Hydrogel microneedle patch enables the extraction of skin interstitial fluid (ISF) through in situ swelling in a minimally invasive manner without assistance of mechano‐chemical peripherals. However, ...existing hydrogel microneedles require tens of minutes with multistep process to collect sufficient volume (1 mL) for effective analysis. This study introduces an osmolyte‐powered hydrogel microneedle patch that can extract ISF three times faster than the existing platforms and provide in situ analysis of extracted biomarkers. The microneedle patch is composed of osmolytes (i.e., maltose) and hydrogel (i.e., methacrylated hyaluronic acid). During the extraction process, the osmolytes dissolve in the matrix and provide the osmotic pressure that increases the diffusion of ISF from skin to the hydrogel matrix. A patch with 100 microneedles can extract 7.90 µL of ISF from pig skin ex vivo and 3.82 µL of ISF from mouse skin in vivo within 3 min, whereas the control (i.e., hydrogel microneedle without osmolytes) requires >10 min to achieve similar results. The extracted ISF allows the quantification of biomarkers such as glucose and/or drugs such as insulin in vivo. Through the integration with the electronic glucose sensors, the whole system permits the direct and rapid analysis of the extracted glucose.
An osmolyte‐powered hydrogel microneedle patch is designed to extract microliters of skin interstitial fluid (ISF) within minutes which is three times faster than the existing platforms. This patch can extract 7.90 µL of ISF from pig skin ex vivo and 3.82 µL of ISF from mouse skin in vivo within 3 min and allow the in vivo quantification of biomarkers.
•Changes of industrial structure reduce China’s coal consumption significantly since 2012.•Increasing trend of economic scale effect on China’s coal consumption has reversed.•China's embodied coal ...exports are falling under increasing trade surplus since 2011.•Intrinsic mechanism results in permanent trend of China’s coal consumption declining.
Coal dominates China’s energy consumption, and academic published papers especially before 2010 usually undervalued China’s coal consumption significantly. However, China’s coal consumption has declined continuously in 2014 and 2015. This seems to indicate that China may have finally reached the peak of its coal consumption in 2013. There is minimal quantitative research on the analysis of this phenomenon. The logarithmic mean Divisia index (LMDI) method is used in this study to analyze the key factors that drive China’s direct coal consumption variation. Approaching the issue from the perspective of indirect coal consumption, an Input-Output model is established to discuss China’s embodied coal exports in this study, aiming to trace the ultimate demand for coal to understand why consumption might have peaked. The research results suggest that changes of industrial structure started to reduce China’s coal consumption significantly since 2012, and the effects of energy intensity and energy mix have continued to play important roles in coal consumption reduction since 2007, especially the energy mix effect since 2012. On the other side of the equation, although the economic scale effect – the only factor apparently driving increases in China’s coal consumption – is still large, the increasing trend has reversed, and its impact has stabilised. China’s embodied coal exports, both absolute volume and the proportion of coal consumption, are falling even though the trade surplus has still been increasing in recent years, which is completely different with the trend before 2011. China’s continuous efforts on export restructuring – shifting from labour & energy-intensive to capital & technology-intensive – will reduce embodied coal exports and coal consumption in the future.
Morphology control of solution coated solar cell materials presents a key challenge limiting their device performance and commercial viability. Here we present a new concept for controlling phase ...separation during solution printing using an all-polymer bulk heterojunction solar cell as a model system. The key aspect of our method lies in the design of fluid flow using a microstructured printing blade, on the basis of the hypothesis of flow-induced polymer crystallization. Our flow design resulted in a ∼90% increase in the donor thin film crystallinity and reduced microphase separated donor and acceptor domain sizes. The improved morphology enhanced all metrics of solar cell device performance across various printing conditions, specifically leading to higher short-circuit current, fill factor, open circuit voltage and significantly reduced device-to-device variation. We expect our design concept to have broad applications beyond all-polymer solar cells because of its simplicity and versatility.
Incomplete coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides, for preventing sexually transmitted infections. We investigated ...vaginal distribution, retention, and safety of nanoparticles with surfaces modified to enhance transport through mucus. We show that mucus-penetrating particles (MPPs) provide uniform distribution over the vaginal epithelium, whereas conventional nanoparticles (CPs) that are mucoadhesive are aggregated by mouse vaginal mucus, leading to poor distribution. Moreover, when delivered hypotonically, MPPs were transported advectively (versus diffusively) through mucus deep into vaginal folds (rugae) within minutes. By penetrating into the deepest mucus layers, more MPPs were retained in the vaginal tract after 6 hours compared to CPs. After 24 hours, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPPs. We then developed MPPs composed of acyclovir monophosphate (ACVp). When administered before vaginal herpes simplex virus 2 challenge, ACVp-MPPs protected 53% of mice compared to only 16% protected by soluble drug. Overall, MPPs improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were nontoxic when administered daily for 1 week.
Helicobacter pylori infection is considered as the most important risk factor in the pathogenesis of gastric cancer. This study aims to evaluate the long-term effects of H pylori eradication ...treatment on the incidence and mortality of gastric cancer among a high-risk population.
This prospective, randomized, placebo-controlled trial was conducted in a high-risk area in southern China in July 1994. A total of 1630 asymptomatic, H pylori–infected individuals were randomly assigned to receive standard triple therapy for H pylori eradication (n = 817) or placebo (n = 813), and were followed up until December 2020. The primary outcome was incidence of gastric cancer. Total and cause-specific mortalities were the secondary outcomes.
During 26.5 years of follow-up, 21 participants (2.57%) in the treatment arm and 35 (4.31%) in the placebo arm were diagnosed with gastric cancer. Participants receiving H pylori treatment had a lower incidence of gastric cancer compared with their placebo counterparts (hazard ratio HR, 0.57; 95% CI, 0.33–0.98). More obvious risk reduction was observed among those without premalignant gastric lesions (HR, 0.37; 95% CI, 0.15–0.95) and those without dyspepsia symptoms at baseline (HR, 0.44; 95% CI, 0.21–0.94). Furthermore, compared with 32 cases of gastric cancer observed among 527 participants with persistent H pylori infection in the placebo group, only 16 were identified in 625 subjects with successful eradication in the treatment group (HR, 0.46; 95% CI, 0.26–0.83). However, there were no statistically significant differences for any mortality end points between the 2 groups.
Eradication of H pylori might confer a long-term protection against gastric cancer in high-risk populations, especially for infected individuals without precancerous gastric lesions at baseline.
Display omitted
Helicobacter pylori eradication might confer a long-term protection against gastric cancer in high-risk populations, especially for infected individuals without precancerous gastric lesions at baseline.
Hepatocellular carcinoma (HCC), a leading cause of cancer-related death, is associated with viral hepatitis, non-alcoholic steatohepatitis (NASH), and alcohol-related steatohepatitis, all of which ...trigger endoplasmic reticulum (ER) stress, hepatocyte death, inflammation, and compensatory proliferation. Using ER stress-prone MUP-uPA mice, we established that ER stress and hypernutrition cooperate to cause NASH and HCC, but the contribution of individual stress effectors, such as activating transcription factor 4 (ATF4), to HCC and their underlying mechanisms of action remained unknown.
Hepatocyte-specific ATF4-deficient MUP-uPA mice (MUP-uPA/Atf4Δhep) and control MUP-uPA/Atf4F/F mice were fed a high-fat diet to induce NASH-related HCC, and Atf4F/F and Atf4Δhep mice were injected with diethylnitrosamine to model carcinogen-induced HCC. Histological, biochemical, and RNA-sequencing analyses were performed to identify and define the role of ATF4-induced solute carrier family 7a member 11 (SLC7A11) expression in hepatocarcinogenesis. Reconstitution of SLC7A11 in ATF4-deficient primary hepatocytes and mouse livers was used to study its effects on ferroptosis and HCC development.
Hepatocyte ATF4 ablation inhibited hepatic steatosis, but increased susceptibility to ferroptosis, resulting in accelerated HCC development. Although ATF4 activates numerous genes, ferroptosis susceptibility and hepatocarcinogenesis were reversed by ectopic expression of a single ATF4 target, Slc7a11, coding for a subunit of the cystine/glutamate antiporter xCT, which is needed for glutathione synthesis. A ferroptosis inhibitor also reduced liver damage and inflammation. ATF4 and SLC7A11 amounts were positively correlated in human HCC and livers of patients with NASH.
Despite ATF4 being upregulated in established HCC, it serves an important protective function in normal hepatocytes. By maintaining glutathione production, ATF4 inhibits ferroptosis-dependent inflammatory cell death, which is known to promote compensatory proliferation and hepatocarcinogenesis. Ferroptosis inhibitors or ATF4 activators may also blunt HCC onset.
Liver cancer or hepatocellular carcinoma (HCC) is associated with multiple aetiologies. Most HCC aetiologies cause hepatocyte stress and death, as well as subsequent inflammation, and compensatory proliferation, thereby accelerating HCCdevelopment. The contribution of individual stress effectors to HCC and their underlying mechanisms of action were heretofore unknown. This study shows that the stress-responsive transcription factor ATF4 blunts liver damage and cancer development by suppressing iron-dependent cell death (ferroptosis). Although ATF4 ablation prevents hepatic steatosis, it also increases susceptibility to ferroptosis, due to decreased expression of the cystine/glutamate antiporter SLC7A11, whose expression in human HCC and NASH correlates with ATF4. These findings reinforce the notion that benign steatosis may be protective and does not increase cancer risk unless accompanied by stress-induced liver damage. These results have important implications for prevention of liver damage and cancer.
Display omitted
•ER and metabolic stresses activate ATF4, which induces SLC7A11 expression.•The ATF4–SLC7A11 axis controls glutathione metabolism and ferroptosis.•ATF4 deficiency potentiates stress-induced ferroptosis and liver tumorigenesis.•Ectopic SLC7A11 abrogates ATF4 ablation-potentiated liver tumorigenesis.•ATF4 and SLC7A11 positively correlate in human HCC and patients with NASH.
Given the rapid increase in the popularity of e-cigarettes and the paucity of associated longitudinal health-related data, the need to assess the potential risks of long-term use is essential.
To ...compare exposure to nicotine, tobacco-related carcinogens, and toxins among smokers of combustible cigarettes only, former smokers with long-term e-cigarette use only, former smokers with long-term nicotine replacement therapy (NRT) use only, long-term dual users of both combustible cigarettes and e-cigarettes, and long-term users of both combustible cigarettes and NRT.
Cross-sectional study.
United Kingdom.
The following 5 groups were purposively recruited: combustible cigarette-only users, former smokers with long-term (≥6 months) e-cigarette-only or NRT-only use, and long-term dual combustible cigarette-e-cigarette or combustible cigarette-NRT users (n = 36 to 37 per group; total n = 181).
Sociodemographic and smoking characteristics were assessed. Participants provided urine and saliva samples and were analyzed for biomarkers of nicotine, tobacco-specific N-nitrosamines (TSNAs), and volatile organic compounds (VOCs).
After confounders were controlled for, no clear between-group differences in salivary or urinary biomarkers of nicotine intake were found. The e-cigarette-only and NRT-only users had significantly lower metabolite levels for TSNAs (including the carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol NNAL) and VOCs (including metabolites of the toxins acrolein; acrylamide; acrylonitrile; 1,3-butadiene; and ethylene oxide) than combustible cigarette-only, dual combustible cigarette-e-cigarette, or dual combustible cigarette-NRT users. The e-cigarette-only users had significantly lower NNAL levels than all other groups. Combustible cigarette-only, dual combustible cigarette-NRT, and dual combustible cigarette-e-cigarette users had largely similar levels of TSNA and VOC metabolites.
Cross-sectional design with self-selected sample.
Former smokers with long-term e-cigarette-only or NRT-only use may obtain roughly similar levels of nicotine compared with smokers of combustible cigarettes only, but results varied. Long-term NRT-only and e-cigarette-only use, but not dual use of NRTs or e-cigarettes with combustible cigarettes, is associated with substantially reduced levels of measured carcinogens and toxins relative to smoking only combustible cigarettes.
Cancer Research UK.
Allocating the Renewable Portfolio Standard (RPS) targets among provinces in an economically viable and fair way is the first critical step to implementing the RPS policy in China. To explore this ...issue, a cost minimizing model was proposed and applied in this paper. The least-cost 2018 – 2020 RPS target allocation scheme for 29 provinces and regions in China was obtained. The efficiency and equity of the RPS target allocation scheme published by China National Energy Administration in 2018 was compared with the obtained least-cost scheme and an equal allocation scheme referring to the practice in countries with only national RPS target from three aspects – energy, environment and economy. The results showed that: (1) the least-cost scheme can reduce the total cost by 3% while increasing the distribution inequity of non-hydro renewable electricity consumption measured by the Gini coefficient by 343% (112% if hydro is included); (2) the equally-allocated scheme did not show a significant advantage in equity over the government published scheme but increased the cost. Based on the results, the possibility of adopting a national renewable energy certificates trade market to reduce the cost while maintaining the equity has been discussed, and the relevant policy suggestions have been proposed.
•A China provincial RPS target allocation model was presented.•A least-cost RPS target allocation scheme was obtained.•3E analyses on the efficiency and equity of the schemes were conducted.•The least-cost scheme produces lower cost and equity than the government one.•The equal-allocated scheme did not show significant advantages in equity.
We report full-dimensional, ab initio potential energy and dipole moment surfaces, denoted PES and DMS, respectively, for arbitrary numbers of water monomers. The PES is a sum of 1-, 2-, and 3-body ...potentials which can also be augmented by semiempirical long-range higher-body interactions. The 1-body potential is a spectroscopically accurate monomer potential, and the 2- and 3-body potentials are permutationally invariant fits to tens of thousands of CCSD(T)/aug-cc-pVTZ and MP2/aug-cc-pVTZ electronic energies, respectively. The DMS is a sum of 1- and 2-body DMS, which are covariant fits to tens of thousands MP2/aug-cc-pVTZ dipole moment data. We present the details of these new 2- and 3-body potentials and then extensive applications and tests of this PES are made to the structures, classical binding energies, and harmonic frequencies of water clusters up to the 22-mer. In addition, we report the dipole moment for these clusters at various minima and compare the results against available and new ab initio calculations.
PDF
