Multi-objective ecological restoration priority in China: Cost-benefit optimization in different ecological performance regimes based on planetary boundaries.

In the context of the "United Nations Decade on Ecosystem Restoration", optimizing spatiotemporal arrangements for ecological restoration is an important approach to enhancing overall socioecological benefits for sustainable development. However, against the background of ecological degradation caused by the human use of most natural resources at levels that have approached or exceeded the safe and sustainable boundaries of ecosystems, it is key to explain how to optimize ecological restoration by classified management and optimal total benefits. In response to these issues, we combined spatial heterogeneity and temporal dynamics at the national scale in China to construct five ecological performance regimes defined by indicators that use planetary boundaries and ecological pressures which served as the basis for prioritizing ecological restoration areas and implementing zoning control. By integrating habitat conservation, biodiversity, water supply, and restoration cost constraints, seven ecological restoration scenarios were simulated to optimize the spatial layout of ecological restoration projects (ERPs). The results indicated that the provinces with unsustainable freshwater use, climate change, and land use accounted for more than 25%, 66.7%, and 25%, respectively, of the total area. Only 30% of the provinces experienced a decrease in environmental pressure. Based on the ecological performance regimes, ERP sites spanning the past 20 years were identified, and more than 50% of the priority areas were clustered in regime areas with increased ecological stress. As the restoration area targets doubled (40%) from the baseline (20%), a multi-objective scenario presents a trade-off between expanded ERPs in areas with highly beneficial effects and minimal restoration costs. In conclusion, a reasonable classification and management regime is the basis for targeted restoration. Coordinating multiple objectives and costs in ecological restoration is the key to maximizing socio-ecological benefits. Our study offered new perspectives on systematic and sustainable planning for ecological restoration.

Global renewable energy trade network: patterns and determinants.

The renewable energy product trade is critically important to global economic prospects and its rapid development, making it a key issue in international economics of much interest to scholars. Previous studies have paid attention to bilateral trade, yet we still know little about the patterns of renewable energy product trade and its evolution from the whole industry perspective. Based on bilateral trade data, complex network, as well as ERGM and TERGM, we build global renewable energy trade networks (GRETNs) during 2000-2018 and explore the patterns and determinants. The results show that (1) the GRETNs expand during 2000-2018, characterized by a small-world, reciprocity, degree disassortative, and export volume heterogeneity. (2) The GRETNs form four communities, and the community patterns greatly fluctuate over time. (3) Economies in North America, Europe, and Asia play dominant roles, while the USA, Germany, and China are the cores of the GRETNs. (4) Endogenous structure of reciprocity, structural embeddedness, and out-degree popularity are essential parts of the evolving patterns of GRETNs. Most trade relationships are developed between economies located within the same continent, participating in APEC or WTO, or having similar areas. There is heterophily in GDP and per capita income, and Matthew effects in GDP, urbanization, and industrialization rate. Countries that share a common geographic border, language, religion, or currency, being former colonies of the same colonialists, and having signed regional trade agreements are more likely to trade in renewable energy products.

Deterioration of single-use biodegradable plastics in high-humidity air and freshwaters over one year: Significant disparities in surface physicochemical characteristics and degradation rates.

More single-use plastics are accumulating in the environment, and likewise biodegradable plastics (BPs), which are being vigorously promoted, cannot escape the fate. Currently, studies on the actual degradation of BPs in open-air and freshwaters are underrepresented despite they are potentially headmost leakage and contamination sites for disposable BPs. Herein, we compared the degradation behavior of six BP materials and non-degradable polypropylene (PP) plastics over a 1-year in situ suspension in the high-humidity air, a eutrophic river, and an oligotrophic lake. Moreover, a 3-months laboratory incubation was performed to detect the release of dissolved organic carbon (DOC) from BPs. In both air and freshwaters, poly(p-dioxanone) (PPDO) degraded significantly while PP and polylactic acid (PLA) showed no signs of degradation. The average degradation rates of three poly(butylene adipate-co-terephthalate) (PBAT)-based films varied: 100% in river, 55% in lake, and 10% in air. In addition to PLA, surface chemical groups, hydrophilicity, and thermal stability of BPs changed, and microplastics were found on their surfaces. Correspondingly, BPs with faster degradation rates released relatively higher amounts of DOC. Environmental microbial and chemical characteristics may contribute to differences in BP degradation besides polymer specificity. Altogether, our results indicate the need for appropriate monitoring of BPs.

