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Nitrite is a common pollutant in aquaculture systems that poses a significant threat to aquatic animals. Energy metabolism is critical in ensuring survival of animals under environmental stressors. However, regulation of energy metabolism in crustaceans under nitrite stress has not been well understood. Here we investigated energy metabolism regulation during nitrite stress and recovery in different tissues of the swimming crab Portunus trituberculatus, an important aquaculture species in China. Our results revealed that nitrite can cause tissue hypoxia and impair energy homeostasis, and energy balance cannot be restored even after a 96-hour recovery. Following exposure, mobilization of glycogen and lipids exhibited different temporal patterns. In response to energy imbalance, AMPK signaling was activated to counter energy imbalance. However, prolonged nitrite stress impaired AMPK signaling, leading to a further decline in energy supply. The findings improve our understanding for nitrite toxicity in P. trituberculatus, and provide valuable information for aquaculture management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Feruloylated oligosaccharides (FOs) generated by decomposing plant hemicellulose, offer a wide range of potential applications in both the food and biomedical areas. As a graminaceous plant, bamboo is rich in hemicellulose. However, the structural composition and activity studies of FOs from it were rarely reported. In this study, FOs from Phyllostachys acuta (pFOs) obtained by enzymatic hydrolysis were isolated by AmberliteXAD-2 and C18 SPE columns. Then, pFOs were qualitatively and quantitatively analyzed by UPLC-ESI-MS/MS after labeled by 3-Amino-9-ethyl-carbazole (AEC), and the chemical antioxidant activity of pFOs and effects of pFOs on H 2 O 2 -induced oxidative damage were investigated. Finally, 14 of pFOs isomers were distinguished and identified, of which 10 did not contain hexoses and 4 did, and the three most abundant pFO structures were 12 (Iso 7, F1A1X2H2-AEC, 29.04 %), 11 (Iso 6, F1A1X1H2-AEC, 17.96 %), and 4 (Iso 3-1, F1A1X3-AEC, 15.57 %). The results of antioxidant studies showed that pFOs possessed certain reducing power, scavenging DPPH radicals, scavenging superoxide anion radicals, and scavenging hydroxyl radicals. Among them, the ability to clear DPPH radicals was particularly significant. pFOs significantly reduced the viability of RAW264.7 cells after H 2 O 2 induction, whereas pFOs had a significant protective effect (p < 0.001). pFOs increased the viability of T-AOC and SOD enzymes in oxidatively damaged cells, as well as had a significant inhibition effect on ROS elevation (p < 0.001). This study lays the foundation for the structural analysis and antioxidant activity evaluation of bamboo-derived feruloyl oligosaccharides for their application in food and pharmaceutical fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Stimuli-responsive polymeric micelles have emerged as a revolutionary approach for enhancing the in vivo stability, biocompatibility, and targeted delivery of functional nanoparticles (FNPs) in biomedicine. This article comprehensively reviews the preparation methods of these polymer micelles, detailing the innovative strategies employed to introduce stimulus responsiveness and surface modifications essential for precise targeting. We delve into the breakthroughs in utilizing these micelles to selectively deliver various FNPs including magnetic nanoparticles, upconversion nanoparticles, gold nanoparticles, and quantum dots, highlighting their transformative impact in the biomedical realm. Concluding, we present an insight into the current research landscape, addressing the challenges at hand, and envisioning the future trajectory in this burgeoning domain. Join us as we navigate the exciting confluence of polymer science and nanotechnology in reshaping biomedical solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

How to increase the usable land area by adhering to environmentally friendly ecological restoration of mines with limited funds is a challenge that many cities are currently facing. Cost-benefit analysis (CBA) can provide efficient and effective restoration decisions for abandoned mine land (AML) ecological restoration with limited financial resources. Thus, this study proposes an integrated approach for coupling ecological benefits and restoration costs, including hotspots/coldspots analysis based on five ecosystem services (ESs), landscape connectivity analysis based on graph theory model, hidden costs, and project implementation costs to prioritize AML restoration. The study was conducted on 54 abandoned mine lands (AMLs) in Chaoyang city, the ecological security barrier of China's northern sand prevention belt (NSPB). The comprehensive analysis prioritized the restoration of AMLs into four levels, of which 9 mines were in priority I, where restoration was recommended as a priority, and 22 mines were in priority II, where restoration could be carried out within the affordability of funds. In addition, our model indicates areas with high ecological benefits, in which the ecological source area (7423.66 km 2 ) and the ecosystem service hotspots area (2028.44 km 2 ) are mostly distributed in the southwestern part of Chaoyang city, the two mountain ranges of Songling mountain and Nuruerhu mountain. This study provides scientific spatial guidance to ensure that the AMLs realizes effective restoration and management., Competing Interests: Declaration of competing interest We have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

