physiological and biochemical indices (i.e., soluble protein, soluble sugar, proline, and malondialdehyde) related to drought stress and the activities of three antioxidant enzymes (i.e., superoxide dismutase, peroxidase, and catalase) revealed enhanced drought tolerance in both transgenic Arabidopsis and soybean. The expressions of three genes (i.e., P5CS, OAT, and P5CR) involved in proline synthesis were decreased in the transgenic soybean hairy roots, while the expression of ProDH involved in the breakdown of proline was increased. This study revealed the molecular mechanisms underlying drought tolerance enhanced by GmNAC19 via regulation of the contents of soluble protein and soluble sugar and the activities of antioxidant enzymes, providing a candidate gene for the molecular breeding of drought-tolerant crop plants.

ALKBH proteins, the homologs of Escherichia coli AlkB dioxygenase, constitute a single-protein repair system that safeguards cellular DNA and RNA against the harmful effects of alkylating agents. ALKBH10B, the first discovered N6-methyladenosine (m6A) demethylase in Arabidopsis (Arabidopsis thaliana), has been shown to regulate plant growth, development, and stress responses. However, until now, the functional role of the plant ALKBH10B has solely been reported in arabidopsis, cotton, and poplar, leaving its functional implications in other plant species shrouded in mystery. In this study, we identified the AlkB homolog SlALKBH10B in tomato (Solanum lycopersicum) through phylogenetic and gene expression analyses. SlALKBH10B exhibited a wide range of expression patterns and was induced by exogenous abscisic acid (ABA) and abiotic stresses. By employing CRISPR/Cas9 gene editing techniques to knock out SlALKBH10B, we observed an increased sensitivity of mutants to ABA treatment and upregulation of gene expression related to ABA synthesis and response. Furthermore, the Slalkbh10b mutants displayed an enhanced tolerance to drought and salt stress, characterized by higher water retention, accumulation of photosynthetic products, proline accumulation, and lower levels of reactive oxygen species and cellular damage. Collectively, these findings provide insights into the negative impact of SlALKBH10B on drought and salt tolerance in tomato plant, expanding our understanding of the biological functionality of SlALKBH10B.

Alzheimer’s disease (AD) is a complex multifactorial disorder that poses a substantial burden on patients, caregivers, and society. Considering the increased aging population and life expectancy, the incidence of AD will continue to rise in the following decades. However, the molecular pathogenesis of AD remains controversial, superior blood-based biomarker candidates for early diagnosis are still lacking, and effective therapeutics to halt or slow disease progression are urgently needed. As powerful genetic regulators, microRNAs (miRNAs) are receiving increasing attention due to their implications in the initiation, development, and theranostics of various diseases, including AD. In this review, we summarize miRNAs that directly target microtubule-associated protein tau (MAPT), amyloid precursor protein (APP), and β-site APP-cleaving enzyme 1 (BACE1) transcripts and regulate the alternative splicing of tau and APP. We also discuss related kinases, such as glycogen synthase kinase (GSK)-3β, cyclin-dependent kinase 5 (CDK5), and death-associated protein kinase 1 (DAPK1), as well as apolipoprotein E, that are directly targeted by miRNAs to control tau phosphorylation and amyloidogenic APP processing leading to Aβ pathologies. Moreover, there is evidence of miRNA-mediated modulation of inflammation. Furthermore, circulating miRNAs in the serum or plasma of AD patients as noninvasive biomarkers with diagnostic potential are reviewed. In addition, miRNA-based therapeutics optimized with nanocarriers or exosomes as potential options for AD treatment are discussed.

Retinitis pigmentosa (RP) is the leading cause of inherited blindness with a genetically heterogeneous disorder. Currently, there is no effective treatment that can protect vision for those with RP. In recent decades, the rd1 mouse has been used to study the pathological mechanisms of RP. Molecular biological studies using rd1 mice have clarified the mechanism of the apoptosis of photoreceptor cells in the early stage of RP. However, the pathological changes in RP over time remain unclear. The unknown pathology mechanism of RP over time and the difficulty of clinical treatment make it urgent to perform more refined and spatially informed molecular biology studies of RP. In this study, spatial transcriptomic analysis is used to study the changes in different retinal layers of rd1 mice at different ages. The results demonstrate the pattern of photoreceptor apoptosis between rd1 mice and the control group. Not only was oxidative stress enhanced in the late stage of RP, but it was accompanied by an up-regulation of the VEGF pathway. Analysis of temporal kinetic trends has further identified patterns of changes in the key pathways of the early and late stages, to help understand the important pathogenesis of RP. Overall, the application of spatial transcriptomics to rd1 mice can help to elucidate the important pathogenesis of RP involving photoreceptor apoptosis and retinal remodeling.

A series of novel derivatives of 18β-glycyrrhetinic acid (GA) were synthesized by introducing aromatic or heterocyclic structures to extend the side chain, thereby enhancing their interaction with amino acid residues in the active pocket of the target protein. These compounds were structurally characterized using 1H NMR, 13C NMR, and HRMS. The compounds were subsequently evaluated for their inhibitory effects on HIV-1 protease and cell viability in the human cancer cell lines K562 and HeLa and the mouse cancer cell line CT26. Towards HIV-1 protease, compounds 28 and 32, which featured the introduction of heterocyclic moieties at the C3 position of GA, exhibited the highest inhibition, with inhibition rates of 76% and 70.5%, respectively, at 1 mg/mL concentration. Further molecular docking suggests that a 3-substituted polar moiety would be likely to enhance the inhibitory activity against HIV-1 protease. As for the anti-proliferative activities of the GA derivatives, incorporation of a thiazole heterocycle at the C3- position in compound 29 significantly enhanced the effect against K562 cells with an IC50 value of 8.86 ± 0.93 µM. The introduction of electron-withdrawing substituents on the C3-substituted phenyl ring augmented the anti-proliferative activity against Hela and CT26 cells. Compound 13 exhibited the highest inhibitory activity against Hela cells with an IC50 value of 9.89 ± 0.86 µM, whereas compound 7 exerted the strongest inhibition against CT26 cells with an IC50 value of 4.54 ± 0.37 µM. These findings suggest that further modification of GA is a promising path for developing potent novel anti-HIV and anticancer therapeutics.

