Human FAM111A inhibits vaccinia virus replication by degrading viral protein I3 and is antagonized by poxvirus host range factor SPI-1.

Zoonotic poxviruses such as mpox virus (MPXV) continue to threaten public health safety since the eradication of smallpox. Vaccinia virus (VACV), the prototypic poxvirus used as the vaccine strain for smallpox eradication, is the best-characterized member of the poxvirus family. VACV encodes a serine protease inhibitor 1 (SPI-1) conserved in all orthopoxviruses, which has been recognized as a host range factor for modified VACV Ankara (MVA), an approved smallpox vaccine and a promising vaccine vector. FAM111A (family with sequence similarity 111 member A), a nuclear protein that regulates host DNA replication, was shown to restrict the replication of a VACV SPI-1 deletion mutant (VACV-ΔSPI-1) in human cells. Nevertheless, the detailed antiviral mechanisms of FAM111A were unresolved. Here, we show that FAM111A is a potent restriction factor for VACV-ΔSPI-1 and MVA. Deletion of FAM111A rescued the replication of MVA and VACV-ΔSPI-1 and overexpression of FAM111A significantly reduced viral DNA replication and virus titers but did not affect viral early gene expression. The antiviral effect of FAM111A necessitated its trypsin-like protease domain and DNA-binding domain but not the PCNA-interacting motif. We further identified that FAM111A translocated into the cytoplasm upon VACV infection by degrading the nuclear pore complex via its protease activity, interacted with VACV DNA-binding protein I3, and promoted I3 degradation through autophagy. Moreover, SPI-1 from VACV, MPXV, or lumpy skin disease virus was able to antagonize FAM111A by prohibiting its nuclear export. Our findings reveal the detailed mechanism by which FAM111A inhibits VACV and provide explanations for the immune evasive function of VACV SPI-1.

A New Sliding Mode Control Algorithm of IGC System for Intercepting Great Maneuvering Target Based on EDO.

To intercept the great maneuvering target, combining with the sliding mode and the extended disturbance observer, a new control algorithm for integrated guidance and control (IGC) system is proposed in this paper. Firstly, the paper formulates the Missile-Target problem. Then the paper establishes an uncertain IGC dynamic model where the nonlinearities, the perturbations and the maneuvering of the target are regarded as disturbance. Secondly, a second-order disturbance observer is designed to estimate the disturbance and their derivatives.. After this, combining with the second-order disturbance observer, a modified sliding surface and the corresponding reaching law are designed to obtain the rudder deflection command directly. Thus, the real sense of IGC system is achieved. Next, the paper uses the Lyapunov stability theory to prove the stability of the system. Finally, the paper provides different simulation cases, which have different maneuver modes of the target, to demonstrate the superiority of the proposed method in reducing the response time, increasing the rudder response, and having a high interception probability.

Trimodal synergistic antitumor drug delivery system based on graphene oxide.

A multifunctional antitumor drug delivery system was synthesized based on graphene oxide (GO) for near-infrared (NIR) light controlling chemotherapeutic/photothermal (PTT) /photodynamic (PDT) trimodal synergistic therapy. The system named ICG-Wed-GO was formed by co-loading wedelolactone (Wed) and indocyanine green (ICG) on the surface of GO through π-π stacking interaction. Under NIR laser irradiation, ICG-Wed-GO could effectively absorb and transform optical energy to heat, generate reactive oxygen species (ROS) to ablating and damage tumor cells. The temperature of ICG-Wed-GO solution reached up to 79.4 °C in 10 min with NIR irradiation. In in vitro and in vivo study, ICG-Wed-GO showed excellent antitumor effect. After 14-day treatment of ICG-Wed-GO with NIR laser irradiation, the tumor disappeared completely on tumor-bearing mice. The low biotoxicity of ICG-Wed-GO was also proved. The system achieved the synergistic trimodal chemotherapeutic/photothermal/photodynamic treatment and demonstrated excellent antitumor effect, which is expected to have a greater potential for cancer therapy.

Gold-nanobranched-shell based drug vehicles with ultrahigh photothermal efficiency for chemo-photothermal therapy.

Development of combined chemo-photothermal nanoplatform is of great interest for enhancing antitumor efficacy. Herein, a multifunctional drug delivery system was synthesized based on gold-nanobranched coated betulinic acid liposomes (GNBS-BA-Lips) for chemo-photothermal synergistic therapy. In this system, GNBS-BA-Lips exhibited broad near-infrared (NIR) absorption, preferable photothermal response and good photostability under NIR irradiation. Importantly, the gold-nanobranched nanostructure possessed high photothermal conversion efficiency (η = 55.7%), and the temperature change (ΔT) reached 43.2 °C after laser irradiation for 5 min. Upon NIR irradiation, the nanocarriers apparently endowed higher cell uptake, resulting in an enhanced intracellular drug accumulation. Furthermore, the tumor growth inhibition ratio achieved from chemo-photothermal therapy of GNBS-BA-Lips was 86.9 ±â€¯1.1%, which was higher than that of the chemotherapy or photothermal therapy alone, showing an outstanding synergistic anticancer effect. Our data suggested that the nanoplatform should be considered as a critical platform in the development of cancer multi-mode therapies.

Genomic analysis of lumpy skin disease virus asian variants and evaluation of its cellular tropism.

Lumpy skin disease virus (LSDV) is a poxvirus that mainly affects cattle and can lead to symptoms such as severe reduction in milk production as well as infertility and mortality, which has resulted in dramatic economic loss in affected countries in Africa, Europe, and Asia. In this study, we successfully isolated two strains of LSDV from different geographical regions in China. Comparative genomic analyses were performed by incorporating additional LSDV whole genome sequences reported in other areas of Asia. Our analyses revealed that LSDV exhibited an 'open' pan-genome. Phylogenetic analysis unveiled distinct branches of LSDV evolution, signifying the prevalence of multiple lineages of LSDV across various regions in Asia. In addition, a reporter LSDV expressing eGFP directed by a synthetic poxvirus promoter was generated and used to evaluate the cell tropism of LSDV in various mammalian and avian cell lines. Our results demonstrated that LSDV replicated efficiently in several mammalian cell lines, including human A549 cells. In conclusion, our results underscore the necessity for strengthening LSD outbreak control measures and continuous epidemiological surveillance.

The role of ferroptosis in virus infections.

Regulated cell death (RCD) is a strategy employed by host cells to defend invasions of pathogens, such as viruses and bacteria. Ferroptosis is a type of RCD characterized by excessive accumulation of iron and lipid peroxidation. While ferroptosis is primarily considered as a mechanism associated with tumorigenesis, emerging evidence begin to suggest that it may play essential role during virus infections. Recent studies illustrated that activation of ferroptosis could either induce or prohibit various types of RCDs to facilitate virus replication or evade host surveillance. More experimental evidence has demonstrated how viruses regulate ferroptosis to influence replication, transmission, and pathogenesis. This review summarizes ferroptosis-related metabolism, including iron metabolism, lipid peroxidation, and antioxidant metabolism. Furthermore, we discuss the interplay between viral infections and host ferroptosis process, with a focus on the mechanism of how viruses exploit ferroptosis for its own replication. Understanding how ferroptosis impacts virus infection can offer valuable insights into the development of effective therapeutic strategies to combat virus infections.

Characteristics of Small-Molecule Migration of Silicone Rubber Insulator in Electrical Power Systems.

The migration of low-molecular-weight components of polysiloxane (small molecules) to the surface of high-temperature-vulcanizing silicone rubber (HTV-SR) ensures its hydrophobicity and tends to coat the surface of pollutants, which would otherwise lower hydrophobicity. The transferability of hydrophobicity will ensure the insulator maintains its higher hydrophobicity after being coated with surface pollutants, thus providing the insulator with higher pollution flashover voltage. This migration process takes a certain time, and in this paper, the time characteristics of hydrophobicity transfer from HTV-SR coated with ten different inert materials were investigated. Ten different inert materials have different migration times and static contact angles, possibly due to the influence of pollution material characteristics on the characteristics of small-molecule migration. Thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), and gas chromatography-mass spectrometry (GC-MS) were used to analyze the migration of small molecules to the polluted surface. The evidence of small molecules migrating to the surface of the polluted material over time was found. Furthermore, the influence of pollution material characteristics on small-molecule migration was analyzed via SEM, specific surface area, and porosity. On that basis, the hydrophobicity migration characteristics of mixtures of kaolin and kieselguhr were also studied and compared to determine how best to simulate the behavior of natural pollution using artificial pollutants and their mixtures.

Design and test of intelligent inspection and monitoring system for cotton bale storage based on RFID.

To solve the inspection problems in cotton storage, as well as the need for environmental monitoring in the process of modern cotton bale storage, an intelligent inspection and temperature and humidity intelligent monitoring system based on RFID cotton bale was developed by adopting RFID (Radio Frequency Identification) technology, wireless temperature and humidity real-time monitoring technology and handheld terminal intelligent inspection technology. The system was composed of RFID positioning inspection module and temperature and humidity real-time monitoring and transmission module. The artificial neural network (ANN) based on the particle swarm optimization (PSO) algorithm was used to process the monitoring data of the system by Gaussian filtering, and an accurate classification model of RSSI and label position was established. The test results showed that: Through the comparative analysis of the RFID indoor positioning algorithm, the positioning error of the PSO-ANN algorithm was small. In the actual cotton bale warehouse test, the relative error of positioning and monitoring for RFID cotton bale intelligent inspection and monitoring system was less than 6.7%, which effectively improved the working efficiency of inspection personnel and the security of cotton bale storage. The relative error of temperature and humidity was less than 8% and less than 7%, which could display the temperature and humidity information in real time and meet the real-time demand. This study improved the management personnel's effective positioning and inspection of the cotton bale, prevented the loss of cotton bale, reduced the deterioration probability of cotton bale, and effectively improved the storage management level of the cotton bale. It was of great practical significance to realize the networking, automation, and intelligence of cotton bale storage management.

Near-infrared fluorescent probe with a large Stokes shift for bioimaging of ß-galactosidase in living cells and zebrafish develop at different period.

Overexpression of ß-galactosidase (ß-gal) in tumor cells may serve as a valuable biomarker for the early diagnosis of some cancers (such as ovarian cancer). In addition, abnormal accumulation of ß-gal is also considered an essential marker of cell senescence. Therefore, it is important to construct fluorescent probes with excellent fluorescence properties to visualize ß-gal in biological systems. Here, we designed and screened a novel fluorescent probe XM for the detection of ß-gal. Spectral data show that the probe has a good affinity (Km = 2.6 µM) for ß-gal, large stokes shift (190 nm), fast response speed (stable within 20 min), and low detection limit (6.7 × 10-3 U/mL). Based on the above advantages, XM can not only detect ß-gal content in cancer cells but also track the changes of ß-gal content in zebrafish at different developmental period. We believe XM will become a powerful tool for the early cancer diagnosis and cellular senescence.

Long-term probiotic intervention mitigates memory dysfunction through a novel H3K27me3-based mechanism in lead-exposed rats.

Chronic lead exposure is associated with the development of neurodegenerative diseases, characterized by the long-term memory decline. However, whether this pathogenesis could be prevented through adjusting gut microbiota is not yet understood. To address the issue, pregnant rats and their female offspring were treated with lead (125 ppm) or separately the extra probiotics (1010 organisms/rat/day) till adulthood. For results, memory dysfunction was alleviated by the treatment of multispecies probiotics. Meanwhile, the gut microbiota composition was partially normalized against lead-exposed rats, which in turn mediated the memory repairment via fecal transplantation trials. In the molecular aspect, the decreased H3K27me3 (trimethylation of histone H3 Lys 27) in the adult hippocampus was restored with probiotic intervention, an epigenetic event mediated by EZH2 (enhancer of zeste homolog 2) at early developmental stage. In a neural cellular model, EZH2 overexpression showed the similar rescue effect with probiotics, whereas its blockade led to the neural re-damages. Regarding the gut-brain inflammatory mediators, the disrupted IL-6 (interleukin 6) expression was resumed by probiotic treatment. Intraperitoneal injection of tocilizumab, an IL-6 receptor antagonist, upregulated the hippocampal EZH2 level and consequently alleviated the memory injuries. In conclusion, reshaping gut microbiota could mitigate memory dysfunction caused by chronic lead exposure, wherein the inflammation-hippocampal epigenetic pathway of IL-6-EZH2-H3K27me3, was first proposed to mediate the studied gut-brain communication. These findings provided insight with epigenetic mechanisms underlying a unique gut-brain interaction, shedding light on the safe and non-invasive treatment of neurodegenerative disorders with environmental etiology.

Dietary intake of polyunsaturated fatty acids alleviates cognition deficits and depression-like behaviour via cannabinoid system in sleep deprivation rats.

Sleep deprivation (SD) is a common feature in modern society. Prolonged sleep deprivation causes cognition deficits and depression-like behavior in the model of animal experiments. Endocannabinoid system are key modulators of synaptic function, which were related to memory and mood. Although the underlying mechanism remains unknown, several studies indicated the benefits of polyunsaturated fatty acids (PUFAs, linolenic acid, 39.7 %; linoleic acid, 28 %; and oleic acid, 22 %) on brain function through the endocannabinoid system. The present study aimed to evaluate the influence of dietary PUFAs on cognition deficits induced by sleep deprivation in Sprague Dawley rats. The rats were sleep deprivation continuously for 7 days and fed with PUFAs at three different dosages (2, 4 and 8 µl/g body weight) at the meantime. The effect of PUFAs on cognition was investigated by object recognition test while depressive-like behavior were detected using sucrose preference test and forced swim test. The mechanism of PUFAs was elucidated by hippocampal synaptic transmission analyses. The resluts revealed that SD led to the disorder of cognition and mood which was improved by the supplement of PUFAs. SD significantly increased the mEPSC frequency, and decreased the protein level of cannabinoid type-1 receptors (CB1R). These changes were restored by supplement of PUFAs, which showed a similar level to the control group. Behaviour tests showed that the positive effects on repairing cognition and anxiety disorders were almost completely abolished when the CB1R receptor antagonist rimonabant was applied to the SD rats. These findings indicated that PUFAs are a factor regulating cognition deficits and depression induced by SD via cannabinoid type-1 receptors.

