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African swine fever virus (ASFV) is a large double-stranded DNA virus with a complex structural architecture and encodes more than 150 proteins, where many are with unknown functions. E184L has been reported as one of the immunogenic ASFV proteins that may contribute to ASFV pathogenesis and immune evasion. However, the antigenic epitopes of E184L are not yet characterized. In this study, recombinant E184L protein was expressed in prokaryotic expression system and four monoclonal antibodies (mAbs), designated as 1A10, 2D2, 3H6, and 4C10 were generated. All four mAbs reacted specifically with ASFV infected cells. To identify the epitopes of the mAbs, a series of overlapped peptides of E184L were designed and expressed as maltose binding fusion proteins. Accordingly, the expressed fusion proteins were probed with each E184L mAb separately by using Western blot. Following a fine mapping, the minimal linear epitope recognized by mAb 1A10 was identified as 119IQRQGFL125, and mAbs 2D2, 3H6, and 4C10 recognized a region located between 153DPTEFF158. Alignment of amino acids of E184L revealed that the two linear epitopes are highly conserved among different ASFV isolates. Furthermore, the potential application of the two epitopes in ASFV diagnosis was assessed through epitope-based ELISA using 24 ASFV positive and 18 negative pig serum and the method were able to distinguish positive and negative samples, indicating the two epitopes are dominant antigenic sites. To our knowledge, this is the first study to characterize the B cell epitopes of the antigenic E184L protein of ASFV, offering valuable tools for future research, as well as laying a foundation for serological diagnosis and epitope-based marker vaccine development.

African swine fever (ASF) continues to cause enormous economic loss to the global pig industry. Since there is no safe and effective vaccine, accurate and timely diagnosis of ASF is essential to implement control measures. Indirect immunofluorescence assay (IFA) is a gold standard serological method recommended by the World Organization for Animal Health (WOAH). In this study, we used primary fetal kidney cells to establish a wild boar cell line (BK2258) that supported the efficient replication of ASF virus (ASFV) SD/DY-I/21 and showed visible cytopathic effect (CPE). Moreover, using BK2258, we established a sensitive and specific IFA for ASFV antibody detection. To standardize and evaluate the performance of this assay, we used serum samples from pigs infected with the low virulent genotype I SD/DY-I/21 and genotype II HLJ/HRB1/20, and immunized with the vaccine candidate HLJ/18-7GD, field samples, and negative serum samples. The IFA reacted with the ASFV-positive sera and displayed bright fluorescence foci. There was no non-specific green fluorescence due to cellular senescence or other cell damage-causing factors. Compared to a commercial indirect enzyme-linked immunosorbent assay (iELISA), ASFV antibodies were detected 1–4 days earlier using our IFA. The detection limits of the IFA and iELISA for the same ASFV-antibody positive serum samples were 1:25,600 and 1:6,400, respectively, indicating that the IFA is more sensitive than iELISA. The newly established IFA was highly specific and did not cross-react with sera positive for six other important porcine pathogens (i.e., Classical swine fever virus (CSFV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcme circovirus type 2 (PCV2), Pseudorabies virus (PRV), Foot-and-Mouth disease virus type O (FMDV/O), and Porcine epidemic diarrhea virus (PEDV)). This study thus provides a sensitive, specific, and reliable detection method that is suitable for the serological diagnosis of ASF.

Utilizing a longitudinal dataset encompassing 30 Chinese provinces and municipalities (with the exception of Tibet, Hong Kong, Macao, and Taiwan) that spans the years 2011 through to 2021, this study adopts the spatial Durbin model to study the path and mechanism behind the promotion of carbon emission reductions through intelligent manufacturing. The results show the following: ① Intelligent manufacturing plays a crucial role in promoting the reduction of carbon emissions. ② Government interventions can amplify the positive influence of intelligent manufacturing in reducing carbon emissions, and intelligent manufacturing promotes carbon emission reductions by accelerating scientific and technological innovation. ③ There is temporal heterogeneity: upgrading intelligent manufacturing exerted a substantial influence in advancing the reduction of carbon emissions during the timeframe from 2011 to 2019, while it exerted a notable impeding impact on the reduction of carbon emissions during the timeframe from 2011 to 2019. ④ There is spatial heterogeneity: in the eastern region, upgrading intelligent manufacturing promoted carbon emission reductions in 2011–2015, but it inhibited carbon emission reductions in 2016–2021. Consequently, here are the insights we have distilled: ① Enhancing the overall advancement level of intelligent manufacturing can effectively promote carbon emission reductions in China; ② It can also play an important role in guiding governments in making these upgrades and actively promoting them in conjunction with technological innovations.

Hemorrhagic transformation (HT) and restrictive therapeutic time window are significant limitations of delayed t-PA (tissue-type plasminogen activator) thrombolytic therapy in ischemic stroke patients. Plant Momordica charantia-derived exosome-like nanovesicles (MC-ELNs) can protect the blood–brain barrier (BBB) and inhibit neuronal apoptosis in stroke rats by inhibiting matrix metalloproteinase 9(MMP-9) expression. This study explored the therapeutic function and underlying mechanisms of MC-ELNs in treating HT. In delayed t-PA-treated ischemia-reperfusion rats, MC-ELNs significantly reduced mortality, HT, and cell apoptosis; MC-ELNs improved neurological function and BBB's integrity. MC-ELNs reduced ONOO− and MMP-9 expression and inhibited the release of HMGB1 from intracellular to extracellular in vivo and in vitro. ONOO− donor SIN-1 directly induced extracellular secretion of HMGB1, MC-ELNs and FeTmPyP (ONOO− decomposition catalyst, PDC) significantly reduced the expression of HMGB1 and inhibited MMP-9 activation in vitro. These findings indicate that MC-ELNs could protect BBB integrity and improve t-PA-induced HT by inhibiting the ONOO−/HMGB1/MMP-9 pathway.

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 μM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 μM) promoted nuclear translocation of β-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the β-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Abstract African swine fever virus (ASFV) poses a great threat to the global pig industry and food security. Currently, 24 ASFV genotypes have been reported but it is unclear whether recombination of different genotype viruses occurs in nature. In this study, we detect three recombinants of genotype I and II ASFVs in pigs in China. These recombinants are genetically similar and classified as genotype I according to their B646L gene, yet 10 discrete fragments accounting for over 56% of their genomes are derived from genotype II virus. Animal studies with one of the recombinant viruses indicate high lethality and transmissibility in pigs, and deletion of the virulence-related genes MGF_505/360 and EP402R derived from virulent genotype II virus highly attenuates its virulence. The live attenuated vaccine derived from genotype II ASFV is not protective against challenge of the recombinant virus. These naturally occurring recombinants of genotype I and II ASFVs have the potential to pose a challenge to the global pig industry.

Blood-brain barrier (BBB) dysfunction plays a pivotal role in the pathology of chronic cerebral hypoperfusion (CCH)-related neurodegenerative diseases. Continuous endothelial cells (EC) that line the blood vessels of the brain are important components of the BBB to strictly control the flow of substances and maintain the homeostatic environment of the brain. However, the molecular mechanisms from the perspective of EC-induced BBB dysfunction after CCH are largely unknown. In this study, the BBB function was assessed using immunostaining and transmission electron microscopy. The EC dysfunction profile was screened by using EC enrichment followed by RNA sequencing. After identified the key EC dysfunction factor, C-kit, we used the C-kit inhibition drug (imatinib) and C-kit down-regulation method (AAV-BR1-C-kit shRNA) to verify the role of C-kit on BBB integrity and EC transcytosis after CCH. Furthermore, we also activated C-kit with stem cell factor (SCF) to observe the effects of C-kit on BBB following CCH. We explored that macromolecular proteins entered the brain mainly through EC transcytosis after CCH and caused neuronal loss. Additionally, we identified receptor tyrosine kinase C-kit as a key EC dysfunction molecule. Furthermore, the pharmacological inhibition of C-kit with imatinib counteracted BBB leakage by reducing caveolae-mediated transcytosis. Moreover, treatment with AAV-BR1-C-kit shRNA, which targets brain EC to inhibit C-kit expression, also ameliorated BBB leakage by reducing caveolae-mediated transcytosis. Furthermore, the SCF increased the permeability of the BBB by actively increasing caveolae-mediated transcytosis. This study provides evidence that C-kit is a key BBB permeability regulator through caveolae-mediated transcytosis in EC after CCH.

