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Human nasal mucosa is susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and serves as a reservoir for viral replication before spreading to other organs (e.g. the lung and brain) and transmission to other individuals. Chronic rhinosinusitis (CRS) is a common respiratory tract disease and there is evidence suggesting that susceptibility to SARS-CoV-2 infection differs between the two known subtypes, eosinophilic CRS and non-ECRS (NECRS). However, the mechanism of SARS-CoV-2 infection in the human nasal mucosa and its association with CRS has not been experimentally validated. In this study, we investigated whether the human nasal mucosa is susceptible to SARS-CoV-2 infection and how different endotypes of CRS impact on viral infection and progression. Primary human nasal mucosa tissue culture revealed highly efficient SARS-CoV-2 viral infection and production, with particularly high susceptibility in the NECRS group. The gene expression differences suggested that human nasal mucosa is highly susceptible to SARS-CoV-2 infection, presumably due to an increase in ACE2-expressing cells and a deficiency in antiviral immune response, especially for NECRS. Importantly, patients with NECRS may be at a particularly high risk of viral infection and transmission, and therefore, close monitoring should be considered.

Aillikites are carbonate-rich ultramafic lamprophyres, and although they are volumetrically minor components of large igneous province (LIP), these rocks provide important clues to melting and meta-somatism in the deep mantle domain during the initial stages of LIPs. In this study, we investigate the Wajilitag “kimberlites” in the northwestern part of the Tarim LIP that we redefine as hypabyssal aillikites based on the following features: (1) micro-phenocrystic clinopyroxene and Ti-rich andradite garnet occurring in abundance in the carbonate-rich matrix; (2) Cr-spinel exhibiting typical Fe-Ti enrichment trend also known as titanomagnetite trend; and (3) olivine showing dominantly low Mg values (Fo < 90). To constrain the magma source and evolution, the major, minor, and trace element abundance in olivine grains from these rocks were analyzed using electron microprobe and laser ablation-inductively coupled plasma-mass spectrometry. Olivine in the aillikites occurs as two textural types: (1) groundmass olivines, as sub-rounded grains in matrix, and (2) macrocrysts, as euhedral-anhedral crystals in nodules. The groundmass olivines show varying Mg (Fo89–80) with high-Ni (1606–3418 ppm) and Mn (1424–2860 ppm) and low-Ca (571–896 ppm) contents. In contrast, the macrocrysts exhibit a restricted Fo range but a wide range in Ni and Mn. The former occurs as phenocrysts, whereas the latter are cognate cumulates that formed from earlier, evolved aillikite melt. The two olivine populations can be further divided into sub-groups, indicating a multi-stage crystallization history of the aillikite melt. The crystallization temperatures of groundmass olivines and macrocrysts in dunite nodules as computed from the spinel-olivine thermometers are 1005–1136 and 906–1041 °C, respectively. The coupled enrichment of Ca and Ti and lack of correlation between Ni and Sc and Co in the olivine grains suggest a carbonate-silicate metasomatized mantle source. Moreover, the high 100·Mn/Fe (average 1.67) at high Ni (up to 3418 ppm), overlapping with OIB olivine, and the 100·Ni/Mg (~1) of primitive Mg-Ni-rich groundmass olivines suggest a mixed source that involved phlogopite- and carbonate-rich metasomatic veins within mantle peridotite.

Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential. The main reason is that malignant glioma holds key cluster cells, glioma stem cells (GSCs). GSCs contribute to tumorigenesis, tumor progression, recurrence, and treatment resistance. Interferon-beta (IFN-β) is well known for its anti-proliferative efficacy in diverse cancers. IFN-β also displayed potent antitumor effects in malignant glioma. IFN-β affect both GSCs and Neural stem cells (NSCs) in the treatment of gliomas. However, the functional comparison, similar or different effects of IFN-β on GSCs and NSCs are rarely reported. Here, we studied the similarities and differences of the responses to IFN-β between human GSCs and normal NSCs. We found that IFN-β preferentially inhibited GSCs over NSCs. The cell body and nucleus size of GSCs increased after IFN-β treatment, and the genomic analysis revealed the enrichment of the upregulated immune response, cell adhesion genes and down regulated cell cycle, ribosome pathways. Several typical cyclin genes, including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), and cyclin D1 (CCND1), were significantly downregulated in GSCs after IFN-β stimulation. We also found that continuous IFN-β stimulation after passage further enhanced the inhibitory effect. Our study revealed how genetic diversity resulted in differential effects in response to IFN-β treatment. These results may contribute to improve the applications of IFN-β in anti-cancer immunotherapy. In addition, these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.