China has experienced rapid population growth and increasing human N and P discharge from point sources. This paper presents a new spatial and temporal model-based, province-scale inventory of N and P in wastewater using detailed information on the location and functioning of 4436 WWTPs covering China for the period 1970-2015. China's nutrient discharge to surface water increased 22-fold from 177 to 3908 Gg N yr -1 and 29-fold from 20 to 577 Gg P yr -1 in urban areas between 1970 and 2015. The ten strongly urbanized and industrialized provinces along the Eastern coast contributed 43 % of China's total N and P discharge to surface water in 2015. At present, the contribution of rural areas to total wastewater discharge (2082 Gg N yr -1 and 434 Gg P yr -1 ) is 35 % for N and 43 % for P. The model approach and sensitivity analysis of this study indicate that policies aiming at improving water quality need to consider these regional differences, i.e., improvement of the wastewater treatment technology level in Eastern regions and increasing both the sewage connection and wastewater treatment in Central and Western regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Coronary artery calcification (CAC) is a crucial pathophysiological characteristic of atherosclerosis. The association between lipoprotein (a) [Lp(a)] and CAC is inconsistent. We aimed to assess the relationship between Lp(a) and CAC by exploring the association between elevated Lp(a) and CAC prevalence, the relationship between Lp(a) level and CAC prevalence, and the correlation between elevated Lp(a) and CAC progression., Methods: We searched the PubMed, Web of Science, and EMBASE databases up to November 01, 2023. Studies exploring the association between serum Lp(a) and CAC (quantified using the Agatston score) were included. Association between Lp(a) level or elevated Lp(a) (higher than the cutoff values of 30 mg/dL, 50 mg/dL, or the highest quartile ranging from 33 to 38.64 mg/dL) and prevalence [CAC score >0 or >100, log (CAC score+1) >0] or progression (an increase in CAC score >0 or ≥100) of CAC were analysed. Odds ratios and 95% confidence intervals were calculated using a random-effects model., Results: 40,073 individuals from 17 studies were included. Elevated Lp(a) was associated with a higher prevalence of CAC (OR, 1.31; 95% CI, 1.06 to 1.61; p = 0.01). As a continuous variable, Lp(a) level was positively correlated with the prevalence of CAC (OR, 1.05; 95% CI, 1.02 to 1.08; p = 0.003). Furthermore, elevated Lp(a) was associated with greater CAC progression (OR, 1.54; 95% CI, 1.23 to 1.92; p = 0.0002)., Conclusions: This meta-analysis suggested that Lp(a) is associated with prevalence and progression of CAC. Further studies are required to explore whether Lp(a)-lowering therapy could prevent or inhibit CAC, ultimately reducing coronary artery disease risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study aimed to compare the regulatory effects of blue honeysuckle anthocyanins (BHA), blueberry anthocyanins (BBA), and blackcurrant anthocyanins (BCA) on the in vitro digestibility of corn starch in terms of starch physicochemical properties and structure, as well as α-amylase inhibition. The results revealed that adding all three anthocyanins lowered digestibility in the following order: BHA > BCA > BBA. The terminal digestibility (C ∞ ) decreased from 73.84 % to 57.3 % with the addition of 10 % BHA, while the resistant starch (RS) content increased from 4.39 % to 48.82 %. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis indicated that anthocyanins and starch interacted through noncovalent bonds. Differential scanning calorimetry (DSC) analysis showed that the gelatinization enthalpy was dramatically lowered in all three anthocyanin groups, with 10 % BHA producing a 38.58 % drop. Rheological property analysis showed that anthocyanins increased the apparent viscosity and modulus with starch. The interaction between anthocyanin and α-amylase was mainly through the formation of hydrogen bonds and hydrophobic forces. This research provides theoretical guidance for developing low glycemic index (GI) anthocyanin starch-based foods., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in the manuscript entitled “Three anthocyanin-rich berry extracts regulate the in vitro digestibility of corn starch: Physicochemical properties, structure and α-amylase”., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this paper, a brain-like navigation scheme based on fuzzy kernel C-means (FKCM) clustering assisted pyramid Lucas Kanade (LK) optical flow algorithm is developed to measure the position of vehicle. The Speed Cell and Place Cell in animals' brain are introduced to construct the brain-like navigation mechanism which involves the optical flow method and image template matching to imitate the cells above-mentioned separately. To eliminate the singular values during optical flow calculation, the output of pyramid LK algorithm is clustered by FKCM algorithm firstly. Then, the velocity is calculated and integrated to get the position of the vehicle, and the brain-like navigation scheme is introduced to correct the position measurement errors by eliminating the accumulated errors resulting from velocity integration. The prominent advantages of the presented method are: (i) a pure visual brain-like position measurement method based on the concept of speed cells and place cells is proposed, making visual navigation more accurate and intelligent; (ii) the FKCM algorithm is used to eliminate the singular value of the pyramid LK algorithm, which improves the calculated velocity accuracy. Also, experimental comparison with classical pyramid LK algorithm is given to illustrate the superiority of the proposed method in position measurement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 ISA. Published by Elsevier Ltd. All rights reserved.)

