Analysis of China's carbon market price fluctuation and international carbon credit financing mechanism using random forest model.

This study aims to investigate the price changes in the carbon trading market and the development of international carbon credits in-depth. To achieve this goal, operational principles of the international carbon credit financing mechanism are considered, and time series models were employed to forecast carbon trading prices. Specifically, an ARIMA(1,1,1)-GARCH(1,1) model, which combines the Generalized Autoregressive Conditional Heteroskedasticity (GARCH) and Autoregressive Integrated Moving Average (ARIMA) models, is established. Additionally, a multivariate dynamic regression Autoregressive Integrated Moving Average with Exogenous Inputs (ARIMAX) model is utilized. In tandem with the modeling, a data index system is developed, encompassing various factors that influence carbon market trading prices. The random forest algorithm is then applied for feature selection, effectively identifying features with high scores and eliminating low-score features. The research findings reveal that the ARIMAX Least Absolute Shrinkage and Selection Operator (LASSO) model exhibits high forecasting accuracy for time series data. The model's Mean Squared Error, Root Mean Squared Error, and Mean Absolute Error are reported as 0.022, 0.1344, and 0.1543, respectively, approaching zero and surpassing other evaluation models in predictive accuracy. The goodness of fit for the national carbon market price forecasting model is calculated as 0.9567, indicating that the selected features strongly explain the trading prices of the carbon emission rights market. This study introduces innovation by conducting a comprehensive analysis of multi-dimensional data and leveraging the random forest model to explore non-linear relationships among data. This approach offers a novel solution for investigating the complex relationship between the carbon market and the carbon credit financing mechanism.

Dataset of the land use pattern optimization in Horqin Sandy Land.

This dataset uses downloadable public datasets such as the Harmonized World Soil Database (HWSD) to account for ecosystem services such as net primary productivity (NPP) in Horqin Sandy Land in 2015 through ecological process models. The land use pattern of Horqin Sandy Land under three scenarios in 2025 was obtained by CLUMondo model. Based on the spatial distribution of ecosystem services in Horqin Sandy Land in 2015, the land use under three scenarios in 2025 was used as a variable to obtain the optimal pattern of ecosystem services in Horqin Sandy Land through Netica software. This dataset combines land use simulation with ecosystem service optimization, and can provide reference for decision makers and stakeholders to formulate ecosystem governance policies [1].

Hepatitis E vaccine candidate harboring a non-particulate immunogen of E2 fused with CRM197 fragment A.

The Hepatitis E vaccine (Hecolin, licensed in China) harbors a potent particulate immunogen, p239, designed from a 26-aa N-terminal extension of its poorly immunogenic parental protein, E2. Although an effective vaccine, we sought to design a fusion protein in a non-particulate form that could improve the delivery and immunogenicity of E2 epitopes. The non-toxic mutant of diphtheria toxin, CRM197 (Cross-Reacting Material 197) has been successfully used as a carrier protein for conjugated vaccines to enhance the immunogenicity of polysaccharides. Here, we designed a fusion non-particulate protein of E2 and the catalytic domain (fragment A) of CRM197 and evaluated its antigenicity, immunogenicity and disease prevention efficacy in primates. This fusion protein, named CRM197(A)-E2, was bacterially expressed and purified by chromatography. CRM197(A)-E2 presented as a homodimer in solution, similar to its parental E2 protein, and exhibited excellent antigenicity against representative neutralizing monoclonal antibodies, like E2 and p239. However, CRM197(A)-E2 manifested higher immunogenicity in mice compared with that achieved by the particulate p239, as indicated by the 10-times lower ED50 value and 2-log higher HEV-specific antibody level that could persist for at least 28 weeks. In addition, both the 1 µg and 10 µg doses of CRM197(A)-E2 adjuvanted with aluminum could protect vaccinated monkeys against HEV challenge, matching that achieved with only the higher (10 µg) dose of the p239 vaccine. These results suggest that the CRM197 fragment A alone serves as an intra-molecular adjuvant to remarkably enhance the immunogenicity of the target of interest in a non-particulate form. These findings may pave the way for rational vaccine design, especially in cases where particulates are not accessible.

Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) combine CpG oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B infection.

Hepatitis B virus infection is a non-cytopathic hepatotropic virus which can lead to chronic liver disease and hepatocellular carcinoma. Traditional therapies fail to provide sustained control of viral replication and liver damage in most patients. As an alternative strategy, immunotherapeutic approaches have shown promising efficacy in the treatment of chronic hepatitis B patients. Here, we investigated the efficacy of a novel therapeutic vaccine formulation consisting of two HBV antigens, HBsAg and HBcAg, and CpG adjuvant. This vaccine formulation elicits forceful humoral responses directed against HBsAg/HBcAg, and promotes a Th1/Th2 balance response against HBsAg and a Th1-biased response against HBcAg in both C57BL/6 and HBV transgenic mice. Vigorous cellular immune response was also detected in HBV transgenic mice, for a significantly higher number of HBs/HBc-specific IFN-γ secreting CD4+ and CD8+ T cells was generated. Moreover, vaccinated mice elicited significantly intense in vivo CTL attack, reduced serum HBsAg level without causing liver damage in HBV transgenic mice. In summary, this study demonstrates a novel therapeutic vaccine with the potential to elicit vigorous humoral and cellular response, overcoming tolerance in HBV transgenic mice.