Safety resilient city is a frontier concept of urban safety development and a hot topic in the field of urban safety research. In this paper, the relevant research results of domestic and foreign scholars are reviewed from the perspectives of concepts and models, the evaluation indicator system of urban safety resilience is compared in terms of risk types, evaluation objects, evaluation dimensions and quantitative methods, and the development of international standards for resilient cities is discussed. Based on the literature review, the connotation of the triangular theoretical model of urban safety resilience is explained, and an urban safety resilience evaluation index system applicable to Chinese cities is proposed, which provides support for the development of the national standard “Guide for safety resilient city evaluation” (GB/T 40947-2021). It is applied to six representative cities as examples for evaluation to explore the direction of Chinese urban safety resilience improvement. The pathway for improving the safety resilience of Chinese cities is discussed.

Lipoteichoic acid (LTA) plays an essential role in bacterial growth and resistance to antibiotics, and LTA synthetase (LtaS) was considered as an attractive target for combating Gram-positive infections. Azalomycin F, a natural guanidyl-containing polyhydroxy macrolide, can target the LTA of Staphylococcus aureus. Using various technologies including enzyme-linked immunosorbent assay, transmission electron microscope, proteomics, and parallel reaction monitoring, here, the experimental results indicated that azalomycin F can accelerate the LTA release and disrupt the cell envelope, which would also lead to the feedback upregulation on the expressions of LtaS and other related enzymes. Simultaneously, the reconstituted enzyme activity evaluations showed that azalomycin F can significantly inhibit the extracellular catalytic domain of LtaS (eLtaS), while this was vague for LtaS embedded in the liposomes. Subsequently, the fluorescence analyses for five incubation systems containing azalomycin F and eLtaS or the LtaS-embedded liposome indicated that azalomcyin F can spontaneously bind to the active center of LtaS. Combining the mass spectroscopy analyses and the molecular dockings, the results further indicated that this interaction involves the binding sites of substrates and the LTA prolongation, especially the residues Lys299, Phe353, Trp354 and His416. All these suggested that azalomycin F has multiple antibacterial mechanisms against S. aureus. It can not only inhibit LTA biosynthesis through the interactions of its guanidyl side chain with the active center of LtaS but also disrupt the cell envelope through the synergistic effect of accelerating the LTA release, damaging the cell membrane, and electrostatically interacting with LTA. Simultaneously, these antibacterial mechanisms exhibit a synergistic inhibition effect on S. aureus cells, which would eventually cause the cellular autolysis.

Although existing studies have proved that autistic traits (AT) may have relations to non-suicidal self-injury (NSSI) behaviors, its associations with anxiety, rumination and experiential avoidance (EA) are still unclear. The current study, based on a sample of 1317 Chinese college students, explored the associations between AT, anxiety and NSSI, and the possible modulating roles of rumination and EA in these associations. The results shows that 1) a total of 334 (25.36%) students reported a history of NSSI and 30 (2.28%) students were categorized as high AT; 2) Students with high AT reported higher rates of NSSI than those with low AT (36.67% vs. 25.10%); 3) AT, anxiety, rumination and EA have positive relations with NSSI; 4) AT predicted NSSI indirectly through anxiety; 5) Rumination and EA significantly moderated the effects of AT on NSSI via anxiety. In conclusion, this study confirms the indirect effect of AT on NSSI through anxiety in Chinese college students, and further clarifies the reinforcing effects of rumination and EA on the associations between AT, anxiety and NSSI. These findings suggest that developing adaptive emotion-regulating strategies and positive coping styles might promote the prevention and treatment of NSSI behaviors among autistic individuals.

Abstract Depression is a common and debilitating condition for which effective treatments are needed. Lepidium meyenii Walp (Maca) is a plant with potential medicinal effects in treating depression. Recently, there has been growing interest in plant‐derived extracellular vesicles (EVs) due to their low toxicity and ability to transport to human cells. Targeting the gut–brain axis, a novel strategy for depression management, may be achieved through the use of Maca‐derived EVs (Maca‐EVs). In this study, we successfully isolated Maca‐EVs using gradient ultracentrifugation and characterized their shape, size, and markers (CD63 and TSG101). The in vivo imaging showed that the Dil‐labeled Maca‐EVs crossed the brain–blood barrier and accumulated in the brain. The behavioral tests revealed that Maca‐EVs dramatically recovered the depression‐like behaviors of unpredictable chronic mild stress (UCMS) mice. UCMS mice fecal were characterized by an elevated abundance of g_Enterococcus, g_Lactobacillus, and g_Escherichia_Shigella, which were significantly restored by administration of Maca‐EVs. The effects of Maca‐EVs on the altered microbial and fecal metabolites in UCMS mice were mapped to biotin, pyrimidine, and amino acid (tyrosine, alanine, aspartate, and glutamate) metabolisms, which were closely associated with the serotonin (5‐HT) production. Maca‐EVs were able to increase serum monoamine neurotransmitter levels in UCMS mice, with 5‐HT showing the most significant changes. We further demonstrated that 5‐HT improved the expression of brain‐derived neurotrophic factor, a key regulator of neuronal plasticity, and its subsequent activation of TrkB/p‐AKT signaling by regulating the GTP‐Cdc42/ERK pathway. These findings suggest that Maca‐EVs enhance 5‐HT release, possibly by modulating the gut–brain axis, to improve depression behavior. Our study sheds light on a novel approach to depression treatment using plant‐derived EVs.

BackgroundPrior studies have proved the relationships between childhood emotional abuse (CEA) histories and suicidal thoughts or behaviors in adulthood, however, how emotion regulation strategies work as the mediating mechanism is necessary to be investigated. This study aimed to further verify the impacts of rumination, experiential avoidance (EA) and depression on the associations between CEA and non-suicidal self-injury (NSSI) and suicidal ideation (SI) on a sample of Chinese college students.MethodsThe Childhood Emotional Abuse Questionnaire, the Non-Suicidal Self-Injury Questionnaire, the Symptom Checklist, the Ruminative Response Scale, the Acceptance and Action Questionnaire-II and the Zung Self-Rating Depression Scale were completed by 1,317 college students.ResultsThe rates of NSSI and SI of students with CEA experiences were 31.70 and 7.90% respectively, both higher than those without such experiences. The mediating roles of rumination, EA and depression between CEA and NSSI and SI were significant (p

Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery. We found that succinate levels increased in serum and brain tissue (cortex and hippocampus) after ischemia/reperfusion injury. Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate. Succinate can be converted into diethyl succinate in cells. Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury. Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells. Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells. Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation, which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.

