Measuring the knot of non-Hermitian degeneracies and non-commuting braids.

Any system of coupled oscillators may be characterized by its spectrum of resonance frequencies (or eigenfrequencies), which can be tuned by varying the system's parameters. The relationship between control parameters and the eigenfrequency spectrum is central to a range of applications1-3. However, fundamental aspects of this relationship remain poorly understood. For example, if the controls are varied along a path that returns to its starting point (that is, around a 'loop'), the system's spectrum must return to itself. In systems that are Hermitian (that is, lossless and reciprocal), this process is trivial and each resonance frequency returns to its original value. However, in non-Hermitian systems, where the eigenfrequencies are complex, the spectrum may return to itself in a topologically non-trivial manner, a phenomenon known as spectral flow. The spectral flow is determined by how the control loop encircles degeneracies, and this relationship is well understood for [Formula: see text] (where [Formula: see text] is the number of oscillators in the system)4,5. Here we extend this description to arbitrary [Formula: see text]. We show that control loops generically produce braids of eigenfrequencies, and for [Formula: see text] these braids form a non-Abelian group that reflects the non-trivial geometry of the space of degeneracies. We demonstrate these features experimentally for [Formula: see text] using a cavity optomechanical system.

The 25-kDa linear polyethylenimine exerts specific antiviral activity against pseudorabies virus through interferencing its adsorption via electrostatic interaction.

Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease, which is responsible for enormous economic losses to the global pig industry. Although vaccination has been used to prevent PRV infection, the effectiveness of vaccines has been greatly diminished with the emergence of PRV variants. Therefore, there is an urgent need to develop anti-PRV drugs. Polyethylenimine (PEI) is a cationic polymer and has a wide range of antibacterial and antiviral activities. This study found that a low dose of 1 µg/mL of the 25-kDa linear PEI had significantly specific anti-PRV activity, which became more intense with increasing concentrations. Mechanistic studies revealed that the viral adsorption stage was the major target of PEI without affecting viral entry, replication stages, and direct inactivation effects. Subsequently, we found that cationic polymers PEI and Polybrene interfered with the interaction between viral proteins and cell surface receptors through electrostatic interaction to exert the antiviral function. In conclusion, cationic polymers such as PEI can be a category of options for defense against PRV. Understanding the anti-PRV mechanism also deepens host-virus interactions and reveals new drug targets for anti-PRV.IMPORTANCEPolyethylenimine (PEI) is a cationic polymer that plays an essential role in the host immune response against microbial infections. However, the specific mechanisms of PEI in interfering with pseudorabies virus (PRV) infection remain unclear. Here, we found that 25-kDa linear PEI exerted mechanisms of antiviral activity and the target of its antiviral activity was mainly in the viral adsorption stage. Correspondingly, the study demonstrated that PEI interfered with the virus adsorption stage by electrostatic adsorption. In addition, we found that cationic polymers are a promising novel agent for controlling PRV, and its antiviral mechanism may provide a strategy for the development of antiviral drugs.

Nonreciprocal control and cooling of phonon modes in an optomechanical system.

Mechanical resonators are important components of devices that range from gravitational wave detectors to cellular telephones. They serve as high-performance transducers, sensors and filters by offering low dissipation, tunable coupling to diverse physical systems, and compatibility with a wide range of frequencies, materials and fabrication processes. Systems of mechanical resonators typically obey reciprocity, which ensures that the phonon transmission coefficient between any two resonators is independent of the direction of transmission1,2. Reciprocity must be broken to realize devices (such as isolators and circulators) that provide one-way propagation of acoustic energy between resonators. Such devices are crucial for protecting active elements, mitigating noise and operating full-duplex transceivers. Until now, nonreciprocal phononic devices3-11 have not simultaneously combined the features necessary for robust operation: strong nonreciprocity, in situ tunability, compact integration and continuous operation. Furthermore, they have been applied only to coherent signals (rather than fluctuations or noise), and have been realized exclusively in travelling-wave systems (rather than resonators). Here we describe a scheme that uses the standard cavity-optomechanical interaction to produce robust nonreciprocal coupling between phononic resonators. This scheme provides about 30 decibels of isolation in continuous operation and can be tuned in situ simply via the phases of the drive tones applied to the cavity. In addition, by directly monitoring the dynamics of the resonators we show that this nonreciprocity can control thermal fluctuations, and that this control represents a way to cool phononic resonators.

