Analyzing driver injury severity in two-vehicle rear-end crashes considering leading-following configurations based on passenger car and light truck involvement.

Rear-end crash is a major type of traffic crashes leading to a large number of injuries and fatalities each year, and passenger cars and light trucks are two main vehicle types in rear-end crashes on US roadways. Passenger cars and light trucks are different in size, vehicle mass and driver's vision. It is necessary to investigate the driver injury outcome patterns in rear-end crashes between passenger cars and light trucks considering crash configurations regarding the leading and following vehicle types. This study employs latent class multinomial logit (MNL) model to examine the risk factors on driver injury severity along with heterogeneity in variable effects presented by the cluster pattern in two-vehicle rear-end crashes involving passenger cars and light trucks, considering four crash configuration types, i.e., a passenger car struck by a passenger car, a light truck struck by a light truck, a passenger car struck by a light truck, and a light truck struck by a passenger car as exploratory variables. A model with two latent classes, which indicates the heterogeneity in variable effects among all the observations, is found to best fit the 7-year crash dataset from Washington State. The pseudo-elasticities are calculated to quantify the marginal effects of the contributing factors. The risk factors curve and sloping road condition, driver without seatbelt, and driver age of 65 and above increase driver fatality and serious injury risk greatly, and these three factors contribute from different latent classes. The crash configuration of a passenger car struck by a light truck is found to be one of class characteristics factors, which indicates that the heterogeneity exists between these two vehicle types. This factor is also a risk factor of injury. Furthermore, the leading vehicle is found to be much more vulnerable and closely related to injury, especially when it is in the crash of a passenger car struck by a light truck. The latent classes discovered give theoretical evidence of how to appropriately select subset data for further model construction for practical interest of serious injury prevention. The risk factors and their influence on injury severity provide beneficial insights on developing relevant countermeasures and strategies for injury severity mitigation on rear-end crashes involving passenger cars and light trucks.

Down-regulation of histone deacetylase 7 reduces biological activities of retinal microvascular endothelial cells under high glucose condition and related mechanism.

AIM: To investigate the expression and effect of histone deacetylase 7 (HDAC7) in human retinal microvascular endothelial cells (HRMECs) under high glucose condition and related mechanism, and the expression of HDAC7 in the retinal tissue in diabetic rats. METHODS: The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot. LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities. Cell count kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, scratch test, Transwell test and tube formation assay were used to examine the ability of cell proliferation, migration, and angiogenesis. Finally, a preliminary exploration of its mechanism was performed by Western blot. RESULTS: The expression of HDAC7 was both up-regulated in retinal tissues of diabetic rats and high glucose-treated HRMECs. Down-regulation of HDAC7 expression significantly reduced the ability of proliferation, migration, and tube formation, and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs. CONCLUSION: High glucose can up-regulate the expression of HDAC7 in HRMECs. Down-regulation of HDAC7 can inhibit HRMECs activities. HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.

HDAC7/c-Myc signaling pathway promotes the proliferation and metastasis of choroidal melanoma cells.

Choroidal melanoma (CM) is the most common type of diagnosed uveal melanoma (UM), which is prone to metastasis and exhibits a poor prognosis. The molecular mechanisms underlying CM progression need further elucidation to research effective therapeutic strategies. Histone deacetylase 7 (HDAC7) is very important in regulating cancer progression, but the significance and effect of HDAC7 on CM progression are unclear. In the present study, we found that HDAC7 is overexpressed in CM tissues versus normal tissues. We built HDAC7 overexpressing CM cell lines to study the functions of HDAC7 in CM progression and verified that upregulation of HDAC7 promoted the proliferation and metastasis of CM cells, while pharmacological inhibition of HDAC7 suppressed both the proliferation and metastasis of CM cells. Furthermore, we found that the aforementioned cancer-promoting effect of HDAC7 was mediated by c-Myc. Targeted inhibition of c-Myc inhibited CM progression by interfering with the HDAC7/c-Myc signaling pathway. Our study highlighted the function of targeting the HDAC7/c-Myc signaling pathway to intervene in the pathological process of CM, which provides potential therapeutic strategies for CM treatment.

Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs.

Lipid nanoparticle (LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology. LNPs can encapsulate and deliver a wide variety of bioactive agents, including the small molecule drugs, proteins and peptides, and nucleic acids. However, as the physicochemical properties of small- and macromolecular cargos can vary drastically, every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner. Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery. In this Review, we highlight our recent progress in the design, synthesis, characterization, evaluation, and optimization of combinatorial LNPs with novel structures and properties for the delivery of small- and macromolecular therapeutics both in vitro and in vivo. These delivery systems have enormous potentials for cancer therapy, antimicrobial applications, gene silencing, genome editing, and more. We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics.

Palladium-catalyzed monoselective C-H borylation of acetanilides under acidic conditions.

A practical Pd-catalyzed reaction was developed to achieve C-H activation/C-B cross-coupling of acetanilides under acidic conditions. The new reaction shows a good functional group tolerance and an exclusive mono-selectivity. This C-H borylation method may provide a generally applicable route for the conversion of C-H moieties into many other types of bonds.