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49–1.99; p = 4.07 × 10−11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20–1.74; p = 1.23 × 10−4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (−) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (−) subtype.

Objective: Site- and structure-specific quantitative N-glycoproteomics study of differential cell-surface N-glycosylation of ovarian cancer SKOV3 cells with the non-cancerous ovarian epithelial IOSE80 cells as the control.Methods: C18-RPLC-MS/MS (HCD with stepped normalized collision energies) was used to analyze the 1: 1 mixture of labeled intact N-glycopeptides from SKOV3 and IOSE80 cells, and the site- and structure-specific intact N-glycopeptide search engine GPSeeker was used to conduct qualitative and quantitative search on the obtained raw datasets.Results: With the control of the spectrum-level false discovery rate ≤1%, 13,822 glycopeptide spectral matches coming from 2,918 N-glycoproteins with comprehensive N-glycosite and N-glycan structure information were identified; 3,733 N-glycosites and 3,754 N-glycan sequence structures were confirmed by site-determining and structure-diagnostic fragment ions, respectively. With the control of no less than two observations among the three technical replicates, fold change ≥1.5, and p-value ≤ 0.05, 746 DEPGs in SKOV3 cells relative to IOSE80 cells were quantified, where 421 were upregulated and 325 downregulated.Conclusion: Differential cell-surface N-glycosylation of ovarian cancer SKOV3 cells were quantitatively analyzed by isotopic labeling and site- and structure-specific N-glycoproteomics. This discovery study provides putative N-glycoprotein biomarker candidates for future validation study using multiple reaction monitoring and biochemical methods.

The present study employed a modified QuEChERS method to systematically analyze the presence of fifteen quinolone and seven tetracycline antibiotic residues in local animal food. Additionally, a multi-level four-factor Box–Behnken design (BBD) within the framework of response surface methodology (RSM) was utilized to evaluate the factors impacting the detection efficiency of the sample pretreatment procedure. Optimization was performed via Design Expert® 10.0.3, and the factors, including the volume of the acetonitrile, the addition of formic acid, the duration of the extraction, and the addition of EDTA, were combined with experimental design until an optimal solution was reached. Finally, the sample was tested via ultra-high performance liquid chromatography-quadrupole-linear ion trap mass spectrometry (UPLC/MS/MS) in both multiple reaction monitoring (MRM) and enhanced product ion (EPI) scan modes on a QTRAP® 5500 instrument (AB SCIEX instruments, Framingham, MA, USA). The overall average recoveries from actual samples fortified with 22 antibiotics at three levels ranged from 73.8% to 98.5% based on the use of matrix-fortified calibration, with variations ranging from 5.80 to 12.4% (n = 6). The limits of detection and quantification were 0.3 μg kg−1 and 1.0 μg kg−1, respectively. Lastly, the modified method was applied to practical sample analysis in the daily risk monitoring and assessment of food safety with satisfactory stability and robustness.

There will be great damage in the process of harvesting, transporting, and storing after grain matures. The injury rate is as high as 8% to 12%. After damage, the germination rate of the grain becomes lower, the quality decreases, and it is easily infected with pests and molds. This study of the grain-crushing characteristics is of great significance to ensure grain quality, and an accurate crushing model is a prerequisite for effectively simulating crushing characteristics. This paper studies the shattering characteristics of wheat grains. Two-dimensional slices of wheat grain were obtained using X-ray tomography technology. Then, an accurate three-dimensional outer contour model of the wheat particle was constructed using image filtering and segmentation algorithms. The particle filling process was conducted using EDEM 2018 software to establish a wheat particle simulation model based on the Hertz–Mindlin with a Bonding contact model. Using the DOE experimental design method, single-factor experiments, Plackett–Burman experiments, steepest-climb experiments, and Box–Behnken were designed to study the fragmentation characteristics of wheat particles combined with parameter calibration and physical experiments. The test results show that the normal stiffness per unit area is 7.392 × 1010 N/m3, critical normal stress is 5.293 × 106 Pa, critical tangential stress is 5.001 × 106 Pa, and the relative error about 3%, which verifies the reliability of the simulation parameters in the discrete-element crushing model of wheat grain. This study focuses on two essential aspects: 1. establishing an accurate wheat-grain contour model; and 2. calibrating the bonding parameters of the discrete-element simulation model of wheat grain. The wheat grain discrete-element crushing model and the calibration of its bonding parameters are constructed to provide a foundation for the study of wheat-grain crushing characteristics. It is of great significance to study the situation of wheat grains and where cracks are produced. In this paper, an accurate model of the wheat-grain contour is established, and the bonding parameters of the discrete-element simulation model of the wheat grain are calibrated. The calibration of the model of the discrete elements of wheat-grain fragmentation and its bonding parameters will provide a basis for studying the crushing characteristics of wheat grain. Understanding the condition of wheat grains and the causes of cracks carries significant academic significance.

A train traction system is an important part of an urban rail transit system. However, a train traction system has many components and a high risk of internal faults. How to systematically evaluate the fault coverage and diagnosis ability of testing equipment is a fundamental problem in the technical field of train operation. In response to this problem, this study attempts to apply testability technology to the test capability analysis of train traction systems for rail transit. In view of the uncertainty in actual tests, a method for constructing a fault diagnosis strategy for a traction system under unreliable testing is proposed. The concept of test credibility is introduced for the first time, and the quantitative evaluation of test credibility is realized using a cloud model, so as to construct a new “fault-test” credibility correlation matrix. On this basis, a single-fault diagnosis strategy of the traction system is constructed and compared based on information theory. The results show that a using a fault diagnosis strategy under the condition of unreliable testing is more similar to actual maintenance work, proving the significance of the diagnosis strategy constructed using this method for the practical application of the project.