Agricultural N losses strongly dominate the N delivery (average 72 % of total N delivery to rivers in the period 1980-2010) in the rivers discharging into the Bohai Sea, a semi-enclosed marginal sea, which has been suffering from eutrophication and deoxygenation since the 1980s. In this paper we investigate the relationship between N loading and deoxygenation in the Bohai Sea, and consequences of future N loading scenarios. Using modeling for the period 1980-2010, the contributions of different oxygen consumption processes were quantified and the main controlling mechanisms of summer bottom dissolved oxygen (DO) evolution in the central Bohai Sea were determined. Model results show that the water column stratification during summer impeded the DO exchange between oxygenated surface water and oxygen-poor bottom water. Water column oxygen consumption (60 % of total oxygen consumption) was strongly correlated with elevated nutrient loading, while nutrient imbalances (increasing N:P ratios) enhanced harmful algal bloom proliferation. Future scenarios show that deoxygenation may be reduced in all scenarios owing to increasing agricultural efficiency, manure recycling and wastewater treatment. However, even in the sustainable development scenario SSP1, nutrient discharges in 2050 will still exceed the 1980 levels, and with further enhancement of water stratification due to climate warming, the risk of summer hypoxia in bottom waters may persist in the coming decades., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and the manuscript has been approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously and is not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the enclosed manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Domestication is the process of modifying the phenotype of a population through anthropic selection from human perspectives. Successive generations of domestication have influenced the physiological characteristics of tench Tinca tinca. In current study, we investigated gene and protein expression alterations in the liver of fifth-generation (F5). A total of 420 genes were found to be upregulated and 351 genes were downregulated, while 410 proteins were upregulated and 279 proteins were downregulated in domesticated T. tinca (DT). The integrated analysis of omics data revealed a total of 55 genes/proteins exhibiting consistent upregulation and 12 genes/proteins displaying consistent downregulation in DT. The upregulated genes/proteins in DT, such as SSR1, DERLIN2, OS9, DNAJB11, and HYOU1, exhibit enrichment in the protein processing in the endoplasmic reticulum pathway. Additionally, upregulated genes/proteins such as IL2RB, F13B, and IRF3 are associated with immune response. Conversely, downregulated genes/proteins in DT, including HSD11B1, CYP24A1, and COMT, play roles in hormone metabolism. These findings indicate that domestication can have a substantial impact on the physiological modifications related to protein processing, immune response, and hormone metabolism in DT. These adaptations potentially enhance their ability to thrive in artificial aquaculture environments, leading to improved growth and development. The exploration of genetic changes in DT will not only improve aquaculture practices but also provide significant insights into the broader process of domestication and its effects on physiological functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8 + T cell immunity in vivo . It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Coupling phosphate-solubilizing microorganisms (PSM) can improve the availability of phosphorous (P) in biochar-based slow-release P fertilizers (BPF). However, the mechanism in release and transformation of P in BPF regulated by PSM is still unclear. Herein, the biocompatibility and the adhesion behaviors of BPF and PSM (Enterobacter hormaechei Rs-198) in soil were firstly studied, and a 90 days' laboratory-scale soil incubation experiment of BPF and Rs-198 was performed to study the transformation of P of BPF. The results show that BPF has a good biocompatibility for Rs-198 due to its low aromaticity, graphitization and free radicals' content (0.084 mg/g). Rs-198 are adhered to the surface of BPF in soil due to the high negative secondary energy minimum and low total interaction energy between Rs-198 and BPF. Available P in the incubation of BPF and Rs-198 (BR treatment) is significantly higher than that of the incubation of BPF (BF treatment) at initial 60 days. However, the content of available P in BR treatment is much lower compared with that in BF treatment on day 90, which is attributed to the entrapment of released P from BPF by Rs-198 and the formation of polyphosphate (polyP) rather than bound with soil mineral. Overall, this study presents new insights into the transformation of P in BPF regulated by PSM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Bacillus subtilis as microbial fertilizers contribute to avoiding the harmful effects of traditional agricultural fertilizers and pesticides. However, there are many restrictions on the practical application of fertilizers. In this study, microbial biochar formulations (BCMs) were prepared by loading biochar with B. subtilis SL-44. Pot experiments were conducted to evaluate the effects of the BCMs on soil fertility, Fusarium wilt control, and radish plant growth. The application of BCMs dramatically improved soil properties and favored plant growth. Compared with SL-44 and biochar treatments, the BCMs treatments increased radish plant physical-chemical properties and activities of several enzymes in the soil. What's more, Fusarium wilt incidence had decreased by 59.88%. In addition, the BCMs treatments exhibited a significant increase in the abundance of bacterial genera in the rhizosphere soil of radish. Therefore, this study demonstrated that BCMs may be an eco-friendly strategy for improving soil fertility, reducing Fusarium wilt, and promoting radish plant growth., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

