ObjectivesSun glare is a serious driving hazard and increases crash risks. Relatively few studies have examined the effects of sun glare on pedestrian fatalities, given that a crash has occurred. The ...primary objective of this study was to investigate the effect of sun glare on pedestrian fatalities.DesignA population-based case–control study.SettingTaiwan.ParticipantsUsing the Taiwan National Traffic Crash Data and sunrise and sunset data from the National Oceanic and Atmospheric Administration for the period 2003 to 2016, 100 411 pedestrians involved in crashes were identified. Of these crashes, 13 355 and 87 056 were glare-related (case) and non-glare-related (control) crashes, respectively.MethodsTo account for unobserved heterogeneity, mixed logit models were estimated to identify the determinants of pedestrian fatalities.Main outcome measuresPedestrian fatalities.ResultsPedestrians involved in glare-related crashes were more likely to be fatally injured than those in non-glare-related crashes (β=0.527; t=3.21). Other contributory factors to fatal injuries among pedestrians were older pedestrians (β=0.553; t=2.33), male drivers (β=0.324; t=2.33), older drivers (β=0.218; t=2.14), intoxicated motorists (β=0.606; t=2.85), rural roadways (β=0.985; t=3.92), overtaking manoeuvres (β=0.472; t=3.58), heavy vehicle crash partners (β=0.248; t=2.78) and sunset hours (β=0.274; t=3.08). Walking against traffic appeared beneficial for decreasing injury severity (β=−0.304; t=−2.76).ConclusionsSun glare is associated with pedestrian fatalities. Older pedestrians, male drivers, older drivers and intoxicated motorists are prevalent determinants of pedestrian fatalities in glare-related crashes.
Background
The role of carbohydrate antigen 19‐9 (CA 19‐9) in response assessment among patients with intrahepatic cholangiocarcinoma (iCCA) remains unknown. The authors studied the association of ...the CA 19‐9 response (defined as a reduction >50% from baseline) with the radiologic response and the outcome in patients with unresectable iCCA.
Methods
A prospective cohort of 422 patients who were initially diagnosed with unresectable iCCA, had baseline CA 19‐9 levels ≥100 U/mL, and received treatment with systemic therapies at the authors' institution between January 2017 and December 2021 were enrolled in this study. The radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A landmark assessment of the CA 19‐9 response and the radiologic response was performed. The associations between CA 19‐9 response and imaging response, progression‐free survival (PFS), and overall survival (OS) were analyzed.
Results
Two hundred sixty‐seven patients (63.3%) had a CA 19‐9 response. A CA 19‐9 response was observed in 123 of 132 (93.2%) radiologic responders and in 144 of 290 (49.7%) radiologic nonresponders (p < .001). CA 19‐9 responders outperformed nonresponders in median PFS (10.6 vs. 3.6 months; hazard ratio HR, 4.8 months; 95% confidence interval CI, 3.8–6.0 months; p < .001) and OS (21.4 vs. 6.3 months; HR, 5.3 months; 95% CI, 4.2–6.7 months; p < .001). The common independent predictors of both OS and PFS included metastasis, CA 19‐9 nonresponder status, and radiologic nonresponder status in multivariable analysis.
Conclusions
CA 19‐9 response is a valuable addition to assess tumor response and is associated with improved outcomes in patients with iCCA. Achieving a CA 19‐9 response should be one of the therapeutic objectives of patients with iCCA after systemic therapies.
Plain language summary
A decline in carbohydrate antigen 19‐9 levels from elevated baseline levels should be one of the therapeutic aims of patients with intrahepatic cholangiocarcinoma who are managed with systemic therapies.
Biomarkers for predicting treatment outcomes are an unmet need for patients with intrahepatic cholangiocarcinoma (iCCA) treated with systemic therapies. This article shows that the carbohydrate antigen 19‐9 response correlates with the radiologic response and outcome of patients with iCCA after treatment.
In order to clarify the chemical constituents of Si-Wu Decoction rapidly and holistically, we analyzed the ethanol extract of Si-Wu Decoction by UPLC/Q-TOF-MSE and UNIFI which based on traditional ...Chinese medicine database, the probable structures of 113 compounds were identified. The results show that this method can rapidly and effectively characterize the chemical compounds of Si-Wu Decoction and provide a new solution for identification of components from complex TCM extract.
Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with ...coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.
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•Spatial proteome maps of COVID-19 myocardia and microvessels are established•SARS-CoV-2-driven inflammation leads to region-resolved dysfunction of the heart•Mechanisms of dysregulated contraction, conduction, and circulation are elaborated•Myocardia and microvessels of the left atrium are affected by inflammation the most
Leng et al. establish a region-resolved proteome map of the inflammatory myocardia and microvessels of COVID-19 hearts. The myocardia and microvessels of the left atrium are the most affected by inflammation storm. These results could provide guidance in improvement of clinical treatments for cardiovascular diseases associated with COVID-19.
The aim of this study was to investigate the effects of chronic intermittent hypoxia (CIH) on atrial electrical remodeling in Sprague-Dawley (SD) rats, which provide the explication for the ...mechanisms of CIH promoting atrial fibrillation (AF).
Eighty SD rats were randomly divided into 2 groups: control group and CIH group (
=40). CIH rats were subjected to CIH 8 h/d for 30 days. After the echocardiography and hemodynamics examination, cardiac electrophysiological experiments, histological experiments, and molecular biological experiments were executed. AF susceptibility was measured by isolated heart electrophysiological experiments. Masson's trichrome stain was used to assess the degree of atrial fibrosis. The protein expression levels of sodium voltage-gated channel alpha subunit 5 (SCN5A/Na
1.5), calcium voltage-gated channel subunit alpha1 C (CACNA1C/Ca
1.2) and potassium voltage-gated channel subfamily D member 3 (KCND3/K
4.3) were measured by Western blot. In whole-cell patch clamp experiments, current
Schematic diagram of fisetin in LPS-induced septic AKI.
Fisetin modulated the activities of TLR4/Src-mediated NF-κB p65 and MAPK pathways, thus alleviating kidney inflammation and apoptosis in ...LPS-induced septic AKI.
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•Fisetin is a polyphenolic flavonoid in many fruits and vegetables.•Fisetin alleviated kidney injury against LPS-induced septic AKI.•Fisetin inhibited LPS-induced kidney inflammation and apoptosis.•Fisetin inhibited renal Src-mediated NF-κB and MAPK signalling pathways in LPS-induced septic AKI.
Sepsis is defined as end-organ dysfunction resulting from the host’s inflammatory response to infection. One of the most common sepsis-injured organs is the kidneys, resulting in acute kidney injury (AKI) that contributes to the high morbidity and mortality, especially patients in the intensive care unit. Fisetin, a naturally occurring flavonoid, has been reported to protect against the rat of lipopolysaccharide (LPS)-induced acute lung injury. However, the effect of fisetin on septic AKI remains unknown.
The current study proposed to systematically investigate the renoprotective effects and the underlying mechanisms of fisetin in septic AKI mice.
The model of septic AKI was established on male C57BL/6 J mice by a single intraperitoneal injection of LPS (10 mg/kg). Fisetin was administrated by gavage at 100 mg/kg for 3 consecutive days before LPS injection and the mice were sacrificed at 16 h after LPS injection. The serum and kidney samples were evaluated for biochemical analysis, histopathological examinations as well as inflammation and apoptosis related gene/protein expression.
Pretreatment with fisetin significantly alleviated the elevated levels of serum creatinine and blood urea nitrogen in LPS-treated mice. Consistently, LPS induced renal damage as implied by histopathological score and the increased injury markers NGAL and KIM-1, which was attenuated by fisetin. Meanwhile, LPS injection triggered proinflammatory cytokine production and inflammation related proteins in the kidneys. However, fisetin inhibited renal expression of IL-6, IL-1β, TNF-α, HMGB1, iNOS and COX-2 to improve inflammatory response. Furthermore, fisetin effectively reduced the number of TUNEL positive apoptotic cells and suppressed apoptotic protein of Bcl-2, BAX and cleaved caspase-3 in the kidneys of LPS-induced septic AKI. Mechanistically, LPS stimulated the expression of TLR4 and the phosphorylation of NF-κB p65, MAPK (p38, ERK1/2 and JNK), Src and AKT in the injured kidneys, while fisetin notably suppressed the corresponding protein expression.
Fisetin alleviated kidney inflammation and apoptosis to protect against LPS-induced septic AKI mice via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways
Cellulase has many potential applications in ethanol production, extraction of medicinal ingredients, food, brewing, oil exploration, environmental protection. However, the widespread use of ...cellulase is limited by its relatively high production costs and low biological activity. Therefore, we studied the enzymatic properties and reusability of cellulase immobilized on multiwalled carbon nanotubes and sodium alginate for the first time. The results showed that the optimum temperature and pH of immobilized cellulase was 40 °C and 3.0, respectively. After 1 month of storage at 4 °C, the enzyme activity of immobilized cellulase dropped to 71.2% of the baseline. Immobilized cellulase was proved to be reusable and maintained ~ 70% of its activity after 7 cycles of repeated use. Versus free cellulase, the immobilized cellulase showed good thermal stability, pH resistance, storage stability and reusability, which could be beneficial in large-scale industrial manufacturing processes.
Nitrogen（N） is one of the macronutrients required for plant growth, and reasonable application of N fertilizers can increase crop yields and improve their quality. However, excessive application of N ...fertilizers will decrease N use efficiency and also lead to increases in N2O emissions from agricultural soils and many other environmental issues. Research on the effects of different N fertilizer management practices on wheat yields and N2O emissions will assist the selection of effective N management measures which enable achieving high wheat yields while reducing N2O emissions. To investigate the effects of different N management practices on wheat yields and soil N2O emissions, we conducted field trials with 5 treatments of no N fertilizer（CK）, farmers common N rate（AN）, optimal N rate（ON）, 20% reduction in optimal rate＋dicyandiamide（ON80%＋DCD）, 20% reduction in optimal rate＋nano-carbon（ON80%＋NC）. The static closed chamber gas chromatography method was used to monitor N2O emissions during the wheat growing season. The results showed that there were obvious seasonal characteristics of N2O emissions under each treatment and N2O emissions were mainly concentrated in the sowing-greening stage, accounting for 54.6–68.2% of the overall emissions. Compared with AN, N2O emissions were decreased by 23.1, 45.4 and 33.7%, respectively, under ON, ON80%＋DCD and ON80%＋NC, and emission factors were declined by 22.2, 66.7 and 33.3%, respectively. Wheat yield was increased significantly under ON80%＋DCD and ON80%＋NC by 12.3 and 11.9%, respectively, relative to AN while there was no significant change in yield in the ON treatment. Compared with ON, overall N2O emissions were decreased by 29.1 and 13.9% while wheat yields improved by 18.3 and 17.9% under ON80%＋DCD and ON80%＋NC, respectively. We therefore recommend that ON80%＋DCD and ON80%＋NC be referred as effective N management practices increasing yields while mitigating emissions.
Green purchasing plays an increasingly significant role in today’s supply chain management. Recycling, as a key factor in sustainable development, is seriously considered by many manufacturers during ...the process of procurement. In order to establish long-term green purchasing relationships between multi-stakeholders (suppliers and manufacturers), in this study the supplier selection concept model suggested by de Boer is updated, and an evolutionary game model is developed to observe the cooperation tendency of multi-stakeholders. The newly proposed game model intensively studies the trade behavior which can be realized as strategies and payoff functions of the suppliers and manufacturers. In addition, a replicator dynamic system is formulated to study evolutionarily stable strategies of multi-stakeholders. To verify the theoretical results, simulation experiments are conducted with meaningful results: the manufacturing industry can form the patterns of sustainable development, and the recycling capability of suppliers directly determines how green a supply chain is. The results can guide stakeholders to make better decisions in the future.
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