Analysis of the recombination and evolution of the new type mutant pseudorabies virus XJ5 in China.

Pseudorabies have caused enormous economic losses in China's pig industry and have recurred on many large pig farms since late 2011. The disease is caused by highly pathogenic, antigenic variant pseudorabies virus (vPRV) strains. Our laboratory isolated a pseudorabies virus in 2015 and named it XJ5. The pathogenic ability of this mutant strain was much stronger than that of the original isolate. After we sequenced its whole genome (GenBank accession number: OP512542), we found that its overall structure was not greatly changed compared with that of the previous strain Ea (KX423960.1). The whole genome alignment showed that XJ5 had a strong genetic relationship with the strains isolated in China after 2012 reported in GenBank. Based on the isolation time of XJ5 and the mutation and recombination analysis of programs, we found that the whole genome homology of XJ5 and other strains with Chinese isolates was greater than 95%, while the homology with strains outside Asia was less than 94%, which indicated that there may be some recombination and mutation patterns. We found that virulent PRV isolates emerged successively in China in 2011 and formed two different evolutionary clades from foreign isolates. At the same time, this may be due to improper immunization and the presence of wild strains in the field, and recent reports have confirmed that Bartha vaccine strains recombine with wild strains to obtain new pathogenic strains. We performed genetic evolution analysis of XJ5 isolated and sequenced in our laboratory to trace its possible mutations and recombination. We found that XJ5 may be the result of natural mutation of a virus in a branch of mutant strains widely existing in China.

Phenotyping of FGF12AV52H mutation in mouse implies a complex FGF12 network.

Pathogenic missense mutation of the FGF12 gene is responsible for a variable disease phenotypic spectrum. Disease-specific therapies require precise dissection of the relationship between different mutations and phenotypes. The lack of a proper animal model hinders the investigation of related diseases, such as early-onset epileptic encephalopathy. Here, an FGF12AV52H mouse model was generated using CRISPR/Cas9 technology, which altered the A isoform without affecting the B isoform. The FGF12AV52H mice exhibited seizure susceptibility, while no spontaneous seizures were observed. The increased excitability in dorsal hippocampal CA3 neurons was confirmed by patch-clamp recordings. Furthermore, immunostaining showed that the balance of excitatory/inhibitory neurons in the hippocampus of the FGF12AV52H mice was perturbed. The increases in inhibitory SOM+ neurons and excitatory CaMKII+ neurons were heterogeneous. Moreover, the locomotion, anxiety levels, risk assessment behavior, social behavior, and cognition of the FGF12AV52H mice were investigated by elevated plus maze, open field, three-chamber sociability, and novel object tests, respectively. Cognition deficit, impaired risk assessment, and social behavior with normal social indexes were observed, implying complex consequences of V52H FGF12A in mice. Together, these data suggest that the function of FGF12A in neurons can be immediate or long-term and involves modulation of ion channels and the differentiation and maturation of neurons. The FGF12AV52H mouse model increases the understanding of the function of FGF12A, and it is of great importance for revealing the complex network of the FGF12 gene in physiological and pathological processes.

Topological energy transfer in an optomechanical system with exceptional points.

Topological operations can achieve certain goals without requiring accurate control over local operational details; for example, they have been used to control geometric phases and have been proposed as a way of controlling the state of certain systems within their degenerate subspaces. More recently, it was predicted that topological operations can be used to transfer energy between normal modes, provided that the system possesses a specific type of degeneracy known as an exceptional point. Here we demonstrate the transfer of energy between two vibrational modes of a cryogenic optomechanical device using topological operations. We show that this transfer arises from the presence of an exceptional point in the spectrum of the device. We also show that this transfer is non-reciprocal. These results open up new directions in system control; they also open up the possibility of exploring other dynamical effects related to exceptional points, including the behaviour of thermal and quantum fluctuations in their vicinity.

Electrochemical label-free immunoassay of HE4 using 3D PtNi nanocubes assemblies as biosensing interfaces.

Human epididymis protein 4 (HE4) is a vital biomarker for early diagnosis of epithelial ovarian cancer (EOC). Herein, a new label-free biosensor was developed using K3[Fe(CN)6] as the electrochemical probe for ultrasensitive immunoassay of HE4 based on PtNi nanocubes assemblies (NCAs) as efficient biosensing interfaces. The PtNi NCAs were synthesized by a simple solvothermal approach, where N-hexadecyltrimethylammonium chloride (HTAC) and 2,2'-bis(4,5-dimethylimidazole) (BDMM) behaved as co-structuring directors. Under the optimal conditions, the obtained HE4 immunosensor displayed a wide detection range from 0.001 to 100 ng mL-1 and a low detection limit (0.11 pg mL-1, S/N = 3). As a result, the current sensing platform would serve as a useful reference for detecting cancer biomarkers in the clinical assay and diagnosis.

Ultrasensitive sandwich-typed electrochemical immunoassay for detection of squamous cell carcinoma antigen based on highly branched PtCo nanocrystals and dendritic mesoporous SiO2@AuPt nanoparticles.

Squamous cell carcinoma antigen (SCCA) is one of the common squamous cell carcinomas (SCC) in women, which usually works as a tumor biomarker for cervical cancer in diagnostic applications. Herein, bimetallic PtCo highly branched nanocrystals (PtCo BNCs) acted as electrode substrates to construct sandwich-typed electrochemical immunosensor for ultrasensitive detection of SCCA, by using dendritic mesoporous SiO2@AuPt nanoparticles (DM-SiO2@AuPt NPs) to adsorb electroactive thionine (Thi) as a signal label. The PtCo BNCs enlarged the loading of the primary antibody (Ab1), showing effective improvement in conductivity and sensitivity. The DM-SiO2 had abundant pores to incorporate more Thi, on which the decorated AuPt NPs created a great number of active sites to immobilize the secondary antibodies (Ab2), thereby obviously amplifying the detection signals. The prepared sensor exhibited a broader linear range (0.001-120 ng mL-1) and a lower detection limit (0.33 pg mL-1, S/N = 3), combined with high reproducibility, a low relative standard deviation (below 2.5%) and acceptable recovery (from 98.5 to 110.0%) even in diluted human serum samples. This research provides a substantial platform for clinical diagnosis of SCCA in practice.

A sandwich-type electrochemical immunosensor for CYFRA 21-1 based on probe-confined in PtPd/polydopamine/hollow carbon spheres coupled with dendritic Au@Rh nanocrystals.

A signal-on sandwich-like electrochemical immunosensor was built for determination of cytokeratin 19 fragments 21-1 (CYFRA 21-1) in non-small cell lung cancer (NSCLC) by confining electroactive dye (e.g., methylene blue, MB) as a probe for amplifying signals. Specifically, core-shell gold@rhodium dendritic nanocrystals (Au@Rh DNCs) behaved as a substrate for primary antibody and accelerate interfacial electron transfer. Besides, hollow carbon spheres (HCSs) were subsequently modified with polydopamine (PDA) and PtPd nanoparticles for sequential integration of the secondary antibody and confinement of MB as a label, termed as MB/PtPd/PDA/HCSs for clarity. The built sensors showed a broad linear range (100 fg mL-1 ~ 100 ng mL-1) for detection of CYFRA 21-1 with an ultra-low detection limit (31.72 fg mL-1, S/N = 3), coupled with satisfactory performance in human serum samples. This work can be explored for assays of other proteins and provides some constructive insights for early and accurate diagnosis of NSCLC.

Glycyrrhizin Inhibits PEDV Infection and Proinflammatory Cytokine Secretion via the HMGB1/TLR4-MAPK p38 Pathway.

Our previous study showed that glycyrrhizin (GLY) inhibited porcine epidemic diarrhea virus (PEDV) infection, but the mechanisms of GLY anti-PEDV action remain unclear. In this study, we focused on the anti-PEDV and anti-proinflammatory cytokine secretion mechanisms of GLY. We found that PEDV infection had no effect on toll-like receptor 4 (TLR4) protein and mRNA levels, but that TLR4 regulated PEDV infection and the mRNA levels of proinflammatory cytokines. In addition, we demonstrated that TLR4 regulated p38 phosphorylation but not extracellular regulated protein kinases1/2 (Erk1/2) and c-Jun N-terminal kinases (JNK) phosphorylation, and that GLY inhibited p38 phosphorylation but not Erk1/2 and JNK phosphorylation. Therefore, we further explored the relationship between high mobility group box-1 (HMGB1) and p38. We demonstrated that inhibition of HMGB1 using an antibody, mutation, or knockdown decreased p38 phosphorylation. Thus, HMGB1 participated in activation of p38 through TLR4. Collectively, our data indicated that GLY inhibited PEDV infection and decreased proinflammatory cytokine secretion via the HMGB1/TLR4-mitogen-activated protein kinase (MAPK) p38 pathway.

Selective interference of liking and beauty judgements on affective working memory and visual working memory.

Aesthetic processing has profound implications for everyday life. Although liking and beauty judgements are outcomes of aesthetic processing and derive from a common hedonic value, there may be some differences in how they engage working memory. This study used maintenance and aesthetic judgement tasks to examine whether liking and beauty judgements make different demands on domain-specific working memory resources. Sixty participants (30 males) were instructed to rate picture for liking or beauty while maintaining the subjective affect or brightness of the presented pictures. Results indicated that liking judgements selectively impaired participants' performance in the affect maintenance task, and beauty judgements selectively impaired their performance in the brightness maintenance task. In addition, maintaining affect and brightness feelings in the mind increased image ratings on beauty but not on liking. Our findings provide evidence that liking judgements draw more on affective working memory resources than beauty judgements, and beauty judgements draw more on visual working memory resources than liking judgements.

Zeroth-order gradient tracking for decentralized learning with privacy guarantees.

This paper proposes a differential privacy decentralized zeroth-order gradient tracking optimization (DP-DZOGT) algorithm for solving optimization problems of decentralized systems, where the gradient information of the function is unknown. To address the challenge of unknown gradient information, a one-point zeroth-order gradient estimator (OPZOGE) is constructed, which can estimate the gradient based on the function value and guide the update of decision variables. Additionally, to prevent privacy leakage of agents, random noise is introduced into both the state and the gradient of the agents, which effectively enhances the level of privacy protection. The linear convergence of the proposed DP-DZOGT under a fixed step size can be guaranteed. Moreover, it has been applied to the fields of smart grid (SG) and decentralized federated learning (DFL). Finally, the effectiveness of the algorithm is validated through three numerical simulations.

Pharmacological Components and Mechanism Research on the Treatment of Myelosuppression after Chemotherapy with Danggui Jixueteng Decoction Based on Spectrum-Effect Relationships and Transcriptome Sequencing.

Danggui Jixueteng decoction (DJD) has been used to treat anemia for many years and has been shown to be effective. However, the mechanism of action and effective components are yet unknown. We want to search for pharmacodynamic components in DJD with therapeutic effects on myelosuppression after chemotherapy (MAC), utilizing a spectrum-effect connection study based on gray relational analysis and partial least-squares regression analysis. Transcriptome sequencing (RNA-Seq) was used to investigate the mechanism by which DJD treats MAC. In this study, fingerprints of different batches of DJD (S1-S10) were established by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), after which the resulting shared peaks were screened and identified. A total of 21 common peaks were screened through the fingerprints of different batches of DJD, and the similarity of each profile was greater than 0.92. The 21 shared peaks were identified by comparison with the standard sample and searching on a MassLynx 4.1 workstation. The rat model of MAC was established by intraperitoneal injection of cyclophosphamide, and DJD treatment was carried out in parallel with the establishment of the model. White blood cell count, red blood cell count, platelet count, interleukin-3, hemoglobin concentration, granulocyte-macrophage colony-stimulating factor, and nucleated cell count were used as efficacy indicators. Pharmacodynamic results indicated that DJD could effectively improve the pharmacodynamic indices of MAC rats. The results of gray relational analysis demonstrated eight peaks with high correlation with efficacy, which were 2, 7, 10, 14, 15, 16, 18, and 21, and the partial least-squares regression analysis showed four peaks with variable importance in projection values greater than 1, which were 10, 12, 13, and 19. RNA-Seq was used to identify DEGs in rat bone marrow cells, Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs were performed. The genes related to the effects of DJD on MAC were mainly involved in the phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K-Akt) signaling pathway, the mitogen-activated protein kinase signaling pathway, actin cytoskeleton regulation, focal adhesion, and Rap1 signaling pathways. The results of the RNA-Seq study were confirmed by a qPCR experiment. The effective compounds of DJD against MAC include albiflorin, paeoniflorin, gallopaeoniflorin, salvianolic acid H/I, albiflorin R1, salvianolic acid B, salvianolic acid E, benzoylpaeoniflorin, and C12H18N5O4. The mechanism by which DJD prevents and treats MAC might involve the control of the PI3K-Akt signaling pathway.

Protamine cleavage specificity of the avian pathogen Escherichia coli OmpT reveals two substrate-binding sites related to virulence.

The pathogenic nature of bacteria can be increased by cleaving antimicrobial peptides using omptins, to avoid or counter the host's natural immune defenses. Plasmid-encoded OmpT (pOmpT or ArlC) in avian pathogenic Escherichia coli (APEC), like the chromosome-encoded OmpT (cOmpT), belongs to the omptin family and both exhibit highly similar sequences and structures. Through sequence alignment and physiological examinations, pOmpT has been identified as a virulence factor, distinct from cOmpT in terms of substrate specificity. When pOmpT is compared with cOmpT regarding their proteolytic activities and target substrates, Asp267 and Ser276 on loop 5 of cOmpT are found to be binding sites that facilitate substrate anchoring and enhance substrate cleavage (protamine or synthetic peptide) by the catalytic center. Conversely, the characteristics of residues at positions 267 and 276 on loop 5 of pOmpT inhibit protamine cleavage, yet allow the specific cleavage of the human antimicrobial peptide RNase 7, which plays a role in host defense. This finding suggests a relationship between these two binding sites and substrate specificity. Furthermore, the substrate-binding sites (residues 267 and 276, particularly residue 267) of cOmpT and pOmpT are determined to be critical in the virulence of APEC. In summary, residues 267 and 276 of pOmpT are crucial for the pathogenicity of APEC and offer new insights into the determinants of APEC virulence and the development of antimicrobial drugs.

Rehmmannia glutinosa polysaccharide exerts antiviral activity against pseudorabies virus and antioxidant activity.

Pseudorabies virus (PRV) is an important pathogen harming the global pig industry. Vaccines available for swine cannot protect against PRV completely. Furthermore, no antiviral drugs are available to treat PRV infections. Rehmmannia glutinosa polysaccharide (RGP) possesses several medicinal properties. However, its antiviral activity is not reported. In the present study, we found that RGP can inhibit PRV/XJ5 infection by western blotting, immunofluorescent assay (IFA), and TCID50 assay quantitative polymerase chain reaction (qPCR). We revealed RGP can inhibit virus adsorption and invasion into PK-15 cells in a dose-dependent manner via western blotting, IFA, TCID50 assay, and quantitative polymerase chain reaction (qPCR), and suppressed PRV/XJ5 replication through western blotting, and qPCR. Additionally, it also reduced PRV/XJ5-induced ROS, lipid oxidation, and improved SOD levels in PK-15 cells, which was observed by using corresponding test kits. To conclude, our findings suggest that RGP might be a novel therapeutic agent for preventing and controlling PRV infection and antioxidant agent.

Multi-omics analysis of kidney tissue metabolome and proteome reveals the protective effect of sheep milk against adenine-induced chronic kidney disease in mice.

Chronic kidney disease (CKD) is characterized by impaired renal function and is associated with inflammation, oxidative stress, and fibrosis. Sheep milk contains several bioactive molecules with protective effects against inflammation and oxidative stress. In the current study, we investigated the potential renoprotective effects of sheep milk and the associated mechanisms of action in an adenine-induced CKD murine model. Sheep milk delayed renal chronic inflammation (e.g., significant reduction in levels of inflammatory factors Vcam1, Icam1, Il6, and Tnfa), fibrosis (significant reduction in levels of fibrosis factors Col1a1, Fn1, and Tgfb), oxidative stress (significant increase in levels of antioxidants and decrease in oxidative markers), mineral disorders, and renal injury in adenine-treated mice (e.g. reduced levels of kidney injury markers NGAL and KIM-1). The combined proteomics and metabolomics analyses showed that sheep milk may affect the metabolic processes of several compounds, including proteins, lipids, minerals, and hormones in mice with adenine-induced chronic kidney disease. In addition, it may regulate the expression of fibrosis-related factors and inflammatory factors through the JAK1/STAT3/HIF-1α signaling pathway, thus exerting its renoprotective effects. Therefore, sheep milk may be beneficial for patients with CKD and should be evaluated in preclinical and clinical studies.

Phylogenomic data resolved the deep relationships of Gymnogynoideae (Selaginellaceae).

The unresolved phylogenetic framework within the Selaginellaceae subfamily Gymnogynoideae (ca. 130 species) has hindered our comprehension of the diversification and evolution of Selaginellaceae, one of the most important lineages in land plant evolution. Here, based on plastid and nuclear data extracted from genomic sequencing of more than 90% species of all genera except two in Gymnogynoideae, a phylogenomic study focusing on the contentious relationships among the genera in Gymnogynoideae was conducted. Our major results included the following: (1) Only single-copy region (named NR) and only one ribosomal operon was firstly found in Afroselaginella among vascular plants, the plastome structure of Gymnogynoideae is diverse among the six genera, and the direct repeats (DR) type is inferred as the ancestral state in the subfamily; (2) The first strong evidence was found to support Afroselaginella as a sister to Megaloselaginella. Alternative placements of Ericetorum and Gymnogynum were detected, and their relationships were investigated by analyzing the variation of phylogenetic signals; and (3) The most likely genus-level relationships in Gymnogynoideae might be: ((Bryodesma, Lepidoselaginella), (((Megaloselaginella, Afroselaginella), Ericetorum), Gymnogynum)), which was supported by maximum likelihood phylogeny based on plastid datasets, maximum likelihood, and Bayesian inference based on SCG dataset and concatenated nuclear and plastid datasets and the highest proportion of phylogenetic signals of plastid genes.

Comparison of the safety and efficacy of the wild-type and lpxL/lpxM mutant inactivated vaccine against the avian pathogenic Escherichia coli O1, O2, and O78 challenge.

Avian pathogenic Escherichia coli (APEC) is primarily responsible for causing septicemia, pneumonitis, peritonitis, swollen head syndrome, and salpingitis in poultry, leading to significant losses in the poultry sector, particularly within the broiler industry. The removal of the lpxL and lpxM genes led to an eightfold decrease in the endotoxin levels of wild APEC strains. In this study, mutant strains of lpxL/lpxM and their O1, O2, and O78 wild-type strains were developed for an inactivated vaccine (referred to as the mutant vaccine and the wild-type vaccine, respectively), and the safety and effectiveness of these two prototype vaccines were assessed in white Leghorn chickens. Findings indicated that chickens immunized with the mutant vaccine showed a return of appetite sooner post-immunization and experienced earlier disappearance of nodules at the injection site compared to those immunized with the wild-type vaccine. Pathological examinations revealed that lesions were still present in the liver, lung, and injection site in chickens vaccinated with the wild-type vaccine 14 days post-vaccination (dpv), whereas no lesions were found in chickens vaccinated with the mutant vaccine at 14 dpv. There were no significant differences in antibody levels on the challenge day or in mortality or lesion scores between challenged birds immunized with either the mutant vaccine or the wild-type vaccine at the same dose. In this study, the safety of a single dose or overdose of the mutant vaccine and its efficacy at one dose were evaluated in broilers, and the results showed that the mutant vaccine had no adverse effects on or protected vaccinated broilers from challenge with the APEC O1, O2, or O78 strains. These results demonstrated that the mutant polyvalent inactivated vaccine is a competitive candidate against APEC O1, O2, and O78 infection compared to the wild-type vaccine.

What Ability Can Predict Mathematics Performance in Typically Developing Preschoolers and Those with Autism Spectrum Disorder?

Research evaluating predictors of mathematics ability in preschoolers with autism spectrum disorder (ASD) is scarce and inconclusive. The present study first compared the mathematics ability and cognitive abilities of preschoolers with ASD and age-matched typically developing (TD) peers. Then, we examined the relative contributions of cognitive abilities to the mathematics ability of preschoolers with ASD and TD. The results show that compared to those of their age-matched TD peers, the mathematics and cognitive abilities of preschoolers with ASD were impaired. The predictors of mathematics ability were found to differ among preschoolers with ASD and their age-matched TD peers. For TD preschoolers, the domain-specific approximate number system (ANS) was the key predictor of mathematics ability. For preschoolers with ASD, domain-general working memory (WM) was most important.

Porcine IGFBP3 promotes porcine circovirus type 2 replication via PERK/eIF2α mediated DNA damage.

The infection of porcine circovirus type 2 (PCV2) triggers activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway and leads to DNA damage. Insulin-like growth factor-binding protein 3 (IGFBP3) may interact with the endoplasmic reticulum (ER). It remains unclear whether IGFBP3 regulates DNA damage via ER stress to mediate PCV2 replication. In this study, we observed an upregulation of porcine IGFBP3 expression during PCV2 infection, and overexpression of IGFBP3 enhanced the expression of PCV2 Cap protein, PCV2 DNA copy number, and viral titers in PK-15 B6 cells and 3D4/21 cells. Additionally, overexpression of IGFBP3 induced an increase in the DNA damage marker γH2AX by activating the PERK/eIF2α pathway without concomitant activation of ATF4, IRE1α, and ATF6α/GRP78 pathways in PK-15 B6 cells and 3D4/21 cells. Knockdown of IGFBP3 had a reverse effect on PCV2 replication in PK-15 B6 cells and 3D4/21 cells. Furthermore, treatment with etoposide enhanced PCV2 replication while KU57788 decreased it. GSK2606414 and salubrinal limited both DNA damage and viral replication. Therefore, our findings suggest that porcine IGFBP3 promotes PCV2 replication through the PERK/eIF2α pathway-mediated induction of DNA damage in PK-15 B6 cells and 3D4/21 cells. Our study provides a basis for exploring novel antiviral strategies via the extensive understanding of the relationships between host cellular proteins and viral replication.