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Abstract The current clinical application of glaucoma drainage devices is made of non-degradable materials. These non-degradable drainage devices often trigger inflammatory responses and scar proliferation, possibly leading to surgical failure. We developed a biodegradable material hydroxyapatite-coated magnesium (HA-Mg) as a glaucoma drainage device. Twelve New Zealand white rabbits were randomly assigned to three groups: HA-Mg drainage plate group (6 right eyes), trabeculectomy group (6 right eyes), and control group (12 left eyes). Results showed that all HA-Mg drainage plates were completely degraded ~4 months postoperatively. At the 5th month postoperatively, there was no statistical difference in the corneal endothelium density between the HA-Mg drainage plate group and the control group (p = 0.857). The intraocular pressure (IOP) level in the HA-Mg drainage plate implantation group was lower than in the other two groups. The trypan blue dye still drained from the anterior chamber to the subconjunctiva 5 months after HA-Mg drainage plate implantation. HE staining revealed the scleral linear aqueous humor drainage channel and anterior synechia were observed after drainage plate completely degraded, with no obvious infiltration with the inflammatory cells. This study showed the safety and efficacy of HA-Mg glaucoma drainage plate in controlling IOP after implantation into the anterior chamber of rabbit eyes. Graphical abstract We developed a biodegradable material hydroxyapatite-coated magnesium (HA-Mg) as a glaucoma drainage device. This study evaluated the safety and efficacy of HA-Mg glaucoma drainage plate in controlling intraocular pressure after implantation into the anterior chamber of rabbit eyes.

Abstract Optical resonators are indispensable tools in optical metrology that usually benefit from an evacuated and highly-isolated environment to achieve peak performance. Even in the more sophisticated design of Fabry-Perot (FP) cavities, the material choice limits the achievable quality factors. For this reason, monolithic resonators are emerging as promising alternative to traditional designs, but their design is still at preliminary stage and far from being optimized. Here, we demonstrate a monolithic FP resonator with 4.5 cm3 volume and 2 × 105 finesse. In the ambient environment, we achieve 18 Hz integrated laser linewidth and 7 × 10−14 frequency stability measured from 0.08 s to 0.3 s averaging time, the highest spectral purity and stability demonstrated to date in the context of monolithic reference resonators. By locking two separate lasers to distinct modes of the same resonator, a 96 GHz microwave signals is generated with phase noise -100 dBc/Hz at 10 kHz frequency offset, achieving orders of magnitude improvement in the approach of photonic heterodyne synthesis. The compact monolithic FP resonator is promising for applications in spectrally-pure, high-frequency microwave photonic references as well as optical clocks and other metrological devices. ©2024. All rights reserved.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by producing remarkable clinical outcomes for patients with various cancer types. However, only a subset of patients benefits from immunotherapeutic interventions due to the primary and acquired resistance to ICIs. Myeloid-derived suppressor cells (MDSCs) play a crucial role in creating an immunosuppressive tumor microenvironment (TME) and contribute to resistance to immunotherapy. V-domain Ig suppressor of T cell activation (VISTA), a negative immune checkpoint protein highly expressed on MDSCs, presents a promising target for overcoming resistance to current ICIs. This article provides an overview of the evidence supporting VISTA's role in regulating MDSCs in shaping the TME, thus offering insights into how to overcome immunotherapy resistance.

This paper proposes a critical clearing time (CCT) estimation method by the domain of attraction (DA) of a state-reduction model of power systems using sum of squares (SOS) programming. By exploiting the property of the Jacobian matrix and the structure of the boundary of the DA, it is found the DA of the state-reduction model and that of the full model of a power system are topological isomorphism. There are one-to-one correspondence relationships between the number of equilibrium points, the type of equilibrium points, and solutions of the two system models. Based on these findings, an expanding interior algorithm is proposed with SOS programming to estimate the DA of the state-reduction model. State trajectories of the full model can be transformed to those of the state-reduction model by orthogonal or equiradius projection. In this way, CCT of a grid fault is estimated with the DA of the state-reduction model. The calculational burden of SOS programming in the DA estimation using the state-reduction model is rather small compared with using the full model. Simulation results show the proposed expanding interior algorithm is able to provide a tight estimation of DA of power systems with higher accuracy and lower time costs.

Herein, the radiation patterns of single-split ring resonators (SSRRs) and double-split ring resonators (DSRRs) in the vertical direction are tailored by reconfiguring the resonator geometries. To design unequal arm lengths for controlling the floating split angle of the resonators and changing their electromagnetic multipole compositions, vertical metamaterials were fabricated using the metal-stress-driven self-folding method. The simulation results well agree with the experimental transmittance and reflectance results and demonstrate the geometry-dependent angle variation of the far-field radiation. Symmetric SSRRs and DSRRs radiate in the vertical and horizontal directions, respectively. With increasing pad shift, the radiation angle of the asymmetric SSRR completely rotates toward the horizontal direction along the ring plane, but the DSRRs can rotate only from 0° to 45° to the horizontal plane. Furthermore, by decomposing the multipoles into their constituents, we show that the directional scattering performance can be verified by manipulating the horizontal and vertical components of the electric dipoles. This novel combination of SSRRs and DSRRs can effectively and efficiently reconfigure the radiation direction in the infrared (IR) region, paving the way for color routers, metasurfaces, and directive IR emitters in compact optical metadevices.

