Exposure risk assessment of 3-chloropropanol esters in 0-3 aged infants

Objective To analyze the chloropropanol monoesters (MCPD esters) levels in the infant formulas available in Hangzhou market from 2017 to 2019, and to assess the exposure risk of MCPD esters for 0-3 years infants. Methods Concentrations of 3-MCPD esters and 2-MCPD esters in the infant formulas were determined with gas chromatography-mass spectrometry (GC-MS). 3-MCPD esters exposure risk in target population was assessed by the level of 3-MCPD esters in infant formulas and the consumption recommendation from diatery guideline. Results The 3-MCPD esters and 2-MCPD esters contamination existed in all infant formulas samples; the median and P97.5 daily dietary exposure of 3-MCPD esters were 0.46-2.50 and 0.87-4.30 μg/kg BW, account for 23.0%-125.0% and 43.5%-215.0% of the tolerable daily intake (TDI, 2 μg/kg BW per day) respectively. For infants aged 0-6 months, the high intake levels (P97.5) of 3-MCPD esters were above TDI. Conclusion The levels of 3-MCPD esters in infant formulas sold in Hangzhou may pose a potential risk. Infants aged 0-6 months had higher exposure level than other age groups

Network pharma cology and GEO chip based elucidation of mechanisms underlying the use of Yi Tieqing for prevention and treatment of postoperative nausea and vomiting

Purpose: To investigate the mechanism(s) involved in the use of Yi Tieqing for the prevention and treatment of postoperative nausea and vomiting (PONV), using network pharmacology and GEO chip. Methods: The chemical constituents and functional targets of five traditional Chinese medicines in Yi Tieqing were obtained by searching TCMSP database. The PONV disease targets were identified through DisGeNET, GeneCards and DrugBank databases, and differential expression genes of the GEO database chip (GSE7762) were mined. From the intersections of the component targets and disease targets, the core targets of drugs and diseases were obtained. The core targets were investigated in R language using GO-biological process and KEGG enrichment analyses, and their biological activities were verified via molecular docking. Finally, the severity and incidence of PONV in control and treatment groups were determined and compared. Results: A total of 254 bioactive components and 301 related potential targets were obtained from the TCMSP database. There were 2092 related targets in PONV, and 6 intersecting targets were obtained from Venn diagram. The results of GO biological process and KEGG enrichment analysis showed that the incidence of PONV was strongly correlated with the negative regulation of response to wounding and nervous system. Clinical results showed that from 24 – 48 h (T2) after operation, the severity and incidence of PONV in the treatment group were significantly lower than those in the control group (p < 0.05). Conclusion: Yi Tieqing alleviates PONV through multi-components, multi-targets, and multi-pathways

Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting

Background: An intimidating challenge to transporting drugs into the brain parenchyma is the presence of the blood-brain barrier (BBB). Glucose is an essential nutritional substance for brain function sustenance, which cannot be synthesized by the brain. Its transport primarily depends on the glucose transporters on the brain capillary endothelial cells. In this paper, the brain-targeted properties of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers were compared and evaluated to establish an optimized drug-delivery system. Methods: Coumarin 6-loaded liposomes (GLU200-LIP, GLU400-LIP, GLU1000-LIP, and GLU2000-LIP) composed of phospholipids and glucose-derived cholesterols were prepared by thin-film dispersion-ultrasound method. The BBB model in vitro was developed to evaluate the transendothelial ability of the different liposomes crossing the BBB. The biodistribution of liposomes in the mice brains was identified by in vivo and ex vivo nearinfrared fluorescence imaging and confocal laser scanning microscopy and further analyzed quantitatively by high-performance liquid chromatography. Results: Glucose-derived cholesterols were synthesized and identified, and coumarin 6-loaded liposomes were prepared successfully. The particle sizes of the four types of glucose-modified liposomes were around or smaller than 100 nm with a polydispersity index less than 0.300. GLU400-LIP, GLU1000-LIP, and GLU2000-LIP achieved higher cumulative cleared volumes on BBB model in vitro after 6 hours compared with GLU200-LIP (P < 0.05) and were significantly higher than that of the conventional liposome (P < 0.001). The qualitative and quantitative biodistribution results in the mice showed that the accumulation of GLU1000-LIP in the brain was the highest among all the groups (P < 0.01 versus LIP). Conclusion: The data indicated that GLU400-LIP, GLU1000-LIP, and GLU2000-LIP all possess the potential of brain targeting, among which GLU1000-LIP, as a promising drug-delivery system, exhibited the strongest brain delivery capacity.Nanoscience & NanotechnologyPharmacology & PharmacySCI(E)0ARTICLE163-175

Effects of Ultrasonic Atomization of Slightly Acidic Electrolyzed Water on the Circulation and Shelf Quality of Postharvest Baby Cabbage

To check the effect of slightly acidic electrolyzed water (SAEW) on the shelf quality of postharvest baby cabbage, the effects of ultrasonic atomization fumigation of SAEW with different concentrations (0, 50, 100 and 150 mg/L) on the postharvest preservation of baby cabbage were analyzed under low temperature circulation (4±1) ℃and shelf conditions (25±1) ℃. The results showed that, compared with the control and other concentrations of SAEW (50 and 150 mg/L), the ultrasonic atomization fumigation treatment of SAEW at 100 mg/L treatment significantly suppressed the increase in malondialdehyde content and the decrease in total glucosinolate content of baby cabbage at the 6th and 9th days of shelf life (P<0.05). Further circulation and shelf simulation results indicated that, compared with the control, the 100 mg/L SAEW ultrasonic atomization fumigation treatment reduced the total number of colonies by 17.04% and increased the total glucosinolate content by 30.11% in baby cabbage; In addition, this treatment significantly inhibited the accumulation of nitrite and malondialdehyde content (P<0.05), delayed the decline of soluble sugar, soluble protein, total phenol, ascorbic acid and isothiocyanate content, and increased the activity of myrosinase in postharvest baby cabbage. It was clear that ultrasonic atomization fumigation treatment of SAEW at 100 mg/L could not only effectively inhibit the growth of the total number of colonies in baby cabbage during circulation and shelf life, but also effectively slow down the degradation of nutritional quality in baby cabbage during this process, thus improving the preservation effect of baby cabbage

Prompt-to-afterglow transition of optical emission in a long gamma-ray burst consistent with a fireball

Long gamma-ray bursts (GRBs), which signify the end-life collapsing of very massive stars, are produced by extremely relativistic jets colliding into circumstellar medium. Huge energy is released both in the first few seconds, namely the internal dissipation phase that powers prompt emissions, and in the subsequent self-similar jet-deceleration phase that produces afterglows observed in broad-band electromagnetic spectrum. However, prompt optical emissions of GRBs have been rarely detected, seriously limiting our understanding of the transition between the two phases. Here we report detection of prompt optical emissions from a gamma-ray burst (i.e. GRB 201223A) using a dedicated telescope array with a high temporal resolution and a wide time coverage. The early phase coincident with prompt {\gamma}-ray emissions show a luminosity in great excess with respect to the extrapolation of {\gamma}-rays, while the later luminosity bump is consistent with onset of the afterglow. The clearly detected transition allows us to differentiate physical processes contributing to early optical emissions and to diagnose the composition of the jetComment: Authors' version of article published in Nature Astronomy, see their website for official versio

Molecularly imprinted polymer based on MWCNTs-QDs as fluorescent biomimetic sensor for specific recognition of target protein

A novel molecularly imprinted optosensing material based on multi-walled carbon nanotube-quantum dots (MWCNT-QDs) has been designed and synthesized for its high selectivity, sensitivity and specificity in the recognition of a target protein bovine serum albumin (BSA). Molecularly imprinted polymer coated MWCNT-QDs using BSA as the template (BMIP-coated MWCNT-QDs) exhibits a fast mass-transfer speed with a response time of 25 min. It is found that the BSA as a target protein can significantly quench the luminescence of BMIP-coated MWCNT-QDs in a concentration-dependent manner that is best described by a Stem-Volmer equation. The K-SV for BSA is much higher than bovine hemoglobin and lysozyme, implying a highly selective recognition of the BMIP-coated MWCNT-QDs to BSA. Under optimal conditions, the relative fluorescence intensity of BMIP-coated MWCNT-QDs decreases linearly with the increasing target protein BSA in the concentration range of 5.0 x 10(-7)-35.0 x 10(-7) M with a detection limit of 80 nM