The Tarim large igneous province (TLIP) comprises a complex suite of lithologies including voluminous ferrobasalts, although the petrogenetic relation of these rocks is still poorly understood. In this study, we report the chemical compositions of olivine in two types of olivine pyroxenites (porphyritic and coarse-grained) from the Wajilitag mafic-ultramafic intrusion in the northwestern TLIP, aiming to characterize the mantle sources of magmas. Olivine in the porphyritic olivine pyroxenites shows low 100 * Mn/Fe (∼1.3) and Mn/Zn ( 1.9) and Mn/Zn (>14), suggesting a heterogeneous mantle source beneath the Wajilitag area. The low olivine V/Sc values (

Extracellular vesicles from adipose derived stem cells (ADSCs-EVs) have shown immunomodulation and anti-photoaging effects; however, the skin barrier prevents their absorption via skin. Meanwhile, microneedle (MN) is a widely used and minimally invasive tool for dermal delivery of drugs, it also has neocollagenesis effect by creating tiny injuries and initiating wound healing process. To investigate the effect of MN combined with ADSCs-EVs on skin aging, photoaging in SKH-1 mice was induced by chronic exposure to ultraviolet radiation. Then the mice were treated following a split-dorsal scheme, in which one side had MN alone or MN + EVs treatment and the other side was left untreated. For the side treated with MN alone or MN + EVs, the epidermal thickness was decreased and the skin barrier function was enhanced compared with the untreated side. However, MN + EVs group showed the least wrinkles, the highest collagen density and the most organized collagen fibers among the three groups. The level of CD11b + cell infiltration was lower in MN + EVs group than that in the MN group at 3 day after the treatment. These results indicated that MN treatment alone could improve epidermal structure and function of photoaging skin, and a combination with ADSCs-EVs would accelerate the restoration of inflammation caused by MN and improve the content of collagen. In all, this study indicated that a combination of MN and topical applied ADSCs-EVs was a feasible and safe strategy to ameliorate photoaging, providing a new avenue for safe administration of EVs.

BackgroundMalignant Glioma is considered to be a highly heterogeneous brain tumor, which may have originated from mutated neural stem cells (NSCs) many years before it was diagnosed. Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential. The main reason is that malignant glioma holds a key cluster cells, glioma stem cells (GSCs). GSCs contribute to tumorigenesis, tumor progression, recurrence, and treatment resistance. Interferon-beta (IFN-β) is well known for its anti-proliferative efficacy in diversity cancers. IFN-β also displayed potent antitumor results in malignant glioma. IFN-β treatments administered in response to gliomas affect both GSCs and NSCs. However, the function comparison, similarities and differences of IFN-β on GSCs and NSCs are rarely reported. MethodsWe used human GSCs and NSCs to detect the response difference between two cells by IFN-β. Human GSCs were constructed by ourselves and human normal NSCs line were differentiated from human embryonic stem cells. Various concentrations of IFN-β were separately used to treat human GSCs (hGSCs) and human NSCs (hNSCs). Cell morphology, growth, expression of special stemness genes, neural-related makers or proliferation related genes were staining and observed, such as SRY-box transcription factor 2 (Sox2), S100 calcium binding protein B (S100-beta) and marker of proliferation Ki-67 (Ki67). Genetic alterations were carefully analyzed by RNA-seq. We used repetitive stimulation treatment and compared the different response between hGSCs and hNSCs with IFN-β. Genomic analysis was also performed to identify genes with changes in expression levels in hGSCs but stable expression levels in hNSCs. ResultsWe found that IFN-β preferentially inhibited GSCs rather than NSCs. The cell body and nucleus size of GSCs increased after IFN-β treatment. The expression of special stemness gene Sox2 and marker of proliferation Ki67 significantly decreased. S100-beta, which was a central nervous system enrichment, cycle progression and differentiation related gene, also reduced after IFN-β treatment. Significant differences were observed between hGSCs and human NSCs after continuous IFN-β treatment. Genomic analysis revealed the enrichment of the immune response, cell adhesion, cell cycle, and ribosome pathways such as proto-oncogene NF-kB subunit ( RELB ), TRAF interacting protein with forkhead associated domain ( TIFA ), nuclear factor kappa B subunit 1 ( NFKB )and signal transducer and activator of transcription 6 ( STAT6 ). Several typical cyclin genes, including cyclin A2 ( CCNA2) , cyclin B1 ( CCNB1) , cyclin B2 ( CCNB2) , and cyclin D1 ( CCND1) , were significantly downregulated in GSCs after IFN-β stimulation. ConclusionsOur study revealed how genetic diversity resulted in differential effects in response to IFN-β treatment. These results may contribute to improve the applications of IFN-β anti-cancer immunotherapy. In addition, these results may also help to design more effective pharmacological strategies to target killing cancer stem cells while protecting normal neural stem cells.

