Discovery and preclinical evaluation of KYS202004A, a novel bispecific fusion protein targeting TNF-α and IL-17A, in autoimmune disease models.

The treatment of autoimmune and inflammatory diseases often requires targeting multiple pathogenic pathways. KYS202004A is a novel bispecific fusion protein designed to antagonize TNF-α and IL-17A, pivotal in the pathophysiology of autoimmune and inflammatory diseases. Our initial efforts focused on screening for optimal structure by analyzing expression levels, purity, and binding capabilities. The binding affinity of KYS202004A to TNF-α and IL-17A was evaluated using SPR. In vitro, we assessed the inhibitory capacity of KYS202004A on cytokine-induced CXCL1 expression in HT29 cells. In vivo, its efficacy was tested using a Collagen-Induced Arthritis (CIA) model in transgenic human-IL-17A mice and an imiquimod-induced psoriasis model in cynomolgus monkeys. KYS202004A demonstrated significant inhibition of IL-17A and TNF-α signaling pathways, outperforming the efficacy of monotherapeutic agents ixekizumab and etanercept in reducing CXCL1 expression in vitro and ameliorating disease markers in vivo. In the CIA model, KYS202004A significantly reduced clinical symptoms, joint destruction, and serum IL-6 concentrations. The psoriasis model revealed that KYS202004A, particularly at a 2  mg/kg dose, was as effective as the combination of ixekizumab and etanercept. This discovery represents a significant advancement in treating autoimmune and inflammatory diseases, offering a dual-targeted therapeutic approach with enhanced efficacy over current monotherapies.

Comparison of surface wind speed and wind speed profiles in the Taklimakan Desert.

Near-surface (10 m) wind speed (NWS) plays a crucial role in many areas, including the hydrological cycle, wind energy production, and the dispersion of air pollution. Based on wind speed data from Tazhong and the northern margins of the Taklimakan Desert in Xiaotang in spring, summer, autumn, and winter of 2014 and 2015, statistical methods were applied to determine the characteristics of the diurnal changes in wind speed near the ground and the differences in the wind speed profiles between the two sites. The average wind speed on a sunny day increased slowly with height during the day and rapidly at night. At heights below 4 m the wind speed during the day was higher than at night, whereas at 10 m the wind speed was lower during the day than at night. The semi-empirical theory and Monin-Obukhov (M-O) similarity theory were used to fit the NWS profile in the hinterland of the Tazhong Desert. A logarithmic law was applied to the neutral stratification wind speed profile, and an exponential fitting correlation was used for non-neutral stratification. The more unstable the stratification, the smaller the n. Using M-O similarity theory, the "linear to tens of" law was applied to the near-neutral stratification. According to the measured data, the distribution of φ M with stability was obtained. The γm was obtained when the near-surface stratum was stable in the hinterland of Tazhong Desert and the ßm was obtained when it was unstable. In summer, γ m and ßm were 5.84 and 15.1, respectively, while in winter, γm and ßm were 1.9 and 27.1, respectively.

Observational Study of Ground-Level Ozone in the Desert Atmosphere.

Arid lands such as deserts cover more than 35% of the Earth's land surface. Concerns regarding ground-level O3 pollution have been widely addressed in many regions in China, but the behavior of the O3 cycles in the desert atmosphere remains poorly understood. An 8-year observation was conducted to investigate the long-term temporal O3 variations in the atmosphere of the Taklimakan Desert, western China. The results showed that the diurnal and seasonal variations of O3 were mainly influenced by natural processes such as temperature, leading to a different temporal pattern compared with other Chinese regions under the intensive influence of anthropogenic activities. Moreover, the long-term pattern indicates that there exists decoupling trends of O3 variations between our study site (i.e., decreasing trend) and the developed regions in China (i.e., increasing trend). Knowledge of the temporal O3 patterns could therefore provide crucial insights for future effective O3 control strategies in China.

Application of a High-Precision Aeolian Sand Collector in Field Wind and Sand Surveys.

Sand collectors are important for quantitatively monitoring aeolian sand activities. In this paper, an automatic high-precision sand collector was designed. Based on the measured data of aeolian transport performed with a piezoelectric saltation sensor (H11-Sensit) and a 10 m high meteorological tower, the sampling efficiency of the automatic sand sampler and the horizontal dust flux of the near surface were analyzed based on observed data. The results were as follows: the best-fitting function between the number of impacting sand particles and the amount of collected sand was a linear relationship. The average value of R2 was 0.7702, and the average sand collection efficiency of the sand collector at a height of 5 cm was 94.3%, indicating good sand collection performance. From all field tests conducted so far, it appeared that a high-precision sand sampler was a useful device for making field measurements of horizontal dust fluxes and ascertaining the relationship between transition particles and wind speed. In the future, the equipment costs and wind drive will continue to be optimized.

Insights into the Molecular Basis of the Acute Contact Toxicity of Diverse Organic Chemicals in the Honey Bee.

Use of chemical pollutants, including pesticides and other industrial chemicals, has resulted in significant risks to the whole ecosystem. Therefore, ecological risk assessment of chemicals is vital and necessary. Since the honey bee (Apis mellifera) is probably among the most exposed species to the polluting chemicals, we focused on the in silico estimation of honey bee toxicity (HBT) of chemicals and the analysis of the relevance of chemical HBT and several key physical-chemical properties and structural characteristics. A total of 40 classification models were developed by combination of five machine learning methods along with seven kinds of fingerprints and a set of molecular descriptors. After 5-fold cross validation and external validation, several models showed good predictive power. The relevance of 12 key physical-chemical properties and chemical HBT was also investigated. Five properties, including AlogP, logD, molecular weight (MW), molecular surface area (MSA), and the number of rotatable bonds (nRTB), indicated positive correlation coefficients with HBT, while molecular solubility (logS) and the number of hydrogen bond donors (nHBD) indicated negative correlation coefficients. Finally, seven privileged substructures responsible for chemical HBT were identified from KRFP and SubFP fingerprints. The results of this study should provide critical information and useful tools for chemical HBT estimation in environmental risk assessment.

