Marine toxin domoic acid alters nitrogen cycling in sediments.

As a red tide algal toxin with intense neurotoxicity distributed worldwide, domoic acid (DA) has attracted increasing concerns. In this work, the integrative analysis of metagenome and metabolome are applied to investigate the impact of DA on nitrogen cycling in coastal sediments. Here we show that DA can act as a stressor to induce the variation of nitrogen (N) cycling by altering the abundance of functional genes and electron supply. Moreover, microecology theory revealed that DA can increase the role of deterministic assembly in microbial dynamic succession, resulting in the shift of niches and, ultimately, the alteration in N cycling. Notably, denitrification and Anammox, the important process for sediment N removal, are markedly limited by DA. Also, variation of N cycling implies the modification in cycles of other associated elements. Overall, DA is capable of ecosystem-level effects, which require further evaluation of its potential cascading effects.

Development of a prediction model for exercise tolerance decline in the exercise assessment of patients with acute myocardial infarction undergoing percutaneous coronary intervention revascularization in the acute phase.

Background: Early cardiopulmonary exercise test (CPET) may predict the prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). However, data from CPET to assess the exercise capacity of patients with AMI PCI are still scarce. This study aimed to evaluate the safety of the CPET and assess the predictors and clinical influence of exercise capacity measured by CPET in patients with AMI within 1 week after PCI. Methods: A total of 275 patients with AMI who underwent PCI in the acute phase were selected. Reduced exercise capacity was defined as peak oxygen uptake (VO2peak) <16 mL/kg/min. According to VO2peak, patients were divided into a normal exercise tolerance group and a reduced exercise tolerance group. The general clinical conditions were compared between the 2 groups to investigate the safety of CPET and the influencing factors of exercise tolerance. A nomogram model for predicting patients' exercise capacity was further developed. Clinical outcomes were recorded. Results: The median time of CPET in all patients was 5 days after PCI. Among the 275 patients, exercise tolerance decreased in 90 cases (32.72%). Multivariate logic analysis showed that E/e', age, glycosylated hemoglobin, and estimated glomerular filtration rate (eGFR) were independent predictors of early exercise capacity reduction in these patients. Utilizing the correlation coefficients from pre-assessment clinical and CPET indicators within the logistic regression framework, we constructed a nomogram model to forecast the diminishing exercise tolerance in AMI patients. The predictive accuracy of this model, as indicated by a C-index of 0.771 and an area under the receiver operating characteristic (ROC) curve of 0.771 (95% CI: 0.710-0.832), demonstrates its potential as a robust tool in clinical settings. During a follow-up of 24 months, the incidence of clinical outcomes in patients with low exercise tolerance was significantly higher than that in patients with normal exercise tolerance, among which all-cause mortality and reinfarction were statistically different (P=0.009 and P=0.043). Conclusions: The reduced exercise capacity in patients with AMI after initial PCI is related to age, diastolic dysfunction, renal function, and blood glucose control, which may lead to poor clinical prognosis. The nomogram prediction model performed well in predicting the declining exercise tolerance of patients with AMI.

Three-Dimensional Quantitative Description of the Implantable Collamer Lens in the Ocular Anterior Segment of Patients With Myopia.

PURPOSE: To describe the 3-dimensional (3D) location of the implantable collamer lens (ICL) quantitatively in the posterior ocular chamber of patients with myopia. DESIGN: Cross-sectional study. METHODS: To obtain visualization models before and after mydriasis, an automatic 3D imaging method based on swept-source optical coherence tomography was created. Parameters like the ICL lens volume (ILV), the tilt of the ICL and crystalline lens, the vault distribution index, and topographic maps were evaluated to describe the ICL location. Using a paired sample t test and the Wilcoxon signed rank test, the difference between nonmydriasis and postmydriasis conditions was compared. RESULTS: The study investigated 32 eyes from 20 patients. The 3D central vault did not differ significantly before (P = .994) or after mydriasis (P = .549) compared with the 2D central vault. After mydriasis, the 5-mm ILV decreased by 0.85 mm2 (P = .016), and the vault distribution index increased significantly (P = .001). The ICL and the crystalline lens exhibited tilt (nonmydriasis: ICL total tilt 3.78 ± 1.85 degrees, lens total tilt 4.03 ± 1.53 degrees; postmydriasis: ICL total tilt 3.84 ± 1.56 degrees, lens total tilt 4.09 ± 1.64 degrees). The phenomenon of asynchronous tilt of the ICL and lens was found in 5 eyes, leading to the spatially asymmetric distribution of the ICL-lens distance. CONCLUSION: The 3D imaging technique provided exhaustive and reliable data for the anterior segment. The visualization models offered multiple perspectives on the ICL in the posterior chamber. Before and after mydriasis, the intraocular ICL position was described by the 3D parameters.

