Publications by authors named "Lin Kuang"

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), an oxidative derivative of tire anti-degradant, has been linked to mortality in coho salmon (Oncorhynchus kisutch) and has exhibited potential human toxicity. Hence, exploring how 6PPD-Q interacts with biomacromolecules like enzymes is indispensable to assess its human toxicity and elucidate its mechanism of action. This investigation aims to explore the impact of 6PPD-Q on lactate dehydrogenase (LDH) through various methods.

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Adiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²).

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Background: Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels.

Methods: The prospective China Kadoorie Biobank recruited >512 000 adults aged 30-79 years in 2004-08 and genotyped a random subset of 76 000 participants.

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  • * A genome-wide association study (GWAS) of over 100,000 Chinese adults uncovered 128 unique genetic loci linked to various BP traits, including 74 newly identified associations.
  • * The study revealed significant genetic differences, showing that Chinese populations have higher heritability and larger genetic effects compared to European or Japanese groups, emphasizing the need for more diverse research to grasp BP genetics and their implications for disease risk.
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  • Scientists looked at the timing of when girls start their periods (called menarche) and how it can affect their health later in life.
  • They studied about 800,000 women and found over a thousand genetic signals that influence when menstruation starts.
  • Some women have a much higher chance of starting their periods too early or too late based on their genetic makeup, suggesting that genes play a big role in this process!
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Lactate dehydrogenase (LDH), a crucial enzyme in anaerobic glycolysis, plays a pivotal role in the energy metabolism of tumor cells, positioning it as a promising target for tumor treatment. Rutin, a plant-based flavonoid, offers benefits like antioxidant, antiapoptotic, and antineoplastic effects. This study employed diverse experiments to investigate the inhibitory mechanism of rutin on LDH through a binding perspective.

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  • Hemorrhagic fever with renal syndrome (HFRS) is a serious infectious disease with five distinct stages and a mortality rate between 1-15%, characterized by increased vascular permeability and renal injury.
  • A comprehensive study analyzed data from 37 articles involving over 140,000 HFRS patients to identify clinical features associated with fatalities, revealing that deceased patients were generally older and had higher incidences of smoking, hypertension, and diabetes.
  • Patients who did not survive exhibited significant differences in various health complications and laboratory results, such as elevated leukocyte counts and altered liver function tests, indicating more severe organ dysfunction and the need for intensive care like continuous renal therapy.
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Objective: Integrated analyses of plasma proteomics and genetic data in prospective studies can help assess the causal relevance of proteins, improve risk prediction, and discover novel protein drug targets for type 2 diabetes (T2D).

Research Design And Methods: We measured plasma levels of 2,923 proteins using Olink Explore among ∼2,000 randomly selected participants from China Kadoorie Biobank (CKB) without prior diabetes at baseline. Cox regression assessed associations of individual protein with incident T2D (n = 92 cases).

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  • - This study conducted a genome-wide association analysis on metabolic traits in over 136,000 participants, revealing over 400 genetic loci that influence human metabolism and complex diseases.
  • - Researchers used advanced techniques like nuclear magnetic resonance spectroscopy to link specific genetic variants with how they affect lipoprotein metabolism and other metabolic processes.
  • - The findings highlight the genetic connections between metabolism and conditions such as hypertension, providing valuable data for further research on metabolic-related diseases.
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  • Type 2 diabetes (T2D) is a complex disease influenced by various genetic factors and molecular mechanisms that vary by cell type and ancestry.
  • In a large study involving over 2.5 million individuals, researchers identified 1,289 significant genetic associations linked to T2D, including 145 new loci not previously reported.
  • The study categorized T2D signals into eight distinct clusters based on their connections to cardiometabolic traits and showed that these genetic profiles are linked to vascular complications, emphasizing the role of obesity-related processes across different ancestry groups.
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Aims: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition.

Methods And Results: In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)].

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  • - A new multi-ancestry genome-wide association study (GWAS) of major depression (MD) analyzed data from 88,316 cases and 902,757 controls, representing various ancestries including African, East Asian, South Asian, and Hispanic/Latin American.
  • - The study discovered 53 novel genetic loci significantly linked to MD, with fewer existing European ancestry loci proving relevant to other ancestry groups.
  • - A transcriptome-wide association study in this research identified 205 new genes associated with MD, highlighting the importance of diverse ancestry in genetic research for better understanding and finding relevant genes.
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  • Alcohol-related liver disease (ARLD) is a significant public health issue, and identifying high-risk individuals can enhance public health strategies.
  • In a study of 312,599 active drinkers from the UK Biobank, both binge drinking and genetic predisposition (measured using a polygenic risk score, PRS) were found to significantly increase the risk of alcohol-related cirrhosis (ARC).
  • Diabetes also raised ARC risk across all drinking patterns and genetic categories, highlighting a complex interplay between drinking behavior, genetics, and diabetes that offers potential for targeted interventions in high-risk individuals.
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Background: Genetic variants that affect alcohol use in East Asian populations could help assess the causal effects of alcohol consumption on cause-specific mortality. We aimed to investigate the associations between alcohol intake and cause-specific mortality using conventional and genetic epidemiological methods among more than 512 000 adults in China.

Methods: The prospective China Kadoorie Biobank cohort study enrolled 512 724 adults (210 205 men and 302 519 women) aged 30-79 years, during 2004-08.

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Background: Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.

Methods: We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake.

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Adiposity is associated with multiple diseases and traits, but little is known about the causal relevance and mechanisms underlying these associations. Large-scale proteomic profiling, especially when integrated with genetic data, can clarify mechanisms linking adiposity with disease outcomes. We examined the associations of adiposity with plasma levels of 1463 proteins in 3977 Chinese adults, using measured and genetically-instrumented BMI.

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The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history.

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  • The study investigates how endophenotypes, which are traits linked to psychosis, connect to genetic factors by examining specific gene sets.
  • It analyzed data from 4,506 participants to compute polygenic risk scores related to schizophrenia and bipolar disorder, ultimately measuring their association with seven different endophenotypes.
  • Results indicated a significant link between reduced P300 amplitude and higher schizophrenia risk linked to forebrain-related genes, suggesting genetic variants influence early brain development and may heighten psychosis risk in the future.
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Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.

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Organophosphate flame retardants (OPFRs) are newly emerging estrogenic environmental pollutants, which attracted widespread public interest owing to their potential threats to human. Here, the interaction between two typical aromatic OPFRs, TPHP/EHDPP and HSA was researched by different experiments. Experimental results indicated that TPHP/EHDPP can insert the site I of HSA and be encircled by several amino acid residues, Asp451, Glu292, Lys195, Trp214 and Arg218 played vital roles in this binding process.

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Background And Aims: We investigated the causal relevance of alcohol intake with measures of carotid artery thickness and atherosclerosis in Chinese adults.

Methods: The study included 22,384 adults from the China Kadoorie Biobank, with self-reported alcohol use at baseline and resurvey, carotid artery ultrasound measurements, and genotyping data for ALDH2-rs671 and ADH1B-rs1229984. Associations of carotid intima media thickness (cIMT), any carotid plaque, and total plaque burden (derived from plaque number and size) with self-reported (conventional analyses) and genotype-predicted mean alcohol intake (Mendelian randomization) were assessed using linear and logistic regression models.

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  • The study investigates the ecological risks of heavy metal pollution, specifically focusing on the Yellow River estuary, under the water-sediment regulation scheme (WSRS).
  • It was found that Cadmium (Cd) posed a moderate ecological risk, and Suaeda salsa, a wetland plant, showed an increased ability to accumulate Cd with higher concentrations in the water, despite experiencing decreased overall biomass.
  • Additionally, deeper water logging negatively impacted S. salsa's growth and Cd absorption, highlighting the complex interaction between heavy metal input and water conditions in wetland ecosystems.
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