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Abstract Human interleukin-10 (IL-10) is an immunosuppressive and anti-inflammatory cytokine, and its expression is upregulated in tumor tissues and serum samples of patients with various cancers. Because of its immunosuppressive nature, IL-10 has also been suggested to be a factor leading to tumor cells’ evasion of immune surveillance and clearance by the host immune system. In this study, we refined a peptide with 20 amino acids, named NK20a, derived from the binding region of IL-10 on the basis of in silico analysis of the complex structure of IL-10 with IL-10Ra, the ligand binding subunit of the IL-10 receptor. The binding ability of the peptide was confirmed through in vitro biophysical biolayer interferometry and cellular experiments. The IL-10 inhibitory peptide exerted anticancer effects on lymphoma B cells and could abolish the suppression effect of IL-10 on macrophages. NK20a was also conjugated with gold nanoparticles to target the chemotherapeutic 5-fluorouracil (5-FU)-loaded nanoparticles to enhance the anticancer efficacy of 5-FU against the breast cancer cell line BT-474. Our study demonstrated that NK20a designed in silico with improved binding affinity to the IL-10 receptor can be used as a tool in developing anticancer strategies.

Diabetic retinopathy (DR) severely affects vision in individuals with diabetes. High glucose (HG) induces oxidative stress in retinal cells, a key contributor to DR development. Previous studies suggest that fibroblast growth factor-1 (FGF-1) can mitigate hyperglycemia and protect tissues from HG-induced damage. However, the specific effects and mechanisms of FGF-1 on DR remain unclear. In our study, FGF-1-pretreated adult retinal pigment epithelial (ARPE)-19 cells were employed to investigate. Results indicate that FGF-1 significantly attenuated HG-induced oxidative stress, including reactive oxygen species, DNA damage, protein carbonyl content, and lipid peroxidation. FGF-1 also modulated the expression of oxidative and antioxidative enzymes. Mechanistic investigations showed that HG induced high endoplasmic reticulum (ER) stress and upregulated specific proteins associated with apoptosis. FGF-1 effectively alleviated ER stress, reduced apoptosis, and restored autophagy through the adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin signaling pathway. We observed that the changes induced by HG were dose-dependently reversed by FGF-1. Higher concentrations of FGF-1 (5 and 10 ng/mL) exhibited increased effectiveness in mitigating HG-induced damage, reaching statistical significance (p < 0.05). In conclusion, our study underscores the promising potential of FGF-1 as a safeguard against DR. FGF-1 emerges as a formidable intervention, attenuating oxidative stress, ER stress, and apoptosis, while concurrently promoting autophagy. This multifaceted impact positions FGF-1 as a compelling candidate for alleviating retinal cell damage in the complex pathogenesis of DR.

The BRI1 EMS suppressor 1(BES1) transcription factor is a crucial regulator in the signaling pathway of Brassinosteroid (BR) and plays an important role in plant growth and response to abiotic stress. Although the identification and functional validation of BES1 genes have been extensively explored in various plant species, the understanding of their role in woody plants—particularly the endangered species Phoebe bournei (Hemsl.) Yang—remains limited. In this study, we identified nine members of the BES1 gene family in the genome of P. bournei; these nine members were unevenly distributed across four chromosomes. In our further evolutionary analysis of PbBES1, we discovered that PbBES1 can be divided into three subfamilies (Class I, Class II, and Class IV) based on the evolutionary tree constructed with Arabidopsis thaliana, Oryza sativa, and Solanum lycopersicum. Each subfamily contains 2–5 PbBES1 genes. There were nine pairs of homologous BES1 genes in the synteny analysis of PbBES1 and AtBES1. Three segmental replication events and one pair of tandem duplication events were present among the PbBES1 family members. Additionally, we conducted promoter cis-acting element analysis and discovered that PbBES1 contains binding sites for plant growth and development, cell cycle regulation, and response to abiotic stress. PbBES1.2 is highly expressed in root bark, stem bark, root xylem, and stem xylem. PbBES1.3 was expressed in five tissues. Moreover, we examined the expression profiles of five representative PbBES1 genes under heat and drought stress. These experiments preliminarily verified their responsiveness and functional roles in mediating responses to abiotic stress. This study provides important clues to elucidate the functional characteristics of the BES1 gene family, and at the same time provides new insights and valuable information for the regulation of resistance in P. bournei.

Abstract MnSe and Co0.85Se embedded in nitrogen‐doped carbon nanofibers (MnSe/Co0.85Se/N‐CNFs) were synthesized by electrospinning and high‐temperature calcination, and evaluated for the first time as sodium/potassium‐ion battery anode material via constant current charge/discharge, cyclic voltammetry, electrochemical impedance spectroscopy.Ex‐situ XRD revealed the potassium storage mechanism of MnSe/Co0.85Se/N‐CNFs, indicating that its capacity was mainly provided by the conversion reaction. Compared with MnSe/N‐CNFs and Co0.85Se/N‐CNFs, the reversible capacity and cycling performance of MnSe/Co0.85Se/N‐CNFs were significantly improved due to the synergistic effect of bimetals. The MnSe/Co0.85Se/N‐CNFs electrode showed a charging capacity of 262.3 mAh g−1 after 700 cycles at 1 A g−1 in Na‐ion batteries and a discharge capacity of 183.4 mAh g−1 after 400 cycles at 0.1 A g−1 in K‐ion batteries, The results showed that binder‐free binary metal MnSe/Co0.85Se/N‐CNFs have a certain development prospect as anode for sodium/potassium‐ion batteries.

Abstract The performance enhancement of integrated circuits relying on dimension scaling (i.e., following Moore’s Law) is more and more challenging owing to the physical limit of Si materials. Monolithic three-dimensional (M3D) integration has been considered as a powerful scheme to further boost up the system performance. Two-dimensional (2D) materials such as MoS2 are potential building blocks for constructing upper-tier transistors owing to their high mobility, atomic thickness, and back-end-of-line (BEOL) compatible processes. The concept to integrate 2D material-based devices with Si field-effect transistor (FET) is technologically important but the compatibility is yet to be experimentally demonstrated. Here, we successfully integrated an n-type monolayer MoS2 FET on a p-type Si fin-shaped FET with 20 nm fin width via an M3D integration technique to form a complementary inverter. The integration was enabled by deliberately adopting industrially matured techniques, such as chemical mechanical planarization and e-beam evaporation, to ensure its compatibility with the existing 3D integrated circuit process and the semiconductor industry in general. The 2D FET is fabricated using low-temperature sequential processes to avoid the degradation of lower-tier Si devices. The MoS2 n-FETs and Si p-FinFETs display symmetrical transfer characteristics and the resulting 3D complementary metal-oxide-semiconductor inverter show a voltage transfer characteristic with a maximum gain of ~38. This work clearly proves the integration compatibility of 2D materials with Si-based devices, encouraging the further development of monolithic 3D integrated circuits.

Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 μM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3β, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2–PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is multifactorial and composite, with the disorder of lipid metabolism‐induced lipotoxicity being one of the main risk factors. Atorvastatin (AT), the most widely prescribed lipid‐lowering drug, has pleiotropic actions benefiting NAFLD treatment. However, low absorption rate in the gut and potential disruption of AT on gut flora hindered its further applications. Notably, gut dysbiosis is involved in and is thus a promising management strategy for NAFLD. In this study, we constructed a prebiotic‐based AT nanoamorphous (PANA) to improve the efficacy of AT against NAFLD by retrieving liver and gut health. After oral administration, PANA showed superior drug accumulation in the liver tissue compared with pure AT. Moreover, PANA intervention effectively restored gut healthiness, indicated by reconstructed gut flora, and improved intestinal immunity, barrier integrity, and inflammation. Consequently, compared with AT, PANA treatment caused profound inhibition of weight gain and fat deposition, decreased plasma lipid levels, and alleviated hepatic steatosis and liver inflammation. The transcriptome analysis in the gut and liver tissues identified improved immunity and inflammation as potential mechanisms. This study suggests a promising strategy to treat NAFLD, assisted with nanotechnology in synergy with functional biomaterials.

Polygalacturonase (PG) is one of the largest families of hydrolytic enzymes in plants. It is involved in the breakdown of pectin in the plant cell wall and even contributes to peel cracks. Here, we characterize PGs and outline their expression profiles using the available reference genome and transcriptome of Akebia trifoliata. The average length and exon number of the 47 identified AktPGs, unevenly assigned on 14 chromosomes and two unassembled contigs, were 5399 bp and 7, respectively. The phylogenetic tree of 191 PGs, including 47, 57, 51, and 36 from A. trifoliata, Durio zibethinus, Actinidia chinensis, and Vitis vinifera, respectively, showed that AktPGs were distributed in all groups except group G and that 10 AktPGs in group E were older, while the remaining 37 AktPGs were younger. Evolutionarily, all AktPGs generally experienced whole-genome duplication (WGD)/segmental repeats and purifying selection. Additionally, the origin of conserved domain III was possibly associated with a histidine residue (H) substitute in motif 8. The results of both the phylogenetic tree and expression profiling indicated that five AktPGs, especially AktPG25, could be associated with the cracking process. Detailed information and data on the PG family are beneficial for further study of the postharvest biology of A. trifoliata.

As a common interface circuit for renewable energy integrated into the power grid, the inverter is prone to work under a three-phase unbalanced weak grid. In this paper, the instability of grid-connected inverters under the unbalanced grid condition is investigated. First, a dual second-order generalized integrator phase-locked loop (DSOGI-PLL)-based inverter under balanced and unbalanced conditions is modeled. A fourth-order impedance model is established to describe its impedance characteristics under the unbalanced grid condition. To analyze this multi-input multi-output system, a simplified stability analysis method based on the generalized Nyquist stability criterion and matrix theory is proposed. Then, the influences of circuit and control parameters on the stability of the grid-connected inverter system under the unbalanced grid condition are investigated. Finally, the accuracy of the derived frequency-coupled impedance model is verified via simulations, and the effectiveness of the proposed simplified stability analysis method on the system stability analysis is verified via both simulations and hardware experiments.

Changes in intestinal mucosal barrier permeability lead to antigen sensitization and mast cell-mediated allergic reactions, which are considered to play important roles in the occurrence and development of food allergies. It has been suggested that protein causes increased intestinal permeability via mast cell degranulation, and we investigated the effect of camellia Moringa oleifera leaves protein on intestinal permeability and explored its role in the development of food allergies. The current study investigated the effect of M. oleifera leaves protein on intestinal permeability through assessments of transepithelial electrical resistance (TEER) and transmembrane transport of FITC-dextran by Caco-2 cells. The expression levels of Toll-like receptor 4 (TLR4), IL-8, Occludin, Claudin-1, and perimembrane protein family (ZO-1) were detected by real-time PCR and Western blotting. The effect of M. oleifera leaves protein on intestinal permeability was verified in mice in vivo. The serum fluorescence intensity was measured using the FITC-dextran tracer method, and the expression of tight junction proteins was detected using Western blotting. The results showed that M. oleifera leaves protein widened the gaps between Caco-2 cells, reduced transmembrane resistance, and increased permeability. This protein also reduced the mRNA and protein levels of Occludin, Claudin-1, and ZO-1. Animal experiments showed that intestinal permeability was increased, and that the expression of the tight junction proteins Occludin and Claudin-1 were downregulated in mice. This study shows that M. oleifera leaves protein has components that increase intestinal permeability, decrease tight junction protein expression, promote transmembrane transport in Caco-2 cells, and increase intestinal permeability in experimental animals. The finding that M. oleifera leaves active protein increases intestinal permeability suggests that this protein may be valuable for the prevention, diagnosis, and treatment of M. oleifera leaves allergy.

Aiming at the low contrast of skin lesion image and inaccurate segmentation of lesion boundary, a skin lesion segmentation method based on multi-level split receptive field and attention is proposed. Firstly, the depth feature extraction module and multi-level splitting receptive field module are used to extract image feature information; secondly, the hybrid pooling module is used to build long-term and short-term dependencies and integrate global information and local information. Finally, the reverse residual external attention module is introduced to construct the decoding part, which can mine the potential relationship between data sets and improve the network segmentation ability. Experiments on ISBI2017 and ISIC2018 data sets show that the Dice similarity coefficient and Jaccard index reach 88.67% and 91.84%, 79.25% and 81.48%, respectively, and the accuracy reaches 93.89% and 96.16%. The segmentation method is superior to the existing algorithms as a whole. Simulation experiments show that the network has a good effect on skin lesion image segmentation and provides a new method for skin disease diagnosis.

Alkali-activated persulfate (PS) is widely used in situ in chemical oxidation processes; however, studies on the innovation of the alkali activation process are very limited. Two supported solid superbases, namely KNO3/γ-Al2O3 (KAl) and KNO3/SBA-15/MgO (KSM), respectively, were prepared and used to activate persulfate to degrade DCF in this work. The results showed that the superbases elevated the solution pH once added and thus could catalyze persulfate to degrade diclofenac efficiently above pH 10.5. The catalytic efficiency of KAl was close to that of sodium hydroxide, and that of KSM was the highest. The mechanism might be that, in addition to raising the solution pH, some potassium existed as K2O2, which had a strong oxidizing effect and was conducive to DCF removal. Hydroxyl, sulfate and superoxide radicals were all found in the reaction system, among which hydroxyl might play the most important role. The material composition ratio, common anion and humic acid all had some influences on the catalytic efficiency. A total of five intermediates were found in the KSM/PS oxidation system, and six oxidation pathways, which were hydroxylation, dehydrogen, dechlorination, dehydration, decarboxylation, and C-N bond breakage, might be involved in the reaction process. Several highly toxic oxidation products that should be paid attention to were also proposed.

This paper presents a screw dynamics method for multi-rigid-body systems. It establishes the relationship between velocity screw (twist) and force screw (wrench) in the theorem of momentum screw. Then, the structure of a 2UPS + 2UPU parallel manipulator is introduced as an example of application. By analyzing the constraint wrench of each limb and the twist of the moving platform in the theorem of momentum screw, the dynamics equation for solving the driving force makes the method very convenient for computer programming. The dynamics equation can be reorganized into a non-homogeneous linear equation and establishes the relationship between the constraint wrench of each limb and the twist of the moving platform in screw coordinate. The outstanding advantage of the algorithm proposed in this paper is that the average calculation time is only 83.21% of that of the Newton–Euler method for the 2UPS + 2UPU parallel manipulator on the same computer. This methodology provides a convenient canonical form for the dynamics analysis of multi-rigid-body systems.

Phthalate esters (PAEs) are widely exposed in the environment as plasticizers in plastics, and they have been found to cause significant environmental and health hazards, especially in terms of endocrine disruption in humans. In order to investigate the processes underlying the endocrine disruption effects of PAEs, three machine learning techniques were used in this study to build an adverse outcome pathway (AOP) for those effects on people. According to the results of the three machine learning techniques, the random forest and XGBoost models performed well in terms of prediction. Subsequently, sensitivity analysis was conducted to identify the initial events, key events, and key features influencing the endocrine disruption effects of PAEs on humans. Key features, such as Mol.Wt, Q+, QH+, ELUMO, minHCsats, MEDC-33, and EG, were found to be closely related to the molecular structure. Therefore, a 3D-QSAR model for PAEs was constructed, and, based on the three-dimensional potential energy surface information, it was discovered that the hydrophobic, steric, and electrostatic fields of PAEs significantly influence their endocrine disruption effects on humans. Lastly, an analysis of the contributions of amino acid residues and binding energy (BE) was performed, identifying and confirming that hydrogen bonding, hydrophobic interactions, and van der Waals forces are important factors affecting the AOP of PAEs’ molecular endocrine disruption effects. This study defined and constructed a comprehensive AOP for the endocrine disruption effects of PAEs on humans and developed a method based on theoretical simulation to characterize the AOP, providing theoretical guidance for studying the mechanisms of toxicity caused by other pollutants.

The design of earth-abundant and highly efficient bifunctional electrocatalysts for hydrogen evolution and oxygen evolution reactions (HER/OER) is crucial for hydrogen production through overall water splitting. Herein, we report a novel nanostructure consisting of vertically oriented CoP hierarchical nanosheet arrays with in situ-assembled carbon skeletons on a Ti foil electrode. The novel Zeolitic Imidazolate Framework-67 (ZIF-67) template-derived hierarchical nanosheet architecture effectively improved electrical conductivity, facilitated electrolyte transport, and increased the exposure of the active sites. The obtained bifunctional hybrid exhibited a low overpotential of 72 mV at 10 mA cm−2 and a small Tafel slope of 65 mV dec−1 for HER, and an improved overpotential of 329 mV and a Tafel slope of 107 mV dec−1 for OER. Furthermore, the assembled C@CoP||C@CoP electrolyzer showed excellent overall water splitting performance (1.63 V) at a current density of 10 mA cm−2 and superior durability. This work provides a structure engineering strategy for metal–organic framework (MOF) template-derived hybrids with outstanding electrocatalytic performance.

In order to effectively prevent and control the problem of water inrush from the through-type fault floor, based on the analysis of the case data of water inrush from the fault structure in the Fengfeng mining area, the types of karst water inrush from the floor are divided into 3 categories, 6 subcategories, and 17 fine categories. Four water inrush modes are summarized: composite structure water inrush, through-type fault water inrush, roof crack expansion water inrush, and floor vertical crack expansion water inrush. Based on the grey correlation theory and combined with the Analytic Hierarchy Process (AHP), this paper evaluates the water inrush risk of the F55-1 through-type fault zone from a micro individual perspective, taking the Xin’an Mine as the engineering background. Based on the water–rock coupling theory, the FLAC3D numerical simulation software is applied to study the disaster mechanism of the water inrush mode of the through-type fault. Through analyzing the changes of primary fracture stress and displacement of the intact floor strata and the aquifuge, and the pressure changes of confined water in fault zones, the collaborative water inrush mechanism of the damage and fracture of the bottom plate rock layer, the expansion and connection of the original fracture, and the seepage and progressive intrusion of the pressure water during the advancing process of the working face is analyzed. The research results indicate that the evaluation result of the water inrush risk of the F55-1 through-type fault in Xin’an Mine is Level I, belonging to the high risk and consistent with the actual situation model, verifying the rationality of the evaluation model. The process of water inrush in the numerical model is summarized as follows: a rock pressure failure zone is caused by the rupture and instability of floor aquifuge; a progressive intrusion zone develops—water inrush is connected between rock pressure failure zone and progressive intrusion zone; floor lagging flood occurs. Under the combined action of mine pressure and confined water pressure, the progressive intrusion height of confined water is significantly increased. The research results have important reference basis for future coal mining planning. This provides engineering reference and practical experience for the prevention and control of water damage in structured bottom plates under similar conditions.

Glycoproteins are involved in a variety of biological processes. More than one-third of the plasma protein biomarkers of tumors approved by the FDA are glycoproteins, and could improve the diagnostic specificity and/or sensitivity. Therefore, it is of great significance to perform the systematic characterization of plasma N-glycoproteome. In previous studies, we developed an integrated method based on the combinatorial peptide ligand library (CPLL) and stepped collision energy/higher energy collisional dissociation (sceHCD) for comprehensive plasma N-glycoproteome profiling. Recently, we presented a new fragmentation method, EThcD-sceHCD, which outperformed sceHCD in the accuracy of identification. Herein, we integrated the combinatorial peptide ligand library (CPLL) into EThcD-sceHCD and compared the performance of different mass spectrometry dissociation methods (EThcD-sceHCD, EThcD, and sceHCD) in the intact N-glycopeptide analysis of prostate cancer plasma. The results illustrated that EThcD-sceHCD was better than EThcD and sceHCD in the number of identified intact N-glycopeptides (two-folds). A combination of sceHCD and EThcD-sceHCD methods can cover almost all glycoproteins (96.4%) and intact N-glycopeptides (93.6%), indicating good complementarity between the two. Our study has great potential for medium- and low-abundance plasma glycoprotein biomarker discovery.

The glass relics are precious material evidence of the early trade and cultural exchange between the East and the West. To explore the cultural differences and trade development between early China and foreign countries, it is extremely important to classify glass cultural relics. Despite their similar appearances, Chinese glass contains more lead, while foreign glass contains more potassium. In view of this, this paper proposes a joint Daen-LR, ARIMA-LSTM, and MLR machine learning algorithm (JMLA) for the analysis and identification of the chemical composition of ancient glass. We separate the sampling points of ancient glass into two systems: lead-barium glass and high-potassium glass. Firstly, an improved logistic regression model based on a double adaptive elastic network (Daen-LR) is used to select variables with both Oracle and adaptive classification characteristics. Secondly, the ARIMA-LSTM model was used to establish the correlation curve of chemical composition before and after weathering and to predict the change in chemical composition with weathering. Thirdly, combining the data processed by the above two methods, a multiple linear regression model (MLR) is used to classify unknown glass products. It was shown that the sample obtained by this processing method has a very good fit. In comparison with other similar types of models like Decision Trees (DT), Random Forests (RF), Support Vector Machines (SVM), and Random Forests based on classification and regression trees (CART-RF), the classification accuracy of JMLA is 97.9% on the train set. The accuracy rate on the test set reached 97.6%. The results of the research demonstrate that JMLA can improve the accuracy of the glass type classification problem, greatly enhance the research efficiency of archaeological staff, and gain a more reliable result.

On the basis of the force and safety factor analysis of traditional retaining walls, a new analytical method of force and displacement of the slope is suggested, the numerical theoretical solution of the stress distribution of the sliding body can be obtained under the conditions, which the stresses distribution are satisfied with the differential equilibrium equations, the boundary conditions, the compatibility equation and the macroscopic equilibrium equations. The interface stresses between the sliding body and the retaining wall is continuous, and the theoretical solution of retaining wall stress distributions can be obtained, while the stress differential equilibrium equation, the compatibility equation, macroscopic force, and moment balance equations are satisfied. The strain and displacement solutions can be obtained by using Duncan Chang and Hooke constitutive equations for the slope and the retaining wall, respectively. The transfer station of landfill in the Guandukou Town of Badong County is taken as an example, the results of the sliding body and retaining wall analysis show: The stress and strain solutions of a slope and a retaining wall can be obtained by the proposed method. The anti-slip force of the retaining wall calculated by the method in this paper contains the positive pressure and shear force along the contact surface and varies with the deformation of the slope, in addition, the numerical theoretical solution of the retaining wall shows that the retaining wall shape and material can be optimized according to the calculation results. It is feasible for the proposed analysis method of slope with retaining wall design to be run many years.

Loquat (Eriobotrya japonica Lindl.) is an evergreen fruit tree of Chinese origin, and its autumn–winter flowering and fruiting growth habit means that its fruit development is susceptible to low-temperature stress. In a previous study, the triploid loquat (B431 × GZ23) has been identified with high photosynthetic efficiency and strong resistance under low-temperature stress. Analysis of transcriptomic and lipidomic data revealed that the fatty acid desaturase gene EjFAD8 was closely associated with low temperatures. Phenotypic observations and measurements of physiological indicators in Arabidopsis showed that overexpressing-EjFAD8 transgenic plants were significantly more tolerant to low temperatures compared to the wild-type. Heterologous overexpression of EjFAD8 enhanced some lipid metabolism genes in Arabidopsis, and the unsaturation of lipids was increased, especially for SQDG (16:0/18:1; 16:0/18:3), thereby improving the cold tolerance of transgenic lines. The expression of ICE-CBF-COR genes were further analyzed so that the relationship between fatty acid desaturase and the ICE-CBF-COR pathway can be clarified. These results revealed the important role of EjFAD8 under low-temperature stress in triploid loquat, the increase expression of FAD8 in loquat under low temperatures lead to desaturation of fatty acids. On the one hand, overexpression of EjFAD8 in Arabidopsis increased the expression of ICE-CBF-COR genes in response to low temperatures. On the other hand, upregulation of EjFAD8 at low temperatures increased fatty acid desaturation of SQDG to maintain the stability of photosynthesis under low temperatures. This study not only indicates that the EjFAD8 gene plays an important role in loquat under low temperatures, but also provides a theoretical basis for future molecular breeding of loquat for cold resistance.

Metal/nitrogen-doped carbon single-atom catalysts (M−N−C SACs) show excellent catalytic performance with a maximum atom utilization and customizable tunable electronic structure. However, precisely modulating the M−Nx coordination in M−N−C SACs remains a grand challenge. Here, we used a N-rich nucleobase coordination self-assembly strategy to precisely regulate the dispersion of metal atoms by controlling the metal ratio. Meanwhile, the elimination of Zn during pyrolysis produced porous carbon microspheres with a specific surface area of up to 1151 m2 g−1, allowing maximum exposure of Co−N4 sites and facilitating charge transport in the oxygen reduction reaction (ORR) process. Thereby, the monodispersed cobalt sites (Co−N4) in N-rich (18.49 at%) porous carbon microspheres (CoSA/N−PCMS) displayed excellent ORR activity under alkaline conditions. Simultaneously, the Zn−air battery (ZAB) assembled with CoSA/N−PCMS outperformed Pt/C+RuO2-based ZABs in terms of power density and capacity, proving that they have good prospects for practical application.

As a kind of plant-specific transcription factor (TF), DNA-Binding One Zinc Finger (Dof) is widely involved in the response to environmental change, and as an evolutionarily important perennial plant species, Akebia trifoliata is ideal for studying environmental adaptation. In this study, a total of 41 AktDofs were identified in the A. trifoliata genome. First, the characteristics, including the length, exon number, and chromosomal distribution of the AktDofs and the isoelectric point (PI), amino acid number, molecular weight (MW), and conserved motifs of their putative proteins, were reported. Second, we found that all AktDofs evolutionarily underwent strong purifying selection, and many (33, 80.5%) of them were generated by whole-genome duplication (WGD). Third, we outlined their expression profiles by the use of available transcriptomic data and RT-qPCR analysis. Finally, we identified four candidate genes (AktDof21, AktDof20, AktDof36, and AktDof17) and three other candidate genes (AktDof26, AktDof16, and AktDof12) that respond to long day (LD) and darkness, respectively, and that are closely associated with phytohormone-regulating pathways. Overall, this research is the first to identify and characterize the AktDofs family and is very helpful for further research on A. trifoliata adaptation to environmental factors, especially photoperiod changes.

One of the key steps in tumorigenic transformation is immortalization in which cells bypass cancer-initiating barriers such as senescence. Senescence can be triggered by either telomere erosion or oncogenic stress (oncogene-induced senescence, OIS) and undergo p53- or Rb-dependent cell cycle arrest. The tumor suppressor p53 is mutated in 50% of human cancers. In this study, we generated p53N236S (p53S) mutant knock-in mice and observed that p53S heterozygous mouse embryonic fibroblasts (p53S/+) escaped HRasV12-induced senescence after subculture in vitro and formed tumors after subcutaneous injection into severe combined immune deficiency (SCID) mice. We found that p53S increased the level and nuclear translocation of PGC–1α in late-stage p53S/++Ras cells (LS cells, which bypassed the OIS). The increase in PGC–1α promoted the biosynthesis and function of mitochondria in LS cells by inhibiting senescence-associated reactive oxygen species (ROS) and ROS-induced autophagy. In addition, p53S regulated the interaction between PGC–1α and PPARγ and promoted lipid synthesis, which may indicate an auxiliary pathway for facilitating cell escape from aging. Our results illuminate the mechanisms underlying p53S mutant-regulated senescence bypass and demonstrate the role played by PGC–1α in this process.

Synthetic musks (SMs), as an indispensable odor additive, are widely used in various personal care products. However, due to their physico-chemical properties, SMs were detected in various environmental media, even in samples from arctic regions, leading to severe threats to human health (e.g., abortion risk). Environmentally friendly and functionally improved SMs have been theoretically designed in previous studies. However, the synthesizability of these derivatives has barely been proven. Thus, this study developed a method to verify the synthesizability of previously designed SM derivatives using machine learning, 2D-QSAR, 3D-QSAR, and high-throughput density functional theory in order to screen for synthesizable, high-performance (odor sensitivity), and environmentally friendly SM derivatives. In this study, three SM derivatives (i.e., D52, D37, and D25) were screened and recommended due to their good performances (i.e., high synthesizability and odor sensitivity; low abortion risk; and bioaccumulation ability in skin keratin). In addition, the synthesizability mechanism of SM derivatives was also analyzed. Results revealed that high intramolecular hydrogen bond strength, electrostatic interaction, qH+ value, energy gap, and low EHOMO would lead to a higher synthesizability of SMs and their derivatives. This study broke the synthesizability bottleneck of theoretically designed environment-friendly SM derivatives and advanced the mechanism of screening functional derivatives.

Single-walled carbon nanotubes (SWCNTs) have an advantage in printing thin film transistors (TFTs) due to their high carrier mobility, excellent chemical stability, mechanical flexibility, and compatibility with solution-based processing. Thus, the printed SWCNT-based TFTs (pSWCNT-TFTs) showed significant technological potential such as integrated circuits, conformable sensors, and display backplanes. However, the long-term environmental stability of the pSWCNT-TFTs hinders their commercialization. Thus, to extend the stability of the pSWCNT-TFTs, such devices should be passivated with low water and oxygen permeability. Herein, we introduced the silicon nitride (SiNx) passivation method on the pSWCNT-TFTs via a combination of roll-to-roll (R2R) gravure and the roll-to-roll plasma-enhanced vapor deposition (R2R-PECVD) process at low temperature (45 °C). We found that SiNx-passivated pSWCNT-TFTs showed ± 0.50 V of threshold voltage change at room temperature for 3 days and ±1.2 V of threshold voltage change for 3 h through a Temperature Humidity Test (85/85 test: Humidity 85%/Temperature 85 °C) for both p-type and n-type pSWCNT-TFTs. In addition, we found that the SiNx-passivated p-type and n-type pSWCNT-TFT-based CMOS-like ring oscillator, or 1-bit code generator, operated well after the 85/85 test for 24 h.

The accurate localization of S1 and S2 is essential for heart sound segmentation and classification. However, current direct heart sound segmentation algorithms have poor noise immunity and low accuracy. Therefore, this paper proposes a new optimal heart sound segmentation algorithm based on K-means clustering and Haar wavelet transform. The algorithm includes three parts. Firstly, this method uses the Viola integral method and Shannon’s energy-based algorithm to extract the function of the envelope of the heart sound energy. Secondly, the time–frequency domain features of the acquired envelope are extracted from different dimensions and the optimal peak is searched adaptively based on a dynamic segmentation threshold. Finally, K-means clustering and Haar wavelet transform are implemented to localize S1 and S2 of heart sounds in the time domain. After validation, the recognition rate of S1 reached 98.02% and that of S2 reached 96.76%. The model outperforms other effective methods that have been implemented. The algorithm has high robustness and noise immunity. Therefore, it can provide a new method for feature extraction and analysis of heart sound signals collected in clinical settings.

The fault detection of the chemical equipment operation process is an effective means to ensure safe production. In this study, an acoustic signal processing technique and a k-nearest neighbor (k-NN) classification algorithm were combined to identify the running states of the distillation columns. This method can accurately identify various fluid flow states in distillation columns, including normal and flooding states. First, the acoustic signals were collected under normal and abnormal states in an experimental distillation column. Then, the method of dual-domain feature extraction was used to extract the features such as the energy ratio and linear prediction coefficient (LPC). Moreover, the extracted feature parameters were analyzed and compared in a general way. Finally, the k-NN model was used to classify the acoustic signals. The results show that this method had high identification accuracy and provided an important reference for further research.

Site-specific N-glycosylation characterization requires intact N-glycopeptide analysis based on suitable tandem mass spectrometry (MS/MS) method. Electron-transfer/higher-energy collisional dissociation (EThcD), stepped collision energy/higher-energy collisional dissociation (sceHCD), higher-energy collisional dissociation-product-dependent electron-transfer dissociation (HCD-pd-ETD), and a hybrid mass spectrometry fragmentation method EThcD-sceHCD have emerged as valuable approaches for glycoprotein analysis. However, each of them incurs some compromise, necessitating the systematic performance comparisons when applied to the analysis of complex clinical samples (e.g., plasma, urine, cells, and tissues). Herein, we compared the performance of EThcD-sceHCD with those previous approaches (EThcD, sceHCD, HCD-pd-ETD, and sceHCD-pd-ETD) in the intact N-glycopeptide analysis, and determined its applicability for clinical N-glycoproteomic study. The intact N-glycopeptides of distinct samples, namely, plasma from prostate cancer (PCa) patients, urine from immunoglobulin A nephropathy (IgAN) patients, human hepatocarcinoma cell line (HepG2), and thyroid tissues from thyroid cancer (TC) patients were analyzed by these methods. We found that EThcD-sceHCD outperformed other methods in the balance of depth and accuracy of intact N-glycopeptide identification, and sceHCD and EThcD-sceHCD have good complementarity. EThcD-sceHCD holds great potential for biomarker discovery from clinical samples.

The densely glycosylated spike (S) proteins that are highly exposed on the surface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitate viral attachment, entry, and membrane fusion. We have previously reported all the 22 N-glycosites and site-specific N-glycans in the S protein protomer. Herein, we report the O-glycosylation landscapes of SARS-CoV-2 S proteins, which were characterized through high-resolution mass spectrometry. Following digestion with trypsin and trypsin/Glu-C, and de-N-glycosylation using PNGase F, we determined the GalNAc-type O-glycosylation pattern of S proteins, including O-glycosites and the six most common O-glycans occupying them, via Byonic identification and manual validation. Finally, 255 intact O-glycopeptides composed of 50 peptides sequences and 43 O-glycosites were discovered by higher energy collision-induced dissociation (HCD), and three O-glycosites were confidently identified by electron transfer/higher energy collision-induced dissociation (EThcD) in the insect cell-expressed S protein. Most glycosites were modified by non-sialylated O-glycans such as HexNAc(1) and HexNAc(1)Hex (1). In contrast, in the human cell-expressed S protein S1 subunit, 407 intact O-glycopeptides composed of 34 peptides sequences and 30 O-glycosites were discovered by HCD, and 11 O-glycosites were unambiguously assigned by EThcD. However, the measurement of O-glycosylation occupancy hasn’t been made. Most glycosites were modified by sialylated O-glycans such as HexNAc(1)Hex (1)NeuAc (1) and HexNAc(1)Hex (1)NeuAc (2). Our results reveal that the SARS-CoV-2 S protein is an O-glycoprotein; the O-glycosites and O-glycan compositions vary with the host cell type. These comprehensive O-glycosylation landscapes of the S protein are expected to provide novel insights into the viral binding mechanism and present a strategy for the development of vaccines and targeted drugs.

As an emerging third-generation fruit, blackberry has high nutritional value and is rich in polyphenols, flavonoids and anthocyanins. Flavonoid biosynthesis and metabolism is a popular research topic, but no related details have been reported for blackberry. Based on previous transcriptome data from this research group, two blackberry flavonol synthase genes were identified in this study, and the encoded proteins were subjected to bioinformatics analysis. RuFLS1 and RuFLS2 are both hydrophobic acidic proteins belonging to the 2OG-Fe(II) dioxygenase superfamily. RuFLS2 was expressed at 27.93-fold higher levels than RuFLS1 in red–purple fruit by RNA-seq analysis. Therefore, RuFLS2-overexpressing tobacco was selected for functional exploration. The identification of metabolites from transgenic tobacco showed significantly increased contents of flavonoids, such as apigenin 7-glucoside, kaempferol 3-O-rutinoside, astragalin, and quercitrin. The high expression of RuFLS2 also upregulated the expression levels of NtF3H and NtFLS in transgenic tobacco. The results indicate that RuFLS2 is an important functional gene regulating flavonoid biosynthesis and provides an important reference for revealing the molecular mechanism of flavonoid accumulation in blackberry fruit.

Semiconductor photocatalysis has received increasing attention because of its potential to address problems related to the energy crisis and environmental issues. However, conventional semiconductor photocatalysts, such as TiO2 and ZnO, can only be activated by ultraviolet light due to their wide band gap. To extend the light absorption into the visible range, the localized surface plasmon resonance (LSPR) effect of noble metal nanoparticles (NPs) has been widely used. Noble metal NPs can couple incident visible light energy to strong LSPR, and the nonradiative decay of LSPR generates nonthermal hot carriers that can be injected into adjacent semiconductor material to enhance its photocatalytic activity. Here we demonstrate that nanoimprint-defined gap plasmonic nanofinger arrays can function as visible light-driven plasmonic photocatalysts. The sub-5 nm gaps between pairs of collapsed nanofingers can support ultra-strong plasmon resonance and thus boost the population of hot carriers. The semiconductor material is exactly placed at the hot spots, providing an efficient pathway for hot carrier injection from plasmonic metal to catalytic materials. This nanostructure thus exhibits high plasmon-enhanced photocatalytic activity under visible light. The hot carrier injection mechanism of this platform was systematically investigated. The plasmonic enhancement factor was calculated using the finite-difference time-domain (FDTD) method and was consistent with the measured improvement of the photocatalytic activity. This platform, benefiting from the precise controllable geometry, provides a deeper understanding of the mechanism of plasmonic photocatalysis.

