Background: Food safety incidents have aroused widespread public health concern, causing food price risk. However, the causal paths remain largely unexplored in previous literature. This paper sets out to identify the relations of local and spatial spillovers of food safety incidents and public health concerns to food price risk in consumer markets within a setting with heterogeneous food safety risk levels. Methods: (i) Theoretically, unlike prior work, this paper decomposes food safety risks into food safety incidents (objective incident component) and public health concern (subjective concern component). This article develops a theoretical framework of causality to capture the underlying causal pathways motivated by the theories of limited attention and two-step flow of communication. (ii) Empirically, using avian influenza shocks in China's poultry markets as natural experiments, this paper differentiates between low- and high-risk food and incidents. The article adopts dynamic spatial panel models to analyze potential nonlinearity, moderation, and mediation in the spillover of food safety risk to food price risk for a long panel of 30 provinces covering the November 2007 to November 2017 period. Results: (i) Food safety incident alone only triggers high-risk food price risk, not low-risk food price risk. (ii) Public health concern amplifies nonlinear food price risk triggered by food safety incident. (iii) High-risk incident intensifies negative pressure of public health concern on food price risk. (iv) Food safety incident indirectly affects high-risk food price risk through public health concern. Conclusions: Using a setting with heterogeneous risk levels, this paper documents that (i) food safety incident itself does not necessarily determine food price risk, whereas it is actually public health concern that directly causes nonlinear food price risk; (ii) public health concern spillover to food price risk is negatively moderated by high-risk incident, and (iii) food safety incident spillover to high-risk food price risk is mediated by public health concern. The findings complement current research by (i) elucidating the diverse impacts of food safety incident and public health concern on food price risk, which are obscure in previous literature, and (ii) highlighting that heterogeneous food and incident risk levels matter for determining food price risk spillover.

The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received <50, 50-500, and 500-1000 μGy/h of 137Cs radiation for 180 d. We found that the pathological changes in liver tissues were more obvious as the irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had ≥ 1.5-fold changes in expression. Twenty-three proteins were selected based on ≥2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.

Uranium tailings (UT) are formed as a byproduct of uranium mining and are of potential risk to living organisms. In the present study, we sought to identify potential biomarkers associated with chronic exposure to low dose rate γ radiation originating from UT. We exposed C57BL/6J mice to 30, 100, or 250 μGy/h of gamma radiation originating from UT samples. Nine animals were included in each treatment group. We observed that the liver central vein was significantly enlarged in mice exposed to dose rates of 100 and 250 μGy/h, when compared with nonirradiated controls. Using proteomic techniques, we identified 18 proteins that were differentially expressed (by a factor of at least 2.5-fold) in exposed animals, when compared with controls. We chose glycine N-methyltransferase (GNMT), glutathione S-transferase A3 (GSTA3), and nucleophosmin (NPM) for further investigations. Our data showed that GNMT (at 100 and 250 μGy/h) and NPM (at 250 μGy/h) were up-regulated, and GSTA3 was down-regulated in all of the irradiated groups, indicating that their expression is modulated by chronic gamma radiation exposure. GNMT, GSTA3, and NPM may therefore prove useful as biomarkers of gamma radiation exposure associated with UT. The mechanisms underlying those changes need to be further studied.

Mammalian lung development consists of a series of precisely choreographed events that drive the progression from simple lung buds to the elaborately branched organ that fulfills the vital function of gas exchange. Strict transcriptional control is essential for lung development. Among the large number of transcription factors encoded in the mouse genome, only a small portion of them are known to be expressed and function in the developing lung. Thus a systematic investigation of transcription factors expressed in the lung is warranted.

