Genome-wide association study on serum alkaline phosphatase levels in a Chinese population

Background: Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated. Results: The association between ABO locus and serum ALP levels was replicated (P = 2.50 × 10-21, 1.12 × 10-56 and 2.82 × 10-27 for SNP rs8176720, rs651007 and rs7025162 on ABO locus, respectively). SNP rs651007 accounted for 2.15% of the total variance of serum ALP levels independently of the other 2 SNPs. When comparing our findings with previously published studies, ethnic differences were observed across populations. A significant interaction between ABO rs651007 and overweight and obesity was observed (FDR for interaction was 0.036); for individuals with GG genotype, those with normal weight and those who were overweight or obese have similar serum ALP concentrations; minor allele A of rs651007 remarkably reduced serum ALP levels, but this effect was attenuated in overweight and obese individuals. Conclusions: Our findings indicate that ABO locus is a major determinant for serum ALP levels in Chinese Han population. Overweight and obesity modifies the effect of ABO locus on serum ALP concentrations

A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population

Background: Uric acid (UA) is a complex phenotype influenced by both genetic and environmental factors as well as their interactions. Current genome-wide association studies (GWASs) have identified a variety of genetic determinants of UA in Europeans; however, such studies in Asians, especially in Chinese populations remain limited. Methods: A two-stage GWAS was performed to identify single nucleotide polymorphisms (SNPs) that were associated with serum uric acid (UA) in a Chinese population of 12,281 participants (GWAS discovery stage included 1452 participants from the Dongfeng-Tongji cohort (DFTJ-cohort) and 1999 participants from the Fangchenggang Area Male Health and Examination Survey (FAMHES). The validation stage included another independent 8830 individuals from the DFTJ-cohort). Affymetrix Genome-Wide Human SNP Array 6.0 chips and Illumina Omni-Express platform were used for genotyping for DFTJ-cohort and FAMHES, respectively. Gene-environment interactions on serum UA levels were further explored in 10,282 participants from the DFTJ-cohort. Results: Briefly, we identified two previously reported UA loci of SLC2A9 (rs11722228, combined P = 8.98 × 10-31) and ABCG2 (rs2231142, combined P = 3.34 × 10-42). The two independent SNPs rs11722228 and rs2231142 explained 1.03% and 1.09% of the total variation of UA levels, respectively. Heterogeneity was observed across different populations. More importantly, both independent SNPs rs11722228 and rs2231142 were nominally significantly interacted with gender on serum UA levels (P for interaction = 4.0 × 10-2 and 2.0 × 10-2, respectively). The minor allele (T) for rs11722228 in SLC2A9 has greater influence in elevating serum UA levels in females compared to males and the minor allele (T) of rs2231142 in ABCG2 had stronger effects on serum UA levels in males than that in females. Conclusions: Two genetic loci (SLC2A9 and ABCG2) were confirmed to be associated with serum UA concentration. These findings strongly support the evidence that SLC2A9 and ABCG2 function in UA metabolism across human populations. Furthermore, we observed these associations are modified by gender

Glycobiology of immune responses

Unlike their protein roommates and their nucleic acid cousins, carbohydrates remain an enigmatic arm of biology. The central reason for the difficulty in fully understanding how carbohydrate structure and biological function are tied is the non-template nature of their synthesis and the resulting heterogeneity. While this Annals of the NYAS issue does not claim to hold all of the answers, the goal is to highlight what is known about how carbohydrates and their binding partners, on the microbial (non-self), tumor (altered-self) and host (self) sides, cooperate within the immune system while identifying areas of great opportunity to those willing to take up the challenge. In the end, these reviews will serve as specific examples of how carbohydrates are as integral to biology as proteins, nucleic acids, and lipids. In this introductory article we attempt to summarize general concepts on glycans and glycan-binding proteins (mainly C-type lectins, siglecs and galectins) and their contribution to the biology of the immune responses in physiologic and pathologic settings.Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Van Kooyk, Yvette. VU University Amsterdam. VU University Medical Center; Países BajosFil: Cobb, Brian A.. Case Western Reserve University; Estados Unido

Different Responses of Invasive Weed Alternanthera philoxeroides and Oryza sativa to Plant Growth Regulators

