Factors associated with different types of freight crashes: A macro-level analysis.

INTRODUCTION: Despite evidence showing higher fatality rates in freight-related crashes, there has been limited exploration of their spatial distribution and factors associated with such distribution. This gap in the literature primarily stems from the focus of existing studies on micro-level factors predicting the frequency or severity of injuries in freight crashes. The present study delves into the factors contributing to freight crashes at the neighborhood level, particularly focusing on different types of freight crashes: collisions involving a freight vehicle and a passenger vehicle, crashes between freight vehicles, and freight vehicle-non-motorized crashes. METHOD: This study analyzes traffic crash data from the urbanized region of Seoul, collected between 2016 and 2019. To effectively deal with spatial autocorrelation and model different types of crashes in a unified framework, a Bayesian multivariate conditional autoregressive model was employed. RESULTS: Findings show substantial differences in the factors associated with various types of freight crashes. The predictors for crashes between freight vehicles diverge significantly from those for freight vehicle-non-motorized crashes. Crashes between freight vehicles are relatively more influenced by road network structure, while freight crashes involving non-motorized users are relatively more affected by the built environment and freight facilities than the other crash types examined. Freight vehicle-passenger vehicle crashes fall into an intermediate category, sharing most predictors with either of the other two types of freight crashes. CONCLUSIONS AND PRACTICAL APPLICATIONS: The findings of this study offer valuable lessons for transportation practitioners and policymakers. They can guide the formulation of effective land use policies and infrastructure planning, specifically designed to address the unique characteristics of different types of freight crashes.

Integrative roles of sphingosine kinase in liver pathophysiology.

Bioactive sphingolipids and enzymes that metabolize sphingolipid-related substances have been considered as critical messengers in various signaling pathways. One such enzyme is the crucial lipid kinase, sphingosine kinase (SphK), which mediates the conversion of sphingosine to the potent signaling substance, sphingosine-1-phosphate. Several studies have demonstrated that SphK metabolism is strictly regulated to maintain the homeostatic balance of cells. Here, we summarize the role of SphK in the course of liver disease and illustrate its effects on both physiological and pathological conditions of the liver. SphK has been implicated in a variety of liver diseases, such as steatosis, liver fibrosis, hepatocellular carcinoma, and hepatic failure. This study may advance the understanding of the cellular and molecular foundations of liver disease and establish therapeutic approaches via SphK modulation.

Pharmacokinetic Characterization of LW6, a Novel Hypoxia-Inducible Factor-1α (HIF-1α) Inhibitor in Mice.

LW6, an (aryloxyacetylamino)benzoic acid derivative, was recently identified to be an inhibitor of hypoxia-inducible factor-1α (HIF-1α), which is an attractive target for cancer therapeutics. Although LW6 is known to act by inhibiting the accumulation of HIF-1α, pharmacokinetics needs to be evaluated to assess its potential as an anti-tumor agent. Here, we investigated the plasma pharmacokinetics and metabolism of LW6 in mice. LW6 exhibited a small volume of distribution (0.5 ± 0.1 L/kg), and a short terminal half-life (0.6 ± 0.1 h). Following intravenous or oral administration, LW6 was rapidly converted to its active metabolite, (4-adamantan-1-yl-phenoxy)acetic acid (APA). Although LW6 was rapidly absorbed, its oral bioavailability, estimated using AUClast values, was low (1.7 ± 1.8%). It was slowly degraded in mouse liver microsomes (t1/2 > 1 h) and serum (t1/2 > 6 h). About 54% or 44.8% of LW6 was available systemically as APA in the mouse after a single intravenous or oral administration, respectively. Thus, our results indicated the need to simultaneously consider the active metabolite as well as the parent compound for successful evaluation during lead optimization.

Metabolite Profiling and Characterization of LW6, a Novel HIF-1α Inhibitor, as an Antitumor Drug Candidate in Mice.