Experimental infections of mosquitoes with severe fever with thrombocytopenia syndrome virus.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified emerging infectious disease, which is caused by a novel bunyavirus (termed SFTSV) in Asia. Although mosquitoes have not been identified as the primary vectors, as revealed by epidemiological surveys, their role in transmitting this SFTSV as a suspicious vector has not been validated. FINDINGS: In this study, we conducted experimental infections of mosquitoes with SFTSV to examine the role of mosquitoes in the transmission of the virus. We did not detect viral replication in Culex pipiens pallens, Aedes aegyptis and Anopheles sinensis as revealed by qRT-PCR assay. In addition, we failed to isolate SFTSV from the Vero cells cultured with suspensions of SFTSV-infected mosquitoes. CONCLUSION: The results of the present study demonstrate little possibility that mosquitoes act as vectors for the emerging pathogen SFTSV.

Japanese Encephalitis Virus Infection Rate and Detection of Genotype I From Culex tritaeniorhynchus Collected From Jiangsu, China.

Information regarding the infection rate and genotype shifts for Japanese encephalitis virus (JEV) are important for JE vaccine application. In Jiangsu province, China, which is one of the provinces with a high prevalence of JE, JEV infection in swine and mosquitoes in certain cities has only been investigated in 2008-2009. Lianyungang City has one of the highest numbers of JE cases in Jiangsu province, and it has a high risk of JEV invasion via migrant birds. JEV infection in vectors in Lianyungang City, which has urban and rural parts, has not been investigated. In 2015-2016, we collected mosquitoes in cowsheds with ultraviolet light traps and detected JEV by reverse transcription-polymerase chain reaction (RT-PCR) method in Culex tritaeniorhynchus in Xintan village, Xuzhuang village, and Xiaogaozhuang village in Lianyungang City, China. The proportion of positive pools, which is calculated by the number of infected pools to the total number of pools tested in these villages, were 16.67%, 20.00%, and 4.17%, respectively, and the minimum infection rates, which is calculated as the ratio of the number of positive pools to the total number of mosquitoes tested, were 3.33‰, 4.00‰, and 0.83‰, respectively. Four JEV strains from positive samples were coded as LYG-1, LYG-2, LYG-3, and LYG-4, and the complete E genes were sequenced. Furthermore, the complete genome of LYG-3 was sequenced. The phylogenetic analysis indicated that all the four JEV strains belonged to genotype I-b. This is the first report of genotype I JEV strain in Jiangsu province. The high JEV infection rate in Culex tritaeniorhynchus indicated a high risk of JE reemergence in Lianyungang. The detected JEV strains may have similar antigenicity to that of SA14-14-2 according to molecular characters. These findings suggest that the vaccine can still be effective in Lianyungang.

An Unmanned Aerial Vehicle-Mounted Cold Mist Spray of Permethrin and Tetramethylfluthrin Targeting Aedes albopictus in China.

Aedes albopictus is the primary vector of dengue fever and dengue hemorrhagic fever in China. Although there are previous studies on the application of adulticides to control this species, the application methods have either been back-pack or vehicle-mounted systems. However, many sites are too large to be effectively treated with back-pack sprayers, and the lack of roads restricts the use of vehicle-mounted sprayers. This paper provides the first study of using unmanned aerial vehicles to conduct cold mist sprays on Ae. albopictus habitats. A spray containing 4% permethrin and 1% tetramethylfluthrin was applied at an effective application rate of 9.0 mg/m(2). This method reduced Ae. albopictus populations by more than 90%. The results indicate this novel spray system is a powerful method to achieve a rapid decline of mosquito population in Ae. albopictus habitats in China.

[Construction and in vitro assay of the sortase BCD geneknock-out mutant of Streptococcus suis 2].

OBJECTIVE: Streptococcus suis 2 is an emerging zoonotic pathogen responsible for a wide range of life-threatening diseases in pigs and humans. In this study, we investigated the functionality of one of Streptococcus suis 2 sortases, known as the srtBCD. METHODS: To obtain the isogenic mutant srtBCD, the competent cells of 05ZYH33 were subjected to electrotrans formation with recombinant plasmid based on the principle of homologous recombination. The resulting mutant strains was further confirmed by a series of PCR and reverse transcription PCR. To better assess the role of srtBCD gene in the virulence of 05ZYH33, cell adherence assays and experimental infection of mice was adopted. RESULTS: A SrtBCD defective mutant of 05ZYH33 was found to be associated with growth curve upon cultivation in standard laboratory used in our in vitro assays. Furthermore, abolishment of the expression of srtBCD result in impaired interactions of S. suis with human laryngeal epithelial cell line. However, there is no differences when infection mice by the WT and mutant strain. CONCLUSION: These results suggest that srtBCD are critical for the pathogen-host interaction of S. suis 2, but abolishment of srtBCD does not impair the full virulence of 05ZYH33. It is to expect that future study carried out with S. suis 2 to verification the conclusions.