Dongmin Liu

• Virginia Tech

A stressful condition such as the emergence of the coronavirus and its related lockdown measures might trigger alterations in college students’ behaviors. This cross-sectional study aimed to identify the changes in college students’ dietary and lifestyle behaviors during the lockdown and the effect of lockdown-related stressors on health-risk behav...

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration, resulting in significant disability and reduced quality of life. Current therapeutic strategies primarily target immune dysregulation, but limitations in efficacy and tolerability highlight the need for alternative treatment...

Type 2 diabetes (T2D) is still a fast-growing health problem globally. It is evident that chronic insulin resistance (IR) and progressive loss of β-cell mass and function are key features of T2D etiology. Obesity is a leading pathogenic factor for developing IR. The aim of the present study was to determine whether sulforaphane (SFN), a natural com...

Antimicrobial resistant (AMR) infections are a leading health threat globally. Previous literature has underscored the farm-to-fork continuum as a potential focal point for the emergence and spread of AMR. In the present study, date (Phoenix dactylifera L.) seed oil was investigated for its chemical composition and antimicrobial activity against co...

Obesity is associated with metabolic abnormalities that increase the risk and severity of several diseases. This study aimed to explore whether the aqueous extract of Annona squamosa Linn leaves (ASE) can ameliorate metabolic abnormalities associated with high fat (HF) diet-induced obesity. Forty-eight male Wistar rats were distributed among four t...

Insulin resistance is a hallmark of type-2 diabetes (T2D) pathogenesis. Because skeletal muscle (SkM) is the major tissue for insulin-mediated glucose disposal, insulin resistance in SkM is considered a major risk factor for developing T2D. Thus, the identification of compounds that enhance the ability of SkM to take up glucose is a promising strat...

Metabolic syndrome (MSyn) is a considerable health concern in developing and developed countries, and it is a critical predictor of all-cause mortality. Obesity, specifically central obesity, is highly associated with MSyn incidence and development. In this study, seven anthropometric indices (Body Mass Index (BMI), Waist circumference (WC), Waist-...

Insulin resistance and progressive decline in functional β-cell mass are two key factors for developing type 2 diabetes (T2D), which is largely driven by overweight and obesity, a significant obstacle for effective metabolic control in many patients with T2D. Thus, agents that simultaneously ameliorate obesity and act on multiple pathophysiological...

Flavonoids, naturally-occurring compounds with multiple phenolic structures, are the most widely distributed phytochemicals in the plant kingdom, and are mainly found in vegetables, fruits, grains, roots, herbs, and tea and red wine products. Flavonoids have health-promoting effects and are indispensable compounds in nutritional and pharmaceutical...

Insulin resistance and progressive decline in functional β-cell mass are two key factors for developing T2D, which is largely driven by overweight and obesity, a significant obstacle for effective metabolic control in many patients with T2D. Thus, agents that simultaneously ameliorate obesity and promote insulin sensitivity and β-cell function coul...

Pseudorabies virus (PRV) was isolated from some human cases recently and the infected patients manifested respiratory dysfunction and acute neurological symptoms. However, no effective drug or vaccine, preventing the progression of PRV infection, is available. Nectin-1 was the only reported receptor for PRV cell entry both swine and human origin, r...

Dietary supplementation of baicalein, a flavonoid, has anti-obesity effects in mammals and broiler chickens. The aim of this study was to determine the effect of dietary baicalein supplementation on broiler growth and adipose tissue and breast muscle deposition. Fifty Hubbard × Cobb-500 day-of-hatch broiler chicks were assigned to a control starter...

Objectives Diabetes mellitus (DM) is a metabolic disorder related to a complicated interplay between genetics, obesity, and modifiable lifestyle factors. This study aimed to identify the major modifiable risk factors for developing overweight, obesity, and Type 2 DM (T2DM) among Jordanian college students. Methods A self-administered questionnaire...

Objectives Obesity is associated with several metabolic abnormalities including insulin resistance (IR), which is a key risk factor of type 2 diabetes mellitus (T2DM). Oxidative stress is linked to both obesity and IR development. Improving antioxidant status using medicinal plants or their bioactive components can be a safe and low-cost alternativ...

Sex difference in adiposity has long been recognized but the mechanism remains incompletely understood. Previous studies suggested that adiposity was regulated by autophagy in response to energy status change. Here, we show that the energy sensor Sirt1 mediates sex difference in adiposity by regulating autophagy and adipogenesis in partnership with...

For years, the consumption of a diet rich in fruits and vegetables has been considered healthy, increasing longevity, and decreasing morbidities. With the assistance of basic research investigating the potential mechanisms, it has become clear that the beneficial effects of plant-based foods are mainly due to the large amount of bioactive phenolic...

Recently, pseudorabies virus (PRV) was isolated from human cases, and infected patients presented with respiratory dysfunction and acute neurological symptoms. However, there was no available effective drug to prevent the progression of PRV infection. In the present study, we screened a stably Drosophila S2 cell line which can secretory express a n...

Type 2 diabetes (T2D) is a fast-increasing health problem globally, and it results from insulin resistance and pancreatic β-cell dysfunction. The gastrointestinal (GI) tract is recognized as one of the major regulatory organs of glucose homeostasis that involves multiple gut hormones and microbiota. Notably, the incretin hormone glucagon-like pepti...

Protein aggregation is associated with a large number of human protein misfolding diseases, yet FDA-approved drugs are currently not available. Amylin amyloid and plaque depositions in the pancreas are hallmark features of type 2 diabetes. Moreover, these amyloid deposits are implicated in the pathogenesis of diabetic complications such as neurodeg...

Porcine parvovirus (PPV) is a major cause of reproductive failure in swine and has caused substantial losses throughout the world. Viral protein 2 (VP2) of PPV is a major structural protein that can self-assemble into virus-like particles (VLP) with hemagglutination (HA) activity. In order to identify the essential residues involved in the mechanis...

In obesity, endocrine and metabolic perturbations, including those induced by chronic activation of the hypothalamus–pituitary–adrenal axis, are associated with the accumulation of adipose tissue and inflammation. Such changes are attributable to a combination of genetic and epigenetic factors that are influenced by the environment and exacerbated...

Porcine parvovirus (PPV) is a major cause of reproductive failure in swine, and has caused huge losses throughout the world. The structural viral protein VP2, which is able to self-assemble into empty capsids, known as virus-like particles (VLPs), is crucial to induce PPV-specific neutralizing antibodies and protective immunity. In this study, twel...

Background: Porcine parvovirus (PPV) is a major cause of reproductive failure in swine, and has caused huge losses throughout the world. Viral protein 2 (VP2) of PPV is a major structural protein that can self-assemble into virus-like particles (VLP) with hemagglutination (HA) activity. In order to identify the essential residues involved in the me...

Porcine parvovirus (PPV) virus-like particles (VLPs) are a potential vaccine candidate for the prevention of parvovirus-induced reproductive failure in pregnant sows. Currently, the Escherichia coli (E. coli) expression system is the most cost-efficient to express recombinant proteins. To overcome the limitations of protein misfolding and to prepar...

Estrogen can elicit pleiotropic cellular responses via a diversity of estrogen receptors (ERs)—mediated genomic and rapid non-genomic mechanisms. Unlike the genomic responses, where the classical nuclear ERα and ERβ act as transcriptional factors following estrogen binding to regulate gene transcription in estrogen target tissues, the non-genomic c...

Scope Loss of functional β‐cell mass is central for the deterioration of glycemic control in diabetes. The incretin hormone glucagon‐like peptide‐1 (GLP‐1) plays a critical role in maintaining glycemic homeostasis via potentiating glucose‐stimulated insulin secretion and promoting β‐cell mass. Agents that can directly promote GLP‐1 secretion, there...

Although adipose tissue metabolism in obesity has been widely studied, there is limited research on the anorexic state, where the endocrine system is disrupted by reduced adipose tissue mass and there are depot-specific changes in adipocyte type and function. Stress exposure at different stages of life can alter the balance between energy intake an...

Epicatechin (EC), a flavonoid present in various foods including cocoa, dark chocolate, berries, and tea, was recently reported to promote general health and survival of old mice fed a standard chow diet. This is considered a novel discovery in the field of identifying natural compounds to extend lifespan, given that presumably popular anti-aging n...

Identification of a Dual-Action Small Molecule with Potent Antidiabetic Activity Yao Wang, Jing Luo, Hana A. Alkhalidy, Bin Xu and Dongmin Liu Abstract Type 2 diabetes (T2D) is a result of insulin resistance and pancreatic β-cell dysfunction. Therefore, identifying agents that simultaneously reverse these two defects could be a novel strategy lea...

In both Type 1 and type 2 diabetes, pancreatic beta‐cell failure plays an important role in the deterioration of glycemic control. In this study, we investigated whether hispidulin, a naturally occurring flavone, can be used to ameliorate diabetes in an animal model of insulin deficiency. Here, we report that oral administration of hispidulin (20 m...

Insulin resistance and loss of functional beta-cell mass are hallmarks for the pathogenesis of type 2 diabetes (T2D). Therefore, the search for agents that simultaneously reverse these two defects could be a more effective strategy to treat T2D. We recently reported that dietary provision of genistein (0.5 g/kg diet) preserved pancreatic b-cell mas...

In type 2 diabetes, the increase in the activity of the key enzymes that control glycogenolysis and gluconeogenesis in the liver causes an increase in hepatic glucose production, which is the main contributor to the development of fasting hyperglycemia. Here, we investigated the anti‐diabetic potential of flavonol kaempferol. Oral administration of...

In diabetes mellitus, the excessive rate of glucose production from the liver is considered a primary contributor for the development of hyperglycemia, in particular, fasting hyperglycemia. In this study, we investigated whether kaempferol, a flavonol present in several medicinal herbs and foods, can be used to ameliorate diabetes in an animal mode...

We recently reported that epicatechin, a bioactive compound that occurs naturally in various common foods, promoted general health and survival of obese diabetic mice. It remains to be determined whether epicatechin extends health span and delays the process of aging. In the present study, epicatechin or its analogue epigallocatechin gallate (EGCG)...

Obesity-associated insulin resistance (IR) is a major risk factor for developing type 2 diabetes and an array of other metabolic disorders. In particular, hepatic IR contributes to the increase in hepatic glucose production and consequently the development of fasting hyperglycemia. In this study, we explored whether kaempferol, a flavonoid isolated...

We previously discovered that phytonutrient genistein rapidly activates cAMP signaling in β-cells and improves islet mass in diabetic mice. However, the mechanism underlying these actions of genistein is still unclear. Here, we show that pharmacological or molecular inhibition of Gαs blocked genistein-stimulated adenylate cyclase activity in plasma...

Type 2 diabetes (T2D) is a progressive metabolic disease that is increasing in prevalence globally. It is well established that insulin resistance (IR) and a progressive decline in functional β-cell mass are hallmarks of developing T2D. Obesity is a leading pathogenic factor for developing IR. Constant IR will progress to T2D when β-cells are unabl...

Excessive adiposity (particularly visceral fat mass) increases the risks of developing metabolic syndrome. Women have lower deposit of visceral fat than men, and this pattern becomes diminished postmenopausally, but the underlying mechanism remains largely unknown. Here, we show that the gender difference in visceral fat distribution is controlled...

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals that has caused tremendous economic losses worldwide. In this study, we designed a chimeric nanoparticles vaccine with the predominant epitope of FMDV (VP1 131–160) displayed on the top of the coat protein (CP) of MS2 phage. The recombinant protein was expressed in...

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals that has caused tremendous economic losses worldwide. In this study, we designed a chimeric nanoparticles vaccine with the predominant epitope of FMDV (VP1 131–160) displayed on the top of the coat protein (CP) of MS2 phage. The recombinant protein was expressed in...

Background Broiler chickens are compulsive feeders that become obese as juveniles and are thus a unique model for metabolic disorders in humans. However, little is known about the relationship between dietary composition, fasting and refeeding and adipose tissue physiology in chicks. Our objective was to determine how dietary macronutrient composit...

Oleuropein, a natural product derived from olive leaves, has reported anti-diabetic functions. However, detailed molecular mechanisms on how it affects β-cell functions remain poorly understood. Here, we present evidence that oleuropein promotes glucose-stimulated insulin secretion (GSIS) in β-cells. The effect is dose-dependent and it stimulates E...

Recent studies showed that GPR30, a seven-transmembrane G-protein-coupled receptor, is a novel estrogen receptor (ER) that mediates some biological events elicited by estrogen in several types of cancer cells. However, its physiological or pathological role in vivo is unclear. Here, we show that GPR30 knockout (GPRKO) female mice were protected fro...

Mitochondrial uncoupling proteins (UCPs) are inducible and play an important role in metabolic and redox homeostasis. Recent studies have suggested that FoxO1 controls mitochondrial biogenesis and morphology, but it remains largely unknown how FoxO1 may regulate mitochondrial UCPs. Here we show that FoxO1 interacted with transcription factor EB (Tf...

Obesity and related metabolic disorders constitute one of the most pressing heath concerns worldwide. Increased adiposity is linked to autophagy upregulation in adipose tissues. However, it is unknown how autophagy is upregulated and contributes to aberrant adiposity. Here we show a FoxO1-autophagy-FSP27 axis that regulates adipogenesis and lipid d...

Prediabetes is a condition affecting 35% of US adults and about 50% of US adults age 65+. Foods rich in polyphenols, including flavanols and other flavonoids, have been studied for their putative beneficial effects on many different health conditions including type 2 diabetes mellitus and prediabetes. Studies have shown that some flavanols increase...

Dietary administration of cocoa flavanols may be an effective complementary strategy for alleviation or prevention of metabolic syndrome, particularly glucose intolerance. The complex flavanol composition of cocoa provides the ability to interact with a variety of molecules, thus allowing numerous opportunities to ameliorate metabolic diseases. The...

Approximately 366 million people worldwide have been diagnosed with type-2 diabetes (T2D). Chronic insulin resistance, decreased functional β-cell mass, and elevated blood glucose are defining characteristics of T2D. Great advances have been made in understanding the pathogenesis of T2D with respect to the effects of dietary macronutrient compositi...

Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significa...

As the pandemic of obesity is growing, a variety of animal models have been generated to study the mechanisms underlying the increased adiposity and development of metabolic disorders. Tamoxifen (Tam) is widely used to activate Cre recombinase that spatiotemporally controls target gene expression and regulates adiposity in laboratory animals. Howev...

Vascular inflammation plays a significant role in the pathogenesis of atherosclerosis. Luteolin, a naturally occurring flavonoid present in many medicinal plants and some commonly consumed fruits and vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechani...

Neuropeptide Y is an evolutionarily conserved neurotransmitter that stimulates food intake in higher vertebrate species and promotes adipogenesis in mammals. The objective of this study was to determine if NPY also enhances adipogenesis in birds, using chickens as a model. The stromal-vascular fraction of cells was isolated from the abdominal fat o...

As a growing epidemic, type 2 diabetes mellitus (T2DM) has significantly affected the individual's quality of life and economy of the society. Understanding the mechanisms of the disease and discovery of new therapeutic options has become more urgent than ever before. Mitochondrial alterations (e.g. functional alterations, and impaired biogenesis a...

Sulforaphane, a naturally-occurring isothiocyanate present in cruciferous vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of sulforaphane at physiological concentrations remain unclear. Here, we report that a sulforaphane concentration as low as...

Abstract Obesity and diabetes are growing health problems worldwide. In this study, dietary provision of Chinese ginseng (0.5 g/kg diet) prevented body weight gain in high-fat (HF) diet-fed mice. Dietary ginseng supplementation reduced body fat mass gain, improved glucose tolerance and whole body insulin sensitivity, and prevented hypertension in H...

In both type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and progressive dysfunction of β-cell, leading to the impaired insulin secretion. Here, we show that dietary supplementation of baicalein, a flavone isolated from the roots of Chinese herb Scutellaria baicalensis...

Aging is well-known an inevitable process that is influenced by genetic, lifestyle, and environmental factors. However, the exact mechanisms underlying the aging process are not well understood. Increasing evidence show that aging is highly associated with chronic increase in reactive oxygen species (ROS) accumulation of a low-grade proinflammatory...

Introduction: TNF-α, plays an important role in endothelial dysfunction and is involved in the pathogenesis of atherosclerosis. Aim: We investigated the protective effect of cruciferous vegetable phytochemical sulforaphane at physiological concentrations on TNF-α-induced vascular inflammation. Methods: Human umbilical vascular endothelial cells (HU...

Loss of pancreatic beta‐cell mass is central to the development of both type 1 and type 2 diabetes (T2D). Chronic hyperglycemia and hyperlipidemia cause beta‐cell apoptosis, thereby contributing to the pathogenesis of T2D. We investigated the effects of phytochemical genistein on apoptosis and function of beta‐cells and further determined the mecha...

Obesity and diabetes are growing health problems world‐wide. In this study, we tested whether sulforaphane, a compound derived from cruciferous vegetables, has anti‐diabetic action using animal model. One year old male mice were fed either a high‐fat diet (FHD) or HFD supplemented with sulforaphane (0.3 g/kg diet) for 7 weeks. We found that dietary...

Insulin resistance is a primary risk factor for developing prediabetes and type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to prevent insulin resistance or promote its sensitivity could be a promising strategy to prevent the pathogenesis of T2D. In the present study, we show that dietary intake of kaempferol (0.5 g/ kg diet),...

The pathogenesis of fungal infection in the cornea remains largely unclear. To understand how the immune system influences the progression of fungal infection in corneas, we inoculated immunocompetent Balb/c mice, neutrophil- or CD4(+) T-cell-depleted Balb/c mice and nude mice with Candida albicans. We found that only immunocompetent Balb/c mice de...

ZBED6 was identified as a transcription factor that affects muscle mass and fat deposition in pigs. Mechanisms mediating effects on fat mass are unclear. The objective was to determine the effect of ZBED6 mRNA knockdown on 3T3-L1 preadipocyte differentiation and gene expression. Differentiation was associated with increased mRNA abundance of CEBP/α...

Flavonoids are polyphenolic compounds that are abundant in fruits and vegetables, and increasing evidence demonstrates a positive relationship between consumption of flavonoid-rich foods and disease prevention. Epidemiological, in vitro and animal studies support the beneficial effects of dietary flavonoids on glucose and lipid homeostasis. It is e...

Purpose: Luteolin, a flavone present in many foods and medicinal plants, may have beneficial effects on various human chronic diseases. In the present study, we investigated the hypothesis that luteolin can directly act on vascular endothelial cells (ECs), leading to nitric oxide (NO) production and subsequent vascular relaxation. Methods: Rat a...

Genistein, a soy isoflavone, has received wide attention for its potential to improve vascular function, but the mechanism of this effect is unclear. Here, we report that genistein at physiological concentrations (0.1μM-5μM) significantly inhibited TNF-α-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pat...

Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective destruction of pancreatic beta-cells. Although successful islet transplantation provides a promising treatment, high cost, lack of donor organs, immune-mediated destruction of transplanted islets, and side effects from immunosuppressive drugs greatly limit its uses. There...

Obesity and diabetes are growing health problems world‐wide. In this study, we found that dietary provision of Chinese ginseng (0.5 g/kg diet) greatly prevented body weight gain in high fat diet‐fed mice. Gensing‐fed mice had lower body fat mass, while lean mass was only moderately modulated. In addition, treatment with ginseng improved fasting blo...

The soy-derived phytoestrogen genistein has received attention for its potential to improve vascular function, but its mechanism remains unclear. Here, we report that genistein at physiologically relevant concentrations (0.1-10 μM) significantly inhibited thrombin-induced increase in endothelial monolayer permeability. Genistein also reduced the fo...

Type 2 diabetes is a result of chronic insulin resistance and loss of functional pancreatic β-cell mass. Strategies to preserve β-cell mass and a greater understanding of the mechanisms underlying β-cell turnover are needed to prevent and treat this devastating disease. Genistein, a naturally occurring soy isoflavone, is reported to have numerous h...

Pancreatic β-cell dysfunction plays an important role in the pathogenesis of both type 1 and type 2 diabetes. Insulin, which is produced in β-cells, is a critical regulator of metabolism. Insulin is synthesized as preproinsulin and processed to proinsulin. Proinsulin is then converted to insulin and C-peptide and stored in secretary granules awaiti...

Hyperglycemia-induced vascular inflammation resulting in the adhesion of monocytes to endothelium is a key event in the pathogenesis of atherosclerosis in diabetes. We investigated whether epigallocatechin gallate (EGCG), a major catechin found in green tea, reduces vascular inflammation in diabetes. Human aortic endothelial cells (HAEC) were pretr...

Type 2 diabetes (T2D) is a growing health problem worldwide. While peripheral insulin resistance is common during obesity and aging in both animals and people, progression to T2D is largely due to insulin secretory dysfunction and significant apoptosis of functional β-cells, leading to an inability to compensate for insulin resistance. It is recogn...

We previously reported that genistein, a phytoestrogen, up-regulates endothelial nitric oxide synthase (eNOS) and prevents hypertension in rats that are independent of estrogen signaling machinery. However, how genistein regulates eNOS expression is unknown. In the present study, we show that genistein enhanced eNOS expression and NO synthesis in p...

While peripheral insulin resistance is common during obesity and aging in mice and people, the progression to type 2 diabetes (T2D) is largely due to loss of β-cell mass and function through apoptosis. We recently reported that genistein, a soy derived isoflavone, can improve glycemic control and β-cell function in insulin-deficient diabetic mice....

Type 2 diabetes (T2D) is a result of chronic insulin resistance and loss of functional â‐cell mass. Thus, a method to simultaneously prevent insulin resistance and protect â‐cells could be a more effective strategy to prevent T2D. Here, we discovered that genistein, an isoflavone present in soybean, directly protects â‐cells from apoptosis ex vivo...

We previously reported that genistein up‐regulates endothelial nitric oxide synthase (eNOS) and prevents hypertension in rats. However, how genistein regulates eNOS expression is unknown. Here, we show that genistein enhanced eNOS expression and nitric oxide (NO) synthesis in human aortic endothelial cells (HAECs). Inhibition of mitogen‐activated p...

Hyperglycemia-induced vascular inflammation resulting in the enhanced monocyte-endothelial cell (EC) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC) were pretreated with genistein before...

Butyrate is a major SCFA produced by microbial fermentation of dietary fiber in the gastrointestinal tract. Butyrate is widely thought to mediate the benefits of fiber and resistant starch consumption to colon health in humans. Besides serving as a substrate for energy production, butyrate has many regulatory effects in animals. Little is known abo...

Considerable evidence shows that chronic hyperglycemia can cause pancreatic beta-cell dysfunction, which contributes to progressive deterioration of glucose homeostasis and overt diabetes. In the present study, we found that kaempferol, a flavonol compound present in various Chinese medicinal herbs, has cytoprotective effects on cultured clonal bet...

The lifespan of diabetic patients is 7-8 y shorter than that of the general population because of hyperglycemia-induced vascular complications and damage to other organs such as the liver and skeletal muscle. Here, we investigated the effects of epicatechin, one of the major flavonoids in cocoa, on health-promoting effects in obese diabetic (db/db)...

In addition to its anti-ischemic and antianginal effects, ranolazine has been shown to lower hemoglobin A(1c) (HbA(1c)) in patients with coronary artery disease and diabetes. The present study was undertaken to test the hypothesis that ranolazine lowers HbA(1c) because of improved glucose homeostasis in an animal model. Diabetes in mice was induced...

Cyclic adenosine monophosphate (cAMP) is a second messenger that plays a vital role in numerous biological processes. It serves as an intracellular signal transducer in many different organisms, exerting its effect through gene expression. In addition to its effects on intermediary metabolism, it has profound effects on cellular events, including g...