A Pilot Study of Ratiometric Creatine CEST MRI Assessment of Rabbit Skeletal Muscle Energy Metabolism at 3 T.

BACKGROUND: pH MRI may provide useful information to evaluate metabolic disruption following ischemia. Radiofrequency amplitude-based creatine chemical exchange saturation transfer (CrCEST) ratiometric MRI is pH-sensitive, which could but has not been explored to examine muscle ischemia. PURPOSE: To investigate skeletal muscle energy metabolism alterations with CrCEST ratiometric MRI. STUDY TYPE: Prospective. ANIMAL MODEL: Seven adult New Zealand rabbits with ipsilateral hindlimb muscle ischemia. FIELD STRENGTH/SEQUENCE: 3 T/two MRI scans, including MRA and CEST imaging, were performed under two B1 amplitudes of 0.5 and 1.25 µT after 2 hours of hindlimb muscle ischemia and 1 hour of reperfusion recovery, respectively. ASSESSMENT: CEST effects of two energy metabolites of creatine and phosphocreatine (PCrCEST) were resolved with the multipool Lorentzian fitting approach. The pixel-wise CrCEST ratio was quantified by calculating the ratio of the resolved CrCEST peaks under a B1 amplitude of 1.25 µT to those under 0.5 µT in the entire muscle. STATISTICAL TESTS: One-way ANOVA and Pearson's correlation. P < 0.05 was considered statistically significant. RESULTS: MRA images confirmed the blood flow loss and restoration in the ischemic hindlimb at the ischemia and recovery phases, respectively. Ischemic muscles exhibited a significant decrease of PCr at the ischemia (under both B1 amplitudes) and recovery phases (under B1 amplitude of 0.5 µT) and significantly increased CrCEST from normal tissues at both phases (under both B1 levels). Specifically, CrCEST decreased, and PCrCEST increased with the CrCEST ratio. Significantly strong correlations were observed among the CrCEST ratio, and CrCEST and PCrCEST under both B1 levels (r > 0.80). DATA CONCLUSION: The CrCEST ratio altered substantially with muscle pathological states and was closely related to CEST effects of energy metabolites of Cr and PCr, suggesting that the pH-sensitive CrCEST ratiometric MRI is feasible to evaluate muscle injuries at the metabolic level. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.

PBT assessment of chemicals detected in effluent of wastewater treatment plants by suspected screening analysis.

Wastewater treatment plants (WWTPs) are the major sources of contaminants discharged into downstream water bodies. Profiling the contaminants in effluent of WWTPs is crucial to assess the potential eco-risks toward downstream organisms. To this end, this study investigated the contaminants in effluent of 10 WWTPs locating in 10 cities of Yangtze River delta region of China by suspected screening analysis. Further, the persistence, bioaccumulation, toxicity (PBT) and the characteristics sub-structures of PBT-like chemicals were analyzed. Totally, 704 chemicals including 155 chemical products, 31 food additives, 52 natural substances, 112 personal care products, 123 pesticides, 192 pharmaceuticals, 17 hormones and 22 others were found. The results of PBT analysis suggested that 42 chemicals (5.97% among the detected chemicals in WWTPs) were with PBT property. Among them, 31 contaminants were not reported previously. 9 characteristics sub-structures (N-methyleneisobutylamine, 1-naphthaldehyde, 2,3,3-trimethylcyclohexene, cyclohexanol, N-sec-butyl-n-propylamine, (5E)-2,6-dimethylocta-1,5-diene, 2-ethylphenol, pentadecane and 6-methoxyhexane) were found for PBT-like chemicals. The sub-structures of highly linear alkyl partially explained the significantly higher PBT score for personal care products. Present study provides fundamental information on PBT properties of contaminants in effluent of WWTPs, which will benefit to prioritize contaminants with high concerns in effluent of WWTPs.

The optimum economic nitrogen rate of blended controlled-release nitrogen fertilizer for rice in the Chanoyu watershed in the Yangtze River Delta, China.