The occurrence of classical swine fever (CSF) poses a significant threat to the global swine industry. Developing an effective and safe vaccine is crucial for preventing and controlling CSF. Here, we constructed self-assembled ferritin nanoparticles fused with the classical swine fever virus (CSFV) E2 protein and a derived B cell epitope (Fe-E2B) using a baculovirus expression system (BVES), demonstrating enhanced immunogenicity. Furthermore, we provide a detailed evaluation of the immunological efficacy of the FeE2B in rabbits. The results showed that robust and sustained antibody responses were detected in rabbits immunized with the Fe-E2B nanoparticle vaccine, comparable to those elicited by commercially available vaccines. Additionally, we demonstrated that the vaccine effectively activated crucial immune factors IFN-γ and IL-4 in vivo, increasing their levels by 1.41-fold and 1.39-fold, respectively. Immunization with Fe-E2B enabled rabbits to avoid viremia and stereotypic fever after CSFV challenge. In conclusion, this study highlights the potential of ferritin nanoparticles as antigen-presenting carriers to induce robust immune responses, proposing a candidate vaccine strategy for the prevention and control of CSF.

Background: Fibro-adipogenic progenitors (FAP) are muscle resident mesenchymal stem cells pivotal for regulation of myofiber repair. Experimental results show in addition involvement in a range of other pathological conditions and potential for pharmacological intervention. FAP histopathology in human muscle biopsies is largely unknown, but has potential to inform translational research. Methods: CD10+ FAPs in 32 archival muscle biopsies from 8 groups (normal, dermatomyositis, inclusion body myositis (IBM), anti-synthetase syndrome, immune-mediated necrotizing myopathy (IMNM), denervation, type 2 atrophy, rhabdomyolysis) were visualized by CD10 immunohistochemistry and their histology compared. Groups are compared by semi-quantitative scoring. Results: Histological activation of endomysial CD10+ FAPs includes prominent expansion of a network of cell processes surrounding muscle fibers, as well as endomysial cell clusters evidencing proliferation. Prominence of periarteriolar processes is a notable feature in some pathologies. FAP activation is often associated with fiber degeneration/regeneration, foci of inflammation, and denervation in keeping with experimental results. Type 2 atrophy shows no evidence of FAP activation. Dermatomyositis and anti-synthetase syndrome associated myositis demonstrate diffuse activation. Conclusion: Assessment of CD10+ FAP activation is routinely possible using CD10 immunohistochemistry and demonstrates several patterns in keeping with preclinical results. Prominent expansion of FAP processes surrounding myofibers suggests enhanced interaction between myofiber/basement membranes and FAPs during activation. The presence of diffuse FAP activation in dermatomyositis biopsies unrelated to fiber repair raises the possibility of FAP activation as part of the autoimmune process. Future diagnostic applications, clinical significance and therapeutic potential remain to be elucidated.

ABSTRACT As an essential component of host defense against infection, necroptosis is a novel highly regulated mode of cell death that is mediated by signaling complexes containing receptor-interacting protein kinase 1 (RIPK1) and RIPK3. Lymphocyte depletion and immunosuppression are typical clinical features of pigs infected with classical swine fever virus (CSFV). Here, we provide the first evidence for the involvement of necroptosis in the necrosis of T lymphocytes in the spleen and peripheral blood of pigs infected in vivo with CSFV. However, it is true for some viruses with non-cytopathic effects, including CSFV, to balance host defense against infection. In vitro, the induction of autophagy by CSFV at a later stage of infection clearly restricts necroptosis. Mechanistic studies revealed that CSFV NS4A protein promoted tripartite motif-containing 25 expression, synergistically induced the occurrence of mitophagy, targeted the autophagic degradation of RIPK3 to block the progression of necroptosis occurrence, and achieved persistent viral infection. Interestingly, we found that RIPK3 was able to specifically localize at the outer mitochondrial membrane, and the autophagy receptor NDP52 was most likely involved in the autophagic degradation of RIPK3 during CSFV infection. Our findings provide evidence supporting that the CSFV-induced autophagy pathway plays an important role in counteracting host cell necrosis, enriching our knowledge of pathogens that may subvert and evade necroptosis this host defense, and shedding new light on understanding the mechanisms of T lymphocyte exhaustion and immunosuppression during CSFV infection. IMPORTANCE CSFV infection in pigs causes persistent high fever, hemorrhagic necrotizing multi-organ inflammation, and high mortality, which seriously threatens the global swine industry. Cell death is an essential immune response of the host against pathogen invasion, and lymphopenia is the most typical clinical feature in the acute phase of CSFV infection, which affects the initial host antiviral immunity. As an “old” virus, CSFV has evolved mechanisms to evade host immune response after a long genetic evolution. Here, we show that necroptosis is a limiting host factor for CSFV infection and that CSFV-induced autophagy can subvert this host defense mechanism to promote its sustained replication. Our findings reveal a complex link between necroptosis and autophagy in the process of cell death, provide evidence supporting the important role for CSFV in counteracting host cell necrosis, and enrich our knowledge of pathogens that may subvert and evade this host defense.

C26H24N2O2, monoclinic, P21/n (no. 14), a = 10.949(6) Å, b = 9.930(5) Å, c = 20.125(13) Å, β = 98.51(3)°, V = 2164(2) Å3, Z = 4, Rgt(F) = 0.0465, wRref(F2) = 0.1260, T = 296(2) K.

