Calibration of Yld2000-2D Anisotropy Yield Criterion with Traditional Testing and Inverse Identification Strategies.

In order to improve predictive capabilities of numerical simulations, Yld2000-2D yield criterion is used to model the plastic anisotropic behaviors of AA5086 sheets. The parameters of Yld2000-2D yield criterion are identified based on the traditional testing strategy and the inverse identification strategy, respectively. The traditional testing strategy considers uniaxial and equi-biaxial tensile tests. The inverse identification strategy relies on the finite element model update (FEMU) method that couples with a biaxial tensile test using a dedicated cruciform specimen or the Pottier bulging test. The identified parameters are preliminarily evaluated by comparing predicted and experimental yield stresses, r-values, and yield loci. Then, the deep drawing test and simulations are performed. The identified parameter sets of Yld2000-2D yield criterion are further evaluated in terms of practical forming by comparing the predicted earing profile height with the experimental results. The results show that the inverse identification strategy can be an effective alternative to identify the parameters of Yld2000-2D yield criterion, and a well-designed heterogeneous test could lead to a better identification result.

Control of evolution of porous copper-based metal-organic materials for electroreduction of CO2 to multi-carbon products.

Electrochemcial reduction of CO2 to multi-carbon (C2+) products is an important but challenging task. Here, we report the control of structural evolution of two porous Cu(ii)-based materials (HKUST-1 and CuMOP, MOP = metal-organic polyhedra) under electrochemical conditions by adsorption of 7,7,8,8-tetracyanoquinodimethane (TNCQ) as an additional electron acceptor. The formation of Cu(i) and Cu(0) species during the structural evolution has been confirmed and analysed by powder X-ray diffraction, and by EPR, Raman, XPS, IR and UV-vis spectroscopies. An electrode decorated with evolved TCNQ@CuMOP shows a selectivity of 68% for C2+ products with a total current density of 268 mA cm-2 and faradaic efficiency of 37% for electrochemcial reduction of CO2 in 1 M aqueous KOH electrolyte at -2.27 V vs. RHE (reversible hydrogen electrode). In situ electron paramagnetic resonance spectroscopy reveals the presence of carbon-centred radicals as key reaction intermediates. This study demonstrates the positive impact of additional electron acceptors on the structural evolution of Cu(ii)-based porous materials to promote the electroreduction of CO2 to C2+ products.

Evolution of bismuth-based metal-organic frameworks for efficient electroreduction of CO2.

Understanding the structural and chemical changes that reactive metal-organic frameworks (MOFs) undergo is crucial for the development of new efficient catalysts for electrochemical reduction of CO2. Here, we describe three Bi(iii) materials, MFM-220, MFM-221 and MFM-222, which are constructed from the same ligand (biphenyl-3,3',5,5'-tetracarboxylic acid) but which show distinct porosity with solvent-accessible voids of 49.6%, 33.6% and 0%, respectively. We report the first study of the impact of porosity of MOFs on their evolution as electrocatalysts. A Faradaic efficiency of 90.4% at -1.1 V vs. RHE (reversible hydrogen electrode) is observed for formate production over an electrode decorated with MFM-220-p, formed from MFM-220 on application of an external potential in the presence of 0.1 M KHCO3 electrolyte. In situ electron paramagnetic resonance spectroscopy confirms the presence of ·COOH radicals as a reaction intermediate, with an observed stable and consistent Faradaic efficiency and current density for production of formate by electrolysis over 5 h. This study emphasises the significant role of porosity of MOFs as they react and evolve during electroreduction of CO2 to generate value-added chemicals.

Improved ClickTags enable live-cell barcoding for highly multiplexed single cell sequencing.

Click chemistry-enabled DNA barcoding of cells provides a universal strategy for sample multiplexing in single-cell RNA-seq (scRNA-seq). However, current ClickTags are limited to fixed samples as they only label cells efficiently in methanol. Herein, we report the development of a new protocol for barcoding live cells with improved ClickTags. The optimized reactions barcoded live cells without perturbing their physiological states, which allowed sample multiplexing of live cells in scRNA-seq. The general applicability of this protocol is demonstrated in diversified types of samples, including murine and human primary samples. Up to 16 samples across these two species are successfully multiplexed and demultiplexed with high consistency. The wide applications of this method could help to increase throughput, reduce cost and remove the batch effect in scRNA-seq, which is especially valuable for studying clinical samples from a large cohort.

Exposure Risk of Global Surface O3 During the Boreal Spring Season.