MicroRNA-1224 Inhibits Tumor Metastasis in Intestinal-Type Gastric Cancer by Directly Targeting FAK

Intestinal-type gastric cancer (GC) of the Lauren classification system has specific epidemiological characteristics and carcinogenesis patterns. MicroRNAs (miRNAs) have prognostic significance, and some can be used as prognostic biomarkers in GC. In this study, we identified miR-1224 as a potential survival-related miRNA in intestinal-type GC patients by The Cancer Genome Atlas (TCGA) analysis. Using quantitative real-time PCR (qRT-PCR), we showed that the relative expression of miR-1224 was significantly decreased in intestinal-type GC tissues compared to matched adjacent normal mucosa tissues (p &lt; 0.01). We found that high miR-1224 expression was associated with no lymph-node metastasis (p &lt; 0.05) and good prognosis (p = 0.028) in 90 intestinal-type GC tissues. Transfection of intestinal-type GC cells with miR-1224 mimics showed that miR-1224 suppressed cell migration in vitro (wound healing assay and Transwell migration assay), whereas the transfection of cells with miR-1224 inhibitor promoted cell migration in vitro. miR-1224 also suppressed intestinal-type GC cell metastasis in a xenograft mouse model. Furthermore, bioinformatics, luciferase reporter, Western blotting, and immunohistochemistry (IHC) studies demonstrated that miR-1224 directly bound to the focal adhesion kinase (FAK) gene, and downregulated its expression, which decreased STAT3 and NF-κB signaling and subsequent the epithelial-to-mesenchymal transition (EMT). Repression of FAK is required for the miR-1224-mediated inhibition of cell migration in intestinal-type GC. The present study demonstrated that miR-1224 is downregulated in intestinal-type GC. miR-1224 inhibits the metastasis of intestinal-type GC by suppressing FAK-mediated activation of the STAT3 and NF-κB pathways, and subsequent EMT. miR-1224 could represent an important prognostic factor in intestinal-type GC

Structure and Influencing Factors of the Global Cooperation Network of E-Sports Teams

With the progress of information technology and the transformation of the global economy, the digital economy is increasingly showing rapid growth and is becoming a key force in restructuring global factor resources, the global economic structure, and the global competitive landscape. E-sports, which is an emerging cultural industry and sport, has great significance in promoting cultural exchanges among countries and enhancing their respective national soft power. Presently, owing to its professionalization, internationalization, and ecologization, e-sports enables broader and multidimensional connections between game participants. However, e-sports cooperation networks based on virtual communities have not yet received widespread attention. Therefore, this study uses the information database of the participating teams of three international e-sports events, namely, the League Of Legends World Championship, The International DOTA2 Championships, and the CS: GO Major, to explore the structure of transnational e-sports team networks and their evolution from a theoretical perspective of virtual communities. This study uses the social network analysis and the gravitational model methods to reveal the multidimensional proximity and national attributes that influence the e-sports cooperative network patterns. The results show that first, the spatial evolution of the global e-sports cooperation network shows rapid expansion and low density, weak association, and strong dynamic network characteristics. The number of nodes increases rapidly while the network density shows a fluctuating decrease. This indicates that the development of Internet technology and the increasing popularity of e-sports have drawn increasingly more countries to participate in international e-sports activities, and the node connection of the e-sports cooperation network tends to be decentralized as a whole. Second, the global e-sports cooperation network has evolved into five associations representing geographical regions: the European associations with Denmark, Sweden, Finland, and Germany as the core, the Asia-Pacific associations with China and South Korea as the main partners, the Commonwealth of Independent States associations with Russia and Ukraine as the main partners, the Latin American associations with Peru and Argentina, as the main partners, and the Intercontinental associations with the United States and Canada as the main partners. Third, the spatial structure of the global e-sports cooperation network is influenced by the interrelationship between countries and their respective industrial bases. Social and organizational proximities drive the formation of e-sports cooperation networks, whereas geographical and cultural proximities do not significantly affect e-sports team cooperation. The interaction between geographical proximity and social proximity on the intensity of e-sports cooperation reflects a substitution effect; scientific research expenditure, e-sports revenue, and e-sports strength are the key elements affecting countries' importance in e-sports cooperation networks. Conversely, economic scale and general factors such as economic size and education level do not have significant effects on global e-sports team cooperation. This reflects the uniqueness of the e-sports industry in a digital economy. This study contributes to the research on the reconfiguration of industrial organization networks driven by the digital economy. Furthermore, this study provides a reference for making China's e-sports industry internationally competitive by improving its e-sports training system

