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Biomedical subjects

Jingping Yang

Publications and source records attributed to Jingping Yang.

10 recordsLinked to original sources

Locus-specific stratification and prioritization unveil genetic risk mechanism underlying complex diseases.

Although genome-wide association studies have identified thousands of disease-associated loci, the mechanistic understanding and drug target discovery remain challenging, particularly for complex diseases. The multi-signal architecture of complex diseases complicates the interpretation of genetic contributions. To address this challenge, we develop an approach comprising locus-specific stratification (LSS) and gene regulatory prioritization score (GRPS), which uniquely considers multi-signals during fine-mapping and target gene identification. LSS significantly enhances the interpretability of genetic risk associated with complex diseases. For loci associated with serum urate levels, the method identifies candidate causal genes in 34.43% of loci, surpassing the performance of other methods by 5.47% to 25.14%. GRPS considers the regulatory network of LSS-variants comprehensively and successfully nominates under-explored drug targets for hyperuricemia with high confidence such as SLC17A4, which is further validated using epigenetic activation and phenotypic assays. This study introduces an approach to efficiently and comprehensively address the multi-signal challenges in complex diseases.

Humans↗

Severe acute respiratory syndrome associated coronavirus is detected in intestinal tissues of fatal cases.

OBJECTIVES: A significant percentage of confirmed severe acute respiratory syndrome (SARS) patients experienced gastrointestinal symptoms, and the viral sequence was detectable in the stool of most patients. At present, the knowledge of the pathology of the digestive system in SARS patients is limited. Because a resurgence of the SARS epidemic is constantly possible, there is an urgent need to understand the involvement of the digestive system in this new disease. METHODS: We performed seven SARS autopsies in which samples of alimentary tract and digestive glands were examined with routine pathology, electron microscopy (EM), in situ hybridization (ISH), immunohistochemistry, and real-time polymerase chain reaction (PCR). RESULTS: The main histopathological finding was atrophy of the mucosal lymphoid tissue. A few mucosal epithelial cells and lymphocytes in the intestine were positively stained for coronavirus with ISH. SARS-coronavirus (CoV)-like particles were found in the mucosal epithelial cells under EM and mild focal inflammation was detected in the alimentary tract. One patient who experienced severe diarrhea had pseudomembranous enteritis of the ileum. Fatty degeneration and central lobular necrosis were observed in the liver. No evidence of direct viral infection was found in the esophagus, the stomach, the salivary gland, the liver, or the pancreas. CONCLUSIONS: In addition to the lungs, the gastrointestinal tract is another target of SARS-CoV infection, as the intestinal epithelial cells and mucosal lymphoid tissue are infected. The findings provide possible explanations for the gastrointestinal symptoms and the presence of virus in the stool of SARS patients.

Adult↗

[Farmland nitrogen loss and its control strategies from the view of water environment].

Nitrogen is a major factor in maintaining crop yield and getting better economic return, but its over-and unreasonable use may cause severe environmental pollution. From the view of water environment, this paper discussed the current effects of farmland nitrogen (N) loss on water pollution, the passes and mechanisms of farmland nitrogen loss, and its control strategies. To reduce the N surface runoff and leaching, effective measures should be taken, which include cutting down the paths from the source to transportation, and taking integrated measures to control N pollution. The BMPs (Best Management Practices) methods for N control suitable to China's situation were discussed on the basis of nitrogen source pollution rate.

Fertilizers↗

Antitumor efficacy and tumor-selective replication with a single intravenous injection of OAS403, an oncolytic adenovirus dependent on two prevalent alterations in human cancer.

A potentially promising treatment of metastatic cancer is the systemic delivery of oncolytic adenoviruses. This requires engineering viruses which selectively replicate in tumors. We have constructed such an oncolytic adenovirus, OAS403, in which two early region genes are under the control of tumor-selective promoters that play a role in two key pathways involved in tumorigenesis. The early region E1A is controlled by the promoter for the E2F-1 gene, a transcription factor that primarily upregulates genes for cell growth. The E4 region is under control of the promoter for human telomerase reverse transcriptase, a gene upregulated in most cancer cells. OAS403 was evaluated in vitro on a panel of human cells and found to elicit tumor-selective cell killing. Also, OAS403 was less toxic in human hepatocyte cultures, as well as in vivo when compared to an oncolytic virus that lacked selective E4 control. A single intravenous injection of 3 x 10(12) vp/kg in a Hep3B xenograft mouse tumor model led to significant antitumor efficacy. Additionally, systemic administration in a pre-established LNCaP prostate tumor model resulted in over 80% complete tumor regressions at a tolerable dose. Vector genome copy number was measured in tumors and livers at various times following tail vein injection and showed a selective time-dependent increase in tumors but not livers over 29 days. Furthermore, efficacy was significantly improved when OAS403 treatment was combined with doxorubicin. This virus holds promise for the treatment of a broad range of human cancers including metastatic disease.

Adenoviridae↗

[Dynamics of three kinds of nitrogen in surface water of rice field with an independent irrigation system].

Studies on the dynamics of NH4+, NO3- and TN concentrations in the surface water of paddy field with an independent irrigation system showed that the concentration of NH4+ and TN in surface water was increased to the maximum after 1day of each urea application, and then decreased rapidly with time. The ratio of NH4+/TN, NO3-/TN and (NH4+ + NO3-)/TN was increased firstly, and then decreased. NH4+ and TN could be used as the main indexes for the water pollution of the paddy field, and NO3- used as the assistant one. There existed a positive relation between the concentration of these three kinds of nitrogen and N application amount. Nine days after urea application was the key time to prevent the gross loss of the three kinds of nitrogen in the water surface of the paddy field. The simulation expressions of NH4+ and TN with time factor could be exponential, logarithmic, power or binomial, while NO3- had no appropriate expression. The simulation with factors of time and N application amount showed that the simulation expressions of NH4+ and TN were the same.

Ammonia↗

[Dynamic modeling of potato phenological development].

By means of systematic demonstration, this study found the mathematical relationship among several temperature driven nonlinear models for crop growth, and amended the limitation of the past nonlinear model in biological usage and the improved model with more general definition. Integrated with four years' field experimental data and Gauss function based temperature effectiveness model submitted in this study, the phenological development model for potato crop was established under different ecological conditions. The phenological development model explained the digital contribution of soil temperature increment on potato growth, and verified by the experimental data from different years and different conditions. There were strict co-relationships between modeling data and experimental data.

Computer Simulation↗

[Effects of different pH values of fixatives and antigen retrieval buffers on immunohistochemical staining].

OBJECTIVE: To evaluate the influence of pH values of fixatives and antigen retrieval buffers on immunostains. METHODS: Samples of normal skin, gastric mucosa, uteri leiomyoma and breast carcinoma were fixed in buffered formalin with different pH values, namely 3.0, 5.0, 7.0, 8.0 and 10.0 to detect EMA, SMA, ER and CK (AE1/AE3) expression. Evinision two-step method was employed. Antigen retrieval was achieved by microwave using sodium citrate solution with pH 6.0, 7.0, 8.0 or pH 8.0 EDTA solution respectively. RESULTS: The number and intensity of positive cells varied due to different conditions. The change of positive cell's number is important for CK (AE1/AE3) expression, and the change of positive intensity is important for SMA and EMA expression. CONCLUSIONS: (1) The best results could be obtained by the use of 10% neutral or alkalescent buffered formalin. (2) Antigen retrieval effect is better in the solution of pH 7.0, 8.0 than in that of pH 6.0. EDTA(pH 8.0) appears better for skin. The best effect of Estrogen Receptor needs pH 8.0 sodium citrate solution. (3) The background could be easily induced by the fixative over pH 8.0. Antigen retrieval solution over pH 8.0 could result in detachment.

Buffers↗

New cationic lipids form channel-like pores in phospholipid bilayers.

Two representatives of a new class of cationic lipids were found to have high pore-forming activity in planar bilayer membranes. These molecules, called BHHD-TADC and BHTD-TADC, have qualitatively similar effects on phospholipid membranes. Addition of 2.5-5 micro M of either of them to the membrane bathing solutions resulted in formation of long-lived anion-selective pores with conductance in the range 0.1-2 nS in 0.1 M KCl. Pore formation was found to be dependent on the potential applied to the membrane. When negative potential was applied to membrane at the side of addition, the rate of pore formation was much lower compared to when the positive potential was applied. Dependence of pore formation on compound concentration was highly nonlinear, indicating that this process requires assembly of molecules in the membrane. Addition of any of these compounds on both sides of the membrane increased the efficiency of pore formation by one to two orders of magnitude. Pore formation was strongly pH dependent. Although pores were formed with high efficiency at pH 6.5, only occasional fluctuations of membrane conductance were observed at pH 7.5. Possible mechanisms of new compounds biological activity are discussed.

Cations↗

[Dynamic simulation of nitrogen application level effects on rice yield and optimization analysis of fertilizer supply in paddy field].

Field and water tank plot experiments were conducted in Zhejiang Province in 1999 to determine the effects of nitrogen application amount and times on rice growth and yield, and rice growth simulation model ORYZA-0 and nitrogen management module were used to establish a modified nitrogen effect-rice growth model. The simulated results presented a higher positive relationship with the measured results. According to the simulated and measured results, 160 kg.hm-2 was the economic nitrogen application amount for two rice varieties production, and the nitrogen application strategies were: 1) < 100 kg.hm-2 nitrogen fertilizer should be applied within 35 days after transplanting; 2) when the nitrogen application level was between 100-200 kg.hm-2, it should be applied within 45 days after transplanting; 3) if the nitrogen application amount exceeded 200 kg.hm-2, it should be put into paddy field within 60 days after transplanting; 4) as the nitrogen application amount increased, the nitrogen supply at the later rice growth stage should be increased. As for the second cropping rice, the more times the nitrogen applied in the field, the more closeness the rice yield reached the APCUM curve(optimized nitrogen curve) suggested. But in real rice production, it is impossible for farmers to adopt more times of N applying, since labor and cost will increase. Based on the experimental parameters and real rice production situation, the reasonable nitrogen application under 160 kg.hm-2 levels for high yielding second cropping rice was split into 4 times with fraction 0.2:0.3:0.3:0.2 at 5, 20, 30, 40 days after transplanting. The rice yield could reach 5,916 kg.hm-2, resulted in a 3.12% increase as compared with the yield under actual fertilizer application amount and timing.

Crops, Agricultural↗