Introduction: The application of controlled-release nitrogen fertilizer (CRN) has become an important production method to achieve high crop yield and ecological safety. However, the rate of urea-blended CRN for rice is usually determined by conventional urea, and the actual rate is still unclear. Methods: A five-year field experiment was carried out in the Chaohu watershed in the Yangtze River Delta to study rice yield, N fertilizer utilization efficiency (NUE), ammonia (NH3) volatilization and economic benefit under the four urea-blended CRN treatments with a 4:3:3 ratio applied at one time (60, 120, 180, 240 kg/hm2, CRN60, CRN120, CRN180, CRN240), four conventional N fertilizer treatments (N60, N120, N180, N240) and a control without N fertilizer (N0). Results and Discussion: The results showed that the N released from the blended CRNs could well satisfy the N demand of rice growth. Similar to the conventional N fertilizer treatments, a quadratic equation was used to model the relationship between rice yield and N rate under the blended CRN treatments. The blended CRN treatments increased rice yield by 0.9-8.2% and NUE by 6.9-14.8%, respectively, compared with the conventional N fertilizer treatments at the same N application rate. The increase in NUE in response to applied blended CRN was related to the reduction in NH3 volatilization. Based on the quadratic equation, the five-year average NUE under the blended CRN treatment was 42.0% when rice yield reached the maximum, which was 28.9% higher than that under the conventional N fertilizer treatment. Among all treatments, CRN180 had the highest yield and net benefit in 2019. Considering the yield output, environmental loss, labor and fertilizer costs, the optimum economic N rate under the blended CRN treatment in the Chaohu watershed was 180-214 kg/hm2, compared with 212-278 kg/hm2 under the conventional N fertilizer treatment. The findings suggest that blended CRN improved rice yield, NUE and economic income while decreasing NH3 volatilization and negative environmental outcomes.

Global intercompany assessment of ICIEF platform comparability for the characterization of therapeutic proteins.

An international team spanning 19 sites across 18 biopharmaceutical and in vitro diagnostics companies in the United States, Europe, and China, along with one regulatory agency, was formed to compare the precision and robustness of imaged CIEF (ICIEF) for the charge heterogeneity analysis of the National Institute of Standards and Technology (NIST) mAb and a rhPD-L1-Fc fusion protein on the iCE3 and the Maurice instruments. This information has been requested to help companies better understand how these instruments compare and how to transition ICIEF methods from iCE3 to the Maurice instrument. The different laboratories performed ICIEF on the NIST mAb and rhPD-L1-Fc with both the iCE3 and Maurice using analytical methods specifically developed for each of the molecules. After processing the electropherograms, statistical evaluation of the data was performed to determine consistencies within and between laboratory and outlying information. The apparent isoelectric point (pI) data generated, based on two-point calibration, for the main isoform of the NIST mAb showed high precision between laboratories, with RSD values of less than 0.3% on both instruments. The SDs for the NIST mAb and the rhPD-L1-Fc charged variants percent peak area values for both instruments are less than 1.02% across different laboratories. These results validate the appropriate use of both the iCE3 and Maurice for ICIEF in the biopharmaceutical industry in support of process development and regulatory submissions of biotherapeutic molecules. Further, the data comparability between the iCE3 and Maurice illustrates that the Maurice platform is a next-generation replacement for the iCE3 that provides comparable data.

Quality comparability assessment of a SARS-CoV-2-neutralizing antibody across transient, mini-pool-derived and single-clone CHO cells.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a serious public health crisis worldwide, and considering the novelty of the disease, preventative and therapeutic measures alike are urgently needed. To accelerate such efforts, the development of JS016, a neutralizing monoclonal antibody directed against the SARS-CoV-2 spike protein, was expedited from a typical 12- to 18-month period to a 4-month period. During this process, transient Chinese hamster ovary cell lines are used to support preclinical, investigational new drug-enabling toxicology research, and early Chemistry, Manufacturing and Controls development; mini-pool materials to supply Phase 1 clinical trials; and a single-clone working cell bank for late-stage and pivotal clinical trials were successively adopted. Moreover, key process performance and product quality investigations using a series of orthogonal and state-of-the-art techniques were conducted to demonstrate the comparability of products manufactured using these three processes, and the results indicated that, despite observed variations in process performance, the primary and high-order structures, purity and impurity profiles, biological and immunological functions, and degradation behaviors under stress conditions were largely comparable. The study suggests that, in particular situations, this strategy can be adopted to accelerate the development of therapeutic biopharmaceuticals and their access to patients.