A Herpesvirus Virulence Factor Inhibits Dendritic Cell Maturation through Protein Phosphatase 1 and IκB Kinase▿

Dendritic cells are sentinels in innate and adaptive immunity. Upon virus infection, a complex program is in operation, which activates IκB kinase (IKK), a key regulator of inflammatory cytokines and costimulatory molecules. Here we show that the γ134.5 protein, a virulence factor of herpes simplex viruses, blocks Toll-like receptor-mediated dendritic cell maturation. While the wild-type virus inhibits the induction of major histocompatibility complex (MHC) class II, CD86, interleukin-6 (IL-6), and IL-12, the γ134.5-null mutant does not. Notably, γ134.5 works in the absence of any other viral proteins. When expressed in mammalian cells, including dendritic cells, γ134.5 associates with IKKα/β and inhibits NF-κB activation. This is mirrored by the inhibition of IKKα/β phosphorylation, p65/RelA phosphorylation, and nuclear translocation in response to lipopolysaccharide or poly(I:C) stimulation. Importantly, γ134.5 recruits both IKKα/β and protein phosphatase 1, forming a complex that dephosphorylates two serine residues within the catalytic domains of IκB kinase. The amino-terminal domain of γ134.5 interacts with IKKα/β, whereas the carboxyl-terminal domain binds to protein phosphatase 1. Deletions or mutations in either domain abolish the activity of γ134.5. These results suggest that the control of IκB kinase dephosphorylation by γ134.5 represents a critical viral mechanism to disrupt dendritic cell functions

H₂ Dissociation on H Precovered Ni(111) Surfaces: Coverage Dependence, Lattice Motion, and Arrangement Effects

Hydrogen molecule dissociation on metal surfaces is a prototype reaction to study the gas–surface interaction. The dissociation rate constants of H₂ on H atom precovered Ni(111) surfaces are calculated using the quantum instanton method in full dimensionality. Four different arrangements of the preadsorbed H and the dissociated H₂, in which the preadsorbed H is located at the nearest (H₂/H¹–Ni­(111)), second-nearest (H₂/H²–Ni­(111)), third-nearest (H₂/H³–Ni­(111)), and fourth-nearest (H₂/H⁴–Ni­(111)) neighbor sites of the bridge site where the H₂ is dissociated, are considered. Compared to the dissociation rates of H₂ on a clean Ni(111) surface (H₂/Ni­(111)), the dissociation rates of H₂/H¹–Ni­(111) are much smaller. For instance, the former is 5.22 times larger than the latter at 300 K. This is because there is a strong repulsive interaction between the preadsorbed H and H₂, which hinders the dissociation of H₂. The dissociation rates of the four arrangements increase in the order of H₂/H¹–Ni­(111), H₂/H²–Ni­(111), H₂/H³–Ni­(111), and H₂/H⁴–Ni­(111). For example, the rate constants ratio of H₂/H²–Ni­(111) to H₂/H¹–Ni­(111) is 4.40 at 300 K. This situation further reveals that the repulsive interaction decreases quickly with the increase of the distance between the preadsorbed H and H₂. For the process of H₂/H¹–Ni­(111), the dissociation rates on the mobile lattice are larger than those on the rigid lattice. For instance, the lattice motion enhances the dissociation rate by 29% at 300 K. The calculated kinetic isotope effects are larger than 1, and increase rapidly with decreasing temperature, which demonstrates that the quantum tunneling effect is remarkable. All of the kinetic isotope effects for H₂/Ni­(111), H₂/H¹–Ni­(111), H₂/H²–Ni­(111), H₂/H³–Ni­(111), and H₂/H⁴–Ni­(111) are close to each other, which indicates that surface coverage, lattice motion, and arrangement effects affect the kinetic isotope effect a little