[Studies on the association between beta 2-glycoprotein I and hepatotropism of hepatitis B virus].

OBJECTIVE: To further study the binding character of hepatitis B surface antigen (HBsAg) and beta 2-glycoprotein I (beta2GP I) and to explore whether beta2GP I plays an important role in the hepatotropism of hepatitis B virus. METHODS: Using Western blot technique, we observed the binding character of the HBsAg with reduced and non-reduced beta2GP I. RESULTS: rHBsAgs with reduced and non-reduced beta2GP I showed identical binding activity. CONCLUSIONS: The binding activity of HBsAg is dependent on tandem residues, but not on conformational structures of beta2GP I. There is a specific binding between HBV and beta2GP I, which may play an important role in HBV infection and is one of the reasons of hepatotropism of HBV.

A possible receptor for beta 2 glycoprotein I on the membrane of hepatoma cell line smmc7721.

OBJECTIVES: To study the interaction of beta-2-glycoprotein I (beta 2GPI) with the membrane of hepatocytes and determine whether beta 2GPI participates in HBV infection. METHODS: Ligand blotting, fluorescence microscopy, and fluorescence activated cell sorter (FACS) analysis were used to detect the specific interaction of beta 2GPI with the hepatoma cell line smmc7721, the gastric carcinoma cell line SGC7901, and the lymphoma cell line HL-60. RESULTS: A specific 40 kDa beta 2GPI band was observed by ligand blotting in the case of smmc7721 cells. No such band was observed in SGC7901 or HL-60 cells. Fluorescence microscopy also revealed specific binding of FITC-beta 2GPI to smmc7721 cells, but neither to SGC7901 nor HL-60 cells. FACS analysis demonstrated that the binding rate of FITC-beta 2GPI to smmc7721 cells was significantly higher than these in SGC7901 and HL-60 cells (P < 0.01). The binding rate to smmc7721 cells did not increase with increasing amounts of FITC-beta 2GPI. CONCLUSIONS: There is a specific beta 2GPI-binding protein on the membrane of hepatoma cells in cell line smmc7721 which as the beta 2GPI receptor may participate in HBV infection of hepatocytes.

Studies on specific interaction of beta-2-glycoprotein I with HBsAg.

AIM: To observe the binding activity of beta-2-glycoprotein I(beta(2)GPI) to hepatitis B surface antigen (HBsAg) and the possible roles of beta(2)GPI in hepatitis B virus (HBV) infection. METHODS: The rationale of ELISA methods and ELISA-based research method and ligand-blotting technique were used to detect the specific interaction of beta(2)GPI with HBsAg. RESULTS: With the increase of rHBsAg, the binding of beta(2)GPI to rHBsAg elevated, and these changes had statistic significance. When we added non- biotinlyated beta(2)GPI, the OD value significantly decreased though they still were positively relevant to rHBsAg, suggesting non- biotinlyated beta(2)GPI competed with biotinlyated beta(2)GPI to saturate the binding sites on rHBsAg. Meanwhile BSA was used as negative control to substitute for rHBsAg coating the plates. The results indicated no interaction between beta(2)GPI and BSA, suggesting the affinity of beta(2)GPI to rHBsAg was specific. The ligand blotling indicated that beta(2)GPI might bind to rHBsAg no matter whether it was under reduced condition or not. CONCLUSION: The binding of beta(2)GPI to HBsAg suggests that beta(2)GPI may be a carrier of HBV and that beta(2)GPI may play important roles in HBV infection.

[Relation between Beta-2-glycoprotein I and hepatitis B virus surface antigen].

OBJECTIVE: To clarify the binding character between Beta-2-glycoprotein I (Beta-2-GPI) and HBsAg. METHODS: Beta-2-GPI was purified from human plasma and labelled with biotin. Solid phase enzyme linked absorbance assay was used to investigate its binding with HBsAg. RESULTS: Biotinylated Beta-2-GPI was found to bind HBsAg and the reaction could be inhibited by excess unlabelled Beta-2-GPI. CONCLUSIONS: Beta-2-GPI may play a role in hepatitis B virus infection.

Effects of the Superoxide Anionic Radicals to the Cultured Cerebral Cortex Neuron of Newborn Rat.

The effect of the superoxide anionic radicals to the cultured cerebral cortex neuron of newborn rat was investigated by using xanthine oxidase/xanthine. The results are as follows. The growth of neuron was inhibited ATPase activity decreased to 4.223 &mgr;mol/(mg.min(-1))(Pr) total cellular carbonyl increased to 295.40 &mgr;mol/g wet weight lipid peroxides(LPO) increased to 4.87 nmol/g(Pr) membrane lipid fluidity decreased (P value 0.398) in nuclear DNA, thesingle strand breaks(SSB) increased in the single cell gel assay(SCG), DNA migration was 7.35 mm ݣ subcellular structures of the neuron changed (mitochondria were swelling, etc.) and SOD gene expression of the neuron increased (the SOD activity and the SOD content increased, SOD mRNA content increased). These suggest that the superoxide anionic radicals could damage proteins, nucleic acids, lipids and subcellular structures in neurons.