Membrane-less organelles (MLOs) formed through liquid-liquid phase separation (LLPS) are associated with numerous important biological functions, but the abnormal phase separation will also dysregulate the physiological processes. Emerging evidence points to the importance of LLPS in human health and diseases. Nevertheless, despite recent advancements, our knowledge of the molecular relationship between LLPS and diseases is frequently incomplete. In this review, we outline our current understanding about how aberrant LLPS affects developmental disorders, tandem repeat disorders, cancers and viral infection. We also examine disease mechanisms driven by aberrant condensates, and highlight potential treatment approaches. This study seeks to expand our understanding of LLPS by providing a valuable new paradigm for understanding phase separation and human disorders, as well as to further translate our current knowledge regarding LLPS into therapeutic discoveries.

As a retrovirus with high recombination and mutation rate， HIV targets CD4+ T lymphocytes， causing damage to the body's immune system and eventually leading to severe immune function defects. Different subtypes of the HIV virus exhibit significant sequence differences in their structural and regulatory genes， and this diversity is closely related to etiology， transmission， diagnosis， drug therapy， disease progression， and vaccine development. As a country with the largest number of HIV subtypes， rapid and accurate typing of the HIV virus holds great significance for China's efforts in disease prevention and control. This study provides a comprehensive reveiw of domestic and international HIV genotyping methods， and summarizes the clinical significance of different subtypes in order to provide reference for further research.

ABSTRACTCSFV (classical swine fever virus) is currently endemic in developing countries in Asia and has recently re-emerged in Japan. Under the pressure of natural selection pressure, CSFV keeps evolving to maintain its ecological niche in nature. CSFV has evolved mechanisms that induce immune depression, but its pathogenic mechanism is still unclear. In this study, using transcriptomics and metabolomics methods, we found that CSFV infection alters innate host immunity by activating the interferon pathway, inhibiting host inflammation, apoptosis, and remodelling host metabolism in porcine alveolar macrophages. Moreover, we revealed that autophagy could alter innate immunity and metabolism induced by CSFV infection. Enhanced autophagy further inhibited CSFV-induced RIG-I-IRF3 signal transduction axis and JAK-STAT signalling pathway and blocked type I interferon production while reducing autophagy inhibition of the NF-κB signalling pathway and apoptosis in CSFV infection cells. Furthermore, the level of CSFV infection-induced glycolysis and the content of lactate and pyruvate, as well as 3-phosphoglyceraldehyde, a derivative of glycolysis converted to serine, was altered by autophagy. We also found that silencing HK2 (hexokinase 2), the rate-limiting enzyme of glycolytic metabolism, could induce autophagy but reduce the interferon signalling pathway, NF-κB signalling pathway, and inhibition of apoptosis induced by CSFV infection. In addition, inhibited cellular autophagy by silencing ATG5 or using 3-Methyladenine, could backfill the inhibitory effect of silencing HK2 on the cellular interferon signalling pathway, NF-κB signalling pathway, and apoptosis.

This study aimed to explore the effects of osteogenic growth peptide C-terminal pentapeptide (G36G), and its analog G48A on bone modeling in rats with ovariectomy-induced osteoporosis. Ovariectomized rats were administered PBS (OVX group), risedronate (RISE group), G36G combined with risedronate (36GRI group), G36G (G36G group), or G48A (G48A group). The sham-operation rats (SHAM group) were administered PBS. Serum osteocalcin and IGF-2 levels in the SHAM, OVX, G36G, G48A, and RISE groups were observably lower than the 36GRI group (P < 0.01) and the bone mineral density of the entire femur, distal metaphysis, and lumbar L1–L4 in the 36GRI group were notably increased (P < 0.05). The bending energy of the 36GRI group was prominently higher than the other groups (P < 0.05). Other features measured in the study that provided significant outcomes was the ratio of femora ash weight/dry weigh, parameters of trabecular bone volume (TBV)/total tissue volume, TBV/sponge bone volume, mean trabecular plate thickness, mean trabecular plate space, bone surface, parameters of sfract(s) and sfract(d), tetracycline-labeled, and osteoid surfaces. Bone loss in ovariectomized rats may be partially inhibited by G36G and G48A. A combination treatment with G36G and risedronate may be an effective intervention for osteoporosis.

Objective To investigate the characteristics of changes in serum degraded monosaccharide levels in children with systemic lupus erythematosus (SLE) and its relationship with the severity of the disease and immune dysfunction. Methods Children firstly diagnosed as SLE and hospitalized in the Affiliated Hospital of Qingdao University from January 2019 to March 2022 were enrolled in the SLE group, healthy childrenwho underwent physical examination at the same period were chosen as the control and matched in a ration of 1∶1 in age and sex with the SLE group. The clinical data of both groups were collected. The serum levels of five kinds of degraded monosaccharides, which were mannose, glucosamine, aminogalactose, N-acetyl glucosamine and galactose, were analyzed in both groups. The correlations between serum levels of degraded monosaccharides and SLE disease activity and immunologic markers were analyzed with Pearson correlation coefficient. Results Totally 45 children with SLE (13 with mild disease activity, 15 with moderate disease activity, and 17 with severe disease activity) and 50 healthy children were enrolled in the experiment. Compared with the control group, the SLE group showed elevated levels of serum mannose, glucosamine, aminogalactose, N-acetyl glucosamine, and galactose (all P < 0.05); and serum levels of mannose, N-acetyl glucosamine, and galactose gradually increased with increasing disease activity (all P < 0.05). There was no significant difference in glucosamine and aminogalactose levels in children with SLE of different disease activity (all P > 0.05). Pearson correlation coefficient showed that serum degraded monosaccharide levels were positively correlated with disease activity indexes and various immunologic markers. Conclusions Serum levels of degraded monosaccharides in children with SLE are elevated and some of which are correlated with disease activity and immune dysfunction.

The safety of high-speed railroads is an important indicator of travelers’ trust, and it is also an important factor in determining whether or not the operation volume can reach the expected goal. Therefore, high-speed railroad companies in Europe, the United States, and Japan have invested heavily in establishing safety monitoring systems in order to avoid the occurrence of disasters and to strengthen the mechanism of crisis response and emergency treatment. High-speed railroad operation may occur in a variety of accidents, different disaster warning, emergency response and rescue, need to have different equipment, contingency measures, and well-trained personnel to deal with. Therefore, the safety standards for high-speed rail systems in advanced countries around the world are much higher than those for traditional train systems. The theories and technologies of disaster prevention and relief have matured both at home and abroad. This study combines the theories and technologies of disaster prevention with GIS, such as monitoring instruments, satellite positioning, remote sensing detection, radio transmission, the Internet, database management, and information management, to provide effective support for decision-making and analysis of commanders, to rapidly assist in crisis management, and to strengthen the mechanism of emergency response.

Fleas represent a group of paramount medical significance, subsisting on blood and acting as vectors for an array of naturally occurring diseases. These pathogens constitute essential elements within the plague biome, exerting deleterious effects on both human and livestock health. In this study, we successfully assembled and sequenced the whole mitochondrial genome of Frontopsylla spadix and Neopsylla specialis using long-range PCR and next-generation sequencing technologies. The mitogenomes of F. spadix and N. specialis both have 37 genes with full lengths of 15,085 bp and 16,820 bp, respectively. The topology of the phylogenetic tree elucidates that species F. spadix is clustered in a branch alongside other members of the family Leptopsyllidae, whereas species N. specialis is a sister taxon to Dorcadia ioffi and Hystrichopsylla weida qinlingensis. It also suggests that Pulicidae form a monophyletic clade, Ctenopthalmidae, Hystrichopsyllidae, Vermipsyllidae form a sister group to Ceratophyllidae/Leptopsyllidae group. The mitochondrial genomes of F. spadix and N. specialis were sequenced for the first time, which will contribute to a more comprehensive phylogenetic analysis of the Siphonaptera order. The foundation for subsequent systematic studies, and molecular biology of fleas was established.

The host restriction factor serine incorporator 5 (SERINC5) plays a key role in inhibiting viral activity and has been shown to inhibit classical swine fever virus (CSFV) infection. However, the action of SERINC5 in the interaction between host cells and CSFV remains poorly understood. This study found that SERINC5 represses CSFV-induced autophagy through MAPK1/3-mTOR and AKT-mTOR signalling pathways. Further research showed that SERINC5 promotes apoptosis by repressing autophagy. Likewise, it was demonstrated that SERINC5 interacting proteins IFITM1/2/3 inhibit CSFV replication and regulate autophagy in a lysosomal-associated membrane protein LAMP1-dependent manner. In addition, IFITM1/2/3 interference promotes the NF-κB signalling pathway for potential immunoregulation by inhibiting autophagy. Finally, the functional silencing of IFITM1/2/3 genes was demonstrated to enhance the inhibitory effect of SERINC5 on autophagy. Taken together, These data uncover a novel mechanism through SERINC5 and its interacting proteins IFITM1/2/3, which mediates CSFV replication, and provides new avenues for controlling CSFV.

Maturity-onset diabetes of the young type 3 (MODY3) is a specific type of diabetes mellitus with inherited impairment of the islet β cell function due to the mutation in the hepatocyte nuclear factor 1α (HNF1α) gene. It is a rare condition and easily misdiagnosed as T1DM or T2DM. In this study, the clinical features of two unrelated Chinese MODY3 probands were described and analyzed. Next-generation sequencing was performed to identify the mutated genes, and Sanger sequencing was employed to verify the location of the pathogenic variant in the related family members. It was found that proband 1 inherited a start codon mutation c.2T>C (p.Met1?) in exon 1 of the HNF1α gene from his affected mother, and proband 2 inherited a frameshift mutation c.1136_1137del (p.Pro379fs) in exon 6 of the HNF1α gene also from her affected mother. Proband 1 and proband 2 differed in islet dysfunction, complications, and treatments due to their different disease durations and levels of hemoglobin A1c (HbA1c). The findings of this study demonstrate that early identification of MODY and diagnosis through genetic testing are critical for the treatment of the patient.