Fibrosis, or the accumulation of extracellular matrix, is a common feature of many chronic diseases. To interrogate core molecular pathways underlying fibrosis, we cross-examine human primary cells from various tissues treated with TGF-β, as well as kidney and liver fibrosis models. Transcriptome analyses reveal that genes involved in fatty acid oxidation are significantly perturbed. Furthermore, mitochondrial dysfunction and acylcarnitine accumulation are found in fibrotic tissues. Substantial downregulation of the PGC1α gene is evident in both in vitro and in vivo fibrosis models, suggesting a common node of metabolic signature for tissue fibrosis. In order to identify suppressors of fibrosis, we carry out a compound library phenotypic screen and identify AMPK and PPAR as highly enriched targets. We further show that pharmacological treatment of MK-8722 (AMPK activator) and MK-4074 (ACC inhibitor) reduce fibrosis in vivo. Altogether, our work demonstrate that metabolic defect is integral to TGF-β signaling and fibrosis.

Diallyl disulfide (DADS) has been demonstrated to exert potent anticancer effects in vitro and in vivo. Previous studies indicate that DADS may induce the differentiation and/or apoptosis of human leukemia cells in vitro. However, the mechanisms underlying these anticancer effects remain elusive. The aim of the present study was to investigate alterations in the subcellular localization of protein deglycase DJ‑1 (also known as Parkinsonism associated deglycase-7, PARK-7) in the cytoplasm, nucleus and mitochondria of human leukemia HL‑60 cells induced by DADS, in order to provide novel experimental evidence for the molecular mechanisms underlying the anticancer mechanisms of DADS in leukemia cells. HL‑60 cells induced by DADS were collected at different time points, and proteins from the cytoplasm, nucleus and mitochondria of the cells were isolated using specific cellular component isolation kits. The protein expression levels of DJ‑1 in these subcellular fractions of HL60 cells following exposure to DADS for varying lengths of time, were determined using western blotting, immunocytochemistry and immunofluorescence techniques. Following exposure of HL‑60 cells to 1.25 mg/l DADS for 8 h, the protein expression levels of DJ‑1 were significantly decreased in the cytoplasm, while nuclear fractions exhibited a significant increase in DJ‑1 expression when compared with untreated controls. The protein expression levels of DJ‑1 in mitochondria of HL‑60 cells were significantly decreased following treatment with 5 and 10 mg/l DADS. These results demonstrate that exposure of HL‑60 cells to low concentrations of DADS may promote DJ‑1 protein translocation from the cytoplasm to the nucleus, which suggests that DJ‑1 may function as a transcription factor or cofactor binding protein in the process of cell differentiation. The expression of DJ‑1 in mitochondria may be associated with induction of apoptosis in HL‑60 cells treated with moderate doses of DADS.

The present study examined the effect of diallyl disulfide (DADS) on the invasion and migration ability of HL-60 cells with a high expression of parkinsonism associated deglycase (DJ-1) in the nucleus (HHDN), and its molecular mechanism. A western blot assay was used to measure the effects of DADS and an Src inhibitor on the expression of DJ-1 and the Src signal pathway in HHDN. The effects of DADS and Src inhibitors on the invasion and migration ability of HHDN was detected using Transwell migration and invasion chamber experiments. The experiments were divided into three groups: A control group (HL-60 cells), an empty vector group and a high expression group (HHDN cells). Western blot assays revealed that the expression of DJ-1 in HHDN was inhibited in a time-dependent manner following treatment with DADS for 24, 48 and 72 h. Following DADS treatment, the expression of phosphorylated Src (p-Src) and phosphorylated Fak (p-Fak) were significantly decreased in all groups compared with the untreated groups, however the expression level of Src, Fak and integrin did not change significantly. Western blot analysis results revealed that following treatment with DADS and Src inhibitor, the expression levels of p-Src and p-Fak significantly decreased in all three groups compared with untreated groups, whereas the expression levels of Src, Fak and integrin did not change significantly. The expression of DJ-1 in HHND was inhibited in time-dependent manner following treatment with DADS and Src inhibitor for 24, 48 and 72 h. Transwell migration and invasion assay results revealed that DADS and Src inhibitors may suppress migration and invasion in leukemic cells, and a combination of the two treatments may result in more efficient suppression. DADS may downregulate DJ-1-mediated invasion and migration in leukemic cells through suppressing the Src-Fak-Integrin signaling pathway, and the Src inhibitor may enhance the antitumor effect of DADS.

Tai Chi and Qigong are the two similar traditional Chinese wellness exercises. A strong body of published clinical randomized controlled trials (RCTs) has investigated the health benefits of Tai Chi and Qigong exercises (TCQE) in patients with essential hypertension (EH). This is the first meta-analysis to evaluate the efficacy of TCQE on blood pressure (BP) and blood levels of nitric oxide (NO) and endothelin-1 (ET-1) in EH patients and explore the potential antihypertensive mechanism of TCQE.

The p53 protein ensures cellular fidelity by suppressing or killing cells under stresses that enhance the mutation rate. Evidence suggests that the p53 protein may also ensure the fidelity of the epigenome. In this study a group of drugs that alter the deoxycytosine methylation patterns in cellular DNA are shown to preferentially kill human and mouse cells that contain p53 mutations or deficiencies. These observations are extended to mice that contain p53 deficiencies or missense mutations in their genome, which are preferentially killed when compared to mice with a wild type p53 gene. This is also the case for human cancer cell xenografts containing p53 mutations, which preferentially are killed by these drugs when compared to similar tumors with wild type p53. The loss of p53 function enhances a synthetic lethality with drugs that block or alter the patterns of deoxycytidine methylation in the genome.

Diallyl disulfide (DADS) has shown potential as a therapeutic agent in various cancers. Previously, calreticulin (CRT) was found to be downregulated in differentiated HL-60 cells treated with DADS. The present study investigated the role of CRT proteins in DADS-induced proliferation, invasion and differentiation in HL-60 cells. The present study demonstrated that DADS treatment significantly changed the morphology of HL-60 cells and caused the significant time-dependent downregulation of CRT. Small interfering RNA (siRNA)-mediated knockdown of CRT expression significantly inhibited proliferation, decreased invasion ability, increased the expression of cluster of differentiation (CD)11b and reduced the expression of CD33 in DADS-treated HL-60 cells. DADS also significantly affected cell proliferation, invasion and differentiation in CRT-overexpressed HL-60 cells. Nitroblue tetrazolium (NBT) reduction assays showed decreased NBT reduction activity in the CRT overexpression group and increased NBT reduction in the CRT siRNA group. Following treatment with DADS, the NBT reduction abilities in all groups were increased. In conclusion, the present study clearly demonstrates the downregulation of CRT during DADS-induced differentiation in HL-60 cells and indicates that CRT is involved in cell proliferation, invasion and differentiation in DADS-treated HL-60 cells.

Diallyl disulfide (DADS), the main active component of the cancer fighting allyl sulfides found in garlic, has shown potential as a therapeutic agent in various cancers. Previous studies showed DADS induction of HL-60 cell differentiation involves down-regulation of calreticulin (CRT). Here, we investigated the mechanism of DADS-induced differentiation of human leukaemia cells and the potential involvement of CRT and CCAAT enhancer binding protein-α (C/EBPα). We explored the expression of CRT and C/EBPα in clinical samples (20 healthy people and 19 acute myeloid leukaemia patients) and found that CRT and C/EBPα expressions were inversely correlated. DADS induction of differentiation of HL-60 cells resulted in down-regulated CRT expression and elevated C/EBPα expression. In severe combined immunodeficiency mice injected with HL-60 cells, DADS inhibited the growth of tumour tissue and decreased CRT levels and increased C/EBPα in vivo. We also found that DADS-mediated down-regulation of CRT and up-regulation of C/EBPα involved enhancement of reactive oxidative species. RNA immunoprecipitation revealed that CRT bound C/EBPα mRNA, indicating its regulation of C/EBPα mRNA degradation by binding the UG-rich element in the 3' untranslated region of C/EBPα. In conclusion, the present study demonstrates the C/EBPα expression was correlated with CRT expression in vitro and in vivo and the molecular mechanism of DADS-induced leukaemic cell differentiation.