An engineered Escherichia coli was constructed by co-expressing L-amino acid deaminase, α-keto acid decarboxylase, alcohol dehydrogenase, and glucose dehydrogenase through two plasmids for tyrosol production. The activity of the rate-limiting enzyme L-amino acid deaminase from Cosenzaea myxofaciens (CmAAD) toward tyrosine was improved by structure-guided modification. The enzyme activity of triple mutant CmAAD V438G/K147V/R151E toward tyrosine was ~5.12-fold higher than that of the wild-type CmAAD. Secondly, the plasmid copy numbers and the gene orders were optimized to improve the titer of tyrosol. Finally, the recombinant strain CS-6 transformed 10 mM tyrosine into 9.56 ± 0.64 mM tyrosol at 45 ℃, and the space-time yield reached 0.478 mM·L -1 ·h -1 . This study proposes a novel idea for the efficient and natural production of tyrosol, which has great potential for industrial application., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Laccase has received extensive attention in pollutant degradation due to its high efficiency and environmental friendliness, but free laccase has poor stability, easy inactivation, and difficulty in recycling, which limited its application. It was a smart strategy to construct a synergistic system for the efficient adsorption and degradation of pollutants by enzyme immobilization to improve the stability and recyclability of the enzyme. In this study, the materials were synthesized by a one-step co-precipitation method. With Cu-MOF as the main body, Co 2+ was introduced to construct bimetallic CoCu-MOF as the protective carrier of the enzyme. The enzyme-carrying capacity and enzyme activity of Lac@CoCu-MOF were 2-fold and 3.5-fold higher than those of Lac@Cu-MOF, respectively. Lac@MOF composites had a good protective effect on enzyme in various interfering environments. At pH = 7, free laccase was completely inactivated and Lac@CoCu-MOF maintained 51.76% enzyme activity. In addition, the removal rate of Congo red by Lac@CoCu-MOF reached 90 % in 1 h at pH = 4 % and 95 % in 5 h at pH = 7, and the final TOC mineralization rate reached 86.05 %. After six cycles, the degradation rate of Lac@CoCu-MOF remained above 75 %. Therefore, Lac@CoCu-MOF was constructed with the advantages of enzyme immobilization (enhanced stability and easy operation), material adsorption, and biocatalysis (fast diffusion and high activity), which has great guiding significance for the industrial application of enzyme., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Previous surveys have revealed that mirtazapine (MIR), one of the most commonly prescribed antidepressants, is associated with a higher risk of adverse cardiac events compared with other newer antidepressants. Chronic ethanol (EtOH) abuse could also lead to myocardial injuries. Concerning the common comorbidity of major depression and alcohol dependence, combined consumption of MIR and EtOH might be prevalent in patients with depression, resulting in an additive or synergistic cardiotoxic effect. To this end, the present study evaluated cardiotoxicity induced by MIR-plus-EtOH in vivo (male C57BL/6J mice) and in vitro (H9c2 cardiomyoblasts), Further research on the role of autophagy and underlying signaling pathway were carried out in H9c2 cells. We found that EtOH exacerbated MIR-induced cardiotoxicity both in vivo and in vitro. Furthermore, EtOH significantly potentiated MIR-induced dysfunctional autophagy as reflected by upregulated protein levels of LC3-II, p62, Beclin1 and LAMP-1. Pharmacological inhibition of autophagy by 3-methyladenine alleviated MIR-plus-EtOH-induced myocardial injury. High mobility group box 1 (HMGB1) is a positive regulator of autophagy. In our work, HMGB1 knockdown decreased autophagosome accumulation and boosted viability in H9c2 cells. Additionally, HMGB1 blockage markedly upregulated p-Akt/Akt and p-mTOR/mTOR levels which were suppressed in MIR-plus-EtOH treated cells. In general, the present study demonstrates that EtOH potentiates MIR-induced cardiotoxicity which might be attributed to dysfunctional autophagy via inhibiting Akt/mTOR signaling pathway, while HMGB1 knockdown might contribute to improve autophagy flux., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Artificial domestication during aquaculture practice has strongly shaped the physiological characteristics of Perca fluviatilis. Thus, revealing the genetic changes in domesticated P. fluviatilis will improve aquaculture and selective breeding. In this study, comparative analysis of the liver transcriptome, proteome, and physiological and biochemical indices of domesticated and wild P. fluviatilis was conducted. Our results indicated that the activity of lipase and the content of glucose were higher; however, the total antioxidant capacity and superoxide dismutase were lower in domesticated P. fluviatilis. Integrated analysis of "omics" data identified 174 and 127 genes and proteins that showed consistent upregulation and downregulation in domesticated P. fluviatilis, respectively. GO and KEGG enrichment of differentially expressed genes and proteins and the protein-protein interaction network indicated that energy metabolism (lipid and carbohydrate metabolism) was enhanced, and that signal transduction and the stress response were reduced in domesticated P. fluviatilis. This study revealed that artificial domestication may significantly shape the physiological changes in energy metabolism and stress resistance in domesticated P. fluviatilis, which makes them more adaptable to the artificial aquaculture environment, thereby promoting growth and development., (Copyright © 2021. Published by Elsevier Inc.)

Di (2-ethylhexyl) phthalate (DEHP) and extremely low-frequency electromagnetic fields (ELF-EMFs) exist far and wide in our surroundings. Studies have reported that both of DEHP and ELF-EMFs could promote cell proliferation which is related with adverse bioeffects. In this study, we investigated whether there is the combined effect between DEHP and 50-Hz magnetic fields (MFs) on cell proliferation in human amniotic (FL) cells. Results revealed that the low-concentration DEHP (1 μM) could promote FL cell proliferation, whereas the high-dose DEHP (100 μM) inhibited cell proliferation. When FL cells were treated jointly by a 50-Hz, 0.2-mT MF and 0.1 μM DEHP, the proliferation rate of cells was significantly higher than that of single factor exposure. Additionally, co-exposure to under-threshold MF and DEHP could cooperatively activate protein kinase B (Akt), sphingosine kinase 1 (SphK1) and extracellular signal regulated kinase (ERK) in a cascade manner, and finally mediate cell proliferation. Taken together, the findings of this study indicated that the co-exposure to under-threshold MF and DEHP could jointly promote cell proliferation through activating proliferation-related signal pathway, which warned us that it should be cautious about assessing the underlying health hazards of co-exposure to MFs and DEHP at under-threshold levels., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Soil abiotic properties and plant diversity have been shown to affect ecosystem functions in alpine meadow ecosystems. However, we know little about the relative importance of these factors in driving the responses of multiple ecosystem functions simultaneously (multifunctionality) to nitrogen (N) enrichment. Here, we measured soil abiotic properties (soil pH; available nitrogen, AN; available phosphorous, AP; and dissolved organic carbon, DOC) and multiple plant diversity metrics (species diversity, SD; functional diversity, FD; and phylogenetic diversity, PD) after a 5-year N fertilization experiment (0, 5, 10, and 15 g N m -2  yr -1 ) to evaluate their roles in mediating the impacts of N addition on aboveground plant functions (APF), soil microbial functions (SMF), and ecosystem multifunctionality (EMF) in a N-limited Tibetan alpine meadow. We found that N addition decreased APF but increased SMF and EMF. Structural equation models (SEMs) showed that APF was co-driven by soil DOC and the community weighted mean for plant traits (CWMs), and SMF was driven by soil DOC, soil AN, CWMs and functional dispersion (FD is ). The effects of N addition on EMF were driven by soil AN and FD is . Our results suggest that the effects of N enrichment on APF, SMF, and EMF are driven by differential mechanisms. Furthermore, the findings suggest that FD is superior to SD and PD in mediating the responses of ecosystem functions to N enrichment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Defective cholesterol metabolism primarily linked to reduced ATP-binding cassette transporter A1 (ABCA1) expression is closely associated with the pathogenesis and progression of kidney diseases, including diabetic kidney disease and Alport Syndrome. However, whether the accumulation of free or esterified cholesterol contributes to progression in kidney disease remains unclear. Here, we demonstrate that inhibition of sterol-O-acyltransferase-1 (SOAT1), the enzyme at the endoplasmic reticulum that converts free cholesterol to cholesterol esters, which are then stored in lipid droplets, effectively reduced cholesterol ester and lipid droplet formation in human podocytes. Furthermore, we found that inhibition of SOAT1 in podocytes reduced lipotoxicity-mediated podocyte injury in diabetic kidney disease and Alport Syndrome in association with increased ABCA1 expression and ABCA1-mediated cholesterol efflux. In vivo, Soat1 deficient mice did not develop albuminuria or mesangial expansion at 10-12 months of age. However, Soat1 deficiency/inhibition in experimental models of diabetic kidney disease and Alport Syndrome reduced cholesterol ester content in kidney cortices and protected from disease progression. Thus, targeting SOAT1-mediated cholesterol metabolism may represent a new therapeutic strategy to treat kidney disease in patients with diabetic kidney disease and Alport Syndrome, like that suggested for Alzheimer's disease and cancer treatments., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Nowadays, antibiotic resistance genes (ARGs) have been characterized as an emerging environmental contaminant, as the spread of ARGs may increase the difficulty of bacterial infection treatments. This study evaluates the combination of ultraviolet (UV) irradiation and chlorination, the two most commonly applied disinfection methods, on the degradation of sulphonamide resistance sul1 genes. The results revealed that although both of individual UV and chlorination processes were relatively less effective, two of the four combined processes, namely UV followed by chlorination (UV-Cl 2 ) and simultaneous combination of UV and chlorination (UV/Cl 2 ), delivered a better removal rate (up to 1.5 logs) with an observation of synergetic effects up to 0.609 log. The mechanisms analysis found that the difference of DNA size affected sul1 genes degradation by UV and chlorination; targeted genes on larger DNA fragments could be more effectively degraded by UV (1.09 logs for large fragments and 0.12 log for small fragments when UV dose reached 432 mJ/cm 2 ), while to degrade ARGs on smaller DNA fragments required less free chlorine dosage (10 mg/L for small fragments and 40 mg/L for large fragments). The sequential combination of UV and chlorination (UV-Cl 2 ) used the corresponding reactivity of both processes, which could be the reason for the synergetic effect. For UV/Cl 2 process, the formation of reactive oxygen species (ROS) contributed to the synergetic effect. Scavenger analysis showed that the contribution of ROS to the sul1 gene reduction was 0.004 to 0.273 log (up to 45.5 % of the total synergy values), and among the two major reactive species in UV/Cl 2 system, HO was the more important radical, while the contribution of Cl was negligible. Besides, UV/Cl 2 process also used the corresponding reactivity of both processes to generate the remaining synergy values when excluding the contribution by reactive radicals. These findings provide a thorough understanding of the effects of UV and free chlorine on the degradation of ARGs and indicate the potential to utilize the combined processes of UV and free chlorine in water or wastewater treatment practice to control the dissemination of antibiotic resistance., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Quetiapine is a common atypical antipsychotic used to treat mental disorders such as schizophrenia, bipolar disorder, and major depressive disorder. There has been increasing number of reports describing its cardiotoxicity. However, the molecular mechanisms underlying quetiapine-induced myocardial injury remain largely unknown. Herein, we reported a novel cell death type, quetiapine-induced necroptosis, which accounted for quetiapine cardiotoxicity in mice and proposed novel therapeutic strategies. Quetiapine-treated hearts showed inflammatory infiltration and evident fibrosis after 21-day continuous injection. The specific increases of protein levels of RIP3, MLKL and the phosphorylation of MLKL showed that quetiapine induced necroptotic cell death both in vivo and in vitro. Pharmacologic blockade of necroptosis using its specific inhibitor Necrostatin-1 attenuated quetiapine-induced myocardial injury in mice. In addition, quetiapine imbalanced the endocannabinoid system and caused opposing effects on two cannabinoid receptors (CB1R and CB2R). Specific antagonists of CB1R (AM 281, Rimonabant), but not its agonist ACEA significantly ameliorated the heart histopathology induced by chronic quetiapine exposure. By contrast, specific agonists of CB2R (JWH-133, AM 1241), but not its antagonist AM 630 exerted beneficial roles against quetiapine cardiotoxicity. The protective agents (AM 281, Rimonabant, AM 1241, and JWH-133) consistently inactivated the quetiapine-induced necroptosis signaling. Quetiapine bidirectionally regulates cannabinoid receptors and induces myocardial necroptosis, leading to cardiac toxic effects. Therefore, pharmacologic inhibition of CB1R or activation of CB2R represents promising therapeutic strategies against quetiapine-induced cardiotoxicity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

As a chronic infectious disease, periodontitis is the main cause of teeth exfoliation due to its severe inflammatory reaction and periodontal tissue destruction. Recent reports have shown that baicalin could inhibit the NF-κB signaling pathway in inflammatory activity of periodontitis, but the efficacy of baicalin is limited due to its poor water solubility. In this work, we report the fabrication and application of baicalin encapsulated D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) polymeric micelles (PMs) through thin-film hydration method. The monodispersed micelles showed a spherical shape in aqueous solution and a prolonged drug-release kinetic. After baicalin was loaded into PMs, cytotoxicity and apoptosis induction were both decreased. The expression of genes (including TNF-α, IL-1β, RANKL and NF-κB) and the phosphorylation level of NF-κB p65 protein in lipopolysaccharide (LPS)-induced rat gingival fibroblasts were also reduced. Further investigation of drug efficacy in a rat periodontal disease model confirmed that the use of baicalin-PMs could reduce the destruction of alveolar bone and gingival fiber. Moreover, the therapeutic effect of baicalin-PMs was significantly better than that of free baicalin. These results suggest that the direct injection of micelles containing water-insoluble drugs may become a simple but effective method for treating periodontitis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This article has been retracted at the request of the authors. The Editor in Chief has agreed to retract this article and the publisher supports the decision. The authors have indicated that their initial results were not reproducible when conducted by their colleagues. They indicated that the levels of autophagy were significantly different in the MI/R mice model in the respective results. The authors of this article would like to apologize to all affected parties. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal., (Copyright © 2017.)

Myocardial ischemia/reperfusion (MI/R) injury is a major cause of cardiac dysfunction during cardiovascular surgery and heart transplantation and characterized by hyperactive oxidative stress and inflammatory response. Barbaloin (BAR) is the main medicinal composition of the Chinese traditional medicine aloe vera. BAR has strong anti-oxidant, anti-inflammatory and anti-tumor properties. However, the effect of BAR on MI/R-induced myocardial injury is not explored. This study aims to investigate whether BAR provides cardio-protection against MI/R injury and the underlying mechanisms. BAR (20 mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for 5 days before MI/R operation. BAR pretreatment conferred cardio-protective effects against MI/R injury by improving hemodynamic function and limiting infarction size. Moreover, BAR pretreatment effectively inhibited I/R-induced myocardial oxidative stress and inflammatory response. Furthermore, BAR pretreatment activated adenosine monophosphate-activated protein kinase (AMPK) signaling in MI/R hearts. AMPK inhibitor compound C inhibited BAR-induced AMPK activation, and blunted BAR-mediated anti-oxidative, anti-inflammatory effects and cardio-protection. Taken together our study has identified a novel function of BAR and provided a molecular basis for BAR potential applications in the treatment of MI/R injury and other ischemic disorders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

As FDA-approved implantable material, polyetheretherketone (PEEK) is becoming a prime candidate to replace traditional surgical metallic implants made of titanium (Ti) and its alloys, since it has a lower elastic modulus than Ti. The bioinertness and defective osteointegration of PEEK, however, limit its clinical adoption as load-bearing dental/orthopedic material. The present work aimed at developing a PEEK bioactive ternary composite, polyetheretherketone/nano-hydroxyapatite/carbon fiber (PEEK/n-HA/CF), and evaluating it as a potential bone-repairing material by assessment of growth and differentiation of osteoblast-like MG63 cells and by estimation of osteointegration in vivo. Our results indicated that the adhesion, proliferation and osteogenic differentiation of cells, as well as the mechanical properties were greatly promoted for the PEEK/n-HA/CF biocomposite compared with pure PEEK matrix. More importantly, the ternary composite implant boosted in vivo bioactivity and osseointegration in canine tooth defect model. Thus, the PEEK/n-HA/CF ternary biocomposite with enhanced mechanics and biological performances hold great potential as bioactive implant material in dental and orthopedic applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

As an FDA-approved implantable material, carbon fiber-reinforced polyetheretherketone (CFRPEEK) possesses excellent mechanical properties similar to those of human cortical bone and is a prime candidate to replace conventional metallic implants. The bioinertness and inferior osteogenic properties of CFRPEEK, however, limit its clinical application as orthopedic/dental implants. The present work aimed at developing a novel carbon fiber-reinforced polyetheretherketone-nanohydroxyapatite (PEEK/CF/n-HA) ternary biocomposite with micro/nano-topographical surface for the enhancement of the osteogenesis as a potential bioactive material for bone grafting and bone tissue-engineering applications. The combined modification of oxygen plasma and sand-blasting could improve the hydrophily and generate micro/nano-topographical structures on the surface of the CFRPEEK-based ternary biocomposite. The results clearly showcased that the micro-/nano-topographical PEEK/n-HA/CF ternary biocomposite demonstrated the outstanding ability to promote the proliferation and differentiation of MG-63 cells in vitro as well as to boost the osseointegration between implant and bone in vivo, thereby boding well application to bone tissue engineering., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Wound healing, angiogenesis, and hair follicle maintenance are often impaired in the skin of diabetic patients, but the pathogenesis has not been well understood. Here, we report that circulation levels of kallistatin, a member of the serine proteinase inhibitor (SERPIN) superfamily with antiangiogenic activities, were elevated in type 2 diabetic patients with diabetic vascular complications. To test the hypothesis that elevated kallistatin levels could contribute to a wound-healing deficiency via the inhibition of Wnt/β-catenin signaling, we generated kallistatin-transgenic (KS-TG) mice. KS-TG mice had reduced cutaneous hair-follicle density, microvascular density, and panniculus adiposus layer thickness, as well as altered skin microvascular hemodynamics and delayed cutaneous wound healing. Using Wnt reporter mice, our results showed that Wnt/β-catenin signaling is suppressed in the dermal endothelium and hair follicles in KS-TG mice. Lithium, a known activator of β-catenin via inhibition of glycogen synthase kinase-3β, reversed the inhibition of Wnt/β-catenin signaling by kallistatin and rescued the wound-healing deficiency in KS-TG mice. These observations suggest that elevated circulating antiangiogenic serpins in diabetic patients may contribute to impaired wound healing through inhibition of Wnt/β-catenin signaling. Activation of Wnt/β-catenin signaling, at a level downstream of Wnt receptors, may ameliorate the wound-healing deficiency in diabetic patients.

Commercially pure titanium (cpTi) and polyetheretherketone (PEEK) are widely used surface-modified implant materials in orthopedics and dental therapeutics. However, there still has not been comprehensive biocompatibility evaluation of them at molecular level. By employing stable isotope labeling with amino acids in cell culture (SILAC), we profiled the dynamic protein expression changes in human osteoblast-like MG-63 cells cultured on cpTi and PEEK, respectively. About 2000 proteins were quantified and 400 proteins showed substantial alterations in expression levels upon each material treatment. Notably, the extent of alterations diminished as the contact prolonged, which suggested adaptive response to the bioinert materials. Similar patterns of expression changes were observed for both cpTi and PEEK. The representative pathways reflected the regulation of biosynthesis, metabolism and cell adhesion in the adaptive process. In addition, PEEK showed stronger inhibition on mRNA processing, which explained the lower proliferation rate of the cells cultured on PEEK. Our results indicated that the widely used bioinert materials cpTi and PEEK could individually induce a cooperative response involving a wide panel of proteins and pathways. This study has established a basis for better understanding the biocompatibility of surface-modified implant biomaterials at molecular level., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Many investigators have conducted studies to determine the biomechanics, causes, complications and treatment of unilateral facet joint dislocation in the cervical spine. However, there is no quantitative data available on morphological changes in the intervertebral foramen of the cervical spine following unilateral facet joint dislocation. These data are important to understand the cause of neurological compromise following unilateral facet joint dislocation., Methods: Eight embalmed human cadaver cervical spine specimens ranging from level C1-T1 were used. The nerve roots of these specimens at C5-C6 level were marked by wrapping a 0.12mm diameter wire around them. Unilateral facet dislocation at C5-C6 level was simulated by serially sectioning the corresponding ligamentous structures. A CT scan of the specimens was obtained before and after the dislocation was simulated. A sagittal plane through the centre of the pedicle and facet joint was constructed and used for measurement. The height and area of the intervertebral foramen, the facet joint space, nerve root diameter and area, and vertebral alignment both before and after dislocation were evaluated., Results: The intervertebral foramen area changed from 50.72+/-0.88mm(2) to 67.82+/-4.77mm(2) on the non-dislocated side and from 41.39+/-1.11mm(2) to 113.77+/-5.65mm(2) on the dislocated side. The foraminal heights changed from 9.02+/-0.30mm to 10.52+/-0.50mm on the non-dislocated side and 10.43+/-0.50mm to 17.04+/-0.96mm on the dislocated side. The facet space area in the sagittal plane changed from 6.80+/-0.80mm(2) to 40.02+/-1.40mm(2) on the non-dislocated side. The C-5 anterior displacement showed a great change from 0mm to 5.40+/-0.24mm on the non-dislocated side and from 0mm to 3.42+/-0.20mm on the dislocated side. Neither of the nerve roots on either side showed a significant change in size., Conclusions: The lack of change in nerve root area indicates that the associated nerve injury with unilateral facet joint dislocation is probably due to distraction rather than due to direct nerve root compression.

Fracture of the medial tubercle of posterior process of talus is a very rare injury. Often, these fractures are not seen on the AP and lateral radiographs of the ankle joint resulting in them being misdiagnosed as an ankle sprain. This study examines 10 ankle specimens simulated with a posteromedial fracture in varying planes, by multiple X-ray views in varying angles of external rotation in order to increase the sensitivity of oblique views to diagnose a fracture of the posteromedial tubercle. True AP and lateral views (0 degrees and 90 degrees of external rotation) of the ankle joint were unable to detect the fracture simulated in the posteromedial tubercle of the posterior process in any specimens. The fractures in all the specimens were clearly visible when the X-ray beam was parallel to the plane of osteotomy. The fractures could still be identified when the plane of X-ray beam was within +/-10 degrees from the plane of osteotomy. Any further increase or decrease in plane of the X-ray beam could not identify the fracture. Two oblique views at 45 degrees and 70 degrees of external rotation could identify the fractures of the posteromedial tubercle at all planes. These oblique views can be used before resorting to the CT scan.

Near-naked hairless (Hr(N)) is a semi-dominant, spontaneous mutation that was suggested by allelism testing to be allelic with mouse Hairless (Hr). Hr(N) mice differ from other Hr mutants in that hair loss appears as the postnatal coat begins to emerge, rather than as an inability to regrow hair after the first catagen and that the mutation displays semi-dominant inheritance. We sequenced the Hr cDNA in Hr(N)/Hr(N) mice and characterized the pathological and molecular phenotypes to identify the basis for hair loss in this model. Hr(N)/Hr(N) mice exhibit dystrophic hairs that are unable to emerge consistently from the hair follicle, whereas Hr(N)/+ mice display a sparse coat of hair and a milder degree of follicular dystrophy than their homozygous littermates. DNA microarray analysis of cutaneous gene expression demonstrates that numerous genes are downregulated in Hr(N)/Hr(N) mice, primarily genes important for hair structure. By contrast, Hr expression is significantly increased. Sequencing the Hr-coding region, intron-exon boundaries, 5'- and 3'-untranslated region, and immediate upstream region did not reveal the underlying mutation. Therefore, Hr(N) does not appear to be an allele of Hr but may result from a mutation in a closely linked gene or from a regulatory mutation in Hr.