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In liver cirrhosis, hepatic inflammation and abundant portal-systemic collaterals are indicated for the development of hepatic encephalopathy. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a type of anti-diabetic agent which exert pleiotropic and anti-inflammatory effects. Diabetes and chronic liver disease often coexist, but the influence of SGLT-2 inhibition on liver cirrhosis and hepatic encephalopathy remains unknown. This study investigated the effect of SGLT-2 inhibition on cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats via common bile duct ligation. A total of two weeks of treatment with the SGLT-2 inhibitor, empagliflozin 30 mg/kg/d, was applied. The motor activities, hemodynamics, biochemistry parameters, plasma levels of vascular endothelial growth factor (VEGF), and the severity of portal-systemic collateral shunts were measured. The hepatic histopathology and protein expressions were examined. We found that empagliflozin treatment did not affect hemodynamics, liver biochemistry, or blood glucose levels in cirrhotic rats. Empagliflozin did not affect hepatic inflammation and fibrosis. The protein expression of factors related to liver injury were not influenced by empagliflozin. However, empagliflozin decreased motor activities in cirrhotic rats and increased portal-systemic collateral shunts and VEGF plasma levels. In summary, SGLT-2 inhibition by empagliflozin did not ameliorate portal hypertension and hepatic inflammation in cirrhotic rats. In contrast, it exacerbated hepatic encephalopathy, which was evidenced by a decrease in motor activity. A possible mechanism could be an increase of portal-systemic shunts related to VEGF upregulation. Therefore, empagliflozin use should be cautious in cirrhotic patients regarding the development of hepatic encephalopathy. SIGNIFICANCE STATEMENT: Sodium-glucose cotransporter-2 inhibition by empagliflozin did not ameliorate portal hypertension and hepatic inflammation in cirrhotic rats. In contrast, it exacerbated hepatic encephalopathy through increased portal-systemic shunts related to VEGF up-regulation.

Soil erosion in East and Southeast Asia is believed to have increased significantly since the regional economic boom of the 1970s-1980s. However, limited records of soil erosion make it difficult to understand and indeed verify such changes. Here we present two new monthly resolved Ba/Ca records from Porites coral skeletons from southern Taiwan and central Vietnam, supplemented with some sporadic monthly and annually resolved coral delta Ba-138/134 data. Our records span the 1980s to the 2000s and suggest that there were intervals of elevated seawater Ba concentrations (Ba-sw) during the intervals 1987-1995 in southern Taiwan and 1992-2001 in central Vietnam. In combination with evidence for insignificant changes in regional seawater delta Ba-138/134 values, model simulations, and other published coral Ba/Ca records from Lanyu (offshore southeast Taiwan) and Hainan, we infer that the intervals of high Ba-sw values are linked to soil erosion associated with land use changes and socioeconomic developments. The increased sediment loads are also likely responsible for the recent degradation of regional coral reefs. Our study provides new insights into regional soil erosion histories, which may prove useful for guiding soil conservation and sustainable land management. ISSN:0148-0227 ISSN:2169-9275

BACKGROUND Portal hypertension is a pathophysiological abnormality with distinct vascular derangements associated with liver cirrhosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors are anti-diabetic agents which exert pleiotropic vascular effects, but their relevant impact on portal hypertension and liver cirrhosis remains unclear. This study aims to clarify this issue. METHODS Rats receiving partial portal vein-ligation (PVL) and common bile duct-ligation (BDL) served as experimental models for portal hypertension and cirrhosis, respectively. After linagliptin (a DPP-4 inhibitor) treatment, the survival rate, hemodynamics, biochemistry parameters and liver histopathology were evaluated. In addition, the collateral vascular responsiveness and severity of portal-systemic shunting were examined. mRNA and protein expression in the vasculature and liver were also examined. RESULTS Linagliptin significantly reduced portal pressure (control vs. linagliptin: 12.9±1.2 vs. 9.1±2.0 mmHg, p=0.001) and up-regulated nitric oxide synthase expression in the collateral vessel, superior mesentery artery and liver of PVL rats. However, the portal hypotensive effect was insignificant in BDL rats. Glucose plasma levels, liver and renal biochemistry parameters were not significantly altered by linagliptin. The degree of portal-systemic shunting and collateral vascular responsiveness were also not significantly altered by linagliptin treatment. Linagliptin did not improve liver fibrosis and hepatic inflammation in BDL rats. CONCLUSION DPP-4 inhibition by linagliptin reduced portal pressure in portal hypertensive rats but not in cirrhotic rats. It may act by decreasing intra-hepatic resistance via up-regulation of hepatic nitric oxide synthase in portal hypertensive rats.

Liver cirrhosis and portal hypertension are accompanied by hyperdynamic circulation, angiogenesis and portosystemic collaterals. Matrix metalloproteinases (MMPs) participate in fibrogenesis and angiogenesis, however, whether they can be targeted in cirrhosis treatment is unclear. Therefore, we performed three series of experiments to investigate this issue. Liver cirrhosis was induced by common bile duct ligation (BDL) in Sprague‐Dawley rats. Sham‐operated rats served as controls. Rats were randomly allocated to receive vehicle, minocycline (a nonselective MMP inhibitor) or SB‐3CT (MMP‐2 and −9 inhibitor) for 28 days in the first and second series, respectively. MMP‐9 knockout mice were used in the third series. The results showed that minocycline ameliorated portal hypertension, hemodynamic abnormalities, reduced collateral shunting, mesenteric vascular density, plasma VEGF level and alleviated liver fibrosis. SB‐3CT attenuated portal hypertension, hemodynamic derangements, reduced shunting, mesenteric vascular density, mesenteric VEGF protein expression, and liver fibrosis. Knockout BDL mice had significantly alleviated portal hypertension, liver fibrosis, liver α‐SMA and mesenteric eNOS protein expressions compared to wild‐type BDL mice. Liver SMAD2 phosphorylation was down‐regulated in all series with MMP inhibition or knock‐out. In conclusion, MMP‐9 inhibition or deletion ameliorated the severity of cirrhosis, portal hypertension, and associated derangements. MMP‐9 may be targeted in the treatment of liver cirrhosis.