Abstract Background Myxomycetes are a group of eukaryotes belonging to Amoebozoa, which are characterized by a distinctive life cycle, including the plasmodium stage and fruit body stage. Plasmodia are all found to be associated with bacteria. However, the information about bacteria diversity and composition in different plasmodia was limited. Therefore, this study aimed to investigate the bacterial diversity of plasmodia from different myxomycetes species and reveal the potential function of plasmodia-associated bacterial communities. Results The bacterial communities associated with the plasmodia of six myxomycetes (Didymium iridis, Didymium squamulosum, Diderma hemisphaericum, Lepidoderma tigrinum, Fuligo leviderma, and Physarum melleum) were identified by 16S rRNA amplicon sequencing. The six plasmodia harbored 38 to 52 bacterial operational taxonomic units (OTUs) that belonged to 7 phyla, 16 classes, 23 orders, 40 families, and 53 genera. The dominant phyla were Bacteroidetes, Firmicutes, and Proteobacteria. Most OTUs were shared among the six myxomycetes, while unique bacteria in each species only accounted for a tiny proportion of the total OTUs. Conclusions Although each of the six myxomycetes plasmodia had different bacterial community compositions, a high similarity was observed in the plasmodia-associated bacterial communities' functional composition. The high enrichment for gram-negative (> 90%) and aerobic (> 99%) bacteria in plasmodia suggest that myxomycetes may positively recruit certain kinds of bacteria from the surrounding environment.

African swine fever (ASF) is a highly infectious, transboundary viral disease of domestic and wild pigs, and is currently the most serious threat to world swine production, resulting in significant economic loss. In the absence of vaccines and treatments, the control of the disease entirely depends on accurate and early diagnosis accompanied by the culling of infected pigs. Thus, a highly specific and sensitive diagnostic assay is required during an outbreak and surveillance of the disease. In this study, a highly sensitive, specific, rapid and repeatable P22-monoclonal antibody-based blocking enzyme-linked immunosorbent assay (bELISA) assay was developed for the detection of antibodies against genotype I and II African swine fever viruses(ASFVs). A total of 806 pig serum samples were tested to evaluate the performance of the diagnostic assay. To determine the PI (percent Inhibition) cut-off value, receiver-operating characteristic (ROC) analysis was applied. According to the ROC analysis of the data, 98.10% specificity and 100% sensitivity were recorded when the threshold cut-off value of PI was established at 47%. In addition, the assay was able to detect ASFV antibodies as early as 9 days post-infection when serum samples from experimentally infected pigs were used. Taking all together, the results of the present study indicated that the P22-mAb based bELISA assay can be used for rapid and accurate detection of antibodies against ASFV, which could play a valuable role in the containment and prevention of ASFV as an alternative to other serological diagnostic methods. Also, this study will assist researchers to further investigate the immunogenic importance of P22 protein in ASFV infection.

Abstract The distinctive layered crystal structures and diverse properties of 2D layered materials (2DLMs) have established them as prospective building blocks for implementing next‐generation optoelectronics. One critical predicament in terms of light sensing is the weak absorption caused by the atomic‐scale thickness, as well as the limited effective wavelength range/low spectral selectivity constrained by the intrinsic band structures. Despite the fact that numerous noble metal antennas are harnessed for enhancing the light–matter coupling, they suffer from exorbitant cost and narrow resonant optical windows. To this end, a number of non‐noble plasmonic optical antennas have been developed to improve the light‐sensing properties of 2DLM photodetectors, and tremendous advances have been accomplished. Herein, a comprehensive overview of this subject is provided based on four aspects; namely, non‐noble metal antenna promoted 2DLM photodetectors, heteroatom doped semiconductor antenna promoted 2DLM photodetectors, non‐stoichiometric semiconductor antenna promoted 2DLM photodetectors, and MXene antenna promoted 2DLM photodetectors. The focus is on the device structures, preparation, and underlying mechanisms. In the end, the challenges are highlighted, and potential strategies addressing them are proposed, which aim to navigate the upcoming exploration in the related domains and fully exert the pivotal role of non‐noble plasmonic optical antennas toward advancing 2DLM photodetectors.

Detecting light from a wealth of physical degrees of freedom (e.g. wavelength, intensity, polarization state, phase, etc) enables the acquirement of more comprehensive information. In the past two decades, low-dimensional van der Waals materials (vdWMs) have established themselves as transformative building blocks toward lensless polarization optoelectronics, which is highly beneficial for optoelectronic system miniaturization. This review provides a comprehensive overview on the recent development of low-dimensional vdWM polarized photodetectors. To begin with, the exploitation of pristine 1D/2D vdWMs with immanent in-plane anisotropy and related heterostructures for filterless polarization-sensitive photodetectors is introduced. Then, we have systematically epitomized the various strategies to induce polarization photosensitivity and enhance the degree of anisotropy for low-dimensional vdWM photodetectors, including quantum tailoring, construction of core–shell structures, rolling engineering, ferroelectric regulation, strain engineering, etc, with emphasis on the fundamental physical principles. Following that, the ingenious optoelectronic applications based on the low-dimensional vdWM polarized photodetectors, including multiplexing optical communications and enhanced-contrast imaging, have been presented. In the end, the current challenges along with the future prospects of this burgeoning research field have been underscored. On the whole, the review depicts a fascinating landscape for the next-generation high-integration multifunctional optoelectronic systems.

The Türkiye-Syria earthquake doublet of 6 February 2023 (Mw 7.8 at 01:17 UTC and Mw 7.6 at 10:24 UTC) resulted in extensive damage and tens of thousands of casualties. We present the surface displacements of the two earthquakes from synthetic aperture radar (SAR) offset tracking measurements. We extracted the geometric parameters of the rupture faults from the surface displacements and early aftershock distribution, based on which we inverted the coseismic slip distributions. We then calculated Coulomb stress to investigate the triggering relationship between the earthquakes and stress transfer to neighbouring faults and regions. The coseismic ruptures of the earthquake doublet were predominantly left-lateral strike-slip motions distributed between 0 and 15 km depth. The maximum fault slip reached > 8 m (Mw 7.8) and almost 10 m (Mw 7.6). The coseismic deformation and fault slip motion are consistent with the overall westward extrusion of the Anatolian Plate relative to the Eurasian and Arabian plates. The Mw 7.8 earthquake increased Coulomb failure stress at the hypocenter of the Mw 7.6 earthquake, implying that the Mw 7.8 event had a strong positive causative effect. Moreover, coseismic stress perturbations revealed a positive Coulomb stress effect on the middle Puturge Fault, northern Dead Sea Fault Zone (DSFZ), Yesemek Fault, Antakya Fault, and Turkoglu Fault, indicating an increasing seismic hazard in these regions.

Aureobasidium pullulans (A. pullulans), a commonly found yeast-like fungus, exhibits adaptability to a wide range of pH environments. However, the specific mechanisms and regulatory pathways through which A. pullulans respond to external pH remain to be fully understood. In this study, we first sequenced the whole genome of A. pullulans using Nanopore technology and generated a circle map. Subsequently, we explored the biomass, pullulan production, melanin production, and polymalic acid production of A. pullulans when cultivated at different pH levels. We selected pH 4.0, pH 7.0, and pH 10.0 to represent acidic, neutral, and alkaline environments, respectively, and examined the morphological characteristics of A. pullulans using SEM and TEM. Our observations revealed that A. pullulans predominantly exhibited hyphal growth with thicker cell walls under acidic conditions. In neutral environments, it primarily displayed thick-walled spores and yeast-like cells, while in alkaline conditions, it mainly assumed an elongated yeast-like cell morphology. Additionally, transcriptome analysis unveiled that A. pullulans orchestrates its response to shifts in environmental pH by modulating its cellular morphology and the expression of genes involved in pullulan, melanin, and polymalic acid synthesis. This research enhances the understanding of how A. pullulans regulates itself in diverse pH settings and offers valuable guidance for developing and applying engineered strains.