Fabrication of the Mg–9Al–1Zn–0.5Mn alloy with excellent mechanical performance using selective laser melting (SLM) technology is quite difficult owing to the poor weldability and low boiling point. To address these challenges and seek the optimal processing parameters, response surface methodology was systematically utilized to determine the appropriate SLM parameter combinations. Mg–9Al–1Zn–0.5Mn sample with high relative density (99.5 ​± ​0.28%) and favorable mechanical properties (microhardness ​= ​95.6 ​± ​5.28 HV0.1, UTS ​= ​370.2 ​MPa, and At ​= ​10.4%) was achieved using optimized SLM parameters (P ​= ​120 ​W, v ​= ​500 ​mm/s, and h ​= ​45 ​μm). Sample ​is dominated by a random texture and microstructure is primarily constituted by quantities of fine equiaxed grains (α-Mg phase), a small amount of β-Al12Mg17 structures (4.96 ​vol%, including spherical: [21¯1¯0]α// [111]β and long lath-like: [21¯1¯0]α// [11¯5]β or [1¯011]α// [32¯1¯]β), and some short rod-shaped Al8Mn5 nanoparticles. Benefiting from grain boundary strengthening, solid solution strengthening, and precipitation hardening of various nanoparticles (β-Al12Mg17 and Al8Mn5), high-performance Mg–9Al–1Zn–0.5Mn alloy biomedical implants can be fabricated. Precipitation hardening dominates the strengthening mechanism of the SLM Mg–9Al–1Zn–0.5Mn alloy.

Interferon (IFN) is a cell-secreted cytokine possessing biological activities including antiviral functioning, immune regulation, and others. Interferon-alpha (IFN-α) mainly derives from plasmacytoid dendritic cells, which activate natural killer cells and regulate immune responses. IFN-α responds to the primary antiviral mechanism in the innate immune system, which can effectively cure acute infectious diseases. Pseudorabies (PR) is an acute infectious disease caused by pseudorabies virus (PRV). The clinical symptoms of PRV are as follows: reproductive dysfunction among pregnant sows and high mortality rates among piglets. These pose a severe threat to the swine industry. Related studies show that IFN-α has broad applications in preventing and treating viral diseases. Therefore, a PRV mouse model using artificial infection was established in this study to explore the pathogenic effect of IFN-α on PRV. We designed a sequence with IFN-α4 (M28623, Genbank) and cloned it on the lentiviral vector. CHO-K1 cells were infected and identified using WB and RT-PCR; a CHO-K1 cell line with a stable expression of the recombinant protein PoIFN-α was successfully constructed. H&E staining and virus titer detection were used to investigate the recombinant protein PoIFN-α’s effect on PR in BALB/c mice. The results show that the PoIFN-α has a preventive and therapeutic impact on PR. In conclusion, the recombinant protein can alleviate symptoms and reduce the replication of PRV in vivo.

Summary: Efficient regeneration requires multiple cell types acting in coordination. To better understand the intercellular networks involved and how they change when regeneration fails, we profile the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells over 14 days following acute muscle damage. We generate a time-resolved computational model of interactions and identify VEGFA-driven endothelial engagement as a key differentiating feature in models of successful and failed regeneration. In addition, the analysis highlights that the majority of secreted signals, including VEGFA, are simultaneously produced by multiple cell types. To test whether the cellular source of a factor determines its function, we delete VEGFA from two cell types residing in close proximity: stromal and myogenic progenitors. By comparing responses to different types of damage, we find that myogenic and stromal VEGFA have distinct functions in regeneration. This suggests that spatial compartmentalization of signaling plays a key role in intercellular communication networks.

Background and purpose: Glioma is the most common and malignant primary brain tumor in the central nervous system (CNS). Glioblastoma is highly malignant and aggressive, and the prognosis of patients with recurrent glioblastoma is very poor. This study aimed to screen the genes related to the recurrent glioblastoma, and analyze the relationship between their expressions, clinicopathological parameters and prognosis in glioma. Methods: By mining the relevant datasets of the primary and recurrent cases of glioblastoma in the GEO database, the differentially expressed gene (DEG) in the samples of primary and recurrent glioblastomas were screened and analyzed. All DEGs analyses were carried out in ontology function and pathway enrichment. Protein-protein interaction (PPI) network was constructed and used for screening Hub gene. Key genes were intersected by PPI network and Venn diagram, and the Gene Expression Profiling Interactive Analysis (GEPIA) and Chinese Glioma Genome Atlas (CGGA) database were analyzed for association of key gene expressions and survival status. Key genes were furtherly analyzed to determine the relationship between their expressions and clinicopathological parameters of glioma. Results: There were 40 DEG screened in the dataset GSE62153, including 34 up-regulated genes and 6 down-regulated genes. There were 19 DEG screened in the dataset GSE58399, including 16 up-regulated genes and 3 down-regulated genes. Go functional analyses showed that the DEG of GSE62153 were mainly involved in 11 physiological processes, such as central nervous system development, myelin sheath, actin binding, central nervous system myelination. The DEG of GSE58399 were mainly enriched in the positive regulation of epithelial cell migration. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed that the datasets GSE62153 and GSE58399 were both enriched in histidine metabolism. By using the STRING database, the core of PPI network was constructed with 20 protein molecules. A total of 10 hub genes were screened, including MOBP, OPALIN, ERMN, PLP1, MOG, CLDN11, ASPA, TMEM125, KLK6 and NKX6-2 gene. The key genes for recurrent glioblastoma were ERMN, MOG and MOBP gene. Based on analyses using The Cancer Genome Atlas (TCGA) and CGGA databases, the prognosis of patients with high expressions of ERMN, MOG and MOBP was favorable compared with the low expression group. The expression levels of key genes in glioblastoma were lower compared with the control tissues (P