Comparison of CAIPIRINHA-accelerated 3D fat-saturated-SPACE MRI with 2D MRI sequences for the assessment of shoulder pathology.

OBJECTIVES: To compare the performance of 6-min MRI with a fat-saturated 3D-controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) Sampling perfection with application-optimized contrast using different flip angle evolution (SPACE) TSE protocol with 10-min 2D TSE MRI protocol for assessment of abnormalities of the shoulder. METHODS: Forty-nine subjects underwent both 3D fat-saturated-CAIPIRINHA SPACE and 2D TSE sequences of the shoulder on a 3.0-T system. Following randomization and anonymization, two musculoskeletal radiologists evaluated the 2D and 3D images independently for image quality and diagnostic capability. Descriptive statistics, inter-observer, and inter-method concordance were investigated. p values < 0.05 were considered significant. RESULTS: For image quality assessment, 2D images were similar to 3D CAIPIRINHA SPACE images (p = 0.05). 3D had lower noise standard deviation (SD) and higher fluid CNR than 2D images (p = 0.00). For diagnostic capability assessment, using 2D TSE as a standard of reference, sensitivity, specificity, and accuracy of 3D SPACE were, respectively, 94.81%, 94.12%, and 94.39% for tendon abnormalities; 97.06%, 80.00%, and 91.84% for acromioclavicular joint abnormalities; 88.89%, 100.00%, and 93.89% for adjacent bone alterations; and 97.30%, 100%, and 97.96% for joint fluid/effusion assessment. The inter-method concordance was moderate to almost perfect. The inter-observer-concordance of the shoulder assessment was also moderate to almost perfect, with SSP lesions demonstrating the greatest concordance. CONCLUSIONS: The performance of 6-min 3D fat-saturated-CAIPIRINHA SPACE MRI for shoulder MRI is similar to that of 10-min 2D TSE MRI. 3D fat-saturated-CAIPIRINHA SPACE MRI can be utilized to reduce scan time without degradation in image quality. KEY POINTS: • CAIPIRINHA acceleration 3D fat-saturated-MRI of the shoulder is achievable in 6 min with high spatial resolution. • 3D fat-saturated CAIPIRINHA MRI is similar to 2D MRI in the shoulder assessment. • 3D CAIPIRINHA MRI images enable rapid diagnosis of shoulder abnormalities without image quality degradation.

Cost-effectiveness analysis of glecaprevir/pibrentasvir regimen for treating Chinese patients with chronic hepatitis C genotype 1 and genotype 2 infection.

BACKGROUND: Hepatitis C virus (HCV) infection is an important health threat in China to which direct acting antivirals (DAAs) are very effective. In 2019, another novel DAA glecaprevir/pibrentasvir (GLE/PIB) was officially approved. Knowledge of its cost-effectiveness would be informative for clinical decision-making but has not been evaluated. This study aims to evaluate the cost-effectiveness of GLE/PIB to inform policy-making on drug reimbursement and HCV eradication. METHODS: Markov models were developed from the payers' perspective and simulated the lifetime experience of adult patients chronically infected with HCV genotype 1 or genotype 2. Two regimens, GLE/PIB and pegylated interferon (pegIFN) plus ribavirin (RBV), were compared in cost and quality adjusted life years (QALY) with both outcomes being discounted to 2020 values. The incremental cost-effectiveness ratio (ICER) was computed to reflect the incremental benefit of GLE/PIB versus pegIFN + RBV. The robustness of the model outcomes was examined using deterministic and probabilistic sensitivity analysis (PSA) to identify influential parameters and to assess the probability of GLE/PIB being cost-effective. The GDP per capita in China in 2019 ($10,275) was used as the threshold for cost-effectiveness. RESULTS: For the entire target population, GLE/PIB was the dominant regimen attaining a cost-saving of $255 and 1.17 more QALYs relative to pegIFN + RBV. The finding was more pronounced for HCV genotype 1 infection by saving $1,656 and creating 1.37 more QALYs. At the $10,275 threshold, the probability of GLE/PIB being cost-effective was 99.32% overall and 99.85% for HCV genotype 1 infection. The age of starting DAA treatment, price of pegIFN + RBV, cost of cirrhosis treatment and duration of the GLE/PIB regimen were the five most influential factors. For the patients with HCV genotype 2 infection, the ICER of GLE/PIB was $12,914/QALY with 95% confidence interval of $4,047/QALY to $37,640/QALY. The GLE/PIB regimen statistically cannot be ruled out as a cost-effective option for HCV genotype 2 infection. CONCLUSIONS: GLE/PIB is a cost-effective strategy to treat chronic HCV genotype 1 and HCV genotype 2 infection in China. This regimen should be initiated at a younger age to maximize its value. To achieve national eradication, it may be timely to consider replacing pegIFN + RBV with DAAs, such as GLE/PIB, as the first-line treatment.

Development and assessment of a duplex droplet digital PCR method for quantification of GM rice Kemingdao.

The implementation of genetically modified organism (GMO) labeling policies requires accurate quantitative methods to measure the GMO content in test samples. A Kemingdao/phospholipase D (KMD/PLD) duplex ddPCR method was established with rice genomic DNA (gDNA) of homozygous KMD as template by optimizing the annealing temperature and cycle number. Duplex ddPCR showed a linear response over the dynamic range from 68 to 175,000 copies, covering four orders of magnitude. The limit of detection (LOD) and limit of quantification (LOQ) for duplex ddPCR were determined to be 9 copies and 34 copies of the rice haploid genome, respectively. A very high dilution factor would result in unacceptable bias and coefficients of variation for determining copy number of the gDNA solution, and more than 1000 copies of the DNA template in one reaction is preferred to obtain accurate quantitative results by duplex PCR. Five blinded DNA samples with copy number ratio of 10%, 5%, 1%, 0.1%, and 0.05%, and three blinded real-life matrix samples with mass fraction of 5%, 1%, and 0.5% were quantified by duplex ddPCR, simplex ddPCR, and qPCR. These three methods all gave comparable GMO content and copy numbers within the required precision, but the duplex ddPCR showed the narrowest uncertainty interval and provided the highest precision in comparison to simplex ddPCR and qPCR. The ddPCR is a more appealing and reliable technology for the accurate quantification of GMO content than simplex ddPCR and qPCR considering the uncertainty and precision of quantitative results, the time consumption of generating droplets, and the cost of ddPCR reagents.

Molecular classification improves risk assessment in adult BCR-ABL1-negative B-ALL.

Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1- B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome data, 29.5% with favorable outcomes (5-year OS 65% to 80%) were deemed standard risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-risk genotypes with 5-year OS of 0% to 27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-hypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); 20.3% had intermediate-risk genotypes with 5-year OS of 33% to 45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like, and TP53 mutations in patients who were low-hypodiploid (54%) and BCL2/MYC-rearranged (33%) but were not independently associated with outcome. Of patients considered high risk based on presenting age and white blood cell count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-risk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like, and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non-risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits.

A personalized 3D-printed plate for tibiotalocalcaneal arthrodesis: Design, fabrication, biomechanical evaluation and postoperative assessment.

Personalized plates (P-Plates) could provide improved clinical outcomes in joint fusion by enabling perfect geometric matching between irregular bone and implants. However, there is no unified application framework for P-Plates for joint fusion. The objective of this study was to develop such a framework for P-Plates for tibiotalocalcaneal arthrodesis. A patient-specific bone model was constructed based on CT images, and the P-Plate was preliminarily designed to match the bones. Finite element method was used to optimize the stress distribution and to evaluate the biomechanical performance of the P-Plate by comparing it with a traditional plate (T-Plate). Then, the P-Plate was manufactured via electron beam melting and implanted into the foot of a patient. Increasing the size of the preliminary designed plate alleviated the stress concentration and reduced the risk of failure. The maximum stresses of the plate and screw (214.3 MPa, 99.05 MPa) and the maximum tensile force of the screw in the P-Plate (181.4 N) fixation system were lower than those in the T-Plate (217.4 MPa, 255.4 MPa, and 230.1 N, respectively). The P-Plate was well-matched to the bone, and no complications occurred. The P-Plate achieved American Orthopaedic Foot & Ankle Society and Short-Form-36 scores of 64 and 75, respectively, 36 months post operation, which suggests that it could improve clinical outcomes. The design and fabrication methods, as well as mechanical and postoperative performance evaluation methods, for the P-Plate were systematically developed and provide a reference for constructing a unified application framework for P-Plate use in tibiotalocalcaneal arthrodesis.

Effectiveness of Levoamlodipine Maleate for Hypertension Compared with Amlodipine Besylate: a Pragmatic Comparative Effectiveness Study.