Invasive plants cause a global loss of biodiversity, pose a major threat to the environment and economy, and also significantly affect agricultural production and food security. Plant growth regulators (PGRs) are widely used in agricultural production and might also affect invasive weeds distributed around crops in various ways. At present, there are few studies concerning whether there are significant effects of PGRs on invasive weeds. In this study, two widely used PGRs in paddy fields, gibberellic acid (GA) and paclobutrazol (PAC), were applied on Oryza sativa and a noxious weed Alternanthera philoxeroides, which is frequently distributed in paddy fields. The purpose of this study was to investigate if there are different responses of rice and weeds to these two plant regulators and the significant effects of PGRs on invasive weeds. The results showed that GA significantly promotes the total biomass of A. philoxeroides by 52.00%, but does not significantly affect that of O. sativa. GA significantly increases the growth of aboveground and belowground A. philoxeroides, but not that of O. sativa. On the other hand, PAC extremely inhibited the aboveground and belowground biomass of A. philoxeroides by more than 90%, but did not significantly inhibit the belowground biomass of O. sativa. PAC also enhanced the leaf nitrogen content and chlorophyll content of A. philoxeroides, but not the traits of O. sativa. Therefore, the effects of PGRs are significantly different between rice and the invasive weed. The potential promotion effects of PGRs on weeds that are frequently distributed in farmland warrant sufficient attention. This is probably one of the important reasons why invasive weeds can successfully invade the agricultural ecosystem with large human disturbance. This study might sound an alarm for weed control in paddy fields

Studies on hyperfine structure of Sc I and Sc II using Fourier-transform spectroscopy

New magnetic dipole hyperfine structure (HFS) constants A of Sc I and Sc II were derived by analyzing of the transition lines ranging from 3998 to 39,979 $$\hbox {cm}^{-1}$$ in the Fourier-transform (FT) spectra which was recorded in the US National Solar Observatory. In this work, we determined the HFS constants for 56 levels of Sc I from 14,926.061 to 41,162.506 cm$$^{{-1}}$$ and for 12 levels of Sc II from 30,815.70 to 77,387.17 cm$$^{{-1}}$$. To our best knowledge, the HFS constants for 50 out of 56 levels in Sc I and for nine out of 12 levels in Sc II are reported for the first time. Our results have good agreements with the experimental values reported in the literature. Most of the estimated uncertainties are less than 10%

Data_Sheet_1_A WeChat-based self-compassion training to improve the treatment adherence of patients with schizophrenia in China: Protocol for a randomized controlled trial.docx

BackgroundAt present, adherence to antipsychotic treatment is often poor, leading to the recurrence of symptoms. This increases the likelihood of the patient experiencing disability and thus increases the disease burden for the patient, their family, and society as a whole. However, to date, there is no clear evidence regarding the effect of medication adherence interventions on outcomes for patients with schizophrenia. Moreover, the traditional intervention methods are limited by manpower and resources in low- and middle-income countries. Recent studies have demonstrated that increasing a patient’s level of self-compassion may improve their treatment adherence. Online mental health care interventions have advantages in terms of feasibility and acceptability for patients with schizophrenia. In this regard, a WeChat-based self-compassion training protocol to improve patient treatment adherence was designed in this study and will be evaluated in the future to determine its impact on patients with schizophrenia.MethodsThe protocol for the randomized controlled trial (RCT) is based on the SPIRIT 2013 statement. This parallel RCT will aim to recruit 392 patients with schizophrenia who will be randomized at a 1:1 ratio into a 3-week intervention or control group. Both groups will receive routine care. The intervention group will also receive WeChat-based self-compassion training, which requires participants to complete three tasks every day, including a reading task, a meditation task, and a self-compassion journal task. The control group will receive WeChat-based psychological health education, which will only require participants to read positive articles about psychological health every day. Medication adherence, self-compassion, stigma, and social support will be measured at baseline (T0), immediately after the intervention (T1), and 3 weeks after the intervention (T2). Program feasibility will be evaluated throughout the course of the study, and acceptability will be measured immediately after the intervention (T1).Expected results:The intervention described here will address the barriers to accessing mental health care for people with schizophrenia, including patients’ desire for independent management, difficulty accessing providers, and concerns about privacy and stigma. The current study provides guidance for clinical nurses to carry out psychological intervention, with the ultimate aim of addressing the problems associated with a shortage of psychological professionals in low- and middle-income countries.</p

The gut microbiome affects response of treatments in HER2‐negative advanced gastric cancer

Abstract Background Common treatments for metastatic/unresectable HER2‐negative gastric cancer include chemotherapy, immune checkpoint inhibitor monotherapy and chemotherapy plus immune checkpoint inhibitor. However, significant drug resistance exists regardless of the treatment regimen. Methods Patients with metastatic/unresectable HER2‐negative gastric/gastroesophageal junction adenocarcinoma were enrolled. All patients were divided into three groups according to the treatment regimen and were further divided into responders and non‐responders according to efficacy evaluation. Metagenomics sequencing were performed to analyze gut microbiome signature of patients receiving different treatments at baseline and throughout treatment. Results One hundred seventeen patients with HER2‐negative advanced gastric or gastroesophageal junction adenocarcinoma receiving chemotherapy alone, anti PD‐1/PD‐L1 immunotherapy alone or combined regimen were included in this study. Microbiome signatures related to clinical response are distinct among the three treatment groups. Among which, 14, 8 and 13 species were significantly different between responders and non‐responders in immunotherapy, immunotherapy plus chemotherapy and chemotherapy group, respectively. Patients with higher relative abundance of Lactobacillus possessed higher microbiome diversity and significantly better response to anti‐PD‐1/PD‐L1 immunotherapy and had a trend to achieve better progression‐free survival. Another cohort of 101 patients has been used as an external validation set to confirm the stability and reliability of these findings. Conclusions Gut microbiome affects response of treatments in HER2‐negative advanced gastric cancer in a treatment‐specific way, immunotherapy plus chemotherapy did not equal to a simple superposition of immunotherapy and chemotherapy. Lactobacillus is expected to become a novel choice as an adjuvant agent in promoting the efficacy of immunotherapy in gastric cancer

Mechanical annealing in the flow of supercooled metallic liquid

Flow induced structural evolution in a supercooled metallic liquid Vit106a (Zr58.5Cu15.6Al10.3 Ni12.8Nb2.8, at. %) was investigated via uni-axial compression combined with differential scanning calorimeter (DSC). Compression tests at strain rates covering the transition from Newtonian flow to non-Newtonian flow and at the same strain rate 2 x 10(-1) s(-1) to different strains were performed at the end of glass transition (Tg-end = 703 K). The relaxation enthalpies measured by DSC indicate that the samples underwent non-Newtonian flow contain more free volume than the thermally annealed sample (703 K, 4 min), while the samples underwent Newtonian flow contain less, namely, the free volume of supercooled metallic liquids increases in non-Newtonian flow, while decreases in Newtonian flow. The oscillated variation of the relaxation enthalpies of the samples deformed at the same strain rate 2 x 10(-1) s(-1) to different strains confirms that the decrease of free volume was caused by flow stress, i.e., &quot;mechanical annealing.&quot; Micro-hardness tests were also performed to show a similar structural evolution tendency. Based on the obtained results, the stress-temperature scaling in the glass transition of metallic glasses are supported experimentally, as stress plays a role similar to temperature in the creation and annihilation of free volume. In addition, a widening perspective angle on the glass transition of metallic glasses by exploring the 3-dimensional stress-temperature-enthalpy phase diagram is presented. The implications of the observed mechanical annealing effect on the amorphous structure and the work-hardening mechanism of metallic glasses are elucidated based on atomic level stress model. (C) 2014 AIP Publishing LLC

Elevated exhaustion levels of NK and CD8⁺ T cells as indicators for progression and prognosis of COVID-19 disease.

BackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity.MethodsDemographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed via flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19.ResultsThe counts and percentages of NK cells, CD4(+) T cells, CD8(+) T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3(-)CD56(dim)CD16(+) cell population significantly decreased, while the CD3(-)CD56(dim)CD16(-) part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10, and TNF-alpha were significantly increased in severe patients. Moreover, the CD3(-)CD56(dim)CD16(-) cells were screened out as an influential factor in severe cases by LASSO logistic regression.ConclusionsThe functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease