Immunotherapy has become a promising alternative therapeutic approach for cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for cancer therapy in clinical trials. mAb targeting PD-L1 has been approved to treat urothelial carcinoma, non-small cell lung cancer, or Merkel cell carcinoma by the FDA. However, the high cost of the antibody can limit its application. In our study, targeting PD-L1 peptide (TPP-1), which specifically binds to PD-L1 with high affinity, was identified through bacterial surface display methods. Using a T-cell activation assay and mixed lymphocyte reaction, TPP-1 was verified to interfere with the interaction of PD-1/PD-L1. To examine the inhibitory effect of TPP-1 on tumor growth , a xenograft mouse model using H460 cells was established. The growth rate of tumor masses in TPP-1 or PD-L1 antibody-treated mice was 56% or 71% lower than that in control peptide-treated mice, respectively, indicating that TPP-1 inhibits, or at least retards, tumor growth. IHC of the tumors showed that IFNγ and granzyme B expression increased in the TPP-1 or PD-L1 antibody-treated groups, indicating that TPP-1 attenuates the inhibitory effect of PD-L1 on T cells and that T cells may get reactivated. On the basis of our data, TPP-1 peptide could work as an alternative to antibodies for tumor immunotherapy..
The metabolic consequences of obesity are well-documented in Western populations. However, limited data are available on the association between body mass index (BMI) and cardiovascular risk factors in developing countries. The authors therefore examined the association between BMI and cardiovascular risk factors in a very lean population in China. A total of 2,542 subjects aged 20-70 years from a rural area of Anqing, China, participated in a cross-sectional survey, and 1,610 provided blood samples in 1993. Mean BMI (kg/m2) was 20.7 for men and 20.9 for women. After adjustment for age, sex, education level, occupation, current alcohol use, and cigarette smoking, BMI was significantly associated with systolic and diastolic blood pressures (p < 0.0001). The adjusted odds ratio for hypertension (systolic pressure > or =140 mmHg or diastolic pressure > or = 90 mmHg) across quintiles of BMI (quintile medians: 18.0, 19.4, 20.6, 21.8, and 24.0) were 1.0, 1.34, 2.46, 2.61, and 4.90 (95% confidence interval: 3.20, 7.50). A higher BMI was directly associated with higher levels of serum total cholesterol, triglycerides, and fasting glucose and lower levels of high density lipoprotein cholesterol. These data from a very lean Chinese population confirm independent relations between body mass and cardiovascular risk factors observed in predominantly overweight Western populations and extend the range of associations to lower BMI levels than do previous studies.
A genomewide screen for quantitative-trait loci (QTLs) that underlie asthma was performed on 533 Chinese families with asthma, by the unified Haseman-Elston method. Nine asthma-related phenotypes were studied, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), airway responsiveness as indicated by methacholine (MTCH)-challenge test, serum total immunoglobulin E (TIgE), serum-specific immunoglobulin E, eosinophil count in peripheral blood, and skin-prick tests with three different allergens (cockroach, Dermatophagoides pteronyssinus, and D. farinae). Our study showed significant linkage between airway responsiveness to MTCH and D2S1780 on chromosome 2 (P<.00002) and provided suggestive evidence (P<.002) for six additional possible QTLs: D10S1435 and D22S685, for FEV1; D16S412, for FVC; D19S433, for airway responsiveness to MTCH; D1S518, for TIgE; and D4S1647, for skin reactivity to cockroach. No significant or suggestive evidence of linkage for the other four traits was found.
Our study suggested that the combined effect between HLA-Cw6 and cigarette smoking or stressful life events may play an important role in the development of psoriasis vulgaris in Han Chinese population.
The structure of the turbulence-driven power fluctuations in a wind farm is fundamentally described from basic concepts. A derived tuning-free model, supported with experiments, reveals the underlying spectral content of the power fluctuations of a wind farm. It contains two power-law trends and oscillations in the relatively low- and high-frequency ranges. The former is mostly due to the turbulent interaction between the flow and the turbine properties, whereas the latter is due to the advection between turbine pairs. The spectral wind-farm scale power fluctuations Φ_{P} exhibit a power-law decay proportional to f^{-5/3-2} in the region corresponding to the turbulence inertial subrange and at relatively large scales, Φ_{P}∼f^{-2}. Due to the advection and turbulent diffusion of large-scale structures, a spectral oscillation exists with the product of a sinusoidal behavior and an exponential decay in the frequency domain.
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