PURPOSE: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

Time-dependent stress evidence in dynamic allocation of physiological metabolism of Nilaparvata lugens in response to elevated CO2.

To assess the time-dependent stress evidence in dynamic allocation of physiological metabolism of Nilaparvata lugens nymphs in response to elevated CO2, we measured the time-dependent allocation of nutrient compositions and physiological metabolism in the bodies of N. lugens at 1h, 4h and 12h under elevated CO2. Elevated CO2 significantly increased the contents of nutrient compositions (protein, glucose and total amino acids) and catalase (CAT) enzyme activity in the body of N. lugens at 12h relative to 1h and 4h (P < 0.05). Significantly higher genes expression levels of acetylcholinesterase (AChE), heat shock protein (HSP70) and vitellogenin gene (vg) were observed in the body of N. lugens compared with those in ambient CO2 at 4h (P < 0.05). These results showed that there was an instantaneous reaction of N. lugens nymphs to elevated CO2, which indicated N. lugens may enhance stress defense response to future increasing CO2 levels.

Skin Toxicity Assessment of Silver Nanoparticles in a 3D Epidermal Model Compared to 2D Keratinocytes.

INTRODUCTION: Increased use of silver nanoparticles (AgNPs) has raised concerns that AgNPs may induce toxic effects. In vitro studies of cell monolayers and in vivo studies have produced conflicting results. The inconsistency of these results has been mainly due to limitations of two-dimensional (2D) monolayer cell systems. METHODS: A three-dimensional (3D) epidermal model called EpiKutis®, which exhibits good tissue viability and barrier function was developed. The cytotoxicity of AgNPs against EpiKutis was compared to that against 2D keratinocytes at equivalent AgNPs doses (0.035, 0.07, 0.14, 0.28, and 0.56 ng per cell). The amount and distribution of AgNPs in the 3D EpiKutis and 2D keratinocytes after exposure were determined. The toxic mechanisms of AgNPs, such as oxidative stress and production of pro-inflammatory cytokines, were investigated. RESULTS: The results demonstrated that cell viability was greater than 80% and lactate dehydrogenase (LDH) release did not increase even at the highest dose of AgNPs in EpiKutis. In contrast, treatment of 2D keratinocytes with AgNPs resulted in dose-dependent decrease in cell viability from 63% to 11%, and a dose-dependent increase in LDH release from 8% to 16%. Cytotoxicity of AgNPs in 2D keratinocytes was related to oxidative damage and inflammation, as evidenced by increased levels of reactive oxygen species (ROS), malondialdehyde (MDA), IL-1α, IL-6, and IL-8. In addition, levels of superoxide dismutase (SOD) were decreased. EpiKutis treated with AgNPs did not exhibit increased oxidative damage or inflammation, which may have been due to the barrier properties of the 3D structure, resulting in reduced penetration of AgNPs. At equivalent per cell doses, total silver penetration into EpiKutis was 0.9 ± 0.1%, and total silver penetration into 2D keratinocytes was 8.8 ± 0.6% detected by ICP-MS. The penetration and distribution of AgNPs in 2D keratinocytes were confirmed by the TEM-EDS analysis, which was not found in the 3D EpiKutis. These results showed that AgNPs penetrated EpiKutis to a lesser degree than they penetrated 2D keratinocytes, which suggested that EpiKutis exhibited significant barrier function. DISCUSSION: The results of this study showed that AgNP toxicity should be evaluated using 3D epidermal models, which may provide better estimates of in vivo conditions than 2D models. The EpiKutis model may be an ideal model for assessment of nanotoxicity.

A Roadmap to Low-Cost Hydrogen with Hydroxide Exchange Membrane Electrolyzers.

Hydrogen is an ideal alternative energy carrier to generate power for all of society's energy demands including grid, industrial, and transportation sectors. Among the hydrogen production methods, water electrolysis is a promising method because of its zero greenhouse gas emission and its compatibility with all types of electricity sources. Alkaline electrolyzers (AELs) and proton exchange membrane electrolyzers (PEMELs) are currently used to produce hydrogen. AELs are commercially mature and are used in a variety of industrial applications, while PEMELs are still being developed and find limited application. In comparison with AELs, PEMELs have more compact structure and can achieve higher current densities. Recently, however, an alternative technology to PEMELs, hydroxide exchange membrane electrolyzers (HEMELs), has gained considerable attention due to the possibility to use platinum group metal (PGM)-free electrocatalysts and cheaper membranes, ionomers, and construction materials and its potential to achieve performance parity with PEMELs. Here, the state-of-the-art AELs and PEMELs along with the current status of HEMELs are discussed in terms of their positive and negative aspects. Additionally discussed are electrocatalyst, membrane, and ionomer development needs for HEMELs and benchmark electrocatalysts in terms of the cost-performance tradeoff.