A novel HIF (hypoxia-inducible factor)-1α inhibitor, the (aryloxyacetylamino)benzoic acid derivative LW6, is an anticancer agent that inhibits the accumulation of HIF-1α. The aim of this study was to characterize and determine the structures of the metabolites of LW6 in ICR mice. Metabolite identification was performed using a predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion (pMRM-IDA-EPI) method in negative ion mode on a hybrid triple quadrupole-linear ion trap mass spectrometer (QTRAP). A total of 12 metabolites were characterized based on their MS/MS spectra, and the retention times were compared with those of the parent compound. The metabolites were divided into five structural classes based on biotransformation reactions: amide hydrolysis, ester hydrolysis, mono-oxidation, glucuronidation, and a combination of these reactions. From this study, 2-(4-((3r,5r,7r)-adamantan-1-yl)phenoxy)acetic acid (APA, M7), the metabolite produced via amide hydrolysis, was found to be a major circulating metabolite of LW6 in mice. The results of this study can be used to improve the pharmacokinetic profile by lowering the clearance and increasing the exposure relative to LW6.

Ameliorative effect of persimmon (Diospyros kaki) in cognitively impaired diabetic mice.

The effects of ethanolic extract of Diospyros kaki (EED) on diabetic cognitive impairment were investigated in high-fat diet (HFD)-induced mouse. After HFD was fed to mouse for 16 weeks, EED was administrated to mouse for 4 weeks. EED reduced fasting blood glucose level and improved cognitive and behavioral dysfunction. EED improved serum biomarkers related to lipid and liver damage better than positive control (PC). In addition, EED ameliorated impaired cholinergic system, increased oxidative stress as well as mitochondrial dysfunction compared with HFD group. In the molecular study, EED downregulated the phosphorylation of c-Jun N-terminal kinase (p-JNK), which phosphorylates the serine residue of insulin receptor substrate-1 (IRS-1pSer). Finally, various physiological compounds such as tannin-based ingredients were identified using UPLC-QTOF/MS2 . These results suggest that EED can help improve cognitive impairment caused by HFD. PRACTICAL APPLICATIONS: Recently, cognitive impairment caused by type 2 diabetes mellitus (T2DM) has become a problem. T2DM, mainly derived from HFD, is characterized by hyperglycemia, which is associated with insulin resistance. In this study, EED not only improved hyperglycemia and insulin resistance, but also restored diabetes-related cognitive dysfunction in HFD-induced diabetic mice. Finally, the decrease in cholinergic and antioxidant systems related to cognitive impairment was recovered by consumption of EED via improvement of insulin signaling pathway. Therefore, this study suggests that persimmon (Diospyros kaki) containing diverse physiological compounds has potential and industrial value as a functional food material for cognitive improvement.

Dielectric Elastomers UV-Cured from Poly(dimethylsiloxane) Solution in Vinyl Acetate.

Poly(dimethylsiloxane) (PDMS) has been extensively used as an electroactive polymer material because it exhibits not only excellent moldability but also mechanical properties sufficient enough for electroactive performance despite low dielectric permittivity. Its low dielectric property is due to its molecular non-polarity. Here, we introduce a polar group into a PDMS elastomer by using vinyl acetate (VAc) as a crosslinker to improve the dielectric permittivity. We synthesized a high-molecular weight PDMS copolymer containing vinyl groups, namely poly(dimethylsiloxane-co-methylvinylsiloxane) (VPDMS), and prepared several of the VPDMS solutions in VAc. We obtained transparent PDMS films by UV curing of the solution layers. Electromechanical actuation-related physical properties of one of the UV-cured films were almost equivalent to or superior to those of platinum-catalyzed hydrosilylation-cured PDMS films. In addition, saponification of the UV-cured film significantly improved the electrical and mechanical properties (ɛ' ~ 44.1 pF/m at 10 kHz, E ~ 350 kPa, ɛ ~ 320%). The chemical introduction of VAc into PDMS main chains followed by saponification would offer an efficacious method of enhancing the electroactive properties of PDMS elastomers.

Anti-Amnesic Effect of Walnut via the Regulation of BBB Function and Neuro-Inflammation in Aß1-42-Induced Mice.

This study was conducted to assess the protective effect of walnut (Juglans regia L.) extract on amyloid beta (Aß)1-42-induced institute of cancer research (ICR) mice. By conducting a Y-maze, passive avoidance, and Morris water maze tests with amyloidogenic mice, it was found that walnut extract ameliorated behavioral dysfunction and memory deficit. The walnut extract showed a protective effect on the antioxidant system and cholinergic system by regulating malondialdehyde (MDA) levels, superoxide dismutase (SOD) contents, reduced glutathione (GSH) contents, acetylcholine (ACh) levels, acetylcholinesterase (AChE) activity, and protein expression of AChE and choline acetyltransferase (ChAT). Furthermore, the walnut extract suppressed Aß-induced abnormality of mitochondrial function by ameliorating reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP contents. Finally, the walnut extract regulated the expression of zonula occludens-1 (ZO-1) and occludin concerned with blood-brain barrier (BBB) function, expression of tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 1 (TNFR1), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IκB), cyclooxygenase-2 (COX-2), and interleukin 1 beta (IL-1ß), related to neuroinflammation and the expression of phosphorylated protein kinase B (p-Akt), caspase-3, hyperphosphorylation of tau (p-tau), and heme oxygenase-1 (HO-1), associated with the Aß-related Akt pathway.

