Low doses of acetyl trihexyl citrate plasticizer promote adipogenesis in hepatocytes and mice.

Accumulating epidemiological evidence underscores the association between pervasive environmental factors and an increased risk of metabolic diseases. Environmental chemicals, recognized disruptors of endocrine and metabolic processes, may contribute to the global prevalence of metabolic disorders, including obesity. Acetyl tributyl citrate (ATHC), categorized as a citric acid ester plasticizer, serves as a substitute for di-(2-ethylhexyl) phthalate (DEHP) in various everyday products.

RIP1 kinase inactivation protects against LPS-induced acute respiratory distress syndrome in mice.

Acute respiratory distress syndrome (ARDS) is characterized by lung tissue oedema and inflammatory cell infiltration, with limited therapeutic interventions available. Receptor-interacting protein kinase 1 (RIPK1), a critical regulator of cell death and inflammation implicated in many diseases, is not fully understood in the context of ARDS. In this study, we employed RIP1 kinase-inactivated (Rip1) mice and two distinct RIPK1 inhibitors to investigate the contributions of RIP1 kinase activity in lipopolysaccharide (LPS)-induced ARDS pathology.

Plasticizer acetyl triethyl citrate (ATEC) induces lipogenesis and obesity.

Environmental chemicals, such as plasticizers, have been linked to increased rates of obesity, according to epidemiological studies. Acetyl triethyl citrate (ATEC) is a plasticizer that is commonly utilized in pharmaceutical products and food packaging as a non-phthalate alternative. Due to its direct contact with the human body and high leakage rate from the polymers, assessment of the potential risk of ATEC exposure at environmentally relevant low doses to human health is needed.

Assessment of lipid metabolism-disrupting effects of non-phthalate plasticizer diisobutyl adipate through in silico and in vitro approaches.

Diisobutyl adipate (DIBA), as a novel non-phthalate plasticizer, is widely used in various products. However, little effort has been made to investigate whether DIBA might have adverse effects on human health. In this study, we integrated an in silico and in vitro strategy to assess the impact of DIBA on cellular homeostasis.

A Temperature-Dependent Model for Tritrophic Interactions Involving Tea Plants, Tea Green Leafhoppers and Natural Enemies.

The tea green leaf hopper, Matsuda, is a severe pest of tea plants. Volatile emissions from tea shoots infested by the tea green leafhopper may directly repel insect feeding or attract natural enemies. Many studies have been conducted on various aspects of the tritrophic relationship involving tea plants, tea green leafhoppers and natural enemies.

Erratum: Dual Feedforward Loops Modulate Type I Interferon Responses and Induce Selective Gene Expression during TLR4 Activation.

[This corrects the article DOI: 10.1016/j.isci.

Pretreatment of umbilical cord derived MSCs with IFN-γ and TNF-α enhances the tumor-suppressive effect on acute myeloid leukemia.

Currently, the standard therapeutic approach of AML consists of chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). However, these strategies are usually associated with adverse side effects and high risk of relapse following HSCT. Thus, it is imperative to find an alternative way against AML progression.

Multi-scale modeling of hippo signaling identifies homeostatic control by YAP-LATS negative feedback.

The Hippo signaling primarily includes LATS1/2 and YAP1. Recent work has demonstrated a novel negative feedback between YAP1 and LATS1/2. However, how YAP-LATS negative feedback regulates cancer progression remains elusive.

Unanchored ubiquitin chain sustains RIG-I-induced interferon-I activation and controls selective gene expression.

Ubiquitination plays a crucial role in retinoic acid-inducible gene I (RIG-I)-induced antiviral responses. However, the precise regulatory mechanisms of RIG-I activity mediated by conjugated and unanchored ubiquitin chains remain to be determined. In this study, we discovered that T55 of RIG-I was required for its binding ability for the unanchored ubiquitin chains.

Modeling the neuro-protection of theaflavic acid from black tea and its synergy with nimodipine via mitochondria apoptotic pathway.

Ischemic stroke presents a leading cause of mortality and morbidity worldwide. Theaflavic acid (TFA) is a theaflavin isolated from black tea that exerts a potentially neuro-protective effect. However, the dynamic properties of TFA-mediated protection remain largely unknown.

Potent inhibition of tributyltin (TBT) and triphenyltin (TPT) against multiple UDP-glucuronosyltransferases (UGT): A new potential mechanism underlying endocrine disrupting actions.

Organotin compounds (OTs) act as potent endocrine disruptors that are often found in polluted food and water. UDP-glucuronosyltransferases (UGTs) are responsible for termination of multiple endogenous hormones. This study was conducted to investigate the inhibitory effects of two tri-submitted OTs tributyltin (TBT) and triphenyltin (TPT), against activities of UGTs.

Modeling COVID-19 epidemic in Heilongjiang province, China.

The Coronavirus Disease 2019 (COVID-19) surges worldwide. However, massive imported patients especially into Heilongjiang Province in China recently have been an alert for local COVID-19 outbreak. We collected data from January 23 to March 25 from Heilongjiang province and trained an ordinary differential equation model to fit the epidemic data.

Estimating the effects of asymptomatic and imported patients on COVID-19 epidemic using mathematical modeling.

The epidemic of Coronavirus Disease 2019 has been a serious threat to public health worldwide. Data from 23 January to 31 March at Jiangsu and Anhui provinces in China were collected. We developed an adjusted model with two novel features: the asymptomatic population and threshold behavior in recovery.

Dual Feedforward Loops Modulate Type I Interferon Responses and Induce Selective Gene Expression during TLR4 Activation.

Although the dynamic features of type I coherent feedforward loop (C1-FFL) has been well studied, how C1-FFL shapes cell-to-cell heterogeneity remains unclear. Here, we found that C1-FFL with OR logic serves as "noise reducer," whereas C1-FFL with AND logic functions as "noise propagator" to fine-tune the heterogeneity of signaling molecule's activation. Within Toll-like receptor 4 (TLR4) signaling pathway, we demonstrated that MyD88 together with TRIF generates a C1-FFL to control TBK1 phosphorylation and reduce its cell-to-cell heterogeneity, whereas noisy TRIF activation induced high heterogeneity of IRF3 activation through another C1-FFL.

Mathematical model identifies effective P53 accumulation with target gene binding affinity in DNA damage response for cell fate decision.

Functional p53 signaling is essential for appropriate responses to diverse stimuli. P53 dynamics employs the information from the stimulus leading to selective gene expression and cell fate decision. However, the decoding mechanism of p53 dynamics under DNA damage challenge remains poorly understood.

Integrated modeling and analysis of intracellular and intercellular mechanisms in shaping the interferon response to viral infection.

The interferons (IFNs) responses to viral infection are heterogeneous, while the underlying mechanisms for variability among cells are still not clear. In this study, we developed a hybrid model to systematically identify the sources of IFN induction heterogeneity. The experiment-integrated simulation demonstrated that the viral dose/type, the diversity in transcriptional factors activation and the intercellular paracrine signaling could strikingly shape the heterogeneity of IFN expression.

Stratified ubiquitination of RIG-I creates robust immune response and induces selective gene expression.

The activation of retinoic acid-inducible gene I (RIG-I), an indispensable viral RNA sensor in mammals, is subtly regulated by ubiquitination. Although multiple ubiquitination sites at the amino terminus of RIG-I have been identified, their functional allocations in RIG-I activation remain elusive. We identified a stratified model for RIG-I amino-terminal ubiquitination, in which initiation at either Lys or Lys allows subsequent ubiquitination at other lysines, to trigger and amplify RIG-I activation.

Modeling amplified p53 responses under DNA-PK inhibition in DNA damage response.

During DNA double strand breaks (DSBs) repair, coordinated activation of phosphatidylinositol 3-kinase (PI3K)-like kinases can activate p53 signaling pathway. Recent findings have identified novel interplays among these kinases demonstrating amplified first p53 pulses under DNA-PK inhibition. However, no theoretical model has been developed to characterize such dynamics.

[Effect of secretin on the expression of cPLA and mPGEs-1 in mouse endometrial stromal cell during early pregnancy].

Secretin, a gastrointestinal peptide, has been found to be expressed in mouse endometrial stromal cells (mESCs) during early pregnancy. In order to further investigate the function of secretin during embryo implantation, the expression levels of secretin, secretin receptor, cytosolic phospholipase A (cPLA) and membrane prostaglandin E synthase 1 (mPGEs-1) were detected in the mice uterus from day 4 to 8 of pregnancy by real-time PCR, ELISA and in situ hybridization. mESCs isolated and cultured from day 4 of pregnancy were transfected with secretin expression vectors or treated with H89, a PKA inhibitor.

A Hierarchical Mechanism of RIG-I Ubiquitination Provides Sensitivity, Robustness and Synergy in Antiviral Immune Responses.

RIG-I is an essential receptor in the initiation of the type I interferon (IFN) signaling pathway upon viral infection. Although K63-linked ubiquitination plays an important role in RIG-I activation, the optimal modulation of conjugated and unanchored ubiquitination of RIG-I as well as its functional implications remains unclear. In this study, we determined that, in contrast to the RIG-I CARD domain, full-length RIG-I must undergo K63-linked ubiquitination at multiple sites to reach full activity.

Microinjection of acetylcholine into cerebellar fastigial nucleus induces blood depressor response in anesthetized rats.

It is well known that the cerebellar fastigial nucleus (FN) is involved in cardiovascular modulation, and has direct evidence of cholinergic activity; however, whether and how acetylcholine (ACh) in the FN modulates blood pressure has not been investigated. In this study, we analyzed mean arterial pressure, maximal change in mean arterial pressure, and the reaction time of blood pressure changes after microinjection of cholinergic reagents into the FN in anesthetized rats. The results showed that ACh evoked a concentration-dependent (10, 30 and 100mM) effect on blood pressure down-regulation.

Reversible ubiquitination shapes NLRC5 function and modulates NF-κB activation switch.

NLRC5 is an important regulator in innate immune responses. However, the ability of NLRC5 to inhibit NF-κB activation is controversial in different cell types. How dynamic modification of NLRC5 shapes NF-κB signaling remains unknown.

Role of Muscarinic Acetylcholine Receptor-2 in the Cerebellar Cortex in Cardiovascular Modulation in Anaesthetized Rats.

Our previous investigations have demonstrated that microinjection of acetylcholine (ACh) or muscarinic ACh receptor activation in the cerebellar cortex induces a systemic blood pressure depressor response. This study aimed to determine the role of muscarinic ACh receptor-2 (M2 receptor) in the cerebellar cortex in cardiovascular function regulation in rats. A nonselective muscarinic receptor agonist (oxotremorine M, OXO; 30 mM), a selective M2 receptor agonist (arecaidine but-2-ynyl ester tosylate, ABET; 3, 10, and 30 mM), 30 mM OXO mixed with a selective M2 receptor antagonist (methoctramine hydrate, MCT; 0.

Modeling the heterogeneity of p53 dynamics in DNA damage response.

The tumor suppressor p53 can be activated by DNA damage and exhibits undamped pulses. Recent reports have demonstrated a non-threshold mechanism for p53 dynamics. However, no related theoretical studies have been proposed.

Dynamics of P53 in response to DNA damage: Mathematical modeling and perspective.

Cells are constantly challenged by intrinsic and extrinsic signals. DNA damage denotes a serious threat to cellular survival due to its extensive destroy to genomic integrity. Appropriate dynamic responses to changing signals are essential for homeostasis.