Abstract Aims To explore the function of phosphorylation of KAP1 (p-KAP1) at the serine-824 site (S824) in the proliferation and apoptosis of endogenous neural stem cells (NSCs) after cerebral ischemic/reperfusion (I/R). Methods The apoptosis and proliferation of C17.2 cells transfected with the p-KAP1-expression plasmids and the expression of proliferation cell nuclear antigen (PCNA) and p-KAP1 were detected by immunofluorescence and Western blotting after the Oxygen Glucose deprivation/reperfusion model (OGD/R). The interaction of p-KAP1 and CUL4A with PCNA was analyzed by immunoprecipitation. In the rats MCAO model, we performed the adeno-associated virus (AAV) 2/9 gene delivery of p-KAP1 mutants to verify the proliferation of endogenous NSCs and the colocalization of PCNA and CUL4A by immunofluorescence. Results The level of p-KAP1 was significantly down-regulated in the stroke model in vivo and in vitro. Simulated p-KAP1(S824) significantly increased the proliferation of C17.2 cells and the expression of PCNA after OGD/R. Simulated p-KAP1(S824) enhanced the binding of p-KAP1 and PCNA and decreased the interaction between PCNA and CUL4A in C17.2 cells subjected to OGD/R. The AAV2/9-mediated p-KAP1(S824) increased endogenous NSCs proliferation, PCNA expression, p-KAP1 binding to PCNA, and improved neurological function in the rat MCAO model. Conclusions Our findings confirmed that simulated p-KAP1(S824) improved the survival and proliferation of endogenous NSCs. The underlying mechanism is that highly expressed p-KAP1(S824) promotes binding to PCNA, and inhibits the binding of CUL4A to PCNA. This reduced CUL4A-mediated ubiquitination degradation to increase the stability of PCNA and promote the survival and proliferation of NSCs.

ObjectiveAdenoid hypertrophy (AH) and otitis media with effusion (OME) are common pediatric otolaryngological diseases and often occur concurrently. The purpose of this study was to comprehensively analyze the factors that influence the occurrence of OME pediatric patients with AH.MethodsPatients younger than 12 years with AH, who were hospitalized for treatment at Beijing Tsinghua Changgung Hospital in Beijing, China, between March 2018 and February 2022 were enrolled. The patients were divided into an AH group and an AH + OME group based on the presence of OME. The authors collected the following clinical data for univariable analysis: sex; age; body mass index (BMI); comorbid nasal congestion/rhinorrhea, recurrent tonsillitis, or allergic rhinitis (AR); adenoid and tonsil grade; tonsillar hypertrophy; food/drug allergy; history of adenoidectomy and congenital diseases; breastfeeding status; preterm birth; exposure to environmental tobacco smoke (ETS); family history of adenotonsillectomy, otitis media, and AR; main data of polysomnography and oropharyngeal conditional pathogen culture data of some patients. Univariate analysis was performed as a basis for logistic regression analysis.ResultsA total of 511 children (329 boys and 182 girls) were included, their mean age was 5.37 ± 2.10 years. Of them, 407 (79.6%) were in the AH group and 104 (20.4%) in the AH + OME group. Univariate analysis revealed statistically significant differences in age, BMI, adenoid grade, AR, breastfeeding status, and ETS exposure between the two groups. Multivariate stepwise logistic regression analysis showed that age, adenoid grade, AR, breastfeeding status, and ETS influenced the occurrence of OME in pediatric patients with AH. The risk of OME decreased with increasing age. High adenoid grade, ETS exposure, and comorbid AR were risk factors for OME in pediatric patients with AH, but breastfeeding was a protective factor. The final analytical results of the oropharyngeal conditional pathogen culture data showed that Streptococcus pneumoniae positivity was associated with OME in AH.ConclusionThe pathogenesis of AH with OME is complex. Young age, high adenoid grade, ETS exposure, non-breastfed status, comorbid AR, and the presence of S. pneumoniae in the oropharynx are risk factors for OME in pediatric patients with AH.

Understanding the kinematic characteristics of the Longitudinal Valley Fault Zone (LVFZ) can help us to better understand the evolution of orogens. The 2022 Mw7.0 Taitung earthquake that occurred in Taiwan provides us with a good opportunity to understand the motion characteristics of the Central Range Fault (CRF) and the strain partitioning pattern within the Longitudinal Valley Fault (LVF). We obtained the coseismic displacement and slip distribution of the 2022 Taiwan earthquake based on the strong-motion and GPS data available. The causative fault of this earthquake is the west-dipping Central Range Fault, which is buried beneath the western boundary of the LVF. The coseismic displacement field exhibits a quadrant distribution pattern, indicating a left-lateral strike-slip mechanism with a maximum displacement exceeding 1.25 m. The joint inversion results show that the size of the main asperity is 40 km × 20 km, and the maximum slip amount of 2.6 m is located at a depth of 10 km, equivalent to an earthquake of Mw7.04. The LVFZ is composed of LVF and CRF, which accommodates nearly half of the oblique convergence rate between the Philippine Sea Plate and the Eurasian Plate. There is a phenomenon of strain partitioning in the southern segment of the Longitudinal Valley Fault Zone. The Central Mountain Range Fault is primarily responsible for accommodating strike-slip motion, while the Longitudinal Valley Fault is mainly responsible for accommodating thrust motion.

Abstract Purpose We aimed to conduct a meta-analysis to accurately evaluate the potential association between ADIPOQ rs2241766 gene SNP and breast cancer risk. Methods A systematic literature search on Cochrane Library, PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) identified 8 articles with 1692 cases and 1890 controls. Strength of association was evaluated by pooled odds ratio (OR), 95 % confidence interval (CI) and p value. Funnel plots and Begger’s regression test were applied for testing the publication bias. Statistical analysis of all data was performed by Stata 12.0. Results The meta-analysis results indicated that the ADIPOQ rs2241766 gene polymorphism did not significantly associated with the risk of breast cancer for these genetic models (TT vs. TG + GG: OR = 1.20, 95 % CI = 0.77–1.89, p=0.417; TT + TG vs. GG: OR = 1.05, 95 % CI = 0.71–1.56, p=0.805; T vs. G: OR =1.17, 95 % CI = 0.79–1.74, p=0.437). Conclusions This study indicated that no significant relationship between the ADIPOQ rs2241766 SNP and breast cancer. Further large-scale and well-designed studies will be indispensable to confirm our result.

Prolonged drought stress caused by global warming poses a tremendous challenge to silage production of maize. Drought during maize growth and development resulted in altered micro-environment for silage fermentation. How fermentation of silage maize responds to moisture scales remains uncharted territory. In this research, Maize water control trials were conducted and the silage quality and microbial community of drought-affected maize were determined. The results showed that drought stress significantly reduced the dry matter but increased root-to-shoot ratio, soluble sugar and malonaldehyde content in maize. Before fermentation, the crude protein, crude ash and acid detergent fiber contents were significantly increased but the ether extract content was decreased under drought. The crude protein and acid detergent fiber were significantly decreased in the drought affected group after fermentation. Furthermore, water stress at maize maturity stage greatly reduced the number of total bacteria in silage fermentation but increased the proportion of the lactobacillus and lactic acid content of silage. Drought stress alters the microbial ecosystem of the fermentation process and reconstitutes the diversity of the bacterial community and its metabolites. This study provides a theoretical basis for the study of changes in silage fermentation as affected by abiotic stresses.

In this work, a new paper-based device (PAD) was developed for the colorimetric detection of multiple heavy metals. The sensing principle of this PAD is based on the analyte-regulated photocatalytic activity of quantum dots (QDs) to certain substrates. The PAD consisted of three filter paper layers, defining a sample area, three channels, and three testing areas. Three photocatalytic reactions between different QDs and their corresponding substrates could be performed in one device, achieving the simultaneous detection of Cu(II), Mn(II), and Hg(II). The detection limits are 7.3 nM for Cu(II), 5.4 nM for Mn(II), and 8.1 nM for Hg(II), respectively. This PAD was applied to analyze real samples and the results were consistent with those obtained by inductively coupled plasma-optical emission spectrometer. This approach may provide a promising colorimetric sensing platform for multi-target analysis.

In this work, a predictor–corrector compact difference scheme for a nonlinear fractional differential equation is presented. The MacCormack method is provided to deal with nonlinear terms, the Riemann–Liouville (R-L) fractional integral term is treated by means of the second-order convolution quadrature formula, and the Caputo derivative term is discretized by the L1 discrete formula. Through the first and second derivatives of the matrix under the compact difference, we improve the precision of this scheme. Then, the existence and uniqueness are proved, and the numerical experiments are presented.

We have successfully identified the transcription factor Cmr1 from the fungus Aureobasidium pullulans Hit-lcy3T, which regulates melanin biosynthesis genes. Bioinformatics analysis revealed that the Cmr1 gene encodes a protein of 945 amino acids, containing two Cys2His2 zinc finger domains and a Zn(II)2Cys6 binuclear cluster domain located at the N-terminus of Cmr1. To investigate the function of the Cmr1 gene, we performed gene knockout and overexpression experiments. Our results showed that Cmr1 is a key regulator of melanin synthesis in Hit-lcy3T, and its absence caused developmental defects. Conversely, overexpression of Cmr1 significantly increased the number of chlamydospores in Hit-lcy3T and improved melanin production. RT-qPCR analysis further revealed that overexpression of Cmr1 enhanced the expression of several genes involved in melanin biosynthesis, including Cmr1, PKS, SCD1, and THR1. Melanin extracted from the Hit-lcy3T was characterized using UV and IR spectroscopy. Furthermore, we assessed the antioxidant properties of Hit-lcy3T melanin and found that it possesses strong scavenging activity against DPPH·, ABTS·, and OH·, but weaker activity against O2−·. These findings suggest that Hit-lcy3T melanin holds promise for future development as a functional food additive.

Plant exosome-like nanoparticles (ELNs) have shown great potential in treating tumor and inflammatory diseases, but the neuroprotective effect of plant ELNs remains unknown. In the present study, we isolated and characterized novel ELNs from Momordica charantia (MC) and investigated their neuroprotective effects against cerebral ischemia-reperfusion injury. In the present study, MC-ELNs were isolated by ultracentrifugation and characterized. Male Sprague–Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and MC-ELN injection intravenously. The integrity of the blood–brain barrier (BBB) was examined by Evans blue staining and with the expression of matrix metalloproteinase 9 (MMP-9), claudin-5, and ZO-1. Neuronal apoptosis was evaluated by TUNEL and the expression of apoptotic proteins including Bcl2, Bax, and cleaved caspase 3. The major discoveries include: 1) Dil-labeled MC-ELNs were identified in the infarct area; 2) MC-ELN treatment significantly ameliorated BBB disruption, decreased infarct sizes, and reduced neurological deficit scores; 3) MC-ELN treatment obviously downregulated the expression of MMP-9 and upregulated the expression of ZO-1 and claudin-5. Small RNA-sequencing revealed that MC-ELN-derived miRNA5266 reduced MMP-9 expression. Furthermore, MC-ELN treatment significantly upregulated the AKT/GSK3β signaling pathway and attenuated neuronal apoptosis in HT22 cells. Taken together, these findings indicate that MC-ELNs attenuate ischemia-reperfusion–induced damage to the BBB and inhibit neuronal apoptosis probably via the upregulation of the AKT/GSK3β signaling pathway.

Objective (s): In this mini-review, we aimed to discuss the Wnt/β-catenin signaling pathway modulation in triple-negative breast cancer, particularly the contribution of lncRNAs and miRNAs in its regulation and their possible entwining role in breast cancer pathogenesis, proliferation, migration, or malignancy.Background: Malignant tumor formation is very high for breast cancer in women and is a leading cause of death all over the globe. Among breast cancer subtypes, triple-negative breast cancer is rife in premenopausal women, most invasive, and prone to metastasis. Complex pathways are involved in this cancer’s pathogenesis, advancement, and malignancy, including the Wnt/β-catenin signaling pathway. This pathway is conserved among vertebrates and is necessary for sustaining cell homeostasis. It is regulated by several elements such as transcription factors, enhancers, non-coding RNAs (lncRNAs and miRNAs), etc.Methods: We evaluated lncRNAs and miRNAs differentially expressed in triple-negative breast cancer (TNBC) from the cDNA microarray data set literature survey. Using in silico analyses combined with a review of the current literature, we anticipated identifying lncRNAs and miRNAs that might modulate the Wnt/β-catenin signaling pathway.Result: The miRNAs and lncRNAs specific to triple-negative breast cancer have been identified based on literature and database searches. Tumorigenesis, metastasis, and EMT were all given special attention. Apart from cross-talk being essential for TNBC tumorigenesis and treatment outcomes, our results indicated eight upregulated and seven downregulated miRNAs and 19 upregulated and three downregulated lncRNAs that can be used as predictive or diagnostic markers. This consolidated information could be useful in the clinic and provide a combined literature resource for TNBC researchers working on the Wnt/β-catenin miRNA/lncRNA axis.Conclusion: In conclusion, because the Wnt pathway and miRNAs/lncRNAs can modulate TNBC, their intertwinement results in a cascade of complex reactions that affect TNBC and related processes. Their function in TNBC pathogenesis has been highlighted in molecular processes underlying the disease progression.

Paroxysmal sympathetic hyperactivity (PSH) is a neurological emergency mostly secondary to traumatic brain injury (TBI). Acute large vessel occlusion (LVO) in the posterior circulation with PSH as the initial manifestation is uncommon. It may lead to catastrophic consequences for patients if not detected and treated timely. Here, we present three patients with acute LVO in the posterior circulation with PSH as the initial symptom. All patients were male and averaged 63 years old. The PSH Assessment Measure (PSH-AM) scores of all cases were > 17. Brain imaging showed that multiple lesions in posterior circulation were involved in three patients. Although the prognosis of all patients was poor, PSH symptoms disappeared in all patients after endovascular treatment. These cases suggests that acute posterior circulation-related ischemic stroke should be considered with PSH occurring as the first symptom. Extensive disconnection due to multiple lesions in posterior circulation may play an important role in the occurrence and development of PSH. Endovascular treatment may be effective for PSH caused by acute posterior circulation-related ischemic stroke. This is worthy of further study in the future.

The ability of the fungus to regulate metabolism on various nitrogen sources makes it survive and metabolize in different environments. The biomass and the β-glucan yield of Aureobasidium pullulans are closely associated with the nitrogen source. This study found the only GATA nitrogen source activation regulating factor Area in HIT-LCY3. In order to testify the Area function, we amplified its conserved domain to build a silencing vector and used the RNAi to obtain the Area silent strain, and then explored its effect on the phenotype of A. pullulans and the yield of β-glucan. We found that the biomass and β-glucan yield of the silent strain decreased significantly after culturing with different nitrogen sources, in particular when using sodium nitrate and glutamate as the source. However, the β-glucan yield increased significantly after overexpression of Area, reaching 5.2 g/L when glutamine was the nitrogen source. In addition, the strain morphology changed as well under different nitrogen sources. At last, we investigated the antioxidant activity in vitro of β-glucan and found that it has a significant clearance effect on OH·, DPPH·, and ABTS·, being best with ABTS. Therefore, this study believed that the Area gene has a certain regulation function on the synthesis of β-glucan with antioxidant activity.

Abstract Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β family, is associated with tumor progression, metastasis, and cell apoptosis. However, controversy persists regarding the role of GDF15 in different tumor types, and its function in glioma stem cells (GSCs) remains unknown. Here, we report that GDF15 promotes the GSC-like phenotype in GSC-like cells (GSCLCs) through the activation of leukemia inhibitor factor (LIF)–STAT3 signaling. Mechanistically, GDF15 was found to upregulate expression of the transcription factor c-Fos, which binds to the LIF promoter, leading to enhanced transcription of LIF in GSCLCs. Furthermore, GDF15 may activate the ERK1/2 signaling pathway in GSCLCs, and the upregulation of LIF expression and the GSC-like phenotype was dependent on ERK1/2 signaling. In addition, the small immunomodulator imiquimod induced GDF15 expression, which in turn activated the LIF–STAT3 pathway and subsequently promoted the GSC-like phenotype in GSCLCs. Thus, our results demonstrate that GDF15 can act as a proliferative and pro-stemness factor for GSCs, and therefore, it may represent a potential therapeutic target in glioma treatment.

The Georgia-07-like genotype II African swine fever virus (ASFV) with high virulence has been prevalent in China since 2018. Here, we report that genotype I ASFVs have now also emerged in China. Two non-haemadsorbing genotype I ASFVs, HeN/ZZ-P1/21 and SD/DY-I/21, were isolated from pig farms in Henan and Shandong province, respectively. Phylogenetic analysis of the whole genome sequences suggested that both isolates share high similarity with NH/P68 and OURT88/3, two genotype I ASFVs isolated in Portugal in the last century. Animal challenge testing revealed that SD/DY-I/21 shows low virulence and efficient transmissibility in pigs, and causes mild onset of infection and chronic disease. SD/DY-I/21 was found to cause necrotic skin lesions and joint swelling. The emergence of genotype I ASFVs will present more problems and challenges for the control and prevention of African swine fever in China.

Thoracic radiotherapy patients have higher risks of developing radiation-induced heart disease (RIHD). Ionizing radiation generates excessive reactive oxygens species (ROS) causing oxidative stress, while Momordica. charantia and its extract have antioxidant activity. Plant-derived extracellular vesicles (EVs) is emerging as novel therapeutic agent. Therefore, we explored the protective effects of Momordica. charantia-derived EVs-like nanovesicles (MCELNs) against RIHD. Using density gradient centrifugation, we successfully isolated MCELNs with similar shape, size, and markers as EVs. Confocal imaging revealed that rat cardiomyocytes H9C2 cells internalized PKH67 labeled MCELNs time-dependently. In vitro assay identified that MCELNs promoted cell proliferation, suppressed cell apoptosis, and alleviated the DNA damage in irradiated (16 Gy, X-ray) H9C2 cells. Moreover, elevated mitochondria ROS in irradiated H9C2 cells were scavenged by MCELNs, protecting mitochondria function with re-balanced mitochondria membrane potential. Furthermore, the phosphorylation of ROS-related proteins was recovered with increased ratios of p-AKT/AKT and p-ERK/ERK in MCELNs treated irradiated H9C2 cells. Last, intraperitoneal administration of MCELNs mitigated myocardial injury and fibrosis in a thoracic radiation mice model. Our data demonstrated the potential protective effects of MCELNs against RIHD. The MCELNs shed light on preventive regime development for radiation-related toxicity.

Degradation of microplastics (MPs) by both physicochemical and biological processes in the natural environment is determined by the enzymes inside the soil, and which was severely influenced by crop growth and straw amendment (SA). However, it is still unclear how crop growth and SA influence degradation of MPs in soils. In this study, both catalase and sucrase were measured, and the stereomicroscope combined with microscopic infrared spectroscopy and scanning electron microscope (SEM) was used to detect the morphology and quantity of low-density polyethylene microplastic (LDPE-MP) and low-density polypropylene microplastic (LDPP-MP), after crop growth (maize and soybean, with and without SA, 1 and 2% MP) in an outdoor pot experiment, in the Mollisols. The results showed that the growth of the crops changed the morphology, functional groups (e.g., methylene, carbonyl), total mass, and abundance ratio of MPs of different sizes. These were possibly caused by enzymes that were significantly influenced by crop types, abundance, and types of MPs in the soils. Maize growth decreased the mass of LDPE-MP and LDPP-MP by 28.7 and 32.7%, respectively, and 2% (w/w) of LDPP-MP addition in soil decreased mass of 9%, which was higher than that in 1% (w/w) LDPP-MP addition in soil. Soybean growth with SA decreased the mass of LDPE-MP and LDPP-MP by 36.6 and 20.7%, respectively, than the control treatment (CK). Compared with CK, both crop growth and SA changed the abundance of MPs of different sizes and decreased the mean size of MPs. The LDPE-MP could be more easily degraded by enzymes in the soils compared to LDPP-MP when the MP size was smaller with surface roughness. Generally, both maize and soybean growth can accelerate MP change in soils, and MP change process was mainly determined by SA, MP types, and the dose effect of MP.

Momordica.charantia has antioxidant and neuroprotective effects, but its anti-glioma capacity remains unclear. Plant-derived nanovesicles have shown therapeutic potential in inflammation and cancer. This study explored the therapeutic effects of Momordica.charantia-derived extracellular vesicles-like nanovesicles (MCELNs) in treating glioma and its underlying mechanisms. The MCELNs were successfully isolated and characterized similarly to animal cell-derived extracellular vesicles. The in vitro assays identified that MCELNs inhibited the proliferation but did not promote apoptosis of U251 glioma cells. MCELNs repressed U251 glioma cells migration and invasion via proceeding the epithelial-mesenchymal transition process and downregulating MMP9. MCELNs penetrated the BBB and suppressed the glioma growth and metastasis in vivo. The ratios of p-AKT/AKT and p-PI3K/PI3K were downregulated in MCELNs treated U251 glioma cells compared with the control. Highly expressed miR5813 in MCELNs might be involved in the PI3K/AKT pathway that needs further investigation. MCELNs could serve as a novel therapeutic strategy for glioma treatment.

This paper reports the non-targeted analysis of unknown volatile chemicals in medical masks through headspace gas chromatography-Orbitrap high-resolution mass spectrometry. In view of the difficulties that may be encountered in the qualitative analysis of unknown substances, several typical cases and the corresponding reliable solutions are given from the perspective of comprehensive score and retention index, chemical ionization identification molecular formula, fragment ion detail comparison for distinguishing isomers, and identification of alkanes. With this method, 69 volatile substances were identified in 60 masks. The identified substances were divided into nine categories. Alkanes, esters, benzenes, and alcohols were the top four groups of substances identified in masks and accounted for 34.8%, 15.9%, 10.1%, and 7.2% of the total substances, respectively. In addition, ketones, ethers, phenolics, amides, and other substances were identified. Ethanol, 1,4-dichlorobenzene, toluene, m-xylene, dimethyl glutarate, and N,N-dimethylacetamide had high detection rates. The identified substances were further filtered and screened according to their detection rate, toxicity, and response intensity. Finally, 12 high-risk volatile chemicals in medical masks were listed. This study could serve as a reference for identifying unknown substances and a guide for monitoring volatile chemicals in masks and promoting chemical safety improvements in products.

Blood–brain barrier (BBB) dysfunction causing edema and hemorrhagic transformation is one of the pathophysiological characteristics of stroke. Protection of BBB integrity has shown great potential in improving stroke outcome. Here, we assessed the efficacy of exosomes extracted from healthy rat serum in protection against ischemic stroke in vivo and in vitro. Exosomes were isolated by gradient centrifugation and ultracentrifugation and exosomes were characterized by transmission electron microscopy (TEM) and nanoparticle tracking video microscope. Exosomes were applied to middle cerebral artery occlusion (MCAO) rats or brain microvascular endothelial cell line (bEnd.3) subjected to oxygen-glucose deprivation (OGD) injury. Serum-derived exosomes were injected intravenously into adult male rats 2 h after transient MCAO. Infarct volume and gross cognitive function were assessed 24 h after reperfusion. Poststroke rats treated with serum-derived exosomes exhibited significantly reduced infarct volumes and enhanced neurological function. Apoptosis was assessed via terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining and the expression of B-cell lymphoma-2 (Bcl-2), Bax, and cleaved caspase-3 24 h after injury. Our data showed that serum exosomes treatment strikingly decreased TUNEL+ cells in the striatum, enhanced the ratio of Bcl-2 to Bax, and inhibited cleaved caspase-3 production in MCAO rats and OGD/reoxygenation insulted bEnd.3 cells. Under the consistent treatment, the expression of microtubule-associated protein 1 light chain 3B-II (LC3B-II), LC3B-I, and Sequestosome-1 (SQSTM1)/p62 was detected by Western blotting. Autolysosomes were observed via TEM. We found that serum exosomes reversed the ratio of LC3B-II to LC3B-I, prevented SQSTM1/p62 degradation, autolysosome formation, and autophagic flux. Together, these results indicated that exosomes isolated from healthy serum provided neuroprotection against experimental stroke partially via inhibition of endothelial cell apoptosis and autophagy-mediated BBB breakdown. Intravenous serum-derived exosome treatment may, therefore, provide a novel clinical therapeutic strategy for ischemic stroke.

Background and Aim Loss of hepatitis B surface antigen (HBsAg) is an important goal in the treatment of chronic hepatitis B. We investigated whether switching from long‐term entecavir (ETV) administration to tenofovir (TFV) (tenofovir alafenamide [TAF] or tenofovir disoproxil fumarate [TDF]) could contribute to the reduction of HBsAg levels. Methods The degree of HBsAg reduction by 48 weeks in 30 patients following switching from ETV to TFV was compared with results from 147 patients who continued ETV as a control. Results TFV group switched to TFV after mean 6.79 years of ETV administration. HBV‐DNA levels remained below 1.0 log IU/mL in all cases in both groups during 48 weeks. Median HBsAg reduction at 48 weeks was 0.075 (−0.05 to 0.38) log/IU/mL in the TFV switch group, and 0.070 (−0.28 to 0.50) in the ETV continuation group, which was not statistically significant (p = 0.5). In a subgroup of hepatitis B e antigen negative patients whose HBsAg had not been reduced (HBsAg reduction ≤0 log IU/mL) in the 48 weeks prior to entry into the study, HBsAg reduction was significantly higher in the TFV switch group than in the ETV continuation group (0.15 [0.07–0.135] in TFV, 0.09 [−0.14 to 0.25] log IU/mL in ETV, p = 0.04). Conclusion Although HBsAg reduction is equivalent with ETV continuation and switching to TFV in all patients at 48 weeks, switching from ETV to TFV could provide an alternative therapeutic strategy toward HBsAg elimination in a specific subpopulation of patients.

AimDespite a significant improvement in the number of studies on myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG)-associated disorder (MOGAD) over the past few years, MOG-IgG-associated cortical/brainstem encephalitis remains a relatively uncommon and less-reported presentation among the MOGAD spectrum. This study aimed to report the clinical course, imaging features, and therapeutic response of MOG-IgG-associated cortical/brainstem encephalitis.MethodsData of four patients who suffered from cortical encephalitis with epileptic seizures and/or brainstem encephalitis during the course of the disease were retrospectively collected and analyzed.ResultsIn this study, three male patients and one female patient, with a median age of onset of 21 years (ranging 20–51 years) were enrolled. An epileptic seizure was the main symptom of cortical encephalitis in these patients, while the manifestations of brainstem encephalitis were diverse. Cranial MRI demonstrated abnormal signals in unilateral or bilateral cortical or brainstem. Cerebrospinal fluid studies showed normal or mildly elevated leukocyte counts and protein levels, and a cell-based assay detected positive MOG-IgG in the serum of all patients. Two patients were misdiagnosed at the first attack, and both experienced a relapse. All of them accepted the first-line immunotherapy after a confirmed diagnosis and had a good outcome.ConclusionEarly suspicion of MOG-IgG-associated encephalitis is necessary for any patient with sudden onset of seizures or symptoms of brainstem damage, especially with lesions on unilateral/bilateral cortical or brainstem on brain MRI.

Bovine respiratory disease complex (BRDC) occurs widely in cattle farms. The main viral pathogens include bovine viral diarrhea virus (BVDV), Bovine herpesvirus 1 (BoHV-1), bovine parainfluenza virus type 3 (BPIV3), and bovine respiratory syncytial virus (BRSV), and the newly emerged influenza D virus (IDV). In this study, we have developed a one-step multiplex real-time Polymerase Chain Reaction (PCR) capable of simultaneously detecting these five viral pathogens causing BRDC. The established assay could specifically detect targeted viruses without cross-reaction with others. The detection limit was ~10 copies/reaction for single real-time PCR and 100 copies/ reaction for multiplex real-time PCR assay. A total of 213 nasal samples from cattle with signs of respiratory tract disease were then collected for performance evaluation of the established platform, proving that the method has good specificity and sensitivity. The surveillance data suggested that BVDV and BoHV-1 infections are the dominant cause of BRDC in the herd, whereas the detection rate of IDV, BIPV3, and BRSV is relatively lower. In summary, the established assay provides technical support for rapid clinical detection of BRDC associated viral pathogens to guide the formulation of BRDC prevention and control measures.

Abstract As a new expression system, Dunaliella salina (D. salina) has bright prospects and applications in various fields. However, its application is currently restricted because of the low expression and instability of foreign gene in D. salina cells. During genetic operation, transformation is a crucial step for genes expression in D. salina system. Although several transformation methods are existing currently, many inherent deficiencies and limitations still can be found in actual practice. Thus, we attempted to set up a rapid transformation method using the change of salt concentrations for D. salina. Based on osmotic pressure difference, exogenous genes can be spontaneously transferred into D. salina cells. After that, transformed D. salina cells were subjected to histochemical and molecular analysis. The results showed that the reporter gene, beta-glucuronidase genes were successfully expressed in the positive transformants, and detected in all of transformed cells by PCR analysis. Moreover, different transformation parameters, containing the salt gradient, time, dye dosage and Triton X-100 concentration, were optimized to obtain an optimal transformation result. Taken together, we preliminarily established a rapid transformation method with the features of fast, simple, economic, and high-efficient. This method will provide a strong genetic manipulation tool for the future transformation of D. salina system.

A carotid web is a thin intraluminal protrusion located in the posterolateral wall of the carotid bulb, which might be a risk factor for cryptogenic stroke. The mechanism of ischemic stroke caused by carotid web is still unclear, but it might be related to hemodynamic changes distal to the web, resulting in flow forces and remote embolization of fibrin-based clots. The diagnosis of a carotid web mainly depends on carotid artery imaging examinations. The main therapeutic strategies include medical treatment with oral antiplatelet agents and anticoagulants, and operative treatment, such as carotid endarterectomy and carotid artery stenting. Few cases of acute large-vessel occlusion undergoing mechanical thrombectomy in the setting of carotid web as the etiology have been reported. We report here a case of a 37-year-old woman who underwent stent retriever embolectomy after acute ischemic stroke. Carotid artery imaging examinations, including digital subtraction angiography and magnetic resonance imaging, and pathology showed that a carotid web was located at the proximal right internal carotid artery. We also discuss the clinical pathophysiological and imaging features, and the treatment of carotid web as described in the currently available literature.