Although human adipose derived stem cells (hADSCs) hold great promises for regenerative medicine, their key biological properties remain poorly understood. In particular, proliferation defects resulted from deep quiescence (dormancy) and senescence represent a major hurdle in hADSC production and clinical application. We have developed a model system for mechanistic dissection of hADSC quiescence and senescence. p57

The emergence of drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has brought great difficulties to clinical treatment. Antibacterial photodynamic therapy (aPDT) is a new non-antibiotic treatment strategy for a variety of drug-resistant bacteria. However, there are few studies on the antimicrobial mechanism of a PDT mediated by 5-aminolevulinic acid (ALA-PDT) for MRSA. In this study, we observed the bactericidal effect of ALA-PDT on MRSA. We found that ALA-PDT had the strongest bactericidal effect when ALA was at 0.05 mM, and the bactericidal activity of aPDT increased with the increase of light dose. MRSA was almost completely eliminated at 0.05 mM and 384 Jcm−2. In addition, the bactericidal morphology was also observed under a fluorescence microscope using a LIVE/DEAD® BacLight™ Bacterial Viability Kit and an electron microscope. It was also found that proteins and DNA were damaged by ALA-PDT. Finally, the transcription level of the specific gene of MRSA, nuc, was decreased by 0.74-fold (P

Mafic dyke swarms are important bar codes for the rifting and breakup of supercontinents. Here we report a Neoproterozoic mafic (ferrodoleritic) dyke swarm from the Aksu area along the northern margin of the Tarim Craton, NW China. Zircon U-Pb analyses of two dyke samples yielded ages of 801 ± 9 Ma and 804 ± 13 Ma. The ferrodoleritic dykes show high total FeO (11.55–14.55 wt%) and TiO2 contents (2.84–3.26 wt%) and variable SiO2 (47.90–52.74 wt%). They display positive anomalies of Rb, Ba, K and negative anomalies of Nb, Ta, Ti and the enrichment of light rare earth elements relative to heavy rare earth elements. The whole-rock eNd(t) values (–5.4 to –7.2) indicate a relatively homogeneous and enriched magma source. Trace element modelling suggests that the ferrodoleritic dykes were generated by low degree of partial melting (garnet lherzolite 3–5%, pyroxenite 5–10%) of a mixed mantle source (60% garnet lherzolite and 40% pyroxenite). The results from our study suggest two major mafic magma pulses at ca. 830–800 Ma and ca. 780–750 Ma during the Neoproterozoic, which we correlate to the onset of Rodinia supercontinent breakup.

Although human adipose derived stem cells (hADSCs) hold great promises for regenerative medicine, their key biological properties remain poorly understood. In particular, proliferation defects resulted from deep quiescence (dormancy) and senescence represent a major hurdle in hADSC production and clinical application. We have developed a model system for mechanistic dissection of hADSC quiescence and senescence. p57Kip2, a major CDK inhibitor, was highly expressed in quiescent and senescent hADSCs but its level quickly declined upon stem cell activation. p57Kip2 overexpression induced quiescence in spite of proliferative signals and its knockdown promoted cell cycle reentry even with induction of quiescence presumably through modulating the CDK2-CyclinE1 complex. Given its key role in quiescence and senescence, p57Kip2 may be exploited for innovative strategies to amplify hADSCs of high quality for clinics.

Platinum-based chemotherapy–induced peripheral neuropathy is one of the most common causes of dose reduction and discontinuation of life-saving chemotherapy in cancer treatment; it often causes permanent impairment of quality of life in cancer patients. The mechanisms that underlie this neuropathy are not defined, and effective treatment and prevention measures are not available. Here, we demonstrate that SIRT2 protected mice against cisplatin-induced peripheral neuropathy (CIPN). SIRT2 accumulated in the nuclei of dorsal root ganglion sensory neurons and prevented neuronal cell death following cisplatin treatment. Mechanistically, SIRT2, an NAD(+)-dependent deacetylase, protected neurons from cisplatin cytotoxicity by promoting transcription-coupled nucleotide excision repair (TC-NER) of cisplatin-induced DNA cross-links. Consistent with this mechanism, pharmacological inhibition of NER using spironolactone abolished SIRT2-mediated TC-NER activity in differentiated neuronal cells and protection of neurons from cisplatin-induced cytotoxicity and CIPN in mice. Importantly, SIRT2’s protective effects were not evident in lung cancer cells in vitro or in tumors in vivo. Taken together, our results identified SIRT2’s function in the NER pathway as a key underlying mechanism of preventing CIPN, warranting future investigation of SIRT2 activation–mediated neuroprotection during platinum-based cancer treatment.

Insect pests have developed resistance to chemical insecticides, insecticidal toxins as bioinsecticides or genetic protection built into crops. Consequently, novel, orally active insecticidal toxins would be valuable biological alternatives for pest control. Here, we identified a novel insecticidal toxin, parasporal crystal toxin (PC), from Bacillus bombysepticus (Bb). PC shows oral pathogenic activity and lethality towards silkworms and Cry1Ac-resistant Helicoverpa armigera strains. In vitro assays, PC after activated by trypsin binds to BmAPN4 and BtR-175 by interacting with CR7 and CR12 fragments. Additionally, trypsin-activated PC demonstrates cytotoxicity against Sf9 cells expressing BmAPN4, revealing that BmAPN4 serves as a functional receptor that participates in Bb and PC pathogenicity. In vivo assay, knocking out BtR-175 increased the resistance of silkworms to PC. These data suggest that PC is the first protein with insecticidal activity identified in Bb that is capable of causing silkworm death via receptor interactions, representing an important advance in our understanding of the toxicity of Bb and the contributions of interactions between microbial pathogens and insects to disease pathology. Furthermore, the potency of PC as an insecticidal protein makes it a good candidate for inclusion in integrated agricultural pest management systems.

Bombyx mori nucleopolyhedrovirus (BmNPV) is the primary pathogen of silkworms, causing severe economic losses in sericulture. To create antiviral silkworm strains, we constructed a transgenic vector in which the dsRNA for five tandem BmNPV genes was controlled by the BmNPV hr3 enhancer and IE1 promoter. The antivirus gene Bmlipase-1 was driven by B. mori midgut-specific promoter P2. Transgenic strains (SW-H) were generated via embryo microinjection using the practical silkworm strain SW. After infection with a high dose of BmNPV, the survival rates of SW-H and non-transgenic SW were 64% and 13%, respectively. SW-H could be the first transgenic animal that is highly antiviral and that might inhibit the virus at multiple stages of infection.

Bacillus bombysepticus is a Gram-positive spore-forming bacterium. Here, we announce the first complete genome sequence of this organism isolated from the cadavers of silkworm larvae that had been sick. The genome contains a single circular chromosome and a circular plasmid. Analyses of the B. bombysepticus genome will provide insights into its pathomechanisms and biology.

The rat sarcoma-extracellular signal regulated kinase mitogen-activated protein kinases pathway, one of the most ancient signaling pathways, is crucial for the defense against Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Sprouty (Spry) proteins can inhibit the activity of this pathway by receptor tyrosine kinases. We cloned and identified a new B. mori gene with a Spry domain similar to the Spry proteins of other organisms, such as fruitfly, mouse, human, chicken, Xenopus and zebrafish, and named it BmSpry. The gene expression analysis showed that BmSpry was transcribed in all of the examined tissues and in all developmental stages from embryo to adult. BmSpry also induced expression of BmNPV in the cells. Our results indicated: (1) the knock-down of BmSpry led to increased BmNPV replication and silkworm larvae mortality; (2) over-expression of BmSpry led to reduced BmNPV replication; and (3) BmSpry regulated the activation of ERK and inhibited BmNPV replication. These results showed that BmSpry plays a crucial role in the antiviral defense of the silkworm both in vitro and in vivo.