In mammalian lungs, airway smooth muscle cells (airway SMCs) are present in the proximal lung adjacent to bronchi and bronchioles, but are absent in the distal lung adjacent to terminal sacs that expand during gas exchange. Evidence suggests that this distribution is essential for the formation of a functional respiratory tree, but the underlying genetic mechanism has not been elucidated. In this study, we test the hypothesis that fibroblast growth factor 9 (Fgf9) signaling is essential to restrict SMC differentiation to the proximal lung. We show that loss of Fgf9 or conditional inactivation of Fgf receptors (Fgfr) 1 and 2 in mouse lung mesenchyme results in ectopic SMCs. Our data support a model where FGF9 maintains a SMC progenitor population by suppressing differentiation and promoting growth. This model also represents our findings on the genetic relationship between FGF9 and sonic hedgehog (SHH) in the establishment of airway SMC pattern.

Cofilin is associated with cell differentiation; however, to the best of our knowledge, no data have indicated an association between the cofilin 1 pathway and leukemia cell differentiation. The present study investigated the involvement of the cofilin 1 signaling pathway in diallyl disulfide (DADS)‑induced differentiation and the inhibitory effects on the proliferation, migration, and invasion of human leukemia HL‑60 cells. First, it was identified that 8 µM DADS suppressed cell proliferation, migration and invasion, and induced differentiation based on the reduced nitroblue tetrazolium ability and increased CD11b and CD33 expression. DADS significantly downregulated the expression of cofilin 1 and phosphorylated cofilin 1 in HL‑60 leukemia cells. Second, it was verified that silencing cofilin 1 markedly promoted 8 µM DADS‑induced differentiation and the inhibitory effect on cell proliferation and invasion. Overexpression of cofilin 1 obviously suppressed 8 µM DADS‑induced differentiation and the inhibitory effect on cell proliferation and invasion. Third, the present study examined the mechanisms by which 8 µM DADS decreases cofilin 1 expression and activation. The results revealed that 8 µM DADS inhibited the mRNA and protein expression of Rac1, Rho‑associated protein kinase 1 (ROCK1) and LIM domain kinase 1 (LIMK1) as well as the phosphorylation of LIMK1 in HL‑60 cells, while 8 µM DADS enhanced the effects of the Rac1‑ROCK1‑LIMK1 pathway in cells overexpressing cofilin 1 compared with that in control HL‑60 cells. These results suggest that the anticancer function of DADS on HL‑60 leukemia cells is regulated by the Rac1‑ROCK1‑LIMK1‑cofilin 1 pathway, indicating that DADS could be a promising anti‑leukemia therapeutic compound.

Gene set enrichment (GSE) analysis plays an essential role in extracting biological insight from genome-scale experiments. ORA (overrepresentation analysis), FCS (functional class scoring), and PT (pathway topology) approaches are three generations of GSE methods along the timeline of development. Previous versions of KOBAS provided services based on just the ORA method. Here we presented version 3.0 of KOBAS, which is named KOBAS-i (short for KOBAS intelligent version). It introduced a novel machine learning-based method we published earlier, CGPS, which incorporates seven FCS tools and two PT tools into a single ensemble score and intelligently prioritizes the relevant biological pathways. In addition, KOBAS has expanded the downstream exploratory visualization for selecting and understanding the enriched results. The tool constructs a novel view of cirFunMap, which presents different enriched terms and their correlations in a landscape. Finally, based on the previous version's framework, KOBAS increased the number of supported species from 1327 to 5944. For an easier local run, it also provides a prebuilt Docker image that requires no installation, as a supplementary to the source code version. KOBAS can be freely accessed at http://kobas.cbi.pku.edu.cn, and a mirror site is available at http://bioinfo.org/kobas.

In recent years, the ability of neural stem cells (NSCs) transplantation to treat Parkinson's disease (PD) has attracted attention. However, it is still a challenge to promote the migration of NSCs to the lesion site and their directional differentiation into dopaminergic neurons in PD. C-C motif chemokine ligand 5 (CCL5) and C-C motif chemokine receptor 5 (CCR5) are expressed in the brain and are important regulators of cell migration. It has been reported that ethyl stearate (PubChem CID: 8122) has a protective effect in 6-OHDA-induced PD rats.

In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai.

In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai.