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Abstract Background Dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid isolated from the root of Menispermum dauricum DC, exhibits promising anti-Alzheimer’s disease (AD) effects, but its underlying mechanisms remain inadequately investigated. This paper aims to identify potential targets and molecular mechanisms of DAU in AD treatment. Methods Network pharmacology and molecular docking simulation method were used to screen and focus core targets. Various transgenic Caenorhabditis elegans models were chosen to validate the anti-AD efficacy and mechanism of DAU. Results There are 66 potential DAU-AD target intersections identified from 100 DAU and 3036 AD-related targets. Subsequent protein-protein interaction (PPI) network analysis identified 16 core targets of DAU for anti-AD. PIK3CA, AKT1 and mTOR were predicted to be the central targets with the best connectivity through the analysis of “compound-target-biological process-pathway network”. Molecular docking revealed strong binding affinities between DAU and PIK3CA, AKT1, and mTOR. In vivo experiments demonstrated that DAU effectively reduced paralysis in AD nematodes caused by Aβ aggregation toxicity, downregulated expression of PIK3CA, AKT1, and mTOR homologues (age-1, akt-1, let-363), and upregulated expression of autophagy genes and the marker protein LGG-1. Simultaneously, DAU increased lysosomal content and enhanced degradation of the autophagy-related substrate protein P62. Thioflavin T（Th-T）staining experiment revealed that DAU decreased Aβ accumulation in AD nematodes. Further experiments also confirmed DAU’s protein scavenging activity in polyglutamine (polyQ) aggregation nematodes. Conclusion Collectively, the mechanism of DAU against AD may be related to the activation of the autophagy-lysosomal protein clearance pathway, which contributes to the decrease of Aβ aggregation and the restoration of protein homeostasis.

Abstract Arboviruses can be paternally transmitted by male insects to offspring for long-term persistence, but the mechanism remains largely unknown. Here, we use a model system of a destructive rice reovirus and its leafhopper vector to find that insect ribosome-rescuer Pelo-Hbs1 complex expressed on the sperm surface mediates paternal arbovirus transmission. This occurs through targeting virus-containing tubules constituted by viral nonstructural protein Pns11 to sperm surface via Pns11-Pelo interaction. Tubule assembly is dependent on Hsp70 activity, while Pelo-Hbs1 complex inhibits tubule assembly via suppressing Hsp70 activity. However, virus-activated ubiquitin ligase E3 mediates Pelo ubiquitinated degradation, synergistically causing Hbs1 degradation. Importantly, Pns11 effectively competes with Pelo for binding to E3, thus antagonizing E3-mediated Pelo-Hbs1 degradation. These processes cause a slight reduction of Pelo-Hbs1 complex in infected testes, promoting effective tubule assembly. Our findings provide insight into how insect sperm-specific Pelo-Hbs1 complex is modulated to promote paternal virus transmission without disrupting sperm function.

Abstract Many devastating plant viruses are transmitted by insect vectors among plant hosts in a persistent-propagative manner. Pelota (Pelo) is an evolutionarily conserved protein involved in the mRNA surveillance system. In this study, it was found that the accumulation of Pelo proteins are slightly decreased during the propagation of the fijivirus southern rice black-streaked dwarf virus (SRBSDV) in rice and transmission vector planthopper (Sogatella furcifera). The tubular protein P7-1 encoded by SRBSDV interacted with Pelo of rice or planthopper vector. Overexpression or knockdown of Pelo expression inhibits the formation of P7-1 tubules in insect cells, further exerting antiviral activity. Furthermore, overexpression or knockout of Pelo expression in transgenic rice plants also inhibits the effective propagation of SRBSDV as well as two other rice viruses of different families. The slight reduction of Pelo accumulation during SRBSDV propagation in rice and insect vectors would avoid Pelo-mediated excessive inhibition of P7-1 tubule formation, ensuring effective virus propagation. Our findings provide insights into how the up- or down-regulated expression of Pelo in rice hosts and insect vectors elevate their resistance to rice viruses.

Many plant arboviruses are persistently transmitted by piercing-sucking insect vectors. However, it remains largely unknown how conserved insect Toll immune response exerts antiviral activity and how plant viruses antagonize it to facilitate persistent viral transmission. Here, we discover that southern rice black-streaked dwarf virus (SRBSDV), a devastating planthopper-transmitted rice reovirus, activates the upstream Toll receptors expression but suppresses the downstream MyD88-Dorsal-defensin cascade, resulting in the attenuation of insect Toll immune response. Toll pathway-induced the small antibacterial peptide defensin directly interacts with viral major outer capsid protein P10 and thus binds to viral particles, finally blocking effective viral infection in planthopper vector. Furthermore, viral tubular protein P7-1 directly interacts with and promotes RING E3 ubiquitin ligase-mediated ubiquitinated degradation of Toll pathway adaptor protein MyD88 through the 26 proteasome pathway, finally suppressing antiviral defensin production. This virus-mediated attenuation of Toll antiviral immune response to express antiviral defensin ensures persistent virus infection without causing evident fitness costs for the insects. E3 ubiquitin ligase also is directly involved in the assembly of virus-induced tubules constructed by P7-1 to facilitate viral spread in planthopper vector, thereby acting as a pro-viral factor. Together, we uncover a previously unknown mechanism used by plant arboviruses to suppress Toll immune response through the ubiquitinated degradation of the conserved adaptor protein MyD88, thereby facilitating the coexistence of arboviruses with their vectors in nature.

In this paper, the design, manufacture and testing of an origami protective shield with a supporting frame structure are presented. It consists of an origami shield surface and a deployable supporting frame structure that needs to be portable and sufficiently stiff. First, for the design of the shield surface, a three-stage origami crease pattern is developed to reduce the shield size in the folded state. The shield surface consists of several stiff modular panels and layered with flexible fabric. The modular panels are made of a multi-layer composite where a ceramic layer is made of small pieces to improve durability as those small pieces enable restriction of crack propagation. Then, the supporting frame structure is designed as a chain-of-bars structure in order to fold into a highly compact state as a bundle of bars and deploy in sequence. Thus, a feature-driven topology structural optimization method preserving component sequence is developed where the inter-dependence of sub-structures is taken into account. A bar with semi-circular ends is used as a basic design feature. The positions of the bar’s end points are treated as design variables and the width of the bars is kept constant. Then, a constraint on the total length of the chain of bars is introduced. Finally, the modular panels made of multi-layer composite and the full-scale prototype of the origami shield are fabricated and tested to verify the bullet-proof performance.

Abstract Nitrogen plays a significant role in influencing various physiological processes in plants, thereby impacting their ability to withstand abiotic stresses. This study used hydroponics to compare the effects of three nitrogen supply levels (1N, 1/2N and 1/4N) on the antioxidant capacity of rice varieties JJ88 (nitrogen efficient) and XN999 (nitrogen inefficient) with different nitrogen use efficiencies. The results show that compared with the XN999 variety, the JJ88 variety has stronger adaptability to low-nitrogen conditions, which is mainly reflected in the relatively small decrease in dry weight and net photosynthetic rate (Pn); In the early stage of low-nitrogen treatment (0–7 d), the $${\mathbf{O}}_{2}^{-}$$ O 2 - production rate, hydrogen peroxide (H2O2) and malondialdehyde (MDA) content of JJ88 variety increased relatively slightly, but the superoxide dismutase (SOD), peroxide The activity of enzyme (POD) and catalase (CAT) increased significantly; After low-nitrogen treatment, the ASA–GSH cycle enzyme activity of JJ88 variety was relatively high, and the dehydroascorbate reductase (DHAR) activity after 14 days of low-nitrogen treatment was higher than that of 1N treatment; The content of reduced ascorbic acid (ASA) in non-enzymatic antioxidants was lower than that of 1N treatment after 14 days of low nitrogen treatment; The contents of oxidized dehydroascorbic acid (DHA) and carotenoids (Car) were higher than those of 1N treatment after 21d and 14d of low nitrogen treatment respectively; The contents of reduced glutathione (GSH), oxidized glutathione (GSSG) and proline (Pro) showed a larger upward trend during the entire low-nitrogen treatment period. In summary, the JJ88 rice variety has a strong ability to regulate oxidative stress and osmotic damage under low nitrogen conditions. It can slow down plant damage by regulating antioxidant enzyme activity and antioxidant content. This provides a basis for achieving nitrogen reduction and efficiency improvement in rice and the breeding of nitrogen-efficient varieties.

Arboviruses and symbiotic viruses can be paternally transmitted by male insects to their offspring, but the mechanism remains largely unknown. Here, the authors identify the sperm-specific serpin protein HongrES1 of the leafhopper Recilia dorsalis as a mediator of paternal transmission of the reovirus rice gall dwarf virus and of a previously undescribed symbiotic virus of the Virgaviridae family, Recilia dorsalis filamentous virus, via direct binding of virions to leafhopper sperm surfaces and subsequent paternal transmission via interaction with both viral capsid proteins.

Objective: To study the effect of mulberry leaf water extract on isolated ileum contractile activity of guinea pig and constipation rats, and to explore the mulberry leaf improving constipation effects and related mechanisms. Methods: The effect of mulberry leaf water extract on isolated ileum movement of guinea pigs was observed by measuring in vitro intestinal muscle tension. Loperamide (10 mg/kg/d) was used to construct 3 d and 7 d constipation rat models, and mulberry leaf water extract (5 g/kg/d) was administered by gavage at the same time to observe the time of first defecation, fecal number for 24 h and small intestine propulsion rate of rats. The ileum contractile reaction induced by carbachol was measured. The histological changes of colon were observed by HE staining of paraffin section, and the expression of AQP3 in colon was detected by immunohistochemistry. Results: Mulberry leaf water extract promoted the voluntary movement of ileum in guinea pigs, which was manifested by increased contraction amplitude and mean tension. The first defecation time, fecal number at 24 h and small intestine propulsion rate were improved in both group of mulberry leaf 3 d and 7 d. Mulberry leaf water extract significantly improved the reduction of the average tension of the isolated ileum induced by carbachol in constipation rats. Mulberry leaf water extract improved the musculature thinning of colon tissue caused by loperamide, and significantly reduced the increase in colon AQP3 expression casued by loperamide. Conclusion: Mulberry leaf water extract can significantly promote ileum movement in guinea pigs, and improve constipation in rats, which may through reducing the expression of AQP3, inhibiting the excessive absorption of colonic water, increasing the water content of feces, and promoting intestinal muscle movement.

Abstract Both viruses and host cells compete for intracellular polyamines for efficient propagation. Currently, how the key polyamine-metabolizing enzymes, including ornithine decarboxylase 1 (ODC1) and its antizyme 1 (OAZ1), are activated to co-ordinate viral propagation and polyamine biosynthesis remains unknown. Here, we report that the matrix protein of rice stripe mosaic virus (RSMV), a cytorhabdovirus, directly hijacks OAZ1 to ensure the proper assembly of rigid bacilliform non-enveloped virions in leafhopper vector. Viral matrix protein effectively competes with ODC1 to bind to OAZ1, and thus, the ability of OAZ1 to target and mediate the degradation of ODC1 is significantly inhibited during viral propagation, which finally promotes polyamines production. Thus, OAZ1 and ODC1 are activated to synergistically promote viral persistent propagation and polyamine biosynthesis in viruliferous vectors. Our data suggest that it is a novel mechanism for rhabdovirus to exploit OAZ1 for facilitating viral assembly.

Summary Huanglongbing (HLB) is currently considered the most destructive disease of citrus worldwide. In the major citrus‐growing areas in Asia and the US, the major causal agent of HLB is the bacterial pathogen Candidatus Liberibacter asiaticus (CLas). CLas is vectored by the Asian citrus psyllid, Diaphorina citri, in a persistent propagative manner. CLas cannot be cultured in vitro because of its unclear growth factors, leading to uncertainty in the infection mechanism of CLas at the cellular level in citrus and in D. citri. To characterize the detailed infection of CLas in the host and vector, the incidence of HLB was first investigated in citrus‐growing fields in Fujian Province, China. It was found that the positive association of the level of CLas infection in the leaves correlated with the symptoms. Then antibodies against peptides of the outer membrane protein (OMP) of CLas were prepared and tested. The antibodies OMP‐225, OMP‐333 and OMP724 showed specificity to citrus plants in western blot analyses, whereas the antibodies OMP‐47 and OMP‐225 displayed specificity to the D. citri vector. The application of OMP‐225 in the immunofluorescence assay indicated that CLas was located in and distributed throughout the phloem sieve cells of the leaf midribs and axile placenta of the fruit. CLas also infected the epithelial cells and visceral muscles of the alimentary canal of D. citri. The application of OMP‐333 in immunoelectron microscopy indicated the round or oval CLas in the sieve cells of leaf midribs and axile placenta of fruit as well as in the epithelial cells and reticular tissue of D. citri alimentary canal. These results provide a reliable means for HLB detection, and enlighten a strategy via neutralizing OMP to control HLB. These findings also provide insight for the further investigation on CLas infection and pathogenesis, as well as CLas–vector interaction.

Bacillus anthracis has gained international attention as a deadly bacterium and a potentially deadly biological warfare agent. Dipicolinic acid (DPA) is the main component of the protective layer of anthracis spores, and is also an anthrax biomarker. Therefore, it is of great significance to explore an efficient and sensitive DPA detection method. Herein, a novel ratio hybrid probe (CQDs-PIL-Eu3+) was prepared by a simple one-step hydrothermal method using carbon quantum dots (CQDs) as an internal reference fluorescence and a covalent bond between CQDs and Eu3+ by using a polyionic liquid (PIL) as a bridge molecule. The ratiometric fluorescence probe was found to have the characteristics of sensitive fluorescence visual sensing in detecting DPA. The structure and the sensing properties of CQDs-PIL-Eu3+ were investigated in detail. In particular, the fluorescence intensity ratio of Eu3+ to CQDs (I616/I440) was linear with the concentration of DPA in the range of 0–50 μM, so the detection limit of the probe was as low as 32 nm, which was far lower than the DPA dose released by the number of anthrax spores in human body (60 μM) and, thus, can achieve sensitive detection. Therefore, the ratiometric fluorescence probe in this work has the characteristics of strong anti-interference, visual sensing, and high sensitivity, which provides a very promising scheme for the realization of anthrax biomarker DPA detection.

Viruses can hijack autophagosomes as the nonlytic release vehicles in cultured host cells. However, how autophagosome-mediated viral spread occurs in infected host tissues or organs in vivo remains poorly understood. Here, we report that an important rice reovirus, rice gall dwarf virus (RGDV) hijacks autophagosomes to traverse multiple insect membrane barriers in the midgut and salivary gland of leafhopper vector to enhance viral spread. Such virus-containing double-membraned autophagosomes are prevented from degradation, resulting in increased viral propagation. Mechanistically, viral nonstructural protein Pns11 induces autophagy and embeds itself in the autophagosome membranes. The autophagy-related protein 5 (ATG5)-ATG12 conjugation is essential for initial autophagosome membrane biogenesis. RGDV Pns11 specifically interacts with ATG5, both in vitro and in vivo. Silencing of ATG5 or Pns11 expression suppresses ATG8 lipidation, autophagosome formation, and efficient viral propagation. Thus, Pns11 could directly recruit ATG5-ATG12 conjugation to induce the formation of autophagosomes, facilitating viral spread within the insect bodies. Furthermore, Pns11 potentially blocks autophagosome degradation by directly targeting and mediating the reduced expression of N-glycosylated Lamp1 on lysosomal membranes. Taken together, these results highlight how RGDV remodels autophagosomes to benefit viral propagation in its insect vector.

The reproductive performance of P. sinensis broodstock has gradually declined due to degenerated wild genetic resources, frequent extreme weathers and inbreeding in recent years. This study investigated the effect of Chinese herbal extract mixture (Herba Epimedii, Herba leonuri and Semen Vaccariae, termed as CHEM) on reproductive performance of turtle broodstock, external and internal quality traits of fertilized eggs. Six levels of CHEM at the rate of 0%, 0.1%, 0.2%, 0.4%, 0.8% and 1.6% were incorporated into the basal diet of turtle broodstock for six weeks. Each diet was randomly allocated into three greenhouse cement spawning ponds with 1000 turtles in each pond. The female-to-male ratio of the broodstock with about 8 years old was around 8: 1. The results revealed that dietary supplementation of 0.1% CHEM significantly improved daily feed consumption (DFC) and daily egg laying amounts (DELA) of turtles compared with that in control group (P

Rice stripe mosaic virus (RSMV), a newly discovered plant cytorhabdovirus, and rice gall dwarf virus (RGDV), a plant reovirus, are transmitted by leafhopper Recilia dorsalis in a persistent-propagative manner. In this study, field surveys in Luoding city, Guangdong province of southern China, showed that RSMV and RGDV frequently co-infected rice plants. Furthermore, this co-infection had a synergistic effect on viral replication potential and pathogenicity in rice plants. Meanwhile, RSMV and RGDV also co-infected R. dorsalis vectors, and RGDV significantly promoted the propagation of RSMV in co-infected vectors. Accordingly, co-infection significantly promoted the acquisition and transmission efficiencies of RSMV by R. dorsalis. However, such co-infection did not significantly affect the propagation of RGDV in vectors. More importantly, we also observed that non-viruliferous R. dorsalis preferred to feed on co-infected rice plants, and this process further affected the feeding behavior of R. dorsalis to enhance viral release into rice phloem. These results provided the clues as to why RSMV had been a gradually expanding problem, creating an increasing risk of damage to rice production. Our findings revealed that synergism between RSMV and RGDV in their host and vector enhanced the propagation and transmission of RSMV, which will help guide the formulation of viral control strategies.

Numerous piercing-sucking insects can horizontally transmit viral pathogens together with saliva to plant phloem, but the mechanism remains elusive. Here, we report that an important rice reovirus has hijacked small vesicles, referred to as exosomes, to traverse the apical plasmalemma into saliva-stored cavities in the salivary glands of leafhopper vectors. Thus, virions were horizontally transmitted with exosomes into rice phloem to establish the initial plant infection during vector feeding. The purified exosomes secreted from cultured leafhopper cells were enriched with virions. Silencing the exosomal secretion-related small GTPase Rab27a or treatment with the exosomal biogenesis inhibitor GW4869 strongly prevented viral exosomal release in vivo and in vitro. Furthermore, the specific interaction of the 15-nm-long domain of the viral outer capsid protein with Rab5 induced the packaging of virions in exosomes, ultimately activating the Rab27a-dependent exosomal release pathway. We thus anticipate that exosome-mediated viral horizontal transmission is the conserved strategy hijacked by vector-borne viruses.

Abstract Most plant reoviruses encode a type of nonstructural protein that assembles tubular structures to package virions for viral spread in planthopper or leafhopper vectors. These tubules are propelled by actin filaments and facilitate viruses to overcome transmission barriers in insect vectors. This is known as actin-based tubule motility (ABTM), in which insect proteins, especially actin-associated proteins participate. To better understand the insect components that play a role in the ABTM, the proteins interacting with tubule protein Pns11 of the Rice gall dwarf virus (RGDV) in the leafhopper vector were investigated. We found that gelsolin, an actin-modulating protein, interacted with Pns11 in the yeast-two-hybrid system and Sf9 cells. The interaction and co-localization of gelsolin and Pns11 were also verified in cultured cells and insect bodies of the leafhopper vector. Further, the expression of gelsolin was up-regulated by the RGDV infection both in cultured cells and insects. The knockdown of the gelsolin gene triggered by RNA interference increased viral accumulation, thus increasing the viruliferous rates of the leafhopper vector. This negative association of gelsolin with Pns11 and virus infection revealed that gelsolin negatively affected the ability of the virus to spread by interacting with Pns11 tubules, finally acting to negatively regulate RGDV infection. The results of this study indicate that ABTM is negatively regulated by insects in the coevolution of the insect vector and virus.

Arbovirus vertical transmission is commonly mediated by transovarial passage of female insect vectors. Here, the authors show that Rice gall dwarf virus can be transmitted by male leafhoppers via interactions of the viral capsid and heparan sulfate proteoglycan on the surface of sperm heads.

In the field, many insect-borne crop viral diseases are more suitable for maintenance and spread in hot-temperature areas, but the mechanism remains poorly understood. The epidemic of a planthopper (Sogatella furcifera)-transmitted rice reovirus (southern rice black-streaked dwarf virus, SRBSDV) is geographically restricted to southern China and northern Vietnam with year-round hot temperatures. Here, we reported that two factors of endoplasmic reticulum-associated degradation (ERAD) machinery, the heat shock protein DnaJB11 and ER membrane protein BAP31, were activated by viral infection to mediate the adaptation of S. furcifera to high temperatures. Infection and transmission efficiencies of SRBSDV by S. furcifera increased with the elevated temperatures. We observed that high temperature (35°C) was beneficial for the assembly of virus-containing tubular structures formed by nonstructural protein P7-1 of SRBSDV, which facilitates efficient viral transmission by S. furcifera. Both DnaJB11 and BAP31 competed to directly bind to the tubule protein P7-1 of SRBSDV; however, DnaJB11 promoted whereas BAP31 inhibited P7-1 tubule assembly at the ER membrane. Furthermore, the binding affinity of DnaJB11 with P7-1 was stronger than that of BAP31 with P7-1. We also revealed that BAP31 negatively regulated DnaJB11 expression through their direct interaction. High temperatures could significantly upregulate DnaJB11 expression but inhibit BAP31 expression, thereby strongly facilitating the assembly of abundant P7-1 tubules. Taken together, we showed that a new temperature-dependent protein quality control pathway in the ERAD machinery has evolved for strong activation of DnaJB11 for benefiting P7-1 tubules assembly to support efficient transmission of SRBSDV in high temperatures. We thus deduced that ERAD machinery has been hitchhiked by insect-borne crop viruses to enhance their transmission in tropical climates.

ABSTRACT Many insect species, such as aphids, leafhoppers, planthoppers, and whiteflies harbor obligate bacterial symbionts that can be transovarially transmitted to offspring through the oocytes of female insects. Whether obligate bacterial symbionts can carry important molecules/resources to the embryos to support egg development is still unknown. Here, we show that the vitellogenin (Vg) precursor of rice leafhopper Nephotettix cincticeps is biosynthesized by the fat body, secreted into the hemolymph and subsequently cleaved into the 35- and 178-kDa subunits, whereas only the 178-kDa subunit is taken up by the leading end of oocytes in a receptor-dependent manner or moves into the posterior pole of the terminal oocyte in association with obligate bacterial symbiont “Candidatus Nasuia deltocephalinicola” (hereafter Nasuia) in a receptor-independent manner. Furthermore, the 178-kDa Vg subunit can directly interact with a surface channel molecule (porin) on the envelope of Nasuia, allowing Vg to enter bacterial cytoplasm. Thus, Vg can hitchhike the ancient oocyte entry path of Nasuia, the common obligate symbiont of leafhoppers. Knocking down a Nasuia growth-related protein expression or treatment with porin antibody strongly prevents the ability of Nasuia to carry Vgs into oocytes and impair insect egg development. Nasuia-carried Vgs provide at least 20% of the total Vgs in the developing eggs. We anticipate that the bacterial symbiont-mediated Vg uptake into oocytes to support efficient egg development may be a common pattern shared by many insects. IMPORTANCE Many insects harbor obligate bacterial symbionts that can be vertically transmitted to offspring by female insects through eggs. Here, we report that leafhopper vitellogenin (Vg) recognizes and binds a surface channel molecule (porin) on the envelope of obligate bacterial symbiont Nasuia, which potentially induces the opening of porin channels for Vg to access the cytoplasm of Nasuia. Thus, Vg can exploit bacterial symbionts as the independent carriers into the oocytes. Such Nasuia-carried Vg contents support efficient insect egg development. Thus, our findings indicate that insects have evolved strategies to exploit the symbionts for carrying additional Vgs to guarantee optimal insect reproduction.

Many plant rhabdoviruses are neurotropic and can persistently infect the central nervous system (CNS) of their insect vectors without causing significant cytopathology. The mechanisms by which the insect CNS resists infection by plant rhabdoviruses are largely unknown. Here, we report that the neural factor Hikaru genki homolog of the leafhopper Nephotettix cincticeps (NcHig) limits the spread of the nucleorhabdovirus rice yellow stunt virus (RYSV) in vector CNS. NcHig is predominantly expressed in the CNS of N. cincticeps, and the knockdown of NcHig expression by RNA interference enhances RYSV infection of the CNS. Furthermore, immuno-blockade of NcHig function by microinjection of N. cincticeps with NcHig antibody also enhances viral infection of the CNS. Thus, we conclude that the neuron-specific factor NcHig can control RYSV propagation in the CNS. Interestingly, we find the Hig homolog of the leafhopper Recilia dorsalis also has antiviral activity during the persistent infection of the cytorhabdovirus rice stripe mosaic virus (RSMV) in vector CNS. We further determine that RYSV and RSMV matrix proteins specifically interact with the complement control protein (CCP) domains of Higs. Thus, the matrix protein-binding ability of Hig is potentially essential for its antiviral activity in rice leafhoppers. Our results demonstrate an evolutionarily conserved antiviral mechanism for Hig to mediate the persistent infection of rice rhabdoviruses in the CNS of leafhopper vectors.

Abstract Background Renal cell carcinoma accounts for 2–3% of all cancers and metastasis increased the malignancy of renal cancer. However, the role of methylation in metastasis of renal cancer is poorly understood. Methods We performed targeted gene array to compare the differential expressions of methylation regulated genes in metastatic and primary renal cancer tissues. Quantitative methylation specific PCR was performed to examine the CpG methylation levels of Runt related transcription factor 3 (RUNX3) and transforming growth factor (TGF)-β. Western blot was performed to detect the expression of target genes. Murine xenograft renal cancer model was established to assay gene expression, methylation level, tumor growth and animal survival in vivo. Results RUNX3 and TGF-β levels were decreased in metastatic renal cancer tissues as a result of their CpG methylation. Metastatic xenograft model displayed decreased expression levels of RUNX3 and TGF-β and higher CpG methylation levels, bigger tumor size and shorter survival time, all which were restored by treatment with a methylation inhibitor. Conclusions Hypermethylation in CpG islands promotes metastasis of renal cancer and is associated with TGF-β and RUNX3 inhibition.