Aminopeptidases N (APNs), the receptors of Bacillus thuringiensis (Bt) toxin in the lepidopteran midgut, are involved in the Bt pathogen infection mechanism. In the present work, we screened 102 APNs from SilkDB, ButterflyBase and MonarchBase; 16 APNs were identified from the silkworm (Bombyx mori) and 24 from the monarch butterfly (Danaus plexippus). Syntenic and phylogenetic tree analysis showed that APN genes have developed multi-family genes before evolutionary divergence of the Lepidoptera. The tissue-expression pattern shows some BmAPNs are specifically or highly expressed in the midgut. Bacillus bombysepticus (Bb) is a specific pathogen of B. mori, leading to acute fuliginosa septicemia of the larva. BmAPNs were modulated by real time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis after Bb or Bt oral infection. There were different patterns of induced expression between Bb and Bt challenges, suggesting that B. mori has different responses to infection by the specific pathogen Bb and the nonspecific pathogen Bt. Research on BmAPNs will help us to better understand the evolutionary conservation and functions in Bb or Bt pathogen interaction with the host and to apply this knowledge in agricultural and forestry pest control.

Bacterial pathogens and their toxins target host receptors, leading to aberrant behavior or host death by changing signaling events through subversion of host intracellular cAMP level. This is an efficient and widespread mechanism of microbial pathogenesis. Previous studies describe toxins that increase cAMP in host cells, resulting in death through G protein-coupled receptor (GPCR) signaling pathways by influencing adenylyl cyclase or G protein activity. G protein-coupled receptor kinase 2 (GRK2) has a central role in regulation of GPCR desensitization. However, little information is available about the pathogenic mechanisms of toxins associated with GRK2. Here, we reported a new bacterial toxin-Bacillus bombysepticus (Bb) α-toxin that was lethal to host. We showed that Bb α-toxin interacted with BmGRK2. The data demonstrated that Bb α-toxin directly bound to BmGRK2 to promote death by affecting GPCR signaling pathways. This mechanism involved stimulation of Gαs, increase level of cAMP and activation of protein kinase A (PKA). Activated cAMP/PKA signal transduction altered downstream effectors that affected homeostasis and fundamental biological processes, disturbing the structural and functional integrity of cells, resulting in death. Preventing cAMP/PKA signaling transduction by inhibitions (NF449 or H-89) substantially reduced the pathogenicity of Bb α-toxin. The discovery of a toxin-induced host death specifically linked to GRK2 mediated signaling pathway suggested a new model for bacterial toxin action. Characterization of host genes whose expression and function are regulated by Bb α-toxin and GRK2 will offer a deeper understanding of the pathogenesis of infectious diseases caused by pathogens that elevate cAMP., Author Summary Interference with regulation of host signaling by pathogens can alter gene expression, leading to functional disarray in the host cells that causes abnormal division or death. Here, we propose a previously undescribed model for how bacterial toxins subvert host processes via interaction with GRK2 that influences cAMP/PKA signaling. Our findings provide new fundamental information about how bacterial pathogens regulate host signal transduction to cause death, which offers additional perspectives in host-pathogen systems. These findings will help to advance our understanding of bacteria pathogenic mechanism. Furthermore, these might extend to other microbial pathogenesis and assist in designing new or safer strategies against pathogens.

Several pathogenic microorganisms have been used to investigate the genome-wide transcriptional responses of Bombyx mori to infection. However, studies have so far each focused on one microorganism, and systematic genome-wide comparison of transcriptional responses to different pathogenic microorganisms has not been undertaken. Here, we surveyed transcriptional responses of B. mori to its natural bacterial, viral, and fungal pathogens, Bacillus bombyseptieus, B. mori nucleopolyhedrovirus (BmNPV), and Beauveria bassiana, respectively, and to nonpathogenic Escherichia coli, by microarray analysis. In total, the expression of 2,436, 1,804, 1,743, and 912 B. mori genes was modulated by infection with B. bombyseptieus, BmNPV, B. bassiana, and E. coli, respectively. Notably, the expression of 620, 400, 177, or 165 of these genes was only modulated by infection with B. bombyseptieus, BmNPV, B. bassiana, or E. coli, respectively. In contrast to the expression of genes related to juvenile hormone synthesis and metabolism, that of genes encoding juvenile hormone binding proteins was microorganism-specific. Three basal metabolic pathways were modulated by infection with any of the four microorganisms, and 3, 14, 5, and 2 metabolic pathways were specifically modulated by infection with B. bombyseptieus, BmNPV, B. bassiana, and E. coli, respectively. Interestingly, BmNPV infection modulated the JAK/STAT signaling pathway, whereas both the Imd and Toll signaling pathways were modulated by infection with B. bombyseptieus, B. bassiana, or E. coli. These results elucidate potential molecular mechanisms of the host response to different microorganisms, and provide a foundation for further work on host–pathogen interaction.

Bombyx mori nucleopolyhedrovirus (BmNPV) is the primary pathogen affecting B. mori. This virus could be combated via RNAi of BmNPV genes in transgenic silkworm. However, several factors may affect the resistance of transgenic RNAi silkworm, such as the connection pattern of gene fragments and spacers ("head to head" or "tail to tail"), and the selection of promoters and target genes. In this study, we constructed several transgenic RNAi vectors using different phase genes (ie-1, helicase, gp64, and vp39) and promoters (BmNPV IE1 promoter (IE1P), IE1P combined with hr3 enhancer of BmNPV, and B. mori A4 promoter (A4P)). Transgenic lines were generated via embryo microinjection using a practical silkworm strain. We analyzed the anti-BmNPV ability, virus gene mRNA level, and BmNPV content of these transgenic larvae. The results showed that "head to head" was better than "tail to tail," IE1P combined with hr3 was better than IE1P and A4P, and an immediate early gene was the best target for RNAi.

The hycu-ep32 gene of Hyphantria cunea NPV can inhibit Bombyx mori nucleopolyhedrovirus (BmNPV) multiplication in co-infected cells, but it is not known whether the overexpression of the hycu-ep32 gene has an antiviral effect in the silkworm, Bombyx mori. Thus, we constructed four transgenic vectors, which were under the control of the 39 K promoter of BmNPV (39 KP), Bombyx mori A4 promoter (A4P), hr3 enhancer of BmNPV combined with 39 KP, and hr3 combined with A4P. Transgenic lines were created via embryo microinjection using practical diapause silkworm. qPCR revealed that the expression level of hycu-ep32 could be induced effectively after BmNPV infection in transgenic lines where hycu-ep32 was controlled by hr3 combined with 39 KP (i.e., HEKG). After oral inoculation of BmNPV with 3 × 10(5) occlusion bodies per third instar, the mortality with HEKG-B was approximately 30% lower compared with the non-transgenic line. The economic characteristics of the transgenic lines remained unchanged. These results suggest that overexpression of an exogenous antiviral gene controlled by an inducible promoter and enhancer is a feasible method for breeding silkworms with a high antiviral capacity.

Transgenic technology is a powerful tool for improving disease-resistant species. Bmlipase-1, purified from the midgut juice of Bombyx mori, showed strong antiviral activity against B. mori nucleopolyhedrovirus (BmNPV). In an attempt to create an antiviral silkworm strain for sericulture, a transgenic vector overexpressing the Bmlipase-1 gene was constructed under the control of a baculoviral immediate early-1 (IE1) promoter. Transgenic lines were generated via embryo microinjection. The mRNA level of Bmlipase-1 in the midguts of the transgenic line was 27.3 % higher than that of the non-transgenic line. After feeding the silkworm with different amounts of BmNPV, the mortality of the transgenic line decreased to approximately 33 % compared with the non-transgenic line when the virus dose was 10(6) OB/larva. These results imply that overexpressing endogenous antiviral genes can enhance the antiviral resistance of silkworms.

One of the important issues which steel enterprises focus on is to reduce the cost occurred in unloading process of ocean-going ship, based on the overseas procurement background of a famous steel enterprise, the unloading problem with random arrival times is investigated in this paper, the cost construction of unloading problem is analyzed and its mathematical models for deterministic and stochastic arrival time are established, respectively. Moreover, Lagrangian relaxation algorithm and genetic algorithm combined with sub-gradient is designed to solve this problem. Finally, some examples are simulated and illustrated to validate the effectiveness and accuracy of the proposed algorithm.