ABSTRACT
Vinyl sulfones, with their exceptional chemical properties, are known as the "chameleons" of organic synthesis and are widely used in the preparation of various sulfur-containing structures. However, their most alluring feature lies in their biological activity. The vinyl sulfone skeleton is ubiquitous in natural products and drug molecules and boasts a unique molecular structure and drug activity when compared to conventional drug molecules. As a result, vinyl sulfones have been extensively studied, playing a critical role in organic synthesis and pharmaceutical chemistry. In this review, we present a comprehensive analysis of the recent applications of vinyl sulfone structures in drug design, biology, and chemical synthesis. Furthermore, we explore the prospects of vinyl sulfones in diverse fields, offering insight into their potential future applications.
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Objective. Conventional transarterial chemoembolization (cTACE) is a common treatment for hepatocellular carcinoma (HCC), often with unsatisfactory local controls. Combining cTACE with radiotherapy shows a promise for unresectable large HCC, with proton therapy preserving healthy liver tissue. However, the proton therapy benefits are subject to the accuracy of tissue relative stopping power (RSP) prediction. The RSP values are typically derived from computed tomography (CT) images using stoichiometric calibration. Lipiodol deposition significantly increases CT numbers in liver regions of post-cTACE. Hence, it is necessary to evaluate the accuracy of RSP in liver regions of post-cTACE.Approach. Liver, water, and iodinated oil samples were prepared. Some liver samples contained iodinated oil. The water equivalent path length (WEPL) of sample was measured through the pullbacks of spread-out Bragg peak (SOBP) depth-dose profiles scanned in a water tank with and without sample in the beam path. Measured RSP values were compared to estimated RSP values derived from the CT number based on the stoichiometric calibration method.Main results. The measured RSP of water was 0.991, confirming measurement system calibration. After removing the RSP contribution from container walls, the pure iodinated oil and liver samples had RSP values of 1.12 and 1.06, while the liver samples mixed with varying oil volumes (5 ml, 10 ml, 15 ml) showed RSP values of 1.05, 1.05 and 1.06. Using the stoichiometric calibration method, pure iodinated oil and liver samples had RSP values of 2.79 and 1.06. Liver samples mixed with iodinated oil (5 ml, 10 ml, 15 ml) had calculated RSP values of 1.21, 1.34, and 1.46. The RSP discrepancy reached 149.1% for pure iodinated oil.Significance.Iodinated oil notably raises CT numbers in liver tissue. However, there is almost no effect on its RSP value. Proton treatment of post-cTACE HCC patients can therefore be overshooting if no proper measures are taken against this specific effect.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Proton Therapy , Humans , Proton Therapy/methods , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/radiotherapy , WaterABSTRACT
The cement industry has become the largest mercury (Hg) emission source in China. Better understanding Hg emission and deposition characteristics and drivers of Hg emission changes can increase the awareness of related risks and support effective policy making. The results show that due to the substantial increase in the use of new suspension preheater and precalciner (NSP) technology in China, an approximate two-fold increase from 80.0 to 144.0 Mg year-1 was observed for the cement-related Hg emissions during 2005-2015, which has resulted in a considerable increase in atmospheric deposition over terrestrial China from 37.9 to 75.9 Mg year-1. Compared to the great majority of emission sectors, the same increase in Hg emissions from cement production can cause more deposition due to the large share of highly water-soluble divalent Hg in the sector. Each 1% increase in the share of divalent Hg can result in an increase of 0.37 Mg year-1 in deposition over terrestrial China. Technical improvement and diversification of cement products are two major driving forces offsetting the economy-induced growth in cement-related Hg emissions during 2005-2015. Measures aimed at reducing the Hg emission intensity against the further increase in the use of NSP technology and avoiding overcapacity against the stimulation of real estate and increasing cement demands are urgently needed for the cement industry in China.
Subject(s)
Air Pollutants , Mercury , Air Pollutants/analysis , China , Construction Materials , Environmental Monitoring , Mercury/analysisABSTRACT
Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs. 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs. 4.35%, P<0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P<0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P<0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P<0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects.
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BACKGROUND: Non-coding RNAs have attracted considerable attention for their vital role in cancer. The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma (HCC) and reveal their regulatory mechanism in the pathophysiological process. METHODS: We measured the expression of mucin 1 (MUC1) and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot, screened for aberrantly expressed microRNAs (miRNAs) by miRNA microarrays. Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1, which were validated by RNA immunoprecipitation assay and luciferase reporter assay. Cell counting kit-8, Transwell assays, and flow cytometry were used to conduct functional experiments. Proteins were examined by western blot and immunohistochemical staining assays. Significant differences between groups were estimated using the one-way analysis of variance. A Pâ<â0.05 was considered statistically significant. RESULTS: MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues (normal vs. tumor, 1.007â±â0.215 vs. 75.213â±â18.403, t = 18.401, P < 0.001) while miR-485-5p was down-regulated (normal vs. tumor, 4.894â±â0.684 vs. 1.586â±â0.398, tâ=â16.191, P < 0.001). Inhibition of miR-485-5p promoted cell proliferation (73.33%â±â5.13% vs. 41.33%â±â3.51%, tâ=â8.913, P < 0.001), migration (102â±â8 cells vs. 46â±â8 cells, tâ=â8.681, P < 0.001), invasion (59â±â7 cells vs. 28â±â2 cells, tâ=â8.034, P < 0.01), and suppressed apoptosis (22.64%â±â6.97% vs. 36.33%â±â3.96%, tâ=â2.958, P < 0.05) of HepG2 cells with which MUC1 is knocked down. Mechanically, miR-485-5p binds to MUC1, while circHECTD1 binds to miR-485-5p, resulting in the indirect up-regulation of the MUC1 level. CONCLUSIONS: Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Mucin-1 , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , MicroRNAs/genetics , Mucin-1/genetics , RNA, Circular , Ubiquitin-Protein LigasesABSTRACT
The relationship between canopy urban heat islands (CUHIs) and surface urban heat islands (SUHIs) at four times daily temporal resolution remains unclear. The CUHI-SUHI relationship is investigated using four observations per day without temporal averaging in Shanghai, Beijing, Birmingham, and Taipei, with 201 of 2232 CUHI-SUHI pairs exhibiting significant UHI differences in their spatial distributions and intensities. These 201 UHI difference cases are determined by the correlation coefficients between air and surface temperature <0.2. The SPAtial EFficiency (SPAEF) multiple-component performance metric is applied to compare the spatiotemporal patterns of SUHIs derived from Moderate Resolution Imaging Spectroradiometer (MODIS) satellite data and CUHIs acquired from either meteorological observations or numerical simulations. The results indicate that 81.09% of the UHI differences occurred during the daytime, and were caused by local air advection related to wind speed ≥2 m/s and land surface conditions in the study areas. We conclude that joint analysis of CUHIs and SUHIs should be conducted to characterize urban thermal environments and that current urban planning procedures should integrate these UHI differences to develop effective mitigation strategies and adaptation measures.
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BACKGROUND@#Non-coding RNAs have attracted considerable attention for their vital role in cancer. The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma (HCC) and reveal their regulatory mechanism in the pathophysiological process.@*METHODS@#We measured the expression of mucin 1 (MUC1) and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot, screened for aberrantly expressed microRNAs (miRNAs) by miRNA microarrays. Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1, which were validated by RNA immunoprecipitation assay and luciferase reporter assay. Cell counting kit-8, Transwell assays, and flow cytometry were used to conduct functional experiments. Proteins were examined by western blot and immunohistochemical staining assays. Significant differences between groups were estimated using the one-way analysis of variance. A P < 0.05 was considered statistically significant.@*RESULTS@#MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues (normal vs. tumor, 1.007 ± 0.215 vs. 75.213 ± 18.403, t = 18.401, P < 0.001) while miR-485-5p was down-regulated (normal vs. tumor, 4.894 ± 0.684 vs. 1.586 ± 0.398, t = 16.191, P < 0.001). Inhibition of miR-485-5p promoted cell proliferation (73.33% ± 5.13% vs. 41.33% ± 3.51%, t = 8.913, P < 0.001), migration (102 ± 8 cells vs. 46 ± 8 cells, t = 8.681, P < 0.001), invasion (59 ± 7 cells vs. 28 ± 2 cells, t = 8.034, P < 0.01), and suppressed apoptosis (22.64% ± 6.97% vs. 36.33% ± 3.96%, t = 2.958, P < 0.05) of HepG2 cells with which MUC1 is knocked down. Mechanically, miR-485-5p binds to MUC1, while circHECTD1 binds to miR-485-5p, resulting in the indirect up-regulation of the MUC1 level.@*CONCLUSIONS@#Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.
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BACKGROUND: This study aimed to measure quality of life (QOL) in primary caregivers of young childrenwith Prader-Willi syndrome (PWS). METHODS: The caregivers of 32 children aged from 6.1 to 71.2 months completed the Chinese version of the World Health Organization Quality of Life-BREF (WHOQOL-BREF). We also evaluated the social adaption capacity of these children with Infants-Junior Middle School Students' Social-Life Abilities Scale. Correlation test was used to explore the related factors to caregivers' QOL. RESULTS: Caregivers of young children with PWS had significantly lower QOL. The correlation analyses revealed that caregivers' QOL was lower in children with young age, combined diseases or symptoms or poor social adaption, or caregivers having concerns about the child. CONCLUSIONS: Rearing a chilld with PWS may lead to decreased QOL. Psychological status of caregivers should be highlighted and social support should be given to families with PWS children.
Subject(s)
Caregivers/psychology , Prader-Willi Syndrome/nursing , Quality of Life , Asian People , Child, Preschool , Female , Humans , Infant , MaleABSTRACT
BACKGROUND: In this study, we compared the effect on diabetic retinopathy (DR) between oral antidiabetic drugs (OADs) alone and in combination with basal insulin-supported OADs therapy (BOT). [Correction added on 11 November 2019, after first online publication: In Abstract under Background section, "DR" has been corrected into "diabetic retinopathy (DR)".] METHODS: Between January 2015 and January 2018, this study enrolled 290 patients (age 18-65 years) with diabetes duration between 0 and 5 years. Patients were randomly assigned to receive OADs or BOT after 14 days intensive insulin treatment. Examinations were performed at the beginning and end of the study. RESULTS: Fewer patients developed DR in the BOT than OADs group (8 [6.06%] vs 12 [8.3%], respectively), and all cases of DR were non-proliferative. Blood glucose concentrations were higher in the BOT than OADs group at the 3rd month, but lower in the former at the 6th and 12th month. The rate of reaching target HbA1c ≤7% was lower in the BOT than OADs group at the 3rd month (63.6% vs 72.2%, respectively), similar between the two groups at the 6th month (60.6% vs 66.6%, respectively) and higher in the BOT group at the 12th month (75.0% vs 61.1%, respectively). The SD of fasting blood glucose (FBG), coefficient of variation of FBG, SD of blood glucose (SDBG), and mean amplitude of glycemic excursions were lower in the BOT than OADs group. Changes in the levels of three cytokines (interleukin [IL]-1ß, IL-6, and IL-17α) were significantly less in the BOT than OADs group. CONCLUSIONS: Twelve months of BOT decreased the incidence of DR in short-duration type 2 diabetes by reducing glycemia more effectively, stably, and completely than OADs alone.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Retinopathy/prevention & control , Hypoglycemic Agents/administration & dosage , Insulin Glargine/administration & dosage , Administration, Oral , Adolescent , Adult , Aged , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , China/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/epidemiology , Drug Therapy, Combination , Female , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/adverse effects , Incidence , Injections , Insulin Glargine/adverse effects , Interleukins/blood , Male , Middle Aged , Prospective Studies , Time Factors , Treatment Outcome , Young AdultABSTRACT
Mercury (Hg) exposure poses substantial risks to human health. Investigating a longer chain from economic activities to human health can reveal the sources and critical processes of Hg-related health risks. Thus, we develop a more comprehensive assessment method which is applied to mainland China-the largest global Hg emitter. We present a map of Hg-related health risks in China and estimate that 0.14 points of per-foetus intelligence quotient (IQ) decrements and 7,360 deaths from fatal heart attacks are related to the intake of methylmercury in 2010. This study, for the first time, reveals the significant impacts of interprovincial trade on Hg-related health risks across the whole country. For instance, interprovincial trade induced by final consumption prevents 0.39 × 10-2 points for per-foetus IQ decrements and 194 deaths from fatal heart attacks. These findings highlight the importance of policy decisions in different stages of economic supply chains to reduce Hg-related health risks.
Subject(s)
Air Pollutants/analysis , Mercury/analysis , Air Pollutants/toxicity , China , Environmental Monitoring , Humans , Intelligence Tests , Mercury/toxicity , Methylmercury Compounds/analysis , Methylmercury Compounds/toxicity , Public Health , Risk AssessmentABSTRACT
Mercury (Hg) is characterized by its ability to migrate between continents and its adverse effects on human health, arousing great concern around the world. The transboundary transport of large anthropogenic Hg emissions from China has attracted particular attention, especially from neighboring countries. Here, we combine an atmospheric transport model, a mass budget analysis, and a multiregional input-output model to simulate the atmospheric Hg outflow from China and investigate the impacts of Chinese interprovincial trade on the outflow. The results show outflows of 423.0 Mg of anthropogenic Hg, consisting of 65.9% of the total Chinese anthropogenic emissions, from China in 2010. Chinese interprovincial trade promotes the transfer of atmospheric outflow from the eastern terrestrial boundary (-6.4 Mg year-1) to the western terrestrial boundary (+4.5 Mg year-1) and a net decrease in the atmospheric outflow for the whole boundary, reducing the chance of risks to foreign countries derived from transboundary Hg pollution from China. These impacts of interprovincial trade will be amplified due to the expected strengthened interprovincial trade in the future. The synergistic promotional effects of interprovincial trade versus Hg controls should be considered to reduce the transboundary Hg pollution from China.
Subject(s)
Air Pollutants , Mercury , China , Environmental Monitoring , Humans , InternationalityABSTRACT
INTRODUCTION: Basal insulin is widely recommended for the treatment of type 2 diabetes mellitus (T2DM) patients who are unable to achieve glycemic control with oral antidiabetic drug(s) (OADs). However, some patients are still unable to control their blood glucose levels even when on basal insulin-supported OAD(s) therapy (BOT). The aim of this study was to investigate the factor(s) predicting patient response to BOT. METHODS: A total of 212 patients with T2DM, ranging in age from 18 to 65 years, admitted to the university hospital of Sun Yat-sen University, Guangzhou, China, were enrolled in the study between January 2013 and July 2016. All patients had fasting blood glucose levels of ≥ 10.0 mmol/L despite receiving OAD(s) treatment. According to study design, these patients first received intensive insulin therapy for 2 weeks to attain and maintain their glycemic goals and then were switched to BOT. Responders were defined as subjects who maintained their glycemic targets with BOT for at least 3 months; all others were considered to be non-responders. The characteristics between responders and non-responders were compared. RESULTS: Compared with non-responders, responders had a shorter duration of diabetes (5.1 ± 5.0 vs. and 10.1 ± 3.2 years; P < 0.001) and a higher 2-h postprandial C-peptide-to-fasting C-peptide ratio (2 h-PCP/FCP: 1.95 ± 0.51 vs. 1.67 ± 0.32; P < 0.01). Responders showed a lower proportion of previous treatment with insulin (69/100 vs 40/3; P < 0.001) and sulfonlureas or glinides (116/50 vs 40/0; P <0.001) than non-responders. Multivariate logistic regression analysis showed that previous insulin treatment (odds ratio [OR] 17.677, 95% confidence interval [CI] 5.205-60.027; P < 0.001) and the 2 h-PCP/FCP ratio (OR 0.241, 95% CI 0.058-0.679; P = 0.007) had predictive value. CONCLUSIONS: A higher 2 h-PCP/FCP ratio and a lack of previous insulin treatment increase the likelihood of BOT success.
ABSTRACT
Mercury (Hg) is of global concern because of its adverse effects on humans and the environment. In addition to long-range atmospheric transport, Hg emissions can be geographically relocated through economic trade. Here, we investigate the effect of China's interregional trade on atmospheric Hg deposition over China, using an atmospheric transport model and multiregional input-output analysis. In general, total atmospheric Hg deposition over China is 408.8 Mg yr-1, and 32% of this is embodied in China's interregional trade, with the hotspots occurring over Gansu, Henan, Hebei, and Yunnan provinces. Interprovincial trade considerably redistributes atmospheric Hg deposition over China, with a range in deposition flux from -104% to +28%. Developed regions, such as the Yangtze River Delta (Shanghai, Jiangsu, and Zhejiang) and Guangdong, avoid Hg deposition over their geographical boundaries, instead causing additional Hg deposition over developing provinces. Bilateral interaction among provinces is strong over some regions, suggesting a need for joint mitigation, such as the Jing-Jin-Ji region (Beijing, Tianjin, and Hebei) and the Yangtze River Delta. Transferring advanced technology from developed regions to their developing trade partners would be an effective measure to mitigate China's Hg pollution. Our findings are relevant to interprovincial efforts to reduce trans-boundary Hg pollution in China.
Subject(s)
Mercury , Beijing , China , Environmental Pollution , Humans , RiversABSTRACT
This study compared the effects on glycaemic variability and glucose control between saxagliptin and acarbose as add-on therapies for aged T2DM inadequately controlled with metformin alone. The results showed that compared with acarbose-metformin, saxagliptin-metformin was more effective in glucose control with similar glycaemic variability.
Subject(s)
Acarbose/therapeutic use , Adamantane/analogs & derivatives , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Dipeptides/therapeutic use , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Acarbose/administration & dosage , Adamantane/administration & dosage , Adamantane/therapeutic use , Aged , Aged, 80 and over , Blood Glucose/drug effects , Diabetes Complications/prevention & control , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Dipeptides/administration & dosage , Double-Blind Method , Drug Therapy, Combination , Female , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/administration & dosage , Male , Metformin/administration & dosage , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: Oral anti-diabetes drugs plus basal insulin (OAD + insulin) therapy in patients with newly diagnosed type 2 diabetes might improve ß-cell function and result in extended glycaemic remission. This randomised trial compared the effect on ß-cell function and diabetes remission rate between oral drug alone or with addition of basal insulin. METHODS: One hundred and twenty-nine patients, aged 35-50 years, were enrolled between June 2005 and June 2009. For initial correction of hyperglycaemia, patients with fasting plasma glucose ≥9.0 mmol/L and HbA(1c) ≥ 9.0%, were randomly assigned to therapy with oral drugs + insulin or oral drugs alone. Treatment was stopped after normoglycaemia was maintained for 3 months. Patients were then followed-up with diet and physical exercise. Blood glucose, HbA(1c) and insulin were measured prior to treatment and at 1-year follow-up. RESULTS: More patients achieved target glycaemic control in the oral drugs + insulin group [98.3% (58 of 59)] in less time [(10.4 ± 2.5) days] than those in the oral drug group [95.7% (67 of 70) and (12.4 ± 3.4) days]. At 1-year follow-up, more patients maintained target glycaemia without any drugs in the oral drug + insulin group than in the oral drug group [37.9% (22 of 58) vs 20.9% (14 of 67)]. Both treatments improved homeostasis model assessment-ß (HOMA-ß) and homeostasis model assessment-insulin resistance (HOMA-IR) significantly. They had similar effects on insulin resistance [lg(HOMA-IR): (0.50 ± 0.09) vs (0.48 ± 0.09), p = 0.23]. However, oral drugs + insulin could recover ß-cell function much more than OAD alone could [lg(HOMA-ß): (2.17 ± 0.14) vs (2.11 ± 0.13), p = 0.03]. CONCLUSION: In newly diagnosed type 2 diabetes, therapy with oral drugs + insulin has had favourable outcomes on recovery and maintenance of ß-cell function and protracted glycaemic remission compared with treatment with oral drugs alone.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin-Secreting Cells/drug effects , Insulin/administration & dosage , Administration, Oral , Adult , Female , Homeostasis , Humans , Insulin Resistance/physiology , Male , Metformin/administration & dosage , Middle Aged , Models, Biological , Sulfonylurea Compounds/administration & dosageABSTRACT
The aim of this study was to compare coefficient of variation of fasting capillary blood glucose (FBG) between insulin glargine and NPH in T2DM with poorly controlled by oral antidiabetic drugs. The results demonstrated that insulin glargine was more potent in improving glycemic control than NPH with stable FBG.