Mammals that live in cold climates endure months of exposure to low temperature in the winter. The incidence of respiratory diseases has increased. The goal of this study was to investigate the effects of chronic cold stress on lung inflammatory networks, apoptosis, and mitochondrial function via Yorkshire pig models, as well as the ameliorative effect of glucose as energy supplements. Here, two trials were conducted (chronic cold stress and glucose supplementation). The results showed that chronic cold stress induced obvious inflammatory cell infiltration in the lungs and damaged the lung tissue structure. Compared with the Y-Con group, the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), high mobility group box 1 (HMGB1), nucleotide-binding domain, and leucine-rich repeat protein 3 (NLRP3), IL-1β, IL-2, IL-6, and IFN-γ in the lungs of the Y-CS group was enhanced by chronic cold stress (p < 0.05). Moreover, chronic cold stress promoted the expression of the Bax and Mfn2 in lungs of Y-CS group (p < 0.05). Interestingly, dietary glucose supplementation significantly reduced inflammatory cell infiltration in the lungs. Moreover, glucose supplementation inhibited the expression of TLR4, MyD88, HMGB1, NLRP3, IL-1β, IL-2, IL-6, IFN-γ, and Bax during chronic cold stress. In conclusion, chronic cold stress promoted inflammatory networks, apoptosis, and mitochondrial fusion in the lungs. Dietary glucose supplementation inhibited the inflammatory network during chronic cold stress.

Radiomics, one of the potential methods for developing clinical biomarker, is one of the exponentially growing research fields. In addition to its potential, several limitations have been identified in this field, and most importantly the effects of variations in imaging parameters on radiomic features (RFs). In this study, we investigate the potential of RFs to predict overall survival in patients with clear cell renal cell carcinoma, as well as the impact of ComBat harmonization on the performance of RF models. We assessed the robustness of the results by performing the analyses a thousand times. Publicly available CT scans of 179 patients were retrospectively collected and analyzed. The scans were acquired using different imaging vendors and parameters in different medical centers. The performance was calculated by averaging the metrics over all runs. On average, the clinical model significantly outperformed the radiomic models. The use of ComBat harmonization, on average, did not significantly improve the performance of radiomic models. Hence, the variability in image acquisition and reconstruction parameters significantly affect the performance of radiomic models. The development of radiomic specific harmonization techniques remain a necessity for the advancement of the field.

In this article, we propose a new approach utilizing diffuse optical tomography (DOT) to monitoring the changes in tissues’ optical properties and temperature in high-intensity focused ultrasound (HIFU) therapy. By correlating the tissue reduced scattering coefficient (μs’) reconstructed by DOT and the temperature measured by a thermocouple, the quantitative relationship between μs’ and temperature in HIFU treatment was explored. The experiments were conducted using porcine and chicken breast muscle tissues during HIFU; the temperature of each tissue sample was recorded using a thermocouple. To incorporate the temperature dependency of tissue optical properties, both polynomial and exponential models were utilized to fit the experimental data. The results show that the change of μs’ during HIFU treatment could be detected in real-time using DOT and that this change of μs’ is quantitatively correlated with tissue temperature. Furthermore, while the tissue-type-dependent relationship between μs’ and temperature is non-linear in nature, it is stable and repeatable. Therefore, our approach has the potential to be used to predict temperature of tissue during HIFU treatment.

Yohimbine (YOH) has antiproliferative effects against breast cancer and pancreatic cancer; however, its effects on vascular proliferative diseases such as atherosclerosis remain unknown. Accordingly, we investigated the inhibitory mechanisms of YOH in vascular smooth muscle cells (VSMCs) stimulated by platelet-derived growth factor (PDGF)-BB, a major mitogenic factor in vascular diseases. YOH (5–20 μM) suppressed PDGF-BB-stimulated a mouse VSMC line (MOVAS-1 cell) proliferation without inducing cytotoxicity. YOH also exhibited antimigratory effects and downregulated matrix metalloproteinase-2 and -9 expression in PDGF-BB-stimulated MOVAS-1 cells. It also promoted cell cycle arrest in the initial gap/first gap phase by upregulating p27Kip1 and p53 expression and reducing cyclin-dependent kinase 2 and proliferating cell nuclear antigen expression. We noted phospholipase C-γ1 (PLCγ1) but not ERK1/2, AKT, or p38 kinase phosphorylation attenuation in YOH-modulated PDGF-BB-propagated signaling pathways in the MOVAS-1 cells. Furthermore, YOH still inhibited PDGF-BB-induced cell proliferation and PLCγ1 phosphorylation in MOVAS-1 cells with α2B-adrenergic receptor knockdown. YOH (5 and 10 mg/kg) substantially suppressed neointimal hyperplasia in mice subjected to CCA ligation for 21 days. Overall, our results reveal that YOH attenuates PDGF-BB-stimulated VSMC proliferation and migration by downregulating a α2B-adrenergic receptor–independent PLCγ1 pathway and reduces neointimal formation in vivo. Therefore, YOH has potential for repurposing for treating atherosclerosis and other vascular proliferative diseases.

Nanocrystalline soft magnetic alloy powders are promising microwave absorbents since they can work at diverse frequencies and are stable in harsh environments. However, when the alloy powders are in austenite phase, they are out of the screen for microwave absorbents due to their paramagnetic nature. In this work, we reported a strategy to enable strong microwave absorption in nanocrystalline austenite FeCoCr powders by deformation-thermal co-induced ferromagnetism via attritor ball milling and subsequent heat treatment. Results showed that significant austenite-to-martensite transformation in the FeCoCr powders was achieved during ball milling, along with the increase in shape anisotropy from spherical to flaky. The saturation magnetization followed parabolic kinetics during ball milling and rose from 1.43 to 109.92 emu/g after milling for 4 h, while it exhibited a rapid increase to 181.58 emu/g after subsequent heat treatment at 500 °C. A considerable increase in complex permeability and hence magnetic loss capability was obtained. With appropriate modulation of complex permittivity, the resultant absorbents showed a reflection loss of below −6 dB over 8~18 GHz at thickness of 1 mm and superior stability at 300 °C. Our strategy can broaden the material selection for microwave absorbents by involving Fe-based austenite alloys and simply recover the ferromagnetism of industrial products made without proper control of the crystalline phase.