Pb exposure induces an imbalance of excitatory and inhibitory synaptic transmission in cultured rat hippocampal neurons.

An appropriate balance of excitatory and inhibitory synapse maintains the network stability of the central nervous system. Our recent work showed lead (Pb) exposure can inhibit synaptic transmission in cultured hippocampal neurons. However, it is not clear whether Pb exposure disrupt the balance of excitatory and inhibitory synaptic transmission. Here, primary cultured hippocampal neurons from Sprague-Dawley (SD) rats were exposed to Pb (0.2 µM, 1 µM, 5 µM, respectively) from Days in Vitro (DIV) 7 to DIV 12 for 5 days and the excitatory and inhibitory synaptic transmission was examined. Patch clamp recording results showed that distinct from exposures of 0.2 µM and 5 µM, 1 µM Pb exposure significantly increased the mIPSC frequency and decreased the mEPSC frequency, leading to a uniform inhibitory outcome. Further, the number of inhibitory presynaptic puncta was significantly increased after 1 µM Pb exposure, while the number of excitatory presynaptic terminals was decreased. In addition 1 µM Pb increased the glutamic acid decarboxylase (GAD65) expression and the surface GABAA receptor (GABAAR) clusters. This shift might potentiate the synthesis of GABA and enhance the surface distribution of postsynaptic GABAAR clusters in hippocampus neurons. Together, these data showed that Pb exposure disrupted the balance of excitatory and inhibitory synaptic transmission via abnormal GABAergic neurotransmission.

Multistimuli-responsive drug vehicles based on gold nanoflowers for chemophotothermal synergistic cancer therapy.

AIM: To design and synthesize a novel multistimuli-responsive drug vehicle based on gold nanoflowers (AuNFs) for chemophotothermal synergistic cancer therapy. MATERIALS & METHODS: Multistimuli-responsive drug-delivery system based on doxorubicin (DOX)/polydopamine (PDA)-functionalized AuNFs (Lan-AuNFs@PDA/DOX) was prepared. The structural characteristics, photothermal properties and stimuli-responsive drug release properties of Lan-AuNFs@PDA/DOX were evaluated. Antitumor studies in vivo and in vitro were performed. RESULTS: Lan-AuNFs@PDA/DOX exhibited uniform morphology, excellent biocompatibility and photothermal conversion efficiency, which could also respond to stimulus including near infrared light and pH to trigger on demand drug release. The excellent synergistic therapeutic efficacy was confirmed both in vitro and in vivo. CONCLUSION: Lan-AuNFs@PDA/DOX would be a promising drug carrier, endowing a great potential for multistimuli-responsive chemophotothermal synergistic cancer therapy.

Self-assembly synthesis of vapreotide­gold hybrid nanoflower for photothermal antitumor activity.

Based on the self-assembly properties of vapreotide acetate (Vap), one kind of novel vapreotide acetate­gold nanoflowers (Vap-AuNFs) was fabricated for the first time by biomimetic mineralization method using Vap as a template. The Vap-AuNFs possessed anisotropic structure with a large absorption cross-section, which were face-centered cubic crystalline, exhibiting a remarkable monodisperse, narrow size (154 nm) distribution and good stability in aqueous solution. The apparent anisotropy of the gold nanostructure with high molar extinction coefficient can cause significantly higher plasmon absorption of Vap-AuNFs in the near infrared (NIR) region compared with Au nanoparticles (AuNPs), so the nanocomplex can induce remarkably enhanced photothermal conversion efficiency under NIR light irradiation. Breathtakingly, Vap-AuNFs exhibited superior biocompatibilities compared to AuNPs, as well as enhanced Hela cells lethality under NIR irradiation. This novel method was simple, low cost and green for the design and preparation of anisotropic gold nanoflowers with outstanding NIR laser-induced local hyperthermia, highlighting their potential applications in biomedical fields.