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody.

Hepatitis E virus (HEV), a non-enveloped, positive-sense, single-stranded RNA virus, is a major cause of enteric hepatitis. Classified into the family Hepeviridae, HEV comprises four genotypes (genotypes 1-4), which belong to a single serotype. We describe a monoclonal antibody (mAb), 8G12, which equally recognizes all four genotypes of HEV, with ∼ 2.53-3.45 nM binding affinity. The mAb 8G12 has a protective, neutralizing capacity, which can significantly block virus infection in host cells. Animal studies with genotypes 1, 3 and 4 confirmed the cross-genotype neutralizing capacity of 8G12 and its effective prevention of hepatitis E disease. The complex crystal structures of 8G12 with the HEV E2s domain (the most protruded region of the virus capsid) of the abundant genotypes 1 and 4 were determined at 4.0 and 2.3 Šresolution, respectively. These structures revealed that 8G12 recognizes both genotypes through the epitopes in the E2s dimerization region. Structure-based mutagenesis and cell-model assays with virus-like particles identified several conserved residues (Glu549, Lys554 and Gly591) that are essential for 8G12 neutralization. Moreover, the epitope of 8G12 is identified as a key epitope involved in virus-host interactions. These findings will help develop a common strategy for the prevention of the most abundant form of HEV infection.

Structural basis for the neutralization and genotype specificity of hepatitis E virus.

Hepatitis E virus (HEV) causes acute hepatitis in humans, predominantly by contamination of food and water, and is characterized by jaundice and flu-like aches and pains. To date, no vaccines are commercially available to prevent the disease caused by HEV. Previously, we showed that a monoclonal antibody, 8C11, specifically recognizes a neutralizing conformational epitope on HEV genotype I. The antibody 8C11 blocks the virus-like particle from binding to and penetrating the host cell. Here, we report the complex crystal structure of 8C11 Fab with HEV E2s(I) domain at 1.9 Å resolution. The 8C11 epitopes on E2s(I) were identified at Asp(496)-Thr(499), Val(510)-Leu(514), and Asn(573)-Arg(578). Mutations and cell-model assays identified Arg(512) as the most crucial residue for 8C11 interaction with and neutralization of HEV. Interestingly, 8C11 specifically neutralizes HEV genotype I, but not the other genotypes. Because HEV type I and IV are the most abundant genotypes, to understand this specificity further we determined the structure of E2s(IV) at 1.79 Å resolution and an E2s(IV) complex with 8C11 model was generated. The comparison between the 8C11 complexes with type I and IV revealed the key residues that distinguish these two genotypes. Of particular interest, the residue at amino acid position 497 at the 8C11 epitope region of E2s is distinct among these two genotypes. Swapping this residue from one genotype to another inversed the 8C11 reactivity, demonstrating the essential role played by amino acid 497 in the genotype recognition. These studies may lead to the development of antibody-based drugs for the specific treatment against HEV.

Homology model and potential virus-capsid binding site of a putative HEV receptor Grp78.

P239, a truncated construct of the hepatitis E virus (HEV) ORF2 protein, has been proven able to bind with a chaperone, Grp78, in both an in vitro co-immune precipitation test and an in vivo cell model. We previously solved the crystal structure of E2s--the C-terminal domain of p239 involved in host interactions. In the present study, we built a 3D structure of Grp78 using homology modeling methods, and docked this molecule with E2s using the Zdockpro module of the InsightII software package. The modeled Grp78 structure was deemed feasible by profile 3D evaluation and molecular dynamic simulations. The docking result consists of six clusters of distinct complexes and C035 was selected as the most reasonable. The interacting interface of the predicted complex is comprised of the Grp78 linker region and nucleotide binding domain along with the E2s groove region and surrounding loops. Using energy, hydrogen bond and solvent accessible surface analyses, we identified a series of key residues that may be involved in the Grp78:E2s interaction. By comparing with the known structure of the Hsp70:J complex, we further concluded that the interaction of Grp78 and E2s could interrupt binding of Grp78 with the J domain, and in turn diminish or even eliminate the binding ability of the Grp78 substrate binding domain. The predicted series of key residues also provides clues for further research that should improve our understanding of the fundamental molecular mechanisms of HEV infection.