Chronic kidney disease (CKD) is a major public health issue around the world. A significant number of CKD patients originates from acute kidney injury (AKI) patients, namely “AKI–CKD”. CKD is significantly related to the consequences of AKI. Damaged renal proximal tubular (PT) cell repair has been widely confirmed to indicate the renal prognosis of AKI. Oxidative stress is a key damage-associated factor and plays a significant role throughout the development of AKI and CKD. However, the relationships between AKI–CKD progression and oxidative stress are not totally clear and the underlying mechanisms in “AKI–CKD” remain indistinct. In this research, we constructed unilateral ischemia–reperfusion injury (UIRI)-model mice and performed single-nucleus RNA sequencing (snRNA-seq) of the kidney samples from UIRI and sham mice. We obtained our snRNA-seq data and validated the findings based on the joint analysis of public databases, as well as a series of fundamental experiments. Proximal tubular cells associated with failed repair express more complete senescence and oxidative stress characteristics compared to other subgroups. Furthermore, oxidative stress-related transcription factors, including Stat3 and Dnmt3a, are significantly more active under the circumstance of failed repair. What is more, we identified abnormally active intercellular communication between PT cells associated with failed repair and macrophages through the APP–CD74 pathway. More notably, we observed that the significantly increased expression of CD74 in hypoxia-treated TECs (tubular epithelial cells) was dependent on adjacently infiltrated macrophages, which was essential for the further deterioration of failed repair in PT cells. This research provides a novel understanding of the process of AKI to CKD progression, and the oxidative stress-related characteristics that we identified might represent a potentially novel therapeutic strategy against AKI.

Heat stress can hinder the growth of perennial ryegrass (Lolium perenne L.). Methyl jasmonate (MeJA) applied exogenously can increase heat stress tolerance in plants; however, the regulatory mechanisms involved in heat tolerance mediated by MeJA are poorly understood in perennial ryegrass. Here, the microRNA (miRNA) expression profiles of perennial ryegrass were assessed to elucidate the regulatory pathways associated with heat tolerance induced by MeJA. Plants were subjected to four treatments, namely, control (CK), MeJA pre-treatment (T), heat stress treatment (H), and MeJA pre-treatment + heat stress (TH). According to the results, 102 miRNAs were up-regulated in all treatments, with 20, 27, and 33 miRNAs being up-regulated in the T, H, and TH treatment groups, respectively. The co-expression network analysis between the deferentially expressed miRNAs and their corresponding target genes showed that 20 miRNAs modulated 51 potential target genes. Notably, the miRNAs that targeted genes related to with regards to heat tolerance were driven by MeJA, and they were involved in four pathways: novel-m0258-5p mediated signal transduction, novel-m0350-5p mediated protein homeostasis, miR397-z, miR5658-z, and novel-m0008-5p involved in cell wall component, and miR1144-z and miR5185-z dominated chlorophyll degradation. Overall, the findings of this research paved the way for more research into the heat tolerance mechanism in perennial ryegrass and provided a theoretical foundation for developing cultivars with enhanced heat tolerance.

Oxidative stress can adversely affect the health status of the body, more specifically by causing intestinal damage by disrupting the permeability of the intestinal barrier. This is closely related to intestinal epithelial cell apoptosis caused by the mass production of reactive oxygen species (ROS). Baicalin (Bai) is a major active ingredient in Chinese traditional herbal medicine that has antioxidant, anti-inflammatory, and anti-cancer properties. The purpose of this study was to explore the underlying mechanisms by which Bai protects against hydrogen peroxide (H2O2)-induced intestinal injury in vitro. Our results indicated that H2O2 treatment caused injury to IPEC-J2 cells, resulting in their apoptosis. However, Bai treatment attenuated H2O2-induced IPEC-J2 cell damage by up-regulating the mRNA and protein expression of ZO-1, Occludin, and Claudin1. Besides, Bai treatment prevented H2O2-induced ROS and MDA production and increased the activities of antioxidant enzymes (SOD, CAT, and GSH-PX). Moreover, Bai treatment also attenuated H2O2-induced apoptosis in IPEC-J2 cells by down-regulating the mRNA expression of Caspase-3 and Caspase-9 and up-regulating the mRNA expression of FAS and Bax, which are involved in the inhibition of mitochondrial pathways. The expression of Nrf2 increased after treatment with H2O2, and Bai can alleviate this phenomenon. Meanwhile, Bai down-regulated the ratio of phosphorylated AMPK to unphosphorylated AMPK, which is indicative of the mRNA abundance of antioxidant-related genes. In addition, knockdown of AMPK by short-hairpin RNA (shRNA) significantly reduced the protein levels of AMPK and Nrf2, increased the percentage of apoptotic cells, and abrogated Bai-mediated protection against oxidative stress. Collectively, our results indicated that Bai attenuated H2O2-induced cell injury and apoptosis in IPEC-J2 cells through improving the antioxidant capacity through the inhibition of the oxidative stress-mediated AMPK/Nrf2 signaling pathway.

Two saline-alkali-tolerant bacterial strains, Priestia aryabhattai JL-5 and Staphylococcus pseudoxylosus XW-4, were isolated, with high capabilities of hydrolyzing phosphate and producing cellulase, respectively. The molecular mechanisms regulating the saline-alkali tolerance in the strain JL-5 were further investigated using transcriptome analysis. The contents of lactic acid and proline and the enzymatic activity of glutamine synthetase in the strain JL-5 were significantly increased. The properties of saline-alkali soils were significantly improved by the enhanced growth of the indicator plant Leymus chinensis under the combined applications of the strains JL-5 and XW-4 mixed with corn straw. The contents of catalase, peroxidase, superoxide dismutase and proline of L. chinensis were significantly increased, and the content of malondialdehyde was significantly decreased in the combined treatment of both bacterial strains. The contents of available nitrogen, phosphorus and potassium and organic matters in the soil treated with both strains were significantly increased, as well as the diversity and abundance of the soil microbiota. Our study evidently demonstrated the synergistic effects of the strains JL-5 and XW-4, indicator plants and the local microbiota in terms of improving the saline-alkali soil properties, providing strong experimental evidence to support the commercial development of the combined application of both strains to improve the properties of saline-alkali soils.

The bridge-type bridge crane is a common lifting equipment used in modern factories and workshops. During the crane’s operation, the positioning of the trolley and the swing of the load can significantly impact the bridge crane’s safety and reliability. In this paper, we propose a variable universe fuzzy multi-parameter self-tuning PID (VUFMS-PID) control strategy for controlling the trolley’s movement. Our control strategy uses scaling factor variation to dynamically adjust the number of fuzzy control rules based on the system error and error rate of change. This approach improves control accuracy and enhances the crane’s stability and safety. Simulation results demonstrate that our proposed control strategy outperforms both the fuzzy PID and traditional PID control strategies. Specifically, it reduces the crane trolley’s positioning time and the maximum swing angle of the load. Our control strategy exhibits good adaptive ability and robustness, which further improves the stability and safety of the bridge-type bridge crane operation.

Methane is the fundamental raw material of the C1 chemical industry, with abundant reserves. Its direct conversion into high-value-added chemicals has great scientific significance and broad commercial potential for the efficient use of methane resources. However, it is difficult to convert methane into more useful hydrocarbons and hydrogen, as the reaction usually requires external energy to overcome thermodynamic limitations. Non-oxidative coupling of methane to produce ethane and hydrogen is a promising supply technology. Catalysts which can be adapted to various energy sources are key to this technology. In recent years, considerable progress has been made in the design and application of these thermal and photocatalysts. This review outlines some typical catalysts, and reviews the progress in the understanding of reaction mechanisms. Finally, suggestions for the development of high-selectivity and high-stability catalysts for the future are presented.

Surface defects in arc magnets constitute the main culprit for performance degradation and safety hazards in permanent magnet motors. Machine-vision methods offer the possibility to identify surface defects automatically. However, the current methods still do not adequately solve the problems of low identification accuracy, excessive dependency on training data, and sizeable computational complexity. This paper proposes a lightweight YOLOv5s-based transfer learning model with network pruning and knowledge distillation to address these issues. Our model was derived from a pre-trained YOLOv5s for general object detection. A transfer learning mechanism was designed to obtain the optimal surface defect identification accuracy of the model from fewer training samples. Network pruning and knowledge distillation were combined to compress the transferred model. The transferred model serves as the teacher model of knowledge distillation, while its pruned model acts as the student model. To weaken the loss of the accuracy after model compression, a new λ factor was introduced into the confidence loss function of the student model to increase the sensitivity of identifying the defects. The experimental results show that our model’s performance is higher than other regular lightweight models. The identification accuracy for different defective arc magnets could reach 100%, the model size could achieve 1.921 MB, and the average inference time was 9.46 ms. Our model also has high accuracy in other defect identification applications besides arc magnets.

The hippocampus is an important part of the limbic system in the human brain that has essential roles in spatial navigation and cognitive functions. It is still unknown how gene expression changes in single-cell in different spatial locations of the hippocampus of Parkinson’s disease. The purpose of this study was to analyze the gene expression features of single cells in different spatial locations of mouse hippocampus, and to explore the effects of gene expression regulation on learning and memory mechanisms. Here, we obtained 74 single-cell samples from different spatial locations in a mouse hippocampus through microdissection technology, and used single-cell RNA-sequencing and spatial transcriptome sequencing to visualize and quantify the single-cell transcriptome features of tissue sections. The results of differential expression analysis showed that the expression of Sv2b, Neurod6, Grp and Stk32b genes in a hippocampus single cell at different locations was significantly different, and the marker genes of CA1, CA3 and DG subregions were identified. The results of gene function enrichment analysis showed that the up-regulated differentially expressed genes Tubb2a, Eno1, Atp2b1, Plk2, Map4, Pex5l, Fibcd1 and Pdzd2 were mainly involved in neuron to neuron synapse, vesicle-mediated transport in synapse, calcium signaling pathway and neurodegenerative disease pathways, thus affecting learning and memory function. It revealed the transcriptome profile and heterogeneity of spatially located cells in the hippocampus of PD for the first time, and demonstrated that the impaired learning and memory ability of PD was affected by the synergistic effect of CA1 and CA3 subregions neuron genes. These results are crucial for understanding the pathological mechanism of the Parkinson’s disease and making precise treatment plans.

The present work demonstrates the optimization of the ligand structure in the series of bis(phosphine oxide) and β-ketophosphine oxide representatives for efficient coordination of Tb3+ and Eu3+ ions with the formation of the complexes exhibiting high Tb3+- and Eu3+-centered luminescence. The analysis of the stoichiometry and structure of the lanthanide complexes obtained using the XRD method reveals the great impact of the bridging group nature between two phosphine oxide moieties on the coordination mode of the ligands with Tb3+ and Eu3+ ions. The bridging imido-group facilitates the deprotonation of the imido- bis(phosphine oxide) ligand followed by the formation of tris-complexes. The spectral and PXRD analysis of the separated colloids indicates that the high stability of the tris-complexes provides their safe conversion into polystyrenesulfonate-stabilized colloids using the solvent exchange method. The red Eu3+-centered luminescence of the tris-complex exhibits the same specificity in the solutions and the colloids. The pronounced luminescent response on the antibiotic ceftriaxone allows for sensing the latter in aqueous solutions with an LOD value equal to 0.974 μM.

Botrytis cinerea, the causal agent of gray mold, is one of the most destructive pathogens of cherry tomatoes, causing fruit decay and economic loss. Fludioxonil is an effective fungicide widely used for crop protection and is effective against tomato gray mold. The emergence of fungicide-resistant strains has made the control of B. cinerea more difficult. While the genome of B. cinerea is available, there are few reports regarding the large-scale functional annotation of the genome using expressed genes derived from transcriptomes, and the mechanism(s) underlying such fludioxonil resistance remain unclear. The present study prepared RNA-sequencing (RNA-seq) libraries for three B. cinerea strains (two highly resistant (LR and FR) versus one highly sensitive (S) to fludioxonil), with and without fludioxonil treatment, to identify fludioxonil responsive genes that associated to fungicide resistance. Functional enrichment analysis identified nine resistance related DEGs in the fludioxonil-induced LR and FR transcriptome that were simultaneously up-regulated, and seven resistance related DEGs down-regulated. These included adenosine triphosphate (ATP)-binding cassette (ABC) transporter-encoding genes, major facilitator superfamily (MFS) transporter-encoding genes, and the high-osmolarity glycerol (HOG) pathway homologues or related genes. The expression patterns of twelve out of the sixteen fludioxonil-responsive genes, obtained from the RNA-sequence data sets, were validated using quantitative real-time PCR (qRT-PCR). Based on RNA-sequence analysis, it was found that hybrid histidine kinase, fungal HHKs, such as BOS1, BcHHK2, and BcHHK17, probably involved in the fludioxonil resistance of B. cinerea, in addition, a number of ABC and MFS transporter genes that were not reported before, such as BcATRO, BMR1, BMR3, BcNMT1, BcAMF1, BcTOP1, BcVBA2, and BcYHK8, were differentially expressed in the fludioxonil-resistant strains, indicating that overexpression of these efflux transporters located in the plasma membranes may associate with the fludioxonil resistance mechanism of B. cinerea. All together, these lines of evidence allowed us to draw a general portrait of the anti-fludioxonil mechanisms for B. cinerea, and the assembled and annotated transcriptome data provide valuable genomic resources for further study of the molecular mechanisms of B. cinerea resistance to fludioxonil.

In this paper, we have demonstrated a dispersion-managed, high-power, Tm-Ho co-doped ultrashort pulse fiber laser using a single walled carbon nanotube (SWNT) dispersed in polyimide film. An in-line type spectral filter was developed to control the output pulse spectra. Two SWNT films with different modulation depths were examined as a mode-locker. Normal dispersion fiber was used in the fiber laser oscillator, and dependence on net cavity dispersion was investigated. Passive mode-locking was achieved in a wide dispersion range, from −0.319 to +0.101 ps2. Stable soliton mode-locking operation and dissipative soliton mode-locking operations were observed. The pumping efficiency was ~3 times higher than that in a Tm-doped fiber laser with a similar configuration. The developed fiber laser showed self-start and stable operations, and this laser is useful for practical applications.

The atomic structure of pure and defective graphite has been modelled using classical many body potentials from which simulated powder X-ray Diffraction (XRD) patterns were produced using the Debyer software. The changes in the XRD patterns due to both heating and the inclusion of defects were investigated. After heating, the results show a shift in the 004 Laue peak in qualitative agreement with experiment. The c parameter is shown to increase over the temperature range 0 – 1000 K but there is a slight reduction in the a parameter over this range. The scattering angle for the 004 peak reduces with the introduction of defects up to ≈5% defect concentration for both vacancies and interstitials with a larger reduction in the case of interstitials. The intensity of the scattering peak is reduced with increasing interstitials (25% reduction at 5% concentration), but remains relatively constant with increasing vacancies. The introduction of a small percentage of interstitials causes an increase in both the a and c parameters but vacancies cause a reduction in the a parameter.

A series of modified montmorillonites were prepared by acid modification method prior to the organosilicon grafting. Aflatoxin B1, zearalenone and deoxynivalenol (DON) were selected to evaluated the mycotoxin adsorption performance of modified montmorrillonites. The experimental results suggest that under acidic conditions, the higher the charge density in the covalent orbital of the active group, the stronger the interaction between it and the DON molecule, and the better the corresponding modified montmorillonite adsorbs DON. Silicified montmorillonite with active groups of cyano group and methacryloyloxy group has the best adsorption performance for DON, and the adsorption degree are 51.6% and 39.0%, respectively. However, under alkaline terms, due to the hydrolysis of active groups, the adsorption degree of montmorillonite on DON dropped steeply.

Soybean transcription factor GmNAC plays important roles in plant resistance to environmental stresses. In this study, GmNAC3 was cloned in the drought tolerant soybean variety “Jiyu47”, with the molecular properties of GmNAC3 characterized to establish its candidacy as a NAC transcription factor. The yeast self-activation experiments revealed the transcriptional activation activity of GmNAC3, which was localized in the nucleus by the subcellular localization analysis. The highest expression of GmNAC3 was detected in roots in the podding stage of soybean, and in roots of soybean seedlings treated with 20% PEG6000 for 12 h, which was 16 times higher compared with the control. In the transgenic soybean hairy roots obtained by the Agrobacterium-mediated method treated with 20% PEG6000 for 12 h, the activities of superoxide dismutase, peroxidase, and catalase and the content of proline were increased, the malondialdehyde content was decreased, and the expressions of stress resistance-related genes (i.e., APX2, LEA14, 6PGDH, and P5CS) were up-regulated. These expression patterns were confirmed by transgenic Arabidopsis thaliana with the overexpression of GmNAC3. This study provided strong scientific evidence to support further investigation of the regulatory function of GmNAC3 in plant drought resistance and the molecular mechanisms regulating the plant response to environmental stresses.

The suspension system is a significant part of a vehicle because it transmits the torque and force between the wheels and the frame, meeting the requirements of ride comfort. In this paper, a novel interconnected air suspension was introduced and a cooperative control between interconnected mode activation (IMA) and outsourced mode activation (OMA) was designed. To improve ride comfort in a bus at a minimal energy consumption, this cooperative control based on model predictive control (MPC) for computing the best force and the rule was defined to distribute the best suspension force generated by IMA and OMA. The simulation and experimental results showed that the proposed control strategy significantly improved ride comfort in different conditions. Compared with traditional control in the test vehicle, the RMS of the front-left sprung mass and unsprung vertical acceleration decreased by 24.2% and 14.5%, respectively, under a straight condition; the RMS of the sprung (unsprung) mass vertical acceleration reduced by 22.38% and 15.43%, respectively, under a bump condition.

RNA degradation can significantly affect the results of gene expression profiling, with subsequent analysis failing to faithfully represent the initial gene expression level. It is urgent to have an artificial intelligence approach to better utilize the limited data to obtain meaningful and reliable analysis results in the case of data with missing destination time. In this study, we propose a method based on the signal decomposition technique and deep learning, named Multi-LSTM. It is divided into two main modules: One decomposes the collected gene expression data by an empirical mode decomposition (EMD) algorithm to obtain a series of sub-modules with different frequencies to improve data stability and reduce modeling complexity. The other is based on long short-term memory (LSTM) as the core predictor, aiming to deeply explore the temporal nonlinear relationships embedded in the sub-modules. Finally, the prediction results of sub-modules are reconstructed to obtain the final prediction results of time-series transcriptomic gene expression. The results show that EMD can efficiently reduce the nonlinearity of the original data, which provides reliable theoretical support to reduce the complexity and improve the robustness of LSTM models. Overall, the decomposition-combination prediction framework can effectively predict gene expression levels at unknown time points.

Insects have a robust capacity to produce offspring for propagation, and the reproductive events of female insects have been achieved at the molecular and physiological levels via regulatory gene pathways. However, the roles of MicroRNAs (miRNAs) in the reproductive development of the brown planthopper (BPH), Nilaparvata lugens, remain largely unexplored. To understand the roles of miRNAs in reproductive development, miRNAs were identified by Solexa sequencing in short-winged (SW) female adults of BPH. Small RNA libraries derived from three developmental phases (1 day, 3 days, and 5 days after emergence) were constructed and sequenced. We identified 905 miRNAs, including 263 known and 642 novel miRNAs. Among them, a total of 43 miRNAs were differentially expressed in the three developmental phases, and 14,568 putative targets for 43 differentially expressed miRNAs (DEMs) were predicted by TargetScan and miRanda. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the predicted miRNA targets illustrated the putative roles for these DEMs in reproduction. The progress events were annotated, including oogenesis, lipid biosynthetic process, and related pathways such as apoptosis, ABC transporters, and amino acid metabolism. Four highly abundant DEMs (miR-9a-5p, miR-34-5p, miR-275-3p, and miR-317-3p) were further screened, and miR-34-5p was confirmed to be involved in the regulation of reproduction. Overexpression of miR-34-5p via injecting its mimics reduced fecundity and decreased Vg expression. Moreover, target genes prediction for miR-34-5p showed they might be involved in 20E signaling cascades, apoptosis, and gonadal development, including hormone receptor 4 (HR4), caspase-1 (Cp-1), and spermatogenesis-associated protein 20 (SPATA20). These findings provide a valuable resource for future studies on the role of miRNAs in BPH reproductive development.

The use of molecular imaging technologies for brain imaging can not only play an important supporting role in disease diagnosis and treatment but can also be used to deeply study brain functions. Recently, with the support of reporter gene technology, optical imaging has achieved a breakthrough in brain function studies at the molecular level. Reporter gene technology based on traditional clinical imaging modalities is also expanding. By benefiting from the deeper imaging depths and wider imaging ranges now possible, these methods have led to breakthroughs in preclinical and clinical research. This article focuses on the applications of magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) reporter gene technologies for use in brain imaging. The tracking of cell therapies and gene therapies is the most successful and widely used application of these techniques. Meanwhile, breakthroughs have been achieved in the research and development of reporter genes and their imaging probe pairs with respect to brain function research. This paper introduces the imaging principles and classifications of the reporter gene technologies of these imaging modalities, lists the relevant brain imaging applications, reviews their characteristics, and discusses the opportunities and challenges faced by clinical imaging modalities based on reporter gene technology. The conclusion is provided in the last section.

An optimization model for the optical imaging system was established in this paper. It combined the modern design of experiments (DOE) method known as Latin hypercube sampling (LHS), Kriging surrogate model training, and the multi-objective optimization algorithm NSGA-III into the optimization of a triplet optical system. Compared with the methods that rely mainly on optical system simulation, this surrogate model-based multi-objective optimization method can achieve a high-accuracy result with significantly improved optimization efficiency. Using this model, case studies were carried out for two-objective optimizations of a Cooke triplet optical system. The results showed that the weighted geometric spot diagram and the maximum field curvature were reduced 5.32% and 11.59%, respectively, in the first case. In the second case, where the initial parameters were already optimized by Code-V, this model further reduced the weighted geometric spot diagram and the maximum field curvature by another 3.53% and 4.33%, respectively. The imaging quality in both cases was considerably improved compared with the initial design, indicating that the model is suitable for the optimal design of an optical system.

Nanozymes have been developed as new generation of biomimetic antibiotics against wound infection. However, most of new-developed nanozymes based on inorganic particles or hybrid ones usually originate from incompatible raw materials or unwanted metal salts, highly limiting their further biomedical usages. To overcome above drawbacks, it is highly required to develop novel nanozymes with great antibacterial activity by using biocompatible reagents and endogenous metal species as raw materials. Here, we demonstrated that bovine serum albumin enwrapped copper phosphate-based protein-inorganic hybrid nanoflowers possessed intrinsic peroxidase-like activity, which could be used as efficient biomimetic antibiotics against bacterial infection via the nanozyme-mediated generation of high toxic reactive oxygen species (ROS). With the admirable peroxidase-like activity, our nanoflowers could efficiently kill drug-resistance bacteria under physiological conditions, improve the wound healing after pathogen-induced infection, as well as avoid the potential tissue injury in time. Comprehensive toxicity exploration of these nanoflowers indicated their high biocompatibility and excellent biosafety. Our current strategy toward the design of protein-inorganic hybrid nanozymes with high biosafety and few side effects could provide a new paradigm for the development of nanozyme-based antibacterial platform in future.

Fibroblast growth factor 21 (FGF21) functions as a polypeptide hormone to regulate glucose and lipid metabolism, and its expression is regulated by cellular metabolic stress. Pyruvate is an important intermediate metabolite that acts as a key hub for cellular fuel metabolism. However, the effect of pyruvate on hepatic FGF21 expression and secretion remains unknown. Herein, we examined the gene expression and protein levels of FGF21 in human hepatoma HepG2 cells and mouse AML12 hepatocytes in vitro, as well as in mice in vivo. In HepG2 and AML12 cells, pyruvate at concentrations above 0.1 mM significantly increased FGF21 expression and secretion. The increase in cellular cAMP levels by adenylyl cyclase activation, phosphodiesterase (PDE) inhibition and 8-Bromo-cAMP administration significantly restrained pyruvate-stimulated FGF21 expression. Pyruvate significantly increased PDE activities, reduced cAMP levels and decreased CREB phosphorylation. The inhibition of exchange protein directed activated by cAMP (Epac) and cAMP response element binding protein (CREB) upregulated FGF21 expression, upon which pyruvate no longer increased FGF21 expression. The increase in plasma pyruvate levels in mice induced by the intraperitoneal injection of pyruvate significantly increased FGF21 gene expression and PDE activity with a reduction in cAMP levels and CREB phosphorylation in the mouse liver compared with the control. In conclusion, pyruvate activates PDEs to reduce cAMP and then inhibits the cAMP–Epac–CREB signaling pathway to upregulate FGF21 expression in hepatocytes.

The thermal catalytic conversion of biomass is currently a prevalent method for producing activated carbon with superb textural properties and excellent adsorption performance. However, activated carbon suffers severely from its poor thermal stability, which can easily result in spontaneous burning. In contrast, silica material is famed for its easy accessibility, high specific surface area, and remarkable thermal stability; however, its broader applications are restricted by its strong hydrophilicity. Based on this, the present review summarizes the recent progress made in carbon-silica composite materials, including the various preparation methods using diverse carbon (including biomass resources) and silica precursors, their corresponding structure–function relationship, and their applications in adsorption, insulation, batteries, and sensors. Through their combination, the drawbacks of the individual materials are circumvented while their original advantages are maintained. Finally, several bottlenecks existing in the field of carbon-silica composites, from synthesis to applications, are discussed in this paper, and possible solutions are given accordingly.

In this work, black phosphorus nanosheets (BPNSs) were prepared by liquid exfoliation in N-methyl-2-pyrrolidone (NMP) and characterized by TEM, AFM, Raman spectroscopy and UV–vis absorption spectroscopy. A novel electrochemical sensor was constructed based on the BPNSs and used to measure pH. As the pH of the solution increases, the oxidation current of the BPNSs decreases. The oxidation degree of the BPNSs may be responsible for their different electrochemical responses to pH. The zeta potentials of the BPNSs also appear to be more negative at higher pH values. The results show that the sensor has a linear response in the pH range 1.0–8.0. The resulting electrochemical sensor could thus be used for accurate pH measurement and was successfully applied to the determination of pH in blood and food samples. The proposed method is simple but is shown to have high accuracy, versatility and applicability.

Cancer stem cells (CSCs) are a small subset of cells that sit atop the hierarchical ladder in many cancer types. Liver CSCs have been associated with high chemoresistance and recurrence rates in hepatocellular carcinoma (HCC). However, as of yet, no satisfactorily effective liver CSC-targeted treatment is available, which drove us to design and investigate the efficacy of a liposome-based delivery system. Here, we introduce a redox-triggered dual-targeted liposome, CEP-LP@S/D, capable of co-delivering doxorubicin (Dox) and salinomycin (Sal) for the synergistic treatment of liver cancer. This system is based on the association of CD133- and EpCAM-targeted peptides to form Y-shaped CEP ligands that were anchored to the surface of the liposome and allowed the selective targeting of CD133+ EpCAM+ liver CSCs. After arriving to the CSCs, the CEP-LP@S/D liposome undergoes endocytosis to the cytoplasm, where a high concentration of glutathione (GSH) breaks its disulfide bonds, thereby degrading the liposome. This then induces a rapid release of Dox and Sal to synergistically inhibit tumor growth. Notably, this effect occurs through Dox-induced apoptosis and concurrent lysosomal iron sequestration by Sal. Interestingly, both in vitro and in vivo studies indicated that our GSH-responsive co-delivery system not only effectively enhanced CSC targeting but also eliminated the non-CSC faction, thereby exhibiting high antitumor efficacy. We believe that the smart liposome nanocarrier-based co-delivery system is a promising strategy to combat liver cancer, which may also lay the groundwork for more enhanced approaches to target other cancer types as well.

Paraphrase detection and generation are important natural language processing (NLP) tasks. Yet the term paraphrase is broad enough to include many fine-grained relations. This leads to different tolerance levels of semantic divergence in the positive paraphrase class among publicly available paraphrase datasets. Such variation can affect the generalisability of paraphrase classification models. It may also impact the predictability of paraphrase generation models. This paper presents a new model which can use few corpora of fine-grained paraphrase relations to construct automatically using language inference models. The fine-grained sentence level paraphrase relations are defined based on word and phrase level counterparts. We demonstrate that the fine-grained labels from our proposed system can make it possible to generate paraphrases at desirable semantic level. The new labels could also contribute to general sentence embedding techniques.

Hydrogen sulfide (H2S) is an important signaling molecule that regulates diverse cellular signaling pathways through persulfidation. Our previous study revealed that H2S is involved in the improvement of rice drought tolerance. However, the corresponding enzymatic sources of H2S and its regulatory mechanism in response to drought stress are not clear. Here, we cloned and characterized a putative l-cysteine desulfhydrase (LCD) gene in rice, which encodes a protein possessing H2S-producing activity and was named OsLCD1. Overexpression of OsLCD1 results in enhanced H2S production, persulfidation of total soluble protein, and confers rice drought tolerance. Further, we found that nitrate reductase (NR) activity was decreased under drought stress, and the inhibition of NR activity was controlled by endogenous H2S production. Persulfidation of NIA2, an NR isoform responsible for the main NR activity, led to a decrease in total NR activity in rice. Furthermore, drought stress-triggered inhibition of NR activity and persulfidation of NIA2 was intensified in the OsLCD1 overexpression line. Phenotypical and molecular analysis revealed that mutation of NIA2 enhanced rice drought tolerance by activating the expression of genes encoding antioxidant enzymes and ABA-responsive genes. Taken together, our results showed the role of OsLCD1 in modulating H2S production and provided insight into H2S-regulated persulfidation of NIA2 in the control of rice drought stress.

G protein-coupled estrogen receptor 1 (GPER1) is a potential therapeutic target for treating triple-negative breast cancers (TNBC). However, modulators for GPER1 that can be used to treat TNBC have not appeared. Berberine (BBR) is a bioactive isoquinoline alkaloid with high oral safety. In recent years, BBR has shown an inhibitory effect on TNBC tumors such as MDA-MB-231, but the molecular target remains unclear, which hinders related clinical research. Our work proved that BBR is a modulator of GPER1 that can inhibit cell viability, migration, and autophagy of MDA-MB-231 cells. The inhibitory effect of BBR on MDA-MB-231 cells has a dependence on estrogen levels. Although BBR promoted the proteasome, which is a major factor in the degradation of GPER1, it could still induce the protein level of GPER1. Correspondingly, the transcription of cellular communication network factor 2 (CCN2) was promoted. BBR could bind to GPER1 directly and change the secondary structure of GPER1, as in the case of 17β-estradiol (E2). In addition, BBR induced not only a high degree of co-localization of GPER1 and microtubule-associated protein 1 light chain 3 (MAP1LC3), but also the accumulation of sequestosome 1 (SQSTM1/p62) by the inhibition of the nuclear translocation of the nuclear factor-kappa B (NF-κB) subunit (RELA/p65), which indicates NF-κB inhibition and anti-cancer effects. This result proved that the promotional effect of BBR on the GPER1/NF-κB pathway was closely related to its inhibitory effect on autophagy, which may serve as a new mechanism by which to explain the inhibitory effect of BBR on MDA-MB-231 cells and expand our understanding of the function of both BBR and GPER1.

Osteoarthritis (OA), a degenerative joint disorder, has been reported as the most common cause of disability worldwide. The production of inflammatory cytokines is the main factor in OA. Previous studies have been reported that obeticholic acid (OCA) and OCA derivatives inhibited the release of proinflammatory cytokines in acute liver failure, but they have not been studied in the progression of OA. In our study, we screened our small synthetic library of OCA derivatives and found T-2054 had anti-inflammatory properties. Meanwhile, the proliferation of RAW 264.7 cells and ATDC5 cells were not affected by T-2054. T-2054 treatment significantly relieved the release of NO, as well as mRNA and protein expression levels of inflammatory cytokines (IL-6, IL-8 and TNF-α) in LPS-induced RAW 264.7 cells. Moreover, T-2054 promoted extracellular matrix (ECM) synthesis in TNF-α-treated ATDC5 chondrocytes. Moreover, T-2054 could relieve the infiltration of inflammatory cells and degeneration of the cartilage matrix and decrease the levels of serum IL-6, IL-8 and TNF-α in DMM-induced C57BL/6 mice models. At the same time, T-2054 showed no obvious toxicity to mice. Mechanistically, T-2054 decreased the extent of p-p65 expression in LPS-induced RAW 264.7 cells and TNF-α-treated ATDC5 chondrocytes. In summary, we showed for the first time that T-2054 effectively reduced the release of inflammatory mediators, as well as promoted extracellular matrix (ECM) synthesis via the NF-κB-signaling pathway. Our findings support the potential use of T-2054 as an effective therapeutic agent for the treatment of OA.

Ambient illuminance and screen luminance have a significant influence on the visual fatigue and visual performance associated with the use of computers. The current study was conducted to investigate optimal screen luminance under different ambient illuminances and fit a curve of the optimum luminance of LCD screens under evening illumination. Thirty-three participants were assigned to rate screen brightness, visual comfort with screen luminance, satisfaction with ambient illuminance and visual fatigue under six screen luminance levels (3.87, 21.47, 42.74, 64.12, 84.77 and 106.7 cd/m2) combined with five ambient illuminance levels (0, 25, 50, 75 and 100 lx) in the evening. The results showed that optimum LCD screen luminance increased with increasing ambient illuminance. Moreover, ambient illuminance and screen luminance levels should be in the range of 13.08–62.16 lx and 20.63–75.15 cd/m2, respectively, to obtain the optimal subjective feelings of visual fatigue and visual comfort during the evening.