Publications by authors named "Yan C Li"

Interactions between protein kinases and their substrates are critical for the modulation of complex signaling pathways. Currently, there is a large amount of information available about kinases and their substrates in disparate public databases. However, these data are difficult to interpret in the context of cellular systems, which can be facilitated by examining interactions among multiple proteins at once, such as the network of interactions that constitute a signaling pathway.

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Protein kinase function and interactions with drugs are controlled in part by the movement of the DFG and ɑC-Helix motifs that are related to the catalytic activity of the kinase. Small molecule ligands elicit therapeutic effects with distinct selectivity profiles and residence times that often depend on the active or inactive kinase conformation(s) they bind. Modern AI-based structural modeling methods have the potential to expand upon the limited availability of experimentally determined kinase structures in inactive states.

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Background: The prevalence of type 2 diabetes mellitus (DM) and pre-diabetes mellitus (pre-DM) has been increasing among youth in recent decades in the United States, prompting an urgent need for understanding and identifying their associated risk factors. Such efforts, however, have been hindered by the lack of easily accessible youth pre-DM/DM data.

Objective: We aimed to first build a high-quality, comprehensive epidemiological data set focused on youth pre-DM/DM.

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Canine circovirus (CanineCV) is a virus associated with respiratory and digestive diseases in dogs and often occurs in coinfections with other pathogens, thereby aggravating the symptoms of infected dogs. CanineCV was first reported in the United States in 2012. Subsequently, it was reported among dogs in Europe, Asia, and South America.

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Article Synopsis
  • Protein kinases rely on the movement of specific motifs (DFG and ɑC-Helix) to switch between different conformations, influencing their interactions with drugs and therapeutic efficacy.
  • There is a scarcity of structural data for kinases in inactive states, limiting advancements in drug discovery for this important protein family.
  • AI-based modeling tools like AlphaFold2 can help explore the uncharted conformational space of kinases, revealing new structures and potential therapeutic targets that could address significant challenges in targeting these proteins.
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The prevalence of type 2 diabetes mellitus (DM) and prediabetes (preDM) is rapidly increasing among youth, posing significant health and economic consequences. To address this growing concern, we created the most comprehensive youth-focused diabetes dataset to date derived from National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. The dataset, consisting of 15,149 youth aged 12 to 19 years, encompasses preDM/DM relevant variables from sociodemographic, health status, diet, and other lifestyle behavior domains.

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Motivation: Integrating multimodal data represents an effective approach to predicting biomedical characteristics, such as protein functions and disease outcomes. However, existing data integration approaches do not sufficiently address the heterogeneous semantics of multimodal data. In particular, early and intermediate approaches that rely on a uniform integrated representation reinforce the consensus among the modalities but may lose exclusive local information.

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  • Integrating multimodal data is crucial for accurately predicting biomedical characteristics, but current methods often overlook localized information due to their emphasis on uniform representation.
  • The proposed Ensemble Integration (EI) method aims to improve prediction by creating local models from diverse data sources and effectively combining them into a comprehensive predictive model, outpacing traditional integration techniques.
  • EI was successfully tested on predicting protein functions and COVID-19 mortality, revealing vital health indicators and proving more accurate than individual modalities and existing integration methods.
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  • Gut stem cells help keep our intestines healthy, but when a specific protein called Mettl14 was removed from mouse gut cells, it caused serious problems like inflammation and stunted growth.
  • This loss of Mettl14 made some important stem cells die off, leading to even more issues in the gut.
  • Adding back a protein called GSDMC helped save the gut cells and prevent the mice from dying too soon, showing how important these proteins are for healthy intestines.
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  • Macrophages are important cells in our body's immune system that help fight diseases and infections.
  • Researchers often use a special method to remove these cells from mice to study how they work.
  • This study explains a new way to take out macrophages and then replace them with modified ones to help understand what happens during infections like sepsis.
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  • Idiopathic pulmonary fibrosis (IPF) is a serious lung disease that causes breathing problems and can't be reversed.
  • In a study with mice, researchers found that a type of vitamin D called paricalcitol helps protect against lung damage caused by a harmful substance called bleomycin.
  • The study showed that vitamin D helps reduce harmful proteins in the lungs and prevents weight loss, suggesting that it may be important for people with lung diseases.
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Background: Our previous studies showed that vitamin D receptor (VDR) depletion promotes lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice, and renal VDR is down-regulated in AKI, but the mechanism of VDR down-regulation is unclear.

Methods: Nutritional vitamin D deficiency was induced by feeding mice a vitamin D-deficient (VD-D) diet. Mice were injected intraperitoneally with LPS (20 mg/kg) to establish LPS-induced AKI.

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  • The study explores the link between vitamin D deficiency and the renin-angiotensin system (RAS) in the context of inflammatory bowel disease (IBD) using a mouse model.
  • Mice on a vitamin D-deficient diet showed worse colitis symptoms and more inflammation compared to those with sufficient vitamin D, as indicated by increased cytokines and RAS activation.
  • Treatment with an angiotensin II receptor blocker, losartan, reduced the severity of colitis in vitamin D-deficient mice, suggesting that RAS plays a role in the inflammation process related to vitamin D levels.
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Because ADAM17 promotes colonic tumorigenesis, we investigated potential miRNAs regulating ADAM17; and examined effects of diet and tumorigenesis on these miRNAs. We also examined pre-miRNA processing and tumour suppressor roles of several of these miRNAs in experimental colon cancer. Using TargetScan, miR-145, miR-148a, and miR-152 were predicted to regulate ADAM17.

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Bacterial infection triggers a cytokine storm that needs to be resolved to maintain the host's wellbeing. Here, we report that ablation of mA methyltransferase subunit METTL14 in myeloid cells exacerbates macrophage responses to acute bacterial infection in mice, leading to high mortality due to sustained production of pro-inflammatory cytokines. METTL14 depletion blunts Socs1 mA methylation and reduces YTHDF1 binding to the mA sites, which diminishes SOCS1 induction leading to the overactivation of TLR4/NF-κB signaling.

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  • Obesity increases the risk of chronic kidney disease, and this study looked at how a high-fat diet (HFD) affects the kidneys of mice.
  • Mice that ate an HFD for 16 weeks became obese and showed signs of kidney damage, like high protein in urine and bad kidney function.
  • The researchers found that the high-fat diet caused too much fat buildup, increased stress in kidney cells, and led to more cell death, which all hurt kidney health.
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Objectives: As a screening index of diabetic kidney disease (DKD), urinary albumin/creatine ratio (UACR) is commonly used. However, approximately 23.3%-56.

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Diets high in animal fats are associated with increased risks of inflammatory bowel disease, but the mechanism remains unclear. In this study, we investigated the effect of high-fat diet (HFD) on the development of experimental colitis in mice. Relative to mice fed low-fat diet (LFD), HFD feeding for 4 wk increased the levels of triglyceride, cholesterol, and free fatty acids in the plasma as well as within the colonic mucosa.

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Group 3 innate lymphoid cells (ILC3) play key roles in protective immunity and mucosal barrier maintenance. Here we showed that vitamin D/vitamin D receptor (VDR) signaling regulates gut ILC3. VDR deletion or 1,25-dihydroxyvitamin D deficiency in mice led to a marked reduction in colonic ILC3 populations at steady state and impaired ILC3 responses following Citrobacter rodentium infection, resulting in substantial increases in intestinal bacterial growth and mouse mortality.

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The publisher regret that Funding statement was incomplete in the original publication; the authors have requested that the revised Funding statement be noted.

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Obesity is a leading cause of chronic kidney disease (CKD), but how obesity promotes renal injury remains poorly understood. Here we showed that ATP-citrate lyase (ACL), an enzyme converting citrate to acetyl-CoA, is highly induced in the kidney of overweight or obese patients with CKD and ob/ob BTBR mice. ACL induction is associated with increased ectopic lipid accumulation (ELA), glomerulosclerosis, and albuminuria.

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Objective: Systemic lupus erythematosus (SLE) is characterized by uncontrolled production of pro-inflammatory cytokines. Vitamin D receptor (VDR) has potent anti-inflammatory activities. The aim of this study was to examine the correlation between VDR expression and inflammation and disease activity in patients with SLE.

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Colorectal cancer is a leading cause of cancer deaths. The renin-angiotensin system (RAS) is upregulated in colorectal cancer, and epidemiologic studies suggest RAS inhibitors reduce cancer risk. Because vitamin D (VD) receptor negatively regulates renin, we examined anticancer efficacy of VD and losartan (L), an angiotensin receptor blocker.

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Previous studies suggest that the renin-angiotensin system (RAS) is a pathogenic factor for colitis. The goal of this study was to elucidate the molecular mechanism whereby angiotensin II (ANG II) promotes colonic inflammation. We found that renin was highly induced in colonic biopsies from patients with ulcerative colitis or Crohn's disease, and colonic renin and ANG II levels were markedly increased in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model, indicating that the colonic RAS is activated in colitis.

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