Chaetoglobosin A (CheA), a well-known macrocyclic alkaloid with prominently highly antimycotic, antiparasitic, and antitumor properties, is mainly produced by Chaetomium globosum. However, a limited understanding of the transcriptional regulation of CheA biosynthesis has hampered its application and commercialization in agriculture and biomedicine. Here, a comprehensive study of the CgXpp1 gene, which encodes a basic helix-loop-helix family regulator with a putative role in the regulation of fungal growth and CheA biosynthesis, was performed by employing CgXpp1-disruption and CgXpp1-complementation strategies in the biocontrol species C. globosum. The results suggest that the CgXpp1 gene could be an indirect negative regulator in CheA production. Interestingly, knockout of CgXpp1 considerably increased the transcription levels of key genes and related regulatory factors associated with the CheA biosynthetic. Disruption of CgXpp1 led to a significant reduction in spore production and attenuation of cell development, which was consistent with metabolome analysis results. Taken together, an in-depth analysis of pleiotropic regulation influenced by transcription factors could provide insights into the unexplored metabolic mechanisms associated with primary and secondary metabolite production.

The addition of fruit juice may improve the physicochemical and functional characteristics of dairy products. The study evaluated the effect of 1–6% (v/v) blue honeysuckle juice (BHJ) on the physicochemical, sensory and antioxidant characteristics of fermented goat milk (FGM) during 21 days of refrigerated storage and in vitro gastrointestinal digestion. The incorporation of BHJ significantly increased (p < 0.05) the water-holding capacity, viscosity, redness (a*) value, total phenolic content (TPC) and ferric ion-reducing antioxidant power during storage. Additionally, BHJ affected the microstructure and sensory score of the samples. FGM treated with 4% (v/v) BHJ exhibited the highest overall acceptability. The supplementation of BHJ diminished the goaty flavor and promoted in vitro protein digestion. Furthermore, the TPC was enhanced in addition to the antioxidant activity of FGM containing BHJ throughout the in vitro digestion. Therefore, FGM supplemented with BHJ serves as a novel and attractive goat dairy product.

This study aims to evaluate the reproducibility and validity of a semi-quantitative food frequency questionnaire (SQFFQ) developed for vegetarians and omnivores in Harbin, China. Participants (36 vegetarians and 64 omnivores) administered SQFFQ at baseline (SQFFQ1) and six months later (SQFFQ2) to assess the reproducibility. The 24 h recalls (24 HRs) for three consecutive days were completed between the administrations of two SQFFQs to determine the validity. For reproducibility, Pearson correlation coefficients between SQFFQ1 and SQFFQ2 for vegetarians and omnivores were 0.45~0.88 and 0.44~0.84, respectively. For validity, unadjusted Pearson correlation coefficients were 0.46~0.83 with an average of 0.63 and 0.43~0.86 with an average of 0.61, respectively; energy-adjusted Pearson correlation coefficients were 0.43~0.82 with an average of 0.61 and 0.40~0.85 with an average of 0.59, respectively. Majority of the correlation coefficients for food groups and macronutrients decreased or remained unchanged after energy adjustment. Furthermore, all correlations were statistically significant (p < 0.05). Bland–Altman plots also showed reasonably acceptable agreement between the two methods. In conclusion, the SQFFQ developed in this study has reasonably acceptable reproducibility and validity.

African swine fever (ASF) is a highly contagious hemorrhagic disease of pigs, posing a significant threat to the world pig industry. Several researchers are investigating the possibilities for developing a safe and efficient vaccine against ASF. In this regard, significant progress has been made and some gene-deleted ASFVs are reported as potential live attenuated vaccines. A seven-gene-deleted live attenuated vaccine candidate HLJ/18-7GD (among which CD2v is included) has been developed in our laboratory and reported to be safe and protective, and it is expected to be commercialized in the near future. There is an urgent need for developing a diagnostic method that can clearly discriminate between wild-type-ASFV-infected and vaccinated animals (DIVA). In the present study, a dual indirect ELISA based on p54 and CD2v proteins was successfully established to specifically distinguish serum antibodies from pigs infected with wild-type ASFV or possessing vaccine immunization. To evaluate the performance of the assay, a total of 433 serum samples from four groups of pigs experimentally infected with the wild-type HLJ/18 ASFV, immunized with the HLJ/18-7GD vaccine candidate, infected with the new lower virulent variant, and specific-pathogen-free pigs were used. Our results showed that the positive rate of immunized serum was 96.54% (p54) and 2.83% (CD2v), and the positive rate of the infection by wild-type virus was 100% (p54) and 97.8% (CD2v). Similarly, the positive rate to infection by the new low-virulent ASFV variant in China was 100% (p54) and 0% (CD2v), indicating the technique was also able to distinguish antibodies from wild-type and the new low-virulent ASFV variant in China. Moreover, no cross-reaction was observed in immune sera from other swine pathogens, such as CSFV, PEDV, PRRSV, HP-PRRSV, PCV2, and PrV. Overall, the developed dual indirect ELISA exhibited high diagnostic sensitivity, specificity, and repeatability and will provide a new approach to differentiate serum antibodies between wild virulent and CD2v-unexpressed ASFV infection, which will play a great role in serological diagnosis and epidemiological monitoring of ASF in the future.

The purpose of this research was to explore the impacts of different homogenization pressures, pasteurization conditions, and process sequence on the physical and chemical properties of soybean oil body (SOB)-substituted low-fat ice cream as well as the storage stability of SOB-substituted ice cream under these process parameters. With the increase of homogenization pressure (10–30 MPa), the increase of pasteurization temperature (65 °C for 30 min–85 °C for 15 min), and the addition of SOB before homogenization, the overrun and apparent viscosity of ice cream increased significantly, and the particle size, hardness, and melting rate decreased significantly. Thus, frozen dairy products of desired quality and condition could be obtained by optimizing process parameters. In addition, the SOB ice cream showed better storage stability, which was reflected in lower melting rate and hardness and more stable microstructure compared with the full-milk-fat ice cream. This study opened up new ideas for the application of SOB and the development of nutritious and healthy ice cream. Meanwhile, this research supplied a conceptual basis for the processing and quality optimization of SOB ice cream.

A metasurface is an array of subwavelength units with modulated wave responses that show great potential for the control of refractive/reflective properties in compact functional devices. In this work, we propose an elastic metasurface consisting of a line of pillars with gradient heights, erected on a homogeneous plate. The change in the resonant frequencies associated with the height gradient allows us to achieve transmitted phase response covering a range of 2π, while the amplitude response remains at a relatively high level. We employ the pillared units to design a focusing metasurface and compare the properties of the focal spots through simulation and experiment. The subwavelength transverse and lateral full width at half maximum of the focusing intensity profiles are observed in both simulation and experiment, with the underlying mechanism being the interference and diffraction of the scattered waves from the resonant pillars as well as the boundaries (especially for experiment). The good correspondence between the experimental and simulated relative focal lengths shows the robustness of the focusing pillared metasurfaces with respect to fabrication imperfections. This proposed compact, simple, and robust metasurface with unaffected mechanical properties provides a new platform for elastic wave manipulation for energy harvesting, wave communication, sensing, and non-destructive testing among others.