Surface ozone (O3) is an oxidizing gaseous pollutant; long-term exposure to high O3 concentrations adversely affects human health. Based on daily surface O3 concentration data, the spatiotemporal characteristics of O3 concentration, exposure risks, and driving meteorological factors in 347 cities and 10 major countries (China, Japan, India, South Korea, the United States, Poland, Spain, Germany, France, and the United Kingdom) worldwide were analyzed using the MAKESENS model, Moran' I analysis, and Generalized additive model (GAM). The results indicated that: in the boreal spring season from 2015 to 2020, the global O3 concentration exhibited an increasing trend at a rate of 0.6 µg/m3/year because of the volatile organic compounds (VOCs) and NOx changes caused by human activities. Due to the lockdown policies after the outbreak of COVID-19, the average O3 concentration worldwide showed an inverted U-shaped growth during the study period, increasing from 21.9 µg/m3 in 2015 to 27.3 µg/m3 in 2019, and finally decreasing to 25.9 µg/m3 in 2020. According to exposure analytical methods, approximately 6.32% of the population (31.73 million people) in the major countries analyzed reside in rapidly increasing O3 concentrations. 6.53% of the population (32.75 million people) in the major countries were exposed to a low O3 concentration growth environment. Thus, the continuous increase of O3 concentration worldwide is an important factor leading to increasing threats to human health. Further we found that mean wind speed, maximum temperature, and relative humidity are the main factors that determine the change of O3 concentration. Our research results are of great significance to the continued implementation of strict air quality policies and prevention of population hazards. However, due to data limitations, this research can only provide general trends in O3 and human health, and more detailed research will be carried out in the follow-up. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-022-00463-7.

Kindlin-2 Mediates Lipopolysaccharide-Induced Acute Lung Injury Partially via Pyroptosis in Mice.

Acute lung injury (ALI) is characteristic of the wholesale destruction of the lung endothelial barrier, which results in protein-rich lung edema, influx of pro-inflammatory leukocytes, and intractable hypoxemia, contributing to high mortality. Kindlin-2 is involved in the process of tumor- and wound healing-associated inflammation. However, the effects of kindlin-2 on lipopolysaccharide (LPS)-induced ALI and its mechanisms remain unknown. In this study, we found that the concentration of kindlin-2 was elevated in the lungs of ALI mice. The specific deletion of kindlin-2 by kindlin-2 siRNA attenuated the severity of lung injury, which was demonstrated by the reduced number of pro-inflammatory cells in bronchoalveolar lavage fluid and lung wet/dry weight ratio, and ameliorated pathologic changes in the lungs of ALI mice. Furthermore, kindlin-2 siRNA decreased the mRNA levels of pro-inflammatory factors (IL-1ß, IL-6, and TNF-α) and the protein levels of pyroptosis-related proteins. In vitro studies confirmed that LPS + ATP promoted the expressions of pro-inflammatory factors and pyroptosis-related proteins, which was prevented by kindlin-2 siRNA pretreatment in endothelial cells (ECs). In conclusion, inhibition of kindlin-2 developes protective effects against LPS-induced ALI and the cytotoxicity of ECs, which may depend on blocking pyroptosis.

Synthesis of l-ascorbic acid-amino acid-norcantharidin conjugates and their biological activity evaluation in vitro.

Three components of L-ascorbic acid, amino acid and functionalized norcantharidins were constructed together in several steps to form 42 norcantharidin derivatives in a high yield. The structure of these synthesized l-ascorbic acid-amino acid-norcantharidin conjugates are determined by 1HNMR, 13CNMR and MS spectrum. The results showed that compounds 6e, 6g, 6j, 6l, 6m, 6b, 6e, 6i, and 6n showed high cytotoxicity to HepG2 and compounds 6b, 6e-g, 6l, 6n, 7b, 7d, 7h, 7i, 7n, 8g, 8i exhibited high cytotoxicity to SW480; Meanwhile, besides 6b, 6e, 6g, and 6k, the other compounds showed less toxic to LO2 at a concentration of 50 µg/mg after 72 h. Compound 6g can induce Mφ-type macrophages derived from mouse bone marrow to polarize to M1-type macrophages.

Identification of toxicity factors and causal analysis of toxicity in surface sediments from Liaohe river basin, Northeast China using an effect guidance strategy.

Sediments play a pivotal role in maintaining the aquatic ecological status of rivers. However, the determination of the key toxicants that consider the combined effects of all sediment-related contaminants are still challenging and necessary for an appropriate sediment risk assessment. The effects of sediments on aquatic organisms have been reported in Liaohe River, but their key toxicity factors are not well known. To determine the key toxicity factors, twenty-six surface sediment samples from Liaohe River tributaries in Northeast China were collected. Acute toxicity test of midge larvae results showed that 6 of 26 tributaries had obvious toxic effects, with survival rates of 37%-57% (p < 0.05). The masking test showed that the main pollutants in the surface sediments of T7 and T16 were metals, that of T8 was an organic pollutant, those of T19 and T26 were organic pollutants and ammonia, and those of T17 were heavy metal and ammonia. Chemical analysis showed that the relatively high concentrations of ammonia were only presented in surface sediments of T17, T19, and T26, with PTU of 1.5, 1.2 and 1.1, respectively, whereas heavy metals were markedly high in surface sediments from T7 and T16, with PTU of 0.92 and 0.61, respectively. Interestingly, the observed toxicity in surface sediments agreed with the toxicity predicted by chemical analysis Moreover, the significant correlation between the survival and volume ratio of the sediment and overlying water confirmed ammonia nitrogen was key toxicity factor in T17, T19, and T26, whereas Cu was the key toxicity factor in T7 that cause the biological toxicity. In conclusion, the major toxic factors of ammonia and copper in the sediments were identified. Moreover, our study suggested that effect guidance strategy was an effective method for sediment quality assessment.

A review on China's constructed wetlands in recent three decades: Application and practice.

Constructed wetlands (CWs) have been introduced to and developed in China for environmental engineering over the most prosperous three decades (1990-2020). To study the origin, development process, and future trend of CWs, this review summarized a wide range of literatures between 1990 and 2020 by Chinese authors. Firstly, the publication number over years, research highlights, and the author contributions with the most published papers in this field were conducted through bibliometric analysis. Secondly, the most principal components of CWs, substrates and macrophytes were summarized and analyzed. Thirdly, the typical application cases from traditional CWs, pond systems to combined pond-wetland systems were presented. In China, CWs were predominately distributed in the east of the so-called 'Hu Huanyong Line'. Therefore CWs were limited by the socio-economic level and climatic conditions. It is unquestionable that the overall level of China's CWs has improved significantly, and one of the most prominent features has started towards the plural pattern development. There has been a trend of large-scale or low-cost CW application in the recent years. However, lifecycle research and management are required for better strategies in the future.

A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection.

Cell-free RNA (cfRNA) is a promising analyte for cancer detection. However, a comprehensive assessment of cfRNA in individuals with and without cancer has not been conducted. We perform the first transcriptome-wide characterization of cfRNA in cancer (stage III breast [n = 46], lung [n = 30]) and non-cancer (n = 89) participants from the Circulating Cell-free Genome Atlas (NCT02889978). Of 57,820 annotated genes, 39,564 (68%) are not detected in cfRNA from non-cancer individuals. Within these low-noise regions, we identify tissue- and cancer-specific genes, defined as "dark channel biomarker" (DCB) genes, that are recurrently detected in individuals with cancer. DCB levels in plasma correlate with tumor shedding rate and RNA expression in matched tissue, suggesting that DCBs with high expression in tumor tissue could enhance cancer detection in patients with low levels of circulating tumor DNA. Overall, cfRNA provides a unique opportunity to detect cancer, predict the tumor tissue of origin, and determine the cancer subtype.

Risks to aquatic environments posed by 14 pharmaceuticals as illustrated by their effects on zebrafish behaviour.

The presence of pharmaceutical residues in aquatic ecosystems is a worldwide problem that may pose serious threats and challenges to the environment, especially to the safety of aquatic biota. In the present study, we investigated the effects of 14 environmentally relevant pharmaceutical compounds on individual and collective-related behaviours in juvenile zebrafish (Danio rerio) for 21 days. The tested concentrations of the compounds spanned three orders of magnitude. This study also compared the potential risks of these compounds in Chinese surface waters based on the data on their toxic effects or only on behavioural effects. In the case of individual behaviours, most antidepressants, but not anti-inflammatory agents or blood lipid-lowering agents, decreased fish locomotor activity (LMA) and individual social activity (IDS); however, all three classes of compounds induced significant disruptions in the light/dark transition locomotor response (LMR-L/D) performance, even at lower treatment levels (0.1-1 µg/L). Furthermore, collective behaviour (CLB) analysis suggested that most of the compounds significantly altered the group sociability of fish and frequently occurred at environmentally relevant concentrations. Finally, a risk assessment suggested that the presence of ibuprofen, fluoxetine, and venlafaxine in the surface waters of China poses a relatively high risk to fish, regardless of the risk ranking based on the data of the toxic or behavioural effects.

Global, continental, and national variation in PM2.5, O3, and NO2 concentrations during the early 2020 COVID-19 lockdown.

Lockdowns implemented in response to COVID-19 have caused an unprecedented reduction in global economic and transport activity. In this study, variation in the concentration of health-threatening air pollutants (PM2.5, NO2, and O3) pre- and post-lockdown was investigated at global, continental, and national scales. We analyzed ground-based data from >10,000 monitoring stations in 380 cities across the globe. Global-scale results during lockdown (March to May 2020) showed that concentrations of PM2.5 and NO2 decreased by 16.1% and 45.8%, respectively, compared to the baseline period (2015-2019). However, O3 concentration increased by 5.4%. At the continental scale, concentrations of PM2.5 and NO2 substantially dropped in 2020 across all continents during lockdown compared to the baseline, with a maximum reduction of 20.4% for PM2.5 in East Asia and 42.5% for NO2 in Europe. The maximum reduction in O3 was observed in North America (7.8%), followed by Asia (0.7%), while small increases were found in other continents. At the national scale, PM2.5 and NO2 concentrations decreased significantly during lockdown, but O3 concentration showed varying patterns among countries. We found maximum reductions of 50.8% for PM2.5 in India and 103.5% for NO2 in Spain. The maximum reduction in O3 (22.5%) was found in India. Improvements in air quality were temporary as pollution levels increased in cities since lockdowns were lifted. We posit that these unprecedented changes in air pollutants were mainly attributable to reductions in traffic and industrial activities. Column reductions could also be explained by meteorological variability and a decline in emissions caused by environmental policy regulations. Our results have implications for the continued implementation of strict air quality policies and emission control strategies to improve environmental and human health.

A feasible strategy to improve confident elemental composition determination of compounds in complex organic mixture such as natural organic matter by FTICR-MS without internal calibration.

Confident elemental composition determination of compounds in complex samples such as natural organic matter (NOM) by ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is challenging due to the interference between multiple components in these samples during detection. Here the performance of Solarix 15T-FTICR-MS in terms of accurate relative natural isotope abundance (RIA) and mass measurements for elemental composition determination of compounds in complex samples such as NOM was systematically evaluated. The optimal sweep excitation power values ranging from 20% to 22% was found to significantly diminish the underestimation of RIA measurement for 13C1 peaks of NOM components by FTICR-MS. Random error was found to be one of the main sources for the RIA errors of 13C1 peaks with S/N ratios <25. The mean averaged RIA errors of less than 10% could be obtained by averaging the measured RIAs of each 13C1 peaks in five replicated runs. By adjusting the total ion abundance of NOM complex sample between 3.8-E7 and 1.4-E8 which was simultaneously similar to that of external calibrant during detection, mass errors of lower than 1 ppm for NOM components with m/z lower than 700 Da could be obtained without internal calibration. Meanwhile, a linear correlation between mass errors of ions in NOM complex sample and their m/z values could be obtained. The mass error deviation derived from the linearity was firstly used as new criterion to reduce the number of false formula candidates. A novel strategy of combination of high mass accuracy, high spectral accuracy, and mass error deviation for elemental composition determination of unknown compounds in complex sample such as NOM by FTICR-MS was proposed and applied for different complex samples. Compared to the traditional method, about one fold increasement in the number of the unique formula assignments for measured ions was obtained by using our strategy.

Synthesis and biological evaluation of camptothecin substituted norcantharimide derivatives.

In this paper, a series of novel derivatives of camptothecin substituted norcantharimide was designed by mimic strategy. These compounds were synthesized in moderate yields by directly coupling CPT with N-amino acid norcantharimides. Their cytotoxicity to four human tumour cell lines (HepG2, BGC-803, SW480 and PANC-1) and normal human cell lines L-O2 and HIEC was evaluated. The synthesized CPT substituted norcantharimide analogs (3g and 3f) showed better anti-hepatocarcinoma activity than CPT. Compounds 3d, 3e, 3g, 3h and 3i also showed strong inhibition activity against BGC803.

High-resolution mapping of cis-regulatory variation in budding yeast.

Genetic variants affecting gene-expression levels are a major source of phenotypic variation. The approximate locations of these variants can be mapped as expression quantitative trait loci (eQTLs); however, a major limitation of eQTLs is their low resolution, which precludes investigation of the causal variants and their molecular mechanisms. Here we report RNA-seq and full genome sequences for 85 diverse isolates of the yeast Saccharomyces cerevisiae-including wild, domesticated, and human clinical strains-which allowed us to perform eQTL mapping with 50-fold higher resolution than previously possible. In addition to variants in promoters, we uncovered an important role for variants in 3'UTRs, especially those affecting binding of the PUF family of RNA-binding proteins. The eQTLs are predominantly under negative selection, particularly those affecting essential genes and conserved genes. However, applying the sign test for lineage-specific selection revealed the polygenic up-regulation of dozens of biofilm suppressor genes in strains isolated from human patients, consistent with the key role of biofilms in fungal pathogenicity. In addition, a single variant in the promoter of a biofilm suppressor, NIT3, showed the strongest genome-wide association with clinical origin. Altogether, our results demonstrate the power of high-resolution eQTL mapping in understanding the molecular mechanisms of regulatory variation, as well as the natural selection acting on this variation that drives adaptation to environments, ranging from laboratories to vineyards to the human body.