A new pathway for anaerobic biotransformation of marine toxin domoic acid.

Domoic acid (DA) is a harmful algal toxin produced by marine diatom Pseudo-nitzschia and seriously threatens ecosystem and human health. However, the current knowledge on its biotransformation behavior in coastal anaerobic environment is lacking. This study investigated the anaerobic biotransformation of DA by a new marine consortium GH1. The results demonstrated that 90% of DA (1 mg L-1) was cometabolically biotransformed under sulfate-reducing condition. A new anaerobic biotransformation pathway involving DA hydration, dehydrogenation, and C-C bond cleavage was proposed, where the conjugated double-bond of DA was interrupted, resulting in the corresponding alcohols and ketones, subsequently cleaved hydrolytically, and yielding the lower molecular weight products. Desulfovibrio and Clostridiales were markedly enriched in the anaerobic biotransformation of DA, which might jointly contribute to the elevated bacterial consortium resistance and degradation to DA. This study could deepen understanding of behavior and fate for DA in marine environments.

Cyclohexanecarboxylic acid degradation with simultaneous nitrate removal by Marinobacter sp. SJ18.

Naphthenic acid (NA) is a toxic pollutant with potential threat to human health. However, NA transformations in marine environments are still unclear. In this study, the characteristics and pathways of cyclohexanecarboxylic acid (CHCA) biodegradation were explored in the presence of nitrate. The results showed that CHCA was completely degraded with pseudo-first-order kinetic reaction under aerobic and anaerobic conditions, accompanied by nitrate removal rates exceeding 70%, which was positively correlated with CHCA degradation (P < 0.05). In the proposed CHCA degradation pathways, cyclohexane is dehydrogenated to form cyclohexene, followed by ring-opening by dioxygenase to generate fatty acid under aerobic conditions or cleavage of cyclohexene through ß-oxidation under anaerobic conditions. Whole genome analysis indicated that nitrate was removed via assimilation and dissimilation pathways under aerobic conditions and via denitrification pathway under anaerobic conditions. These results provide a basis for alleviating combined pollution of NA and nitrate in marine environments with frequent anthropogenic activities.

Human Vascular Endothelial Cells Promote the Secretion of Vascularization Factors and Migration of Human Skin Fibroblasts under Co-Culture and Its Preliminary Application.

The good treatment of skin defects has always been a challenge in the medical field, and the emergence of tissue engineering skin provides a new idea for the treatment of injured skin. However, due to the single seed cells, the tissue engineering skin has the problem of slow vascularization at the premonitory site after implantation into the human body. Cell co-culture technology can better simulate the survival and communication environment of cells in the human body. The study of multicellular co-culture hopes to bring a solution to the problem of tissue engineering. In this paper, human skin fibroblasts (HSFs) and human vascular endothelial cells (HVECs) were co-cultured in Transwell. The Cell Counting Kit 8 (CCK8), Transwell migration chamber, immunofluorescence, Western blot (WB), and real time quantitative PCR (RT-qPCR) were used to study the effects of HVECs on cell activity, migration factor (high mobility group protein 1, HMGB1) and vascularization factor (vascular endothelial growth factor A, VEGFA and fibroblast growth factor 2, FGF2) secretion of HSFs after co-cultured with HVECs in the Transwell. The biological behavior of HSFs co-cultured with HVECs was studied. The experimental results are as follows: (1) The results of cck8 showed that HVECS could promote the activity of HSFs. (2) HVECs could significantly promote the migration of HSFs and promote the secretion of HMGB1. (3) HVECs could promote the secretion of VEGFA and FGF2 of HSFs. (4) The HVECs and HSFs were inoculated on tissue engineering scaffolds at the ratio of 1:4 and were co-cultured and detected for 7 days. The results showed that from the third day, the number of HSFs was significantly higher than that of the control group without HVECs.

HMGB1/RAGE axis accelerates the repair of HUVECs injured by pathological mechanical stretching via promoting bFGF expression.

AIM: During hypertension-induced endothelial dysfunction, periodic mechanical stretching (MS) activates related inflammatory pathways and leads to endothelial damage, but the underlying mechanisms remain unknown. The present study aimed to determine the injury of HUVECs caused by overstretching and the role of HMGB1-RAGE pathway in HUVECs after injury. MAIN METHODS AND KEY FINDINGS: Human umbilical vein endothelial cells (HUVECs) were cultured and seeded in BioFlex™ plates (six wells). Cells were exposed to 5% (physiological state) and 20% (pathological state) mechanical stretch at 1 Hz for 12 or 24 h in a Flexcell-5000™, with unstretched cells serving as controls. It was found that excessive MS can inhibit cell viability, proliferation, and tube-forming ability resulting in disordered cell arrangement and orientation, slowing cell migration. All these changes cause endothelial damage compared to physiological MS. Endothelial cells (ECs) promote cell migration and self-repair after injury by increasing the High-mobility group box 1 (HMGB1) expression. Experiments and protein prediction networks have shown that HMGB1 can also promote the expression of downstream protein bFGF by binding to receptor for advanced glycation end products (RAGE). Interestingly, VEGF protein expression did not change significantly during this repair process, implying that bFGF replaces the role of VEGF in vascular endothelial repair. SIGNIFICANCE: The present study demonstrates that in the context of endothelial injury caused by excessive MS, the HMGB1/RAGE/bFGF pathway is activated and promotes endothelial repair after injury. Therefore, understanding these mechanisms will help find new therapies for diseases such as hypertension, atherosclerosis, and aneurysm formation.

The Effectiveness and Rotational Stability of Vertical Implantation of the Implantable Collamer Lens for the Treatment of Myopia.

PURPOSE: To explore the effectiveness and rotational stability of vertical implantation of the Implantable Collamer Lens (ICL) (STAAR Surgical) to treat myopia. METHODS: This was a prospective, randomized, controlled study, including 78 eyes from 46 patients with myopia who underwent ICL implantation. The patients were randomly divided into vertical and horizontal implantation groups. At 1 day, 1 week, 1 month, and 3 months after surgery, rotational stability was evaluated using the postoperative axis deviation from the intended axis by the digital anterior segment photograph. The vault, crystalline lens rise, anterior chamber depth, manifest refraction spherical equivalent, intraocular pressure, and visual acuity values were obtained before and after surgery. RESULTS: A 3-month follow-up period showed significant differences between the efficacy indexes in the horizontal (1.11 ± 0.02) and vertical (1.13 ± 0.02) groups (P = .455). No significant difference was observed in the postoperative manifest refraction spherical equivalent between the horizontal (-0.27 ± 0.18 diopters) and vertical (0.01 ± 0.08 diopters) groups (P = .151). Also, no statistically significant difference was observed in the corneal endothelial cells and intraocular pressure between groups (P = .555, P = .464). The rotation angle of the horizontal group was greater at 1 week, 1 month, and 3 months (3.14° ± 2.13°, 2.97° ± 2.01°, 3.27° ± 2.12°, respectively) compared to that of the vertical group (1.30° ± 1.29°, 1.85° ± 1.60°, 1.74° ± 1.33°, respectively) (P < .001 for all). From 1 week to 3 months, the changing angle of horizontal (0.31° ± 1.86°) and vertical (0.49° ± 1.33°) ICL rotation displayed a positive correlation with the changing vault of horizontal (48.41 ± 86.02 mm) and vertical (39.64 ± 78.43 mm) ICL rotation (r = 0.242, 0.335, P = .033, .037). CONCLUSIONS: The study supports great efficacy and safety in both vertical and horizontal implantation, with the vertical implantation group displaying better stability. [J Refract Surg. 2022;38(10):641-647.].

Response mechanism of microbial community during anaerobic biotransformation of marine toxin domoic acid.

Domoic acid (DA) is a potent neurotoxin produced by toxigenic Pseudo-nitzschia blooms and quickly transfers to the benthic anaerobic environment by marine snow particles. DA anaerobic biotransformation is driven by microbial interactions, in which trace amounts of DA can cause physiological stress in marine microorganisms. However, the underlying response mechanisms of microbial community to DA stress remain unclear. In this study, we utilized an anaerobic marine DA-degrading consortium GLY (using glycine as co-substrate) to systematically investigate the global response mechanisms of microbial community during DA anaerobic biotransformation.16S rRNA gene sequencing and metatranscriptomic analyses were applied to measure microbial community structure, function and metabolic responses. Results showed that DA stress markedly changed the composition of main species, with increased levels of Firmicutes and decreased levels of Proteobacteria, Cyanobacteria, Bacteroidetes and Actinobacteria. Several genera of tolerated bacteria (Bacillus and Solibacillus) were increased, while, Stenotrophomonas, Sphingomonas and Acinetobacter were decreased. Metatranscriptomic analyses indicated that DA stimulated the expression of quorum sensing, extracellular polymeric substance (EPS) production, sporulation, membrane transporters, bacterial chemotaxis, flagellar assembly and ribosome protection in community, promoting bacterial adaptation ability under DA stress. Moreover, amino acid metabolism, carbohydrate metabolism and lipid metabolism were modulated during DA anaerobic biotransformation to reduce metabolic burden, increase metabolic demands for EPS production and DA degradation. This study provides the new insights into response of microbial community to DA stress and its potential impact on benthic microorganisms in marine environments.

Prenatal Morphine Exposure Differentially Alters Addictive and Emotional Behavior in Adolescent and Adult Rats in a Sex-Specific Manner.

The effects of prenatal opioid exposure in adult animals has been widely studied, but little is known about the effects of prenatal opioid on adolescents. Most of the risk behaviors associated with drug abuse are initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiate drug use and susceptible to drug-induced brain changes. In this study, pregnant rats were subcutaneously injected with an increasing dose of morphine (5 mg/kg, 7 mg/kg, 10 mg/kg) for 9 days since the gestation day 11. The effects of prenatal morphine (PNM) on learning and memory, anxiety- and depressive- like behavior, morphine induced conditioned place preference (CPP) as well as locomotor sensitization were tested in both adolescent and adult rats. The results showed that: (1) PNM decreased anxiety-like behavior in both adolescent and adult female rats, but not males; (2) PNM decreased depressive-like behavior in adolescent but increased depressive -like behavior in adult females; (3) PNM increased low dose morphine induced locomotor sensitization in females; (4) PNM decreased tyrosine hydroxylase (TH) expression in the prefrontal cortex but decreased dopamine D1 receptor expression in the nucleus-accumbens (NAc) in female rats. These results suggested that PNM altered the emotional and addictive behavior mainly in female rats, with female rats being less anxiety and depressive during adolescence, but more depressive in adult, and more sensitive to low dose morphine induced locomotor activity sensitization, which might be mediated in part by the differential expression of the TH, dopamine D1 receptors in the female brain.

Serine active site containing protein 1 depletion alters lipid metabolism and protects against high fat diet-induced obesity in mice.

OBJECTIVE: Although the serine active site containing 1 (SERAC1) protein is essential for cardiolipin remodeling and cholesterol transfer, its physiological role in whole-body energy metabolism remains unclear. Thus, we investigated the role of SERAC1 in lipid distribution and metabolism in mice. METHODS: CRISPR/Cas9 was used to create homozygous Serac1 knockout mice. A range of methods, including electron microscopy, histological analysis, DNA sequencing, glucose and insulin tolerance tests, and biochemical analysis of serum lipid levels, were used to assess lipid distribution and rates of lipid synthesis in mice. RESULTS: We found that Serac1 depletion in mice prevented high-fat diet-induced obesity but did not affect energy expenditure. The liver was affected by Serac1 depletion, but adipose tissues were not. Serac1 depletion was shown to impair cholesterol transfer from the liver to the serum and led to an imbalance in cholesterol distribution. The livers from mice with Serac1 depletion showed increased cholesterol synthesis because the levels of cholesterol synthesis enzymes were upregulated. Moreover, the accumulation of hepatic lipid droplets in mice with Serac1 depletion were decreased, suggesting that SERAC1 depletion may decrease the risk for hepatic steatosis in high fat diet-induced mice. CONCLUSION: Our findings demonstrate that SERAC1 can serve as a potential target for the treatment or prevention of diet-induced hepatic lipid metabolic disorders.

SERAC1 is a component of the mitochondrial serine transporter complex required for the maintenance of mitochondrial DNA.

SERAC1 deficiency is associated with the mitochondrial 3-methylglutaconic aciduria with deafness, (hepatopathy), encephalopathy, and Leigh-like disease [MEGD(H)EL] syndrome, but the role of SERAC1 in mitochondrial physiology remains unknown. Here, we generated Serac1-/- mice that mimic the major diagnostic clinical and biochemical phenotypes of the MEGD(H)EL syndrome. We found that SERAC1 localizes to the outer mitochondrial membrane and is a protein component of the one-carbon cycle. By interacting with the mitochondrial serine transporter protein SFXN1, SERAC1 facilitated and was required for SFXN1-mediated serine transport from the cytosol to the mitochondria. Loss of SERAC1 impaired the one-carbon cycle and disrupted the balance of the nucleotide pool, which led to primary mitochondrial DNA (mtDNA) depletion in mice, HEK293T cells, and patient-derived immortalized lymphocyte cells due to insufficient supply of nucleotides. Moreover, both in vitro and in vivo supplementation of nucleosides/nucleotides restored mtDNA content and mitochondrial function. Collectively, our findings suggest that MEGD(H)EL syndrome shares both clinical and molecular features with the mtDNA depletion syndrome, and nucleotide supplementation may be an effective therapeutic strategy for MEGD(H)EL syndrome.

Research on the coordinated development of ecosystem services and well-being in agricultural and pastoral areas.

Payment for Ecosystem Services (PES) has been widely accepted as a policy tool for promoting ecological and social progress. However, PES development and implementation in traditional agricultural and pastoral areas are often more challenging than in other areas. The contradiction between ecological protection and people's livelihood development in traditional agricultural and pastoral areas is related to developing country's sustainable development strategy. Based on this, we evaluate the PES (ERCCP: the Ecological Relocation and Capital Compensation Program) program in Tianzhu County, as a case study to investigated the impact of ERCCP on the local natural and social ecosystems on a 20-year scale. The results of indicated that ERCCP has achieved "win-win" gains of restoring environment and promoting socioeconomic development: in the 10 years since ERCCP was implemented, the area of forest land and grassland increased significantly, increasing by 1135.6 ha and 919.62 ha, respectively. 57.5% of farmland was converted to grassland and 30.8% to forest, respectively. In addition, 92.2% and 7.5% of bare land were replaced by grassland and forest, respectively, indicating a gradual recovery of green land during this period. We also analyzed the effects of ERCCP on social systems, and found that the change of agro-pastoralists' attitude towards ERCCP promoted the transfer of labor force from the primary industry to the tertiary industry, accelerated the development of urbanization, and made the poor population completely out of poverty by 2020. In addition, we predict that the income level of households, the PES return on investment of local governments, and the value of regional ecosystem services will increase significantly after 2025. In this context, We establish a theoretical model to explain the win-win plan for the coordinated development of ecosystem services and regional well-being to explore the sustainability of PES and provided a typical case for the similar research area in the world, especially in the areas with the ecological fragility and poverty problems.

A novel degradation mechanism of naphthenic acids by marine Pseudoalteromonas sp.