Facile Functionalization of Poly(Dimethylsiloxane) Elastomer by Varying Content of Hydridosilyl Groups in a Crosslinker.

Crosslinked poly(dimethylsiloxane) (PDMS) has been widely used as a dielectric elastomer for electrically driven actuators because it exhibits high elasticity, low initial modulus, and excellent moldability in spite of low dielectric constant. However, further improvement in the characteristics of the PDMS elastomer is not easy due to its chemical non-reactivity. Here, we report a simple method for functionalizing the elastomer by varying content of hydridosilyl groups in PDMS acted as a crosslinker. We synthesized poly(dimethylsiloxane-co-methylvinylsiloxane) (VPDMS) and poly(dimethylsiloxane-co-methylsiloxane) (HPDMS). Tri(ethylene glycol) divinyl ether (TEGDE) as a polar molecule was added to the mixture of VPDMS and HPDMS. TEGDE was reacted to the hydridosilyl group in HPDMS during crosslinking between VPDMS and HPDMS in the presence of platinum as a catalyst. Permittivity of the crosslinked film increased from ca. 25 to 36 pF/m at 10 kHz without a decline in other physical properties such as transparency and elasticity (T > 85%, E ~150 kPa, ɛ ~270%). It depends on the hydridosilyl group content of HPDMS. The chemical introduction of a new molecule into the hydridosilyl group in HPDMS during crosslinking would provide a facile, effective method of modifying the PDMS elastomers.

Structural features of lignin macromolecules extracted with ionic liquid from poplar wood.

1-Ethyl-3-methylimidazolium acetate ([Emim][CH3COO]) was used for the extraction of lignin from poplar wood (Populus albaglandulosa), which was called to ionic liquid lignin (ILL) and structural features of ILL were compared with the corresponding milled wood lignin (MWL). Yields of ILL and MWL were 5.8±0.3% and 4.4±0.4%, respectively. The maximum decomposition rate (V(M)) and temperature (T(M)) corresponding to V(M) were 0.25%/ °C and 308.2 °C for ILL and 0.30%/ °C and 381.3 °C for MWL. The amounts of functional groups (OMe and phenolic OH) appeared to be similar for both lignins; approximately 15.5% and 6.7% for ILL and 14.4% and 6.3% for MWL. However, the weight average molecular weight (M(w)) of ILL (6347 Da) was determined to be 2/3-fold of that of MWL (10,002 Da) and polydispersity index (PDI: M(w)/M(n)) suggested that the lignin fragments were more uniform in the ILL (PDI 1.62) than in the MWL (PDI 2.64).

Laparoscopic repair of paraduodenal hernia: comparison with conventional open repair.

Paraduodenal hernia is a congenital internal hernia caused by abnormal retroperitoneal fixation of the intestinal mesentery. The management of paraduodenal hernia consists of reduction of the herniated intestine and repair of the defect. Recently, laparoscopic surgery has been increasingly performed in abdominal procedures. To evaluate the feasibility and efficacy of laparoscopic repair of paraduodenal hernia, we present our experience in 2 cases of laparoscopic repair, compared with 3 other cases treated with conventional open repair; all 5 cases were successfully treated. All patients had symptoms of intestinal obstruction and were diagnosed by preoperative abdominal computed tomography. Two cases were right-sided hernias, and 3 cases were left sided. Among them, 2 patients with left-sided paraduodenal hernia underwent laparoscopic reduction (LR group) of the herniated small bowel, and the other 3 cases underwent open reduction (OR group). In the LR group, the duration of hospital stay, time to first flatus, and time to first intake of a soft diet were shorter than in the OR group. Thus, with an accurate preoperative diagnosis of paraduodenal hernia, laparoscopic surgery may be a feasible and efficient procedure, with good postoperative outcomes.