Diffusion kurtosis imaging provides quantitative assessment of the microstructure changes of disc degeneration: an in vivo experimental study.

OBJECTIVE: Our aim was to assess the microstructural changes of intervertebral disc degeneration induced by annulus needle puncture in rats by diffusion kurtosis imaging (DKI). METHODS: Eighteen rats (36 discs) were punctured percutaneously at the intervertebral disc between C6/7, C7/8 (C-coccygeal vertebrae) with a 21-gauge needle. The rats were divided into six groups according to the time after the puncture: 3 h, 48 h, 3 days, 7 days, 10 days and 14 days. There were six discs in three rats in the control group. The rats' tail was imaged at 3T MRI with T2-weighted and diffusion-weighted and diffusion kurtosis imaging (DWI)/DKI sequences. The discs were categorized using a five-grade degeneration system based on the T2 images. The height of the discs and the parameters in DWI/DKI were measured and compared between the different time points. The histological images were also obtained from the discs. RESULTS: The histological study revealed that the discs in the rat of the punctured groups were degenerated. The T2 grades of different groups presented an increasing trend from 7 to 10 days after puncture (R2 = 0.9424, P < 0.001), while the DWI/DKI parameters changes were consistent with the histological changes at the different time points and showed significant differences between the different groups (P < 0.05). CONCLUSIONS: DKI provides quantitative assessment of the microstructure changes of disc degeneration, and it is a non-invasive method. The DKI multi-parameter analysis is sensitive to discs changes caused by puncture. These slides can be retrieved under Electronic Supplementary Material.

A novel three-dimensional tumorsphere culture system for the efficient and low-cost enrichment of cancer stem cells with natural polymers.

Cancer stem cells (CSCs) are considered to serve a key role in tumor progression, recurrence and metastasis. Tumorsphere culture is the most important method for enriching CSCs and is widely used in basic research and drug screening. However, the traditional suspension cell culture system has several disadvantages, including low efficiency, high cost and difficult procedure, making it difficult to produce tumorspheres on a large scale. In the present study, two biomaterials, methylcellulose (MC) and gellan gum (GG), were used to construct a novel culture system based on the traditional system. Subsequently, the characteristics of the novel three-dimensional (3D) culture system were evaluated, the design scheme was optimized, and the morphological and biological features of the tumorspheres cultured in this 3D system were compared with the traditional system. The results revealed that the tumorspheres cultured in the novel 3D system presented a higher seeding density and improved morphology, while maintaining stem-like properties. This evidence suggests that a simple, efficient and low-cost culture system that produces tumorspheres on a large scale was successfully constructed, which can be widely used in various aspects of stem cell research.

Assessment of urban sustainability efficiency based on general data envelopment analysis: a case study of two cities in western and eastern China.

Sustainable urban development focuses on enhancing urban well-being, while also balancing the demands of urban social and economic development, natural resource consumption, and environmental pollution. This work used general data envelopment analysis to assess the urban sustainability efficiency (USE) and sustainability potential (SP) in Lanzhou and Xiamen, two cities that are characteristic of urban areas in western and eastern China. The assessment indicator system included important natural and urban welfare factors as input and output indices, respectively. The results showed that overall urban sustainability efficiency increased in Lanzhou and Xiamen from 1985 to 2010, but that the sustainability of natural resources clearly decreased. The urban sustainability efficiency of Xiamen was higher than that of Lanzhou, and the sustainability potential of Xiamen was lower than that of Lanzhou; this indicates that Xiamen performed better in terms of urban sustainable development. The urban sustainability efficiency in Xiamen has increased with increasing urban population, and the rate and scale of economic development have been higher than in Lanzhou. The assessment and analysis performed in this study show that cities with different natural resources and development characteristics have different forms, patterns, and trajectories of sustainable development.