To investigate the role of microglia in the process of cognitive impairment caused by local ionizing radiation, eighteen male mice from the institute of cancer research (ICR) were randomly divided into a control group (Control) and a head 10 Gy irradiation group (Irradiation, 10 Gy-IR). The head ionization irradiation group underwent X-ray (Siemens linear accelerator) single head irradiation illuminated to an absorbed dose of 10 Gy. Fifty-six days later, the new and old object recognition test and the new and old place recognition test were used to test the cognitive function of the mice; immunohistochemistry was used to detect the mouse hippocampal microglia marke (IBA-1) change; RT-PCR was used to detect changes at the mRNA level of hippocampal M1/M2 microglia markers (CD16, INOS, CD68, CXCL10, Arg1, CD206). The results showed that compared with the control group, the time discrimination index of new things (p

Endoplasmic reticulum stress (ERS)-mediated autophagy is indispensable for modulation of replication and pathogenesis of numerous mammalian viruses. We have previously shown that classical swine fever virus (CSFV) infection induces ERS-mediated autophagy for maintaining viral replication both in vivo and in vitro, however, the underlying mechanism remains unclarified. Here we found that CSFV infection activates the PERK pathway-dependent complete autophagy to promote viral replication in cultured PK-15 and 3D4/2 cells. Likewise, our results also suggested the essential roles of the IRE1/GRP78-mediated complete autophagy in CSFV replication in vitro. Furthermore, we suggested that CSFV infection induces activation of the PERK and IRE1 pathway for potential immunoregulation via promoting transcription of proinflammatory cytokine (IFN-γ and TNF-α) genes in the CSFV-infected cells. Finally, pharmacological treatment of PERK- or IRE1-pathway regulators, and the corresponding SiRNAs interventions did not affect the viabilities of the cells, excluding the potential interference elicited by altered cell viabilities. Taken together, our results suggest that CSFV infection induces complete autophagy through activation of the PERK and IRE1 pathway to facilitate viral replication in cultured cells, and modulation of proinflammatory cytokines may be a potential mechanism involved in this event. Our findings will open new horizons for molecular mechanisms of sustainable replication and pathogenesis of CSFV, and lay a theoretical foundation for the development of ERS-autophagy-targeting therapeutic strategies for clinical control of CSF.

The rotating resonant magnetic perturbation (RMP) could lock the tearing mode (TM) and prevent disruption. It is found that the TM instantaneous frequency oscillates during TM locking on the RMP. In this work, the TM frequency oscillation was derived analytically based on the toroidal torque balance, which was verified experimentally. It is found that two peaks with higher frequency (2fTM0-fRMP) and lower frequency (fRMP) occurred in the spectrum when the window width of FFT was shorter than the TM frequency oscillating period. Those two peaks were explained analytically based on the description of TM instantaneous frequency. The independence of the temporal information and the spatial information of the TM was explained analytically and verified by the spatial structure analysis of each peaks. This work is important for mode structure identification and provides a scheme for mode coupling control.

Okun's law is generally interpreted in economic terms. This paper is interpreted from a social perspective through regression and mediating effect models. Okun's law is demonstrated based on data from the World Development Indicators (WDI) dataset. There is indeed a relationship between unemployment and economic growth, with unemployment negatively affecting economic growth after controlling for the two-way causality problem. This result remains robust after replacing the core explanatory variables. This paper interprets the asymmetry of Okun's law from a social perspective, using alcohol consumption as a mediating variable to measure the harm caused by unemployment to the unemployed. Analysis of the data reveals that alcohol consumption mediates between unemployment and economic growth. Unemployment increases alcohol consumption, which causes incurable harm to the unemployed. It reduces the willingness and probability of the unemployed to re-employ and further reduces the potential for economic growth. This is why the economic expansion did not lead to employment growth, revealing the asymmetry of Okun's law. The gender-specific heterogeneity analysis found that the impact of unemployment on economic growth did not vary much by gender.

Background: Specific tumor markers have yet to be identified in rectal cancer. This study aims to identify a novel genetic signature in rectal cancer to provide clues for survival and immunotherapy. Methods: DEGs were obtained from two GEO datasets of rectal cancer. By using data from TCGA and GSE133057, two cohorts of rectal cancer were applied to establish and evaluate the signature. A nomogram was constructed for training and validation. We integrated the risk-score with clinicopathological features and assessed its interplay with immune cells and molecules. Finally, our study performed functional annotations, gene-targeted miRNAs, and single-cell analysis. Results: A total of 468 DEGs were identified, and a signature consisting of 5 genes (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) was selected to calculate the risk-score. The model exhibited high performance in time-dependent ROC and a nomogram. Further results showed that overall survival was significantly worse in the high-risk group. As an independent prognostic factor, the risk-score was associated with vascular invasion. There was a dramatic difference in nonregulatory CD4+ and CD8+ T cells between the high and low-risk groups, and the 5 genes were correlated with immune inhibitors. There was a considerable difference in autophagy, immune, cell cycle, infection, and apoptosis-associated terms and pathways in GO and KEGG. The functional states of differentiation, apoptosis, and quiescence were closely related to the 5-gene signature in single-cell analysis. Conclusion: Our results suggest that the signature could serve as a novel prognostic biomarker in rectal cancer, which might benefit decision-making regarding immunotherapy.

Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), is a highly contagious and fatal viral disease, posing a significant threat to the swine industry. Heat shock protein 90 kDa alpha class A member 1 (HSP90AA1) is a very conservative chaperone protein that plays an important role in signal transduction and viral proliferation. However, the role of HSP90AA1 in CSFV infection is unknown. In this study, we found that expression of HSP90AA1 could be promoted in PK-15 and 3D4/2 cells infected by CSFV. Over-expression of HSP90AA1 could inhibit CSFV replication and functional silencing of HSP90AA1 gene promotes CSFV replication. Further exploration revealed that HSP90AA1 interacted with CSFV NS5A protein and reduced the protein levels of NS5A. Since NS5A has an important role in CSFV replication and is closely related to type I IFN and NF-κB response, we further analyzed whether HSP90AA1 affects CSFV replication by regulating type I IFN and NF-κB pathway responses. Our research found HSP90AA1 positively regulated type I IFN response by promoting STAT1 phosphorylation and nuclear translocation processes and promoted the nuclear translocation processes of p-P65. However, CSFV infection antagonizes the activation of HSP90AA1 on JAK/STAT and NF-κB pathway. In conclusion, our study found that HSP90AA1 overexpression significantly inhibited CSFV replication and may inhibit CSFV replication by interacting with NS5A and activating JAK/STAT and NF-κB signaling pathways. These results provide new insights into the mechanism of action of HSP90AA1 in CSFV infection, which abundant the candidate library of anti-CSFV.

Foot-and-mouth disease virus (FMDV), Senecavirus A (SVA) and swine vesicular disease virus (SVDV) are members of the family Picornaviridae, which can cause similar symptoms - vesicular lesions in the tissues of the mouth, nose, feet, skin and mucous membrane of animals. Rapid and accurate diagnosis of these viruses allows for control measures to prevent the spread of these diseases. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR are traditional and reliable methods for pathogen detection, while their amplification reaction requires a thermocycler. Isothermal amplification methods including loop-mediated isothermal amplification and recombinase polymerase amplification developed in recent years are simple, rapid and do not require specialized equipment, allowing for point of care diagnostics. Luminex technology allows for simultaneous detection of multiple pathogens. CRISPR-Cas diagnostic systems also emerging nucleic acid detection technologies which are very sensitivity and specificity. In this paper, various nucleic acid detection methods aimed at vesicular disease pathogens in swine (including FMDV, SVA and SVDV) are summarized.

The increasingly intensified development of coastal cities causes excessive consumption of natural resources, leading to environmental damage and increasing conflict between development and ecological protection. In addition to emphasizing ecological development, planners should pay more attention to the practical optimization and regulation of the developed landscape pattern. Taking Dafeng as an example, this study constructs a landscape-pattern optimization method suitable for the spatial distribution heterogeneity of ecological risk-level units in the coastal zone. The study is based on (a) an analysis of the composition and evolution characteristics of Dafeng’s coastal landscape elements, (b) the landscape pattern index of the ecosystem’s overall risk assessment, and (c) the minimal cumulative resistance (MCR) model. The study uses an ecosystem service value to build a resistance model by analyzing the medium and high-risk composition and distribution characteristics of space unit elements. Finally, 23 ecological sources, 14 ecological nodes, and 17 ecological corridors (total length 169.63 km) were built. The optimized coastal zone landscape pattern jointly protects the landscape area of high ecological value by 462.02 km2. The total ecological value is 105,01.71 million yuan. Landscape connectivity has been optimized, as well as the ecosystem’s stability and total service value. The optimization method proposed in this paper can reduce the protection area and cost. The spatial optimization unit is highly targeted, providing new ideas for the coastal cities to implement their ecological development and protection strategies.

BackgroundIn recent years, technological advancements have increased the importance of innovation activities. Therefore, firms invest millions of dollars in innovation activities to ensure long-term business sustainability. Similarly, consumer concerns have increased dramatically over the past years. Thus, brand loyalty has become a top priority for firms and consumers. In this background, this research examines how firms’ innovation activities translate into consumer brand loyalty to assure business sustainability in Asian markets, particularly China, Pakistan, and Indonesia.ObjectivesThis study’s specific objectives are to comprehend the concept of firms’ innovation activities and their effect on the brand prototype. Examine the effect of the brand prototype on global brand preference, recommendation, and loyalty among Asian consumers. Find out the impact of brand preference on brand recommendations and the influence of brand recommendations on brand loyalty among Asian consumers.Materials and methodsA total of 814 consumers from Asian countries (China, Pakistan, and Indonesia) participated in this study, and structural equation modeling was used to analyze the data.ResultsThe findings indicate that firms’ innovation activities, such as processes, products, and store environment, positively influenced the brand prototype, thereby increasing consumer brand knowledge. Likewise, brand prototype contributes to developing brand preference, brand recommendation, and brand loyalty among Asian consumers. Lastly, consumer brand preference significantly influenced brand recommendation, which positively improves consumer brand loyalty in Asia.ConclusionThis study concluded that Asian (Chinese, Pakistani, and Indonesian) consumers have favorable perceptions of firms’ innovation activities (i.e., process, product, and store environment innovation), which influences their ability to develop brand prototypes to increase consumer brand knowledge. Similarly, brand prototype fosters brand preference, recommendation, and loyalty. Likewise, favorable brand preference encourages consumers to recommend the brand to others, strengthening brand loyalty. Thus, firms should invest in innovation activities to strengthen consumer brand loyalty in Asian markets. Consequently, this study may assist multinational corporations in increasing their business volumes and market shares in Asia.Managerial recommendationsThis study provides important managerial recommendations. The findings revealed that global managers can develop and implement several branding strategies for sustaining their businesses in the Asian environment.