This research is an investigation of public transport carbon footprints using a life cycle assessment (the model of total carbon footprint as Eq. 1 on page 17) considering four different types of fuel (diesel, electric, liquefied natural gas, and hydrogen). This paper refers to ISO 14040:2006 and ISO 14067:2018 to evaluate the carbon footprints of these four different types of fuel. The bus transportation service in Kaohsiung, Taiwan, is the object, focusing on the route with the largest number of passengers. The results reveal that the hydrogen fuel cell bus emitted the least GHGs over its life cycle, with a reduction of − 67.52% compared to a diesel bus, while the electronic bus emitted − 55.13% less GHG over its life cycle, and the liquefied natural gas bus emitted − 45.81% less. These mean diesel buses and liquefied natural gas buses accounted for the most emissions in the bus service fuel phase of the carbon footprint life cycle. However, electric and hydrogen fuel cell buses do not emit GHGs in the bus service phase in terms of fuel. The phases involving the extraction and manufacturing of raw materials for both kinds of buses account for most of the life cycle emissions. In conclusion, the results of this study show that the hydrogen fuel cell bus has the greatest effects with regard to reducing GHG emissions among the three types of buses under consideration, and so, it is recommended that hydrogen fuel cell buses be widely applied in bus transportation in the future.

Exposure to low temperatures has been associated with increased gastroesophageal variceal bleeding in patients with cirrhosis and portal hypertension; however, the mechanism remains unclear. Therefore, the aim of the present study was to evaluate the impact of environmental temperature reduction on portal hypertension and the role of adrenergic signaling pathways in this phenomenon. Male Sprague-Dawley rats underwent common bile duct ligation or partial portal vein ligation to induce liver cirrhosis and/or portal hypertension. The impacts of acute or chronic changes in environmental temperature were surveyed. The results showed that acute cooling from 25 to 15°C and 5°C increased the portal pressure by 10.6% and 15.5% in cirrhotic rats, and by 22.2% and 36.1% in portal hypertensive rats, respectively. The transient portal pressure surge started shortly after cooling, reached a peak within 5 min and returned to baseline after 10 min. Systemic vascular resistance, mean arterial pressure and splanchnic blood flow increased significantly at the same time. Plasma epinephrine and norepinephrine concentrations, phospholipase C, protein kinase C activity and myosin phosphorylation of peripheral arteries increased significantly in response to cooling. Phentolamine (an α-blocker) but not propranolol (a non-selective β-blocker) dose-dependently inhibited the transient portal pressure surge and aforementioned molecular changes. In conclusion, environmental temperature reduction induced peripheral vasoconstriction via α-adrenergic pathways, and redistribution of blood flow to the splanchnic system led to a surge in transient portal pressure. Treatment with α-adrenergic receptor antagonists may exert additional benefits in controlling portal hypertension, especially on exposure to low temperatures.

BACKGROUND This study aimed to evaluate whether the role-play (RP) of real patients by medical students as part of interactive clinical reasoning training can improve medical students' clinical performance. METHODS A total of 26 medical students volunteered to portray real patients within this program and were treated as the RP group while the other 72 students as the non-RP group. In the interactive morning meeting, the medical students practiced how to approach the RP student as if they were encountering a real patient. All students were evaluated by mini-clinical evaluation exercises (mini-CEX) before and after this training program. RESULTS We found that all students had an increased total mini-CEX score after 4-week training, especially for interviewing skills. Notably, after training, the RP students had significantly elevated total mini-CEX scores (51.23 ± 1.06 vs 53.12 ± 1.11, p = 0.028), and for counselling (7.15 ± 0.14 vs 7.54 ± 0.18, p = 0.015) and overall clinical competence (7.27 ± 0.15 vs 7.65 ± 0.16, p = 0.030). In contrast, the non-RP students had lower scores compared with the RP group, as revealed by both the pre- and post-training tests. Moreover, their mini-CEX scores were not improved after training. CONCLUSION Medical students who were motivated to RP real patients had better performance scores than those who did not. In addition, RP can enhance their counselling skills and clinical competences.

Liver cirrhosis is characterized by liver fibrosis and pathological angiogenesis, which results in hyperdynamic circulation, portal-systemic collateral vascular formation, and abnormal angiogenesis. Lycopene is a nutrient mostly found in tomatoes. The beneficial effects of lycopene include anti-inflammation, anti-oxidation, anti-fibrosis, and anti-angiogenesis; however, the association between liver cirrhosis and pathological angiogenesis has yet to be studied. This study aimed to investigate the effects of lycopene on biliary cirrhotic rats.The efficacy of lycopene treatment in common bile duct ligation (BDL)-induced biliary cirrhotic rats was evaluated. Sham-operated rats served as surgical controls. Lycopene (20 mg/kg/day, oral gavage) or vehicle was administered to BDL or sham-operated rats for 4 weeks, after which the hemodynamics, liver biochemistry, portal-systemic shunting, liver and mesenteric angiogenesis, and hepatic angiogenesis-related protein expressions were examined.Lycopene alleviated hyperdynamic circulation as evidenced by decreased cardiac index and increased peripheral vascular resistance (p0.05), but it did not affect portal pressure or liver biochemistry in the BDL rats (p0.05). Lycopene significantly diminished the shunting degree of portal-systemic collaterals (p = 0.04) and mesenteric vascular density (p = 0.01), and also ameliorated intrahepatic angiogenesis and liver fibrosis. In addition, lycopene upregulated endothelial nitric oxide synthase, protein kinase B (Akt) and phosphatidylinositol 3-kinases (PI3K), and downregulated vascular endothelial growth factor receptor 2 (VEGFR-2) protein expressions (p0.05) in the livers of the BDL rats.Lycopene ameliorated liver fibrosis, hyperdynamic circulation, and pathological angiogenesis in biliary cirrhotic rats, possibly through the modulation of intrahepatic Akt/PI3K/eNOS and VEGFR-2 pathways.

Portal hypertension develops along with liver cirrhosis then induces the formation of portal-systemic collaterals and lethal complications. Extrahepatic angiogenesis plays an important role. Glycyrrhizin has been found to exhibit anti-angiogenic features, which leads to its extensive use. However, the relevant effects of glycyrrhizin on liver cirrhosis and portal hypertension have not been evaluated. This study thus aimed to investigate the impact of glycyrrhizin on portal hypertension-related derangements in cirrhotic rats. Male Sprague-Dawley rats received bile duct ligation (BDL) to induce cirrhosis or sham operation as control. The rats were subdivided to receive glycyrrhizin (150 mg/kg/day, oral gavage) or vehicle beginning on the 15th day post operation, when BDL-induced liver fibrosis developed. The effects of glycyrrhizin were determined on the 28th day, the typical timing of BDL-induced cirrhosis. Glycyrrhizin significantly reduced portal pressure (p = 0.004). The splanchnic inflow as measured by superior mesenteric arterial flow decreased by 22% (p = 0.029). The portal-systemic collateral shunting degree reduced by 30% (p = 0.024). The mesenteric angiogenesis and phospho-VEGFR2 protein expression were also downregulated (p = 0.038 and 0.031, respectively). Glycyrrhizin did not significantly influence the liver biochemistry data. Although glycyrrhizin tended to reverse liver fibrosis, statistical significance was not reached (p = 0.069). Consistently, hepatic inflow from portal side, hepatic vascular resistance, and liver fibrosis-related protein expressions were not affected. Glycyrrhizin treatment at the stage of hepatic fibrosis still effectively attenuated portal hypertension and portosystemic collateral shunting. These beneficial effects were attributed to, at least in part, the suppression of mesenteric angiogenesis by VEGF signaling pathway downregulation.

BACKGROUND Medical students in Taiwan start their clerkship in their fifth year. A lack of early clinical exposure can mean they have a lack of medical professionalism and collaborative practice. This study investigates whether early engagement in hospital-based clinical practice could improve their understanding of these requirements. METHODS From 2017 to 2019, a total of 59 medical students at the end of their third year joined a 2-week summer camp at the hospital. Every participant was assigned to work with one patient and they accompanied this patient throughout their hospital course. The students were also asked to interview other medical professionals within the hospital and to write up interview reports. In addition, they had to complete pre- and postcamp questionnaires which included 10 questions to evaluate their recognition of professionalism, doctor-patient relationships, and interprofessional collaboration. Answers to the questions were all rated using a 5-score Likert scale. RESULTS The total postcamp Likert scores were significantly increased after the 2-week training camp compared with the precourse scores (pre- vs postcourse: 44.08 ± 0.45 vs 46.66 ± 0.33, p < 0.001). In addition, the students' recognition of medical professionalism, the importance of communication with patients, and their respect for other medical professionals were significantly improved after the 2-week training. CONCLUSION Our data showed that early clinical exposure through a preclerkship summer camp can help medical students improve their recognition of medical professionalism and interprofessional collaboration.

NSF [EAR1313588]; Taiwan, MOST [107-2116-M-002-001-MY3]; European Union; State of Hungary; European Regional Development Fund [GINOP-2.3.2-15-2016-00009]

This article presents a microcontroller unit (MCU) based simplified discrete wavelet transform (Sim-DWT) algorithm that can detect high-voltage spindles (HVSs) in local field potential (LFP) signals. The Sim-DWT algorithm operates in an 8-bit MCU, 8MHz operating clock and 16 sample points of buffers to detect HVSs with a frequency range of 5−15Hz. The requirement of only sixteen 8-bit sample points as the window length for calculation and no need for a multiplier render the Sim-DWT easy to implement in an MCU with limited hardware resources. The Sim-DWT is applied in an 8-bit MCU with 6mW power consumption (including IO ports) and was tested for detecting LFP signals in vivo. The design methods and the accuracy of three typical types of mother wavelet functions (Haar, DB4, Morlet) in the Sim-DWT were also tested and compared with those of a PC-based system. The experimental results showed that with appropriately designed cMW functions in the Sim-DWT, HVSs could be detected more accurately than they could be in PC-based software. The present study indicates that the optimized HVS detector (Sim-DWT) can be implemented in an 8-bit MCU with limited hardware resources and is suitable to serve as the digital core in a closed-loop deep brain stimulator microsystem in the future.

Human activities have exacerbated the global greenhouse effect, resulting in extreme climate changes that have caused disasters and food and water shortages in recent years. Transportation is one of the main causes of global greenhouse gas (GHG) emission. Therefore, policy makers must develop feasible strategies to reduce GHG emission. One of Taiwan's policy is to replace traditional diesel fuel urban buses with alternative energy buses. This paper uses a case study of city bus route No. 2 in Tainan City following the international standard ISO/TS 14067:2013 to measure the carbon footprint of different energy buses. The bus carbon footprints measured from high to low as: LNG buses, 63.14 g CO2e/pkm; traditional diesel buses, 54.6 g CO2e/pkm; liquefied petroleum gas (LPG) buses, 47.4 g CO2e/pkm; plug-in electric buses, 37.82 g CO2e/pkm, and hydrogen fuel cell buses, 29.17 g CO2e/pkm. If all urban area public buses in Taiwan were switched to hydrogen fuel cell buses, this would reduce CO2e footprint by 227,832.39 t annually. This reduction is equivalent to planting 22.78 million trees.

Human activities have exacerbated global greenhouse effects, resulting in extreme climate changes that have caused disasters and food and water shortages in recent years. Transport activities are the one of the main causes of global greenhouse gas (GHG) emissions. Therefore, policy makers must develop some strategies to reduce GHG emissions. One of the Taiwan’s transportation policies intended to reduce CO2 emissions is to replace all traditional diesel fuel urban buses with alternative energy buses. This paper uses a case study of bus route NO. 2 in Tainan City and follows the international standard ISO/TS 14067 and PAS2050 to measure the carbon footprints of different energy buses. The purpose is to measure the environmental benefits of alternative energy buses. The results of the bus carbon footprints from high to low were LNG buses, 63.14g CO2e/pkm; traditional diesel buses, 54.6g CO2e/pkm; liquefied petroleum gas buses, 47.4g CO2e/pkm; plug-in electric buses, 37.82g CO2e/pkm, and hydrogen fuel cell bus es, 29.17g CO2e/pkm, respectively. It was also found that the use of hydrogen fuel cell buses would potentially reduce CO2e emissions in Tainan City by 1,244,081 tons, which at this time is only city bus No. 2. If all the Taiwan city buses were switched to hydrogen fuel cell buses, this would potentially reduce CO2e by 227,832.39 tons. The effect of the reduction in carbon emissions from the use of hydrogen fuel cells buses in all Taiwanese urban areas is the equivalent of planting 22.78 million trees. It is thus suggested that the government use hydrogen fuel cell buses as the future of the country’s major alternative energy buses since they are the most environmentally friendly alternative to reducing CO2 emissions.

This study aims to design a safe and sustainable food supply chain with food safety mechanisms so that confidence-dependent demand can be positively affected by centralized, decentralized and combined supply chain contracts. To determine the optimal order quantity, buy-back price, rebate/penalty and sales target with the proposed framework, we derive the optimality conditions of corresponding models and use the results to analyze the lard oil supply chain. It is found that supply chain contracts together with the food safety mechanism can drastically improve food safety, consumer confidence and the resulting profits of a food supply chain. What differentiates our work from earlier research efforts is that only few studies have focused primarily on food safety mechanisms that embed a closed-loop supply chain to benefit all stakeholders of a supply chain and we attempt to bridge the gap. Further improvements can be developed based on the models developed in this study.

Ivabradine is a funny current inhibitor which is administered to patients with congestive heart failure to reduce their heart rate (HR) and attenuate oxidative stress. Chronic liver diseases are characterized by portal hypertension and hyperdynamic circulation with tachycardia. The present study aimed to investigate the effect of ivabradine on portal hypertension.Male Sprague-Dawley rats received partial portal vein ligation (PVL) to induce portal hypertension. The PVL rats were randomly allocated to receive either vehicle or ivabradine treatment for 10 days. Then the hemodynamic data were collected. The levels of oxidative stress markers and the mRNA expression of nitric oxide synthase (NOS) were measured in the collateral vessel, the superior mesentery artery and the liver. In addition, the collateral vascular responsiveness to arginine vasopressin (AVP) was examined in the ivabradine-treated and vehicle-treated PVL rats.Treatment with ivabradine significantly lowered the HR (174 ± 20 vs. 374 ± 9 beats/min; p0.001) and the superior mesentery arterial flow (SMAf) (6.6 ± 0.3 vs. 9.1 ± 0.7 mL/min/100 g BW; p = 0.005) of the PVL rats compared with the control group. The mean arterial pressure, cardiac index, systemic vascular resistance, portal pressure and serum levels of oxidative stress markers were not significantly affected by ivabradine treatment. In addition, the NOS expression and collateral vascular responsiveness to AVP were not significantly influenced by ivabradine treatment, either.Ivabradine reduced the HR and SMAf in PVL rats, which alleviated the hyperdynamic circulatory state and splanchnic hyperemia of portal hypertension. However, whether these effects would help alleviate portal hypertension-related complications requires further clinical investigations.

Hyperlipidemia and oxidative stress with elevated oxidized low-density lipoprotein (ox-LDL) exacerbate hepatic inflammation and fibrosis. The plasma level of low-density lipoprotein (LDL) is controlled by proprotein convertase subtilisin/kexin 9 (PCSK9). Alirocumab is a monoclonal antibody that decreases LDL via inhibiting PCSK9 function. Apart from lipid-lowering effects, alirocumab exerts anti-inflammation, anti-angiogenesis and anti-oxidant effects. This study aims to investigate the impact of alirocumab treatment on common bile duct ligation (BDL)-induced biliary cirrhotic rats. After a 4-week treatment of alirocumab, the hemodynamic data, blood biochemistry, ox-LDL level, oxidative stress markers, severity of hepatic encephalopathy and abnormal angiogenesis of BDL rats were measured and compared to the control group. BDL rats presented cirrhotic pictures and elevated ammonia, total cholesterol, LDL and ox-LDL levels compared to the control group. Alirocumab decreased plasma levels of total cholesterol, LDL, and oxidative stress markers; however, it did not affect the hemodynamics, liver and renal biochemistry, and the plasma levels of ammonia and ox-LDL. The motor activities, portal-systemic collaterals and mesenteric vascular density were not significantly different between alirocumab-treated and control groups. In addition, it did not affect hepatic inflammation, intrahepatic angiogenesis, liver fibrosis and free cholesterol accumulation in the liver of BDL rats. In conclusion, PCSK9 inhibition by alirocumab treatment ameliorates hyperlipidemia and systemic oxidative stress in biliary cirrhotic rats. However, it does not affect the plasma level of ox-LDL, intrahepatic inflammation and fibrosis. In addition, PCSK9 inhibition has a neutral effect on abnormal angiogenesis and hepatic encephalopathy in biliary cirrhotic rats.

Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis-related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation (BDL) in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P=0.010, 0.044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated endothelial nitric-oxide synthase (eNOS) was down-regulated. Portosystemic shunts determined by splenorenal shunt (SRS) flow decreased in both transplantation groups (P=0.037, 0.032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared with sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.

This study employs an activity-based model to estimate the PM2.5 particle emissions from ships, cargo-handling equipment, and heavy-duty vehicles in the Port of Kaohsiung, Taiwan. External health costs, the index of health impact (IHI), and external environmental costs are assessed to quantify the impact of PM2.5 particle emissions. The mitigation regulations applied in this study are the Intended Nationally Determined Contribution Act (INDC) and the Greenhouse Gas Reduction and Management Act (GGRMA). The provisions in these acts are incorporated into Scenario-INDC and Scenario-GGRMA. The results are as follows: from 2005 to 2017, PM2.5 particle emissions caused an external health cost of 3238.30 DALY (disability-adjusted life year), an IHI value of 8.53%, and environmental cost of USD 2176.04 million annually. For Scenario-INDC and Scenario-GGRMA, it is predicted that PM2.5-related external health costs, IHI value, and external environmental cost will decrease by 927.64 DALY, 2.45%, and USD 608.86 million and by 1736.28 DALY, 4.58%, and USD 1139.84 million, respectively, as compared to BAU-2030 and BAU-2050. The results indicate that compliance with INDC and GGRMA regulations will lead to a significant mitigation of PM2.5 particle emissions, resulting in a significant improvements in air quality and human health in addition to a reduction in environmental costs.

Background: Non-alcoholic fatty liver disease (NAFLD) is linked with metabolic syndrome. Previous studies showed that obesity may disrupt adrenal function and adversely affect its counter-regulations against shock. This study hence evaluated adrenal function abnormalities in NAFLD with shock. Methods: Sprague-Dawley rats were fed with regular chow-diet (control) or high fat diet (HFD, 60% energy derived from fat). Blood tests were performed at the end of the 4th, 6th and 8th week, respectively. Experiments were performed at the end of the 8th week. Results: HFD rats developed NAFLD. HFD rats had 27% and 51% increase in plasma corticosterone at the 6th and 8th week in usual status. However, HFD rats had 5 times more reduction of mean arterial pressure in response to lipopolysaccharide-induced sepsis as compared to control rats. The corticosterone increment ratio was also lower in HFD rats, even after ACTH administration. 11&beta, HSD system tended to generate more corticosterone in HFD rats under hemodynamic stable status without shock and the trend was lost in HFD rats with septic shock. Conclusion: Rats with NAFLD had profound septic shock due to inadequate corticosterone response. This is, at least partly, due to 11&beta, HSDs dysregulation in sepsis.

In this article, we present a study of seawater 129I/127I time-series data from several coastal sites in Taiwan, including Yehliu Geopark (north–northeast coast), Kaohsiung (southwest coast), and Zhuwei Fishing Village (northwest coast). The objective of this study was to document how 129I/127I responds to known seasonal variations in the surface ocean currents that carry 129I to each of these sites. The responses were shown to be quite distinct. The Zhuwei site, across Mainland China, had elevated spring and summer 129I/127I values, with abrupt peaks that reflected transient cross-strait currents that carry seawater with elevated 129I to the northwest coast of Taiwan. The Yehliu site, which receives all of its seawater from the Kuroshio Current, had relatively low and uniform 129I/127I values year-round. The Kaohsiung site showed a summertime minimum that likely stems from upwelling upstream induced by oceanic eddies associated with the Kuroshio intrusion. To our knowledge, these are the first continuous coastal 129I/127I time-series data published for Asian waters and the first to show large, abrupt, and regional 129I/127I changes in the surface seawater. We also documented 129I/127I values from multiple surface ocean sites in the South China Sea (SCS), including a vertical profile from the South East Asia Time-Series Station that extends to a depth of 3,700 m. The 129I from both coastal Taiwan and surface waters of the SCS is >98% anthropogenic, primarily released to the environment as a byproduct of nuclear fuel reprocessing.

In the transportation industry, crew management is typically decomposed into two phases: crew scheduling and crew rostering. Due to the complexity of scheduling and rostering, bus transportation is not an exception and many relevant studies do not consider both procedures simultaneously. However, such a decomposition can yield inferior schedules/rosters. To address this issue, this paper proposes an integrated scheduling and rostering model for bus drivers and devises a branch-and-price-and-cut (BPC) algorithm to solve the complex problem. The proposed solution framework is empirically applied to real-world instances with various problem sizes whose data is collected from H Bus Company located in southern Taiwan. To validate the effectiveness and evaluate the efficiency of the proposed solution framework, this paper compares the solution obtained from the BPC algorithm with that of a benchmark optimization package. The results show that the proposed BPC algorithm can solve problems with large real-world instances within a reasonable computational time. Moreover, in the numerical experiments, this paper finds that the scheduling and rostering results of the bus drivers are more sensitive to the rostering constraints. Also, the proposed integrated framework can yield a better solution than the solution from a conventional two-phase approach, which demonstrates the advantage of the integration in this paper. The proposed method provided can be employed to deal with the challenges in driver planning for bus companies.

The main concept of this paper is derived from the Government of Taiwan's Greenhouse Gas Reduction and Management Act (GGRMA), which mandates that greenhouse gas emissions in 2050 should be reduced to half of the rate of greenhouse gas emissions in 2005. To reach this carbon emission goal by 2050, this paper examines three potential policy options (each accompanied with four illustrative scenarios). The results show that: (1) it is impossible to reach the goals of the GGRMA solely through the use of carbon allowance allocations and the use of alternative fuels if the use of vehicles is allowed to grow. (2) By keeping the increase in the use of vehicles to zero, by encouraging a use of PHEVs, and by implementing a carbon allowance allocation, it will be possible to reach the government's 2050 carbon emissions goals. (3) If the use of vehicles can actually be reduced, it will be possible to achieve carbon emissions which are lower than the 2050 targets by 1.30–5.18%. The use of alternative fuels proves to be a reliable way to decrease carbon emission. Carbon emissions could also be lowered by encouraging the use of public transportation.

Hepatorenal syndrome (HRS), a severe complication of advanced cirrhosis, is defined as hypoperfusion of kidneys resulting from intense renal vasoconstriction in response to generalized systemic arterial vasodilatation. Nevertheless, the mechanisms have been barely investigated. Cumulative studies demonstrated renal vasodilatation in portal hypertensive and compensated cirrhotic rats. Previously, we identified that blunted renal vascular reactivity of portal hypertensive rats was reversed after lipopolysaccharide (LPS). This study was therefore conducted to delineate the sequence of renal vascular alternation and underlying mechanisms in LPS-treated cirrhotic rats. Sprague-Dawley rats were randomly allocated to receive sham surgery (Sham) or common bile duct ligation (CBDL). LPS was induced on the 28th day after surgery. Kidney perfusion was performed at 0.5 or 3 h after LPS to evaluate renal vascular response to endothelin-1 (ET-1). Endotoxemia increased serum ET-1 levels ( P < 0.0001) and renal arterial blood flow ( P < 0.05) in both Sham and CBDL rats. CBDL rats showed enhanced renal vascular reactivity to ET-1 at 3 h after LPS ( P = 0.026). Pretreatment with endothelin receptor type A (ETA) antagonist abrogated the LPS-enhanced renal vascular response in CBDL rats ( P < 0.001). There were significantly lower inducible nitric oxide synthase (iNOS) expression but higher ETAand phosphorylated extracellular signal-regulated kinase (p-ERK) expressions in renal medulla of endotoxemic CBDL rats ( P < 0.05). We concluded that LPS-induced renal iNOS inhibition, ETAupregulation, and subsequent ERK signaling activation may participate in renal vascular hyperreactivity in cirrhosis. ET-1-targeted therapy may be feasible in the control of HRS.NEW & NOTEWORTHY Hepatorenal syndrome (HRS) occurred in advanced cirrhosis after large-volume paracentesis or bacterial peritonitis. We demonstrated that intraperitoneal lipopolysaccharide (LPS) enhanced renal vascular reactivity to endothelin-1 (ET-1) in cirrhotic rats, accompanied by inducible nitric oxide synthase inhibition, endothelin receptor type A (ETA) upregulation, and subsequent extracellular signal-regulated kinase activation in renal medulla. Pretreatment with ETAantagonist abrogated the LPS-enhanced renal vascular response in common bile duct ligation rats. These findings suggest that further clinical investigation of ET-1-targeted therapy may be feasible in the control of HRS.

Chronic hepatitis is the major cause of liver cirrhosis and portal hypertension. Several factors affect portal pressure, including liver fibrosis, splanchnic vasodilatation, and pathologic angiogenesis. Nucleos(t)ide analogs (NUCs), the oral antiviral agents, effectively attenuate chronic hepatitis B-related liver cirrhosis and portal hypertension via viral suppression and alleviation of hepatitis. On the other hand, NUCs affect tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and nitric oxide, which participate in fibrogenesis, vasodilatation, and angiogenesis. However, whether NUCs independently influence liver fibrosis and portal hypertension beyond viral suppression is unknown. This study thus aimed to evaluate the influences of three frequently used NUCs in rats with nonviral cirrhosis. Male Sprague-Dawley rats received common bile duct ligation (CBDL) to induce cholestatic cirrhosis and portal hypertension. The rats were randomly allocated into four groups, treated by mouth with lamivudine (30 mg/kg per day), entecavir (0.09 mg/kg per day), tenofovir (50 mg/kg per day), or distilled water (vehicle control) from the 15th day after CBDL. On the 29th day, liver cirrhosis- and portal hypertension-related parameters were evaluated. The results showed that chronic NUCs treatment did not affect hemodynamic parameters, plasma TNF-α concentration, and hepatic fibrogenesis protein expressions in rats with nonviral cirrhosis. Though the mesenteric VEGF receptor 2 phosphorylation was downregulated in NUCs-treated groups, the splanchnic angiogenesis was not influenced. In conclusion, lamivudine, entecavir, and tenofovir had no additional effects on liver cirrhosis and portal hypertension in rats with nonviral cirrhosis.

Background: Failure to transfer procedural skills learned in a laboratory to the bedside is commonly due to a lack of peer support/stimulation. A digital platform (Facebook) allows new clinical clerks to share experiences and tips that help augment their procedural skills in a peer-assisted learning/teaching method. This study aims to investigate the effectiveness of the innovation of using the digital platform to support the transfer of laboratory-trained procedural skills in the clinical units. Methods: Volunteer clinical clerks (n = 44) were enrolled into the peer-assisted learning (PAL) group, which was characterized by the peer-assisted learning of procedural skills during their final 3-month clinical clerkship block. Other clerks (n = 51) did not join the procedural skills-specific Facebook group and served as the self-directed learning regular group. The participants in both the PAL and regular groups completed pre- and post-intervention self-assessments for general self-assessed efficiency ratings (GSER) and skills specific self-assessed efficiency ratings (SSSER) for performing vein puncture, intravenous (IV) catheter and nasogastric (NG) tube insertion. Finally, all clerks received the post-intervention 3-station Objective Structured Clinical Skills Examination (OSCE) to test their proficiency for the abovementioned three procedural skills. Results: Higher cumulative numbers of vein punctures, IV catheter insertions and NG tube insertions at the bedside were carried out by the PAL group than the regular group. A greater improvement in GSERs and SSSERs for medical procedures was found in the PAL group than in the regular group. The PAL group obtained higher procedural skills scores in the post-intervention OSCEs than the regular group. Conclusion: Our study suggested that the implementation of a procedural skill-specific digital platform effectively helps clerks to transfer laboratory-trained procedural skills into the clinical units. In comparison with the regular self-directed learning group, the peer-assisted learning characteristics of Facebook give additional benefits to the PAL group by enhancing their procedural skills. Keywords: Facebook, Peer-assisted learning, Procedural skills

Cirrhosis is often associated with portal hypertension and portal-systemic collateral vessels formation attributed to angiogenesis, which leads to severe complications as hepatic encephalopathy. Sirolimus has anti-fibrosis and anti-angiogenesis effects, but whether it influences the severity of portal-systemic collaterals and hepatic encephalopathy is unknown. This study was thus designed to address this issue in rats with common bile duct ligation-induced liver cirrhosis. Sham-operated rats were surgical controls. Rats were intraperitoneally administered with 0.5 and 2 mg/kg/day sirolimus or vehicle for 2 weeks. Four weeks post operations, motor activities, body weight, biochemistry and hemodynamic data were measured. The liver was dissected for histopathology, immunohistochemical stains and protein analysis. On the parallel cirrhotic groups, the portal-systemic shunting was determined. The results showed that the body weight gain was significantly lower in sirolimus-treated rats. Sirolimus reduced portal pressure and plasma levels of alanine aminotransferase, aspartate aminotransferase and ammonia, and attenuated hepatic inflammation and fibrosis in cirrhotic rats. In addition, the hepatic phosphorylated mammalian target of rapamycin (mTOR) and P70S6K protein expressions were significantly downregulated and endothelial nitric oxide synthase (eNOS) expression upregulated by sirolimus. Sirolimus did not influence portal-systemic shunting and motor activities of cirrhotic rats. In conclusion, sirolimus significantly improved hepatic inflammation and fibrosis accompanied by portal pressure reduction in cirrhotic rats, in which down-regulated mTOR/P70S6K and up-regulated eNOS expressions might play a role. However, sirolimus did not significantly change the severity of portal-systemic collaterals and motor activities, suggesting that the multifactorial pathogenesis of hepatic encephalopathy could not be fully overcome by sirolimus.

The study uses life cycle assessment to analyze the carbon footprint of an ecological shrimp farm located at Yijhu, Taiwan. The procedural study contains primary and secondary data. The quantization procedure follows the ISO/TS 14067. This study aims to estimate the white shrimp full life cycle carbon footprint using a function unit per kilogram. SimoPro 8.0 is used to calculate the carbon footprint in this study. The results show that the life cycle total carbon footprint of white shrimp is 6.9389 kgCO 2 e/kg. The top five factors in terms of carbon emissions were as follows: electricity (2.0093 kgCO 2 e/kg, 29.39%), feed (1.6395 kgCO 2 e/kg, 23.98%), indirect raw materials (1.4782 kgCO 2 e/kg, 21.62%), waste treatment (0.7783 kgCO 2 e/kg, 11.40%) and transport and refrigerant (0.7524 kgCO 2 e/kg, 11.01%). The results showed that wastewater treatment is one of the emission hotspots over the whole life cycle. To conclude, the carbon footprint of the shrimp supply chain can be reduced by employing energy-conserving technology, by utilizing simple wastewater treatment procedures, and by using territorial plants as feed, and such moves could help this industry achieve its goals with regard to a sustainable environment.

Background Hepatopulmonary syndrome (HPS) is characterized by oxygen desaturation and increased intrapulmonary shunting formation in cirrhosis. Due to an unclarified mechanism, there is still no effective therapy except liver transplantation. Recent studies revealed that pulmonary angiogenesis may participate in pathogenesis, in which nitric oxide (NO) and vascular endothelial growth factor (VEGF) play roles. Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, exerts anti-angiogenesis effect. However, whether pioglitazone influences pulmonary angiogenesis, shunting and HPS remains unexplored. Methods Cirrhosis with HPS was induced in Spraque-Dawley rats with common bile duct ligation (CBDL). Pioglitazone (10 mg/kg/day, oral gavage) or vehicle was administered from 8th to 28th day post CBDL. On the 28th day, the mortality rate, hemodynamic parameters, concentrations of plasma glucose and liver biochemistry parameters, and arterial blood gas data were evaluated. Lungs were dissected for protein expression analyses. In another series, intrapulmonary shunting degree was determined by color microsphere method in paralleled groups. Results The survival rates were similar in HPS rats with or without pioglitazone administration. Pioglitazone did not influence the hemodynamic parameters, glucose and liver biochemistry levels, oxygen saturation and alveolar arterial gradient, but significantly down-regulated pulmonary VEGF protein expression, endothelial NO synthase (eNOS) activation, and decreased intrapulmonary shunts. Pioglitazone significantly decreased intrapulmonary shunts as compared with the vehicle (18.1 ± 4.5 vs. 9.8 ± 3.6, p = 0.015). Conclusion Pioglitazone down-regulated VEGF, eNOS and decreased intrapulmonary shunts without improving oxygenation. The current finding suggests a multifactorial mechanism of HPS that could not be successfully overcome merely by pioglitazone-induced anti-angiogenesis and shunting reduction.

Background Liver fibrosis causes portal hypertension which dilates collateral vasculature and enhances extra-hepatic angiogenesis including intrapulmonary shunts, which subsequently complicates with hepatopulmonary syndrome. Metformin is an anti-diabetic agent which possesses anti-inflammation and anti-angiogenesis properties. This study evaluated the effect of metformin treatment on liver and lung in a non-diabetic rat model with biliary cirrhosis induced via common bile duct ligation (CBDL). Methods CBDL rats were fed with metformin 150 mg/kg/day during the 8th–28th day post operation. The hemodynamic and biochemistry parameters were tested, and blood gas analysis was performed. The liver and lung were dissected for protein analysis and immuno-histochemical stains. Intrapulmonary shunting degree was determined using color microsphere method. Results Metformin treatment neither induced obvious hypoglycemic event nor altered hemodynamics in cirrhotic rats. The plasma levels of alanine aminotransferase were significantly reduced by metformin (control vs. metformin: 269 ± 56 vs. 199 ± 21 IU/L, P = 0.02). Sirius Red stains and CD-68 stains showed that metformin reduced intrahepatic fibrosis and CD-68-positive macrophages. Metformin did not influence hypoxia and intrapulmonary angiogenesis; however, it significantly reduced intrapulmonary shunts (31.7 ± 10.1 vs. 15.0 ± 6.6%, P = 0.006.). Furthermore, metformin reduced the protein expressions of COX-2 and PI3K in liver and COX-1 in lung. Conclusion Metformin reduced liver injury and improved hepatic fibrosis in cirrhotic rats. It also attenuated the intrapulmonary shunts. However, the effects of metformin on pulmonary angiogenesis and hypoxia were insignificant.