Naphthenic acids (NAs) are a persistent toxic organic pollutant that occur in different environment worldwide and cause serious threat to the ecosystem and public health. However, knowledge on the behavior and fate of NAs in marine environments still remains unknown. In this study, the degradation mechanism of NAs (cyclohexylacetic acid, CHAA) was investigated using an common indigenous marine Pseudoalteromonas sp. The results showed that CHAA could be degraded completely under aerobic condition, but could not be utilized directly under anaerobic condition. Interestingly, transcriptome and key enzyme activity results showed the CHAA degradation pathway induced under aerobic condition could still work in anaerobic condition. The degradation was activated by acetyl-CoA transferase and sequentially formed the corresponding cyclohexene, alcohol, and ketone with the assistance of related enzymes, and finally cleaved by hydroxymethylglutarate-CoA lyase. Besides, there was a positive correlation between chemotaxis and aerobic degradation genes (r = 0.976, P < 0.05), the chemotaxis would enhance bacterium movement and NAs biodegradation. It is proposed that bacterium could translocate to NAs and accomplish biodegradation from aerobic to anaerobic environments, which was a new anaerobic degradation pathway of NAs. This study provides new insights into the fate of NAs and other organic contaminants in marine environment.

Zinc finger and BTB domain-containing protein 20 aggravates angiotensin II-induced cardiac remodeling via the EGFR-AKT pathway.

Zinc finger and BTB domain-containing protein 20 (ZBTB20) play an important role in glucose and lipid homeostasis. ZBTB20 was shown to be a crucial protein for the maintenance of cardiac contractile function. However, the role of ZBTB20 in cardiac response remodeling has not been elucidated. Thus, this study aimed to explore the role of ZBTB20 in cardiac remodeling following angiotensin II insult. Mice were subjected to angiotensin II infusion to induce a cardiac adverse remodeling model. An adeno-associated virus (AAV) 9 system was used to deliver ZBTB20 to the mouse heart. Here, we demonstrate that ZBTB20 expression is elevated in angiotensin II-induced cardiac remodeling and in response to cardiomyocyte insults. Furthermore, AAV9-mediated overexpression of ZBTB20 caused cardiac wall hypertrophy, chamber dilation, increased fibrosis, and reduced ejection fraction. Additionally, ZBTB20 siRNA protected cardiomyocytes from angiotensin II-induced hypertrophy. Mechanistically, ZBTB20 interferes with EGFR and Akt signaling and modulates the remodeling response. Overexpression of constitutively active Akt counteracts ZBTB20 knockdown-mediated protection of adverse cardiac remodeling. These findings illustrate the role of ZBTB20 in the transition of adverse cardiac remodeling toward heart failure and provide evidence for the molecular programs inducing adverse cardiac remodeling. KEY MESSAGES: ZBTB20 is a transcription factor from the POK family. ZBTB20 is upregulated in heart tissue treated with angiotensin II. ZBTB20 influences cardiomyocyte hypertrophy via the EGFR-Akt pathway. Akt continuous activation leads to similar results to ZBTB20 overexpression.

Anaerobic biotransformation mechanism of marine toxin domoic acid.

Domoic acid (DA) is a major marine neurotoxin, occurs frequently in most of the world's coastlines and seriously threatens ecosystem and public health. However, information on its biotransformation process in coastal anaerobic environments remains unclear. In this study, the underlying mechanism of anaerobic biotransformation of DA by marine consortium GLY was investigated using the combination of liquid chromatography-high-resolution Orbitrap mass spectrometry and comparative metatranscriptomics analysis. The results demonstrated that DA could be cometabolically biotransformed under anaerobic conditions with pseudo-first-order reaction. Anaerobic biotransformation pathway of DA was clarified, including decarboxylation, dehydrogenation, carboxylation activation with CoA and multiple ß-oxidation steps occurring at aliphatic side chain, which facilitated DA detoxification. Furthermore, anaerobic cometabolic biotransformation mechanism of glycine-DA by consortium GLY was established for the first time, a number of genes related to the metabolic pathways of glycine fermentation, fatty acid synthesis and ß-oxidation were responded in the consortium GLY transcriptome and involved in the anaerobic biotransformation of DA. This study could deepen understanding of interaction mechanism between toxin DA and marine microorganisms, which provides a new insight into the DA fate and its effects on benthic microbial community in marine environments.

Designed to Be Green, Economic, and Efficient: A Ketone-Ester-Alcohol-Alkane Blend for Future Spark-Ignition Engines.

Model-based fuel design can tailor fuels to advanced engine concepts while minimizing environmental impact and production costs. A rationally designed ketone-ester-alcohol-alkane (KEAA) blend for high efficiency spark-ignition engines was assessed in a multi-disciplinary manner, from production cost to ignition characteristics, engine performance, ecotoxicity, microbial storage stability, and carbon footprint. The comparison included RON 95 E10, ethanol, and two previously designed fuels. KEAA showed high indicated efficiencies in a single-cylinder research engine. Ignition delay time measurements confirmed KEAA's high auto-ignition resistance. KEAA exhibits a moderate toxicity and is not prone to microbial infestation. A well-to-wheel analysis showed the potential to lower the carbon footprint by 95 percent compared to RON 95 E10. The findings motivate further investigations on KEAA and demonstrate advancements in model-based fuel design.

[Effects of warming on radial growth of Picea crassifolia in the eastern Qilian Mountains, China]. / 升温对祁连山东部青海云杉径向生长的影响.

Tree-rings of Picea crassifolia from high (3000 m), middle (2750 m) and low (2500 m) altitudes were collected from the Xiying River basin in the eastern Qilian Mountains, with the standard chronology being established using dendrochronological methods. Results of the correlation analysis between tree-ring width index and temperature and precipitation during different periods showed that radial growth of P. crassifolia at different altitudes responded differently to climate warming in the eastern Qilian Mountains. Water and heat availability were the main limiting factors for the radial growth of P. crassifolia in the eastern part of Qilian Mountains. The growth limiting factors at different altitudes were generally the same. Before the prominent warming (1961-1986), radial growth of P. crassifolia at the three sampling altitudes was significantly negatively correlated with mean maximum temperature in July-August of the previous year and August of the current year, and significantly positively correlated with the relative humidity in June of the current year. After the prominent warming period (1986-2014), tree growth at high, middle, and low altitudes remained significantly negatively correlated with air temperature, changed from non-significantly negative to significantly positive correlation with relative humidity in February of the current year, and changed from significantly positive to non-significantly negative correlation with precipitation and relative humidity in June. Warming caused a slowing growth of P. crassifolia tree-ring at all altitudes, with the highest altitude being the most sensitive. Drought stress caused by climate warming might be the main reason for the changes of radial growth of P. crassifolia.

A condensate-hardening drug blocks RSV replication in vivo.

Biomolecular condensates have emerged as an important subcellular organizing principle1. Replication of many viruses, including human respiratory syncytial virus (RSV), occurs in virus-induced compartments called inclusion bodies (IBs) or viroplasm2,3. IBs of negative-strand RNA viruses were recently shown to be biomolecular condensates that form through phase separation4,5. Here we report that the steroidal alkaloid cyclopamine and its chemical analogue A3E inhibit RSV replication by disorganizing and hardening IB condensates. The actions of cyclopamine and A3E were blocked by a point mutation in the RSV transcription factor M2-1. IB disorganization occurred within minutes, which suggests that these molecules directly act on the liquid properties of the IBs. A3E and cyclopamine inhibit RSV in the lungs of infected mice and are condensate-targeting drug-like small molecules that have in vivo activity. Our data show that condensate-hardening drugs may enable the pharmacological modulation of not only many previously undruggable targets in viral replication but also transcription factors at cancer-driving super-enhancers6.

Green toxicological investigation for biofuel candidates.

To avoid potential risks of biofuels on the environment and human, ecotoxicity investigation should be integrated into the early design stage for promising biofuel candidates. In the present study, a green toxicology testing strategy combining experimental bioassays with in silico tools was established to investigate the potential ecotoxicity of biofuel candidates. Experimental results obtained from the acute immobilisation test, the fish embryo acute toxicity test and the in vitro micronucleus assay (Chinese hamster lung fibroblast cell line V79) were compared with model prediction results by ECOSAR and OECD QSAR Toolbox. Both our experimental and model prediction results showed that 1-Octanol (1-Oct) and Di-n-butyl ether (DNBE) were the most toxic to Daphnia magna and zebrafish among all the biofuel candidates we investigated, while Methyl ethyl ketone (MEK), Dimethoxymethane (DMM) and Diethoxymethane (DEM) were the least toxic. Moreover, both in vitro micronucleus assay and OECD QSAR Toolbox evaluation suggested that the metabolites present higher genotoxicity than biofuel candidates themselves. Overall, our results proved that this green toxicology testing strategy is a useful tool for assessing ecotoxicity of biofuel candidates.