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Vaccination is crucial for the prevention and mitigation of avian influenza infections in China. The inactivated H7N9 vaccine, when administered to poultry, significantly lowers the risk of infection among both poultry and humans, while also markedly decreasing the prevalence of H7N9 detections. Highly pathogenic (HP) H7N9 viruses occasionally appear, whereas their low pathogenicity (LP) counterparts have been scarcely detected since 2018. However, these contributing factors remain poorly understood. We conducted an exploratory investigation of the mechanics via the application of comprehensive bioinformatic approaches. We delineated the Yangtze River Delta (YRD) H7N9 lineage into 5 clades (YRD-A to E). Our findings highlight the emergence and peak occurrence of the LP H7N9-containing YRD-E clade during the 5th epidemic wave in China's primary poultry farming areas. A more effective control of LP H7N9 through vaccination was observed compared to that of its HP H7N9 counterpart. YRD-E exhibited a tardy evolutionary trajectory, denoted by the conservation of its genetic and antigenic variation. Our analysis of YRD-E revealed only minimal amino acid substitutions along its phylogenetic tree and a few selective sweep mutations since 2016. In terms of epidemic fitness, the YRD-E was measured to be lower than that of the HP variants. Collectively, these findings underscore the conserved evolutionary patterns distinguishing the YRD-E. Given the conservation presented in its evolutionary patterns, the YRD-E LP H7N9 is hypothesized to be associated with a reduction following the mass vaccination in a relatively short period owing to its lower probability of antigenic variation that might affect vaccine efficiency.
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Evolución Molecular , Subtipo H7N9 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Aviar , Filogenia , Aves de Corral , Subtipo H7N9 del Virus de la Influenza A/genética , Subtipo H7N9 del Virus de la Influenza A/inmunología , Subtipo H7N9 del Virus de la Influenza A/clasificación , Subtipo H7N9 del Virus de la Influenza A/patogenicidad , Animales , Gripe Aviar/virología , Gripe Aviar/prevención & control , China/epidemiología , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/genética , Aves de Corral/virología , Vacunación Masiva , Gripe Humana/prevención & control , Gripe Humana/virología , Gripe Humana/epidemiología , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/prevención & control , Humanos , Pollos/virología , Variación Antigénica/genéticaRESUMEN
Animals such as raccoon dogs, mink and muskrats are farmed for fur and are sometimes used as food or medicinal products1,2, yet they are also potential reservoirs of emerging pathogens3. Here we performed single-sample metatranscriptomic sequencing of internal tissues from 461 individual fur animals that were found dead due to disease. We characterized 125 virus species, including 36 that were novel and 39 at potentially high risk of cross-species transmission, including zoonotic spillover. Notably, we identified seven species of coronaviruses, expanding their known host range, and documented the cross-species transmission of a novel canine respiratory coronavirus to raccoon dogs and of bat HKU5-like coronaviruses to mink, present at a high abundance in lung tissues. Three subtypes of influenza A virus-H1N2, H5N6 and H6N2-were detected in the lungs of guinea pig, mink and muskrat, respectively. Multiple known zoonotic viruses, such as Japanese encephalitis virus and mammalian orthoreovirus4,5, were detected in guinea pigs. Raccoon dogs and mink carried the highest number of potentially high-risk viruses, while viruses from the Coronaviridae, Paramyxoviridae and Sedoreoviridae families commonly infected multiple hosts. These data also reveal potential virus transmission between farmed animals and wild animals, and from humans to farmed animals, indicating that fur farming represents an important transmission hub for viral zoonoses.
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H5N1 is an avian influenza virus that causes respiratory disease in birds and several land and sea mammals. The recent outbreak in the United States, including infection of dairy workers, has increased the concern around potential transmission and spread. We asked virologists, epidemiologists, and public health experts what the most urgent questions and action points are at this stage of the outbreak.
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Brotes de Enfermedades , Subtipo H5N1 del Virus de la Influenza A , Gripe Aviar , Gripe Humana , Humanos , Gripe Humana/epidemiología , Gripe Humana/transmisión , Gripe Humana/virología , Animales , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Subtipo H5N1 del Virus de la Influenza A/genética , Estados Unidos/epidemiología , Gripe Aviar/virología , Gripe Aviar/transmisión , Gripe Aviar/epidemiología , Aves/virologíaRESUMEN
GaN HEMT devices are sensitive to the single event effect (SEE) caused by heavy ions, and their reliability affects the safe use of space equipment. In this work, a Ge ion (LET = 37 MeV·cm2/mg) and Bi ion (LET = 98 MeV·cm2/mg) were used to irradiate Cascode GaN power devices by heavy ion accelerator experimental device. The differences of SEE under three conditions: pre-applied electrical stress, different LET values, and gate voltages are studied, and the related damage mechanism is discussed. The experimental results show that the pre-application of electrical stress before radiation leads to an electron de-trapping effect, generating defects within the GaN device. These defects will assist in charge collection so that the drain leakage current of the device will be enhanced. The higher the LET value, the more electron-hole pairs are ionized. Therefore, the charge collected by the drain increases, and the burn-out voltage advances. In the off state, the more negative the gate voltage, the higher the drain voltage of the GaN HEMT device, and the more serious the back-channel effect. This study provides an important theoretical basis for the reliability of GaN power devices in radiation environments.
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Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.
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Aves , Salud Global , Virus de la Influenza A , Gripe Aviar , Gripe Humana , Zoonosis , Animales , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Gripe Humana/virología , Gripe Aviar/epidemiología , Gripe Aviar/virología , Aves/virología , Zoonosis/epidemiología , Zoonosis/virología , Virus de la Influenza A/genética , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/clasificación , Zoonosis Virales/epidemiología , Zoonosis Virales/transmisiónRESUMEN
Various low-density lipoprotein receptors (LPRs) have been identified as entry factors for alphaviruses, and structures of the corresponding virion-receptor complexes have been determined. Here, we analyze the similarities and differences in the receptor binding modes of multiple alphaviruses to understand their ability to infect a wide range of hosts. We further discuss the challenges associated with the development of broad-spectrum treatment strategies against a diverse range of alphaviruses.
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Alphavirus , Antivirales , Receptores de LDL , Internalización del Virus , Animales , Humanos , Alphavirus/efectos de los fármacos , Alphavirus/fisiología , Alphavirus/genética , Infecciones por Alphavirus/tratamiento farmacológico , Infecciones por Alphavirus/virología , Antivirales/uso terapéutico , Antivirales/farmacología , Unión Proteica , Receptores de LDL/metabolismo , Receptores de LDL/genética , Receptores Virales/metabolismo , Receptores Virales/química , Virión/metabolismo , Internalización del Virus/efectos de los fármacosRESUMEN
Getah virus (GETV) is a re-emerging mosquito-borne alphavirus that is highly pathogenic, mainly to pigs and horses. There are no vaccines or treatments available for GETV in swine in China. Therefore, the development of a simple, rapid, specific, and sensitive serological assay for GETV antibodies is essential for the prevention and control of GETV. Current antibody monitoring methods are time-consuming, expensive, and dependent on specialized instrumentation, and these features are not conducive to rapid detection in clinical samples. To address these problem, we developed immunochromatographic test strips (ICTS) using eukaryotically expressed soluble recombinant p62-E1 protein of GETV as a labelled antigen, which has good detection sensitivity and no cross-reactivity with other common porcine virus-positive sera. The ICTS is highly compatible with IFA and ELISA and can be stored for 1 month at 37 °C and for at least 3 months at room temperature. Hence, p62-E1-based ICTS is a rapid, accurate, and convenient method for rapid on-site detection of GETV antibodies. KEY POINTS: ⢠We established a rapid antibody detection method that can monitor GETV infection ⢠We developed colloidal gold test strips with high sensitivity and specificity ⢠The development of colloidal gold test strips will aid in the field serologic detection of GETV.
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Alphavirus , Anticuerpos Antivirales , Oro Coloide , Sensibilidad y Especificidad , Animales , Oro Coloide/química , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Alphavirus/inmunología , Porcinos , Cromatografía de Afinidad/métodos , Infecciones por Alphavirus/diagnóstico , Infecciones por Alphavirus/inmunología , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/virología , Tiras Reactivas , China , Ensayo de Inmunoadsorción Enzimática/métodosRESUMEN
Porcine reproductive and respiratory syndrome virus (PRRSV) infection inhibits swine leukocyte antigen class I (SLA-I) expression in pigs, resulting in inefficient antigen presentation and subsequent low levels of cellular PRRSV-specific immunity as well as persistent viremia. We previously observed that the non-structural protein 4 (nsp4) of PRRSV contributed to inhibition of the ß2-microglobulin (ß2M) and SLA-I expression in cells. Here, we constructed a series of nsp4 mutants with different combination of amino acid mutations to attenuate the inhibitory effect of nsp4 on ß2M and SLA-I expression. Almost all nsp4 mutants exogenously expressed in cells showed an attenuated effect on inhibition of ß2M and SLA-I expression, but the recombinant PRRSV harboring these nsp4 mutants failed to be rescued with exception of the rPRRSV-nsp4-mut10 harboring three amino acid mutations. However, infection of rPRRSV-nsp4-mut10 not only enhanced ß2M and SLA-I expression in both cells and pigs but also promoted the DCs to active the CD3+CD8+T lymphocytes more efficiently, as compared with its parental PRRSV (rPRRVS-nsp4-wt). These data suggested that the inhibition of nsp4-mediated ß2M downregulation improved ß2M/SLA-I expression in pigs.
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Regulación hacia Abajo , Antígenos de Histocompatibilidad Clase I , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Proteínas no Estructurales Virales , Microglobulina beta-2 , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/inmunología , Animales , Porcinos , Síndrome Respiratorio y de la Reproducción Porcina/virología , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Síndrome Respiratorio y de la Reproducción Porcina/genética , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/inmunología , Microglobulina beta-2/genética , Microglobulina beta-2/metabolismo , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/metabolismo , Antígenos de Histocompatibilidad Clase II/inmunología , Línea Celular , Linfocitos T CD8-positivos/inmunología , MutaciónRESUMEN
Cerebral small vessel disease (CSVD), as the most common, chronic and progressive vascular disease on the brain, is a serious neurological disease, whose pathogenesis remains unclear. The disease is a leading cause of stroke and vascular cognitive impairment and dementia, and contributes to about 20% of strokes, including 25% of ischemic strokes and 45% of dementias. Undoubtedly, the high incidence and poor prognosis of CSVD have brought a heavy economic and medical burden to society. The present treatment of CSVD focuses on the management of vascular risk factors. Although vascular risk factors may be important causes or accelerators of CSVD and should always be treated in accordance with best clinical practice, controlling risk factors alone could not curb the progression of CSVD brain injury. Therefore, developing safer and more effective treatment strategies for CSVD is urgently needed. Recently, mesenchymal stem cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of central nervous system disease, given their paracrine properties and immunoregulatory. Herein, we discussed the therapeutic potential of MSCs for CSVD, aiming to enable clinicians and researchers to understand of recent progress and future directions in the field.
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Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors have been identified for alphavirus entry; however, they cannot explain the broad host range and tissue tropism of certain alphaviruses, such as Getah virus (GETV), indicating the existence of additional receptors. Here we identify the evolutionarily conserved low-density lipoprotein receptor (LDLR) as a new cell entry factor for GETV, Semliki Forest virus (SFV), Ross River virus (RRV) and Bebaru virus (BEBV). Ectopic expression of LDLR facilitates cellular binding and internalization of GETV, which is mediated by the interaction between the E2-E1 spike of GETV and the ligand-binding domain (LBD) of LDLR. Antibodies against LBD block GETV infection in cultured cells. In addition, the GST-LBD fusion protein inhibits GETV infection both in vitro and in vivo. Notably, we identify the key amino acids in LDLR-LBD that played a crucial role in viral entry; specific mutations in the CR4 and CR5 domain of LDLR-LBD reduce viral entry to cells by more than 20-fold. These findings suggest that targeting the LDLR-LBD could be a potential strategy for the development of antivirals against multiple alphaviruses.
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Infecciones por Alphavirus , Alphavirus , Culicidae , Animales , Humanos , Alphavirus/genética , Internalización del Virus , Virus de los Bosques Semliki/genética , Virus de los Bosques Semliki/metabolismo , Infecciones por Alphavirus/genéticaRESUMEN
The retransmissions of SARS-CoV-2 from several mammals - primarily mink and white-tailed deer - to humans have raised concerns for the emergence of a new animal-derived SARS-CoV-2 variant to worsen the pandemic. Here, we discuss animal species that are susceptible to natural or experimental infection with SARS-CoV-2 and can transmit the virus to mates or humans. We describe cutting-edge techniques to assess the impact of a mutation in the viral spike (S) protein on its receptor and on antibody binding. Our review of spike sequences of animal-derived viruses identified nine unique amino acid exchanges in the receptor-binding domain (RBD) that are not present in any variant of concern (VOC). These mutations are present in SARS-CoV-2 found in companion animals such as dogs and cats, and they exhibit a higher frequency in SARS-CoV-2 found in mink and white-tailed deer, suggesting that sustained transmissions may contribute to maintaining novel mutations. Four of these exchanges, such as Leu452Met, could undermine acquired immune protection in humans while maintaining high affinity for the human angiotensin-converting enzyme 2 (ACE2) receptor. Finally, we discuss important avenues of future research into animal-derived viruses with public health risks.
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COVID-19 , Enfermedades de los Gatos , Ciervos , Enfermedades de los Perros , Animales , Perros , Gatos , Humanos , SARS-CoV-2/genética , Ciervos/metabolismo , Visón/metabolismo , Medición de Riesgo , Glicoproteína de la Espiga del Coronavirus/genética , Mutación , Unión ProteicaRESUMEN
Human coronavirus 229E (HCoV-229E) represents one of the known coronaviruses capable of infecting humans and causes mild respiratory symptoms. It is also considered to have a zoonotic source, originating from animals and being transmitted the humans. In this study, a comprehensive phylogenetic and codon usage analysis of the spike (S) gene of HCoV-229E was conducted. Utilizing phylogenetic analysis and principal component analysis, HCoV-229E was categorized into four distinct clusters, each demonstrating unique host affiliations. Furthermore, it was observed that the codon usage bias within the S gene of HCoV-229E is relatively low, primarily influenced by natural selection patterns, with contributions from mutation pressure and dinucleotide abundance. Comparative analysis involving Codon Adaptation Index (CAI) and Relative Codon Deoptimization Index (RCDI) revealed that the codon usage pattern of HCoV-229E mirrors more closely that of camels, as opposed to alpacas and humans. The elucidation of the codon usage pattern within HCoV-229E, which we have meticulously examined, offers valuable insights for a more comprehensive comprehension of viral features, history, and evolutionary trajectory.
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Coronavirus Humano 229E , Coronavirus , Animales , Humanos , Coronavirus Humano 229E/genética , Filogenia , Uso de Codones , Glicoproteína de la Espiga del Coronavirus/genética , Coronavirus/genéticaRESUMEN
Swine pathogens have a long history of zoonotic transmission to humans, occasionally leading to sustained outbreaks or pandemics. Through a retrospective epidemiological study of swine populations in China, we describe novel lineages of porcine hemagglutinating encephalomyelitis virus (PHEV) complex coronaviruses (CoVs) that cause exclusively respiratory symptoms with no signs of the neurological symptoms typically associated with classical PHEV infection. Through large-scale epidemiological surveillance, we show that these novel lineages have circulated in at least eight provinces in southeastern China. Phylogenetic and recombination analyses of twenty-four genomes identified two major viral lineages causing respiratory symptoms with extensive recombination within them, between them, and between classical PHEV and the novel respiratory variant PHEV (rvPHEV) lineages. Divergence times among the sampled lineages in the PHEV virus complex date back to 1886-1958 (mean estimate 1928), with the two major rvPHEV lineages separating approximately 20 years later. Many rvPHEV viruses show amino acid substitutions at the carbohydrate-binding site of hemagglutinin esterase (HE) and/or have lost the cysteine required for HE dimerization. This resembles the early adaptation of human CoVs, where HE lost its hemagglutination ability to adapt to growth in the human respiratory tract. Our study represents the first report of the evolutionary history of rvPHEV circulating in swine and highlights the importance of characterizing CoV diversity and recombination in swine to identify pathogens with outbreak potential that could threaten swine farming.
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IMPORTANCE: Alphaviruses threaten public health continuously, and Getah virus (GETV) is a re-emerging alphavirus that can potentially infect humans. Approved antiviral drugs and vaccines against alphaviruses are few available, but several host antiviral factors have been reported. Here, we used GETV as a model of alphaviruses to screen for additional host factors. Tetrachlorodibenzo-p-dioxin-inducible poly(ADP ribose) polymerase was identified to inhibit GETV replication by inducing ubiquitination of the glycoprotein E2, causing its degradation by recruiting the E3 ubiquitin ligase membrane-associated RING-CH8 (MARCH8). Using GETV as a model virus, focusing on the relationship between viral structural proteins and host factors to screen antiviral host factors provides new insights for antiviral studies on alphaviruses.
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Alphavirus , Interacciones Microbiota-Huesped , Proteínas de Transporte de Nucleósidos , Poli(ADP-Ribosa) Polimerasas , Transcriptoma , Humanos , Alphavirus/crecimiento & desarrollo , Alphavirus/inmunología , Glicoproteínas/metabolismo , Proteínas de Transporte de Nucleósidos/genética , Proteínas de Transporte de Nucleósidos/metabolismo , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , Ubiquitinación , Proteínas Estructurales Virales/metabolismo , Replicación ViralRESUMEN
Divergence time estimation is crucial to provide temporal signals for dating biologically important events from species divergence to viral transmissions in space and time. With the advent of high-throughput sequencing, recent Bayesian phylogenetic studies have analyzed hundreds to thousands of sequences. Such large-scale analyses challenge divergence time reconstruction by requiring inference on highly correlated internal node heights that often become computationally infeasible. To overcome this limitation, we explore a ratio transformation that maps the original $N-1$ internal node heights into a space of one height parameter and $N-2$ ratio parameters. To make the analyses scalable, we develop a collection of linear-time algorithms to compute the gradient and Jacobian-associated terms of the log-likelihood with respect to these ratios. We then apply Hamiltonian Monte Carlo sampling with the ratio transform in a Bayesian framework to learn the divergence times in 4 pathogenic viruses (West Nile virus, rabies virus, Lassa virus, and Ebola virus) and the coralline red algae. Our method both resolves a mixing issue in the West Nile virus example and improves inference efficiency by at least 5-fold for the Lassa and rabies virus examples as well as for the algae example. Our method now also makes it computationally feasible to incorporate mixed-effects molecular clock models for the Ebola virus example, confirms the findings from the original study, and reveals clearer multimodal distributions of the divergence times of some clades of interest.
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Algoritmos , Filogenia , Teorema de Bayes , Factores de Tiempo , Método de MontecarloRESUMEN
Fusion tag technology is an important tool for rapid separation, purification, and characterization of proteins. Combined with monoclonal antibodies, tag epitope systems can be rapidly adapted to many assay systems. A monoclonal antibody that reacts with the matrix protein of the rabies virus CVS-11 strain was reported. The epitope (termed M) targeted by this antibody contains only six amino acids. We examine whether this specific sequence epitope can be applied as a protein tag. We show ectopic expression of M-tagged proteins has little impact on cell viability or major signaling pathways. The M tag system can be used for western blotting, immunoprecipitation, immunofluorescence staining, and flow cytometry assays. The results indicate the specificity, sensitivity, and versatility of this novel epitope tag system are comparable to the widely used FLAG tag system, providing researchers with an additional tool for molecular analysis. KEY POINTS: ⢠A short peptide (Pro Pro Tyr Asp Asp Asp) can be applied as a new tag. ⢠The new epitope-tagging fusion system has no effect on the main cellular signaling pathway. ⢠The epitope-tagging fusion system can be widely used for western blotting, immunoprecipitation, immunofluorescence, flow cytometry, etc.
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Virus de la Rabia , Epítopos , Virus de la Rabia/genética , Péptidos/metabolismo , Anticuerpos Monoclonales , Western BlottingRESUMEN
Farmed mammals may act as hosts for zoonotic viruses that can cause disease outbreaks in humans. This SnapShot shows which farmed mammals, and to what extent, are of particular risk of harboring and spreading viruses from viral families that are commonly associated with zoonotic disease. It also discusses genome surveillance methods and biosafety measures. To view this SnapShot, open or download the PDF.
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Virus , Zoonosis , Animales , Humanos , Mamíferos , Brotes de Enfermedades , Medición de RiesgoRESUMEN
CONTEXT: Viscosity and viscosity index are the crucial properties of lubricant base stocks. Molecular dynamics simulation and quantum calculation were used to simulate the five isomers of C26H54 to study the intrinsic relationship between viscosity, viscosity index, and the molecular structure of isoalkanes. The results showed that the intermolecular interaction energy and the volume of rigid-like groups were the intrinsic factors that affected the viscosity and which could describe the viscosity quantitatively. The molecule conformation was studied by calculating the rotational energy barrier of the dihedral angle in the isoalkane molecule, and combined with molecular dynamics, the effect of temperature on the molecular conformation at 313 K and 373 K was further investigated. The α, ß, and γ carbon atoms adjacent to the tertiary carbon in the isoalkane molecule were difficult to rotate due to steric hindrance and could be regarded as rigid-like groups at 313 K. The tertiary carbon and the three adjacent carbon atoms formed a regular tetrahedral rigid-like group at 373 K. The changes in the intermolecular interaction energy and the volume of the rigid-like group with temperatures could better describe the viscosity index and reveal the fundamental reasons that affect the viscosity and the viscosity index. The molecular-level understanding of the relationship between the molecular structure and properties of isoalkanes provided theoretical support and scientific guidance for designing isoalkane molecules with specific properties. METHODS: Molecular dynamics simulation and quantum calculation were performed using Material Studio 8.0 software. The Amorphous Cell module was used to create an amorphous cell. The Foricite module was used for molecular dynamics simulation; the forcefield was assigned as COMPASS II. Nose-Hoover thermostat and Berendsen barostat were applied to maintain the temperature and pressure, respectively. To describe the non-bond interactions, the Ewald method was applied to calculate the van der Waals and electrostatic interactions. The Conformers module was used to study the conformation and the Dmol3 module was used to calculate the conformational energy with fine quality; the functional of GGA-PW91 and the basis set of DNP were used to calculate the energy.