Cis-regulatory evolution in prokaryotes revealed by interspecific archaeal hybrids.

The study of allele-specific expression (ASE) in interspecific hybrids has played a central role in our understanding of a wide range of phenomena, including genomic imprinting, X-chromosome inactivation, and cis-regulatory evolution. However across the hundreds of studies of hybrid ASE, all have been restricted to sexually reproducing eukaryotes, leaving a major gap in our understanding of the genomic patterns of cis-regulatory evolution in prokaryotes. Here we introduce a method to generate stable hybrids between two species of halophilic archaea, and measure genome-wide ASE in these hybrids with RNA-seq. We found that over half of all genes have significant ASE, and that genes encoding kinases show evidence of lineage-specific selection on their cis-regulation. This pattern of polygenic selection suggested species-specific adaptation to low phosphate conditions, which we confirmed with growth experiments. Altogether, our work extends the study of ASE to archaea, and suggests that cis-regulation can evolve under polygenic lineage-specific selection in prokaryotes.

Separation and determination of estrogen in the water environment by high performance liquid chromatography-fourier transform infrared spectroscopy.

The components for connecting high-performance liquid chromatography (HPLC) with Fourier-transform infrared spectroscopy (FTIR) were investigated to determine estrogen in the water environment, including heating for atomization, solvent removal, sample deposition, drive control, spectrum collection, chip swap, cleaning and drying. Results showed that when the atomization temperature was increased to 388 K, the interference of mobile phase components (methanol, H2O, acetonitrile, and NaH2PO4) were completely removed in the IR measurement of estrogen, with 0.999 of similarity between IR spectra obtained after separation and corresponding to the standard IR spectra. In experiments with varying HPLC injection volumes, high similarity for IR spectra was obtained at 20 ul injection volume at 0.01 mg/L BPA while a useful IR spectrum for 10 ng/L BPA was obtained at 80 ul injection volume. In addition, estrogen concentrations in the natural water samples were calculated semi-quantitatively from the peak intensities of IR spectrum in the mid-infrared region.

[Effect of Recycled Water Irrieation on Heavy Metal Pollution in Irrigation Soil].

With acceleration of urbanization, water shortages will become a serious problem. Usage of reclaimed water for flushing and watering of the green areas will be common in the future. To study the heavy metal contamination of soils after green area irrigation using recycled wastewater from special industries, we selected sewage and laboratory wastewater as water source for integrated oxidation ditch treatment, and the effluent was used as irrigation water of the green area. The irrigation units included broad-leaved forest, bush and lawn. Six samples sites were selected, and 0-20 cm soil of them were collected. Analysis of the heavy metals including Cr, Mn, Ni, Cu, Zn, As, Cd and Pb in the soil showed no significant differences with heavy metals concentration in soil irrigated with tap water. The heavy metals in the soil irrigated with recycled water were mainly enriched in the surface layer, among which the contents of Cr, Ni, Cu, Zn and Pb were below the soil background values of Beijing. A slight pollution of As and Cd was found in the soil irrigated by recycled water, which needs to be noticed.

Dissecting the Genetic Basis of a Complex cis-Regulatory Adaptation.

Although single genes underlying several evolutionary adaptations have been identified, the genetic basis of complex, polygenic adaptations has been far more challenging to pinpoint. Here we report that the budding yeast Saccharomyces paradoxus has recently evolved resistance to citrinin, a naturally occurring mycotoxin. Applying a genome-wide test for selection on cis-regulation, we identified five genes involved in the citrinin response that are constitutively up-regulated in S. paradoxus. Four of these genes are necessary for resistance, and are also sufficient to increase the resistance of a sensitive strain when over-expressed. Moreover, cis-regulatory divergence in the promoters of these genes contributes to resistance, while exacting a cost in the absence of citrinin. Our results demonstrate how the subtle effects of individual regulatory elements can be combined, via natural selection, into a complex adaptation. Our approach can be applied to dissect the genetic basis of polygenic adaptations in a wide range of species.