In order to reduce the x-direction and Y-direction displacement disturbance of the barrel and improve the firing accuracy, based on Bernoulli Euler’s theoretical assumption of beam and taking M134 barrel machine gun as the calculation model, the pre-stress modal analysis and optimization of cantilever supported rotor under unbalanced force and moving mass are carried out in this paper. The main work of this paper is as follows: (1) M134 physical model is established, and the unbalanced force in the motion process of projectile in bore is solved by interior ballistic theory; (2) Based on the unbalanced rotor theory, the barrel vibration model considering the projectile weight and acceleration is established; (3) The critical speed model of high-speed rotating system is established, and the critical speed is determined by finite element modal analysis to determine the rigid/flexible state of barrel components in different speed regions; (4) Based on the above model, take the x-direction and Y-direction displacement of the barrel as the output value, and take the elastic modulus of the barrel, the relative position between the barrel hoop and the fuselage components and the cross-sectional area as the variable values, carry out the optimization design, and verify the firing accuracy before and after optimization through experiments.

In the research on the influence of pore structure on the macroscopic mechanical properties of concrete, the experimental method cannot realize the accurate control of the pore structure parameters, and the research based on the numerical simulation method is insufficient in the scientific simulation and parameterization of the complex pore structure. A new numerical concrete modeling method is proposed, which introduces the total porosity, pore gradation, pore size, and sub-porosity of each gradation segment to realize the accurate simulation and parameterization of the pore structure. Based on the control variable method, 25 concrete mesoscopic models with the same aggregate structure and different pore structures are established, and uniaxial tensile experiments are performed. The pore structure accelerates the process of damage expansion from the periphery to the center of the specimen and makes the damage inside the cement mortar more localized. There are obvious exponential function relationships of three pairs: total porosity and elastic modulus, PSSA and elastic modulus, and tensile strength and total porosity. There is an obvious quadratic polynomial function relationship between tensile strength and specific surface area. For specimens with the same aggregate structure and total porosity, the elastic modulus increases with the increase of the macropore content, and the tensile strength and elastic modulus are basically not affected by the average pore radius. The effect of pore space distribution and sub-porosity on peak strain is greater than that of total porosity, but no obvious regularity is shown. For pores with a radius in the range of 0.15–0.8 mm, the smaller the pores, the greater the effect of their porosity on the elastic modulus and tensile strength, and the less effect on the peak strain.

Abstract The large number of chemical and pharmaceutical patents has attracted researchers doing biomedical text mining to extract valuable information such as chemicals, genes and gene products. To facilitate gene and gene product annotations in patents, BioCreative V.5 organized a gene- and protein-related object (GPRO) recognition task, in which participants were assigned to identify GPRO mentions and determine whether they could be linked to their unique biological database records. In this paper, we describe the system constructed for this task. Our system is based on two different NER approaches: the statistical-principle-based approach (SPBA) and conditional random fields (CRF). Therefore, we call our system SPBA-CRF. SPBA is an interpretable machine-learning framework for gene mention recognition. The predictions of SPBA are used as features for our CRF-based GPRO recognizer. The recognizer was developed for identifying chemical mentions in patents, and we adapted it for GPRO recognition. In the BioCreative V.5 GPRO recognition task, SPBA-CRF obtained an F-score of 73.73% on the evaluation metric of GPRO type 1 and an F-score of 78.66% on the evaluation metric of combining GPRO types 1 and 2. Our results show that SPBA trained on an external NER dataset can perform reasonably well on the partial match evaluation metric. Furthermore, SPBA can significantly improve performance of the CRF-based recognizer trained on the GPRO dataset.

Apples (Malus domestica) are rich in flavonols, and 5-aminolevulinic acid (ALA) plays an important role in the regulation of plant flavonoid metabolism. To date, the underlying mechanism of ALA promoting flavonol accumulation is unclear. Flavonol synthase (FLS) is a key enzyme in flavonol biosynthesis. In this study, we found that ALA could enhance the promoter activity of MdFLS1 in the ‘Fuji’ apple and improve its expression. With MdFLS1 as bait, we screened a novel transcription factor MdSCL8 by the Yeast One-Hybrid (Y1H) system from the apple cDNA library which we previously constructed. Using luciferase reporter assay and transient GUS activity assay, we verified that MdSCL8 inhibits the activity of MdFLS1 promoter and hinders MdFLS1 expression, thus reducing flavonol accumulation in apple. ALA significantly inhibited MdSCL8 expression. Therefore, ALA promoted the expression of MdFLS1 and the consequent flavonol accumulation probably by down-regulating MdSCL8. We also found that ALA significantly enhanced the gene expression of MdMYB22 and MdHY5, two positive regulators of MdFLS. We further demonstrated that MdMYB22 interacts with MdHY5, but neither of them interacts with MdSCL8. Taken together, our data suggest MdSCL8 as a novel regulator of MdFLS1 and provide important insights into mechanisms of ALA-induced flavonol accumulation in apples.

Oncolytic bovine herpesvirus type 1 (BoHV-1) infection induces DNA damage in human lung adenocarcinoma cell line A549. However, the underlying mechanisms are not fully understood. We found that BoHV-1 infection decreased the steady-state protein levels of p53-binding protein 1 (53BP1), which plays a central role in dictating DNA damage repair and maintaining genomic stability. Furthermore, BoHV-1 impaired the formation of 53BP1 foci, suggesting that BoHV-1 inhibits 53BP1-mediated DNA damage repair. Interestingly, BoHV-1 infection redistributed intracellular β-catenin, and iCRT14 (5-[[2,5-Dimethyl-1-(3-pyridinyl)-1H-pyrrol-3-yl]methylene]-3-phenyl-2,4-thiazolidinedione), a β-catenin-specific inhibitor, enhanced certain viral protein expression, such as the envelope glycoproteins gC and gD, and enhanced virus infection-induced DNA damage. Therefore, for the first time, we provide evidence showing that BoHV-1 infection disrupts 53BP1-mediated DNA damage repair and suggest β-catenin as a potential host factor restricting both virus replication and DNA damage in A549 cells.