This paper presents a physical model that provides a comprehensive understanding of the motion behavior of boron nitride nanosheets (BNNSs) immersed in ultrapure deionized water and subjected to a series of nanosecond pulses. In a study conducted by Y. Mi et al. The authors explored the global alignment behavior of BNNSs and fitted the experimental data with an exponential decay function. However, this function lacks clear physical mechanisms and the significance of the fitting parameters remains unclear. To address this issue, we have developed a kinetic model that explicitly describes the underlying physical mechanisms. Furthermore, we propose a simplified mathematical model that not only predicts the displacement of BNNSs but also estimates the total time, velocity, and acceleration of the motion process.

A endo-1,4-β-mannanase (CcMan5C) gene was cloned from Coprinopsis cinerea and heterologously expressed in Pichia pastoris, and the recombinant enzyme was purified by Ni-affinity chromatography and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). CcMan5C hydrolyzed only locust bean gum galactomannan (LBG) but not α-mannan from S. cerevisiae or Avicel cellulose, oat spelt xylan, or laminarin from Laminaria digitata. CcMan5C exhibited distinctive catalytic features that were different from previously reported β-mannanases. (1) CcMan5C is the first reported fungal β-mannase with an optimal alkalic pH of 8.0–9.0 for hydrolytic activity under assay conditions. (2) CcMan5C is the first reported alkalic fungal β-mannase with an optimal temperature of 70 °C for hydrolytic activity under assay conditions. (3) The organic solvents methanol, ethanol, isopropanol, and acetone at concentrations of 10% or 20% did not inhibit CcMan5C activity, while 10% or 20% isopropanol and acetone even enhanced CcMan5C activity by 9.20–34.98%. Furthermore, CcMan5C tolerated detergents such as Tween 20 and Triton X-100, and its activity was even enhanced to 26.2–45.6% by 1% or 10% Tween 20 and Triton X-100. (4) CcMan5C solution or lyophilized CcMan5C exhibited unchanged activity and even increasing activity after being stored at −20 °C or −80 °C for 12 months and retained above 50% activity after being stored at 4 °C for 12 months. These features make CcMan5C a suitable candidate for the detergent industry and paper and pulp industry.

Literati music is an important part of Chinese traditional music. After a long period of development, it has formed a unique aesthetic experience and has had a profound impact on Chinese music culture. By analyzing the basic conditions and main characteristics of the formation of music national aesthetic psychology, we can understand the reasons and characteristics of the formation of literati music. Taking the ancient song "Fishermen’s Song At Eventide " as an example, the literati thought contained in the music is discussed.

In the context of a high proportion of renewable energy integrated to the power grid, the net load may has significant fluctuations, and it is necessary to quantify peak regulation demand of power system. This paper stablishes a peak regulation demand prediction model based on long short-term memory (LSTM) method by training historical data. The typical data such as load and renewable energy output are selected as the input vector, and correlation coefficients are used to process and simplify the input vector. The historical prediction errors are used to set margins for peak regulation demand prediction. The case study shows that the proposed model can effectively predict the peak regulation demand of the power system.

China has a vast territory, and the development scale of venture capital varies significantly among different regions. The geographical distribution of venture capital is unbalanced, which makes it difficult for venture capital to choose to invest in local enterprises or cross-regional investment. Many studies have shown that geographical distance is related to the formation of social networks, the strength of information asymmetry and the amount of transaction costs. Therefore, depending on geographical distance, venture capital will face different investment situations, investment costs and investment returns, and entrepreneurial enterprises will therefore receive different levels of super-vision, value-added and post-investment management services. Therefore, this paper analyses the impact of geographical distance between VCs and start-ups on the operating performance of start-ups from a unique geographical distance perspective, and takes relevant data of listed start-ups from 2009 to 2019 as samples for empirical test. The study finds that the closer the geographical distance between VCs and start-ups, the higher the short-term operating performance of start-ups. Geographical distance has an insignificant effect on the long-term performance of startups. In addition, poor internal control of start-ups will weaken the positive impact of geographical proximity on operating performance of start-ups.

Introduced the concept of “ergodic theory” and “cultural omnivore”, this article takes Masters In Forbidden City—a representative documentary film—as an example, analyses online cultural consumption in China and We-Media consumer behavior from cultural studies and frame analysis perspectives. By doing case study and qualitative research, this article first suggests that although derived from popular culture, online cultural consumers can not only be seen as extensions of popular culture consumers, nor unitary sub-culture groups. Youth sub-cultural groups were supposed to be differentiated and exclusive, but nowadays they are becoming increasingly “mainstreamed” due to the development of internet enterprises and cultural omnivores. Secondly, online cultural consumers have their own decision-making and information-processing system based on virtual community culture criteria. This system distinguishes internet cultural consumer behaviors from traditional offline ones. Therefore, the model of AIINDAS may be adjusted accordingly: “investigating” can be simplified into “filtrating”, “experience” can be complicated as “ergodicity”, and accurate information can be replaced by dynamic information.