Varying the structures of conjugated side chains can be an efficient approach toward tailoring the optoelectronic properties of conjugated polymers. In this study, we synthesized four indacenodithiophene (IDT)-based side chain conjugated donor–acceptor alternating polymers. We introduced four different acceptor units (difluorobenzothiadizole: PIDTHT-FBT ; difluoroquinoxaline: PIDTHT-QF ; dicyanoquinoxaline: PIDTHT-QCN ; diketopyrrolopyrrole: PIDTHT-DPP ) to study the effects of the conjugated side chains on the optoelectronic properties (absorption spectra, energy levels, hole mobility) of the polymers and their resulting organic photovoltaic (OPV) devices. The energy levels of the highest occupied molecular orbitals for the new polymers were deeper when they featured alkylthiophene side chains. Films of these materials blended with PC 71 BM exhibited sufficiently high space-charge-limited current (SCLC) hole mobilities (>1.2 × 10 −5 cm 2 V −1 s −1 ) for efficient charge carrier extraction. The greatest OPV performance was that of the device incorporating PIDTHT-QF , with a power conversion efficiency of 5.15% under illumination with AM 1.5G solar light (1000 W m −2 ). Thus, side chain conjugated (two-dimensional) IDT polymers incorporating optimized acceptor groups are prospective materials for OPV applications.

Raloxifene, a selective estrogen receptor modulator, has been used extensively for osteoporosis. In addition to the effect of osteoporosis treatment, emerging evidences show that raloxifene affects the vascular function in different tissues. Cirrhosis is characterized with portal hypertension and complicated with hepatic encephalopathy. Portal hypertension affects portal-systemic shunt which leads to hepatic encephalopathy that the vascular modulation might influence severity of hepatic encephalopathy. Herein, we evaluated the impact of raloxifene on bile duct ligation (BDL)-induced cirrhotic rats. The female Sprague-Dawley rats received BDL plus ovariectomy or sham-operation. Four weeks later, rats were divided into 2 subgroups respectively to receive of raloxifene (10mg/kg/day) or saline (vehicle) for 14 days. On the 43th day, motor activities and hemodynamic parameters were measured. Hepatic and vascular mRNA and protein expressions were determined. The histopathological change of liver was examined. We found that the liver biochemistry, ammonia level and motor activity were similar between cirrhotic rats with or without raloxifene administration. The hemodynamic parameters were not significantly different except that raloxifene reduced portal venous inflow. Raloxifene exacerbated hepatic fibrosis and up-regulated hepatic endothelin-1 and cyclooxygenase 2 protein expressions. In addition, raloxifene modulated the mRNA expressions of endothelial nitric oxide synthase, cyclooxygenase and endothelin-1 in the superior mesenteric artery and collateral vessel. In conclusion, raloxifene aggravates hepatic fibrosis and decreases portal venous inflow in cirrhotic rats without adversely affecting portal hypertension and hepatic encephalopathy. The modulation of hepatic and vascular endothelin-1, endothelial nitric oxide synthase and cyclooxygenase expressions may play a role in the mechanism.

Recently, thermally activated delayed fluorescence (TADF) materials have become the most promising hosts for realizing high-performance phosphorescent and fluorescent organic light-emitting diodes (OLEDs) because of their ability to upconvert triplet excitons to singlet excitons. However, despite a few TADF hosts having been introduced for low energy phosphorescent and fluorescent dopants, developing host materials with TADF properties for blue phosphorescent and TADF OLEDs is still a great challenge to date. In this study, bipolar hosts exhibiting TADF behavior and high triplet energy, consisting of the carbazole group as the donor, diphenylsulphone moiety as the acceptor, and m-bitolyl as the π-conjugated bridge, are synthesized and applied for the first time to blue devices. The ΔEST value of the TADF host is tuned via the introduction of a cyano group in the carbazole moiety due to the increase of the LE contribution in the CT excited state. Detailed photophysical studies confirm the efficient TADF pr...

Background The Accreditation Council for Graduate Medical Education (ACGME) core competencies (CC) in general medicine-based primary care are essential for junior medical trainees. In this country, a regular faculty development (FD) program aimed at training faculty in instructing (teaching and assessing) these CC had operated. However, leadership was not emphasized. In a new intervention module, the roles and associated responsibilities of clinical instructors to conduct, design, and lead CC-based education were emphasis. Aims This follow-up explanatory case study compares the effectiveness of intervention module with that of the previous regular module. Methods The regular group (n = 28) comprised clinical instructors who participated in the FD module during the 2013–2014 year while the intervention group (n = 28) was composed of 2015–2016 participants. Prior to the formal (hands-on) training, participants in the intervention group were asked to study the online materials of the regular module. These participants then received a 30-h hands-on training in conducting, designing, and leading skills. Finally, they prepared a 10-h reflective end-of-module presentation of their real-world practices. Results Following the training, a higher degree improvement in participants self-reported familiarity with CC education, self-confidence in their ability to deliver CC education and sustained involve CC education were noted among the intervention FD group, compared with the regular FD group. In the intervention group, senior academicians (associate and full professor) are more substantially involved in designing and leading CC-based courses than junior academicians (lecturers and assistant professors). Among non-teaching award winners of in the intervention FD group, the follow-up degree of sustained involvement in delivering, designing and leading CC-based courses was significantly higher than that of the regular group. Conclusions Our study demonstrated that leadership training in the intervention FD modules substantially motivated clinical instructors to become leaders in CC education.