Background Height is an important anthropometric measurement and is associated with many health-related outcomes. Genome-wide association studies (GWASs) have identified hundreds of genetic loci ...associated with height, mainly in individuals of European ancestry. Methods We performed genome-wide association analyses and replicated previously reported GWAS-determined single nucleotide polymorphisms (SNPs) in the Taiwanese Han population (Taiwan Biobank; n = 67,452). A genetic instrument composed of 251 SNPs was selected from our GWAS, based on height and replication results as the best-fit polygenic risk score (PRS), in accordance with the clumping and p-value threshold method. We also examined the association between genetically determined height (PRS.sub.251) and measured height (phenotype). We performed observational (phenotype) and genetic PRS.sub.251 association analyses of height and health-related outcomes. Results GWAS identified 6843 SNPs in 89 genomic regions with genome-wide significance, including 18 novel loci. These were the most strongly associated genetic loci (EFEMP1, DIS3L2, ZBTB38, LCORL, HMGA1, CS, and GDF5) previously reported to play a role in height. There was a positive association between PRS.sub.251 and measured height (p < 0.001). Of the 14 traits and 49 diseases analyzed, we observed significant associations of measured and genetically determined height with only eight traits (p < 0.05/14 + 49). Height was positively associated with body weight, waist circumference, and hip circumference but negatively associated with body mass index, waist-hip ratio, body fat, total cholesterol, and low-density lipoprotein cholesterol (p < 0.05/14 + 49). Conclusions This study contributes to the understanding of the genetic features of height and health-related outcomes in individuals of Han Chinese ancestry in Taiwan. Keywords: Height, Genome-wide association studies, Genetic single nucleotide polymorphisms, Polygenic risk score, Health-related outcomes
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic inflammation caused by
infection increases the risk of developing gastric cancer. Even though the prevalence of
infection has been decreased in many regions, the development of antibiotic ...resistance strains has increased the difficulty of eradicating
. Therefore, exploring alternative approaches to combat
infection is required. It is well-known that probiotic therapy can improve
clearance. In this study,
-infected mice were treated with
P2 (P2),
L21 (L21),
JB3 (JB3), or a mixture including the aforementioned three (multi-LAB) for three days. All the lactic acid producing bacteria (LAB) treatments decreased
loads in the stomach and
gene expression,
specific immunoglobulin (Ig) A, and IgM levels in stomach homogenates, as well as serum levels of interferon-gamma and interleukin-1 beta. The multi-LAB and JB3 treatments further restored the superoxide dismutase and catalase activities suppressed by
infection. Furthermore,
infection decreased serum concentrations of 15 kinds of amino acids as well as palmitic acid. The multi-LAB treatment was able to recover the serum levels of alanine, arginine, aspartate, glycine, and tryptophan, which are all important in modulating immune functions. In addition, butyric acid, valeric acid, palmitic acid, palmitoleic acid, stearic acid, and oleic acid levels were increased. In this study, multi-LAB revealed its ability to adjust the composition of metabolites to improve health. To date, the mechanisms underlying how LAB strains crosstalk with the host are not fully understood. Identifying the mechanisms which are regulated by LABs will facilitate the development of effective therapies for infection in the future.
Autophagy, a double-edged sword for cell survival, is the research object on 2016 Nobel Prize in Physiology or Medicine. Autophagy is a molecular mechanism for maintaining cellular physiology and ...promoting survival. Defects in autophagy lead to the etiology of many diseases, including diabetes mellitus (DM), cancer, neurodegeneration, infection disease and aging. DM is a metabolic and chronic disorder and has a higher prevalence in the world as well as in Taiwan. The character of diabetes mellitus is hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and failure of producing insulin on pancreatic beta cells. In T2DM, autophagy is not only providing nutrients to maintain cellular energy during fasting, but also removes damaged organelles, lipids and miss-folded proteins. In addition, autophagy plays an important role in pancreatic beta cell dysfunction and insulin resistance. In this review, we summarize the roles of autophagy in T2DM.
To investigate immune profile consisting of stromal PD‐L1 expression, inhibitory or non‐T‐cell inflamed tumor microenvironment that may predict response to anti‐PD‐L1/PD‐1 immunotherapy in prostate ...cancer, we validated the specificity of a PD‐L1 monoclonal antibody (E1L3N) and identified PD‐L1 specific expression in prostatic stromal nerve cells. PD‐L1 expression was analyzed in 73 primary prostate cancers and 7 castration‐resistant prostate cancers (CRPC) by immunohistochemistry (IHC) and resulting data from primary prostate cancers were correlated with tumor‐associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome. PD‐L1 was expressed in the tumor cells in only one primary prostate cancer case and none of the CRPC. However, PD‐L1 was frequently observed in the nerve branches in the tumor‐associated stroma (69 of 73 cases, 94.5%), supported by colocalization with axonal marker PGP9.5. FoxP3‐, CD3‐ and CD8‐positive T lymphocytes were observed in 74.6% (47/63), 98.4% (62/63) and 100% (61/61) of the cases, respectively. The density of PD‐L1+ tumor‐associated nerves (TANs) was inversely correlated with that of CD8+ TALs. Higher density of PD‐L1+ TANs was significantly associated with biochemical recurrence (BCR) in Kaplan–Meier survival analysis (p = 0.016). In both univariate and multivariate Cox analysis, the density of PD‐L1+ TANs was independently prognostic of BCR. In conclusion, PD‐L1 expression is rare in prostate tumor cells but prevalent in TANs and negatively correlated with CD8+ TALs. Neuro‐immunological interaction may be a contribution to immune‐suppressive microenvironment. Combinatorial treatment regimen designs to neural PD‐L1 and TALs should be warranted in future clinical application of anti‐PD‐L1/PD‐1 immunotherapy in prostate cancer.
What's new?
Immunotherapies targeting programmed cell death protein 1 (PD‐1) and its ligand PD‐L1 display durable clinical benefit across various cancer types. However, an immunosuppressive tumor microenvironment has been suggested to underlie the resistance to anti‐PD‐L1/PD‐1 monotherapy in prostate cancer patients. This study investigates stromal PD‐L1 and its relationship with tumor‐associated lymphocytes (TALs) in prostate cancer. The findings indicate that PD‐L1 is expressed in tumor‐associated nerves (TANs) and that high density of PD‐L1+ TANs correlates with reduced CD8+ TALs and predicts poor prognosis of prostate cancer. Combinatorial treatment targeting neural PD‐L1 and TALs should be warranted in anti‐PD‐L1/PD‐1 immunotherapies for prostate cancer.
To help doctors and patients evaluate lumbar intervertebral disc degeneration (IVDD) accurately and efficiently, we propose a segmentation network and a quantitation method for IVDD from T2MRI. A ...semantic segmentation network (BianqueNet) composed of three innovative modules achieves high-precision segmentation of IVDD-related regions. A quantitative method is used to calculate the signal intensity and geometric features of IVDD. Manual measurements have excellent agreement with automatic calculations, but the latter have better repeatability and efficiency. We investigate the relationship between IVDD parameters and demographic information (age, gender, position and IVDD grade) in a large population. Considering these parameters present strong correlation with IVDD grade, we establish a quantitative criterion for IVDD. This fully automated quantitation system for IVDD may provide more precise information for clinical practice, clinical trials, and mechanism investigation. It also would increase the number of patients that can be monitored.
Conservation practices from the perspective of functional diversity (FD) and conservation prioritization need to account for the impacts of exotic species in freshwater ecosystems. This work first ...simulated the influence of exotic species on the values of FD in a schemed mechanistic model, and then a practical case study of conservation prioritization was performed in the Min River, the largest river in southeastern China, to discuss whether including exotic species alters prioritization. The mechanistic model revealed that exotic species significantly altered the expected FD if the number of exotic species occupied 2% of the community. Joint species distribution modelling indicated that the highest FD occurred in the west, northwest and north upstreams of the Min River. Values of FD in 64.69% of the basin decreased after the exotic species were removed from calculation. Conservation prioritization with the Zonation software proved that if first the habitats of exotic species were removed during prioritization, 62.75% of the highest prioritized areas were shifted, average species representation of the endemic species was improved and mean conservation efficiency was increased by 7.53%. Existence of exotic species will significantly alter the metrics of biodiversity and the solution for conservation prioritization, and negatively weighting exotic species in the scope of conservation prioritization is suggested to better protect endemic species. This work advocates a thorough estimate of the impacts of exotic species on FD and conservation prioritization, providing complementary evidence for conservation biology and valuable implications for local freshwater fish conservation.
摘要
从功能多样性 (FD)角度的生物多样性保护需要考虑淡水生态系统中外来物种的影响。本研究首先在预设的机械模型中模拟了外来物种对FD值的影响，然后以中国东南部最大的河流，即闽江为例，讨论了引入外来物种是否会改变鱼类多样性保护的优先级顺序。机械模型表明，如果外来物种的数量占群落的2%，则外来物种将显著改变FD的期望值。联合物种分布模型对鱼类物种的分布模拟表明，最高的FD值出现在闽江的西部、西北部和北部上游。剔除外来物种后，64.69%的流域中FD的值下降。Zonation优先级排序的结果表明，如果在优先排序过程中首先移除外来物种的栖息地，62.75%的最高优先级区域被转移，对本地物种的平均保护效率提高了7.53%，本地物种得到了更好的保护。外来物种的存在将显著改变生物多样性的衡量标准和保护优先级的排序结果；多样性保护优先级排序过程中优先剔除外来物种的核心栖息地，可以更好地保护本地物种。本研究建议在多样性保护工作中需完整评估对外来物种对FD的影响，并确定外来物种对保护优先级排序的影响，为本地淡水鱼类的保护提供补了有价值的信息。
The effect of hydrogen peroxide on the cell integrity of a cyanobacterium, Microcystis aeruginosa, and on the release and degradation of microcystins (MCs) under simulated sunlight was investigated. ...The cyanobacterium was exposed to H2O2 in the range of 0–60 mg·L–1 for 3.5 h. Production of OH radical in the solution was estimated by a chemical probe method. More than 99% (2 log) of the M. aeruginosa cells were ruptured or damaged by 3 h for all the treatments. Loss of cell integrity over time revealed two distinct phases. Cells retained their integrity during the initial lag phase and rapidly ruptured following first-order reaction afterward. A linear relationship was found between the duration of the lag phase and the steady-state concentration of OH radical. Release of MCs was closely correlated with the loss of cell integrity. Sequential reaction models were developed to simulate the release and degradation of MCs. These models were able to quantitatively describe the kinetics of all reactions under different H2O2 doses and extended exposure time. In particular, the models successfully predicted the concentration change of MCs using independently measured parameters. These models provide a simple and quantitative means to estimate the interaction of oxidants and cells and the consequent release of metabolites during oxidation treatment of cyanobacterium-laden waters.
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