Quantum computing promises to offer substantial speed-ups over its classical counterpart for certain problems. However, the greatest impediment to realizing its full potential is noise that is ...inherent to these systems. The widely accepted solution to this challenge is the implementation of fault-tolerant quantum circuits, which is out of reach for current processors. Here we report experiments on a noisy 127-qubit processor and demonstrate the measurement of accurate expectation values for circuit volumes at a scale beyond brute-force classical computation. We argue that this represents evidence for the utility of quantum computing in a pre-fault-tolerant era. These experimental results are enabled by advances in the coherence and calibration of a superconducting processor at this scale and the ability to characterize
and controllably manipulate noise across such a large device. We establish the accuracy of the measured expectation values by comparing them with the output of exactly verifiable circuits. In the regime of strong entanglement, the quantum computer provides correct results for which leading classical approximations such as pure-state-based 1D (matrix product states, MPS) and 2D (isometric tensor network states, isoTNS) tensor network methods
break down. These experiments demonstrate a foundational tool for the realization of near-term quantum applications
.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Avian reovirus (ARV), which commonly induces viral arthritis or tenosynovitis and immunosuppression in chickens, is associated with the nonstructural protein p17 that plays a crucial role in viral ...replication and regulates cellular signaling pathways through its interaction with cellular proteins. In our previous study, we identified the host protein IFN-γ-inducible protein-16 (IFI16) as an interacting partner of ARV p17 through yeast two-hybrid screening. In the current study, we further confirmed the interaction between IFI16 and p17 protein using coimmunoprecipitation, glutathione S-transferase (GST)-pulldown assay, and laser confocal microscopy techniques. Additionally, we found that the amino acid of p1761-119 is responsible for mediating the interaction with the HINa and HINb domains of IFI16. Interestingly, we observed a significant increase in IFI16 expression upon ARV infection or p17 protein exposure. Moreover, the replication of ARV was found to be largely influenced by the quantity of IFI16 protein. Overexpression of IFI16 led to a significant decrease in ARV replication, while knockdown of the IFI16 expression led to the contrary result. Additionally, our findings demonstrate that IFI16 plays a crucial role in the induction of inflammatory cytokines IFN-β and IL-1β during ARV infection as confirmed by qRT-PCR and ELISA analyses. In conclusion, our study provides novel insights into the functional role of p17 protein and the pathogenic mechanism underlying ARV infection, particularly its association with inflammatory response. Furthermore, it offers new perspectives for identifying potential therapeutic targets against ARV infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Avian infectious bronchitis (IB) causes great economic losses to the chicken industry worldwide. IB virus (IBV) exhibits extensive variability, and differing serotypes are often prevalent in ...different countries or regions. Therefore, the identification of local circulating strains is essential for the selection of appropriate vaccines. China is a worldwide leader in poultry meat and egg production, and IBV is one of the most important infectious diseases affecting this industry. In this review, the history and current IB occurrence in China, as well as the development and use of vaccines, are summarized. Based on recent epidemics, reasonable vaccination strategies are recommended, and some inadequate measures commonly used in the field are analyzed.
Infectious coryza (IC) is an acute infectious upper respiratory disease in chickens. Recently, the prevalence of IC has increased in China. In this study, to clarify the pathogenic mechanism and ...innate immune response of Avibacterium paragallinarum (A. paragallinarum), an infection experiment with A. paragallinarum was conducted. Our results showed that the whole course of IC was approximately 7 d. The clinical signs score was highest at 3 dpi and decreased from 5 dpi. A large amount of mucus and exudates was found in the infraorbital sinuses and nasal cavity. The A. paragallinarum contents in blood remained the highest, reaching 9.16 × 105 CFU/g at 5 dpi, which indicated that A. paragallinarum could rapidly invade the host, replicate in the blood and cause bacteremia. A. paragallinarum targets the upper respiratory tract. The infiltration of inflammatory cells, macrophages, and heterophilic granulocytes was only observed in the nasal cavity and infraorbital sinus. The Tlr4 and Nod1 pathways were activated and induced proinflammatory responses in chickens after infection with A. paragallinarum. The expression of Il1β and Il6 in the nasal cavity was significantly higher than that in the spleen, and it was consistent with the gross lesions and pathological changes. In particular, the expression of Il6 increased 229.07-fold at 1 dpi in the nasal cavity and increased 3.12-fold in the spleen. The high level of proinflammatory cytokines in the nasal cavity at an early stage of infection may be the main factor related to acute upper respiratory inflammation in chickens. These findings provide a reference for the occurrence and development of diseases mediated by A. paragallinarum.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The cellular mitophagy induced by CSFV NS5A protein.•CSFV NS5A induce mitophagy correlate with ROS production.•Mitophagy promote CSFV replication.
The classical swine fever virus (CSFV) is one of ...the most harmful pathogens of swine and causes considerable economic loss. Mitophagy is a selective form of autophagy that degrades damaged mitochondria by combining with lysosomes. Previous studies have been reported that CSFV infection can induce mitophagy, but which effector protein is responsible for this process remains unclear. Herein, we revealed here that the CSFV nonstructural protein 5A (NS5A) plays a critical role in inducing cellular mitophagy. Specifically, the expression of CSFV NS5A in the PK-15 cells induces membrane potential loss and mitochondrial fission, and the quantities of mitophagosomes, the expression of Parkin and PINK1 were significantly increased compared with mock cells. Intriguingly, we found that Parkin-overexpression promotes CSFV propagation. Furthermore, the expression level of reactive oxygen species (ROS) was increased by CSFV NS5A protein, while NS5A-induced mitophagy correlated with the quantity of ROS production. In summary, our results reveal a new function of NS5A in inducing cellular mitophagy and broaden our understanding of the mechanism of CSFV-induced mitophagy, which may provide a new way to develop an antiviral strategy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bacillus subtilis
(
B. subtilis
) has a variety of proposed beneficial effects for chickens, including growth promotion and disease prevention. In this study, chickens were fed a diet containing
B. ...subtilis
for 21 days and growth performance, intestinal morphology, intestinal microbiota, immune responses, and disease resistance were investigated. After 21 days of feeding, chickens fed a diet containing
B. subtilis
had higher body weights. The concentrations of serum immunoglobulins IgA and IgM were significantly increased by
B. subtilis
in the diet. Moreover, chickens fed with
B. subtilis
had greater villus height (VH), shallower crypt depth (CD), and a higher VH/CD ratio in the jejunum than chickens fed a standard control diet. Diet with
B. subtilis
can balance intestinal microbiota, facilitate an increase in beneficial bacteria, and inhibit the pathogenic bacteria after 21 days of feeding. After an
Escherichia coli
(
E. coli
) challenge, the survival rate of chickens fed with
B. subtilis
was 66.67%, which was significantly higher than the controls. The
E. coli
contents in spleens and lungs from chickens fed a diet with
B. subtilis
were lower than those in controls. In addition,
B. subtilis
can trigger the toll-like receptor 4 and cause induction of proinflammatory cytokine (
Il1
β,
Il6
, and
Il8
) production to develop innate immune responses in chickens. In conclusion, diets containing
B. subtilis
can improve growth performance, serum immunoglobulin levels, the intestinal villus-crypt system, intestinal homeostasis, immune responses, and disease resistance against
E. coli
in chickens.
Lacticaseibacillus rhamnosus
is a recognized probiotic that is widely used in scientific research and clinical applications. This study found that the
Lacticaseibacillus rhamnosus
GG (LGG) strain can ...reduce the adhesion of
Escherichia coli
(
E. coli
) to primary chicken intestinal epithelial cells by 75.7% and inhibit 41.7% of the
E. coli
that adhere to intestinal epithelial cells. Additionally, LGG showed strong inhibitory ability on the growth of
E. coli
,
Staphylococcus aureus
,
Salmonella
Paratyphi B, and
Salmonella
Enteritidis
in vitro
. Furthermore, the influence of LGG on the growth performance, intestinal flora, immunity, and disease resistance of chickens was explored. Chickens fed with LGG exhibited increased average daily weight gain and concentrations of sIgA, IgG, and IgM than did controls. After 21 days of feeding, a diet with LGG increased the diversity of intestinal microbiota and maintained intestinal health. Moreover, LGG promoted immunologic barriers by upregulating cytokines and chemokines via the Toll-like receptor. The major pro-inflammatory factors, including
Myd88
,
NF-
κ
B
,
Il6
, and
Il8
, were upregulated compared to controls. After being challenged with
E. coli
, the survival rate of chickens fed with LGG was significantly higher than those in the control group, and decreased numbers of
E. coli
were detected in the heart and lungs of the LGG group. In summary, oral administration of LGG to chickens could improve growth performance, maintain intestinal homeostasis, and enhance innate immune response and disease resistance.
Avian reovirus (ARV) causing viral arthritis/tenosynovitis and viral enteritis in domestic fowl has significantly threatened on the poultry industry worldwide. ARV is a non-enveloped fusogenic virus ...that belongs to the Reoviridae family. Previous research revealed that cellular cholesterol in lipid rafts is essential for ARV replication. It has been reported that cholesterol 25-hydroxylase (CH25H) and its product 25-hydroxycholesterol (25HC) have antiviral activities against enveloped viruses. However, few studies characterized the association of non-enveloped viruses with CH25H and the role of CH25H in the regulation of ARV replication. In this study, the expression of chicken CH25H (chCH25H) was found to be upregulated in ARV-infected cells at the early stage of infection. The results of overexpression and knockdown assays revealed that chCH25H has a significant antiviral effect against ARV infection. Furthermore, a 25HC treatment significantly inhibited ARV replication in a dose-dependent manner at both the entry and post-entry stages, and a chCH25H mutant lacking hydroxylase activity failed to inhibit ARV infection. These results indicate that CH25H, depending on its enzyme activity, exerts the antiviral effect against ARV via the synthesis of 25HC. In addition, we revealed that 25HC produced by CH25H inhibits viral entry by delaying the kinetics of ARV uncoating, and CH25H blocks cell-cell membrane fusion induced by the p10 protein of ARV. Altogether, our findings showed that CH25H, as a natural host restriction factor, possessed antiviral activity against ARV targeting viral entry and syncytium formation, through an enzyme activity-dependent way. This study may provide new insights into the development of broad-spectrum antiviral therapies.
Classical swine fever is a world organization for animal health listed disease and is caused by classical swine fever virus (CSFV). CSFV can induced unfolded protein response (UPR) and whether NS5A ...protein plays a role in this process remains unknown. Here, we demonstrate that CSFV induced all the three signal pathways ATF6, IRE1 and PERK of UPR. Furthermore, this phenomenon may be mediated by the NS5A protein since expression of NS5A alone can achieve the same effect. In the current study, we show that NS5A can interact with GRP78 as measured by using the CO-IP and GST pulldown assays. This interaction plays a positive role in the promotion of CSFV replication. Overexpression or knockdown of GRP78 mediated by lentivirus can enhance or decrease viral replication, respectively. Our findings provide the evidence that CSFV infection can activate the cellular UPRs, in which NS5A and GRP78 play key roles in the process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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