Numerous plant viruses that cause significant agricultural problems are persistently transmitted by insect vectors. We wanted to see if apoptosis was involved in viral infection process in the vector. We found that a plant reovirus (rice gall dwarf virus, RGDV) induced typical apoptotic response during viral replication in the leafhopper vector and cultured vector cells, as demonstrated by mitochondrial degeneration and membrane potential decrease. Fibrillar structures formed by nonstructural protein Pns11 of RGDV targeted the outer membrane of mitochondria, likely by interaction with an apoptosis-related mitochondrial protein in virus-infected leafhopper cells or nonvector insect cells. Such association of virus-induced fibrillar structures with mitochondria clearly led to mitochondrial degeneration and membrane potential decrease, suggesting that RGDV Pns11 was the inducer of apoptotic response in insect vectors. A caspase inhibitor treatment and knockdown of caspase gene expression using RNA interference each reduced apoptosis and viral accumulation, while the knockdown of gene expression for the inhibitor of apoptosis protein improved apoptosis and viral accumulation. Thus, RGDV exploited caspase-dependent apoptotic response to promote viral infection in insect vectors. For the first time, we directly confirmed that a nonstructural protein encoded by a persistent plant virus can induce the typical apoptotic response to benefit viral transmission by insect vectors.

Rice stripe mosaic virus (RSMV), a novel species of Cytorhabdovirus, is transmitted by the leafhopper Recilia dorsalis in a persistent-propagative manner. In this study, we firstly confirmed that N protein of RSMV is a component of viroplasm and virion in vector culture cells of R. dorsalis. Confocal microscopy revealed that RSMV initially accumulated in epithelial cells of the filter chamber of R. dorsalis, from where it proceeded to the visceral muscles surrounding the filter chamber. Subsequently, RSMV spread quickly throughout the suspensory ligament to the salivary glands. Meanwhile, RSMV spread from the filter chamber to midgut, hindgut, esophagus, hemolymph, and central nervous system. We further observed that RSMV particles displayed as non-enveloped form when propagating in cytoplasm of different tissues, and became enveloped when spread within insect body by electron microscopy. Additionally, we found that the leafhopper Nephotettix virescens was also able to acquire and transmit RSMV. These results clarified the infection characteristics of RSMV in its leafhopper vectors, which will help guide the formulation of RSMV prevention and control strategies.

Many viral pathogens are persistently transmitted by insect vectors and cause agricultural or health problems. Generally, an insect vector can use autophagy as an intrinsic antiviral defense mechanism against viral infection. Whether viruses can evolve to exploit autophagy to promote their transmission by insect vectors is still unknown. Here, we show that the autophagic process is triggered by the persistent replication of a plant reovirus, rice gall dwarf virus (RGDV) in cultured leafhopper vector cells and in intact insects, as demonstrated by the appearance of obvious virus-containing double-membrane autophagosomes, conversion of ATG8-I to ATG8-II and increased level of autophagic flux. Such virus-containing autophagosomes seem able to mediate nonlytic viral release from cultured cells or facilitate viral spread in the leafhopper intestine. Applying the autophagy inhibitor 3-methyladenine or silencing the expression of Atg5 significantly decrease viral spread in vitro and in vivo, whereas applying the autophagy inducer rapamycin or silencing the expression of Torc1 facilitate such viral spread. Furthermore, we find that activation of autophagy facilitates efficient viral transmission, whereas inhibiting autophagy blocks viral transmission by its insect vector. Together, these results indicate a plant virus can induce the formation of autophagosomes for carrying virions, thus facilitating viral spread and transmission by its insect vector. We believe that such a role for virus-induced autophagy is common for vector-borne persistent viruses during their transmission by insect vectors.

Rice stripe virus (RSV), a tenuivirus, is transmitted by small brown planthopper (SBPH) in a persistent-propagative manner. In this study, sequential infection of RSV in the internal organs of SBPH after ingestion of virus indicated that RSV initially infected the midgut epithelium, and then progressed to the visceral muscle tissues, through which RSV spread to the entire alimentary canal. Finally, RSV spread into the salivary glands and reproductive system. During viral infection, the nonstructural protein NS4 of RSV formed cytoplasmic inclusions in various tissues of viruliferous SBPH. We demonstrated that the ribonucleoprotein particles of RSV were closely associated with NS4-specific inclusions in the body of viruliferous SBPH through a direct interaction between NS4 and nucleoprotein of RSV. Moreover, the knockdown of NS4 expression due to RNA interference induced by dsRNA from NS4 gene significantly prevented the spread of RSV in the bodies of SBPHs without a significant effect on viral replication in continuous cell culture derived from SBPH. All these results suggest that the nonstructural protein NS4 of RSV plays a critical role in viral spread by the vector insects.

The abalone shell, a composite material whose cross-section is composed of inorganic and organic layers, has high strength and toughness. Inspired by the abalone shell, several multi-layer composite plates with different layer sequences and thicknesses are studied as bullet-proof material in this paper. To investigate the ballistic performance of this multi-layer structure, the complete characterization model and related material parameters of large deformation, failure and fracture ofAl2O3 ceramics andCarbon Fiber Reinforced Polymer (CFRP) are studied. Then, 3D finite element models of the proposed composite plates with different layer sequences and thicknesses impacted by a 12.7 mm armor-piercing incendiary (API) are built using Abaqus to predict failure. The simulation results show that the CFRP/Al2O3 ceramic/Ultrahigh Molecular Weight Polyethylene (UHMWPE)/CFRP (1 mm/4 mm/4 mm/1 mm) composite is the optimized stack of layers. The simulation results under specified layer sequence and thickness have a reasonable correlation with the experimental results and reflect the failure and fracture of the multi-layer composite protective armor. [ABSTRACT FROM AUTHOR]

BACKGROUND: Barberry plants can be considered as useful additives and functional compounds in various industries, especially in the food industry. Berberine (BBR), the most important functional compound in the barberry roots, has recently been used to treat obesity, diabetes, and atherosclerosis. Gut microbiota and the intestinal barrier play an important role in the development of glucolipid metabolism disorders (GLMDs). However, the association of gut microbiota metabolism disorder and the intestinal barrier dysfunction effect of BBR in GLMDs remains elusive. RESULTS: The results showed that administration of BBR could increase the number of colonic glands and goblet cell mucus secretion, improve the intestinal barrier function, and reduce the serum glycolipid level in GLMD hamsters. Interestingly, BBR was metabolized into 12 metabolites by gut microbiota, and the main metabolic pathways were oxidation, demethylation, and hydrogenation. In addition, BBR significantly improved the species diversity and uniformity of gut microbiota and promoted the proliferation of beneficial microbiota. Furthermore, the levels of tryptophan metabolites, such as indole, indole-3-acetamide, indole-3-acetaldehyde, indole-3-pyruvic acid, and indole-3-acetic acid were significantly altered by BBR. Both the intestinal tight junction proteins and intestinal immune factors were altered by BBR. CONCLUSION: BBR could alleviate intestinal barrier dysfunction of GLMDs by modulating gut microbiota and gut-microbiotarelated tryptophan metabolites, which may be one of the pharmacological mechanisms for the treatment of GLMDs. [ABSTRACT FROM AUTHOR]

ObjectiveTo detect individuals at high risk of cardiovascular disease (CVD) and to explore influencing factors of the risk among 35 – 75-year-old residents in Hebei province for prevention and treatment of CVD in the population. MethodsTotally 140 632 permanent residents aged 35 – 75 years were recruited with stratified random cluster sampling in 11 districts/counties/prefectures covered by the CVD high-risk population screening and comprehensive intervention program across Hebei province. Face-to-face interview with a questionnaire designed by domestic researchers, physical examination, and detections of serum lipids and fasting blood glucose were conducted among the participants from September 2016 through November 2020. The CVD risk was evaluated based on any of the followings: history of cardiovascular and cerebrovascular diseases, hypertension, dyslipidemia and with 10-year risk of ≥ 20% for CVD assessed according the ‘risk prediction charts’ published by World Health Orgaization. The detection rate of individuals at high risk of CVD and influencing factors of CVD risk were analyzed. ResultsAmong the 137 115 participants (97.50% of all residents surveyed) with eligible responses, 33 297 (24.3%) were assessed as being at high CVD risk. The results of multivariate unconditional logistic regression analysis showed that aged 50 years and above, living in rural areas, smoking, hypertension, diabetes, dyslipidemia, and obesity were risk factors of having a high-risk of CVD, while, being female and with the education of junior middle school were protective factors against CVD risk among 35 – 75 years old residents in Hebei province. ConclusionThe proportion of individuals at high risk of CVD is relatively high and the risk is mainly influenced by gender, age, education, living residence, hypertension, diabetes, dyslipidemia, and obesity among 35 – 75-year-old residents in Hebei province.

Abstract Although beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, the underlying regulatory mechanisms remain unknown. Here, we elucidated an epigenetic pathway driven by microRNA regulation of β-EP synthesis in ARC neurons to control neuropathic pain. In pain-injured rats miR-203a-3p was the most highly upregulated miRNA in the ARC. A similar increase was identified in the cerebrospinal fluid of trigeminal neuralgia patients. Mechanistically, we found histone deacetylase 9 was downregulated following nerve injury, which decreased deacetylation of histone H3 lysine-18, facilitating the binding of NR4A2 transcription factor to the miR-203a-3p gene promoter, thereby upregulating miR-203a-3p expression. Further, increased miR-203a-3p was found to maintain neuropathic pain by targeting proprotein convertase 1, an endopeptidase necessary for the cleavage of proopiomelanocortin, the precursor of β-EP. The identified mechanism may provide an avenue for the development of new therapeutic targets for neuropathic pain treatment.